FIT Board Review Corner April 2017
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1 FIT Board Review Corner April 2017 Welcome to the FIT Board Review Corner, prepared by Tammy Peng, MD, and Amar Dixit, MD, senior and junior representatives of ACAAI's Fellows-In-Training (FITs) to the Board of Regents. The FIT Board Review Corner is an opportunity to help hone your Board preparedness. Review Questions Allergy and Immunology Review Corner: Middleton s Allergy Principles and Practice, 8th Edition N. Franklin Adkinson Jr., MD, Bruce S Bochner, MD, A Wesley Burks, MD, William W Busse, MD, Stephen T Holgate, MD, DSc, FMedSci, Robert F Lemanske, Jr., MD and Robyn E O'Hehir, FRACP, PhD, FRCPath Chapter 36 (pages ): Urticaria and angioedema Prepared by: Tammy Peng, MD 1. Which of the following characteristics are more consistent with urticarial vasculitis? a. Lesions are pruritic and raised in appearance. b. Lesions are painful, last longer than 48 hours and may leave purpura or ecchymosis. c. Lesions may be erythematous with central pallor. d. Lesions are more common in areas in which there is compression or friction of the skin. 2. Which condition is characterized by fever, urticarial and monoclonal gammopathy? a. Mastocytosis b. Cryoglobulinemia c. Muckle-Wells syndrome d. Schnitzler syndrome 3. Which of the following represents the most effective, first-line treatment for chronic urticaria? a. Second-generation H1 antihistamine (cetirizine, fexofenadine, loratadine) b. Corticosteroids c. H2 blocker d. First-generation H1 antihistamine (diphenhydramine, hydroxyzine) 4. Which of the following characteristics is typical of polymorphic eruption of pregnancy (PEP), also called pruritic urticarial papules and plaques of pregnancy (PUPPP)? a. Rash involves the face, palms and soles. b. Urticarial lesions that occur around the umbilicus. c. Lesions are triggered by pressure applied to the skin. d. Rash begins as papules within abdominal striae and spreads to involve the extremity.
2 Page 2 of 5 5. Which of the following histamine-release associated features is seen in a chronic idiopathic urticarial (CIU) responder? a. 10% of cellular histamine content is released to optimal dose of cross-linking anti-ige b. Syk same as or below normal c. Reduced SH2 domain-containing inositol 5-phosphatase (SHIP)-1 levels d. Tenfold higher dose response to anti-ige in active disease e. Increased SH2 domain-containing inositol 5-phosphatase (SHIP)-2 levels 6. Skin biopsy of a lesion demonstrating a predominance of neutrophils consistent with neutrophilic urticaria would be seen in which disease? a. Hereditary autoinflammatory fever syndromes b. Chronic idiopathic urticaria c. Aquagenic Urticaria d. Dermatographism 7. Which of the following is the most common cause of chronic urticaria? a. Food allergies b. Physical urticaria c. Idiopathic urticaria d. Malignancy 8. Which of the following medications that can be used as an alternative therapy in antihistamine refractory chronic urticarial is preferred in urticarial vasculitis, delayed pressure urticarial and angioedema? a. Sulfasalazine b. Dapsone c. Omalizumab d. Calcineurin inhibitors (cyclosporine, tacrolimus) 9. Which of the following systemic diseases associated with urticarial lesions involves a mutation in cryopyrin? a. Mastocytosis b. Cryoglobulinemia c. Familial cold autoinflammatory syndrome d. Muckle-Wells syndrome
3 Page 3 of A 42-year-old woman presents to clinic with a two-month history of recurrent, pruritic rash. She reports that the rash usually develops in the evening often under the waistband of her pants. She also notes that she often has this same itchy rash on her shoulder after carrying her purse around for a few hours. What type of physical urticaria is most consistent with this patient s history? a. Cholinergic urticaria b. Pressure-related urticaria c. Solar urticaria d. Vibratory urticaria
