Urticaria overview

# Overview

# Classification
There are numerous types of urticaria. Based on the way wheals appear, they can be divided into spontaneous and physical urticaria. Spontaneous urticaria is further divided into acute and chronic urticaria, based on their duration. Mechanical forces and pressure on the skin or the ambient air temperature are responsible factors in development of physical urticaria, which can be divided into more subtypes, such as demographic urticaria, delayed pressure urticaria, cold contact urticaria, heat contact urticaria, solar urticaria and vibratory urticaria. Besides these two main classes of urticaria there are other particular types such as, cholinergic urticaria, adrenergic urticaria, aquagenic urticaria, contact urticaria and drug-induced urticaria.

# Pathophysiology
There are numerous mechanisms hypothesized to be responsible in pathogenesis of urticaria. One of the prominent urticaria pathogenesis seems to be inflammatory processes due to increased immune cells activity. Basophils, mast cells, macrophages, neutrophils and T cells are some of the most common immune cells known to be responsible in pathogenesis of urticaria. Among them, basophils and mast cells have more eminent role in urticaria development and their activation has been related to some intracellular signal defect and/or autoimmune disorders. Some immunoglobins, such as IgE have been detected in patients suffering from urticaria. For instance, IgE anti-IL-24 is one of these IgE autoantigens that have been found in all patients with chronic spontaneous urticaria. Moreover, complement system is also responsible in pathogenesis of chronic spontaneous urticaria and role of some complements, such as C3, C4 and C5 have been established. Based on numerous studies, urticaria patients may have some genetical changes. Upregulation of 506 genes and downregulation of 51 genes have been reported in the affected skin with chronic spontaneous urticaria. Most of the upregulated genes were involve in adhesion (such as SELE (1q24)), cell activation (such as CD69), and chemotaxis (such as CCL2). It is crystal clear that urticaria is associated with autoimmune diseases such as hashimoto's thyroiditis. Other associations are mastocytisis such as urticaria pigmentosa, atopic diseases such as atopic dermatitis, hay fever and allergic asthma and systemic lupus erythematosus and angioedema.

# Causes
Urticaria may be caused idiopathically or due to immunological disorders such as autoimmune diseases, food allergies, medications and specific infections. There are also some non-immunological causes for urticaria development, such as physical triggers, dietary pseudo-allergen and hereditary urticaria.

# Differentiating Urticaria from other Diseases
It is critical to differentiate urticaria from other similar disorders to utilize the best approach for the treatment. Hereditary or acquired deficiency of complement factor C1, cutaneous mastocytosis such as urticaria pigmentosa, certain malignancies, connective tissue diseases, angioedema and exerciseinduced anaphylaxis are some of the differential diagnosis of urticaria.

# Epidemiology and Demographics
Since a considerable number of patients with urticaria only experience short lived symptoms and they may not seek any medical attention, it is difficult to determine the exact number of incidence and prevalence. However based on studies have been done, incidence of urticaria has been approximately 0.154% in one year and it's prevalence is approximately 12-23.5%. Patients of all age groups may develop urticaria, nevertheless 20-40 years old patients are the most frequent patients who develop urticaria. Females are more commonly affected by urticaria than males. The overall female to male ratio is approximately 2 to 1. Although delayed pressure urticaria is the exception and involves males more than females, with a male to female ratio of 2 to 1. There is no racial predilection to urticaria.

# Risk Factors
Common risk factors in the development of urticaria include atopy, air pollution, female gender, certain foods, medications and occupations.

# Natural History, Complications and Prognosis
Remission rate, complications and prognosis of urticaria is tightly related to patient characteristic (such as age and gender), subtype of urticaria and concurrent angioedema. 10% to 60% of cases go into remission within the first 510 years of disease diagnosis. Moreover treatments usually alleviate symptoms in most cases. Mean duration of urticaria presence is different among distinct sub-types. Urticaria patients are prone to some complications, such as superimposed bacterial infection, anaphylaxis and excoriation due to intense pruritus. Most patients improve over time, even stubborn cases. Prognosis and treatment response is better in patients younger than 19 years old, compared to older adults. Female gender, prolonged period of disease at the first visit, concurrent angioedema, subtypes such as physical urticaria and cholinergic urticaria  and chronic use of non-steroidal anti-inflammatory drug are related to worse prognosis.

# Diagnosis

## History and Symptoms
Acute urticaria usually appears few minutes after contact with the allergens and can lasts from few hours to several weeks. On the other hand, chronic urticaria refers to hives that persists for at least 6 weeks. Both of them are often presented with the same symptoms. Appearance of wheals could be spontaneous or occurs after ingesting certain foods, contact with the allergens, exercise, medication use and pressure that have been applied on the skin based on urticaria subtype. Skin involvement in the form of wheals and pruritus are the common symptoms of urticaria. Less common symptoms of urticaria are dizziness, nausea, headache and burning sensation.

## Physical Examination
All types are characterized by raised red skin welts appearing anywhere on the body. They are itchy and about 5 mm in diameter.

## Laboratory Findings
Laboratory evaluation can be used as a measure to determine disease severity, responsiveness to treatment and prognosis, in addition to their role as a diagnostic tool. Tests such as autologous serum skin test (ASST) and basophil activation test (BAT) are useful for detection of autoantibodies against IgE. Moreover elevated levels of c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), certain interleukins and tumor necrosis factor-alpha have been reported in urticaria patients. Laboratory evaluations that can determine disease activity are autologous serum skin test (ASST), c-reactive protein (CRP) and IL-6.

## Other Diagnostic Findings
Urticaria activity score (UAS7) is a questionnaire-based scoring system which inquires about pruritus and wheals experienced by the patients. It is helpful to determine the spontaneous urticaria severity. Moreover, there is another diagnostic test, named ice cube test which is used to diagnose cold-induced urticaria. The aforementioned test is a practical method to observe wheals appearance after cold exposure.

# Treatment

## Medical Therapy
Medical treatment is required for patients who are annoyed by wheals appearance and pruritus. First line treatment is H1 antihistamine medications, such as diphenhydramine, hydroxyzine, cetirizine and other H1 antihistamine. Some patients might require high doses of antihistamines for a complete control of their symptoms, but fortunately it's high doses are tolerated by most patients. If antihistamines as the first line treatment didn't successfully controlled the symptoms, omalizumab and cyclosporine should be tried as the second line treatment. Omalizumab has been effective in different sub-types of urticaria, such as solar urticaria, cold urticaria, cholinergic urticaria, urticarial vasculitis and symptomatic dermatographic urticaria. There are some other alternatives if the aforementioned medications didn't help, alternatives such as dapsone, hydroxychloroquine, sulfasalazine, colchicine, methotrexate, intravenous gamma globulin, plasmapheresis, corticosteroids, H2 antagonists and leukotriene antagonists. Some studies recommended specific alternative treatment for each subtypes of urticaria.

## Primary Prevention
If patients notice any specific factor that leads to wheals development, avoiding that factor may reduce attack severity and frequency. These factors could be any food allergens, cold temperature, or sharp edges. It is also recommended to avoid wearing tight-fitting clothes and a hot bath just after an episode of urticaria.w