[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.

[Update on cutaneous dirofilariasis]. / La dirofilariose cutanée.

Dirofilariasis is a worldwide zoonotic infection that rarely affects humans and is caused by filarial nematodes of the genus Diroflaria transmitted by mosquitoes. Cutaneous dirofilariasis, due to D. repens, presents as inflammatory lesions that develop into subcutaneous nodules. These clinical symptoms may be consistent with Wells' cellulitis. Diagnosis of dirofilariasis involves demonstration of the presence of the nematode during skin biopsy and identification of the worm through macroscopic, histological and PCR analysis. Surgical resection of the nodule remains the gold standard treatment. The number of cases of human cutaneous dirofilariasis has increased in the recent years and the disease must not be misdiagnosed.

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.

Cutaneous and pulmonary dirofilariasis due to Dirofilaria repens.

Dirofilariasis is a worldwide zoonotic infection that accidentally affects humans. It is caused by filarial nematodes of the genus Dirofilaria, which are transmitted by mosquitoes. Cutaneous dirofilariasis appears as inflammatory lesions that could be consistent with Wells' cellulitis. We present a remarkable case of human infection with Dirofilaria repens, causing both subcutaneous and pulmonary nodules.

[Pyoderma gangrenosum revealing colonic diverticulitis: Two cases]. / Pyoderma gangrenosum révélant une diverticulite colique: deux cas.

BACKGROUND: The association of pyoderma gangrenosum (PG) with colonic diverticulitis infection (DI) is relatively unknown. Herein, we describe two cases of PG with full recovery after colonic surgery. PATIENTS AND METHODS: Case 1: an 83-year-old man presented with lesions on his legs that had been present for several weeks, and a diagnosis of PG was confirmed histologically. Abdominopelvic computed tomography (CT) performed on account of biological inflammatory syndrome revealed DI complicated by abscesses. Following the failure of two different antibiotic regimens, sigmoidectomy was performed. Postoperatively, the skin lesions healed without local or systemic corticosteroids. Case 2: a 63-year-old woman presented PG resistant to local and systemic corticosteroids and dapsone for several months. A particularly severe flare was accompanied by abdominal pain and inflammatory syndrome. CT revealed perforated sigmoid DI. Sigmoidectomy was performed after failure of drug therapy. The patient's PG subsequently improved and had disappeared without recurrence at 24months. DISCUSSION: Both of these cases of PG revealed DI. The hypothesis is that DI constituted a source of colonic inflammation, sending out bacterial antigenic stimuli that resulted in PG through deposition of circulating immune complexes. Removal of this inflammatory source appears to have enabled healing of PG. CONCLUSION: DI must be added to the list of systemic diseases associated with PG. In the case of isolated PG, CT may be used to detect asymptomatic DI. Early diagnosis could prevent serious gastrointestinal complications.

[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.

[Papular mycosis fungoides]. / Mycosis fongoïde papuleux.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review. PATIENTS AND METHODS: A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions. DISCUSSION: Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF. CONCLUSION: Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity.

Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy.