4 Page 4 of 5 Answers 1. B, pages 579 & 582. Skin lesions that are painful, that last more than 48 hours and that leave residual skin changes including ecchymosis are more suspicious for urticarial vasculitis. Eliciting a history with the presence of such lesions should prompt consideration for skin biopsy. 2. D, page 582. Schnitzler syndrome is a rare systemic disorder in patients with monoclonal IgM or IgG (monoclonal gammopathy). Patients have associated symptoms of fever, weight loss, bone pain, adenopathy and urticaria thought to be secondary circulating immune complexes and complement activation. 3. A, page 582. The most effective, first-line therapy for chronic urticarial is the use of new-generation antihistamines which include fexofenadine, loratadine and cetirizine. These medications are nonsedating, alleviate pruritus and reduce occurrence of wheals. Other options if these agents are only partial effective, one can consider 1) increasing the dose of the nonsedating antihistamine 2) addition of a sedating, oldergeneration antihistamine (diphenhydramine, hydroxyzine) 3) addition of H2 blocker 4) trial of a leukotriene pathway inhibitor. 4. D, page 583. Polymorphic eruption of pregnancy (PEP), also called pruritic urticarial papules and plaques of pregnancy (PUPPP) is a pruritic dermatitis that affects pregnant women. Typically, dermatitis begins as erythematous papules within abdominal striae with periumbilical sparing that then spread to the extremities and coalesce into urticarial plaques. Lesions can be target-like and usually spare the face, palms and soles. Of note, because of limited safety data, only loratadine and cetirizine are currently recommended for use in pregnancy. 5. C, page 579, table Blood basophil IgE receptor responses in patients with chronic idiopathic urticarial (CIU) have been divided into two basophil phenotypes CIU responders and CIU nonresponders. CIU nonresponder basophils do not degranulate to ex vivo IgE receptor activation and have elevated levels of IgE receptor regulating inhibitor phosphatases, SHIP-1 and SHIP-2. These two phenotypes are independent of autoimmune serum factor and reflect some differences in clinical features. While underlying disease mechanisms are still unclear, available evidence supports basophil responsiveness relevance to urticarial pathogenesis. 6. A, page 576. Histopathologic examination of an urticarial lesion will show pervascular leukocyte infiltrate composed of lymphocytes, eosinophils, neutrophils, and basophils as well as mast cells that have degranulated in the dermis. Neutrophilic predominance on skin lesion biopsy should prompt for evaluation of associated systemic diseases including adult-onset Still disease, Schnitzler syndrome, systemic lupus erythematosus and the hereditary autoinflammatory fever syndromes.
5 Page 5 of 5 7. C, page 575. In 80% of cases of chronic urticaria where no external allergic cause or other disease process can be identified, the condition is called chronic idiopathic urticarial. Approximately 20% of patients with chronic urticaria have a reproducible physical trigger for their skin lesions (called physical urticarial). 8. B, page 582. There is limited evidence on use of dapsone in chronic urticaria, especially in neutrophilic urticarial. Dapsone is preferred in treatment of urticarial vasculitis, delayed pressure urticarial and angioedema. Patients on dapsone should be monitored for anemia, neuropathy and methemoglobinemia. Other treatments of chronic urticaria that serve as alternative to corticosteroids in antihistamine resistant cases include sulfasalazine, hydroxychloroquine, calcineurin inhibitors, mycophenolate and omalizumab. 9. D, page 582. Muckle-Wells syndrome is associated with mutations in cryopyrin. Patients often have sensorineural hearing loss and are similar to patients with familial cold autoinflammatory syndrome, with the exception that patients are not cold-sensitive. Patients with familial cold autoinflammatory syndrome often present in infancy with symptoms including periodic fever, urticaria, leukocytosis, conjunctivitis and muscle and skin tenderness after exposure to cold. 10. B, page 583, table There are two described forms of pressure-related physical urticarial/angioedema. In the first form, urticarial develops shortly after pressure is applied to the skin, similarly to dermatographism. A second delayed-onset form appears several hours after at the site of pressure (in our patient s example, under the waistband of her pants or under the strap of her purse). Skin biopsies from patients with delayed-onset urticarial demonstrate both neutrophils and eosinophils.
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