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## Complete Summary

#### GUIDELINE TITLE

Consultation and referral guidelines citing the evidence: how the
allergist-immunologist can help.

#### BIBLIOGRAPHIC SOURCE(S)

American Academy of Allergy, Asthma & Immunology. Consultation and
referral guidelines citing the evidence: how the allergist-immunologist
can help. J Allergy Clin Immunol 2006 Feb;117(2 Suppl
Consultation):S495-523. \[371 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16553071)

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Allergies and allergic reactions, including:

-   Allergic bronchopulmonary aspergillosis

-   Anaphylaxis

-   Asthma

-   Conjunctivitis

-   Cough

-   Dermatitis (atopic and contact)

-   Drug allergy

-   Food allergy

-   Hypersensitivity pneumonitis

-   Insect hypersensitivity

-   Occupational allergic diseases

-   Primary immune deficiency

-   Rhinitis, sinusitis, & rhinosinusitis

-   Urticaria with or without angioedema (e.g., caused by ingestants,
    contactants, C1 esterase inhibitor deficiency)

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Management\
Treatment

#### CLINICAL SPECIALTY

Allergy and Immunology

#### INTENDED USERS

Allied Health Personnel\
Health Care Providers\
Health Plans\
Patients\
Physicians

#### GUIDELINE OBJECTIVE(S)

-   To define both the expertise of the allergist-immunologist and under
    what circumstances they can be of added value in the treatment of
    patients

-   To assist patients and health care professionals in determining when
    referral to an allergist-immunologist could be helpful

#### TARGET POPULATION

Adults and children with allergies or asthma

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis/Evaluation**

1.  Allergen skin testing for specific immunoglobulin E (IgE)

2.  In vitro tests for specific IgE

3.  History-specific IgE correlation

4.  Allergy challenges (e.g., to methacholine, histamine, cold air,
    exercise, food ingestion, drug challenges)

5.  Pulmonary function tests (e.g., spirometry, peak flow)

6.  Immune competence

**Nonpharmacologic Management**

1.  Education regarding appropriate avoidance behavior

2.  Written management plan

3.  Industrial hygiene survey assistance

4.  Education regarding self-monitoring

5.  Education regarding self-treatment

**Pharmacologic and Immunologic Management**

1.  Inhaled and oral corticosteroids

2.  Immunomodulator therapy

3.  Inhalant immunotherapy

4.  Venom immunotherapy

5.  Desensitization therapy (e.g., to antibiotics, insulin, aspirin and
    other nonsteroidal anti-inflammatory drugs)

#### MAJOR OUTCOMES CONSIDERED

-   Sensitivity/specificity of diagnostic tests

-   Accuracy of diagnosis

-   Direct and indirect outcomes of interventions performed by the
    allergist/immunologist

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Many American Academy of Allergy, Asthma and Immunology committees and
individuals:

-   Determined the guideline scope and clinical objectives

-   Defined and conducted appropriate and comprehensive literature
    searches

-   Sorted and evaluated the evidence

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

-   Ia. Meta-analysis of randomized controlled trials

-   Ib. Randomized controlled trial

-   II\. Nonrandomized, controlled intervention study

-   III\. Observational cohort or case-control study

-   IV\. Review article, expert opinion

#### METHODS USED TO ANALYZE THE EVIDENCE

Review\
Review of Published Meta-Analyses

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Recommendations were based on expert interpretation of the evidence.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

Published cost analyses were reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The guidelines were reviewed and approved by the American Academy of
Allergy, Asthma and Immunology (AAAAI) leadership and presented to the
AAAAI membership for comments before being finalized.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

This document includes specific referral guidelines for 14 categories of
allergic diseases, along with the rationale for the referral,
references, and the type and grade of evidence provided (Tables I to
XIV). The tables are presented alphabetically for easy navigation and do
not refer to the prevalence of the individual disease. Guideline grades
of evidence (Ia, Ib, II, III, IV) are defined at the end of the \"Major
Recommendations\" field.

**TABLE I. Allergic Bronchopulmonary Aspergillosis (ABPA)**

  ---------------------------------------------------------------------------
  **Referral         **Rationale**                 **Evidence   **Evidence
  Guideline**                                      Grade**      Type**
  ------------------ ----------------------------- ------------ -------------
  Patients with      Allergen skin testing and *in IV           Diagnostic
  suspected or       vitro* tests, when correlated              
  proven asthma or   with history and other                     
  cystic fibrosis    findings, can establish the                
  who have pulmonary diagnosis of ABPA                          
  infiltrates and    (Greenberger, 2002)                        
  peripheral blood                                              
  eosinophilia                                                  

  Patients with      Allergist-immunologists are   III, IV      Indirect
  known ABPA for     specifically trained to                    outcome (ABPA
  management         manage this disease                        management)
                     (\"Allergy and immunology                  
                     core curriculum,\" 1996), and              
                     outcomes of such management                
                     have been reported by                      
                     allergist-immunologists                    
                     (Patterson et al., 1982;                   
                     Patterson et al., 1986;                    
                     Patterson et al., 1987).                   
  ---------------------------------------------------------------------------

**TABLE II. Anaphylaxis** (see also \"Drug allergy\" \[Table VII\],
\"Food allergy\" \[Table VIII\], and \"Insect hypersensitivity\" \[Table
X\] for anaphylaxis caused by these agents)

  -------------------------------------------------------------------------------
  **Referral         **Rationale**                  **Evidence   **Evidence
  Guideline**                                       Grade**      Type**
  ------------------ ------------------------------ ------------ ----------------
  Individuals with a After a severe allergic        III, IV      Diagnostic\
  severe allergic    reaction without a known                    Indirect outcome
  reaction           cause, a trigger should be                  (trigger
  (anaphylaxis)      identified if at all possible.              avoidance)
  without an obvious An allergist-immunologist is                
  or previously      the most appropriate medical                
  defined trigger    professional to perform this                
                     evaluation (\"Allergy and                   
                     immunology core curriculum,\"               
                     1996), which might include                  
                     skin testing, *in vitro*                    
                     tests, and challenges when                  
                     indicated (including with                   
                     exercise, see below). Major                 
                     triggers for anaphylaxis are                
                     foods and food constituents,                
                     medications and biologic                    
                     agents, latex, and insect                   
                     stings (Cianferoni et al.,                  
                     2001; Brown, McKinnon, & Chu,               
                     2001; Lee & Greenes, 2000;                  
                     Yocum et al., 1999; Akin &                  
                     Metcalfe, 2004). Future                     
                     avoidance of the identified                 
                     triggers should prevent                     
                     subsequent anaphylactic                     
                     episodes.                                   

                     Management of idiopathic       III          Direct outcome
                     anaphylaxis by an                           (idiopathic
                     allergist-immunologist is                   anaphylaxis)
                     associated with a reduction in              
                     hospitalizations and emergency              
                     department visits (Wong,                    
                     Dykewicz, & Patterson, 1990).               

  Persons with       Food allergy is the most       III, IV      Diagnostic\
  anaphylaxis        common cause of anaphylaxis                 Indirect outcome
  attributed to food outside of the hospital                     (food avoidance,
                     setting (Cianferoni et al.,                 early
                     2001; Brown, McKinnon, & Chu,               interventions)
                     2001; Yocum et al., 1999).                  
                     Allergist-immunologists use                 
                     diagnostic modalities to                    
                     confirm the trigger and use                 
                     their specific training                     
                     (\"Allergy and immunology core              
                     curriculum,\" 1996) and                     
                     clinical experience to educate              
                     patients regarding avoidance                
                     and immediate management to                 
                     prevent potentially deadly                  
                     outcomes (Bock, Munoz-Furlong,              
                     & Sampson, 2001).                           

  Exercise-induced   After an anaphylactic reaction II, III      Diagnostic\
  anaphylaxis and    that appears to have a                      Indirect outcome
  food-dependent     significant relationship to                 (avoidance)
  exercise-induced   exercise, it is crucial to be               
  anaphylaxis        certain whether exercise is                 
                     the cause and to determine                  
                     whether a food might be                     
                     involved (Sheffer et al.,                   
                     1983; Casale, Keahey, &                     
                     Kaliner, 1986; Romano et al.,               
                     2001; Aihara et al., 2001).                 

  Drug-induced       Allergist-immunologists use                 Diagnostic
  anaphylaxis        diagnostic agents to confirm                
                     the drug responsible for the                
                     reaction, if these agents are               
                     available (see \"Drug                       
                     allergy\" \[Table VII\]).                   
  -------------------------------------------------------------------------------

**TABLE III, A. Asthma Diagnosis**

  ------------------------------------------------------------------------------
  **Referral           **Rationale**                  **Evidence   **Evidence
  Guideline**                                         Grade**      Type**
  -------------------- ------------------------------ ------------ -------------
  Patients with        Allergists-immunologists       III          Diagnostic
  respiratory symptoms perform methacholine                        
  suggestive of asthma challenges, which have a high               
  but with normal PFT  sensitivity for current asthma              
  results (FEV~1~      (Hopp, et al., 1984; Cockcroft              
  \>80% of predicted   et al., 1992).                              
  value) and no                                                    
  significant                                                      
  reversibility (\<12%                                             
  and 200-mL increase                                              
  in FEV~1~)                                                       

  Exercise-induced     Further objective evaluation   III          Diagnostic
  symptoms that are    and confirmation with                       
  atypical or do not   pulmonary function testing                  
  respond well to      (including exercise challenge)              
  pretreatment with    in conjunction with                         
  albuterol,           appropriate                                 
  nedocromil, or       allergist-immunologist                      
  cromolyn             evaluation will define                      
                       diagnosis or differential                   
                       diagnosis (Holzer, Anderson, &              
                       Douglass, 2002).                            

  Subjects wishing to  There is a theoretic risk of   IV           Diagnostic\
  scuba dive with a    increased barotraumas, as well              Indirect
  history of asthma    as exercise-induced                         outcome
                       bronchospasm, in patients with              (scuba diving
                       asthma who scuba dive.                      avoidance)
                       Bronchoprovocation with                     
                       exercise has been recommended               
                       to exclude asthma in scuba                  
                       divers (Anderson et al.,                    
                       1995).                                      
  ------------------------------------------------------------------------------

PFT = pulmonary function test; FEV~1~ = 1-second forced expiratory
volume

**TABLE III, B. Asthma: Environmental Diagnosis and Management**

  ------------------------------------------------------------------------------
  **Referral         **Rationale**                    **Evidence   **Evidence
  Guideline**                                         Grade**      Type**
  ------------------ -------------------------------- ------------ -------------
  Patients with a    Exposure to indoor and outdoor   III, IV      Diagnostic
  history of         allergens can worsen asthma                   
  seasonal or        (Bjornsson et al., 1995; Marks                
  persistent asthma  et al., \"Mite allergen\", 1995;              
  for evaluation of  Henderson et al., 1995; Newson                
  inhalant           et al., 1997; Marks et al.,                   
  sensitization to   2001; Pollart et al., 1988;                   
  confirm the        Subiza et al., 1994; Epton et                 
  diagnosis          al., 1997; Neas et al., 1996;                 
                     Targonski, Persky, &                          
                     Ramekrishnan, 1995; Dales et                  
                     al., 2000; Vervloet et al.,                   
                     1991; Kivity et al., 1993;                    
                     Custovic et al., 1996;                        
                     Rosenstreich et al., 1997).                   
                     Allergy cannot be diagnosed on                
                     the basis of history alone (Host              
                     et al., 2003). Diagnosis is                   
                     derived from correlation of                   
                     clinical history and diagnostic               
                     tests (Host et al., 2003), with               
                     which allergist-immunologists                 
                     are expert (\"Allergy and                     
                     immunology core curriculum,\"                 
                     1996.                                         

  Patients who need  Allergists have familiarity with Ib, II, III, Indirect
  management and     the wide variety of both indoor  IV           outcome
  education          and outdoor aeroallergen                      (avoidance)
  concerning         exposures that have been shown                
  environmental      to affect asthma and respiratory              
  triggers           function (Core Curriculum                     
                     Subcommittee, 1996). Allergists               
                     are specifically trained to                   
                     provide education regarding                   
                     appropriate avoidance measures                
                     (\"Allergy and immunology core                
                     curriculum,\" 1996). Allergen                 
                     avoidance can improve asthma                  
                     (Platts-Mills et al., 1982;                   
                     Dorward et al., 1988; Ehnert et               
                     al., 1992; Boner et al., 1985;                
                     Grootendorst et al., 2001; Marks              
                     et al., \"The effect of                       
                     changes\", 1995; Carswell et                  
                     al., 1996; Halken et al., 2003;               
                     Frederick et al., 1997; Shapiro               
                     et al., 1999; Cloosterman et                  
                     al., 1999; Warner et al., 2000;               
                     Van der Heide et al., 1997).                  

