[Our best wishes for 2004].
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INTRODUCTION: Xanthoma disseminatum is a non-Langerhans histiocyte proliferation, described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis, associated with diabetes insipidus and normal lipid metabolism. In this case report, vinblastine produced the regression of the lesions. OBSERVATION: A 51 year-old man presented in 1999 with a four-year history of progressive xanthomatous papulonodular lesions of his trunk, axillary and inguinal folds, neck and face (leonin facies). Treatment with thalidomide for 6 months was ineffective. A rapid extension of the lesions to the pharynx, larynx and trachea with dyspnea occurred and required a tracheotomy. Histopathological study showed a dense histiocytic infiltrate within the upper and mid dermis with Touton giant cells and inflammatory cells. The histiocyte cells were positive for CD68. Neither lungs nor hypophysis were involved. A treatment with 6 cures of cyclophosphamide was insufficient. Vinblastine therapy (32 cycles: 0.1 mg/kg/cycle) produced a spectacular regression of the mucous-cutaneous papulonodular lesions leaving cheloid scars. The patient required a transitory tracheotomy and a bilateral commissuroplasty. DISCUSSION: Prognosis of xanthoma disseminatum is in related to the mucous membrane manifestations (50 p. 100 of cases) and involvement of the upper respiratory tract. The response to any form of therapy in xanthoma disseminatum is unsatisfactory. Surgical excision or laser therapy can improve physical and functional aspects but the evolution is characterized by very frequent relapses. Treatment with antimitotic drugs seems to be ineffective in many cases. In our patient, vinblastine induced a spectacular regression of mucocutaneous lesions without neurologic toxicity. To our knowledge, this is the first report of vinblastine efficacy in this rare and severe disorder.
INTRODUCTION: The interest of intravenous immunoglobulins (Igi.v.) in the treatment of pemphigus is discussed. Pemphigus is not a recognized indication for this treatment by the CEDIT (French Committee for the assessment and diffusion of technological innovations). The aim of this study was to assess the efficacy of Igi.v. in the treatment of severe corticosteroid-dependent or resistant pemphigus. MATERIAL AND METHODS: A retrospective study using a standardized questionnaire was conducted in the various departments of dermatology among the "Groupe Bulles" of the French Society of Dermatology. The study collected the following information from 12 patients suffering from pemphigus and treated with Igi.v.: 1) general demographical data; 2) characteristics of the pemphigus; 3) different treatments applied, and 4) efficacy and side effects of treatments. RESULTS: Among the 12 patients studied at the end of treatment with Igi.v., 8 were in complete remission (1 fleetingly for 2 months and 1 preceding initiation of Igi.v.), and 2 were improved (1 temporarily for 4 months). A reduction in corticosteroid therapy was possible in 75 p. 100 of cases (9 patients). During treatment with Igi.v., immunosuppressors were combined with oral corticosteroids in 3 cases. It was possible to reduce their dose 1 one case and to stop them in another case. No major side effect related to treatment with Igi.v. was observed. Six months and one year after the treatment, complete remission rates were respectively 6/10 and 5/8. One patient relapsed more than one year after the end of Igi.v. treatment. CONCLUSIONS: Although very expensive, treatment with Igi.v. appears of interest in the treatment of severe corticosteroid-dependent or resistant pemphigus. Moreover tolerance is excellent. The results of our study warrant confirmation in a prospective study.
BACKGROUND: Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that can have a considerable impact on those affected. There are a number of instruments available to measure outcome in dermatological conditions but none have been developed specifically for AD. In addition, most measure symptoms and/or daily functioning, which are potential influences on quality of life (QoL) rather than assessments of the construct itself. OBJECTIVES: The aim of the current study was to develop a new instrument specifically designed to measure QoL in adults with AD-the Quality of Life Index for Atopic Dermatitis (QoLIAD). METHODS: The instrument was developed based on the needs-based model of QoL and was produced in several different countries simultaneously. Its content was derived from 65 in-depth interviews with relevant patients in the U.K., Italy and the Netherlands. The initial version of the measure was produced in U.K. English and translations were produced for the Netherlands, Italy, Germany, France and the U.S.A. using a dual translation panel methodology. A Spanish version was developed using the same adaptation process after the instrument was finalized. Field-test interviews were conducted with approximately 20 patients in each country to assess face and content validity. The instrument [in addition to the Dermatology Life Quality Index (DLQI) and the Psychological General Well-Being Schedule (PGWB)] was then administered to up to 300 AD patients in each country at two time points to finalize the instrument and test its psychometric properties. RESULTS: The initial version of the QoLIAD had 56 items that reflected the areas of need fulfillment identified in the qualitative interviews as having been affected by AD: mental and emotional stimulation, physical and emotional stability, security, sharing and belonging, self-esteem, personal development and fulfillment. Comments from patients in field-test interviews resulted in the removal of 14 items, to leave a 42-item instrument that was considered relevant and acceptable. The number of patients participating in the survey were 286 in the U.K., 46 in the Netherlands, 213 in France, 187 in Germany, 178 in the U.S.A. and 83 in Spain. Application of the Rasch model to these data identified the final 25-item QoLIAD. Unidimensionality was confirmed, with deviation of the total scale from the Rasch model evident at a single time point in one country only (the U.K.). All language versions, with the exception of the Dutch measure, had test-retest reliability coefficients in excess of 0.85. The test-retest in the Netherlands was 0.80. However, this country had the smallest sample size and the corresponding reliability for the DLQI was only 0.40. The QoLIAD had adequate internal consistency and the initial indications of construct validity were good. The levels of association with the DLQI indicated that the two instruments measure related but distinct constructs. CONCLUSIONS: The QoLIAD is a practical, reliable, valid and culturally applicable instrument for measuring the impact of AD and its treatment on QoL in clinical trials or in routine clinical practice.
