Urticaria 11/12/2010

BY: MOHAMMED ALSAIDAN

Urticaria

• Recurrent wheals that are usually pruritic, pink-to-red edematous plaques that often have pale centers

• May occur anywhere on the skin, Any age

• Itch is relieved more by rubbing rather than by scratching

• Purpura rather than excoriations

Urticaria

• lifetime occurrence of urticaria in the general population ranges from 1% to 5%.

• Classification: clinical characteristics Vs. etiology

pathogenesis

• The mast cell is the principal effector cell of urticaria

• All mast cells express high-affinity IgE receptors (FceRIs) that enable the involvement in IgE-dependent allergic reactions, leading to degranulation

• Mast cell degranulation also occurs through a variety of other mechanisms

• These stimuli initiate calcium and energy-dependent steps

pathogenesis

• One study has shown that the serologic immune profile of patients with chronic autoimmune urticaria is a mixed T helper-1 (Thl)/ Th2 pattern with a slight Th2 predominance

pathogenesis

• Histology of chronic urticaria (both idiopathic and autoimmune) demonstrates a perivascular non-necrotizing infiltrate of lymphocytes consisting of a mixture of Thl and Th2 subtypes, plus monocytes, neutrophils, eosinophils, and basophils.

Chronic urticaria aetiology

• Most cases of chronic urticaria remain idiopathic

• 35-50% of chronic urticaria cases are related to autoimmunity, specifically the presence of autoantibodies to (FceRl) located on mast cells, 5-10% have IgG antibodies to IgE itself.

• Other identifiable causes of chronic urticaria include: IgE-dependent, complement-mediated, or immune complex deposition.

• Non-immunologic causes ?

Genetics

• Prevalence of the disease was much higher among first-degree relatives than in the general population.

• Patients with chronic idiopathic urticaria have an increased frequency of HLA-DR4 and HLA-D8Q.

• HLA-DR4 is strongly associated with autoimmune chronic urticaria.

• 

Food

• Food allergy and food additives such as preservatives and coloring agents do not appear to be significant causes of chronic urticaria

• Most physicians feel that elimination diet approach is unnecessary

• Food allergies typically would cause a reaction within 30 minutes of ingestion

Autoimmune associations

• Autoimmune conditions associated with chronic urticaria :• Thyroid diseases • vitiligo• insulin-dependent diabetes mellitus• rheumatoid arthritis• pernicious anemia

Thyroid diseases

• Both Hashimoto thyroiditis and Graves disease have been associated with chronic urticaria.

• Antithyroid antibodies, antimicrosomal antibodies, or both have been found in up to 27% of patients with chronic urticaria

• Positive ASST result had significantly more autoimmune thyroid disease

• No evidence that the antibodies involved in thyroid disorders play a role in the pathogenesis of chronic urticaria

H.pylori

• Increased frequency of H. pylori IgG antibodies in patients with chronic urticaria

• Helicobacter pylori, has an immunogenic cell envelope, can reduce immune tolerance and induce autoantibody formation, such as anti-FceRI.

• Efficacy of eradication of H. pylori in the treatment of chronic urticaria is a controversial (Federman et al., 2003)

• Association with (MALT) lymphoma and gastric adenocarcinoma?

Malignancy + other diseases

• There is no association between chronic urticaria and malignancy

• Little supporting evidence for association between urticaria and occult infections such as:• dental abscesses• gastrointestinal candidiasis • Parasitic infections such as intestinal in endemic areas.• The fish nematode Anisakis simplex (IgG4 antibodies).• hepatitis C (conflicting results)

• No conclusive evidence is available linking chronic urticaria with hepatitis B, EBV, CMV, or HIV.

Acute Urticaria

• Wheals for <6 weeks

• Individual lesions typically resolve in <24 hours

• More commonly in pediatric population

• Associated with atopy.

• 20% progress to chronic or episodic

Acute Urticaria

• IgE dependent :• foods, drugs, insects, contact, or parasites

• Direct mast cell degranulation and proinflammatory mediator:• Opioids, muscle relaxants, radio-contrast agents, and vancomycin.

• Complement-mediated acute urticaria :• serum sickness, transfusion reactions, and viral or bacterial

infections

• Metabolism of arachidonic acid:• aspirin and NSAIDs

Chronic Urticaria

• Cutaneous wheals on a regular basis (usually daily) for >6 weeks with individual lesions lasting from 4 to(24 36) hours.

• Establishing cause and effect is difficult and many cases remain idiopathic.

• Significant portion of idiopathic urticarias may have an autoimmune etiology

• Chronic urticaria is more prevalent in female patients, occurring at a 2 : 1 female-to-male ratio

Contact Urticaria

• Urticarial wheals at the site where an external agent makes contact with skin or mucosa.

