Morphological features of naevoid melanoma: results of a multicentre study of the International Dermoscopy Society.

BACKGROUND: Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. OBJECTIVES: To describe the clinical and dermoscopic features associated with NeM. METHODS: Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. RESULTS: Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern (n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. CONCLUSIONS: While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM.

[Sneddon-Wilkinson disease: efficacy of intermittent adalimumab therapy after lost response to infliximab and etanercept]. / Maladie de Sneddon-Wilkinson échappant à l'infliximab et à l'étanercept: efficacité de l'adalimumab.

BACKGROUND: Sneddon-Wilkinson disease (SWD) is a rare chronic neutrophilic dermatosis. The first-line treatment is dapsone but resistance to treatment may sometimes pose a challenge. CASE REPORT: We report a multidrug-resistant patient who responded dramatically before gradually losing response to infliximab and then etanercept. Complete remission was again obtained with adalimumab. DISCUSSION: Our case confirms the previously reported dramatic efficacy of anti-TNF biological agents in recalcitrant SWD but highlights the possibility of subsequent loss of response. Furthermore, it illustrates the efficacy of adalimumab in this indication.

Rab27a: A key to melanosome transport in human melanocytes.

Normal pigmentation depends on the uniform distribution of melanin-containing vesicles, the melanosomes, in the epidermis. Griscelli syndrome (GS) is a rare autosomal recessive disease, characterized by an immune deficiency and a partial albinism that has been ascribed to an abnormal melanosome distribution. GS maps to 15q21 and was first associated with mutations in the myosin-V gene. However, it was demonstrated recently that GS can also be caused by a mutation in the Rab27a gene. These observations prompted us to investigate the role of Rab27a in melanosome transport. Using immunofluorescence and immunoelectron microscopy studies, we show that in normal melanocytes Rab27a colocalizes with melanosomes. In melanocytes isolated from a patient with GS, we show an abnormal melanosome distribution and a lack of Rab27a expression. Finally, reexpression of Rab27a in GS melanocytes restored melanosome transport to dendrite tips, leading to a phenotypic reversion of the diseased cells. These results identify Rab27a as a key component of vesicle transport machinery in melanocytes.

[595 nm pulse dye laser therapy for viral warts: a single-blind randomized comparative study versus placebo]. / Traitement des verrues palmo-plantaires par le laser à colorant pulsé à 595 nm: étude randomisée en simple insu contre placebo.

INTRODUCTION: Pulse dye laser (PDL) appears an attractive method to treat warts. However, data concerning the efficacy of this approach are based chiefly upon open clinical studies or case reports and results vary widely from one study to another. The purpose of this study was to compare the efficacy and safety of PDL with a placebo in the treatment of a homogeneous group of patients presenting palmoplantar warts. METHODS: This was a randomized, prospective, placebo-controlled, single-blind study conducted between December 2004 and July 2005 in patients consulting for palmoplantar warts at the Dermatology Department of the University Teaching Hospital of Nice. The treatment settings used for the 595-nm PDL were as follows: spot diameter 5 mm, pulse duration 0.45 ms, fluence 9 J/cm2 with 5 passes at a frequency of 1 Hz. Cryogen spray cooling (system incorporated in the machine) was given at a rate of 50 spurts of 40 ms prior to each laser pulse. In patients in the placebo group, cooling pulses alone were given. For the plantar warts (in both groups), hyperkeratosis was removed manually with a scalpel before each session. A maximum of three sessions was administered at 3-week intervals. The type and number of warts was counted and recorded in a treatment schedule before the start of therapy, at each session and 5 weeks after the final session. The global safety of the treatment was evaluated using a visual analog scale between 0 (intolerable) and 10 (completely safe). RESULTS: Nineteen patients were included in the laser group and 16 were included in the placebo group. Sixty-four per cent (48/75) of warts in the laser group resolved completely compared with 13% (4/30) in the placebo group (p<0.001). In the PDL group, 6 of 19 patients (31.5%) no longer had warts by the end of the study compared with 3 of 16 patients (18.75%) in the placebo group (p=0.46). The global safety score of the treatment as assessed by the patients themselves was 8.31 in the laser group and 9.81 in the placebo group. DISCUSSION: Pulse dye laser appears to be an effective treatment in palmoplantar warts but the efficacy of this method seems to be only equivalent to that of standard treatments (cryotherapy or salicylic acid preparations). Safety is excellent and constitutes one of the major advantages of this technique. The absence of any proven superiority over the standard treatments in terms of efficacy, coupled with the high costs involved, means that PDL should only be used second-line therapy in patients wishing to avoid constraints affecting their professional activity.

