[Acute generalized exanthematous pustulosis induced by phloroglucinol]. / Pustulose exanthématique aiguë généralisée induite par le phloroglucinol (Spasfon®).

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a severe drug eruption. We report herein the first case of AGEP induced by phloroglucinol (Spasfon®). PATIENTS AND METHODS: A 27-year-old pregnant woman developed a febrile exanthematous pustulosis eruption three days after treatment with intravenous phloroglucinol and paracetamol for nephritic colic. She had no previous history of psoriasis. The laboratory workup showed hyperleukocytosis with neutrophilia. A cytobacteriological sample of the pustules was negative. Skin biopsy revealed marked neutrophilic and leukocytoclastic vasculitis. Reintroduction of phloroglucinol after delivery resulted in the same clinical symptoms within a few hours of intake. A diagnosis of phloroglucinol-induced AGEP was made on the basis of intrinsic imputability of I4 (S3 C3) using the imputability criteria of Begaud et al. The outcome was favorable after withdrawal of the drug. DISCUSSION: To the best of our knowledge, this is the first case of phloroglucinol-induced AGEP confirmed by reintroduction of the drug.

Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy.

BACKGROUND: Sentinel lymph-node (LN) biopsy (SLNB) is a valuable tool to assess the regional LN status in Merkel cell carcinoma (MCC). However, its prognostic value is still debated. This study was undertaken to assess SLNB usefulness for MCC management and to determine the impact of SLNB status on disease-free survival (DFS) and overall survival (OS) by comparing SLNB-positive versus -negative patients according to demographic, clinical and treatment characteristics. PATIENTS AND METHODS: In this retrospective, multicenter observational study, SLNB was proposed to all patients referred for clinically N0 MCC. Treatment schedule consisted of wide-margin surgical resection of primary MCC followed by adjuvant radiation therapy (aRT) to the primary site and, for SLNB-positive patients, radical LN dissection followed by regional aRT. Univariate and multivariate analyses determined factors associated with DFS and OS. RESULTS: Among 87 patients with successful SLNB, 21 (24.1%) were SLNB-positive. Median follow-up for the entire series was 39 months; respective 3-year DFS and OS rates were 73% and 81.4%, respectively. Univariate analysis (all patients) identified SLNB-negativity as being associated with prolonged OS (P = 0.013) and aRT (all sites considered) was associated with longer DFS (P = 0.004) and OS (P = 0.018). Multivariate analysis (all patients) retained SLNB status and aRT (all sites considered) as being associated with improved DFS (P = 0.014 and 0.0008) and OS (P = 0.0020 and 0.0019). Moreover, for SLNB-negative patients, tumor-bed irradiation was also significantly associated with prolonged DFS (P = 0.006) and OS (P = 0.014). CONCLUSIONS: The present study demonstrates that SLNB-negativity is a strong predictor of longer DFS and OS in stage I and II MCC patients. The similar benefit for aRT on tumor bed observed in this study has to be confirmed by a prospective study. The results advocate for SLNB being considered to all MCC patients.

[Stevens-Johnson syndrome concurrent with primary Epstein-Barr virus infection]. / Syndrome de Stevens-Johnson au cours d'une primo-infection par le virus d'Epstein-Barr.

BACKGROUND: Primary EBV infection mainly affects children and young adults. Most patients present the characteristic triad of fever, pharyngitis and lymphadenopathy. Symptoms may include a morbilliform eruption, occasionally induced by amoxicillin. We report a case of Stevens-Johnson syndrome concurrent with EBV infection. CASE REPORT: A 17-year-old boy consulted for an eruption suggestive of Stevens-Johnson syndrome, which was supported by the histopathology results. The patient had taken no medication during the previous weeks. Laboratory examinations showed atypical activated T lymphocytes. Serological tests and PCR results confirmed the diagnosis of primary EBV infection. The outcome was spontaneously favorable with only symptomatic treatment being required. DISCUSSION: Stevens-Johnson syndrome is characterized by "target" lesions and profuse mucous membrane involvement. Stevens-Johnson syndrome is frequently drug-induced, being due less frequently to infections. Stevens-Johnson syndrome is very rarely a manifestation of infectious mononucleosis, with only one case being reported in the literature. When confronted with Stevens-Johnson syndrome without any imputable medication, complete screening for infection should be performed, in particular for primary EBV infection.

[Melanoma in HIV patients: 14 cases]. / Mélanomes chez des patients séropositifs pour le VIH : 14 cas.

