[Nodulocystic eruption induced by sorafenib]. / Éruption nodulo-kystique induite par le sorafénib.

INTRODUCTION: Sorafenib is a multikinase inhibitor used in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid carcinoma. Cutaneous adverse events are numerous and occur frequently. PATIENTS AND METHODS: We present two cases of nodulocystic lesions associated with comedones in patients treated with sorafenib for hepatocellular carcinoma. In the first patient, a 64-year-old man, lesions appeared on the trunk one year after beginning sorafenib. Histopathological examination revealed a non-granulomatous, perivascular and perisudoral polymorphic cellular infiltrate associated with comedones and microcysts. These lesions progressed via inflammatory episodes interrupted by long periods of spontaneous remission without any specific treatment. In the second patient, a 53-year-old woman, a rash appeared on the buttocks three months after starting sorafenib and then spread to the lumbar region and thighs. Histopathological examination was consistent with granulomatous acne lesions. The initial treatment (oral tetracycline and zinc) given for 3 months proved ineffective. Patient follow-up over 3 years showed gradual regression without the appearance of any further lesions. DISCUSSION: In the literature, several reports discuss acneiform rashes in patients treated with targeted therapy. In most cases, these lesions were papulopustular without retentional lesions. There are few reports of nodulocystic eruptions associated with comedones following sorafenib therapy. The mechanisms of emergence of these lesions seem to involve inhibition of the RAF pathway, C-KIT, and the PDGF signaling pathway.

Cutaneous basidiobolomycosis: Seven cases in southern Benin.

BACKGROUND: Cutaneous basidiobolomycosis is the most common form of entomophthoramycosis. Herein we report seven cases of cutaneous basidiobolomycosis. PATIENTS AND METHODS: A retrospective observational study was conducted at the Buruli ulcer treatment centre in Pobè and at the national teaching hospital in Cotonou from 2010 to 2015. RESULTS: Seven cases of cutaneous basidiobolomycosis were diagnosed. The mean patient age was 9.53 years. There were 4 female and 3 male patients, all from southeast Benin. Clinically, the disease presented in all cases as a hard, well-defined, subcutaneous plaque with little inflammation, and which could easily be lifted from the deep structures but remained attached to the surface structures. The overlying skin was hyperpigmented. Plaques were localized to the buttocks or thighs. All patients had inflammatory anaemia with an accelerated erythrocyte sedimentation rate (30 to 70mm over the first hour), and a low haemoglobin count (8.7 to 11.4g/dL). Blood hypereosinophilia (650 to 3784elements/mm3) was present in six of the seven subjects. Histopathology (performed for 5 of the 7 subjects) showed granulomatous lesions with foreign-body giant cells, and inflammatory cells, with occasional eosinophils surrounding fungal hyphae (Splendore-Hoeppli phenomenon). Mycological analysis revealed Basidiobolus ranarum in three cases. The patients were treated with ketoconazole (5/7) and itraconazole (2/7), with good outcomes after 10 to 24 weeks of therapy. DISCUSSION: Cutaneous basidiobolomycosis is uncommon in southern Benin, with only seven cases being diagnosed over 6 years. The diagnosis of cutaneous basidiobolomycosis is a challenge in the field in Benin due to the non-specific clinical presentation, the lack of technical resources, and the existence of numerous differential diagnoses. CONCLUSION: Cutaneous basidiobolomycosis is an uncommon fungal infection in southern Benin chiefly affecting children.

Scabietic vasculitis: Report of 2 cases.

