Urticaria

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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.

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.

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.

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 exercise‐induced anaphylaxis are some of the differential diagnosis of urticaria.

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.

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

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 5–10 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.

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.

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

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.

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.

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.

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

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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.

Urticaria may be classified according to roles of triggers into two subtypes:

• • Acute urticaria: Spontaneous appearance of wheals, most days in a period less than 6 weeks.
  • Chronic urticaria: Spontaneous appearance of wheals with more than 6 weeks duration.^[3]
    • Chronic continuous: Involvement in every day or most days.
    • Chronic recurrent: There are symptom free intervals.

• • Dermographic urticaria (factitial urticaria): Appearance of wheals 1-5 minutes after a mechanical shearing force, which mainly involves young adults.
  • Delayed pressure urticaria:
    • Appearance of wheals 3-8 hours after a vertical pressure, which usually lasts for 8–48 hours.
    • Frequently seen on palms and soles, buttocks and back (sitting on a hard chair).
  • Cold contact urticaria:^[6]
    • Appearance of wheals due to cold temperatures, such as ice and cold air, water, or wind.
    • It is divided into primary and secondary subtypes. In primary form there is no known trigger causing the urticaria, besides cold temperature. Nevertheless, secondary form of cold contact urticaria is also associated to other triggers in addition to cold temperature, such as medications, bacterial or viral infections, hymenoptera stings, immunotherapy and hematological malignancies.
  • Heat contact urticaria
  • Solar urticaria: Appearance of wheals due to sunlight/ultraviolet light with wavelengths ranging between 280 and 760 nm.
  • Vibratory urticaria: Appearance of wheals due to vibratory forces, such as pneumatic hammer.^[7]
  • Cholinergic urticaria:
    • Usually due to causes that elevate core body temperatures, such as exercise, emotional stress and passive warmth (hot shower) and less commonly due to alcoholic drinks or warm or spicy foods.
  • Adrenergic urticaria:
    • Elicited by stress
  • Aquagenic urticaria
    • Urticaria appearance is not due to water itself, nevertheless water delivers some water-soluble allergens to the dermis.
  • Contact urticaria (allergic or pseudoallergic)
    • Chemical substances contact (such as industrial chemicals, animal product, textiles, plants, drugs, cosmetics and food) with skin leads to urticaria appearance.
  • Drug-induced urticaria (such as aspirin-intolerant chronic urticaria (AICU))

‡ Can also be classified as physical urticaria.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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.

There are some factors responsible in pathogenesis of wheals:^[1]

• There are some endogenous anti-angiogenic mediators, which are degraded from extracellular matrix components such as endostatin (ES) and thrombospondin-1 (TSP-1). These mediators regulate functional activity of vascular endothelial growth factor (VEGF).
• Endostatin (ES) and thrombospondin-1 (TSP-1) levels are elevated in patients with urticaria. Apart from their anti-angiogenic effects, they are responsible for destabilizing the endothelial cells contact, which leads to formation of wheals, the famous dermatologic presentation of urticaria.
• NO synthesis is one of the responses to endostatin (ES) which can also acts as a vasoactive mediator. The consequent vasodilation eventually leads to wheals formation through vascular leakage.

• The pathophysiology of acute urticaria is production of specific IgE antibody against food protein antigens.^[2]
• Viral infection is the most common cause of acute urticaria, mainly upper respiratory tract infections.^[3]

There are numerous mechanisms hypothesized to be responsible in pathogenesis of chronic spontaneous urticaria:^{[4][5][6][7][8][9][10][11][12][13][14][15][16]}

• Inflammation has been known as a responsible factor in the pathogenesis of urticaria, especially in chronic spontaneous urticaria.
  • One of the findings that supports the role of inflammation in the urticaria pathogenesis is IL-31. This interleukin is primarily produced by activated Th2 lymphocytes and mast cells, as well as a skin-homing T cell (CD45R0 CLA+T cell) and plays a cardinal role in chronic skin inflammation.
  • An imbalance in some anti-inflammatory adipokines (such as adiponectin) and proinflammatory adipokines (such as lipocalin-2 (LCN2)) has been found in chronic urticaria.
  • Matrix metallopeptidases (MMPs) are elevated in patients with chronic spontaneous urticaria. MMPs are responsible in the inflammation process as shown below:

Macrophages, neutrophils, T cells, and mast cells → MMP-9 → Cleavage of pro-inflammatory chemokines/cytokines → Migration and activation of more immune cells