  Patients with      Exposure to furred pets in       Ib, III, IV  Diagnostic\
  asthma who         allergic patients can worsen                  Indirect
  experience a       asthma symptoms (Sporik et al.,               outcome
  worsening of       1995; Bollinger et al., 1996).                (avoidance)
  symptoms after a   Avoidance of pets in allergic                 
  new pet has been   patients can improve asthma                   
  introduced into    symptoms (Van der Heide et al.,               
  the home           1999), reduce airway                          
                     responsiveness (Shirai et al.,                
                     2005), and reduce the need for                
                     inhaled corticosteroids (Shirai               
                     et al., 2005).                                
  ------------------------------------------------------------------------------

**TABLE III, C. Asthma Treatment: Immunotherapy**

+------------------------+---------------------+-------+--------------+
| **Referral Guideline** | **Rationale**       | **Evi | **Evidence   |
|                        |                     | dence | Type**       |
|                        |                     | Gr    |              |
|                        |                     | ade** |              |
+========================+=====================+=======+==============+
| Consider referral for  | The efficacy of     | Ia,   | Indirect     |
| allergen immunotherapy | allergen            | Ib,   | outcome      |
| for asthmatic patients | immunotherapy in    | IV    | (im          |
| if there is a clear    | the treatment of    |       | munotherapy) |
| relationship between   | allergic asthma has |       |              |
| asthma and exposure to | been demonstrated   |       |              |
| an unavoidable         | in many             |       |              |
| aeroallergen to which  | double-blind,       |       |              |
| specific IgE           | placebo-controlled  |       |              |
| antibodies have been   | studies to multiple |       |              |
| demonstrated and the   | allergens (e.g.,    |       |              |
| following:             | pollen, animal      |       |              |
|                        | allergen, fungi,    |       |              |
| -   poor response to   | and dust mite)      |       |              |
|     pharmacotherapy or | (\"Allergen         |       |              |
|     avoidance measures | immunotherapy,\"    |       |              |
|                        | 2003; Abramson,     |       |              |
| -   unacceptable side  | Puy, & Weiner,      |       |              |
|     effects of         | 1995; Ross, Nelson, |       |              |
|     medications        | & Feingold,         |       |              |
|                        | \"Effectiveness of  |       |              |
| -   desire to avoid    | specific            |       |              |
|     long-term          | immunotherapy in    |       |              |
|     pharmacotherapy    | the treatment of    |       |              |
|                        | asthma,\" 2000).    |       |              |
| -   coexisting         |                     |       |              |
|     allergic rhinitis  |                     |       |              |
|                        |                     |       |              |
| -   long duration of   |                     |       |              |
|     symptoms           |                     |       |              |
|     (perennial or      |                     |       |              |
|     major portion of   |                     |       |              |
|     the year)          |                     |       |              |
+------------------------+---------------------+-------+--------------+
| Consider referral for  | One study suggests  | Ib,   | Indirect     |
| children with allergic | that allergen       | II,   | outcome      |
| rhinitis because       | immunotherapy has   | III   | (im          |
| immunotherapy can      | been shown to       |       | munotherapy) |
| potentially prevent    | reduce the          |       |              |
| the development of     | development of      |       |              |
| asthma                 | asthma in children  |       |              |
|                        | with allergic       |       |              |
|                        | rhinitis compared   |       |              |
|                        | with a group of     |       |              |
|                        | children treated    |       |              |
|                        | with medication     |       |              |
|                        | alone (Moller et    |       |              |
|                        | al., 2002)          |       |              |
|                        | Immunotherapy might |       |              |
|                        | also prevent the    |       |              |
|                        | development of new  |       |              |
|                        | allergen            |       |              |
|                        | sensitivities       |       |              |
|                        | (                   |       |              |
|                        | Purello-D\'Ambrosio |       |              |
|                        | et al., 2001; Des   |       |              |
|                        | Roches et al.,      |       |              |
|                        | 1997; Pajno et al., |       |              |
|                        | 2001)               |       |              |
+------------------------+---------------------+-------+--------------+

IgE = immunoglobulin E

**TABLE III, D. Asthma Treatment: Prevention of Morbidity**

  -----------------------------------------------------------------------------------
  **Referral           **Rationale**                     **Evidence   **Evidence
  Guideline**                                            Grade**      Type**
  -------------------- --------------------------------- ------------ ---------------
  Patients with asthma Allergist care reduces subsequent Ib, II, III  Direct outcome
  who require          asthma emergency department                    
  emergency department visits (Moore et al., 1997; Vilar              
  care for an acute    et al., 2000; Wu et al., 2001;                 
  episode              Kelly et al., 2000; Zeiger et                  
                       al., 1991; Westley et al., 1997;               
                       Sperber et al., 1995; Weinstein                
                       et al., 1992; Weinstein et al.,                
                       1996; Schatz et al., 2003; Schatz              
                       et al., 2005).                                 

                       Allergist care reduces subsequent Ib, II, III  
                       hospitalization (Vilar et al.,                 
                       2000; Wu et al., 2001; Kelly et                
                       al., 2000; Zeiger et al., 1991;                
                       Westley et al., 1997; Sperber et               
                       al., 1995; Weinstein et al.,                   
                       1992; Weinstein et al., 1996;                  
                       Schatz et al., 2003; Schatz et                 
                       al., 2005).                                    

  Patients with        Allergist care reduces asthma     II, III      Direct outcome
  uncontrolled asthma  symptoms and improves physical                 
                       functioning and asthma-related                 
                       quality of life (Moore et al.,                 
                       1997; Wu et al., 2001; Schatz et               
                       al., 2005; Vollmer et al., 1997).              

  Patients with        Inhaled corticosteroid use leads  Ib           Indirect
  persistent asthma,   to reduction in asthma symptoms,               outcome
  particularly         exacerbations, hospitalizations,               (controllers)
  moderate-to-severe   and asthma death (Schatz et al.,               
  persistent asthma    2003).                                         

                       Allergist care is more likely to  Ib, II, III  
                       lead to use of asthma controller               
                       medications (particularly inhaled              
                       corticosteroids) (Zeiger et al.,               
                       1991; Sperber et al., 1995;                    
                       Schatz et al., 2003; Vollmer et                
                       al., 1997; Stempel, Carlson, &                 
                       Buchner, 1997; Diette et al.,                  
                       2001; Mahr & Evans, 1993).                     

                       Allergists administer anti-IgE,   Ib           Indirect
                       which prevents exacerbations,                  outcome
                       improves symptoms, and reduces                 (anti-IgE)
                       the use of inhaled steroids in                 
                       patients with moderate-to-severe               
                       asthma (Corren et al., 2003;                   
                       Lanier et al., 2003).                          

  Patients who need    Use of written action plans       II, III      Indirect
  education on asthma  improves asthma self-management                outcome\
  and guidance in      (Wu et al., 2001; Diette et al.,               (education,
  techniques for       2001; Mahr & Evans, 1993).                     action plan)
  self-management                                                     

                       Allergist care is more likely to  II, III      
                       lead to provision of a written                 
                       management plan and objective                  
                       monitoring of asthma with peak                 
                       flow meters (Wu et al., 2001;                  
                       Diette et al., 2001; Mahr &                    
                       Evans, 1993).                                  

                       Asthma self-management education  Ia, III      
                       improves outcomes in children and              
                       adults (Wolf et al., 2003; Gibson              
                       et al., 2002). Allergist care is               
                       associated with more effective                 
                       self-management education and                  
                       knowledge (Wu et al., 2001;                    
                       Schatz et al., 2005; Engel et                  
                       al., 1989; Wolle & Cwi, 1995).                 

  Patients who use     Excessive short-acting            II           Direct outcome
  excessive amounts of beta-agonist use indicates                     
  reliever medications uncontrolled asthma. Allergist                 
                       care reduces overuse of                        
                       short-acting beta-agonists                     
                       (Diette et al., 2001).                         

  Patients with severe Allergist care reduces cost of    III          Direct outcome
  asthma               care for asthma (Westely et al.,               
                       1997; Weinstein et al., 1992;                  
                       Weinstein et al., 1996; Freund et              
                       al., 1989).                                    
  -----------------------------------------------------------------------------------

**TABLE III, E. Asthma Treatment: Prevention of Mortality**

  --------------------------------------------------------------------------------
  **Referral         **Rationale**                   **Evidence   **Evidence
  Guideline**                                        Grade**      Type**
  ------------------ ------------------------------- ------------ ----------------
  Patients with      **Improved Pharmacologic                      
  potentially fatal  Therapy**                                    
  asthma (prior                                                   
  severe,                                                         
  life-threatening                                                
  episode; prior                                                  
  intubation)                                                     

                     Inhaled steroids have been      III          Indirect outcome
                     associated with significant                  (inhaled\
                     reductions in risk for fatal                 and oral
                     and near-fatal exacerbation of               steroids)
                     asthma (Suissa et al., 2000).                

                     Allergist-immunologists         III          
                     prescribe inhaled steroids more              
                     frequently than primary care                 
                     physicians, and patients seen                
                     and managed by                               
                     allergist-immunologists are                  
                     more likely to be taking                     
                     inhaled steroids regularly                   
                     (Legorretta et al., 1998;                    
                     Hartert et al., 1996; Blais et               
                     al., 2001; Donahue et al.,                   
                     2000; Schatz et al., 2003).                  

                     Oral steroid use for attacks    Ib, III      
                     reduces the risk of fatal                    
                     asthma (Abramson et al., 2001;               
                     Leung, Santiago, &                           
                     Klaustermeyer, 1983;                         
                     \"CONTROLLED trial,\" 1956).                 

                     Patients managed by             III          
                     allergist-immunologists are                  
                     more likely to appropriately                 
                     receive oral steroids (Schatz                
                     et al., 2003; Engel et al.,                  
                     1989; Bucknall et al., 1988).                

                     **Immunologic Therapy**                       

                     Allergens can trigger severe    III          Indirect outcome
                     and fatal asthma episodes                    (avoidance,
                     (O\'Hollaren et al., 1991).                  immunotherapy)

                     Allergist-immunologists have    IV           
                     expertise in performance and                 
                     interpretation of skin tests                 
                     for immediate hypersensitivity,              
                     education to encourage                       
                     aeroallergen avoidance, and                  
                     provision of inhalant allergen               
                     immunotherapy in properly                    
                     selected patients (\"Allergy                 
                     and immunology core                          
                     curriculum,\" 1996).                         

                     Allergen immunotherapy provides Ia, Ib, III, 
                     significant clinical benefit    IV           
                     (\"Allergen immunotherapy,\",                
                     2003; Abramson, Puy, & Weiner,               
                     2003), including for                         
                     *Alternaria* species (Horst et               
                     al., 1990), which has been                   
                     associated with                              
                     life-threatening asthma                      
                     (O\'Hallaren et al., 1991).                  