OBJECTIVE: To establish the prevalence and serum levels of IgE to commercial Der p 1, Der p 2, Der p 10 and the carbohydrate MUXF3 in house dust-mite allergic patients. To compare individual vs. allergen microarray methods. METHODS: Prevalence and serum levels of IgE to Dermatophagoides pteronyssinus extract and components Der p 1, Der p 2, Der p 10 and MUXF3, specific IgG4 to D. pteronyssinus, total serum IgE levels, and clinical features (age, asthma, rhinitis and atopic dermatitis) were determined in 123 patients (64 children) with the ImmunoCAP® method. ImmunoCAP ISAC® was performed in 24 patients. RESULTS: All patients had serum IgE to D. pteronyssinus. Prevalences of serum IgE to commercial components were Der p 1 93%, Der p 2 77% (Der p 1 or Der p 2 94%), Der p 10 28% and MUXF3 25%. Levels of D. pteronyssinus IgE strongly correlated with Der p 1 and Der p 2 IgE (r = 0.89 and 0.85 respectively), but not Der p 10 and MUXF3. ImmunoCAP® and ImmunoCAP ISAC® were concordant, but the quantitative correlation was poor. No clinical implication for the prevalence, levels, or molecular IgE reactivity profile to house dust mite components was found. CONCLUSIONS AND CLINICAL RELEVANCE: Commercially available Der p 1 and Der p 2 strongly correlate with IgE D. pteronyssinus. The lack of Der p 1 and Der p 2 IgE may help with differential diagnosis. Der p 10 serum IgE prevalence and levels suggest different patterns in food and mite-related tropomyosin sensitization. Serum IgE to carbohydrate MUXF3, although unexpectedly prevalent, were low and did not modify D. pteronyssinus IgE levels. Follow-up may be best carried out with individual rather than microarrayed components.

[Evaluation of the activity of skin tumor's excision in dermatology (France, 2009)]. / Bilan de l'activité de chirurgie d'exérèse des tumeurs cutanées en dermatologie en France en 2009.

BACKGROUND: Dermatosurgery has been gaining in importance in recent years. STUDY AIMS: The aim of our study was to describe this activity to increase its value and to inform the other specialists and the general public. PATIENTS AND METHODS: We performed a national prospective study during one month in the hospital centers and university teaching hospitals in France and among the members of the Surgical Group of the Société française de dermatologie. Data were collected with a pre-established questionnaire. They were captured on EpiData 3.1 and Excel software package and were analysed using the SPSS 15.0 software package. RESULTS: The participation of dermatology departments in hospital was 66.7 %. For the members of the surgical group, it was 43.1 %. A total of 2308 dermatological surgical procedures was performed. The mean age was 55.5 years ± 20.7. Three hundred and thirty-six (14.6 %) procedures were performed with antiplatelet agents or anticoagulants. The excisions of skin cancers were carry out with no previous biopsy in 71.3 % of cases. We described repairs in one time in the majority of cases (92.2 %), and the most frequent type of procedure was direct closure (83.4 %). Complete excision was obtained directly in 95.2 % of cases and the clinicopathological correlation was also excellent (89.5 %). Three percent of patients suffered complications during or following surgery and these complications were more frequent with the patients treated by antithrombotic medications. CONCLUSION: This is, in our knowledge, the first prospective study on dermatosurgery activity practised by dermatologists in France. The important rate of participation exemplified the implications of dermatologists in the treatment of skin cancers with an optimal follow-up.

[Retinoids: mechanisms of action]. / Rétinoïdes: mécanismes d'action.

Retinoids, vitamin A derivatives, are natural or synthetic molecules with pleiotropic effects, which regulate cell differentiation, proliferation and apoptosis. In target cell, the active natural metabolites retinoic acid (RA) and 9-cis-retinoic acid are synthetized from retinol by a two-step process with intermediate metabolite retinaldehyde. In 1987, the identification of the nuclear retinoic acid receptors that belong to the superfamily of nuclear receptors led to a significant progress in the comprehension of the mechanism of action of retinoids. There are two families of Retinoid Nuclear Receptors (RNR), the RA receptors (RAR), which natural ligand is RA, and the Retinoid X Receptors (RXR), which natural ligand is 9-cis-retinoic acid. Among synthetic retinoids, isotretinoin, acitretin, tazarotene and adapalene are ligands of the RAR, bexarotene is the first rexinoid (ligand of the RXR), alitretinoin the first panagonist (RAR+ RXR). For each family, there are 3 isotypes (α, ß, γ), and for each isotype several isoforms. Each NRR is composed of 6 regions (A-F). 3 regions are of importance: the A/B region has a ligand-independent transcriptional activation function, the C region harbors the DNA binding domain, the E region harbors the ligand binding domain. To regulate the expression of target genes, NRR have to dimerize. RXR are obligatory in dimers (heterodimers RAR-RXR, homodimers RXR-RXR). Dimers binds specific sequences of DNA, present in the promoters of target genes. When the ligand, natural or synthetic, bind to RNR, coactivators are recruited and transcription factors are activated. In target cell, retinoids not utilized are degradated in polar metabolites by enzymes of cytochrome P450.