[Myiasis caused by Dermatoba hominis after an organized tours in Amazonia]. / Myiases à Dermatobia hominis après voyages organisés en Amazonie.

BACKGROUND: Human cutaneous myiasis is a common disease in endemic tropical zones. The incidence of imported cases follows the development of organized tours in the tropics. CASE REPORTS: We report 2 cases of Dermatobia hominis furonculoid myiasis in patients who took 2 different organized tours which both visited the same Amazonian site in Peru (Puerto Maldonado). DISCUSSION: In Latin American countries, D. hominis myiasis is transmitted by Diptera (generally mosquitos, rarely flies) who carry eggs laid by an adult fly to man. This phenomena is called "phoresia" and explains the preferential localization of lesions in exposed areas unlike African myiasis caused by Cordylobia anthropophaga which contaminates clothing soiled when drying.

[Cutaneous Waldenström's macroglobulinemia]. / Localisations cutanées de la maladie de Waldenström.

BACKGROUND: We report the case of a patient in whom the first manifestation of Waldenström' s macroglobulinemia was specific skin lesions, treated with chlorambucil chemotherapy. CASE REPORT: A 76-years old woman was referred to us because of chronic red nodular lesions on her face. A biopsy specimen showed a dense lymphocytic dermal infiltrate and immunohistochemistry identified a monoclonal B lymphoid population with an IgM-kappa phenotype. The patient's disease was diagnosed as Waldenström's macroglobulinemia with cutaneous localization, on the basis of a high level of circulating macroglobulinemia and a lymphoplasmocytic infiltrate in the bone marrow expressing the same monoclonal IgM-kappa as in blood and skin. Treatment with radiotherapy (12 Grays) was unsuccessful. Chlorambucil (16 mg per day, 7 days per month) was then introduced with rapid disappearance of the skin lesions. Neutropenia led to withdrawal of this treatment after 4 courses. The skin lesions relapsed 18 months later and were cured with chlorambucil at a lower dose. DISCUSSION: Specific skin infiltrates have been rarely described during Waldenström's macroglobulinemia. Review of the literature showed eight cases of such lesions treated by chemotherapy with only two successes with oral cyclophosphamide and polychemotherapy (cyclophosphamide, vincristine and CCNU). Chlorambucil was used unsuccessfully three times. We hypothesize that primary resistance to alkylating-agent and the small number of cases of cutaneous Waldenström's macroglobulinemia may explain the poor response to systemic chemotherapy previously reported.

[Hallucinations during treatment with hydrochloroquine]. / Hallucinations au cours d'un traitement par hydroxychloroquine.

INTRODUCTION: We report an unexpected cenesthetic hallucination-type neuropsychiatric side effect with hydrochloroquine (Plaquenil) in a patient treated for an erosive plantar lichen planus. OBSERVATION: A 75 year-old woman was hospitalized for a handicapping erosive plantar lichen. Treatment with hydrochloroquine (400 mg/day) was initiated, associated with topical corticosteroids and a short course of oral acorticosteroids (0.5 mg/kg/day of methylprednisolone). After 10 days of treatment, a short episode of temporo-spatial disorientation occurred, followed by a feeling of depersonalization and cenesthetic hallucinations with feelings in the body. These manifestations were preceded by nightmares. Hydrochloroquine was spontaneously stopped by the patient one week later and led to the progressive disappearance of the hallucinations and a return to a normal mental state within one month. Two and a half years later, no relapse of the psychiatric manifestations has been noted. DISCUSSION: Chloroquine and hydrochloroquine may be at the origin of severe psychosis-like psychiatric side effects. Such manifestations are exceptional, little known and principally described during treatment of malaria. The clinical presentation of the psychosis induced by synthetic ani-malarials is fairly homogeneous from one case to the next: onset in a patient without psychiatric past of manifestations such as delirium, hallucinations, maniac episodes or depression after an interval of a few hours to 40 days, usually regressing one week after suspension of the synthetic antimalarial. There is no relationship between the dose of synthetic anti-malarial administered and the onset of psychiatric problems. The triggering-off mechanism is unknown and appears to be an idiosyncratic reaction. Our case report draws the dermatologists' attention to the possibility of the occurrence of potentially severe psychiatric side effects.

[Flutamide-induced late cutaneous pseudoporphyria]. / Pseudo-porphyrie cutanée tardive induite par le flutamide.

