Anna Belloni-Fortina

Methotrexate treatment in juvenile localized scleroderma: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE Juvenile localized scleroderma is a chronic progressive fibrotic disorder of the skin that causes permanent disability and aesthetic damage. This study was undertaken to assess the safety and efficacy of methotrexate (MTX) in the treatment of juvenile localized scleroderma. METHODS In this double-blind study, patients with active juvenile localized scleroderma were randomized (2:1) to receive oral MTX (15 mg/m², maximum 20 mg) or placebo once weekly, for 12 months or until treatment failure. Both groups received oral prednisone (1 mg/kg/day, maximum 50 mg) for the first 3 months. A target lesion was evaluated clinically, with infrared thermography and using a computerized scoring system with skin score rate (SSR) evaluation. Response to treatment was defined as the absence of new lesions, SSR ≤ 1, and a decrease in lesion temperature of at least 10% compared to baseline. Treatment failure was defined as the occurrence of new lesions, SSR > 1, or increased lesion temperature. All analyses were done on the intent-to-treat population. RESULTS Of the 85 patients screened, 70 (ages 6-17 years) were randomized (46 to the MTX group, 24 to the placebo group). The mean disease duration was 2.3 years. After an initial response in all patients, disease relapsed in 15 MTX-treated patients (32.6%) and 17 placebo-treated patients (70.8%) (P < 0.005). New lesions appeared in 3 MTX-treated patients (6.5%) versus 4 placebo-treated patients (16.7%). The mean SSR decreased from 1 to 0.79 in the MTX group and increased from 1 to 1.1 in the placebo group, and the mean target lesion temperature decreased by 44.4% in the MTX group versus 12.1% in the placebo group. Twenty-six patients in the MTX group (56.5%) and 11 patients in the placebo group (45.8%) developed mild side effects related to treatment. None of the side effects were severe enough to necessitate treatment discontinuation. CONCLUSION Our findings indicate that MTX is efficacious in the treatment of juvenile localized scleroderma and is well tolerated.

A long-term follow-up study of methotrexate in juvenile localized scleroderma (morphea).

BACKGROUND Recent studies report that methotrexate (MTX) is beneficial in the treatment of juvenile localized scleroderma (JLS) but little is known about its long-term effectiveness. OBJECTIVE We assessed the therapeutic role of MTX in children with JLS who were followed up for a prolonged period. METHODS A cohort of patients with JLS, previously enrolled in a double-blind, randomized controlled trial and treated with oral MTX (15 mg/m(2)/wk) and prednisone (1 mg/kg/d, maximum 50 mg) for the first 3 months, were prospectively followed up. Lesions were evaluated clinically, with infrared thermography, and by a computerized skin score. Response to treatment was defined as: (1) no new lesions; (2) skin score rate less than 1; and (3) decrease in lesion temperature by at least 10% compared with baseline. Clinical remission (CR) on medication was defined when response was maintained, on treatment, for at least 6 months, and complete CR when response was maintained, without treatment, for at least 6 months. RESULTS Of 65 patients treated with MTX, 48 (73.8%) were responders, 10 (15.4%) relapsed by 24 months since MTX start, and 7 (10.8%) were lost to follow-up. Among the responders, 35 (72.9%) maintained CR for a mean of 25 months and 13 (27.1%) were in CR on medication. Adverse effects seen in 28 patients (48.3%) were generally mild and never required treatment discontinuation. LIMITATIONS The use of objective measures not widely available, such as infrared thermography and computerized skin score, makes it difficult to compare data from previous studies. CONCLUSIONS Long-term MTX therapy is beneficial and well tolerated for JLS.

Eruptive melanocytic nevi in patients with renal allografts: report of 10 cases with dermoscopic findings.

Eruptive nevi have been reported after renal allograft transplantation, particularly in children and adolescents, and immunosuppression has been suggested to favor both benign and malignant melanocyte proliferation. In this study, we describe the dermoscopic features of eruptive melanocytic nevi in 10 children, adolescents, and young adults with renal allografts in whom multiple melanocytic nevi developed during a short period after transplantation. Dermoscopy of the eruptive pigmented lesions revealed a peripheral rim of brown globules. This rim of peripheral globules was present in 80% of the patients with eruptive nevi and in most of the lesions of the same patient. The other standard dermoscopic criteria for melanocytic nevi were normal. In our study, we confirm previous reports concerning the development of eruptive nevi in children and adolescents receiving immunosuppressive therapies. In particular, we showed by dermoscopy the presence of a characteristic symmetrical rim of peripheral brown globules. This finding is consistent with the hypothesis that a symmetrical peripheral rim of globules may indicate rapid enlargement of melanocytic lesions. Moreover, we have identified a new group of patients characterized by this dermoscopic feature. These patients are children, adolescents, and young adults with renal allografts receiving immunosuppressive therapy and it is plausible that this dermoscopic characteristic may be found in eruptive nevi developed in association with immunosuppression from any cause.

Detection of autoantibodies against recombinant desmoglein 1 and 3 molecules in patients with pemphigus vulgaris: correlation with disease extent at the time of diagnosis and during follow-up.

