Use of bosentan for digital ulcers related to systemic sclerosis: a real-life retrospective French study of 89 patients treated since specific approval.

OBJECTIVES: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. METHOD: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. RESULTS: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. CONCLUSIONS: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

[Assessment of tele-expertise among elderly subjects in retirement homes]. / Une expérience de télé-expertise en établissement d'hébergement de personnes âgées dépendantes (EHPAD).

BACKGROUND: Chronic wounds (leg ulcers, pressure ulcers, diabetic foot ulcers, etc.) constitute a real public health problem and engender high economic and human costs. Due to the declining physical and mental conditions of our elderly subjects and their rural environment, we created a computer program to assist with chronic wound management in elderly subjects living in retirement homes and to reduce the amount of ambulance transportation. MATERIALS AND METHODS: Each participating establishment was provided with a digital camera and its own secure e-mail address in order to allow photographs to be sent anonymously. Patients with chronic wounds entailing treatment difficulties were included. Details were recorded of the number of tele-expertise consultations given, the chronic wound type, the number of hospitalizations or medical consultations, and the number of ambulance trips avoided. The project was evaluated at 1 year. RESULTS: Of the 40 establishments invited to take part, 22 agreed to do so but only the first 10 respondents were accepted for participation in the pilot feasibility study. Funding ("Health and social prize" provided by the Haute-Vienne region Social Security Office - CPAM) was used to purchase the cameras. Beginning on 15 April 2010, 10 establishments for the elderly sent photographs of 34 patients presenting 26 chronic wounds and tele-expertise was provided for 10 pressure ulcers, two diabetic feet and 14 leg ulcers. CONCLUSION: Over a two-year period, this program helped avoid 20 trips for patients and enabled rapid hospitalization of nine patients by the university hospital by optimizing chronic wound management for patients residing in establishments for the elderly.

Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial.

BACKGROUND: Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-ß signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. OBJECTIVES: We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. METHODS: We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. RESULTS: Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30-71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. -0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. CONCLUSIONS: This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.

[Historic malignant tumour: 27 observations]. / Tumeur maligne historique: 27 cas.

BACKGROUND: When used in the French medical literature to describe a pathological state, the word "historic" normally refers to tumours of startling appearance because of their size. It is difficult to understand how a patient can allow such tumours to continue to grow. We attempt to define this concept. PATIENTS AND METHODS: Two dermatologists carried out a retrospective, independent and comparative selection of photographs taken between 1978 and 2008 of malignant cutaneous tumours of unusual size given the histological diagnosis. Socio-professional, demographic, clinical, histological psychological data, and details of treatment history and progress were collected. RESULTS: Twenty-seven patients (11 M, 16 F) of mean age 74 years (34-99 years) presented a "historic" tumour. Twelve patients lived in rural regions. Five patients were company executives. The average duration of development of the "historic" tumours was 4.5 years (6-420 months). The tumours were classed histologically as epidermoid carcinomas (nine) and melanomas (seven). The mean size was 13 cm (6-30 cm). Psychiatric problems, membership of sects or dementia were noted for 13 patients. Treatment consisted of chemotherapy, radiotherapy or, less frequently, surgery. Eighteen patients died on average 13 months after diagnosis. DISCUSSION: "Historic" malignant tumour (also described in the literature as "giant" tumour) is a real-life fact. No studies have been made of a series of such patients. Despite histological diagnosis, the size was associated with slow tumoral progress and/or late treatment, chiefly accounted for by psychiatric disorders. Socio-professional data indicate that "historic" tumours are equally common in urban and rural areas.

[Photodynamic therapy for the treatment of extramammary Paget's disease]. / Traitement de la maladie de Paget extramammaire par photothérapie dynamique topique.