BACKGROUND: The infectious causes of cutaneous vasculitis are well known and include streptococcal infections among others. Cases resulting from parasitic infection are less frequent. Scabies, which is currently on the increase, has only been reported in a few isolated cases. Herein, we report two noteworthy cases of profuse scabies complicated by cutaneous vasculitis. PATIENTS AND METHODS: Case 1: a 90-year-old woman, residing in a nursing home, was admitted to our dermatology department complaining of pruritus, present for one month, predominantly on the inside of the thighs and on the buttocks, associated with purpuric lesions on the lower limbs. A skin biopsy revealed leukocytoclastic vasculitis. A diagnosis of scabies was based on severe pruritus and hypereosinophilia and was confirmed by microscopic examination of the parasitology sample and the skin biopsy sample. Despite thorough investigation, no other cause of vasculitis could be found. Complete regression of the skin lesions was achieved with scabies treatment only, without any specific treatment for the vasculitis. Case 2: a 74-year-old man, living in a nursing home, was hospitalized for purpuric papules on the lower limbs, present for one month. Physical examination revealed linear patterns in the interdigital spaces associated with scabies evident on dermoscopic examination. The skin biopsy revealed signs of vasculitis. As in our first case, no aetiology of vasculitis was found and a favorable outcome was achieved by means of scabies treatment alone with no specific treatment for vasculitis. DISCUSSION: Both of our patients presented scabies and vasculitis. In view of the absence of other causes of vasculitis and of the complete regression of lesions due to vasculitis without recurrence achieved with the scabies treatment alone, a diagnosis was made of scabietic vasculitis, probably as a result of cutaneous hypersensitivity reaction to humeral mediators.

Development of a seminar on medical professionalism accompanying the dissection course.

INTRODUCTION: Medical professionalism is an increasingly important issue in medical education. The dissection course represents a profound experience for undergraduate medical students, which may be suitable to address competencies such as self-reflection and professional behavior. MATERIAL AND METHODS: Based on a needs assessment, a seminar on medical professionalism was developed to parallel the dissection course. The conceptual framework for the teaching intervention is experiential learning. Specific learning goals and an interview guideline were formulated. After a pilot run, peer-teaching was introduced. RESULTS: Over three terms (winter 2012/13, 2013/14, 2014/15), an average of 129 students voluntarily participated in the seminar, corresponding to 40% of the student cohort. The evaluation (n=38) shows a majority of students agreeing that the seminar offers support with this extraordinary situation in general and also that the seminar helps them to become first impressions on how to cope with death and dying in their later professional life as a doctor, and, that it also provides them the means to reflect upon their own coping mechanisms. CONCLUSION: Although not yet implemented as an obligatory course, the seminar is appreciated and positively evaluated. Medical professionalism is an implicit aspect of the dissection course. To emphasize its importance, a teaching intervention to explicitly discuss this topic is advisable.

The influence of tutor training for peer tutors in the dissection course on the learning behavior of students.

INTRODUCTION: Student tutors in the dissection course are expected to meet high demands in their job, to fulfill these expectations they receive training. Combined tutor training is well accepted by tutors and tutees, however, it is not known how tutor training influences student learning. Deduced from the learning goals of the tutor training, a randomized, controlled, single-blinded study was set up with a quantitative cross-sectional analysis to compare student learning behavior. METHODS: A total of 197 medical students, coached either by ten trained or ten untrained tutors, were enlisted in the study. To assess the students' learning behavior we employed the LIST questionnaire. A common factor analysis was calculated to extract dimensions. Factor scores of the extracted dimensions were calculated for both groups to estimate differences in learning behavior. RESULTS: Factor analysis of the LIST questionnaire revealed eight factors explaining 47.57% of the overall variance. The eight factors comprise: deep learning, attention, learning organization, cooperative learning, time management, learning effort, superficial learning and learning environment. Comparing the factor scores of the extracted dimensions, students coached by trained tutors learned significantly more with their fellow students (factor score in cooperative learning 0.194 vs. -0.205, p<0.05), than students trained by untrained tutors. Students coached by trained tutors also tend to be better organized in their learning (factor score in learning organization 0.115 vs. -0.122, p=0.16). CONCLUSION: The learning behavior of students coached by trained tutors differs from the learning behavior of students coached by untrained tutors. Students coached by trained tutors learn significantly more often in teams than their colleagues and are better organized.

German MedicalTeachingNetwork (MDN) implementing national standards for teacher training.