The recent availability of cDNA clones for pemphigus antigens has allowed the production of recombinant desmoglein 1 and desmoglein 3 molecules and the development of an ELISA approach in order to determine levels of antibodies to them. The aim of the study was to determine the relationship between autoantibodies levels and the extent of both mucosal and skin lesions in 20 patients with pemphigus vulgaris at the time of diagnosis and during follow-up. For the detection of autoantibodies by ELISA we used the recombinant proteins expressing overlapping sequences with the entire extracellular desmoglein 1 and desmoglein 3 domains. We showed that in presence of mucosal lesions there was a correlation between extension of mucosal involvement and autoantiboidies titres against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions there was a statistically significant correlation between extension of skin lesions and autoantibodies titres against desmoglein 3, but not against desmoglein 1. A not negligible number of patients showed variations of the desmoglein 3 autoantibodies titre which did not correlate with the severity of both cutaneous and mucosal involvement. Similar results were obtained analyzing autoantibodies titres against desmoglein 1. In conclusion, we believe that the utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should be used with caution to monitor disease severity and response to therapy, although it remains a high specific test for the initial diagnosis of pemphigus and the identification of a change in the clinical phenotype of this condition.

Primary Cutaneous CD30+ Anaplastic Large Cell Lymphoma in a Heart Transplant Patient: Case Report and Literature Review

Solid organ transplant recipients are at risk of developing a wide range of viral-associated malignancies, including skin tumours and lymphoproliferative disorders. The risk of a post-transplant lymphoproliferative disorder is 28-49 times the risk of a lymphoproliferative disorder in the normal population. Most cases are of B-cell phenotype and are associated with Epstein-Barr virus infection. Post-transplant lymphoproliferative disorders presenting clinically in the skin are rare and usually of B-cell phenotype. Only rare cases of cutaneous T-cell post-transplant lymphoproliferative disorder have been reported previously, mostly mycosis fungoides type. We describe here a rare primary cutaneous T-cell lymphoma CD30+ arising in a heart transplant patient who had a nodule on the right leg, several years after heart transplantation. The morphology and immunohistochemical findings were consistent with a CD30+ anaplastic large cell lymphoma with a T-cell phenotype. Excisional biopsy and radiotherapy of the affected area were performed. In this patient, the presence of a solitary lesion and the lack of systemic involvement represented the main factors taken into account in choosing the therapy and the patient was therefore treated using a non-aggressive approach, although with systemic immunosuppression. In conclusion, the diagnosis of a CD30+ anaplastic large cell lymphoma in transplant recipients does not imply aggressive clinical behaviour by the lymphoma.

Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy

Acrodermatitis continua of Hallopeau (ACH) consists of a relapsing pustular eruption of the distal portions of hands and feet. We described a case of a 9‐year‐old boy affected by ACH, successfully treated with targeted ultraviolet B 311 nm phototherapy, which seems to be an effective and safe therapy for this condition.

Vohwinkel syndrome: treatment of pseudo-ainhum

Background  Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare autosomal dominant palmoplantar keratosis which manifests in infants and becomes more evident in adulthood.

Biochip Technology for the Serological Diagnosis of Bullous Pemphigoid

Bullous pemphigoid is an autoimmune blistering skin disease characterized by the presence of circulating autoantibodies which recognize specific proteins of the epidermis and dermoepidermal junction. Diagnosis is based on clinical criteria and laboratory investigations, notably histology, direct and indirect immunofluorescence, and ELISA. This study describes a new immunofluorescence assay for parallel determination of anti-BP180 and anti-BP230 based on recombinant antigenic substrates. The aim of the study was to detect BP180 and BP230 autoantibodies by BIOCHIP technology using both a specially designed recombinant BP180-NC16A protein and cells expressing the BP230-gc antigen fragment. 18 patients with bullous pemphigoid were included in the study. Autoantibodies to BP180 were detected by the BIOCHIP technique in 83.33% of patients with clinical, serological, and immunohistological confirmed bullous pemphigoid while autoantibodies against BP230-gC were detected only in 39% of patients. The detection of anti-BP180-NC16A and anti-BP230-gC by a new biochip-based immunoassay is a suitable alternative to indirect immunofluorescence and ELISA. This method has the advantage of easily discriminating the different autoantibody specificities. The BIOCHIP method is faster, cheaper, and easy to use when compared with the ELISA approach. For this reason, the new method could be used as an initial screening test to identify patients with bullous pemphigoid, and doubtful results could then be confirmed by ELISA.

Melanoma and immunosuppression.

In a recent article, Richtig et al. [1] suggested that immunosuppression may be a risk factor for melanoma development and, in order to support this view, cited a study demonstrating an increased frequency of melanoma in organ transplant recipients receiving long-term immunosuppression [2] . There are also several laboratory findings indicating that immune surveillance has a fundamental role in melanoma genesis and this has led to the development of different immunotherapeutic approaches for the treatment of metastatic melanoma [3] . Therefore, if the immune system has a central role in the defense mechanisms against melanoma, then there should be a markedly higher incidence of melanoma among organ transplant recipients. However, published studies including at least 1,000 organ transplant recipients have demonstrated that there is only a slight increase in melanoma incidence (1.6–2.5 times more common if compared with the general population) [4] and some authors found no real increase of melanoma among these patients. To this regard, a large study including over 5,000 solid organ transplant recipients showed that there was no increase in incidence if compared with the general population [5] . In contrast to the controversial findings in melanoma, several studies have demonstrated that the risk of skin carcinomas, in particular squamous cell carcinoma, is consistently and greatly increased in organ transplant patients who receive long-term immunosuppression [6, 7] . Furthermore, there is eviPublished online: October 2, 2008

Nevus Spilus and Melanoma: Case Report and Review of the Literature

Background: Nevus spilus is characterized by a pigmented patch with scattered flat or maculopapular speckles. Nevus spilus was first described by Burkley in 1842. Since then, this lesion has been widely debated in the literature, particularly for the possible occurrence of melanoma within the lesion. Objective: We describe the case of a 65-year-old female presenting with a nodular achromic melanoma that occurred within a nevus spilus on the left thigh. Conclusion: Our observation is consistent with the idea that this entity in some circumstances may have the ability to evolve into a malignant melanoma.