BACKGROUND: a clinical study of 14 patients presenting both malignant melanoma and HIV infection, and analysis of the literature to determine the frequency and specific features of this association. PATIENTS AND METHODS: ten men and four women of median age 43 years were included. In 50% of cases, the primary melanoma consisted of spreading superficial melanoma with a mean Breslow thickness of 2.83 mm. In two cases, regional lymph node metastasis was discovered but with no primary melanoma being identified. HIV infection was already documented on diagnosis of melanoma in 11 cases, and it was discovered in three cases at the time of surgery for melanoma (treatment of the primary melanoma in two cases, and in one case, regional lymph node dissection two years after the initial diagnosis). Eight patients died within a mean period of 39 months, with melanoma being the cause of death in six cases. Following relapse of melanoma, the course of the disease was severe, with mean stage IV survival of 3.6 months. No response to chemotherapy was observed where such treatment was feasible. DISCUSSION: the presence of HIV appears to be an aggravating factor for the outcome of metastatic melanoma. CONCLUSION: our study suggests the importance of clinical examination of pigmented lesions in HIV patients in order to ensure early identification of melanoma.

Place of human amniotic membrane immunoblotting in the diagnosis of autoimmune bullous dermatoses.

BACKGROUND: Fine analysis of antiskin autoantibodies can contribute to the differential diagnosis of autoimmune bullous dermatoses. OBJECTIVES: To develop a high-performance immunoblotting method using human amniotic membrane as the antigen source, and to compare it with current laboratory methods. METHODS: Sera from 113 patients were tested by immunoblotting (IB), rat and monkey oesophagus and salt-split skin indirect immunofluorescence (IIF), and enzyme-linked immunosorbent assay (ELISA) quantification of anti-BP180-NC16a and anti-BP230, or antidesmoglein (Dsg) 1 and 3 antibodies. There were 56 cases of bullous pemphigoid (BP), 22 cases of mucous membrane pemphigoid (MMP), eight cases of epidermolysis bullosa acquisita (EBA), two cases of bullous systemic lupus erythematosus (BSLE), 17 cases of pemphigus vulgaris (PV), and four cases each of pemphigus foliaceus (PF) and paraneoplastic pemphigus (PNP). RESULTS: In BP, the three methods had similar sensitivity (84-89%) for both anti-BP180-NC16a and anti-BP230 antibody detection. In MMP, autoantibodies (mainly directed against BP180 or laminin 332 subunits) were detected in 77% of patients by IB, compared with only 9% by IIF on rat and monkey oesophagus and 36% on salt-split skin, and 14% by anti-BP180-NC16a and anti-BP230 ELISA. In patients with pemphigus, ELISA had 92% sensitivity for anti-Dsg1 and 3, but IB and rat bladder IIF were necessary to confirm PNP by revealing specific and rare patterns (antidesmoplakin I/II, antienvoplakin and antiperiplakin antibodies). IB also revealed anticollagen VII antibodies in 60% of patients with EBA and BSLE, and antibodies to BP180, BP230 and Dsg3 in a few patients who were negative using the other two techniques. CONCLUSION: Amniotic membrane immunoblotting is an interesting diagnostic tool for bullous diseases, as the entire panel of autoantibodies can be detected with a single extract. This method improves the identification of complex and heterogeneous autoimmune processes in conjunction with IIF and ELISA, and is particularly useful for MMP characterization.

[Long-term efficacy of autologous stem cell transplantation for stage IV mycosis fungoides]. / Efficacité a long terme d'une autogreffe de cellules souches au cours d'un mycosis fongoïde de stade IV.

BACKGROUND: Mycosis fungoides during large cell transformation to lymphoma has a poor prognosis with mean survival of 36 months. Autologous stem cell transplantation is rarely proposed in this indication. We report the case of a young man still in complete remission for transformed mycosis fungoides 14 years after autologous stem cell transplantation. CASE REPORT: A 25-year-old man presenting eczema-like patches since childhood was treated by chemotherapy for multiple lymphadenopathies considered as Hodgkin's lymphoma. He was referred with diffuse skin tumours and infiltrated patches. Histology of tumour samples revealed atypical T-cell infiltrate with epidermotropism and presence of more than 25% of large CD30-positive cells. Non-infiltrated patches showed small T-cell lymphoma with epidermotropism. Histological verification of a previous lymphadenopathy confirmed the diagnosis of transformed mycosis fungoides. Despite multiple courses of chemotherapy, the disease progressed, with neurological involvement in particular. Because of tumour aggressiveness, autologous stem cell transplantation was performed and resulted in rapid regression of the tumours, lymphadenopathy and neurological symptoms. Non-transformed mycosis fungoides patches persisted but were controlled with topical mechlorethamine. This patient is still in complete remission for tumour and extracutaneous lesions 14 years after the autograft. DISCUSSION: This was probably a case of juvenile mycosis fungoides diagnosed and transformed in adult age. Neurological involvement by mycosis fungoides is rare and usually carries a drastic prognosis. To our knowledge, this is the longest remission of transformed mycosis fungoides seen after autograft. It highlights the value of this method in aggressive transformed mycosis fungoides, especially in patients ineligible for allograft.

