Neonatal onset multisystem inflammatory syndrome (NOMID)

Abstracts S105

J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2

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Progesterone Associated Angioedema and Vasculitis

A. S. Bagg1, D. K. Ledford2, R. F. Lockey2; 1Internal Medicine, University of South Florida, Tampa, FL, 2Allergy and Immunology, University of South Florida, Tampa, FL. RATIONALE: Physiologic hormone changes associated with menstruation have been associated with dermatitis, angioedema, anaphylaxis, and asthma. Immunologic responses against physiologic hormones, including type I hypersensitivity reactions, have been proposed to explain these phenomena. Cyclic perimenstrual reactions to progesterone are rare and only 50 published cases have been reported. METHODS: A 41-year old white female has a 20-year history of angioedema and purpuric rashes occurring in proximity to her menstrual cycle. A skin biopsy of the menstrually related rash and intradermal skin testing with progesterone, 0.1 ml of 1mg/ml medroxyprogesterone, were done. RESULTS: The skin biopsy of the perimenstrual dermatitis showed a leukocytoclastic vasculitis with eosinophils. The progesterone skin test initially resulted in erythema around the skin test site but no wheal and flare and limited pruritus. Within 5 minutes urticarial lesions developed on the shoulder and lower back. At 30 minutes urticaria developed along the upper arm, forearm, and wrist of the test site arm. Oral antihistamine without epinephrine resulted in improvement and no vasculitis type rash developed. CONCLUSIONS: This is the first case of menstrually associated angioedema and vasculitis with intradermal progesterone resulting in a systemic urticarial reaction and a negative local wheal-and-flare response. The immunologic mechanism for this phenomenon is unknown. This case supports the potential value of skin testing with progesterone to guide treatment options. If sensitivity to progesterone is documented, the reduction of the progesterone surge by suppressing ovulation will likely be of benefit. Funding: University

Neonatal Onset Multisystem Inflammatory Syndrome (NOMID) D. F. German1, A. Goodman2, P. Strub1, F. Bocobo1; 1Allergy, Kaiser Permanente Medical Center, San Francisco, CA, 2Pediatrics, Kaiser Permanente Medical Center, San Francisco, CA. BACKGROUND: Urticaria presenting neonatally is an unusual finding. We present a case ultimately diagnosed as NOMID. CASE REPORT: This 5 year old white male was born prematurely; placenta showed chronic necrotizing funisitis. Neonatally, he exhibited generalized urticaria-like variable persistent maculopapular rash. At 11 months, he still exhibited generalized non-pruritic lesions with raised erythematous borders and central clearing, relapsing fevers, and irritability. RAST was positive to egg. He had neutrophilia, anemia, elevated ESR, negative ANA and ANCA. Skin biopsy revealed perivascular interstitial dermatitis with neutrophils and perieccrine infiltrates. He continued with rash, fevers, and arthralgia. Ibuprofen and cetirazine offered partial relief; rash improved with viral infections, and MMR and varicella vaccines. Subsequent evaluations revealed adenopathy, mild sensorineural hearing loss, increased CSF pressure and papilledema. Laboratory findings included neutrophilia and elevated ESR. Genome DNA study revealed abnormal C1ASI gene associated with cryopyrin disorders; NOMID was diagnosed. Anakinra (recombinant IL1 receptor antagonist) therapy instituted at N.I.H. resulted in regression of rash, irritability, fever, decrease in CSF pressure and papilledema, and ESR normalization. DISCUSSION: This patient exhibits features of NOMID, including neonatal onset urticaria-like rash, relapsing fevers, irritability, adenopathy, bony abnormalities, elevated CSF pressure, papilledema, neutrophilia, and elevated ESR. Skin biopsy showing perieccrine infiltrates is characteristic. Genome DNA study demonstrated abnormal C1ASI gene consistent with cryopyrin disorders (familial cold urticaria, Muckle-Wells Syndrome, and NOMID). Treatment with anakinra is effective. CONCLUSION: NOMID is a rare condition. Physicians should be alerted in neonates presenting with a plethora of urticaria-like lesions which persist through infancy.

