Urticaria : Overview

Dr.AhmadDr.Ahmad مدير عام


Urticaria, or hives, is a common skin condition that affects 15-25% of the population at some point in their lives. Most cases of urticaria are self-limited and of short duration, but when urticaria becomes chronic, it can be a very problematic and frustrating condition, both for the patient and for the clinician. Urticaria is classified as either acute or chronic. Acute urticaria is defined as urticaria that has been present for less than 6 weeks. Chronic urticaria is defined as urticaria that has been continuously or intermittently present for at least 6 weeks. The 6-week period is a guide and not an absolute demarcation.
When no underlying cause is found, chronic urticaria is referred to as chronic idiopathic urticaria (CIU).
Angioedema is a condition that involves swelling of the deep dermal and subcutaneous/submucosal tissues. Some patients can have both urticaria and angioedema, occurring simultaneously or separately. Approximately 50% of patients have both urticaria and angioedema, while 40% have urticaria alone, and 10% have angioedema alone. See Angioedema for more details.


Skin lesions and pruritus occur, caused by an allergic or nonallergic mechanism. Histamine is thought to be the most important biochemical mediator in urticaria. It is known to cause the classic wheal-and-flare response that is observed with urticaria and with positive results on allergy skin tests. Studies have shown that histamine is present in fluid taken from urticarial wheals.
Mast cells are the major histamine-releasing cells of the skin. Some studies report increased numbers of mast cells in urticarial lesions. The mast cell possesses high-affinity receptors for immunoglobulin E (IgE). In allergic reactions, adjacent IgE molecules, which are bound to the surface of mast cells by the high-affinity IgE receptors, are cross-linked by allergens, leading to the release of histamine and other mediators.
Histamine and the other mediators can be released by other nonallergic mechanisms as well. For example, neuropeptides are known to cause mast cell degranulation by a nonallergic mechanism. Neuropeptides may well be involved in dermographism and in emotional exacerbation of urticaria. In addition to histamine, other mast cell mediators are also thought to play a role in urticaria.
Basophils also possess the high-affinity IgE receptor and may be involved in urticaria. Other inflammatory cells (ie, vide infra) are recruited into the lesional area in urticaria, particularly in chronic urticaria. These cells can release cytokines and chemokines that can cause histamine release or otherwise contribute to the pathology.
A lymphocytic infiltrate is commonly found in the lesions of both acute and chronic types of urticaria. Some urticarial lesions have a mixed cellular infiltrate, ie, a mixture of lymphocytes, polymorphonuclear leukocytes (PMNs), and other inflammatory cells. This mixed type of infiltrate seems to be particularly characteristic of certain refractory forms of chronic urticaria, such as autoimmune-mediated urticaria (see Causes).
The mixed infiltrate is similar to the histopathology of the allergic late-phase response. Some patients with particularly severe or atypical urticaria are found to have vasculitis on skin biopsy. Indeed, a spectrum in histopathology seems to exist, ranging from lymphocytic to vasculitic, that correlates approximately with disease severity, from mild to severe.



Urticaria (chronic, acute, or both) affects 15-25% of the population at some time in their lives. CIU affects up to 3% of the population at some time in their lives. The incidence of acute urticaria is higher in people with atopy. The incidence of chronic urticaria is not increased in people with atopy.

  • Mortality is rare, unless the condition is accompanied by severe anaphylaxis or severe respiratory tract angioedema.
  • Morbidity depends on the severity and duration of the condition. Of patients who have CIU, up to 20% can have symptoms for longer than 10 years. Some studies show chronic urticaria to be quite debilitating. One study finds that urticaria patients can have as much psychological, social, and occupational distress as patients who are awaiting triple coronary artery bypass surgery.

Chronic urticaria affects females more often than males (the female-to-male ratio is approximately 4:1).


Acute urticaria occurs most commonly in children and young adults. CIU is more common in adults; middle-aged women seem to be most affected.


