Achilles tendinitis as a rare extraintestinal manifestation of ulcerative colitis.

Patients with inflammatory bowel disease often have extraintestinal manifestations (EIMs) involving almost all organ systems, but little has been reported on Achilles tendinitis. Herein, we present a unique case of Achilles tendinitis, which manifested shortly after initiation of mesalazine therapy for ulcerative colitis. A 26-year-old Japanese woman with bloody diarrhea and abdominal cramps lasting for 7 days was referred to our hospital. The Lichtiger clinical activity index (CAI) score was 9 at the first visit. Based on the clinical symptoms and examination results, she was diagnosed with ulcerative pancolitis in the active phase, and treatment with mesalazine (2.4 g/day) and probiotics was initiated. Her symptoms resolved within 7 days of treatment (CAI 3). However, she then developed bilateral Achilles tendinitis without any apparent cause. The Achilles tendinitis subsided with conservative management within 2 weeks, despite continuation of mesalazine therapy. This case instructively suggests that Achilles tendinitis should be noted as an EIM of ulcerative colitis.

Development of bullous pemphigoid after change of dialysis membrane.

A 75-year-old Japanese man presented with pruritic blisters and macules on his trunk and extremities. He had been on hemodialysis for 4 years because of chronic renal failure, and in recent months, a polymethylmethacrylate membrane had been used for dialysis. After a change in dialysis membrane to a cellulose triacetate membrane, pruritic tense blisters developed on the extremities in combination with marked blood eosinophilia. Physical examination showed erythematous macules and tense blisters on the trunk and extremities. A biopsy specimen of an erythematous macule showed subepidermal vesicles and eosinophils that attached to the dermal-epidermal junction. Serum level of eosinophilic cationic protein was elevated. From clinical, histological, and immunological findings, a diagnosis of bullous pemphigoid was made. New blisters continued to erupt during the period in which the patient used the cellulose triacetate membrane dialyzer, and even after the use of clobetasol propionate. It resolved only after the patient came back to the use of a synthetic membrane dialyzer. We discontinued the use of clobetasol propionate, and neither bullous eruptions nor blood eosinophilia recurred. These observations suggest that cellulose membrane may be involved in the development of bullous pemphigoid through activation of eosinophils in the blood and the skin lesion, as in the present case.

Elevated serum levels of APRIL, but not BAFF, in patients with atopic dermatitis.

Elevated serum levels of B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and/or a proliferation-inducing ligand (APRIL) are shown in autoimmune diseases. We determined serum levels of BAFF and APRIL, and clinical association in patients with atopic dermatitis (AD). Serum levels of BAFF and APRIL from 35 patients with AD, 25 patients with psoriasis vulgaris, 25 patients with systemic lupus erythematosus and 25 normal healthy subjects were examined by enzyme-linked immunosorbent assay. Serum levels of APRIL, but not BAFF, were significantly elevated in patients with AD than in healthy controls or patients with psoriasis vulgaris. Patients with severe AD exhibited significantly increased APRIL levels compared to patients with moderate AD and mild AD, and serum APRIL levels were significantly decreased after treatment compared with those before treatment. In addition, increased APRIL levels were significantly associated with serum immunoglobulin E levels and blood eosinophil numbers. These results suggest that elevated serum levels of APRIL are associated with disease severity and activity in AD, and APRIL may have an important role in the pathogenesis of AD.

The cutaneous reverse Arthus reaction requires intercellular adhesion molecule 1 and L-selectin expression.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-selectin (L-selectin(-/-)), ICAM-1 (ICAM-1(-/-)), or both (L-selectin/ICAM-1(-/-)). Edema and hemorrhage, which peaked 4 and 8 h after IC challenge, respectively, were significantly reduced in L-selectin(-/-), ICAM-1(-/-), and L-selectin/ICAM-1(-/-) mice compared with wild-type littermates. In general, edema and hemorrhage were more significantly inhibited in ICAM-1(-/-) mice than in L-selectin(-/-) mice, but were most significantly reduced in L-selectin/ICAM-1(-/-) mice compared with ICAM-1(-/-) or L-selectin(-/-) mice. Decreased edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesion molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1(-/-) mice. Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritoneal Arthus reaction. Furthermore, cutaneous TNF-alpha production was inhibited in each deficient mouse, which paralleled the reductions in cutaneous inflammation. These results indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction by regulating neutrophil and mast cell recruitment and suggest that ICAM-1 and L-selectin are therapeutic targets for human IC-mediated disease.