S322 A b s t r a c t s J ALLERGY CLIN IMMUNOL FEBRUARY 2003

0 1 ~ Hydroxyzine from Various Topical Phospholipid Liposomal J Formulations: Evaluation of Peripheral Antihistaminic Activ-

ity and Systemic Absorption in a Rabbit Model A. A. W. Elzainy l, X. Gu l, E. R. Simons 2, K. J. Simonst; Ipharmacy, University of Manitoba, Winnipeg, MB, CANADA, 2pediatrics, Universi- ty of Manitoba, Winnipeg, MB, CANADA. RATIONALE: To assess hydroxyzine peripheral Hi-antihistamine activ- ity and extent of systemic absorption from hydroxyzine liposome formu- lations applied to the skin in a rabbit model. METHODS: Using L-t~-phosphatidylcholine, small unilamellar vesicles (SUV) and multilamellar vesicles (MLV) were prepared by the ethanol injection and a thin-lipid film hydration methods respectively. Hydroxyzine in Glaxal Base (GB) was the control. In a randomized, crossover study, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 female New Zealand rabbits (3,08 -+0.05 kg). Intradermal tests with 0.05 ml histamine phosphate (1 mg/ml), and blood sampling were per- formed before application, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 24 h. RESULTS: Compared to baseline, hydroxyzine from all formulations signif- icantly suppressed histamine-induced wheal formation by 75-95% for up to 24 h. Maximum suppression (95%) occurred from 3-6 h, with no differences among the products. Plasma hydroxyzine concentrations from SUV (1.1-+0.5 to 7.8-+3.1 ng/mL) and from MLV (0.45-+0.45 to 6.7-+2.8 ng/mL) were lower than from GB (9.9-+3.5 to 39.9-+12.7 ng/mL) (p< 0.05). Plasma cetirizine con- centrations from all formulations ranged from 18.4+_3.7 to 70.2-+7.4 with no differences among the products (p< 0.05). Only 0.02-0.06% of the initial hydroxyzine dose applied remained on the skin after 24 h. CONCLUSIONS: In this model, hydroxyzine from SUV and MLV has excellent topical Hi-antihistamine activity, and systemic exposure to hydroxyzine is reduced when these vehicles are used. Cetirizine formed in vivo contributed to the peripheral Hi-antihistamine effects of hydroxyzine. Funding: Pfizer USA

1014 Treatment of Keratodermam Hereditara Mutilans with Topi- cal Tacrolimus: A Case Study with Histopathology Pre- and Post-Treatment

M. A. Guanzon z, B. B. Faltay I , A. lshida-Yamamoto 2, B. A. Silverman ], A. T. Schneiderl; IAllergy/Immunology, Long Island College Hospital, Brooklyn, NY, 2Department of Dermatology, Asahikawa Medical Col- lege, Asahikawa, JAPAN. RATIONALE: Keratoderma Hereditaria Mutilans (KHM) is due to a frameshift mutation in the loricrin gene of chromosome 1. Loricrin, a major component of the stratum corneum, plays a role in the formation of keratohyalin granules and an intact water barrier. KHM manifests as thick- ening of the stratum corneum with an altered water barrier function and evidence of parakeratotic cell deposition. Loricrin protein is used as a marker for end differentiation in the stratum corneum. Successful selective antibody staining of mutant and wild type loricrin has been performed. In vitro studies have demonstrated inhibition of loricrin expression via sup- pression of calcineurin using mouse epidermis (Santini, 2001). METHODS: A 3 week trial of topical tacrolimus was conducted to inhib- it the mutant loricrin gene to produce a phenotypically normal stratum corneum and decrease Langerhan cells in a patient with KHM. A com- parison of baseline and repeat skin biopsies after 3 weeks of treatment with topical tacrolimus was done. RESULTS: Baseline biopsies showed marked hyperkeratosis, paraker- atosis and presence of CDla markers, lmmunofluorescence revealed the presence of the mutant loricrin protein in the granular and basal areas of the stratum corneum with perinuclear distribution and evidence of depo- sition in parakeratotic nuclei. Post-treatment H&E and anti-CDla immunohistochemical staining were unchanged; loricrin immunofluores- cence pending. Clinical findings showed no difference. CONCLUSIONS: Short-term trial with topical tacrolimus does not appear to affect the histologic and clinical manifestations of KHM. Effi- cacy of long term treatment is currently being evaluated. Funding: Long Island College Hospital