[A case of acute and necrotizing cutaneous Mycobacterium marinum infection in a patient treated with infliximab for Crohn's disease]. / Infection cutanée aiguë et nécrosante a Mycobacterium marinum chez un patient traité par infliximab pour une maladie de Crohn.

BACKGROUND: The increasing use of anti-TNFalpha exposes patients to emerging risks, particularly that of infection. We report a case of severe cutaneous Mycobacterium marinum infection in a patient treated with infliximab and we discuss therapeutic options. PATIENTS AND METHODS: A man treated with infliximab for Crohn's disease developed a severe cutaneous infection with M. marinum. Despite withdrawal of infliximab and the introduction of triple antibiotic therapy, the patient's lesions worsened and surgical treatment was required. DISCUSSION: The worsening experienced by our patient 1 week after the beginning of the treatment is comparable with the immune reconstitution syndrome occasionally observed in tuberculosis in immunocompromised hosts, thus raising the question of the potential value of continuing infliximab treatment. Recommendations are needed concerning the prevention and treatment of M. marinum infections in patients on anti-TNFalpha biotherapies.

[Pyoderma gangrenosum with aseptic spleen abscess]. / Pyoderma gangrenosum et abcès splénique aseptique.

BACKGROUND: Pyoderma gangrenosum is a neutrophilic dermatosis in which systemic involvement is rare. It may be associated with systemic disease. We report a case of pyoderma gangrenosum in the spleen. CASE REPORT: A 68-year-old man presenting pyoderma gangrenosum with pustules and stage I multiple myeloma was admitted for asthenia and abdominal pain. There were no skin lesions. Laboratory tests showed inflammatory syndrome with polynuclear leucocytes of 25,000/mm(3). CAT scans and abdominal ultrasound revealed a splenic abscess. A spleen biopsy was performed and histological examination showed polynuclear leukocyte infiltration, while cultures were negatives. Diagnosis of pyoderma gangrenosum with splenic involvement was made. Increased systemic corticosteroid therapy produced a successful outcome. Haematological findings remained unchanged. DISCUSSION: Spleen involvement in pyoderma gangrenosum is very rare and can mimic an infectious process. In such cases, routine screening is essential for associated diseases, particularly haematological malignancies.

[Metastatic extraskeletal osteosarcoma revealed by an occipital mass]. / Ostéosarcome extrasquelettique d'emblée métastatique révélé par une masse occipitale.

BACKGROUND: Extraskeletal osteosarcoma is a rare mesenchymatous tumour occurring in adults aged over 50 years and is located mainly in the limbs or retroperitoneum. We report a case of metastatic extraskeletal osteosarcoma revealed by a cutaneous occipital tumour site. CASE-REPORT: A 53-year-old woman was admitted for dyspnea and weight loss. An occipital tumour, noticed for one year by the patient, was discovered. It was freely movable on the bone, of hard consistency and responsible for alopecia. In addition to left-sided pleural effusion, a chest CAT revealed a large mass in the left lung, including areas of necrosis and calcifications with intracardiac extension. Histological examination of biopsies of the skin and of pulmonary and intracardiac lumps showed an osteosarcomatous proliferation. No primary osteosarcoma was found in the bones. A diagnosis was made of metastatic extraskeletal osteosarcoma. Intravenous chemotherapy was given followed by radiotherapy. After a six-month stabilization period, the disease progressed. DISCUSSION: Extraskeletal cutaneous locations of osteosarcoma are extremely rare. They may comprise either the primary tumour or a metastatic lesion. In this patient, the immediately metastatic nature of the disease was a poor prognostic factor for this high-grade sarcoma.

[Implantable medical devices]. / Dispositifs médicaux implantables.

Medical devices have been individualized to include a category of implantable medical devices, "designed to be totally implanted in the human body or to replace an epithelial surface or a surface of the eye, through surgery, and remain in place after the intervention" (directive 93/42/CEE and decree of 20 April 206). Each implantable medical device has a common name and a commercial name for precise identification of the model (type/references). The users' service and the implanting physician should be clearly identified. There are a number of rules concerning health traceability to rapidly identify patients exposed to risks in which the implantable medical devices of a particular batch or series were used and to monitor the consequences. The traceability data should be preserved 10 years and the patient's medical file for 20 years.

