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(24­36) 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