# Presentation: 481029

## Eczema Vaccinatum

**Notes:**
Three days after initiation of treatment with VIG, she has marked edema of the face, exudation, crusting and confluence of the lesions.
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Annotation:  3 days later just after initiation of treatment with VIG.  She has marked edema of the face, exudation, crusting and confluence of the lesions.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Eczema Vaccinatum

**Notes:**
14 days after vaccination and 3 days after treatment with VIG, with marked resolution of her lesions and some pitting and scarring.
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Annotation:  14 days after vaccination and 3 days after treatment with VIG, with marked resolution of her lesions and some pitting and scarring.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Eczema Vaccinatum

**Notes:**
These are the lesions of eczema vaccinatum in a 3-year-old girl who acquired vaccinia from a recently vaccinated playmate.  She was extremely ill and hospitalized for 2 weeks.  The lesions showed typical umbilication and developed similarly to the lesions of normal primary vaccination.  Despite vigorous therapy with VIG and careful fluid and electrolyte balance, she had extensive residual scarring after recovering.
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Annotation:  Lesions of eczema vaccinatum in a 3-year-old girl who acquired vaccinia from a recently vaccinated playmate.  She was extremely ill and hospitalized for 2 weeks.  The lesions showed typical umbilication and developed similarly to the lesions of normal primary vaccination.  Despite vigorous therapy with VIG and careful fluid and electrolyte balance, she had extensive residual scarring after recovering.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Eczema Vaccinatum

**Notes:**
One study found that the mortality from eczema vaccinatum was reduced from 30-40% to 7% following the introduction of VIG.  Therefore it is important to establish early diagnosis and not delay treatment with VIG.  Patients are severely ill and often require large doses of VIG. Virus can be isolated from eczema vaccinatum lesions, making these patients highly infectious.  Infection control precautions should be used to prevent secondary transmission and nosocomial infection.

This 13-month-old boy acquired vaccinia from a recently vaccinated cousin.  He died despite treatment with VIG, steroids, transfusions and antibiotics.
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Reference:[i] Kempe CH. Studies on smallpox and complications of smallpox vaccination. Pediatrics 1960; 26:176-189.
Annotation:  Severe eczema vaccinatum in a 13-month-old boy who acquired vaccinia from a recently vaccinated cousin.  He died despite treatment with VIG, steroids, transfusions and antibiotics.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Progressive Vaccinia

**Notes:**
Progressive vaccinia (PV), (also called vaccinia necrosum, vaccinia gangrenosa, prolonged vaccinia, and disseminated vaccinia), is a rare, severe, and often lethal complication in persons with immunodeficiencies.  This diagnosis should be suspected if the initial vaccination lesion continues to progress without apparent healing 15 or more days after smallpox vaccination.  Anecdotal experience suggests that despite treatment with VIG, hosts with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits.  
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References:
[i] CDC. Vaccinia necrosum after smallpox vaccination-Michigan. MMWR 1982; 31:501-502.
[ii] Krugman,Infectious Disease of Children and Adults pg 280
[iii] Redfield RR, Wright DC, James WD, et al. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987; 316:673-676.
Annotation:  Young boy with progressive vaccinia.  Note the extensive involvement with minimal inflammation.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Progressive Vaccinia

**Notes:**
Progressive vaccinia is characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites such as skin, bones and other viscera.    The vaccination lesion does not heal, presumably secondary to an immune derangement, and progresses to an ulcerative lesion, often with central necrosis.  Initially, there is little to no inflammation at the site and histopathology can reveal absence of inflammatory cells in the dermis.  After several weeks, patients may develop bacterial super-infection and signs of inflammation.  In the 1963 Four Statewide Survey, Neff reported that the majority of the 66 cases initially reported to be progressive vaccinia, and on follow-up were declared to be severe primary (also known as major) reactions.  All cases of the severe major reactions cleared within 1-2 weeks without VIG treatment.

This was a mild and nonfatal atypical case of vaccinia necrosum in a 64-year-old male who had a reduction of immunoglobulin G, A, and M, with a lymphoma.  In addition to this large, necrotic vaccination site, he had a metastatic lesion on his wrist.  His lesions healed after a 2-month course and extensive therapy with VIG.
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Reference:  [i] Keidan, SE, McCarthy K and Haworth, JC. (1953)  Fatal generalized vaccinia with failure of antibody production and absence of serum gamma globulin.  Archive of disease in childhood, 28:110-116.
Annotation:  Mild and nonfatal atypical case of vaccinia necrosum in a 64-year-old male who had a reduction of immunoglobulin G, A, and M, with a lymphoma.  In addition to this large, necrotic vaccination site, he had a metastatic lesion on his wrist.  His lesions healed after a 2-month course and extensive therapy with VIG.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Enlarged Site vs PV

**Large Reaction Differentiation**

**Notes:**
The differential diagnosis of progressive vaccinia includes severe bacterial infection, severe chickenpox, other necrotic conditions (e.g., gangrene) and disseminated herpes simplex infections.  Persons at highest risk for progressive vaccinia include those with congenital or acquired immunodeficiencies, HIV/AIDS, cancer, and those on immunosuppressive therapies for organ transplant or autoimmune disease.  It is likely that the degree and type of immunocompromise correlates with the risk of progressive vaccinia, although the protective level of T-cell count or humoral immunity is unknown. 