• Activation of mast cells and basophils has been increased in urticaria. There are two known mechanisms that lead to mast cell and basophil activation in the process of urticaria:^[17]
  1: Defect in intracellular signaling: Improper activation of spleen tyrosine kinase (Syk) or improper inhibition of Src homology 2 (SH2)-containing inositol phosphatases (SHIP).
  2: Autoimmune mechanisms: Antibody-mediated mast cell and basophil activation via IgG or IgE mediated pathways.
  • At least 200 IgE autoantigens (soluble or membrane-bound), were recently found in patients with chronic spontaneous urticaria. IgE anti-IL-24 is one of these IgE autoantigens that have been found in all patients with chronic spontaneous urticaria.
  • Approximately, 35%–40% of patients have IgG anti-FcεRIα (an α subunit of the high affinity IgE receptor).
• A basophilic abnormality has been seen in a number of patients with chronic spontaneous urticaria. Elevated levels of phosphatases, such as Src homology tyrosine phosphatase-1 (SHP-1), have been detected in the defective basophils.^[18]
• Complement system is also responsible in pathogenesis of chronic spontaneous urticaria.
  • In-vitro experiments have been demonstrated the role of C5a in enhancement of IgG-dependent histamine release from basophils and mast cells in chronic urticaria.^[5]
  • In a study done on 70 patients with chronic spontaneous urticaria significant elevated levels of C3 and C4 have been detected, compared to the normal population.
  • Increased production of C3 and C4 by liver is probably due to elevation in pro-inflammatory cytokines, such as IL-1β, IL-6 or tumor necrosis factor (TNF). C3a itself further stimulates the secretion of other pro-inflammatory cytokines and chemokines and expresses on cells responsible in urticaria formation, such as mast cells, basophils, eosinophils, neutrophils and monocytes. Anaphylatoxin C3a is also able to stimulate histamine release which is capable of causing vasodilatation and consequent increased permeability of small blood vessels.
• Increased expression of tissue factor by activated eosinophils first activates extrinsic coagulation pathway and then the intrinsic coagulation pathway and consequent generation of thrombin has been reported.
• Tumor necrosis factor alpha (TNF-alpha) produced by dermal mast cells has been detected at the site of urticaria lesions.
• The following table is a summary of some elevated mediators in chronic urticaria.^[17][19][20]

• Mechanisms other than allergen–antibody interactions are known to cause histamine release from mast cells.
• Many drugs, such as morphine, can induce direct histamine release not involving any immunoglobulin molecule. Also a diverse group of signaling substances called neuropeptides have been found to be involved in emotionally induced urticaria.
• Dominantly inherited cutaneous and neurocutaneous porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been associated with solar urticaria. The occurrence of drug-induced solar urticaria may be associated with porphyrias.

• In one study 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).^[21]
• CIAS1 gene mutation has been linked to cryopyrin-associated periodic syndrome (CAPS) a neonatal-onset multisystem inflammatory disorder (NOMID) which presents with urticaria.^[2]
• The following table is a summary of genes that have been significantly associated with some phenotypes of urticaria and list of countries which the studies have been done in the,: ^[22]

Abbreviations: AICU: aspirin-intolerant chronic urticaria; AIU: aspirin-intolerant urticaria; CU: chronic urticaria;

• Autoimmune disease: Presence of autoimmune conditions, such as autoimmune thyroid disease has been found in a fraction of patients with urticaria. Moreover, some studies detected IgE and IgG anti-TPO antibodies in some patients with chronic spontaneous urticaria. These antibodies might be responsible for mast cells and basophils degranulation.^{[23][24][25][26][27]}
  • Elevated antithyroid antibodies, such as IgG antithyroglobulin, immunoglobulin E (IgE) antithyroperioxidase and immunoglobulin G (IgG) antithyroperioxidase, have been detected in patients with chronic spontaneous urticaria.
  • Hashimoto’s thyroiditis has been detected in a sub-population of patients with chronic spontaneous urticaria.
• Mastocytisis such as urticaria pigmentosa.
• Atopic disease
  • There are some reports on urticaria presentation in 50% of patients who suffer from atopic dermatitis, hay fever and allergic asthma.^[3]
  • Another study done on children with atopic dermatitis delineated that approximately 16% of them developed urticaria within a 18 months surveillance.^[28]
• Systemic lupus erythematosus.^[12]
• Concurrent angioedema has been seen in 40% of patients who suffer from chronic urticaria.^[22]
• Patients with urticaria have higher chance of hypertension development.^[4]
• Higher chance of urticaria is reported among patients with metabolic syndrome, compared to the normal population.^[29][30]
• Osteoporosis^[31]

The following changes have been found in microscopic evaluation of urticaria:^{[4][32][21][3]}

• Angiogenesis
  • Vascular formation has been detected in urticaria biopsies, especially in chronic urticaria.
  • Elevation in some pro-angiogenic mediators, such as VEGF, has been directly linked with formation of new blood vessels in the skin of chronic spontaneous urticaria patients.
• High concentration of inflammatory cells (predominantly mononuclear cells) per high-powered field.
• Increased endothelial adhesion molecules.
• Microscopic evaluation of delayed pressure urticaria demonstrated inflammatory mediatorrs in the mid‐ to lower dermis.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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.