1 0 1 5 Netherton Syndrome: Probably a Frequently Misdiagnosed Entity

C. L. Hedberg I, D. J. Hogan 2, S. L BahnaL; IDepartment of Pediatrics, Section of Allergy/Immunology, Louisiana State University Health Sci- ences Center, Shreveport, LA, 2Department of Medicine, Section of Der- matology, Louisiana State University Health Sciences Center, Shreveport, LA. Netherton syndrome, an autosomal recessive disorder, seems very rare and is probably underdiagnosed. It comprises generalized ichthyosis, morpho- logic hair abnormalities, highly elevated IgE, and atopy. Recently, various mutations in the serine protease inhibitor Kasal type-5 (SPINK-5) have been demonstrated in patients and carriers. We evaluated a 14-month-old girl with severe red scaly rash involving her entire body and scalp. She was breastfed for 7 months and exhibited severe failure-to-thrive requiring gas- trostomy tube feeding at 8 months. Skin biopsy was described as ichthyosis vulgaris. Mother has asthma and a half-sister has atopic dermatitis and allergic rhinitis. Mother is unaware of a similar condition in the family. At 14 months she was <5th percentile in height and weight. Her hair was sparse and markedly thin. Serum lgE was elevated (285 IU/ml). RAST was positive to egg white, peanut, and wheat, and negative to corn, cow milk, and soybean. Microscopic hair examination revealed twisting, invagination and cane-stick appearance. GI endoscopy was normal and liver biopsy showed intrahepatic bile duct obstruction and cirrhosis. SPINK-5 genetic testing revealed a compound heterozygote for two deletion mutations: 316DelGA and 2441-1DelGTGA. The skin showed no improvement with moisturizers, slight improvement with tacrolimus ointment, and moderate improvement on topical steroids. Netherton syndrome should be suspected in infants with generalized ichthyosis, atopy and abnormal hair morpholo- gy with confirmation by SPINK-5 testing. Differential diagnosis should inlude Leiner's disease and Omenn syndrome. Funding: Self-funded

0 1 6 Relapsing Post-infectious Rash with Desquamation

B. Mahboub I, E Vadas2; IAllergy and Clinical immunology, University of Toronto, Toronto, ON, CANADA, 2St. Michael's Hospital, University of Toronto, Toronto+ ON, CANADA. RATIONALE: Skin rash followed by desquamation is a characteristic manifestation of toxic shock syndrome. This condition is caused by bac- terial exotoxins which act as superantigens to induce a dysregulated immune response. METHODS: Herein, we report three cases of otherwise healthy adults who experienced relapsing rash with desquamation following respiratory tract infections. A 46-year-old woman had a history of tonsillar carcinoma treated with surgical excision and postoperative irradiation several years earlier. She presented with 8 episodes of erythematous skin rash involving the face, neck and anterior chest that persisted for about 4 weeks and set+ tied with desquamation of the involved skin. All the episodes of rash were preceded by pharyngitis. A 54-year-old woman presented with a 15-year history of recurrent episodes of cough and sinus congestion that, over the course of a day, progressed to erytheroderma of the head and neck fol- lowed by desquamation of the affected areas as well as her palms and soles. A 75-year-old man reported recurrent upper respiratory tract infections, always followed three days later by development of an erythematous patch on the left calf, then the right cal l leading to desquamation of his palms and soles. Laboratory investigations, including CBC, protein electrophore- sis, immunoglobulin quantitation and ASOT were negative. Neither pred- nisone nor antibiotics shortened the duration or severity of relapses. RESULTS: The patients described above experienced a relapsing desqua- mative skin disorder following respiratory tract infections. However, there was no associated cardiopulmonary involvement. CONCLUSION: The cutaneous manifestations resemble an attenuated form of toxic shock syndrome. Funding: Self-funded