This child had a large ulcer at the vaccination site, 9 days after vaccination.  This lesion is larger than most cases of PV at 9 days.  It is distinguished by the well demarcated, heaped-up, inflamed border, and extensive surrounding areas of redness and tenderness, and should not be confused with the indolent painless early PV.
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Annotation:  Enlarge vaccination site, not to be mistaken for Progressive Vaccinia.  Child with a large ulcer at the vaccination site, 9 days after vaccination.  This lesion is larger than most cases of PV at 9 days.  It is distinguished by the well demarcated, heaped-up, inflamed border, and extensive surrounding areas of redness and tenderness, and should not be confused with the indolent painless early PV.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Enlarged Site vs PV

**Large Reaction Differentiation**

**Notes:**
This is not progressive vaccinia. This lesion is well circumscribed and does not have vaccinial vesicles at its margin.  Most important, this patient did not have an underlying immunologic disease.  This is an unusually severe ulcer following first-time vaccination.
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Annotation:  Ulceration of vaccination site, not to be mistaken for Progressive Vaccinia.  Unusually severe ulcer following first-time vaccination.  This is not progressive vaccinia. This lesion is well circumscribed and does not have vaccinial vesicles at its margin.  Most important, this patient did not have an underlying immunologic disease.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Progressive Vaccinia

**Notes:**
Vaccinia virus continues to spread locally and can metastasize to distant sites through viremia.  Live vaccinia virus can be isolated from the skin lesions of these patients.  Infection control precautions, which include contact isolation is required to avoid vaccinial infection of other persons and to limit risk of secondary infections. 

Vaccinia immune globulin has been used since the 1960’s to treat PV.  Infrequently, surgical debridement was used with variable success to treat the primary progressive necrotic lesions of PV.  Prior to the introduction of VIG, PV was always fatal (28), but once VIG was used in the treatment of progressive vaccinia, the survival rate improved.  Current day management of PV should include aggressive therapy with VIG, intensive monitoring and tertiary-level supportive care.  Antiviral chemotherapy has been used to treat progressive vaccinia, and if elected, should be done with careful monitoring for toxicity and response, preferably in the setting of an IND and with reporting of data to contribute to future treatment decisions.   Despite advances in medical care, it is likely that progressive vaccinia will continue to be associated with a high mortality rate.
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Reference: [i] Vince Fulginiti, presentation ACIP Bioterrorism work group presentation, September 2002.
Annotation:  Progressive vaccinia in a 62-year-old woman with chronic lymphocytic  leukemia.  Note the distant lesions on her face, neck and chest and the progression of the vaccination site over time.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Post-Vaccinial EncephalitisDiagnosis

- Cerebral or cerebellar dysfunction
- Headache
- Fever
- Vomiting
- Altered mental status
- Lethargy
- Seizures
- Coma

**Notes:**
Neurological complications following smallpox vaccination include post-vaccinial encephalopathy (PVE) and post-vaccinial encephalomyelitis (or encephalitis) (PVEM).  Clinical symptoms of post-vaccinial encephalopathy and encephalitis reflect cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures and coma.  

## Central nervous system lesions
Cerebrum
Medulla
Spinal cord
Lumbar Puncture
Increased opening CSF
Monocytosis
Lymphocytosis
Elevated CSF protein

- Cerebrum
- Medulla
- Spinal cord
- Lumbar Puncture
- Increased opening CSF
- Monocytosis
- Lymphocytosis
- Elevated CSF protein

**Post-Vaccinial Encephalitis****Diagnosis**

**Notes:**
Central nervous system lesions occur in the cerebrum, medulla, and spinal cord.  Lumbar puncture can reveal an increased opening cerebral spinal fluid (CSF) pressure, and examination of the CSF may show monocytosis, lymphocytosis and elevated CSF protein. 

## Post-Vaccinial Encephalopathy

- Infants under 2 years
- Acute onset 6-10 days post-vaccination
- Seizures
- Hemiplegia
- Aphasia
- Transient Amnesia
- Generalized cerebral edema
- Mild lymphocytic meningeal infiltration
- Widespread ganglion dengerative changes

**Notes:**
Post-vaccinial encephalopathy typically affects infants under 2 years of age and reflects cerebral damage as a result of vascular changes.  Acute onset of symptoms occurs 6-10 days post-vaccination and may include by seizures, hemiplegia, aphasia, and transient amnesia.  Associated histopathological changes include generalized cerebral edema, mild lymphocytic menigineal infiltration, widespread ganglion degenerative changes, and occasionally, perivascular hemorrahages.  Patients are often left with cerebral impairment and hemiplegia (2) 

## Post-Vaccinial Encephalomyelitis

- Older than 2 years
- 11-15 days after vaccination
- Fever
- Vomiting
- Headache
- Malaise
- Anorexia

**Notes:**
Post-vaccinial encephalomyelitis (or encephalitis) affects persons older than 2 years of age and includes abrupt onset of fever, vomiting, headache, malaise and anorexia approximately 11-15 days following vaccination.  Symptoms may progress to loss of consciousness, amnesia, confusion, disorientation, restlessness, delirium, drowsiness, seizures and coma with incontinence or urinary retention, obstinate constipation and sometimes menigismus.  The cerebral spinal fluid, though under increased pressure, reveals normal chemistries and cell count.    Histopathological features include perivenous demyelination and microglial proliferation in demyleniated areas with some lymphocytic infiltration but very little cerebral edema.  These pathological features are similar to what is seen in other post-infectious encephalitides.
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Reference:
[i] Vries, E. de  (1960)  Post vaccinial perivenous encephalitis, Amsterdam, Elsevier.