BACKGROUND: Pseudoporphyria is a condition characterized by clinical and histological changes resembling porphyria cutanea tarda, in the absence of any demonstrable abnormality in porphyrin metabolism. Etiologies of pseudoporphyria are hemodialysis for chronic renal failure, chronic UV irradiation, and several drugs, particularly naproxen. We report a case of flutamide induced pseudoporphyria. CASE REPORT: A 75-year-old man had prostatic carcinoma and was treated with flutamide for 1-1/2 years. He presented with a several months history of blisters on the back of the hands and fingers, occurring after sun exposures. The bullae were associated with skin fragility and atrophic scarring. Histopathological examination and direct immunofluorescence showed ultrastructural features close to those described in porphyria cutanea tarda. Quantitative analysis of porphyrins in urine and laboratory blood tests were normal. Flutamide was stopped, leading to healing of the lesions, with no relapse after 11 months. DISCUSSION: Flutamide is an antiandrogen used for the treatment of prostatic carcinoma. Its principal side-effect is represented by liver toxicity. Cutaneous side-effects of flutamide are uncommon; three cases of photo-allergic dermatitis have been described, and we report with our observation, the third case of cutaneous pseudoporphyria induced by flutamide.

[Mycobacterium fortuitum skin infection occurring after a facelift]. / Infection cutanée à Mycobacterium fortuitum après lifting.

INTRODUCTION: Mycobacterium fortuitum skin infections are rare and usually iatrogenic. We report a case with cervical involvement following a facelift. OBSERVATION: A 65 year-old woman, without past history, underwent bilateral surgical facelift, complicated by cutaneous necrosis and treated with directed healing at home. Six weeks later, an abscessed nodule appeared under the left maxillary and was drained surgically. Then other pre-auricular and left cervical inflammatory nodules appeared without adenopathy or fever. M. fortuitum was isolated in bacteriological samples. The initially probabilistic antibiotherapy with carithromycin, subsequently adapted with amikacine and cirprofloxacine and then imipeneme for a total duration of 3 months, led to the clinical cure. DISCUSSION: Mycobacterium fortuitum is a rapidly growing, ubiquitous, mycobacteria responsible for nosocomial infections in immunocompetent patients, notably following plastic surgery. Contamination occurs where there has been a rupture in the skin barrier through contact with a vector (water, surgical material, antiseptic.). Treatment, which is not codified, consists in the association of surgery and antibiotics for several months.

Clinical variants of the preprotuberant stage of dermatofibrosarcoma protuberans.

BACKGROUND: Some cases of dermatofibrosarcoma protuberans (DFSP) do not protrude above the skin. OBJECTIVES: To assess the prevalence of these DFSPs and further to describe their presentation and course. METHODS: One hundred and forty-three patients were retrospectively collected. They were asked to complete a standardized questionnaire indicating the history and appearance of the DFSP from the first skin changes identified to the time of diagnosis. RESULTS: Eighty-one DFSPs were described as protuberant ab initio, and 62 as initially nonprotuberant (npDFSP). The latter remained at this stage for a mean period of 7.6 years. Twenty-nine per cent of npDFSPs were 'morphoea-like', 19% were 'atrophoderma-like' and 42% were 'angioma-like'. Age at diagnosis was similar for both initial presentations. npDFSPs were most often misdiagnosed by physicians. CONCLUSIONS: Nearly half the patients first identified their early DFSP-related skin changes as patches. Both this frequency and the long duration at this preprotuberant stage should prompt dermatologists to consider the diagnosis of DFSP earlier, in order to make surgical treatment easier.

Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes.

In melanocytes and melanoma cells, cAMP activates extracellular signal-regulated kinases (ERKs) and MEK-1 by an unknown mechanism. We demonstrate that B-Raf is activated by cAMP in melanocytes. A dominant-negative mutant of B-Raf, but not of Raf-1, blocked the cAMP-induced activation of ERK, indicating that B-Raf is the MEK-1 upstream regulator mediating this cAMP effect. Studies using Clostridium sordelii lethal toxin and Clostridium difficile toxin B have suggested that Rap-1 or Ras might transduce cAMP action. We show that Ras, but not Rap-1, is activated cell-specifically and mediates the cAMP-dependent activation of ERKs, while Rap-1 is not involved in this process in melanocytes. Our results suggest a novel, cell-specific mechanism involving Ras small GTPase and B-Raf kinase as mediators of ERK activation by cAMP. Also, in melanocytes, Ras or ERK activation by cAMP is not mediated through protein kinase A activation. Neither the Ras exchange factor, Son of sevenless (SOS), nor the cAMP-responsive Rap-1 exchange factor, Epac, participate in the cAMP-dependent activation of Ras. These findings suggest the existence of a melanocyte-specific Ras exchange factor directly regulated by cAMP.