We herein describe a 54 year-old female patient with a 5-year history of persistent and painful benign migratory glossitis (BMG), which was remarkably improved by systemic administration of cyclosporin. She had noted some white patches leaving smooth denuded red areas with whitish elevated borders on the dorsum of her tongue, and finally felt strong pain. The lesion was refractory to the previous treatment with topical corticosteroid treatment for the last 2 years. Because clinicopathological findings were compatible with BMG, systemic administration of 20 mg/day prednisolone and topical 0.1% dexamethasone application were started, however, she suffered a severe relapse after tapering the dosage of prednisolone to 10 mg/day. Because some investigations have suggested that BMG is an oral manifestation of psoriasis, we introduced cyclosporin administration. The systemic treatment of cyclosporin microemulsion pre-concentrate, 3 mg/kg/day, resulted in a satisfactory improvement. Two months later, we could reduce cyclosporin microemulsion pre-concentrate dosage to 1.5 mg/kg/day for maintenance therapy, and the disease has been well controlled so far.
We recently identified the efficacy and safety of a botulinum toxin (BTX)-A/B in Raynaud's phenomenon (RP) and digital ulcers (DU) in Japanese patients with systemic sclerosis (SSc). Detailed assessments of peripheral vascular disorder using angiography and dermoscopic images of nail fold capillaries have not been performed previously. This study aimed to evaluate the effect of BTX-B on SSc-associated peripheral vascular disorder. Two SSc patients who suffered with RP and DU were treated with a BTX-B injection, and thereafter the symptoms of RP were improved and DU healed in both patients. Furthermore, angiography showed an increased blood flow to the palm and fingers, and dermoscopic images of nail fold capillary changes showed improvement. These results suggest that a BTX-B injection may increase peripheral blood flow and improve RP and DU in SSc patients.
We aimed to evaluate the effect of small interfering RNA (siRNA) targeting CTGF on extracellular matrices (ECMs) metabolism in normal and SSc fibroblasts. Normal and SSc fibroblasts were transfected with CTGF-specific siRNAs to silence CTGF synthesis. After silencing CTGF, production of type I collagen and matrix metalloproteinase (MMP)-1 by fibroblasts stimulated with TGF-b was examined. Then quantitative analyses of protein production or mRNA expression of type I collagen, MMP-1,-2,-9 and tissue inhibitor of metalloproteinase (TIMP)-1 with TGF-b stimulation were carried out. Furthermore, after silencing CTGF, proliferations of normal and SSc fibroblasts were investigated. CTGF-specific siRNA significantly reduced CTGF production. The production of type I collagen was significantly reduced by CTGF silencing in normal fibroblasts. The CTGF silencing significantly increased the production of MMP-1 and decreased the production of TIMP-1 in SSc fibroblasts. The mRNA expression of MMP-1 was increased in CTGF-silenced SSc fibroblasts, but not in normal fibroblasts. There were no significant changes in the production or mRNA expression of other ECM-related genes in normal and SSc fibroblasts. Fibroblast proliferations were suppressed by CTGF silencing in normal and SSc fibroblasts. Our data showed that MMP-1 was increased by CTGF-specific siRNA transfection only in SSc fibroblasts. RNAi targeting CTGF could be a novel therapeutic strategy for SSc.Key words: connective tissue growth factor -matrix metalloproteinase-1 -small interfering RNA -systemic sclerosistype I collagen Please cite this paper as: Induction of matrix metalloproteinase-1 by small interfering RNA targeting connective tissue growth factor in dermal fibroblasts from patients with systemic sclerosis. Experimental Dermatology 2010; 19: e111-e116.
The Japanese guidelines for psoriasis therapy with cyclosporin microemulsion preconcentrate (CyA MEPC) has been revised, and the clinical application of CyA MEPC is being expanded to include mild to moderate psoriasis. In this study, we aimed to confirm the clinical efficiency of low-dose cyclosporin therapy in patients with moderate psoriasis vulgaris. After informed consent was obtained, 19 patients with psoriasis vulgaris were enrolled in this study. Each patient basically administrated CyA MEPC, 2.5 mg/kg/day, orally over 12 weeks. When the psoriasis area and severity index (PASI) score showed a 75% reduction from the initial value, the dosage of CyA MEPC was reduced to 1.5 mg/kg/day and added a topical application of active vitamin D3 ointment. We interviewed the patients as to their satisfaction for the usefulness and cost of the treatment. All patients obtained improvement within 12 weeks. In 10 patients whose PASI score reduced over 75%, we could reduce CyA MEPC dosage. No adverse effects were noted in any patients during the treatment. It is of note that the cost for 1.5 mg/kg/day administration of CyA MEPC was accepted by all the patients. In conclusion, this preliminary study suggests that the CyA MEPC is effective, safe and would provide patients with acceptable costs.
