ABSTRACT
Lower-limb ulcers in systemic sclerosis patients are rarely reported. The aim of this study was to describe the main causes and outcomes of lower-limb ulcers in systemic sclerosis patients and to assess factors associated with ischaemic causes (arterial disease and/or microvascular impairment). A retrospective, multicentre, case-control study was conducted in 2013 and 2014, including 45 systemic sclerosis patients presenting lower-limb ulcers between 2008 and 2013. The estimated prevalence of lower-limb ulcers among systemic sclerosis patients was 12.8%. Ulcers were related to venous insufficiency in 22 cases (49%), ischaemic causes in 21 (47%) and other causes in 2 (4%). Complete healing was observed in 60% of cases in a mean time of 10.3 months; 59% relapsed during a mean follow-up of 22 months. Ischaemic lower-limb ulcer outcomes were poor, with a 28.6% amputation rate. Logistic-regression multivariate analyses between ischaemic lower-limb ulcer cases and matched systemic sclerosis-controls identified past or concomitant digital ulcer and cutaneous sclerosis of the feet as independent risk factors associated with ischaemic lower-limb ulcers.
Subject(s)
Ischemia/epidemiology , Leg Ulcer/epidemiology , Scleroderma, Systemic/epidemiology , Adult , Aged , Aged, 80 and over , Amputation, Surgical , Chi-Square Distribution , Disease Progression , Female , France/epidemiology , Humans , Ischemia/diagnosis , Ischemia/therapy , Leg Ulcer/diagnosis , Leg Ulcer/therapy , Limb Salvage , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prevalence , Recurrence , Retrospective Studies , Risk Factors , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/therapy , Time Factors , Treatment Outcome , Wound Healing , Young AdultABSTRACT
IMPORTANCE: There is an increasing interest in BRAF V600 mutations in melanomas and their associated sensitivity to vemurafenib, a BRAF inhibitor. However, physicians cannot find information in the literature about vemurafenib response for rare and/or atypical BRAF mutations. OBSERVATIONS: We describe the identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. Using a pyrosequencing method, we determined that the tumor positive for mutated BRAF, uncovering a novel c.1799_1803delinsAT; p.V600-K601>D variant. We uncovered this atypical BRAF mutation with 2 different sequencing methods, both in the primary lesion and in 1 metastasis. The patient was immediately treated with vemurafenib as monotherapy and achieved a prolonged (5.5-month) positive response. CONCLUSIONS AND RELEVANCE: We analyzed the consequences of the BRAF V600-K601>D mutation in terms of amino acids. We referred to the published data and databases to screen chemical properties of well-known BRAF V600 mutations and other complex BRAF mutations to find common features of activated BRAF mutations. Importantly, we highlighted that both the site of the mutation and the involved amino acids are important to predict vemurafenib response. Our conclusion is that complex BRAF mutation surrounding codon 600 could also be sensitive to BRAF inhibitors.
Subject(s)
Indoles/therapeutic use , Melanoma/drug therapy , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/drug therapy , Sulfonamides/therapeutic use , Antineoplastic Agents/therapeutic use , Humans , Male , Melanoma/genetics , Middle Aged , Mutation , Neoplasm Metastasis , Sequence Analysis, DNA , Skin Neoplasms/genetics , Time Factors , Treatment Outcome , VemurafenibSubject(s)
Acute Generalized Exanthematous Pustulosis/pathology , Hashimoto Disease/pathology , Acute Generalized Exanthematous Pustulosis/drug therapy , Adult , Antithyroid Agents/therapeutic use , Carbimazole/therapeutic use , Colchicine/therapeutic use , Diagnosis, Differential , Female , Hashimoto Disease/drug therapy , Humans , Thyroxine/therapeutic use , Tubulin Modulators/therapeutic useABSTRACT
Fixed drug eruption (FDE) is one of the most typical cutaneous drug adverse reactions. This localized drug-induced reaction is characterized by its relapse at the same sites. Few large series of FDE are reported. The aim of this study was to retrospectively collect and analyse well informed cases observed in a hospital setting. This study involved 17 academic clinical centers. A French nation-wide retrospective multicentric study was carried out on a 3-year-period from 2005 to 2007 by collecting data in seventeen departments of dermatology in France. Diagnosis of FDE was based essentially on clinical findings, at times confirmed by pathological data and patch-testing. Records were reviewed for demographics, causative drugs, localization, severity, and patch-tests, when available. Fifty nine cases were analysed. Patients were 59-years-old on average, with a female predilection. The most common drug was paracetamol, followed by the non-steroidal anti inflammatory drugs. The time between drug intake and skin symptoms was, on average, two days. Beside these classical characteristics, some original findings were found including, a frequent non pigmentation course and a sex-dependent pattern of distribution. Women often had lesions on the hands and feet, and men on the genitalia. Given the fact that skin pigmentation is an inconstant feature of FDE, its French name (erythème pigmenté fixe) should be reconsidered. The sex-dependent distribution could help our understanding of the pathophysiology of fixed drug eruption.