BACKGROUND: An increasing demand for proof of professionalism in higher education strives for quality assurance (QA) and improvement in medical education. A wide range of teacher trainings is available to medical staff in Germany. Cross-institutional approval of individual certificates is usually a difficult and time consuming task for institutions. In case of non-acceptance it may hinder medical teachers in their professional mobility. AIM: The faculties of medicine aimed to develop a comprehensive national framework, to promote standards for formal faculty development programmes across institutions and to foster professionalization of medical teaching. METHODS AND RESULTS: Addressing the above challenges in a joint approach, the faculties set up the national MedicalTeacherNetwork (MDN). Great importance is attributed to work out nationally concerted standards for faculty development and an agreed-upon quality control process across Germany. Medical teachers benefit from these advantages due to portability of faculty development credentials from one faculty of medicine to another within the MDN system. CONCLUSION: The report outlines the process of setting up the MDN and the national faculty development programme in Germany. Success factors, strengths and limitations are discussed from an institutional, individual and general perspective. Faculties engaged in similar developments might be encouraged to transfer the MDN concept to their countries.

[Plaque-like leiomyomas on a chemical burn: First case report]. / Léiomyomes en plaque sur brûlure chimique : première observation.

BACKGROUND: Cutaneous leiomyomas are uncommon benign smooth muscle neoplasms of skin of unknown pathogenesis. We report a sporadic case of multiple cutaneous leiomyomas at the site of a chemical burn. OBSERVATION: A 47-year-old male presented with multiple grouped red nodules on the right calf painful to cold and to touch. The lesions were located on the site of a chemical wound that had occurred 5 years earlier. Histopathological examination revealed a proliferation of smooth muscle fibres, leading to diagnosis of leiomyoma. DISCUSSION: To our knowledge, the literature contains no previous reports of sporadic multiple cutaneous leiomyomas occurring at a chemical burn site. While a chance association cannot be ruled out, there is also the possibility of a physiopathological mechanism similar to that of vascular tumours following exposure to 4-hydrazinobenzoic acid. This compound, a hydrazine derivative of the fungus Agaricus bisporus, can cause smooth-muscle tumours in the aorta and large vessels with morphological characteristics similar to those seen in vascular leiomyomas.

[Desmoplastic melanoma: a study of 23 cases at 3 centres in the Bouches-du-Rhône region]. / Mélanome desmoplastique : une série de 23 cas dans trois centres des Bouches-du-Rhône.

BACKGROUND: Desmoplastic melanoma (DM) is a rare form of melanoma, often with atypical and potentially misleading aspects that result in difficult and late diagnosis. Because of the high likelihood of local relapse, practitioners must have a good knowledge of such tumours. PATIENTS AND METHODS: A retrospective study of the activities of 3 centres in the Bouches-du-Rhône region between 1998 and 2010 enabled us to collate 23 cases of DM and analyse the clinical and histological features of the disease as well as patient survival. RESULTS: Fifteen of the 23 patients (65.2%) were male with a median age of 64.4 years. Mean Breslow thickness was 7.56 mm. The numbers of AJCC (American Joint Committee for Cancer) stages I, II, III, IV were respectively 4.1, 66.7, 20.8 and 4.1%. Thirteen patients presented relapse, with a mean time to onset of 21 months. The initial relapse involved the skin in 1 case, the lymph nodes in 2 cases, the organs in 5 cases, the organs and subcutaneous region in 1 case, the organs and lymph nodes in 2 cases, and the organs, lymph nodes and skin in 1 case. DISCUSSION: While DM presents a higher rate of local relapse than classical melanoma, this trend appears to subside in the case of thick DM, in which relapse also involves the lymph nodes and/or organs.

[Cutaneous events during anti-TNF alpha therapy: a prospective observational study of 41 cases]. / Evénements cutanéomuqueux au cours des traitements par anti-TNF alpha : étude observationnelle prospective de 41 cas.

BACKGROUND: The cutaneous adverse effects of TNFalpha inhibitors and their potential implication in the onset of associated dermatoses remain poorly understood. PURPOSE: To describe the different clinical dermatological situations seen in patients treated with TNFalpha inhibitors. PATIENTS AND METHODS: We conducted a prospective, observational study of patients followed at the Dermatology Department of the CHU Nord university teaching hospital of Marseilles. All patients, referred by various departments, were treated with TNFalpha inhibitors and presented cutaneous events. RESULTS: Forty-one patients were included in the study. Various cutaneous manifestations were observed, including: 15 psoriatic rashes, six skin infections, three eczema rashes, three cases of lupic syndrome, two anaphylactic reactions to infusion and two cutaneous drug reactions. An original case of parapsoriasis was observed. Cutaneous tumors are rarely described. DISCUSSION: This study confirms the multiple clinical dermatological situations observed in patients treated with TNFalpha inhibitors and illustrates the need for good coordination between dermatologists and other specialists in order to ensure optimal management of this population.

p21-activated protein kinase gamma-PAK suppresses programmed cell death of BALB3T3 fibroblasts.