                     Anti-IgE therapy has been shown Ia, Ib       
                     to improve outcomes in                       
                     high-risk patients (Bousquet et              
                     al., 2004; Holgate et al.,                   
                     2001).                                       

                     **Objective Monitoring of                     
                     \"Poor Perceivers\"**                        

                     A major factor contributing to  III          Diagnostic
                     risk for fatal asthma outcomes               
                     is underrecognition of asthma;               
                     some asthmatic patients are                  
                     \"poor perceivers\" (Kikuchi et              
                     al., 1994).                                  

                     Allergist-immunologists perform III          
                     objective measurements of lung               
                     function more frequently than                
                     other physicians (Janson &                   
                     Weiss, 2004; Freund et al.,                  
                     1988).                                       

                     **Action Plans**                              

                     Action plans can reduce asthma  III          Indirect outcome
                     mortality (Abramson et al.,                  (action plans)
                     2001).                                       

                     Asthma specialists are more     III          
                     likely to provide action plans               
                     to their patients (Diette et                 
                     al., 2001).                                  
  --------------------------------------------------------------------------------

**TABLE III, F. Asthma Treatment: Adherence**

  -------------------------------------------------------------------------------
  **Referral        **Rationale**                       **Evidence   **Evidence
  Guideline**                                           Grade**      Type**
  ----------------- ----------------------------------- ------------ ------------
  Patients with     Patients with a visit to an         III          Direct
  asthma in whom    allergist-immunologist in the prior              outcome
  adherence         year were significantly more likely              
  problems might be to have been dispensed an optimally              
  limiting optimal  effective number of inhaled steroid              
  control           canisters (Schatz et al., 2003).                 

                    Specialty care is associated with   III          
                    more refills of anti-inflammatory                
                    medications (Stempel, Carlson, &                 
                    Buchner, 1997).                                  

                    Patient compliance with national    IV           
                    asthma guidelines was higher in                  
                    patients of specialists (Meng et                 
                    al., 1999).                                      

                    Misunderstanding of asthma          III          
                    controller medications, which was                
                    associated with decreased                        
                    adherence, was more likely in                    
                    patients not treated by specialists              
                    (Farber et al., 2003).                           
  -------------------------------------------------------------------------------

**TABLE III, G. Occupational Asthma**

  ------------------------------------------------------------------------------
  **Referral            **Rationale**                 **Evidence   **Evidence
  Guideline**                                         Grade**      Type**
  --------------------- ----------------------------- ------------ -------------
  Patients with a       History and physical          III, IV      Diagnostic\
  history suggesting    examination are insufficient               Indirect
  occupational asthma   to confirm occupational                    outcome
  should undergo        asthma, and inaccurate                     (avoidance)
  testing to confirm    conclusions can easily be                  
  the diagnosis of      drawn (Malo et al., 1991;                  
  asthma and referral   Baur et al., 1998).                        
  to an allergist for   Allergists can interpret                   
  evaluation to         spirometry when performed as               
  establish that the    a baseline, with response to               
  asthma is caused by   bronchodilator, serial                     
  or triggered by       assessment of spirometry or                
  agents at the         peak flows, and changes in                 
  workplace and to      methacholine response during               
  initiate appropriate  work periods versus off-work               
  avoidance therapy.    periods (\"Allergy and                     
                        immunology core curriculum,\"              
                        1996; Moscato et al., 1995;                
                        Vandenplas et al., 2001;                   
                        Chan-Yeung, 1995; Tarlo et                 
                        al., 1998; Cartier, Pineau, &              
                        Malo, 1984; Cockroft & Mink,               
                        1979).                                     

                        Allergists can outline the    III, IV      
                        algorithm for the clinical                 
                        investigation of suspected                 
                        occupational asthma and                    
                        interpret other studies to                 
                        confirm bronchial                          
                        hyperresponsiveness,                       
                        including challenges with                  
                        methacholine, histamine, cold              
                        air, or exercise, yet realize              
                        that such study results might              
                        be negative if performed when              
                        the patient is off work and                
                        free of symptoms (\"Allergy                
                        and immunology core                        
                        curriculum,\" 1996;                        
                        Vandenplas et al., 2001;                   
                        Cartier, Pineau, & Malo,                   
                        1984).                                     

                        Allergists can review         III, IV      
                        Material Safety Data Sheets                
                        and other specific details of              
                        the workplace obtained either              
                        through specific questioning,              
                        direct observation during an               
                        onsite work evaluation, or                 
                        assistance in obtaining an                 
                        industrial hygiene survey in               
                        an effort to identify                      
                        exposure to possible causal                
                        agents. Allergists can                     
                        arrange and interpret                      
                        workplace challenges and be                
                        able to provide assistance in              
                        referring to centers that can              
                        perform specific agent                     
                        laboratory challenges if                   
                        indicated (\"Allergy and                   
                        immunology core curriculum,\"              
                        1996; Vandenplas et al.,                   
                        2001; Tarlo et al., 1998).                 

                        The importance of identifying III, IV      
                        the agent responsible for                  
                        asthma is that continued                   
                        exposure can lead to                       
                        worsening asthma and possibly              
                        persistent disease, even                   
                        after exposure ceases. Early               
                        accurate diagnosis and                     
                        removal from further exposure              
                        to specific work sensitizers               
                        carries the best medical                   
                        prognosis for those with                   
                        occupational lung disease                  
                        (Moscato et al., 1999;                     
                        Paggiaro, et al., 1987;                    
                        Gannon et al., 1993;                       
                        Chan-Yeung, MacLean, &                     
                        Paggiaro, 1987; Rosenberg et               
                        al., 1987; Tarlo et al.,                   
                        1997; Perfetti et al., 1998).              

  Consider referral of  Exposure to workplace         III          Indirect
  a worker with asthma  irritants is a known cause of              outcome
  for evaluation of     and known exacerbator of                   (avoidance)
  workplace exposures   asthma (Tarlo et al., 2000).               
  that could worsen or                                             
  exacerbate the                                                   
  asthma.                                                          
  ------------------------------------------------------------------------------

**TABLE IV. Conjunctivitis**

  -----------------------------------------------------------------------------
  **Referral        **Rationale**                 **Evidence   **Evidence
  Guideline**                                     Grade**      Type**
  ----------------- ----------------------------- ------------ ----------------
  Patients with     Allergy cannot be diagnosed   III, IV      Diagnostic
  prolonged or      on the basis of history alone              
  recurrent         (Martin et al., 2003).                     
  manifestations of Diagnosis is derived from a                
  allergic          correlation of clinical                    
  conjunctivitis\   history and diagnostic tests,              
  \                 with which                                 
  Patients with     allergist-immunologists are                
  comorbid          experienced (\"Allergy and                 
  conditions (e.g,. immunology core curriculum,\"              
  asthma, rhinitis, 1996). Allergists can help to              
  recurrent         suspect and diagnose corneal               
  sinusitis)        involvement in vernal and                  
                    atopic keratoconjunctivitis                
                    (Bonini et al., 1999; Bonini               
                    et al., 2000).                             

  Patients with     A thorough allergy evaluation Ib, III, IV  Indirect outcome
  symptoms          will complement the patient                (avoidance,
  interfering with  history and aid in the                     immunotherapy)
  quality of life,  development of specific                    
  ability to        treatment plans, including                 
  function, or      immunotherapy and                          
  both\             environmental controls. These              
  \                 treatments can benefit                     
  Patients who have patients with allergic                     
  found medications conjunctivitis in terms of                 
  to be ineffective reduced symptoms, medication               
  or have had       use, and cost. Allergen                    
  adverse reactions immunotherapy can be highly                
  to previously     effective in controlling the               
  prescribed        symptoms of allergic                       
  medications       conjunctivitis (Mimura et                  
                    al., 2004; Cakmak et al.,                  
                    2002; \"Allergen                           
                    immunotherapy,\" 2003).                    
                    Efficacy parameters include                
                    symptom and medication                     
                    scores, conjunctival                       
                    challenge, and immunologic                 
                    cell markers and cytokine                  
                    profiles. Allergen                         
                    immunotherapy can provide                  
                    lasting benefits after                     
                    immunotherapy is discontinued              
                    (Alvarez-Cuesta et al., 1994;              
                    Varney et al., 1991; Bachert               
                    et al., 2002).                             
  -----------------------------------------------------------------------------

**TABLE V. Cough**

  -----------------------------------------------------------------------------
  **Referral    **Rationale**                     **Evidence   **Evidence
  Guideline**                                     Grade**      Type**
  ------------- --------------------------------- ------------ ----------------
  Patients with Asthma, postnasal drainage, and   III, IV      Diagnostic
  chronic cough gastroesophageal reflux disease                
  of 3 to 8     are the most common causes of                  
  weeks or more cough (Irwin et al., 1998;                     
                Kastelik et al., 2005).                        
                Spirometry and a chest radiograph              
                have been suggested as the                     
                minimum investigations required                
                in the evaluation of chronic                   
                cough (Kastelik et al., 2005;                  
                Chang & Robertson, 2000; Morice                
                et al., 2004). Allergists have                 
                extensive training to evaluate                 
                the upper, as well as lower,                   
                airways in a patient with chronic              
                cough (\"Allergy and immunology                
                core curriculum,\" 1996).                      

  Patients with Cough occurs in all asthmatic     IV           Diagnostic
  coexisting    subjects (Irwin et al., 1998).                 
  chronic cough However, cough alone is a poor                 
  and asthma    marker of asthma, and asthma                   
                might be overdiagnosed in                      
                children with cough alone (Chang               
                & Robertson, 2000). The allergist              
                can both provide expert                        
                consultation to ensure the                     
                diagnosis of asthma is correct                 
                and to maximize therapy in the                 
                asthmatic subject (see \"Asthma\"              
                \[Tables III, A, through III,                  
                G\]).                                          

                                                               Indirect outcome
                                                               (avoidance,
                                                               pharmacologic,
                                                               and immunologic
                                                               therapy)

  Patients with Postnasal drip is the single most IV           Diagnostic
  coexisting    common cause of chronic cough                  
  chronic cough (Irwin et al., 1998). Allergy                  
  and rhinitis  skin testing and history-testing               
                correlation can differentiate                  
                allergic from nonallergic                      
                rhinitis (see \"Rhinitis\"                     
                \[Table XIII, A\]). Treatment of               
                rhinitis can improve the cough                 
                (Irwin et al., 1998). Treatment                
                of rhinitis by allergists                      
                improves patient outcomes (see                 
                \"Rhinitis\" \[Table XIII, A\]).               

                                                               Indirect outcome
                                                               (avoidance,
                                                               pharmacologic,
                                                               and immunologic
                                                               therapy)

  Patients with Tobacco smoke exposure clearly    IV           Indirect outcome
  chronic cough increases cough prevalence and                 (smoking
  and tobacco   exacerbates any pulmonary                      cessation)
  use or        condition (Chang & Robertson,                  
  exposure      2000). Chronic cough in cigarette              
                smokers is dose related (Morice                
                et al., 2004). Allergists can                  
                assist with active steps to                    
                minimize or eliminate tobacco                  
                smoke exposure (\"Allergy and                  
                immunology core curriculum,\"                  
                1996).                                         
  -----------------------------------------------------------------------------

**TABLE VI, A. Atopic Dermatitis**

  -----------------------------------------------------------------------------
  **Referral    **Rationale**                     **Evidence   **Evidence
  Guideline**                                     Grade**      Type**
  ------------- --------------------------------- ------------ ----------------
  To confirm    Allergist-immunologists are       IV           Diagnostic
  the diagnosis specifically trained to diagnose               
  of atopic     atopic dermatitis (\"Allergy and               
  dermatitis in immunology core curriculum,\"                  
  a patient     1996). Defining IgE-mediated                   
  with          sensitivity (by means of skin or               
  dermatitis    *in vitro* testing) is useful in               
                the differential diagnosis                     
                (Schultz-Larsen & Hanifin, 2002).              