  • Typical features
  • Typical lesions are described as edematous pink or red wheals of variable size and shape, with surrounding erythema. The lesions are often described as welts or hives.
  • The lesions are generally pruritic. A painful or burning sensation may be described (such lesions are often associated with angioedema). Pruritus of nonlesional skin may also occur.
  • Dermographism is often observed in conjunction with urticaria. Itching, erythema, and a raised wheal occur in areas that are scratched or stroked (see Image 1). Patients also may report pressure-induced hives, which can occur with elastic or tight clothing.
  • Individual lesions usually fade within 24 hours, but new lesions may be developing continuously. With delayed pressure urticaria, lesions may last as long as 48 hours. The lesions of urticarial vasculitis, which are palpable and purpuric, may last for several days or more and may lead to residual hyperpigmented changes.
Questions asked to determine possible allergic and nonallergic causes
  • Are the hives associated with any foods? Have any new foods been added to the diet?
  • Is the patient taking any regular medications or have any new medicines been started? In particular, ask about aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, over-the-counter medications, herbs, and supplements.
  • Does the patient have any recent or chronic infections?
  • Are the hives caused by any physical stimuli (eg, heat, cold, pressure, vibration)?
  • Does the patient have any chronic medical conditions?
  • Is the urticaria associated with any substances that are inhaled or in contact with the skin (which may occur in an occupational setting)?
  • Is the urticaria associated with insect bites or stings?

  • If any features of anaphylaxis (eg, hypotension, respiratory distress, stridor, gastrointestinal distress) are present, immediate medical intervention should occur.
Look for typical skin lesions, which are edematous pink or red wheals of variable size and shape, with surrounding erythema. Also, look for any atypical skin lesions. Lesions that are purpuric, nonblanchable, and palpable are characteristic of urticarial vasculitis. These lesions may leave residual pigmented changes. Tiny pinpoint hives are characteristic of cholinergic urticaria.

Examine for dermographism. The skin can be scratched with the end of a tongue blade or similar blunt object and observed over the next 5-15 minutes for the development of whealing with erythema (see Image 1).

Look for any features of angioedema (deep tissue or submucosal edema).

The remainder of the physical examination should be used to investigate any suspicions that were raised by the history.

  • Food allergies
  • Food allergy should be considered in acute urticaria and urticaria in children.
  • Food allergy is unlikely to be a cause in adults with chronic urticaria, especially if it is not obvious by the history. It occurs in fewer than 2% of cases.
  • Food additives or preservatives have been reported to be a cause of chronic urticaria in 3-4% of cases. Data are scarce and questionable.
Drug allergies
  • Allergic reactions to a wide variety of drugs can occur. Theoretically, almost any drug can cause an allergic reaction.
  • Antibiotics, such as penicillin, have been implicated most frequently. Urticarial reactions to penicillin can occur as long as 14 days after a course of treatment has stopped. In this situation, serum sickness may be present.
Contact urticaria is an allergic reaction to a substance that comes into contact with the skin (eg, an occupational exposure).

Papular urticaria is a variation of urticaria caused by insect bites; the lesions may last longer than 24 hours.

Other immediate hypersensitivity allergic reaction to an ingested, inhaled, or percutaneously inoculated substance (eg, latex, stinging insects, occupational exposures)

Nonallergic release of mediators

  • A number of drugs, such as aspirin, NSAIDs, opiates, succinylcholine, and certain antibiotics (eg, polymyxin, ciprofloxacin, rifampin, vancomycin, some beta-lactams) can cause urticaria by a nonallergic mechanism rather than by IgE-mediated hypersensitivity.
Certain foods or beverages, such as spoiled fish (scombroidosis), aged cheeses, or red wine: These foods can contain histidine, which is closely related to histamine. These foods often are listed as causes of urticaria in the literature, but experimental evidence is scarce.