Common causes of urticaria may include:^[1][2][3][4]

• Idiopathic
  • Unknown etiology
• Immunological:
  • Autoimmune: IgG autoantibodies to IgE receptor or IgE on mast cells could be the responsible mechanism.
  • IgE/contact urticaria:
    • Contact with allergen cross-links specific IgE (SIgE) on mast cells.
    • Could be due to food protein antigens (such a mold or storage mite), insect venoms, animal dander’s and/or saliva, penicillin, protease enzymes in biological detergents and latex proteins.
    • In patients with urticaria due to latex allergy, there is a higher chance of a wide variety of food allergy due to cross-reactivity between the latex protein antigens and food antigens. The following list is a summary of foods capable of cross-reactivity with latex proteins:

• • Food allergy:^{[1] [5]}
    • Studies suggest that foods such as nuts, seafood (such as shellfish), eggs (especially egg white), fish, meat, chocolate, cow’s milk, fruits (such as citrus fruits, plums, pineapples, grapes, apples, bananas, and strawberries), vegetables (such as tomatoes, peas, garlic, onion, beans, and carrot), mushrooms, fermented foods, spirits and spices are capable of causing urticaria.
    • Although food allergy is known as a less common cause of adult urticaria, it is a common cause of urticaria in children. In a study done on adults with urticaria, 63% of patients suspected foods to be the reason of their symptoms, however food allergy was responsible for urticaria development in only 0.9% of them.
  • medications:
    • Sensitivity to Cyclo-oxygenase (COX)-inhibitors (aspirin, NSAIDs)
    • Penicillin
    • Thiazide diuretics
    • Oral contraceptives
    • Angiotensin-converting enzyme inhibitors
    • Sulfonamides
    • Vitamins
    • Codeine and morphine
    • Curare and its derivatives
    • Synthetic adrenocorticotropic hormone
    • Radiocontrast substances
    • Acetylcysteine
    • Aminohippurate
    • Antimalarial drugs, such as atovaquone and proguanil hydrochloride or artemether and lumefantrin
    • Aztreonam
    • Benzphetamine
    • Boceprevir
    • Penciclovir
    • Polidocanol
    • Probenecid
    • Carbinoxamine
    • Cephalosporins, such as Cefoxitin sodium and Cefotaxime sodium
    • Clobazam
    • Dexamethasone and Prednisone
    • Doxorubicin hydrochloride
    • Lamivudine
    • Dextran
    • Caspofungin
    • Oxaprozin
    • Dapsone
    • Idursulfase
    • Tetracycline
    • Tiagabine
    • Tolbutamide
    • Ferric Carboxymaltose
    • Flavoxate
    • Rifampin
    • Pegademase
    • Pegaspargase
    • Streptomycin
    • Indinavir and ritonavir
    • Ivermectin
    • Sulfamethoxazole/Trimethoprim (oral)
    • Spironolactone
    • Lidocaine (ointment)
    • Lincomycin Hydrochloride
    • Meropenem
    • Niacin
    • Nizatidine
    • Von Willebrand factor
    • Hepatitis B immunoglobulin
  • Infections^[4][6][7][8]
    • Viral infections are the most common cause of acute urticaria, mainly upper respiratory tract infections, such as tonsillitis and rhinosinusitis. Prevalence of upper respiratory tract infections in acute urticaria has been estimated between 28 to 62%, based on reports of five studies.
    • Urinary tract infections
    • Parasitism
    • Hepatitis
    • Infectious mononucleosis
    • Dental abscesses
    • Helicobacter pylori infection
    • Syphilis
    • Lyme disease
    • Varicella
    • HIV infection
  • Urticarial vasculitis^[9]
• Non-immunological:
  • Physical urticaria: Physical factors trigger histamine release from mast cells.
  • Dietary pseudo-allergen:^{[1][10][11][4][9][12]}
    • Sensitivity to natural salicylates, colorings (both azo dyes and non-azo dyes), preservatives (such as sulphites, nitrates and nitrites), anti-oxidants (such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)) and aspartame (an artificial sweetener).
    • Histamine poisoning is one of the non-IgE-mediated food-related urticaria, which occur when foods have high histamine content, such as improperly stored scombroid fish (such as mackerel, tuna and swordfish), with high level of decarboxylated histidine due to bacterial activities. Decarboxylated histidine then produces histamine. Although spoiled non-scombroid fish, such as herring, sardines and anchovies can also be responsible, due to high histamine content.
  • Mold spores, pollen, mites, animal hair and dandruff and other respiratory allergens might cause urticaria through respiration. Furthermore, smoking is related to urticaria development.^[4]
  • Hereditary urticaria
  • Medical conditions:
    • Urticaria pigmentosa: Increased mast cell load
    • Cryopyrin-associated periodic syndrome (CAPS): Due to a mutation in CIAS1 gene.
    • Familial form of cold-induced urticaria^[13]
    • Mental disorders^[14][4]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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 exercise‐induced anaphylaxis are some of the differential diagnosis of urticaria.