  To identify   Dust mite allergy can trigger     Ib, II, III, Diagnostic\
  the role of   atopic dermatitis. In such        IV           Indirect outcome
  dust mite     patients mite avoidance should be              (mite avoidance)
  allergy in    helpful (Platts-Mills et al.,                  
  patients with 1983; Tupker et al., 1996; Huang               
  atopic        et al., 2001; Wheatley &                       
  dermatitis    Platts-Mills, 2000; Palmer &                   
                Friedmann, 2001; Ricci et al.,                 
                2000; Gutgesell et al., 2001; Tan              
                et al., 1996; Holm et al., 2001).              

  To identify   Approximately 35% of young        Ib, III      Diagnostic\
  the role of   children with moderate-to-severe               Indirect outcome
  food allergy  atopic dermatitis have food                    (food avoidance)
  in patients   allergy; the association appears               
  with atopic   less common in adults but is                   
  dermatitis    possible (Sampson & Albergo,                   
                1984; Lever et al., 1998;                      
                Woodmansee & Christiansen, 2001;               
                Sampson, 2001; Sicherer, Morrow,               
                & Sampsom, 2000; Niggemann et                  
                al., 2001; Eigenmann et al.,                   
                \"Prevalence of IgE-mediated,\"                
                1998; Reekers et al., 1999).                   

  Patients      Allergist-immunologists are       Ia, Ib, II,  Indirect outcome
  whose atopic  specifically trained and          IV           (pharmacologic
  dermatitis    experienced in managing atopic                 therapy)
  responds      dermatitis in both children and                
  poorly to     adults (Leung et al., 1997; Leung              
  treatment     et al., 2004; Hoare, Li Wan Po, &              
                Williams, 2000; Van Der Meer et                
                al., 1999; Devillers et al.,                   
                2002; Sowden et al., 1991; Salek               
                et al., 1993; Harper et al.,                   
                2001).                                         
  -----------------------------------------------------------------------------

**TABLE VI, B. Contact Dermatitis**

  -----------------------------------------------------------------------------
  **Referral    **Rationale**                        **Evidence   **Evidence
  Guideline**                                        Grade**      Type**
  ------------- ------------------------------------ ------------ -------------
  To confirm    Allergist-immunologists are          III, IV      Diagnostic\
  the diagnosis specifically trained to diagnose                  Indirect
  of and        contact dermatitis (\"Allergy and                 outcome
  identify the  immunology core curriculum,\" 1996).              (avoidance)
  cause of      More allergist-immunologists than                 
  contact       dermatologists currently perform                  
  dermatitis    patch testing (Fonacier et al.,                   
                2002; Fonacier & Charlesworth,                    
                2003). If a cause is defined,                     
                avoidance therapy can be initiated                
                (Nettis et al., 2003; Mitchell et                 
                al., 1982; Lindberg et al., 2004;                 
                Li, Sujan, & Wang, 2003; Adams,                   
                1990; Reitschel et al., 2002; Drake               
                et al., 1995; Marks & DeLeo, 1993;                
                Bernstein & Storms, 1995; Marks et                
                al., 1998).                                       

  -----------------------------------------------------------------------------

**TABLE VII. Drug Allergy**

  --------------------------------------------------------------------------------
  **Referral            **Rationale**              **Evidence   **Evidence Type**
  Guideline**                                      Grade**      
  --------------------- -------------------------- ------------ ------------------
  Patients with a       The vast majority of       II           Diagnostic\
  history of penicillin patients with a history of              Indirect outcome
  allergy who have a    penicillin allergy can                  (needed penicillin
  significant           safely use penicillins if               treatment)
  probability of        an allergy evaluation,                  
  requiring future      often including a                       
  antibiotic therapy    penicillin skin test, is                
                        performed (Mendelson et                 
                        al., 1984).                             

                        History alone is           III          
                        inadequate to rule out                  
                        IgE-mediated allergy to                 
                        penicillin (Solensky,                   
                        Earl, & Gruchalla, 2000).               

                        Penicillin skin testing in II, III      
                        advance of need does not                
                        cause significant                       
                        resensitization (Solensky,              
                        Earl, & Gruchalla, 2002;                
                        Macy, Mangat, & Burchette,              
                        2003; Nugent et al., 2003;              
                        Bittner & Greenberger,                  
                        2004).                                  

                        Patients who are shown not III          
                        to be allergic to                       
                        penicillin might be able                
                        to use more appropriate                 
                        and potentially less toxic              
                        antibiotics, less                       
                        expensive antibiotics, or               
                        both (Macy & Burchette,                 
                        2002).                                  

  Patients with a       Skin test responses might  III, IV      Indirect outcome
  history of penicillin be negative in such                     (needed penicillin
  allergy in which a    patients, who can then                  treatment)
  penicillin-class      safely receive                          
  antibiotic is the     penicillin.(Macy, Mangat,               
  drug of choice        & Burchette, 2003)                      
                        Antibiotic desensitization              
                        in patients with positive               
                        skin test responses                     
                        renders them transiently                
                        tolerant and induces                    
                        negative skin test                      
                        responses, indicating                   
                        blocking of mast cell--IgE              
                        activation events                       
                        (Naclerio, Mizrahi, &                   
                        Adkinson, 1983; Stark et                
                        al., 1987; Solensky, 2004;              
                        Borish, Tamir, &                        
                        Rosenwasser, 1987).                     

  Patients with         Allergist-immunologists    IV           Diagnostic\
  histories of multiple provide a comprehensive                 Indirect outcome
  drug                  plan to evaluate the                    (treatment with
  allergy-intolerance   historical adverse drug                 needed
                        reactions and provide                   medications)
                        suggestions on future                   
                        therapies to minimize                   
                        risks (\"Allergy and                    
                        immunology core                         
                        curriculum,\" 1996; Demoly              
                        et al., 1999; Gruchalla,                
                        2000; Macy, 2004; Vemuir,               
                        Tripathi, & Keefe, 2004;                
                        Rotskoff et al., 2004).                 

  Patients who might be Allergist-immunologists    II, III, IV  Diagnostic\
  allergic to           perform skin testing with               Indirect outcome
  protein-based         appropriate concentrations              (treatment with
  biotherapeutics and   and techniques to                       needed
  require use of these  determine current                       biotherapeutics)
  materials             sensitivity (\"Allergy and              
                        immunology core                         
                        curriculum,\" 1996;                     
                        Vemuir, Tripathi, & Keefe,              
                        2004; Rotskoff et al.,                  
                        2004; Grammer et al.,                   
                        1988; Dykewicz et al.,                  
                        1994; Leonard et al.,                   
                        2002). For example,                     
                        insulin desensitization                 
                        allows for continued                    
                        insulin therapy in                      
                        patients with prior                     
                        systemic reactions                      
                        (Grammer, Metzger, &                    
                        Patterson, 1984; Gossain,               
                        Rovner, & Mohan, 1985).                 

  Patients with         Allergist-immunologists    IV           Diagnostic
  histories of adverse  accurately diagnose NSAID               
  reactions to NSAIDs   sensitivity through                     
  who require aspirin   challenge testing (Simon,               
  or other NSAIDs       2003).                                  

                        Allergist-immunologists    IV           Indirect outcome
                        perform aspirin                         (needed NSAID
                        desensitization in                      treatment)
                        patients with documented                
                        aspirin sensitivity who                 
                        require aspirin for other               
                        medical conditions                      
                        (Solensky, 2004; Simon,                 
                        2003).                                  

                        Desensitization in         IV           Indirect outcome
                        patients with                           (improved
                        aspirin-exacerbated                     respiratory
                        respiratory disease can                 symptoms)
                        improve the control of                  
                        both upper and lower                    
                        respiratory tract disease               
                        in these patients                       
                        (Solensky, 2004; Simon,                 
                        2003; Stevenson, 2003).                 

  Patients who require  Desensitization allows for III          Indirect outcome
  chemotherapy          transient tolerance to                  (needed
  medication for cancer chemotherapy medications                chemotherapy)
  or other severe       when there is no                        
  conditions and have   alternative treatment                   
  experienced a prior   (Markman et al., 2000;                  
  hypersensitivity      Robinson et al., 2001;                  
  reaction to those     Lee, Matulonis, &                       
  medications           Castells, 2004).                        

  Patients with a       Allergist-immunologists    II, III      Indirect outcome
  history of possible   are able to perform skin                (needed local
  allergic reactions to testing and graded                      anesthetic
  local anesthetics     challenge to find a safe                treatment)
                        local anesthetic for                    
                        future use. Virtually all               
                        patients with histories of              
                        reactions to local                      
                        anesthetics can                         
                        subsequently tolerate the               
                        same or an alternate agent              
                        (Gall, Kaufmann, &                      
                        Kalveram, 1996; Schatz,                 
                        1984; Macy, Schatz, &                   
                        Zeiger, 2002).                          

  HIV-infected patients Graded TM-S challenges can Ib, III      Diagnostic\
  with a history of     identify patients who are               Indirect outcome
  adverse reactions to  not currently sensitive to              (needed TM-S
  TM-S who need this    the drug and allow                      therapy)
  therapy               patients with reactions                 
                        during challenge to                     
                        subsequently tolerate the               
                        drug and safely continue                
                        therapy (Leoung et al.,                 
                        2001; Bonfanti et al.,                  
                        2000; Asar, Daneshvar, &                
                        Beall, 1994; Nguyen,                    
                        Weiss, & Wallace, 1995;                 
                        Belchi-Hernandez &                      
                        Espinosa-Parra, 1996; Rich              
                        et al., 1997; Demoly et                 
                        al., 1998).                             

  Patients with a       Allergist-immunologists    IV           Diagnostic\
  history of reactions  provide a comprehensive                 Indirect outcome
  to induction agents   plan to evaluate the                    (treatment with
  or to nonpenicillin   historical adverse drug                 needed
  antibiotics           reactions and provide                   medications)
                        suggestions on future                   
                        therapies to minimize                   
                        risks (\"Allergy and                    
                        immunology core                         
                        curriculum,\" 1996; Demoly              
                        et al., 1999; Gruchalla,                
                        2000; Macy, 2004; Vemuir,               
                        Tripathi, & Keefe, 2004;                
                        Rotskoff et al., 2004).                 
  --------------------------------------------------------------------------------

HIV = human immunodeficiency virus; NSAID = nonsteroidal
anti-inflammatory drug; TM-S = trimethoprim-sulfamethoxazole

**TABLE VIII. Food Allergy**

  -------------------------------------------------------------------------------
  **Referral Guideline**  **Rationale**             **Evidence   **Evidence
                                                    Grade**      Type**
  ----------------------- ------------------------- ------------ ----------------
  Persons who have        After allergy evaluation, II, III      Indirect outcome
  limited their diet on   an estimated one third of              (avoiding
  the basis of perceived  perceived adverse                      unnecessary diet
  adverse reactions to    reactions to foods and a               restriction)
  foods or additives      small fraction of adverse              
                          reactions to additives                 
                          are verified (Young et                 
                          al., 1994; Bock, 1987;                 
                          Sloan & Powers, 1986;                  
                          Altman & Chiaramonte,                  
                          1996; Sampson &                        
                          McCaskill, 1985; Young et              
                          al., 1987). Evaluation by              
                          an allergist-immunologist              
                          is likely to result in an              
                          individual\'s ability to               
                          liberalize his or her                  
                          diet (thereby likely                   
                          improving nutrition and                
                          quality of life).                      

  Persons with a          The                       II, III, IV  Diagnostic\
  diagnosed food allergy  allergist-immunologist                 Indirect outcome
                          can apply and interpret                (food avoidance,
                          diagnostic tests (skin                 early
                          prick tests, serum                     pharmacologic
                          food-specific IgE assays,              treatment of
                          and oral food challenges)              reaction)
                          and advise patients on                 
                          dietary avoidance and                  
                          emergency care measures                
                          (Bock, 1987; Sampson &                 
                          McCaskill, 1985;                       
                          \"Allergy and immunology               
                          core curriculum,\" 1996;               
                          Sampson, 2001). These are              
                          important aspects of care              
                          because (1) many                       
                          allergies are not                      
                          permanent and should be                
                          monitored for resolution               
                          (Bock, 1987), and (2)                  
                          avoidance of allergenic                
                          foods and action taken in              
                          the event of exposure are              
                          difficult to undertake,                
                          are prone to errors, and               
                          can be dangerous, thus                 
                          mandating proper                       
                          education (Sicherer,                   
                          Forman, & Noone, 2000;                 
                          Bock, Munoz-Furlong, &                 
                          Sampson, 2001).                        