Certain venoms

Radiocontrast media sensitivity is not related to iodine, fish, or shellfish allergy.

Medical causes
  • Infectious causes
    • Urticaria has been reported with certain viral infections, such as acute viral syndromes, hepatitis (A, B, and C), Epstein-Barr virus, and herpes simplex virus. Urticaria has also been reported with chronic parasitic infections.
    • Urticaria may possibly be caused by sinusitis, cutaneous fungal infections, Helicobacter pylori infection, or other occult infection. These causes have been reported in the literature, but data are not strongly supported.
  • Hormonal causes
    • Endocrine tumors (rare)
    • Ovarian pathology (rare)
    • Oral contraceptive use or changes in the menstrual cycle: Patients commonly report worsening of hives with the menstrual cycle. Be sure to consider cyclical use of analgesics as a possible etiology.
  • Cryoglobulinemias (eg, associated with hepatitis C, chronic lymphocytic leukemia)
  • Serum sickness
  • Other immune complex–mediated inflammation
  • Systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, or other rheumatological diseases (these are rare causes of urticaria)
  • Urticaria has been reported with both hypothyroidism and hyperthyroidism and in euthyroid patients with antithyroid antibodies (ie, vide infra).
  • Lymphoreticular malignancies (eg, chronic lymphocytic leukemia
Physical causes (physical urticaria)
  • Cold
  • Pressure: A delayed response to pressure (delayed pressure urticaria) occurs in up to 40% of patients with CIU.
  • Vibration
  • Cholinergic (triggered by heat, exercise, or emotional stress)
  • Sunlight
  • Water
  • Dermographism can occur concomitantly with CIU.
  • Exercise
Chronic idiopathic urticaria
  • Urticaria is classified as idiopathic when no specific cause is identified by history, physical examination, or laboratory findings.
  • Eighty to 90% of cases of chronic urticaria can be classified as idiopathic.
  • These patients may have concomitant physical urticaria.
  • Causes are separated into 2 categories, autoimmune or unknown.
  • Autoimmune causes
    • Studies have shown that as many as 40-60% of cases of CIU have an autoimmune component. These studies found that sera from many of these patients, when injected intradermally, cause a wheal-and-flare reaction. This is called an autologous serum skin test. Furthermore, these sera can cause a release of histamine from basophils in vitro.
    • Further studies have found that 25-60% of patients have autoantibodies directed against their high-affinity IgE receptors. The role of these autoantibodies is still unclear. They may bind to the high-affinity IgE receptors on mast cells and basophils, triggering the release of mediators, in a process that is thought to be complement-dependent.
    • Five to 10% of patients have autoantibodies directed against the IgE molecule. The role of these autoantibodies is still unclear. They may attach to IgE molecules that are bound to mast cells (or basophils), triggering the release of mediators.
  • Unknown causes
    • In the remaining 40-60% of cases of CIU, the cause is unidentified. Numerous other possible causes have been suggested but have not been substantiated in the literature.
    • A higher frequency of thyroid autoimmunity occurs in patients with chronic urticaria. These patients have autoantibodies directed against thyroid proteins but may be euthyroid. Some authors have found that treatment of these euthyroid patients with thyroxine leads to an improvement in urticaria, but other authors have not been able to reproduce this finding. Some have speculated that the thyroid autoantibodies cause inflammation in the thyroid, leading to release of cytokines, which, in turn, decreases the threshold for mast cell mediator release. Others have suggested that the thyroid autoantibodies are merely markers for autoimmunity. For example, patients with thyroid autoantibodies are more likely to have other autoantibodies, such as the anti-IgE receptor and anti-IgE discussed above.
    • Occult infections and food additives have been reported to be causes of CIU in a small number of patients, but the data are scarce and questionable, as discussed previously.
    • Other histamine-releasing factors in the serum that cause a wheal-and-flare reaction independent of IgE or the high-affinity IgE receptor may be present. Experimental evidence for this is lacking.