In response to stress stimulants, cells activate opposing signaling pathways for cell survival and programmed cell death. p21-activated protein kinase gamma-PAK is involved in both cell survival and cell death pathways. Many stress stimulants activate gamma-PAK as a full-length enzyme and as a proteolytic fragment. Caspase-mediated proteolytic activation parallels cell death and appears to be a pro-apoptotic factor in stress-induced cell death. Here, we show that activation of full-length gamma-PAK promotes cell survival and suppresses stress-induced cell death. Expression of constitutively active gamma-PAK-T402E, which mimics activated full-length gamma-PAK, stimulates cell survival of BALB3T3 fibroblasts in response to tumor necrosis factor alpha, growth factor withdrawal, and UVC light. This stimulation of cell survival is mainly due to protection of cells from cell death rather than by stimulation of proliferation. Expression of gamma-PAK-T402E increases phosphorylation of the pro-apoptotic Bcl-2 family protein Bad and protects from cell death induced by ectopic expression of Bad. In response to tumor necrosis factor alpha, expression of gamma-PAK-T402E increases the early but reduces the late activation of ERK, JNK, and p38. Our results indicate that the ubiquitous gamma-PAK may have a crucial function in cell survival by regulating the pro-apoptotic activity of Bad and the stress-induced activation of ERK, JNK, and p38 pathways.

Dyshidrotic eczema and occupation: a descriptive study.

Dyshidrotic eczema (DE) is a chronic and/or recurrent vesicular eczema of the palmar sides of the hands and sometimes the soles of the feet. The major aetiologies to be considered are atopic DE, contact DE, systemic contact DE and DE due to fungal or microbial allergy. To clarify the role of occupational contact allergens, 59 workers with DE were examined to determine whether they had atopy, environmental contact sensitization and/or contact allergy coupled with work activity. For all, patch testing was carried out using the European standard series and the material brought in by the patients. No significant difference was found between the rate (42.4%) of history of atopy among the 59 workers with DE and that (30.6%) observed among 160 workers with other forms of hand eczema (HE). Positive patch test reactions were found in 72.8% of dyshidrotic patients. A relationship to occupational activity was strong for 18 (30.5%) of them but this rate was significantly lower than that (55%) observed among the 160 with other types of eczema. Results of the present study showed that contact sensitization is as much involved in workers with DE as in workers with other form of HE, even though the relationship to work is significantly less frequent for DE. It also suggests that atopic histories are no more involved in DE than in other forms of HE.

[KID syndrome (keratitis, ichthyosis and deafness)]. / Syndrome KID (kératite, ichtyose et surdité).

Keratitis, ichthyosis and deafness are the dominant signs of KID syndrome. The lesions involving cornea, epidermis and internal ear are probably the result of a congenital ectodermal abnormality. Associated signs such as increased sensitivity to infections, and dermoskeleton dystrophies are also useful for the diagnosis. There are no specific biological signs. Most cases are sporadic but familial cases have been described with unclear mode of inheritance. Treatment is disappointing. Thus management mainly relies upon early detection of complications.

Granulomatous mycosis fungoides.

We report a new observation of granulomatous mycosis fungoides. The diagnosis was able to be made only after performing multiple biopsies during the course of the disease. Initial evolution was rapidly favourable with electrontherapy. A granulomatous reaction is, except in Hodgkin's disease, a rare phenomenon in lymphoproliferative disorders, particularly in cutaneous T cell lymphoma. This variant of mycosis fungoides raises the problem of the histological differentiation from other granulomatous dermatoses, mainly sarcoidosis. Its prognostic significance is disputed and its pathogenesis remains unknown.

Radiosurgery without whole brain radiotherapy in melanoma brain metastases. Club de Cancérologie Cutanée.

To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.