  Atopic families with or Family history is the     Ia, II, IV   Diagnostic\
  expecting a newborn who strongest predictor of                 Indirect outcome
  are interested in       allergy. A sibling born                (prevention of
  identifying risks for   to a family who already                sensitization)
  and preventing allergy  has a child with peanut                
                          allergy has a risk for                 
                          that allergy that is more              
                          than 10 times greater                  
                          than that of the general               
                          population (Sicherer et                
                          al., 2000). Specific                   
                          guidelines are in place                
                          to approach potential                  
                          allergy in a food                      
                          allergy--prone child (eg,              
                          breast-feeding and                     
                          avoidance of allergenic                
                          foods) (American Academy               
                          of Pediatrics, Committee               
                          on Nutrition, 2000;                    
                          Muraro et al., 2004).                  
                          Meta-analyses of studies               
                          shows breast-feeding and               
                          avoidance of cow\'s                    
                          milk--soy in the first                 
                          year might reduce the                  
                          risk for allergic disease              
                          (Gdalevich et al., 2001;               
                          Osborn & Sinn, 2003). The              
                          allergist-immunologist                 
                          can evaluate the risks                 
                          and explain possible                   
                          approaches.                            

  Persons who have        The                       II, III, IV  Diagnostic\
  experienced allergic    allergist-immunologist                 Indirect outcome
  symptoms (urticaria,    can perform diagnostic                 (food avoidance)
  angioedema, itch,       tests, such as skin                    
  wheezing, and           tests, serum IgE tests,                
  gastrointestinal        and oral food challenges               
  responses) in           to determine the cause of              
  association with food   the reaction (Bock, 1987;              
  exposure                \"Allergy and immunology               
                          core curriculum,\" 1996;               
                          Sampson, 2001; Eigenmann               
                          & Sampson, 1998).                      

  Persons who experience  These symptoms are        II, III      Diagnostic\
  an itchy mouth from raw typical of pollen-food                 Indirect outcome
  fruits and vegetables   allergy syndrome, or oral              (food avoidance)
                          allergy syndrome, which                
                          can sometimes progress to              
                          or overlap with more                   
                          severe allergic reactions              
                          (Ortolani et al., 1989;                
                          Ortolani et al., 1988;                 
                          Crespo et al., 2002). The              
                          allergist-immunologist                 
                          evaluates the reactions                
                          to determine the cause                 
                          and to advise which foods              
                          to avoid, identify other               
                          potential problematic                  
                          foods, and assess risks                
                          for a severe reaction.                 

  Infants with            Food allergy might be a   II, III      Diagnostic\
  recalcitrant            cause of infantile                     Indirect outcome
  gastroesophageal reflux reflux, and evidence of                (food avoidance)
  or older individuals    food responsiveness is                 
  with recalcitrant       high (about 40%) for                   
  reflux symptoms,        children in whom symptoms              
  particularly if they    do not respond well to                 
  experience dysphagia    standard therapies                     
                          (Iacono et al., 1996).                 
                          Older individuals might                
                          have reflux symptoms and               
                          possibly dysphagia caused              
                          by eosinophilic                        
                          esophagitis, a disorder                
                          that is also commonly                  
                          food responsive                        
                          (Orenstein et al., 2000;               
                          Spergel et al., 2002).                 

  Infants with            There are a group of      II, III, IV  Diagnostic\
  gastrointestinal        food-responsive                        Indirect outcome
  symptoms, including     gastrointestinal                       (food avoidance)
  vomiting, diarrhea      disorders of infancy                   
  (particularly with      (including food                        
  blood), poor growth,    protein--induced                       
  and/or malabsorption,   enteropathy,                           
  whose symptoms are      enterocolitis, and                     
  otherwise unexplained,  proctocolitis) that can                
  not responsive to       be diagnosed, treated,                 
  medical management,     and monitored with                     
  and/or possibly food    modalities with which                  
  responsive (even if     allergist-immunologists                
  screening allergy test  are expert, including                  
  results are negative)   elimination diets and                  
                          oral food challenges                   
                          (\"Allergy and immunology              
                          core curriculum,\" 1996;               
                          Lake, Whitington, &                    
                          Hamilton, 1982; Sampson &              
                          Anderson, 2000; Sampson,               
                          Sicherer, & Birnbaum,                  
                          2001; Sicherer,                        
                          Eigenmann, & Sampson,                  
                          1998). Most of the                     
                          disorders affecting                    
                          infants cannot be                      
                          identified with simple                 
                          screening tests (Lake,                 
                          Whitington, & Hamilton,                
                          1982; Sampson & Anderson,              
                          2000; Sampson, Sicherer &              
                          Birnbaum, 2001; Sicherer,              
                          Eigenmann, & Sampson,                  
                          1998).                                 

  Persons with known      Eosinophilic              II, III      Diagnostic\
  eosinophilic            gastroenteritis,                       Indirect outcome
  inflammation of the gut esophagitis, and/or                    (food avoidance)
                          gastroenterocolitis might              
                          be food responsive                     
                          (Orenstein et al., 2000;               
                          Spergel et al., 2002).                 
                          Patients\' symptoms could              
                          improve after                          
                          identification and                     
                          elimination of causal                  
                          foods (Spergel et al.,                 
                          2002), modalities for                  
                          which the                              
                          allergist-immunologist is              
                          expert.                                
  -------------------------------------------------------------------------------

**TABLE IX. Hypersensitivity Pneumonitis (HP)**

  -------------------------------------------------------------------------------
  **Referral          **Rationale**               **Evidence   **Evidence Type**
  Guideline**                                     Grade**      
  ------------------- --------------------------- ------------ ------------------
  Early referral of   Early accurate diagnosis    III, IV      Diagnostic\
  patients with       and removal from further                 Indirect outcome
  suspected           exposure to specific                     (avoidance)
  hypersensitivity    sensitizers carries the                  
  pneumonia to avoid  best medical prognosis for               
  continued           those with HP (Weltermann                
  environmental       et al., 1998; Banaszak,                  
  exposure resulting  Thiede, & Fink, 1970;                    
  in permanent lung   Kawai, Tamura, & Murao,                  
  injury              1984; Zacharisen et al.,                 
                      1998). Allergists are                    
                      trained and experienced in               
                      environmental exposure                   
                      history, physical                        
                      examination, and clinical                
                      and laboratory diagnosis of              
                      HP (\"Allergy and                        
                      immunology core                          
                      curriculum,\" 1996).                     

  Diagnostic          Histologic diagnosis of HP  IV           Diagnostic\
  consultation in     varies from the acute                    Indirect outcome
  patients found to   stage, subacute stage, and               (avoidance and
  have NSIP           chronic form. Findings of                corticosteroids)
                      NSIP should initiate the                 
                      diagnostic consideration of              
                      HP because avoidance of the              
                      offending antigen and                    
                      pharmacologic therapy might              
                      result in resolution of the              
                      disease or stop the                      
                      progression of disease                   
                      (American Thoracic Society,              
                      2001).                                   

  Patients with known Allergist-immunologists are III, IV      Indirect outcome
  HP for management   specifically trained to                  (avoidance and
                      evaluate environmental                   corticosteroids)
                      exposures, evaluate                      
                      immunologic results, and                 
                      treat and follow HP,                     
                      including oral                           
                      corticosteroid treatment                 
                      (\"Allergy and immunology                
                      core curriculum,\" 1996;                 
                      Tripathi & Grammer, 2001;                
                      Bernstein et al., \"Machine              
                      Operator\'s lung\", 1995;                
                      Dykewicz et al.; 1988; Malo              
                      & Zeiss, 1982; Vandenplas                
                      et al., 1993; Baur, 1995).               
  -------------------------------------------------------------------------------

NSIP = nonspecific interstitial pneumonia

**TABLE X. Insect Hypersensitivity**

  -----------------------------------------------------------------------------
  **Referral            **Rationale**             **Evidence   **Evidence
  Guideline**                                     Grade**      Type**
  --------------------- ------------------------- ------------ ----------------
  Consider referral of  Up to 3% of the           II, III, IV  Diagnostic\
  patients with         population is at risk for              Indirect outcome
  systemic reactions    anaphylaxis to insect                  (avoidance,
  suspected or possibly stings, with                           early
  caused by insect      approximately 40                       pharmacologic
  stings for accurate   documented deaths                      treatment of
  identification of     annually (Chafee, 1970;                reaction,
  specific allergen and Settipane & Boyd, 1970;                immunotherapy)
  consideration for     Antonicelli, Beatrice                  
  venom immunotherapy   Bilo, & Bonifazi, 2002;                
  (or whole-body        Golden, 1989; Charpin,                 
  extract in case of    Birnbaum, & Vervloet,                  
  fire ant)             1994; Barnard, 1973;                   
                        DeShazo, Butcher, &                    
                        Banks, 1990; Freeman et                
                        al., 1992).                            

                        Patient identification of              
                        the specific insect                    
                        species causing an                     
                        allergic reaction is                   
                        frequently incorrect.                  

                        Allergy testing and       II, III, IV  
                        history-test correlation               
                        can more accurately                    
                        identify specific insects              
                        responsible for an                     
                        allergic reaction and can              
                        be helpful in diagnosis,               
                        treatment, and avoidance               
                        recommendations (DeShazo,              
                        Butcher, & Banks, 1990;                
                        Hunt et al., 1976; Rueff               
                        et al., 1996; Georgitis &              
                        Reisman, 1985; Golden et               
                        al., 1997; Golden et al.,              
                        2001; Moffitt, Barker, &               
                        Stafford, 1997; Oude                   
                        Elberink & Dubois, 2003;               
                        Reisman, 1994; Portnoy et              
                        al., 1999; Moffitt et                  
                        al., 2004).                            

                        Skin testing is generally II, IIII, IV 
                        preferred over in vitro                
                        testing for the initial                
                        evaluation of                          
                        venom-specific IgE                     
                        antibodies (Golden, 1989;              
                        Charpin, Birnbaum, &                   
                        Vervloet, 1994; Golden,                
                        2001; Oude, 2003; Portnoy              
                        et al., 1999; Moffitt et               
                        al., 2004; Valentine,                  
                        1993; Valentine, 1984;                 
                        Schwartz et al., 1981).                

                        Venom immunotherapy (or   Ib, II, III, 
                        fire ant whole-body       IV           
                        extract) greatly reduces               
                        the risk of systemic                   
                        reactions in stinging                  
                        insect--sensitive                      
                        patients (Settipane &                  
                        Boyd, 1970; Antonicelli,               
                        Beatrice Bilo, &                       
                        Bonifazi, 2002; Charpin,               
                        Birnbaum, & Vervloet,                  
                        1994; Feeman et al.,                   
                        1992; Oude Elberink &                  
                        Dubois, 2003; Hunt et                  
                        al., 1978; Triplett,                   
                        1973; Valentine,                       
                        Schuberth, &                           
                        Kagey-Sobotka, 1990).                  

                        Venom immunotherapy can   III, IV      
                        prevent death caused by                
                        subsequent stings in                   
                        hypersensitive patients                
                        (Antonicelli, Beatrice                 
                        Bilo, & Bonifazi, 2002;                
                        Charpin, Birnbaum, &                   
                        Vervloet, 1994; Oude                   
                        Elberink & Dubois, 2003;               
                        Sasvary & Muller, 1994).               

