Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children

BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a benign self-limiting condition confined to the skin and subcutaneous tissue. However, the course of the disease is unpredictable and severe functional and cosmetic disability may result. Drug treatment with systemic corticosteroids in combination with methotrexate has been reported to be beneficial in LS, but data in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of systemic corticosteroids in combination with methotrexate in children with LS. METHODS: Treatment and outcome of 34 patients with LS were retrospectively analysed. Pulsed intravenous methylprednisolone was given, followed by oral prednisolone on a reducing regimen and maintenance treatment with methotrexate. We assessed treatment outcome clinically and by thermography and monitored adverse events. RESULTS: From the onset of treatment, the disease stopped progressing in 94% of the patients. All patients demonstrated significant clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%) patients therapy was discontinued when the disease was considered to be inactive clinically; however, seven (44%) of the 16 developed a relapse, necessitating repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34 patients had completely inactive disease. Observed adverse events were moderate and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest that systemic corticosteroids and methotrexate in combination are beneficial and well tolerated in the treatment of children with LS. Because of the risk of relapse after discontinuing therapy, long-term monitoring is mandatory.     

大剂量丙种球蛋白静脉滴注联合甲泼尼龙治疗重症多形红斑型药疹1例

报告1例别嘌醇引起的重症多形红斑型药疹伴外周血红细胞、白细胞和血小板降低,经甲泼尼龙60mg／d同时加用大剂量免疫球蛋白静脉冲击疗法(HDIVID)成功治愈,并且缩短了疗程。     

英夫利西单抗联合小剂量甲氨蝶呤治疗10例重度银屑病临床观察

生物制剂能靶向性阻断T淋巴细胞活化,阻断特异的细胞因子参与免疫反应,在欧美国家已广泛应用于银屑病等免疫介导的炎症性疾病［１］,显示出显著的疗效及良好的安全性。我们采用英夫利西单抗（infliximab）联合甲氨蝶呤（MTX）治疗10例重度银屑病,取得良好效果,报道如下……     

Interest of high-dose pulse corticosteroid therapy combined with methotrexate for severe alopecia areata: a retrospective case series

Background: The combination of systemic pulse corticosteroids and methotrexate in the treatment of severe alopecia areata has never been reported. Objective: The objective of this work was to give arguments for the efficacy and safety of this combined treatment. Methods: This was a retrospective case series of patients treated with intravenous 500 mg methylprednisolone per day for 3 consecutive days monthly during 3 months plus methotrexate initiated at the end of the second pulse regimen. We reviewed all case notes of patients who received this regimen between January 1 2007 and December 1 2010. Results: Twenty patients were treated. Data on hair regrowth at month 12 were available for all patients; 14 patients were still receiving the treatment on December 1 2010, 2 patients were lost of follow-up, and 4 patients had stopped the treatment. Of the 14 patients who were still receiving the treatment regimen at month 18, 10 (10/20, 50%) had total hair regrowth and 4 (4/20, 20%) had incomplete but satisfactory hair regrowth. The treatment was well tolerated. Conclusion: The initial treatment by pulse intravenous corticosteroids may influence the overall response. This approach should be evaluated in a larger series of patients.     

Treatment of severe localized scleroderma by plasmapheresis report of three cases

Summary We report three patients with severe, localized scleroderma, and with elevated titres of antinuclear antibodies, who were treated by plasmapheresis in combination with systemic steroid therapy. The therapeutic effectiveness of plasmapheresis was assessed on the basis of improvement in cutaneous and joint lesions. In all cases, significant improvement occurred after 2 months of therapy. Thus, in addition to treating systemic sclerosis, plasmapheresis can also be recommended for treatment of severe cases of localized scleroderma with elevated titres of antinuclear antibodies and antibodies to ss-DNA.     

Longitudinal melanonychia in localized scleroderma

Longitudinal melanonychia associated with scleroderma is rare. This is paradoxical, as increased skin pigmentation is frequent in the latter disease. This article reports 4 cases of longitudinal melanonychia that were found concurrently with various types of localized scleroderma. These 4 cases may be a coincidental finding despite the fact that pigmentation is so frequent a manifestation of scleroderma. In 2 cases, biopsy specimen of the nail matrix showed well-defined melanocytes without cellular atypia. This, in keeping with the pigmentation of scleroderma, appears to result from the functional activation of the matrix melanocytes.     

Case of localized scleroderma associated with osteomyelitis

We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T₂-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.     