• Allergic (IgE-mediated) contact urticaria occurs in persons sensitized to environment allergens such as grass, animals, or latex gloves

• Non-allergic contact urticaria occurs as a result of the direct effects of urticants on blood vessels. E.g. sorbic acid in eye solutions, cinnamic aldehyde in cosmetics, and chemicals from the stinging nettle

Physical Urticaria

• Typically localized to the stimulated area and resolve within 2 hours with the exception of delayed (pressure and dermatographism)

• Symptomatic dermatographism - the most common form of physical urticaria - is not associated with systemic disease, atopy, food allergy, or autoimmunity.

Physical Urticaria

Delayed-pressure urticaria:

• May present with systemic symptoms (malaise, influenza-like symptoms, and arthralgias)

• Deep erythematous swellings at sites of sustained pressure to the skin after a delay of 30 minutes to as long as 12 hours.

• Waistline ,elastic band of socks.

• Many patients with delayed-pressure urticaria also have concurrent chronic idiopathic urticaria.

Physical Urticaria

Cholinergic urticaria • The second most common type of physical urticaria • Around 3mm wheal surrounded by an obvious flare in

response to physical exertion, hot baths, or sudden emotional stress,

Adrenergic urticaria• blanched, vasoconstricted skin surrounding small pink wheals.

Schnitzler syndrome

• Chronic urticaria vs. Urticarial vasculitis!

• Recurrent non-pruritic wheals

• Intermittent fever, bone pain, arthralgias or arthritis, an elevated (ESR), and a monoclonal IgM gammopathy.

• +/- IgG antibodies directed against (IL)-l

• Biopsies of lesions often demonstrate an increased polymorphonucleocyte count with occasional leukocytoclasia.

Schnitzler syndrome

• 10% to 15% of patients subsequently develop a lymphplasmic malignancy, such as Waldenstrom macroglobulinemia, lymphoplasmacytic lymphoma, or IgM myeloma

• Anakinra, an IL-1 receptor antagonist, appears to be a promising agent

• Rituximam and thalidomide have also been used

Muckle-Wells syndrome

• An autoinflammatory disorder associated with cold-induced autoinflammatory syndrome-1 gene mutations

• Characterized by urticaria, arthralgias, progressive sensorineural deafness, and amyloidosis

(PUPPP)

• Also known as polymorphic eruption of pregnancy• The most common dermatosis associated with pregnancy. Its

lesions are often urticarial and involve the trunk, particularly abdominal striae.

• Benign, self-resolving course with an onset in the third trimester.

• Serious DDx : pemphigoid gestationis, a bullous pemphigoid like-disorder associated with pregnancy

Urticarial vasculitis

• Rare, with reported ranges of 1-10% in patients with chronic urticaria

• In contrast to chronic urticaria, tend to last longer than 24 h.

• Associated with burning and pain in addition to itching

• Healing with purpura or petechiae

Urticarial vasculitis

• Skin biopsy typically shows evidence of leukocytoclastic vasculitis.

• Typically a component of a chronic systemic illness such as:• systemic lupus erythematosus• hypocomplementemic urticarial vasculitis syndrome• Sjogren syndrome• mixed cryoglobulinemia.

Diagnostic work up

• A detailed history is usually adequate to establish a diagnosis of chronic urticaria

• if laboratory tests are warranted, ESR and WBC count with differential

• Test for H. pylori infection, If no cause found

• Thyroid function tests and tests for thyroid antibodies are necessary only when symptomatic

• Skin Bx for suspected urticarial vasculitis

Diagnostic work up

• Challenge testing is indicated when a patient is being evaluated for a physical urticaria

• Patients with angioedema but without urticaria should have C4 levels measured to screen for CI-inhibitor deficiency

• CI-inhibitor levels can be measured if the C4 level is low

Chronic autoimmune urticaria

• Patients with autoantibodies have:• more wheals with a wider distribution• higher itch scores• more systemic symptoms• and lower serum IgE levels• more likely to require and benefit from immunosuppressive therapy

• Results with ELISA and immunobinding techniques have been disappointing

• A decrease in basophils (basopenia)

• ASST is currently not widely used (chronic autoimmune urticaria, more aggressive and resistant than chronic idiopathic urticaria)

ASST

• patient's own serum (during a flare) is injected intradermally into uninvolved skin of the forearm

• Saline and histamine controls are injected at the same time.

• the serum-injected site is 1.5 mm> saline-injected site

• The sensitivity (65-81%) and the specificity (71-78%)

ASST

• The ASST is useful in monitoring the course of chronic urticaria,(positive test consistent with an exacerbation) vs.(negative test with remission of symptoms)

• positive reaction, should be confirmed by the more specific in vitro testing (the gold standard), which demonstrates histamine release from target basophils and dermal mast cells

RefLab needs a sample of 1-2 mL of serum per patient to perform the test for autoantibodies. Serum is sent by ordinary mail at ambient temperature. In our laboratory serum and donor basophils are incubated and the % histamine release is detected. A histamine release > 16,5 % is a positive test result

Answer : D

Answer : c

Answer : E