  Consider referral of  Biting insects, such as   II, III, IV  Diagnostic\
  patients with         *Triatoma* species and                 Indirect outcome
  systemic reactions    mosquitoes, have been                  (avoidance,
  suspected or possibly identified as a cause of               appropriate
  caused by biting      systemic reactions                     pharmacologic
  insects for accurate  (Feingold & Benjamin,                  therapy)
  identification of     1961; Hoffman, 2003;                   
  specific allergen     McCormack et al., 1995;                
                        Rohr, Marshall, & Saxon,               
                        1984; Simons & Peng,                   
                        2003.)                                 

                        RASTs and skin tests to   III, IV      
                        *Triatoma* species                     
                        salivary gland extracts                
                        and whole-body extracts                
                        of other biting insects                
                        have been used to                      
                        identify antigen-specific              
                        IgE in sera of                         
                        hypersensitive patients                
                        (Gauci et al., 1990;                   
                        Hoffman, 2004; Peng et                 
                        al., 1998; Peng, Yang, &               
                        Simons, 1995; Pinnas,                  
                        Chen, & Hoffman, 1978;                 
                        Reunala et al.,                        
                        \"Frequent occurrence of               
                        IgE\", 1994; Reunala et                
                        al., \"Passive transfer                
                        of cutaneous\", 1994,                  
                        Shan et al., 1995;                     
                        Trudeau et al., 1993; Van              
                        Wye et al., 1991).                     

                        Patient education by an   II, III, IV  
                        allergist-immunologist,                
                        including the cause of                 
                        the allergy, specific                  
                        avoidance measures,                    
                        recognition and treatment              
                        of anaphylaxis, and                    
                        management of local side               
                        effects, might reduce                  
                        patient anxiety and                    
                        potentially reduce                     
                        morbidity from future                  
                        bites (Feingold &                      
                        Benjamin, 1961; Hoffman,               
                        2003; McCormack et al.,                
                        1995; Rohr, Marshall, &                
                        Saxon, 1984; Simons &                  
                        Peng, 2003).                           

  Consider referral of  Regular review of         IV           Indirect outcome
  patients receiving    interval history,                      (avoidance,
  venom (or fire ant    immunotherapy dosing                   early
  whole-body extract)   schedule, and adverse                  pharmacologic
  immunotherapy         events can contribute to               therapy,
  annually for review   reduced complications of               immunotherapy)
  of interval history,  treatment (Portnoy et                  
  tolerance of          al., 1999; Moffitt et                  
  immunotherapy, need   al., 2004).                            
  for repeat testing,                                          
  and need for                                                 
  continued therapy                                            

                        Regular review might      II, III, IV  
                        identify new                           
                        comorbidities or                       
                        medications that increase              
                        the risk of poor outcomes              
                        from natural stings or                 
                        insect immunotherapy                   
                        reactions (Portnoy et                  
                        al., 1999; Moffitt et                  
                        al., 2004; Hepner et al.,              
                        1990; Hermann & Ring,                  
                        1997; Simon, Potier, &                 
                        Thebaud, 1996; Toogood,                
                        1988).                                 

                        Assessment of reactions   II, III, IV  
                        to interval stings can be              
                        used to monitor the                    
                        effectiveness of                       
                        immunotherapy and might                
                        be cause for                           
                        consideration of changes               
                        in dose and schedule                   
                        (Portnoy et al., 1999;                 
                        Moffitt et al., 2004;                  
                        Golden et al., 1981;                   
                        Rueff, Wenderoth, &                    
                        Przybilla, 2001; Tracy et              
                        al, 1995; Reisman &                    
                        Livingston, 1992).                     

                        The interval between      II, III, IV  
                        maintenance dose                       
                        injections can be                      
                        increased to 4-week                    
                        intervals during the                   
                        first year of                          
                        immunotherapy and                      
                        eventually to every 6-12               
                        weeks in some patients                 
                        (Portnoy et al., 1999;                 
                        Moffitt et al., 2004;                  
                        Reisman & Livingston,                  
                        1992; Goldberg &                       
                        Confino-Cohen, 2001).                  

                        Many patients can safely  II, III, IV  
                        discontinue venom                      
                        immunotherapy after at                 
                        least 3-5 years of                     
                        treatment, although some               
                        patients might need to                 
                        continue immunotherapy                 
                        indefinitely. An                       
                        allergist-immunologist                 
                        with experience in                     
                        treating patients with                 
                        insect venom allergy is                
                        best suited to facilitate              
                        individualized patient                 
                        decisions (Portnoy                     
                        et.al., 1999; Moffitt et               
                        al., 2004; Golden et al.,              
                        1981; Golden,                          
                        Kwiterovich, &                         
                        Kagey-Sobotka, 1996;                   
                        Golden, Kagey-Sobotka, &               
                        Lichtenstein, 2000;                    
                        Golden et al., 1998;                   
                        \"The discontinuation of               
                        Hymenoptera,\" 1998;                   
                        Hauguaard, Norregard, &                
                        Dahl, 1991; Keating et                 
                        al., 1991; Lerch &                     
                        Muller, 1998; Light,                   
                        2001; Muller, Berchrold,               
                        & Helbring, 1991; \"The                
                        diagnosis and management               
                        of anaphylaxis,\" 1998;                
                        Reisman, 1993; Ross,                   
                        Nelson, & Finegold,                    
                        \"Effectiveness of                     
                        specific immunotherapy in              
                        the treatment of                       
                        hymenoptera venom,\"                   
                        2000).                                 
  -----------------------------------------------------------------------------

RAST = radioallergosorbent test

**TABLE XI. Occupational Allergic Diseases**

  ------------------------------------------------------------------------------
  **Referral Guideline**    **Rationale**             **Evidence   **Evidence
                                                      Grade**      Type**
  ------------------------- ------------------------- ------------ -------------
  Workers (1) who           Workers with congenital   III, IV      Diagnostic
  anticipate being exposed  urogenital tract                       Indirect
  to an agent or agents to  abnormalities, patients                outcome
  which they are at risk of with spina bifida, health              (avoidance)
  allergy development or    care workers, and rubber               
  (2) who are presently     workers have a very high               
  being exposed to and are  prevalence of latex                    
  at risk for an allergic   allergy (Yassin et al.,                
  reaction to an agent,     1992; Liss et al., 1997;               
  including rhinitis,       Wartenberg & Buckler,                  
  conjunctivitis, asthma or 2001; Rueff et al., 2001;              
  eczema, should be         Tarlo et al., 2001).                   
  referred to an                                                   
  allergist-immunologist                                           
  for assessment to                                                
  determine whether the                                            
  worker might be                                                  
  susceptible to rhinitis,                                         
  asthma, dermatitis,                                              
  urticaria, or anaphylaxis                                        
  from the exposure. An                                            
  example is a worker who                                          
  will be exposed to latex                                         
  and has spina bifida,                                            
  congenital urogenital                                            
  tract abnormalities, or a                                        
  worker with a past                                               
  history suggestive of                                            
  latex allergy.                                                   

                            Workers with an allergy   III          
                            who might not be able to               
                            prevent exposure or are                
                            prone to accidental                    
                            exposure should be                     
                            educated on                            
                            self-treatment of asthma,              
                            rhinitis, urticaria,                   
                            eczema, and anaphylaxis                
                            and have appropriate                   
                            medications to use to                  
                            control symptoms and                   
                            signs. Specifically, if                
                            the patient has a history              
                            of anaphylaxis,                        
                            prescribing and educating              
                            the patient on the proper              
                            use of an EpiPen or                    
                            similar device for                     
                            self-administration of                 
                            epinephrine might be life              
                            saving.                                
                            Allergist-immunologists                
                            are specifically trained               
                            to educate patients                    
                            regarding self-treatment               
                            of such reactions                      
                            (Hamilton & Adkinson,                  
                            1998).                                 

  Workers in whom the cause Skin testing and RAST     IV           Diagnostic
  of occupationally induced testing often can                      Indirect
  lung disease, including   identify the cause of a                outcome
  asthma or                 hypersensitivity reaction              (avoidance)
  hypersensitivity          (\"Allergy and immunology              
  pneumonitis, skin         core curriculum,\" 1996).              
  disease, or upper                                                
  respiratory disease, such                                        
  as rhinitis or                                                   
  conjunctivitis, is unable                                        
  to be determined on the                                          
  basis of history alone,                                          
  or objective evidence is                                         
  necessary to confirm                                             
  cause and effect between                                         
  exposure and disease.                                            

                            Continued exposure to an  III          
                            allergen might result in               
                            progressive lung volume                
                            loss, which could be                   
                            irreversible (Perfetti et              
                            al., 1998).                            

                            In most cases avoidance   III          
                            of the identified agent                
                            is the optimal treatment               
                            for occupational diseases              
                            (Vedal et al., 1986).                  

                            Correlation of the        III, IV      
                            history with the results               
                            of IgE testing helps                   
                            prevent inappropriate                  
                            avoidance, which might be              
                            suggested by RASTs alone               
                            (Bernstein et al., 1999;               
                            Chan-Yeung & Malo, 1995).              
                            In cases in which the                  
                            cause cannot be isolated               
                            adequately on the basis                
                            of history, skin tests,                
                            or RASTs, inhalation                   
                            challenge, which is the                
                            gold standard, can be                  
                            arranged to provide                    
                            objective evidence of a                
                            hypersensitivity reaction              
                            (Vandenplas & Malo,                    
                            1997).                                 

  Workers with              Workers with              III          Diagnostic\
  occupationally induced    rhinoconjunctivitis are                Indirect
  rhinoconjunctivitis       at an increased risk of                outcome
                            asthma. Early avoidance                (avoidance)
                            might decrease the risk                
                            of further respiratory                 
                            disease (Malo et al.,                  
                            1997). By means of                     
                            history, skin tests,                   
                            and/or RASTs and                       
                            correlating the history                
                            and objective findings,                
                            the causative agent can                
                            often be identified,                   
                            allowing appropriate                   
                            avoidance and preventing               
                            possible loss of                       
                            occupation or serious                  
                            lung disease (Rodier et                
                            al., 2003). Prognosis of               
                            occupationally induced                 
                            respiratory disease is                 
                            dependent on the extent                
                            and duration of exposure               
                            (Nguyen et al., 2003).                 

  Referral to an            On the basis of history   III, IV      Indirect
  allergist-immunologist    and relevant studies,                  outcome
  for career counseling     allergist-immunologists                (avoidance)
  should be considered for  can assess the future                  
  adolescents with allergic relative risks of such                 
  disease who might be      patients in the workplace              
  considering careers with  (\"Allergy and immunology              
  exposure to animals or    core curriculum,\" 1996;               
  other allergens.          Sjostedt & Willers,                    
                            1989). These individuals               
                            can then be aware of any               
                            degree of increased risk               
                            of sensitization and be                
                            able to modify career                  
                            plans with suitable                    
                            advice.                                

  Workers in occupations    Upper respiratory and     III          Diagnostic\
  with animal exposure who  lower respiratory tract,               Indirect
  experience rash, upper    skin, and eye symptoms                 outcome
  respiratory tract         might be due to allergic               (avoidance)
  symptoms, eye symptoms,   sensitization to the                   
  or lung symptoms          animals. Allergy testing               
                            can confirm sensitization              
                            and lead to appropriate                
                            interventions (Sjostedt &              
                            Willers, 1989).                        

