The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side-effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0.1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.

PUVA therapy was carried out on four patients with scleroderma; three of them had cutaneous manifestations of progressive systemic sclerosis and one other exhibited generalized morphea. PUVA therapy was given with daily doses of 0.25J/cm2 or 0.4J/cm2 for 3-8 weeks, resulting in total doses between 3.5J/cm2 and 9.6J/cm2. All four patients responded well to this treatment; improvements of hand closure, skin sclerosis index, and flexion of fingers or knee joints were obtained. Thus, PUVA appeared to be beneficial for treating scleroderma.

Tissue inhibitors of metalloproteinases (TIMP), common inhibitors of matrix proteinases, have cell-promoting activity. We studied the effects of recombinant human tissue inhibitor of metalloproteinases-2 (rh-TIMP-2) on the migration of normal human epidermal keratinocytes (NHEK). An in vitro migration assay revealed that rh-TIMP-2 enhanced random migration (up to 170%, p<0.05) in a dose-dependent manner. When we applied rh-TIMP-2 solution (20 microg/20 microl/wound) daily to full-thickness wounds made with an 8-mm punch on the backs of healthy (n=8), aged (n=9), and diabetic (n=15) rodents, we observed faster wound closure (p<0.05) than in vehicle-treated controls. Accelerated wound closure was dose-dependent (0-20 microg/wound) in diabetic mice (n=6), and the optimal concentration was 10-20 microg of rh-TIMP-2/wound. Histological examinations performed on days 0, 5, 10, 15, and 20 in diabetic mice revealed faster migration of epidermal keratinocytes from wound edges. These results suggest that rh-TIMP-2 plays an important role in wound healing.

Pachyonychia congenita type 2 (PC-2; MIM#167210), also known as Jackson-Lawler type (Jackson and Lawler, 1951), is a rare autosomal dominantly inherited disease characterized by hypertrophic nail dystrophy, focal keratoderma, multiple pilosebaceous cysts, natal teeth, and hair abnormalities (McKusick, 2001). Heterozygous missense mutations of the keratin 17 (K17) gene have been identi®ed in PC-2 (McLean et al, 1995). A mutation in the keratin 6b gene, which encodes K6b, the expression partner of K17, has also been reported in PC-2 (Smith et al, 1998). By sequencing genomic DNA from our PC-2 patient, we found a novel heterozygous mutation (G®A transition at nucleotide 452, 452G>A) in the helix initiation motif of the K17 gene resulting in a predicted substitution of valine (GTG) for methionine (ATG) at codon 102, V102M.A 19-y-old Japanese man visited our university clinic in March 2000. All of his nails had become thick 2 mo after birth. He had multiple normally colored papules and cysts on his scalp and axilla since he was 5 y old, and had hyperkeratosis with blister formation on his soles since he was 10 y old. At 16, the cysts on his scalp and axilla became painful and were repeatedly infected. His father, mother, and younger brother are healthy.Physical examination showed that he had many cysts and nodules all over his body, pachyonychia on all his ®ngers and toes, pili torti (twisted hair), and plantar hyperkeratosis with bullae. His eyebrows stand erect (Fig 1A). His mouth, tongue, and teeth were normal. Histologic examination of a subcutaneous cyst showed that the cyst wall was composed of several layers of epithelial cells accompanied by sebaceous gland lobules. Therefore, a diagnosis of steatocystoma was made.After informed consent, genomic DNA was extracted from a sample of his peripheral blood lymphocytes by a standard method (Qiagen, Hilden, Germany). Genomic DNA from 50 normal healthy Japanese people was used as a control. Exon 1 of the K17 gene was ampli®ed by polymerase chain reaction (PCR) with speci®c primers for the K17 gene as described previously (McLean et al, 1995). Nested PCR was initially performed using primers K17p8 (5¢-GCC TAT AAA GGA AGC GGG C-3¢) and K17p10 (5¢-CTC CTT TCT GCC TCC TCC T-3¢) and then primers K17p3 (5¢-TAT GGC AGC AGC TTT GGG-3¢) and K17p4 (5¢-GGT ACC AGT CAC GGA TCT TCA-3¢). Ampli®cation conditions were 95°C for 1 min, followed by 35 cycles of 95°C for 40 s, 58°C for 40 s, and 72°C for 1 min, and a ®nal extension at 72°C for 3 min. PCR products (157 bp) were puri®ed using a QIA quick PCR puri®cation kit (Qiagen), and were sequenced on an Applied Biosystem 310 automated sequencer using an ABI PRISM ¯uorescent dye terminator system (Perkin Elmer, Foster City, CA).Direct sequencing of DNA from the patient revealed a point mutation, 452G>A. This transition results in the substitution of a valine for a methionine (V102M). Another sequence change was found (T®C transition at nucleotide 457, 457T>C) but this transition does not change the predicted amino acid. To con®rm whethe...

Adult Still's disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Still's disease. A 33-year-old woman with adult Still's disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5-day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Still's disease. We present a detailed description of the patient and this novel therapy.