• Hereditary or acquired deficiency of complement factor C1
• Cutaneous mastocytosis/urticaria pigmentosa
• Malignancy
• Exercise‐induced anaphylaxis^[1]
• Connective tissue diseases
• Photosensitive diseases
• Poison ivy contact dermatitis: The rash that develops from poison ivy, poison oak, and poison sumac contact are commonly mistaken for urticaria. This rash is caused by contact with urushiol and results in a form of contact dermatitis called urushiol-induced contact dermatitis.
• Angioedema:
  • Although it might be related to urticaria, angioedema occurs due to swelling of the lower layers of dermis.^[2]
  • Edema can occur around the mouth, in the throat, in the abdomen, or in other locations. Urticaria and angioedema sometimes occur together in response to an allergen and should be a concern in severe cases because angioedema of the throat can be fatal.
• A possible differential diagnosis for diseases that cause urticaria, and rash include:
  • Schnitzler syndrome
  • Deficiency in interleukin-1 receptor antagonist
  • Juvenile idiopathic arthritis
  • Adult-onset Still’s disease
  • Viral rashes
• Table below differentiates some of the aforementioned conditions:

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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.

• In a prospective study in a rural area the incidence of urticaria has been approximately 0.154% in one year.^[1]

• The prevalence of acute urticaria is approximately 12-23.5%. Although the real prevalence is estimated to be even more, since mild cases usually don’t seek medical attention. ^[1][2]
• Cholinergic urticaria has a 11.2% prevalence in the age group of 16–35 years.
• Physical urticarias prevalence has been estimated 44.6% in normal subjects.^[3][1]

• Patients of all age groups may develop urticaria, nevertheless 20-40 years old patients are the most frequent patients who develop urticaria.^[4][5]
• The age of onset is 30 years old in delayed‐pressure urticaria.^[1]
• There are some studies demonstrating an inverse relationship between age and disease severity. Based on these studies, older adults have shorter periods of disease.^[6]

• There is no racial predilection to urticaria.

• Females are more commonly affected by urticaria than males. The female to male ratio is approximately 2 to 1.^[4]
• The female to male ratio is approximately 5 to 1 in aquagenic urticaria.^[1][7]
• Interestingly delayed pressure urticaria involves males more than females, with a male to female ratio of 2 to 1.^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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

Common risk factors in the development of urticaria include:^[1][2][3]

• Atopy
• Air pollution
• Female gender
• Certain foods
• Medications
• Occupations with high contact to latex or high skin friction
• Positive familial history
• Insect bites and stings

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

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 5–10 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.

• Remission rate of chronic urticaria has been estimated from 10% to 60% within the first 5–10 years of disease diagnosis. Moreover, data showed higher remission rate in patients younger than 20 years old. ^[1]
• Most cases with cholinergic urticaria have mild symptoms and 80% of patient’s don’t seek medical attention.
• The following table contains mean duration of some subtypes of urticaria.^[2]

Common complications of urticaria include:^[2][3]

• Superimposed bacterial infection
• Anaphylaxis
• Excoriation due to intense pruritus
• Pressure urticaria might turn into a debilitating disease in some occupations.

• Most patients improve over time, even stubborn cases.^[4]
• Prognosis and treatment response is better in patients younger than 19 years old, compared to older adults.^[4][5]
• The following are some factors related to worse urticaria prognosis:^{[6][7][8][2][9]}
  • Female gender
  • Prolonged period of disease at the first visit
  • Concurrent presentation of angioedema
  • Physical urticaria, specially delayed pressure urticaria
  • Cholinergic urticaria
  • Non-steroidal anti-inflammatory drug use

Template:WH Template:WS