The mechanisms that lead to the development of skin lesions in patients with dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing immune response in the gut of patients with DH would result in an increase in circulating cytokines and be associated with endothelial cell activation, creating a proinflammatory environment in the skin. Skin biopsies from the normal-appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase antibodies, and serum IL-8 levels were significantly increased in patients with DH. These studies demonstrate that patients with DH have evidence of endothelial cell activation in the skin and systemic manifestations of the ongoing inflammation associated with the mucosal immune response. Endothelial cell activation may play a critical role in the development of skin lesions in patients with DH and may represent a common mechanism for cutaneous manifestations of inflammatory gastrointestinal diseases.
A 64‐year‐old white woman presented to our clinic with a 3‐month history of multiple blisters on her right breast which had been unresponsive to acyclovir, amoxicillin/clavulanate and fluconazole. She denied taking any antibiotics prior to the eruption. Physical examination revealed grouped vesicles on an erythematous base and shallow ulcerations in an annular pattern localized to the right breast, without areolar involvement (Fig. 1). There were no oral or mucosal lesions. Past medical history was significant only for a distant history of uterine carcinoma which had been successfully treated with hysterectomy/oophorectomy. No history of liver or autoimmune disease was present. Further examination failed to reveal any history of unusual contact allergens. There was no family history of similar eruptions. 1 Shallow ulcerations and blisters on erythematous bases in an annular pattern Punch biopsy specimen from lesional skin revealed a subepidermal blister with a dermal infiltrate consisting of numerous neutrophils and scattered eosinophils (Fig. 2). Direct immunofluorescence of perilesional skin demonstrated the presence of a homogeneous linear band of IgA deposits along the dermoepidermal junction and in dermal microvascular basement membranes (Fig. 3). IgG and C3 immunoreactants were not identified. 2 Subepidermal blister with a dermal infiltrate consisting of numerous neutrophils and scattered eosinophils (hematoxylin & eosin, × 20) 3 Linear deposits of IgA along the dermoepidermal junction and in dermal microvascular basement membranes (direct immunofluorescence of perilesional skin, × 40) After starting the patient on oral colchicine, 0.6 mg twice daily, no new blisters appeared, and within 1 week the eruption was nearly resolved. The patient tolerated therapy without any side‐effects, and at a follow‐up visit 5 weeks later had only minimal postinflammatory changes on the skin of the right breast. She then discontinued colchicine and remains free of any recurrence 6 months later.
Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.
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