  Persons with occupational Occupational disease      III, IV      Diagnostic\
  exposure to food proteins might be related to                    Indirect
  and chronic skin          exposure to food                       outcome
  symptoms, respiratory     proteins, such as wheat                (avoidance)
  symptoms, or both,        (\'\'Baker\'s\'\'                      
  attributable to the work  asthma), or food handling              
  environment               (contact urticaria,                    
                            contact dermatitis) that               
                            is diagnosed through                   
                            modalities available to                
                            the                                    
                            allergist-immunologist                 
                            (\"Allergy and immunology              
                            core curriculum,\" 1996).              
                            Avoidance is the                       
                            treatment of choice                    
                            (Carmona et al., 1992;                 
                            Thiel & Ulmer, 1980).                  
  ------------------------------------------------------------------------------

**TABLE XII. Primary Immune Deficiency**

+-------------------+----------------------------+-------+-----------+
| **Referral        | **Rationale**              | **Evi | *         |
| Guideline**       |                            | dence | *Evidence |
|                   |                            | Gr    | Type**    |
|                   |                            | ade** |           |
+===================+============================+=======+===========+
| Any of the        | Frequent infection,        | III,  | D         |
| following warning | unusual infections, or     | IV    | iagnostic |
| signs:            | unusual complications of   |       |           |
|                   | usual infections are the   |       |           |
| -   8 or more new | most frequent presentation |       |           |
|     infections    | of immune deficiency       |       |           |
|     within 1 year | (Bonilla et al., 2005;     |       |           |
|                   | Ballow, 2002; Buckley,     |       |           |
| -   2 or more     | 2002; \"Primary            |       |           |
|     serious sinus | immunodeficiency           |       |           |
|     infections    | diseases,\" 1999;          |       |           |
|     within 1 year | Amaiz-Villena et al.,      |       |           |
|                   | 1995; Champi, 2002;        |       |           |
| -   2 or more     | Fleisher, 1996). Advanced  |       |           |
|     months on     | diagnostic strategies are  |       |           |
|     antibiotics   | necessary to ensure        |       |           |
|     with little   | appropriate diagnosis and  |       |           |
|     or no effect  | treatment (Bonilla et al., |       |           |
|                   | 2005; Champi, 2002;        |       |           |
| -   2 or more     | Fleisher, 1996; Wasserman  |       |           |
|     pneumonias    | & Sorensen, 1999).         |       |           |
|     within 1 year | Allergist-immunologists    |       |           |
|                   | are trained to diagnose    |       |           |
| -   failure of an | and treat primary          |       |           |
|     infant to     | immunodeficiency           |       |           |
|     gain weight   | (\"Allergy and immunology  |       |           |
|     or grow       | core curriculum,\" 1996).  |       |           |
|     normally      |                            |       |           |
|                   |                            |       |           |
| -   recurrent     |                            |       |           |
|     deep skin or  |                            |       |           |
|     organ         |                            |       |           |
|     abscesses     |                            |       |           |
|                   |                            |       |           |
| -   persistent    |                            |       |           |
|     thrush in the |                            |       |           |
|     mouth or      |                            |       |           |
|     elsewhere on  |                            |       |           |
|     skin after    |                            |       |           |
|     age 1 year    |                            |       |           |
|                   |                            |       |           |
| -   need for      |                            |       |           |
|     intravenous   |                            |       |           |
|     antibiotics   |                            |       |           |
|     to clear      |                            |       |           |
|     infections    |                            |       |           |
|                   |                            |       |           |
| -   2 or more     |                            |       |           |
|     deep-seated   |                            |       |           |
|     infections    |                            |       |           |
|                   |                            |       |           |
| -   a family      |                            |       |           |
|     history of    |                            |       |           |
|     immune        |                            |       |           |
|     deficiency    |                            |       |           |
+-------------------+----------------------------+-------+-----------+
|                   | Immunologic therapy        | Ib,   | Indirect  |
|                   | improves immunity          | II,   | outcome   |
|                   | (Hershfield, 1995;         | III,  | (im       |
|                   | Cunningham-Rundles et al., | IV    | munologic |
|                   | 2001), reduces infections  |       | therapy)  |
|                   | (Nydahl-Persson,           |       |           |
|                   | Petterson, & Fasth, 1995;  |       |           |
|                   | Gallin et al., 2003;       |       |           |
|                   | Busse, Razvi, &            |       |           |
|                   | Cunningham-Rundles, 2002), |       |           |
|                   | improves organ function    |       |           |
|                   | (de Gracia et al., 2004),  |       |           |
|                   | prevents complications     |       |           |
|                   | (Bonilla et al., 2005),    |       |           |
|                   | improves quality of life   |       |           |
|                   | (Gardulf et al., 2004),    |       |           |
|                   | and might be curative      |       |           |
|                   | (Horwitz et al., 2001,     |       |           |
|                   | Buckley et al., 1999) in   |       |           |
|                   | patients with primary      |       |           |
|                   | immune deficiencies.       |       |           |
+-------------------+----------------------------+-------+-----------+

**TABLE XIII, A. Rhinitis**

  ---------------------------------------------------------------------------------
  **Referral Guideline**   **Rationale**             **Evidence   **Evidence Type**
                                                     Grade**      
  ------------------------ ------------------------- ------------ -----------------
  Patients with prolonged  Allergist-immunologist    III          Direct outcome
  or severe manifestations care for rhinitis is                   
  of rhinitis with         associated with improved               
  comorbid conditions (eg, quality of life,                       
  asthma or recurrent      compliance, and                        
  sinusitis); with         satisfaction with care                 
  symptoms interfering     (Demoly et al., 2002;                  
  with quality of life,    Bagenstose & Bernstein,                
  ability to function, or  1999).                                 
  both; or who have found                                         
  medications to be                                               
  ineffective or have had                                         
  adverse reactions to                                            
  medications (Dykewicz et                                        
  al., 1998; \"Allergen                                           
  immunotherapy,\" 2003;                                          
  Bousquet, van                                                   
  Cauwenberge, & Khaltaev,                                        
  2001)                                                           

                           Allergy cannot be         III, IV      Diagnostic
                           diagnosed on the basis of              
                           history alone (Williams                
                           et al., 2003).                         
                           Allergist-immunologists                
                           are highly trained to                  
                           interpret the clinical                 
                           history and allergy                    
                           diagnostic test results                
                           in both upper and lower                
                           airway conditions                      
                           (\"Allergy and immunology              
                           core curriculum,\" 1996).              

                           Allergist-immunologists   IV           Indirect outcome
                           have familiarity with the              (avoidance)
                           wide variety of both                   
                           indoor and outdoor                     
                           aeroallergen exposures                 
                           that have been shown to                
                           affect the upper                       
                           respiratory tree and have              
                           the expertise to provide               
                           avoidance education                    
                           (\"Allergy and immunology              
                           core curriculum,\" 1996).              

                           Allergen immunotherapy    Ib, IV       Indirect outcome
                           can be highly effective                (immunotherapy)
                           in controlling the                     
                           symptoms of allergic                   
                           rhinitis (Bousquet,                    
                           Lockey, & Malling, 1998).              
                           Allergen immunotherapy                 
                           might provide lasting                  
                           benefits after                         
                           immunotherapy is                       
                           discontinued (Durham et                
                           al., 1999).                            

  Patients with nasal      Allergist-immunologists   IV           Indirect outcome
  polyps                   are specifically trained               (pharmacologic
                           and experienced in the                 therapy)
                           medical management of                  
                           nasal polyps, including                
                           intranasal steroids, oral              
                           steroids, and treatment                
                           of complicating sinusitis              
                           (Dykewicz et al., 1998;                
                           \"Allergy and immunology               
                           core curriculum,\" 1996).              

  In addition to the above Allergen immunotherapy    Ib           Indirect outcome
  guidelines, consider     has been shown to reduce               (immunotherapy)
  referral of the child    development of new                     
  with allergic rhinitis   sensitizations and asthma              
  because of the potential in children with allergic              
  preventive role of       rhinitis compared with                 
  allergen immunotherapy   children with allergic                 
  in progression of        rhinitis treated with                  
  allergic disease.        medication alone (Moller               
                           et al., 2002).                         
  ---------------------------------------------------------------------------------

**TABLE XIII, B. Sinusitis**

  --------------------------------------------------------------------------------
  **Referral       **Rationale**                  **Evidence   **Evidence Type**
  Guideline**                                     Grade**      
  ---------------- ------------------------------ ------------ -------------------
  Patients with    This set of conditions related III, IV      Direct outcome
  chronic          to chronic inflammation of the              
  rhinosinusitis   sinus and contiguous nasal                  
  of any type      mucosa often coexists with                  
                   allergic rhinitis (Steinke &                
                   Borish, 2004).                              
                   Allergist-immunologist care is              
                   associated with improved                    
                   outcomes (McNally, White, &                 
                   Kaliner, 1997).                             

                   Allergy immunotherapy is       III          Indirect outcome
                   demonstrated to improve                     (immunotherapy)
                   outcomes in patients with                   
                   concomitant allergic rhinitis               
                   (Nathan et al., 2004).                      

  Patients with    Many patients with this        IV           Diagnostic\
  chronic or       condition have humoral                      Indirect outcome
  recurrent        immunodeficiency, cystic                    (avoidance,
  Infectious       fibrosis, fungal sinusitis, or              pharmacologic, and
  rhinosinusitis   granulomatous diseases                      immunologic
                   (Steinke & Borish, 2004).                   therapy)
                   Allergist-immunologists are                 
                   trained in the evaluation and               
                   management of these disorders               
                   (\"Allergy and immunology core              
                   curriculum,\" 1996).                        

  Patients with    This is a chronic inflammatory IV           Diagnostic\
  chronic          disease with characteristics                Indirect outcome
  eosinophilic     of allergic inflammation                    (avoidance,
  rhinosinusitis   (Steinke & Borish, 2004). It                pharmacologic, and
                   often coexists with aspirin                 immunologic
                   sensitivity, asthma, and                    therapy)
                   sinus-nasal polyposis Borish,               
                   2002; Szczeklik & Stevenson,                
                   2003). Allergist-immunologists              
                   are experts in allergic                     
                   inflammation and can evaluate               
                   and treat both environmental                
                   allergy and aspirin                         
                   sensitivity (\"Allergy and                  
                   immunology core curriculum,\"               
                   1996).                                      

  Patients with    This is a chronic inflammatory III, IV      Diagnostic\
  allergic fungal  disease with characteristics                Indirect outcome
  rhinosinusitis   of IgE and eosinophilic                     (pharmacotherapy,
                   inflammatory response to fungi              immunotherapy)
                   in sinuses (Schubert, 2004;                 
                   Schubert, & Goetz,                          
                   \"Evaluation and treatment of               
                   allergic fungal sinusitis.                  
                   I.\", 1998). Evaluation                     
                   involves allergy skin testing               
                   and other laboratory testing                
                   (Schubert & Goetz,                          
                   \"Evaluation and treatment of               
                   allergic fungal sinusitis.                  
                   II,\" 1998). Management                     
                   involves medical management,                
                   allergen immunotherapy, and                 
                   surgery (Schubert & Goetz,                  
                   \"Evaluation and treatment of               
                   allergic fungal sinusitis.                  
                   II,\" 1998; Mabry et al.,                   
                   1998). Allergist-immunologists              
                   are experts in the evaluation               
                   and management of allergic                  
                   diseases, including allergy                 
                   immunotherapy (\"Allergy and                
                   immunology core curriculum,\"               
                   1996).                                      
  --------------------------------------------------------------------------------

**TABLE XIV. Urticaria and Angioedema** (see also \"Anaphylaxis\"
\[Table II\]), \"Drug Allergy\" \[Table VII\], and \"Food Allergy\"
\[Table VIII\])