[Melanoma in invisible naevus spilus]. / Mélanome développé sur naevus spilus inapparent.

BACKGROUND: Diagnosis of naevus lesions may be complex where they contain little or no pigmentation. Naevus spilus (or naevus on naevus) is, generally, readily identified by the difference in pigmentation between overlying and underlying naevi and healthy skin. Malignant transformation of naevus spilus is rare. We report two cases of melanoma in which surgical procedures revealed underlying melanocyte lesions, diagnosed at histology but undetectable on clinical examination. PATIENTS AND METHODS: Two patients were operated for melanoma in which surgery, at a site remote from the melanoma, suggested incomplete relapse despite the fact that previous clinical examination had indicated healthy skin. A diagnosis was made of melanoma in invisible naevus spilus. DISCUSSION: Diagnosis of melanoma in invisible naevus spilus may be suspected where several naevi are found together in a specific area. The main problem is the therapeutic stance to be adopted since complete excision of the underlying naevi is difficult in practice. Wood's light examination may be helpful.

[Bullous pemphigoid and acquired hemophilia]. / Pemphigoïde et hémophilie acquise.

INTRODUCTION: Acquired hemophilia is a rare disease. Associated pemphigoid is extremely uncommon. We report a case of acquired hemophilia in the course of this dermatosis illustrating the severity of the disease. OBSERVATION: An 83 year-old woman was followed for 3 years for pemphigoid treated with topical corticosteroids following a recent relapse. She was hospitalized for surgical treatment of extensive and painful hematoma of the anterior aspect of the right leg following a fall. Preoperative clotting tests showed an extremely long cephalin coagulation time (> 2 x normal) not corrected by addition of control plasma, with a normal prothrombin time, due to acquired hemophilia type A and the presence of factor VIII inhibitor (17 Bethesda units/ml). The coagulant activity of factor VIII was reduced by 3%. The patient was treated with recombinant human factor VII (NovoSeven) and systemic corticosteroids were subsequently administered at a dose of 1 mg/kg/d to ensure direct action on antibody production. Seven days later, the patient presented intense abdominal pain and extension deficit in the right lower limb. An abdominal-pelvic scan revealed spontaneous hematoma of the right psoas-iliac muscle. Despite replacement therapy with NovoSeven and oral corticosteroids, worsening of the hematoma occurred, complicated by hemorrhagic shock, resulting in death. DISCUSSION: Acquired hemophilia, as revealed by cutaneous-mucosal bleeding, is a rare disease (1 to 4 cases per million subjects) more commonly seen in adults. It is associated with the presence of antibodies directed against factor VIII. Its complications, particularly hemorrhagic, are fatal in 15 to 20% of cases. While acquired hemophilia seems to occur in isolation in one of every two cases, it may be associated with autoimmune diseases, lymphoproliferative syndromes, solid tumors, the post-partum period, or use of certain drugs. In dermatology, acquired hemophilia has been reported in association with pemphigoid (9 cases), in which case the prognosis is consistently very poor, with pemphigus vulgaris (5 cases), more recently with acquired epidermolysis bullosa (3 cases), and finally with mucosal pemphigoid (1 case). CONCLUSION: Given the severity of associated hemorrhagic accidents, early identification of this clotting disorder is warranted in order to allow initiation of treatment as soon as possible.

[Haemolytic uremic syndrome and acute mesenteric ischemia caused by interferon-alpha-2b in the treatment of Kaposi's sarcoma in an AIDS patient]. / Syndrome hémolytique et urémique et ischémie mésentérique aiguë lors d'un traitement par interféron alpha-2b pour une maladie de Kaposi associée au VIH.

BACKGROUND: Interferon alpha is approved for the treatment of Kaposi's sarcoma in HIV infected patients. Hemolytic and uremic syndrome (HUS) is a rare side-effect of interferon alpha and has been reported primarily in chronic myelogenous leukemia. CASE REPORT: A 44-year-old HIV-infected woman from Cameroon was admitted for treatment of cutaneous Kaposi's sarcoma. Two days later, she presented severe HUS. Abdominal pains subsequently revealed non-occlusive mesenteric ischemia. The patient rapidly improved after interferon withdrawal. DISCUSSION: To our knowledge this is the first case of HUS induced by interferon alpha given for Kaposi's sarcoma. Further, no cases of acute mesenteric ischemia have been reported with interferon alpha. It is possible that the condition may have been induced or aggravated by HUS or a low infusion rate. Interferon can exert vascular toxicity on both the mesenteric vessels and the renal vessels in a setting of microangiopathy.