BACKGROUND: The usual treatment for extramammary Paget's disease (EMPD) is surgery, but this approach may have grave functional and physical consequences, as well as high recurrence rates. Topical photodynamic therapy (PDT) offers an optional approach for EMPD; it has a high complete response rate and there is no dose restriction. The aim of this study was to evaluate the efficacy and safety of PDT in the treatment of EMPD. PATIENTS AND METHODS: This series of patients was seen at a single centre between 1 December 2005 and 31 December 2010. All patients with histologically confirmed EMPD were included. Patients received two courses of PDT 21 days apart: 3 hours after topical application of methyl aminolevulinic acid emulsion, they underwent illumination with red light (570-670 nm) at a dose of 37 J/cm(2) for 10 minutes. In the event of relapse, a further cycle was given at week 6. RESULTS: Eight patients (seven female, one male) of a mean age of 69 years were included. After two series of two illuminations, seven patients were in complete clinical remission at 3 months and one patient was in partial remission. Five patients were still in complete clinical remission at 6 months. All patients had relapsed after a mean 8.4 months (4-14 months). The limiting factor appears to be pain occurring during illumination. Patients reported satisfaction with the disappearance of symptoms and a notable improvement in quality of life. DISCUSSION: The complete clinical response rate to PDT at month 6, after two series of two illuminations, was equivalent to that for surgery. Although the recurrence rate was high, this treatment may be repeated without functional or physical consequences. PDT resulted in disappearance of pain and improved quality of life.

[Gardasil®-induced erythema nodosum]. / Erythème noueux induit par le Gardasil®.

Erythema nodosum is a panniculitis occurring more frequently in young women. We report a 16-year-old woman who presented with erythema nodosum that occurred following Gardasil® administration (vaccine against HPV types 6, 11, 16 and 18) and that is proposed to young female. This adverse effect is not a contraindication to the HPV vaccination because its benefit against the oncogene risk of Papillomavirus is documented.

[Dermohypodermitis on the face revealing TIBOLA]. / Dermohypodermite de la face révélatrice d'un syndrome TIBOLA.

Tick-borne lymphadenopathy (TIBOLA) is an emerging rickettsiosis in Europe, transmitted by the Dermacentor tick. This syndrome is defined as the association of an inoculation eschar on the scalp that may be surrounded by an erythema scalp, fever, and painful cervical lymphadenopathy in colder months. Children and women are at higher risk for TIBOLA. We report the case of a 9 year-old French child with an acute hemifacial edema and erythema revealing TIBOLA. Early empirical antibiotic therapy should be prescribed in any suspected TIBOLA, before confirmation of the diagnosis. The recommended treatment is doxycycline or macrolide.

High prevalence and risk factors of thromboembolism in stage IV melanoma.

BACKGROUND: Patients with cancer are at a high risk of thromboembolism (TE), which contributes to morbidity and mortality. Several case reports of thromboembolic events have been reported in patients with melanoma in the literature. OBJECTIVE: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in stage IV melanoma and determine risk factors, outcomes associated with the development of VTE and the number of haemorrhagic complications in patients under anti-coagulant treatment. PATIENTS AND METHODS: In this retrospective study, we included all consecutive patients with stage IV melanoma among 290 patients followed-up in the department of Dermatology each year between January 2005 and 31 December 2007. The diagnosis of VTE was confirmed by venous ultrasound, pulmonary perfusion-ventilation technetium scan and angiography. The primary outcome was to evaluate the number of TE diagnosed in stage IV melanoma patients. The secondary outcomes were to study the influence of TE on survival, its prevalence according to metastatic sites and to evaluate the number of haemorrhagic complications. RESULTS: Twenty-four VTE events were found [25.2% (CI: 16.5-34)]. Eighteen VTE were deep venous thrombosis in lower limbs associated with pulmonary embolism (PE) in 50% of cases. Twenty-five percent were asymptomatic and were revealed in the pulmonary scan performed for follow-up. Eight percent of VTE events revealed stage IV melanoma. Seventeen patients developed thrombosis at home after stopping heparin prophylaxis. Seven thrombotic events occurred during oral anti-coagulant therapy. CONCLUSION: We found as high a prevalence of VTE in stage IV melanoma as in lung and gastrointestinal cancers. All patients suffered thrombotic events when they were treated with chemotherapy and at home when they stopped heparin prophylaxis. Therefore, heparin prophylaxis should be maintained at home.