[Hyaluronan in inflammation, auto-immunity and cardio-vascular diseases]. / Acide hyaluronique et pathologie inflammatoire, auto-immune et cardio-vasculaire.

Hyaluronan (H) is an ubiquitous high-molecular size glycosaminoglycan involved in many physiological functions. Evidences are numerous implying H in various pathological pathways, such as inflammation, cancer cardio-vascular diseases. CD44 is the principal membrane cell receptor of H. In inflammation, H has size-specific different biological activities. The high molecular weight H are anti-angiogenic, anti-inflammatory and immunosuppressive. Smaller H oligomers are angiogenic, inflammatory and immuno-stimulatory. H is strongly involved in the recruitment of leucocytes at the site of inflammation (role of CD44). Data giving evidence for a role of H in allergic pathways and auto-immunity are scarce. H is implicated in pathogenetic process leading to atherosclerosis.

[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.

[Evaluation of dermatology consultations in a prospective multicenter study involving a French teaching hospital]. / Evaluation de l'activité hospitalière de consultation liaison en dermatologie à partir d'une enquête prospective multicentrique au sein d'un CHU français.

BACKGROUND: Dermatologic practice occurs mainly in the inpatient setting. This activity is also referred to as consultation-liaison dermatology (DL). STUDY AIMS: To describe and quantify this dermatologic consultation activity in a hospital setting in Marseille; to establish the relationship between presumptive dermatologic diagnosis and the final diagnosis retained by the dermatologist. PATIENTS AND METHODS: This was a prospective study carried out three university teaching hospitals and an army teaching hospital for a period of three months. Of particular note is that services requesting consultation were asked in each case to supply their presumptive dermatologic diagnosis at the time consultation was requested. The statistical analysis was carried out using the SPSS 15.0 software package. A total of 352 notes for dermatology consultations were requested and 336 of these were evaluated, representing 5% of all consultations activities within these dermatology departments over this period. Ninety-three percent of the consultations were established by dermatology interns and 86% of consultations took place within 24 hours following their demand. Thirty-one percent of consultations were for patients aged over 75 years and 61% of the requests emanated from medical departments. The main requests concerned elementary lesions, symptoms or non-specific eruptions (56%), recommendations for treating infectious skin diseases (17%), inflammatory diseases (7%) and skin cancer (5%), recommendations for nursing care (14%) and the remainder for various reasons. No diagnosis was established in the face of of non-specific signs in 26.4% of cases. The diagnosis made by dermatologists differed from that initially evoked by the non-specialists in 56.3% of cases. Initial dermatological diagnosis was least successful regarding drug-induced eruption and skin cancer. The majority of consultations (57%) were considered unrelated to the patients' previous histories or reasons for admission. Twenty-six percent of patients were prescribed systemic therapy and 80% were prescribed topical treatment, of whom a quarter received dressings. Therapeutic acts were prescribed for 40% of the patients. Five percent of the patients were hospitalized after their consultation at the respective dermatology department and 14% were referred for outpatient dermatology consultations. DISCUSSION: This study confirms a number of expected features: common dermatological diseases are often not recognized or is misdiagnosed by non-dermatologists, excessive bedside consultations and very particular profiles of the common diagnoses in this activity (nursing care, drug-induced eruption, fungal infections). Less predictable were the absence of links between the requests and the moderate impact of the activity on hospitalization. CONCLUSION: The study of these dermatologic diagnoses in an in-patient setting suggests a number of approaches to more successful management of these consultations.