[Clinical tolerance of cutaneous antiseptics in 3,403 patients in France]. / Tolérance clinique des antiseptiques cutanés chez 3 403 malades en pratique de ville.

INTRODUCTION: We prospectively studied the prevalence and the clinical forms of adverse cutaneous reactions associated with the main antiseptics used in France, the incidence of which is not well known. PATIENTS AND METHODS: Patients were included by 773 French dermatologists from May to June 2003. The 8 first consecutive adult patients for whom ambulatory treatment with a cutaneous antiseptic was prescribed were included. Patients were evaluated at inclusion and after treatment, either in person or by telephone. All reported adverse cutaneous reactions were validated by two independent experts. RESULTS: 3,403 patients (61% women, 39% men; mean age: 47) were included. Antiseptics were indicated for ambulatory surgery (45%), technical procedures (33%), and in combination with other treatments for various dermatoses, wounds and burns (12%). The 6 most widely used treatments (96% of prescriptions) were hexamidine (37%), chlorhexidine-benzalkonium (28%), chlorhexidine-alcohol (16.5%), aqueous chlorhexidine (7%), polyvidone iodine (6%) and hexamidine-chlorhexidine (1.8%). The antiseptic was prescribed for application by dabbing (57%) or spraying (40%), twice daily for a mean 10 days (3-30 days). A transient burning sensation was noticed by 4 to 7% of the patients, without any significant difference between antiseptics. Twelve adverse events were reported: contact dermatitis in 9 patients, persistent burning sensation in 2 and yellow discoloration of the skin in one. This latter case, caused by the colour of the antiseptic, cannot be considered as an adverse event. Furthermore one patient with contact dermatitis should have not been included because he had a history of cutaneous reaction related to the use of the same antiseptic. Therefore only 10 cutaneous reactions were eventually taken into account (overall prevalence=2.9 per thousand, ranging from 0% to 0.5% according to the antiseptic). There was no significant difference in terms either of the antiseptic used or the site of the treated lesion. A history of contact dermatitis was associated with a significant risk of adverse reaction (OR=7.2; CI 95: 2.0-26.4; p=0.007). The median time from onset of treatment to appearance of contact dermatitis was 4 days (0-90 days). The condition resolved following discontinuation of treatment; spontaneously in 5 patients and with dermocorticoid therapy in 5 others. DISCUSSION: The results of this study give a precise idea of how the antiseptics are used by French dermatologists in clinical practice in outpatients and how often their use is complicated by the occurrence of adverse cutaneous reactions. The low rate of such reactions (2.9 per thousand) in our study is thus in contrast with the impression given by the large number of publications related to this complication. It also tempers the high rates of sensitisation to various antiseptics found in selected at-risk patients. The most common adverse event observed was contact dermatitis and a history of this condition conferred a significant risk of cutaneous reaction. CONCLUSION: Although cutaneous antiseptics are well tolerated with a low prevalence of adverse reactions, generally mild, they should nevertheless be prescribed with caution in patients with a history of contact dermatitis.

[Kimura's disease associated with extracapillary glomerulonephritis]. / Maladie de Kimura associée à une glomérulonéphrite extra-capillaire nécrosante.

BACKGROUND: Kimura's disease is a rare and benign chronic inflammatory soft-tissue disorder of unknown origin. Most cases involve young Asian males. The typical presentation consists of painless papules or nodules with a predilection for the head and neck region, associated with lymphadenopathy, parotid gland involvement, peripheral blood eosinophilia and raised immunoglobulin E. PATIENTS AND METHODS: A 49-year-old Mauritian man was hospitalized for nephrotic syndrome. Examination revealed a painless 3 cm nodule in the left pre-auricular region and multiple enlarged left cervical lymph nodes. Histopathologic examination of a nodule confirmed the diagnosis of Kimura's disease, which was associated with necrotic extracapillary glomerulonephritis. Corticosteroids were initiated, resulting in rapid improvement of renal function and partial regression of the patient's cutaneous nodules and lymph node disorder. DISCUSSION: Renal manifestations are the only visceral localization of Kimura's disease, and proteinuria is seen in 12% of cases, of which 50% are accompanied by nephrotic syndrome. Many different histologic types of renal involvement may be observed with potentially severe lesions. To our knowledge, this is the first case of Kimura's disease associated with extracapillary glomerulonephritis.

PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study.

The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common.