Rheumatoid factor isotypes in localized scleroderma

Localized scleroderma is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with localized scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or normal controls (P < 0.0005). The levels of IgG RF were significantly higher in patients with GM than normal controls (P < 0.05). The levels of IgA RF were significantly higher in patients with GM or LS than normal controls (P < 0.001 and P < 0.01, respectively). The count of sclerotic lesions was significantly higher in patients with IgM RF than those without (P < 0.05). These results suggest that the presence of RF isotypes is one of the immunological abnormalities of localized scleroderma. IgM RF seemed to be most useful of these three factors to determine the severity of disease.     

Anti-U1RNP antibodies in patients with localized scleroderma

Abstract Antibodies to U1 ribonucleoproteins (RNP) have been detected in serum from patients with various autoimmune diseases. However, the presence of anti-U1RNP antibodies in patients with localized scleroderma has not been reported. In this study, we examined the frequency of anti-U1RNP antibodies using immunoprecipitation of U small nuclear RNAs and determined the antigen specificity by immunoblotting. Of 70 serum samples from patients with localized scleroderma, 2 (3%) immunoprecipitated U1 small nuclear RNA. Indirect immunofluorescence using HEp-2 cells as substrate showed coarse speckled nuclear fluorescence without nucleolar staining in both of the samples positive for anti-U1RNP antibodies. In addition, the presence of anti-U1RNP antibodies in each serum sample was confirmed by immunodiffusion against HeLa cell extracts. Immunoblotting analysis showed anti-70 kDa antibodies in each serum sample. This reaction against 70 kDa protein in the patients with localized scleroderma was analogous to that in patients with systemic sclerosis or mixed connective tissue disease. Both patients with positive serum were diagnosed as having linear scleroderma, but neither had evidence of Raynaud’s phenomenon or sclerodactyly. These results indicate that the presence of anti-U1RNP antibodies is one of the serological abnormalities in localized scleroderma, and that the mechanism of induction of anti-U1RNP antibodies in patients with localized scleroderma might be similar to that in patients with systemic sclerosis and mixed connective tissue disease. Received: 12 February 2001 / Revised: 27 April 2001 / Accepted: 11 July 2001     

UVA1联合外用他克莫司软膏治疗局限型硬皮病的疗效评价

目的:探讨UVA1联合外用他克莫司软膏治疗局限型硬皮病的临床疗效。方法:收集2016-2018年我院经过皮肤活检确诊为局限型硬皮病的22例患者,随机分为试验组(12例)与对照组(10例)。试验组采用UVA1联合外用他克莫司软膏治疗,对照组单独外用他克莫司软膏,比较治疗3个月后的Rodan修订评分(mRSS)值以及主要不良反应事件。结果:治疗3个月后,试验组的mRSS评分明显低于对照组(t=2.65,P=0.02);两组在不良反应方面差异无统计学意义(P值均>0.05)。结论:UVA1联合外用他克莫司软膏治疗局限型硬皮病有较好的疗效,安全性高。     

Misdiagnosis and delay in referral of children with localized scleroderma

Summary Background Localized scleroderma (LS) usually begins in childhood with a broad clinical spectrum and the diagnosis is often delayed. Objectives To investigate the diagnostic pathway in a large cohort of paediatric patients with LS, to identify the duration until correct diagnosis and to characterize clinical clues for early diagnosis. Methods A retrospective case note review of 50 children with LS. Results The median (range) age at disease onset was 5·2 (0·1–14·4) years and disease duration until diagnosis 11·1 (1·8–79) months. The patients were first seen by a general practitioner (or paediatrician) after 1·2 (0·2–48·7) months and in none of the cases was the condition recognized at presentation according to a parental questionnaire (no diagnosis in 44%, misdiagnosis of atopic eczema 20%, melanocytic naevus 8%, fungal infection 6%, bruise 4%, varicose vein 4%, bacterial infection 4% and others). The patients were referred to a local specialist (dermatologist in 72%) after a disease duration of 7·5 (1·0–70·9) months and in 64% the correct diagnosis was established. In 20% the diagnosis remained unknown, 8% were misdiagnosed as port‐wine stains and others as atopic eczema and melanocytic naevus. The correct diagnosis was eventually identified by the referring dermatologists, the paediatric dermatologists at our hospital, external maxillofacial surgeons and a paediatrician in 29 (58%), 17 (34%), 3 (6%) and 1 (2%), respectively. Histology was performed in 15 (30%). The patients were commenced on appropriate treatment after a disease duration of 16·6 (1·8–113·4) months. The main clinical diagnostic clues were: Blaschko‐linear distribution 76%, atrophic changes 68%, skin fibrosis 40% and loss of scalp hair or eyelashes 36%. Conclusions Physicians involved in the care of these children need to be aware of the characteristic clinical appearance of LS for early recognition and prompt initiation of treatment.