Dear Editor, Dermatomyositis (DM) is an autoimmune, idiopathic inflammatory disease affecting skeletal muscles and skin. A variety of autoantibodies, including anti-aminoacyl-tRNA synthetases (ARS), anti-clinically amyopathic DM (CADM)-140/melanoma differentiation-associated gene 5 (MDA5), anti-Mi-2, anti-transcriptional intermediary factor 1 gamma and anti-NXP2 antibody (Ab), are detected in the serum of patients with DM. Because each Ab is closely associated with certain clinical features, to identify Ab is important for classification of the clinical Table 1. Demographic and clinical characteristics of dermatomyositis patients with anti-ARS antibody Anti-ARS positive (n = 11) Anti-ARS negative (n = 40) P Age (years, mean AE SE) 49.2 AE 4.3 46.5 AE 3.1 0.61 Sex Male (%) 27.3 (3/11) 20 (8/40) 0.6 Female (%) 72.7 (8/11) 80 (32/40) CADM (%) 18.2 (2/11) 12.5 (5/40) 0.54 Skin eruption Heliotrope rash (%) 54.5 (6/11) 65 (26/40) 0.53 Periungual erythema (%) 27.3 (3/11) 35 (14/40) 0.63 Gottron's lesions (%) 63.6 (7/11) 90 (36/40) 0.03 Flagellate erythema (%) 9.1 (1/11) 35 (14/40) 0.1 Mechanic's hand (%) 45.5 (5/11) 17.5 (7/40) 0.05 Muscle involvement Myositis (%) 81.8 (9/11) 87.5 (35/40) 0.54 CK (IU/L, mean AE SE) 803.6 AE 325.6 1023.4 AE 287.9 0.62 Lung involvement ILD(%) 100 (11/11) 40 (16/40) <0.01 KL-6 (U/mL, mean AE SE) 1618 AE 566.6 1386.8 AE 619 0.78 FVC (%, mean AE SE) 86.4 AE 5.3 99.5 AE 4.9 0.14 DLCO (%, mean AE SE) 82.6 AE 9.5 86.4 AE 3.6 0.7 Others Arthralgia (%) 63.6 (8/11) 32.5 (13/40) 0.02 ANA (%) 0 (0/11) 15 (6/40) 0.17 Internal malignancy (%) 0 (0/11) 7.5 (3/40) 0.35 Use of the other immunosuppressive agents in addition to oral steroid 36.4 (4/11) 32.5 (13/40) 0.81 Histology Infiltration of mononuclear cells in epidermis 27.3 (3/11) 40 (14/35) 0.63Liquefaction or vacuolar degeneration of basal cells 63.6 (7/11) 88.6 (31/35) 0.06 DM was diagnosed by the Bohan and Peter criteria. CADM was diagnosed by the criteria by Sontheimer. This study was approved by the institutional review board of Gunma University. Patients were diagnosed as having myositis, when at least one abnormality was detected; muscle weakness, myalgia, elevated serum CK levels (>163 IU/L), histological myositis by muscle biopsy and findings of myositis by T 2 -weighted images on magnetic resonance imaging. Histological examination was performed on the hand (n = 3), arm (n = 2), trunk (n = 2), elbow (n = 1), knee (n = 1), thigh (n = 1) and face (n = 1) in anti-ARS antibody-positive patients, and at hand (n = 8), arm (n = 8), trunk (n = 6), elbow (n = 5), knee (n = 4), thigh (n = 2) and face (n = 2) in anti-ARS antibody-negative patients. P-values were calculated using Student's t-test or v 2 -test analysis. ANA, antinuclear antibody; ARS, anti-aminoacyl-tRNA synthetases; CADM, clinically amyopathic dermatomyositis; CK, creatine kinase; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; ILD, interstitial lung disease; SE, standard error.
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