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Evaluation of Skin Reactions to Pimecrolimus Cream 1% in Patients Allergic to Propylene Glycol J. F. Fowler1, D. J. Lorenz2, A. Parneix-Spake3; 1University of Louisville Medical School, Louisville, KY, 2University of Louisville, Louisville, KY, 3Novartis Pharmaceuticals Corp., E Hanover, NJ. BACKGROUND: Topical formulations containing propylene glycol (PG), may induce irritant and allergic contact dermatitis (ACD). Pimecrolimus cream 1% is a non-steroid cytokine inhibitor containing low concentrations of PG (5%). OBJECTIVES: Assess incidence, nature and severity of skin reactions to pimecrolimus cream in patients allergic to PG. METHODS: Double-blind, randomized, vehicle-controlled, withinpatient study of 20 subjects. Subjects underwent 48-hour patch-testing on the back with PG (30% and 100%), pimecrolimus cream and vehicle, followed by a 7-day repeated open application test on the forearms (ROAT), where pimecrolimus and vehicle were applied BID under normal use conditions without occlusion. Application sites were assessed using a scale ranging from 0 (no reaction) to 7 (spreading bullous reaction), 48 and 120 hours after patch removal and at completion of ROAT. RESULTS: PG allergy was confirmed in 16 subjects. In 2 of these, patchtest scores with pimecrolimus cream were compatible with ACD (scores of 4 and 6). However, no signs of ACD were observed in these 2 patients when pimecrolimus cream was applied by ROAT. Two other subjects demonstrated scores higher than 1 (2 and 3) at the pimecrolimus site during ROAT, but the allergic component in these patients is unlikely since there was no reaction with vehicle. Patch-test reactions with pimecrolimus cream were significantly less frequent (p<0.01) and their median severity was significantly lower than with PG (p=0.02 vs. PG 30% and p<0.01 vs. PG 100%). CONCLUSIONS: This pilot study suggests that pimecrolimus cream 1% can be used safely in patients with PG allergy when applied under normal conditions. Funding: Novartis

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Clinical Pharmacology of Levocetirizine, the Active Enantiomer of Cetirizine, in Children Age 6-11 Years E. R. Simons1, S. S. Goritz1, K. J. Simons2,1; 1Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, CANADA, 2Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, CANADA. RATIONALE: The pharmacokinetics and pharmacodynamics of a medication sometimes differ between children and adults, necessitating different dose regimens. The clinical pharmacology of levocetirizine, used for allergic rhinitis and urticaria treatment in Europe, has not been studied prospectively in school-age children. We hypothesized that it would have a prompt onset of action and a 24-hour duration of action in children age 6-11 years. METHODS: Before levocetirizine 5 mg was ingested, and at specified intervals from 0.5 to 28 hours thereafter, blood samples were obtained for quantification of levocetirizine in plasma by HPLC-MS/MS. Concurrently, epicutaneous tests with histamine phosphate 1 mg/mL were performed. Wheals and flares were traced at 10 minutes and the areas were measured using a computerized digitizing system. RESULTS: In 14 children, mean (±SEM) age 9.1±0.7 years, the peak levocetirizine concentration was 450±37 ng/mL, and the time at which peak concentrations occurred was 1.2±0.2 hours. The terminal elimination half-life was 5.7±0.2 hours, the oral clearance was 0.82±0.05 mL/min/kg, and the volume of distribution was 0.4±0.02 L/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate were significantly decreased from 1 to 28 hours (p<0.05); mean maximum inhibition occurred at 2-10 hours (97%±1%) and 2-24 hours (93%±1%), respectively. CONCLUSIONS: Levocetirizine had a prompt onset of action and significant, long-lasting peripheral H1-activity. Once-daily dosing appears to be optimal in this pediatric population, as it is in adults. Funding: UCB Pharma

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