Atopic dermatitis (AD) is a chronic skin condition that affects 10% to 20% of children and 1% to 3% of adults. 1 Individuals with atopic dermatitis are at an increased risk for cutaneous infections with Staphylococcus aureus, herpes simplex, and the small pox or vaccinia virus. 2 Recently, it has been shown that defects in the innate immune system, such as the capacity to increase the production of broad spectrum antimicrobial peptides like cathelicidin, may account for this increase in infections. 3,4 Important insight into the mechanism responsible for the production of antimicrobial peptides came with the discovery of the vitamin D response element in the cathelicidin promoter and the finding that the conversion of 25-hydroxyvitamin D to the active 1,25 dihydroxyvitamin D by CYP27B1 can occur in keratinocytes and monocytes and is under the control of Toll-like receptor 2. 4-6 Thus, with infection or wounding, activation of Toll-like receptor 2 results in expression of CYP27B1, causing conversion of 25-hydroxyvitamin D to the active 1,25 dihydroxy-vitamin D, and subsequent induction of cathelicidin. 5,6 Our study sought to examine whether supplementation with oral cholecalciferol could provide the CYP27B1 enzyme enough substrate to overcome this relative deficiency in induction of cathelicidin in atopic patients.This was a single-center, controlled study of 14 normal controls and 14 atopic subjects with moderate to severe atopic dermatitis with an average Rajka-Langeland score of 6 (range, 4-9). Two-millimeter punch biopsies of uninvolved skin were collected from all subjects, and subjects with AD also received 2-mm punch biopsies of lesional skin. Baseline calcium and 25-hydroxyvitamin D levels were obtained. Supplementation with oral vitamin D3 (cholecalciferol) at 4000 IU per day was given for 21 days. At 21 days, subjects with AD received a 2-mm punch of involved skin, and all subjects had repeat biopsies of uninvolved skin, repeat serum calcium, and vitamin D levels. The study was approved by the Human Research Protection Program at the University of California, San Diego. All subjects gave written informed consent.Analysis of cathelicidin expression in skin was performed by qRT-PCR and normalized to GAPDH. Total RNA was isolated from the 2-mm skin biopsy samples from the subjects by homogenization. Briefly, the biopsy samples were placed into 2.0-mL polypropylene tubes
Recent progress in onchocerciasis research has led to improved understanding of the immunopathology of Onchocerca volvulus, as well as improvements in diagnosis and treatment of this morbid disease. This article reviews the recent literature, highlighting breakthroughs in sensitive means of antigen testing and an unusual new approach to therapy that targets an endosymbiotic bacterium required for filarial worm fecundity.
A 22-year-old male U.S. Navy airman with new nontender subcutaneous, 4-cm mass inferior to the right anterior costal margin was sent for routine biopsy. Sudden appearance of axillary lymph nodes prompted immediate excisional biopsy of the primary mass. Pathological evaluation was initially read as Onchocerca volvulus, the filarial nematode classically responsible for river blindness. Subsequent evaluation by Armed Forces Institute of Pathology resulted in a change of diagnosis to Dirofilaria species, not pathogenic in humans. The author discusses the literature of Dirofilaria infestations in humans, and how they may affect U.S. servicemen and women traveling to endemic areas.
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