+--------------------+-----------------------+-------+----------------+
| **Referral         | **Rationale**         | **Evi | **Evidence     |
| Guideline**        |                       | dence | Type**         |
|                    |                       | Gr    |                |
|                    |                       | ade** |                |
+====================+=======================+=======+================+
| Patients with      | After a severe        | IV    | Diagnostic     |
| acute urticaria or | allergic reaction     |       |                |
| angioedema without | without a known       |       |                |
| an obvious or      | cause, a trigger      |       |                |
| previously defined | should be identified, |       |                |
| trigger            | if at all possible    |       |                |
|                    | (\"The diagnosis and  |       |                |
|                    | management of         |       |                |
|                    | urticaria,\" 2000).   |       |                |
|                    | An                    |       |                |
|                    | a                     |       |                |
|                    | llergist-immunologist |       |                |
|                    | is the most           |       |                |
|                    | appropriate medical   |       |                |
|                    | professional to       |       |                |
|                    | perform this          |       |                |
|                    | evaluation (\"Allergy |       |                |
|                    | and immunology core   |       |                |
|                    | curriculum,\" 1996),  |       |                |
|                    | which might include a |       |                |
|                    | detailed history,     |       |                |
|                    | physical examination, |       |                |
|                    | skin testing, *in     |       |                |
|                    | vitro* testing, and   |       |                |
|                    | challenges when       |       |                |
|                    | indicated.            |       |                |
+--------------------+-----------------------+-------+----------------+
|                    | Future avoidance of   |       | Indirect       |
|                    | the identified        |       | outcome        |
|                    | triggers should       |       | (avoidance)    |
|                    | prevent subsequent    |       |                |
|                    | anaphylactic          |       |                |
|                    | episodes.             |       |                |
+--------------------+-----------------------+-------+----------------+
| Patients with      | See \"Food Allergy\"  |       | Diagnostic\    |
| acute urticaria or | (Table VIII) and      |       | Indirect       |
| angioedema caused  | \"Drug Allergy\"      |       | outcome        |
| by a presumed food | (Table VII)           |       | (avoidance)    |
| or drug with need  |                       |       |                |
| for diagnostic     |                       |       |                |
| confirmation or    |                       |       |                |
| assistance with    |                       |       |                |
| avoidance          |                       |       |                |
| procedures         |                       |       |                |
+--------------------+-----------------------+-------+----------------+
| Patients with      | Allergists and        | Ib,   | Diagnostic\    |
| chronic urticaria  | dermatologists have   | III,  | Indirect       |
| or angioedema (ie, | more expertise in     | IV    | outcome        |
| those with lesions | caring for patients   |       | (avoidance,    |
| recurring          | with urticaria than   |       | ph             |
| persistently over  | other specialists     |       | armacotherapy) |
| a period of 6      | (Henderson,           |       |                |
| weeks or more)     | Fleischer, & Feldman, |       |                |
|                    | 2000). Chronic        |       |                |
|                    | urticaria often has   |       |                |
|                    | an autoimmune         |       |                |
|                    | pathogenesis (Kaplan, |       |                |
|                    | 2004). Consultation   |       |                |
|                    | with an               |       |                |
|                    | a                     |       |                |
|                    | llergist-immunologist |       |                |
|                    | would include (1)     |       |                |
|                    | reviewing possible    |       |                |
|                    | causative factors     |       |                |
|                    | (medications,         |       |                |
|                    | supplements, dietary  |       |                |
|                    | factors, animal       |       |                |
|                    | exposures, and        |       |                |
|                    | physical factors),    |       |                |
|                    | (2) possible skin     |       |                |
|                    | testing, (3) possible |       |                |
|                    | physical challenges,  |       |                |
|                    | (4) recommended       |       |                |
|                    | changes in ingestants |       |                |
|                    | or contactants, and   |       |                |
|                    | (5) optimal           |       |                |
|                    | pharmacotherapy       |       |                |
|                    | (\"The diagnosis and  |       |                |
|                    | management of         |       |                |
|                    | urticaria,\" 2000;    |       |                |
|                    | \"Allergy and         |       |                |
|                    | immunology core       |       |                |
|                    | curriculum,\" 1996;   |       |                |
|                    | Henderson, Fleischer, |       |                |
|                    | & Feldman, 2000;      |       |                |
|                    | Kaplan, 2004; Dibbern |       |                |
|                    | & Dreskin, 2004; Finn |       |                |
|                    | et al., 1999; Kalivas |       |                |
|                    | et al., 1990; Greene, |       |                |
|                    | Reed, & Schroeter,    |       |                |
|                    | 1985).                |       |                |
|                    | Allergy-immunology    |       |                |
|                    | specialists are also  |       |                |
|                    | knowledgeable of the  |       |                |
|                    | minimal benefit of    |       |                |
|                    | multiple laboratory   |       |                |
|                    | tests in urticaria    |       |                |
|                    | with an otherwise     |       |                |
|                    | normal examination    |       |                |
|                    | (\"The diagnosis and  |       |                |
|                    | management of         |       |                |
|                    | urticaria,\" 2000;    |       |                |
|                    | \"Allergy and         |       |                |
|                    | immunology core       |       |                |
|                    | curriculum,\" 1996;   |       |                |
|                    | Henderson, Fleischer, |       |                |
|                    | & Feldman, 2000).     |       |                |
+--------------------+-----------------------+-------+----------------+
| Patients who might | A                     | III,  | Diagnostic\    |
| have urticarial    | llergist-immunologist | IV    | Indirect       |
| vasculitis or      | training and          |       | outcome        |
| urticaria with     | expertise should      |       | (avoidance,    |
| systemic disease   | allow appropriate     |       | ph             |
| (vasculidities,    | differential          |       | armacotherapy) |
| connective tissue  | diagnosis,            |       |                |
| disease, rarely    | determination of the  |       |                |
| malignancies):     | need for biopsy,      |       |                |
|                    | elimination of a      |       |                |
| a.  Lesions last   | specific inciting     |       |                |
|     more than 24   | agent, and optimal    |       |                |
|     hours; leave   | pharmacotherapy       |       |                |
|     ecchymotic,    | (\"Allergy and        |       |                |
|     purpuric, or   | immunology core       |       |                |
|     hyperpigmented | curriculum,\" 1996;   |       |                |
|     residua on or  | Dibbern & Dreskin,    |       |                |
|     under the      | 2004; Davis & Brewer, |       |                |
|     skin; or are   | 2004; Mehregan, Hall, |       |                |
|     associated     | & Gibson, 1992).      |       |                |
|     with pain or   |                       |       |                |
|     burning        |                       |       |                |
|                    |                       |       |                |
| b.  Patients who   |                       |       |                |
|     have typical   |                       |       |                |
|     ur             |                       |       |                |
| ticaria-angioedema |                       |       |                |
|     but have signs |                       |       |                |
|     and symptoms   |                       |       |                |
|     suggestive of  |                       |       |                |
|     systemic       |                       |       |                |
|     illness        |                       |       |                |
|                    |                       |       |                |
| c.  Patients whose |                       |       |                |
|     symptom        |                       |       |                |
|     control        |                       |       |                |
|     requires       |                       |       |                |
|     regular        |                       |       |                |
|     steroid use    |                       |       |                |
+--------------------+-----------------------+-------+----------------+
| Patients with      | Such patients might   | Ib,   | Diagnostic\    |
| chronically        | have hereditary or    | III,  | Indirect       |
| recurring          | acquired angioedema,  | IV    | outcome        |
| angioedema without | paraproteinemia, or   |       | (ph            |
| urticaria          | B-cell malignancies.  |       | armacotherapy) |
|                    | A                     |       |                |
|                    | llergist-immunologist |       |                |
|                    | expertise should      |       |                |
|                    | allow optimal         |       |                |
|                    | differential          |       |                |
|                    | diagnosis,            |       |                |
|                    | determination of the  |       |                |
|                    | need for              |       |                |
|                    | hematology-oncology   |       |                |
|                    | evaluation, and       |       |                |
|                    | pharmacologic therapy |       |                |
|                    | of hereditary or      |       |                |
|                    | acquired angioedema   |       |                |
|                    | caused by C1 esterase |       |                |
|                    | inhibitor deficiency  |       |                |
|                    | (Cicardi et al.,      |       |                |
|                    | 2003; Agostoni et     |       |                |
|                    | al., 2004; Gelfand et |       |                |
|                    | al., 1976).           |       |                |
+--------------------+-----------------------+-------+----------------+
| Patients with      | Al                    | IV    | Diagnostic\    |
| suspected or       | lergist-immunologists |       | Indirect       |
| proved cutaneous   | are trained to        |       | outcome        |
| or systemic        | diagnose and treat    |       | (ph            |
| mastocytosis       | this disease          |       | armacotherapy) |
|                    | (\"Allergy and        |       |                |
|                    | immunology core       |       |                |
|                    | curriculum,\" 1996;   |       |                |
|                    | Brockow, 2004; Akin & |       |                |
|                    | Metcalf, 2004; Valent |       |                |
|                    | et al., 2004).        |       |                |
+--------------------+-----------------------+-------+----------------+

**[Definitions]{.underline}**:

The evidence cited is graded according to the following system:

-   Ia. Meta-analysis of randomized controlled trials

-   Ib. Randomized controlled trial

-   II\. Nonrandomized, controlled intervention study

-   III\. Observational cohort or case-control study

-   IV\. Review article, expert opinion

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### REFERENCES SUPPORTING THE RECOMMENDATIONS

[References open in a new
window](http://www.guideline.gov/summary/select_ref.aspx?doc_id=9334)

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence supporting each referral guideline is specifically
stated and graded (see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

For many patients with asthma and allergic diseases, working with an
allergist-immunologist can assist them in managing their disease and
preventing morbidity and mortality.

#### POTENTIAL HARMS

Not stated

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   The consultation and referral guidelines were based on evidence that
    allergist-immunologist care improves patient outcomes. This was
    either direct evidence that outcomes improved with
    allergist-immunologist care or evidence that diagnostic or
    therapeutic interventions performed by allergist-immunologists
    improved outcomes. Because there has been a paucity of controlled
    intervention trials addressing this issue, the evidence is often
    observational. Some of the rationale statements are only supported
    by consensus or expert opinion. The Academy believes that trying to
    provide a rationale for each guideline and citing the best available
    evidence is a step forward in creating rational, useful, and
    evidence-based guidelines for consultation and referral.

-   Although some patients will require ongoing allergist-immunologist
    management, others might require just a single or a limited number
    of consultations. Still others might benefit from coordinated
    primary care and allergist-immunologist follow-up (co-management).

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

The American Academy of Allergy, Asthma, and Immunology has promoted the
availability of these guidelines to primary care providers through their
professional associations and journals. In addition, they have made
these guidelines available to managed care organizations through
America\'s Health Insurance Plans.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

American Academy of Allergy, Asthma & Immunology. Consultation and
referral guidelines citing the evidence: how the allergist-immunologist
can help. J Allergy Clin Immunol 2006 Feb;117(2 Suppl
Consultation):S495-523. \[371 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16553071)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2006 Feb

#### GUIDELINE DEVELOPER(S)

American Academy of Allergy, Asthma and Immunology - Medical Specialty
Society

#### SOURCE(S) OF FUNDING

American Academy of Allergy, Asthma and Immunology

#### GUIDELINE COMMITTEE

Task Force of the American Academy of Allergy Asthma and Immunology

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Editors*: Donald Leung, MD, PhD, FAAAAI; Michael Schatz, MD, MS, FAAAAI

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

-   M. Schatz has received research grants from GlaxoSmithKline and
    Sanofi-Aventis and has received honoraria for lecturing on the
    subjects of asthma control, asthma and pregnancy, and the burden of
    rhinitis from AstraZeneca, Genentech, GlaxoSmithKline, and Merck.

-   D. Leung---none disclosed

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the Journal of Allergy and Clinical
Immunology Web site:

-   [HTML
    format](http://www.jacionline.org/article/PIIS0091674905025790/fulltext)

-   [Portable Document Format
    (PDF)](http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS0091674905025790.pdf)

Print copies: Available from the American Academy of Allergy, Asthma &
Immunology, 555 East Wells Street, Suite 1100, Milwaukee, WI 53202-3823;
Phone: (414) 272-6071

#### AVAILABILITY OF COMPANION DOCUMENTS

None available

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on August 8, 2006. The
information was verified by the guideline developer on September 20,
2006.

#### COPYRIGHT STATEMENT

A complimentary copy of the guidelines (originally published as a
supplement to the Journal of Allergy and Clinical Immunology) can be
obtained from the AAAAI Web site at
[www.aaaai.org](http://www.aaaai.org/).

### DISCLAIMER

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