Urticaria 11/12/2010 BY: MOHAMMED ALSAIDAN. Urticaria Recurrent wheals that are usually pruritic,...
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Transcript of Urticaria 11/12/2010 BY: MOHAMMED ALSAIDAN. Urticaria Recurrent wheals that are usually pruritic,...
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Urticaria 11/12/2010
BY: MOHAMMED ALSAIDAN
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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
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Urticaria
• lifetime occurrence of urticaria in the general population ranges from 1% to 5%.
• Classification: clinical characteristics Vs. etiology
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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
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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
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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.
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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 ?
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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.
•
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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
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Autoimmune associations
• Autoimmune conditions associated with chronic urticaria :• Thyroid diseases • vitiligo• insulin-dependent diabetes mellitus• rheumatoid arthritis• pernicious anemia
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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
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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?
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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.
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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
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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
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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
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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
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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.
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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.
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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.
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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.
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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
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Muckle-Wells syndrome
• An autoinflammatory disorder associated with cold-induced autoinflammatory syndrome-1 gene mutations
• Characterized by urticaria, arthralgias, progressive sensorineural deafness, and amyloidosis
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(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
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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
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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.
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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
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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
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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)
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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%)
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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
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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
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Answer : D
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Answer : c
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Answer : E