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INTRODUCTION: Kaposi-Juliusberg's syndrome is a severe herpes simplex virus cutaneous infection, accompanied by general signs. Darier's disease is a rare genodermatosis characterised by keratinisation disorders. OBSERVATION: In a 51 year-old patient suffering from Darier's disease since the age of 20, a diffuse vesicular eruption occurred following a herpes eruption on the lower lip. Culture of a vesicle revealed a type 1 Herpes simplex virus. The diagnosis of Kaposi-Juliusberg's syndrome was made. COMMENTS: Kaposi-Juliusberg's syndrome is a "classical" herpes complication of atopic dermatitis. It may also develop on other predisposing territories such as acantholytic dermatitis: pemphigus vulgaris, Hailey-Hailey's disease and Darier's disease. Although a rare complication and life threatening for the patient, Kaposi-Juliusberg's syndrome can now be treated efficiently with intravenous and subsequently oral aciclovir.
Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.
There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. These lymphomas are mainly B-cell nonHodgkin's lymphomas associated with Epstein-Barr virus. Most cases concern classical immunosuppressive treatments including ciclosporin and methotrexate. A relationship between the new antitumour necrosis factor (TNF)-alpha agents and lymphoproliferative malignancies is debated. Patients with psoriasis on immunosuppressive therapies, mainly ciclosporin, are considered to have a low risk of developing lymphoid proliferation. We report a patient with erythrodermic psoriasis treated with ciclosporin and infliximab who developed a CD30+ T-cell lymphoma. This lymphoma regressed after stopping these treatments. In this case, the anti-TNF-alpha agent may have played a role in association with ciclosporin in the development of the lymphoproliferative disorder. Whereas the combination of anti-TNF-alpha therapies with methotrexate has been well studied, their combination with ciclosporin has been evaluated only in a few patients. Psoriatic patients who may require anti-TNF-alpha treatment have often been or will be treated with ciclosporin. The combination of ciclosporin and anti-TNF-alpha warrants further investigation.
BACKGROUND: Psoriasis is a T-cell-mediated immunological disease characterized by epidermal proliferation. The nature of the antigen(s) responsible for T-cell activation is still unknown. It has been suggested that the human papillomaviruses (HPVs) associated with epidermodysplasia verruciformis (EV), including the oncogenic HPV5, may contribute to the pathogenesis of psoriasis. OBJECTIVES: To determine whether EV-HPVs may play a role early in the disease, we searched for these viruses in children with psoriasis. The influence of clinical data on EV-HPV infection was investigated. METHODS: We studied scrapings of involved skin from 26 children aged 1.5-13 years with psoriasis. As controls, we analysed scrapings from 28 adults with psoriasis and 15 children with atopic dermatitis, as well as scrapings from normal skin of 28 adults with no known history of HPV infection. We searched for EV-HPV DNA sequences with a nested polymerase chain reaction method using degenerate primers specific for EV-HPVs and primers specific for HPV5 and HPV36, two EV-HPVs frequently detected in adults with psoriasis. RESULTS: Similar high prevalences were observed in children and adults with psoriasis for EV-HPVs (38.5% vs. 35.7%), HPV5 (46.2% vs. 46.4%) and HPV36 (15.4% vs. 25.0%). As in adults, we found several EV-HPV genotypes and HPV5 and HPV36 variants. A novel HPV36 subtype, HPV36b, was identified. Lower prevalences were observed in children with atopic dermatitis and in adults from the general population (6.7-10.1%). No correlation was observed between frequency of detection of HPVs and clinical data. It is noteworthy that HPV5 was identified in an 18-month-old girl and in a boy with psoriasis developing for only 1 week. CONCLUSIONS: The early detection of several EV-HPV genotypes in children further supports the link between psoriasis and EV-HPVs and suggests a putative role for these viruses in the pathogenesis of psoriasis.
BACKGROUND: Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions in hospital settings. OBJECTIVES: A 6-month prospective study was managed in our hospital among hospitalized patients to: (i) evaluate the incidence of cutaneous allergic reactions from systemic drugs; (ii) study characteristics of patients with cutaneous drug reactions; (iii) describe the adverse cutaneous reactions; and (iv) evaluate drug reaction imputability and preventability. METHODS: All suspected allergic cutaneous reactions to systemic drugs were collected during a 6-month period (November 2000 to May 2001). Exhaustivity of recording was ensured by regular dissemination of information about this study to the practitioners; a simple method for inclusion by fax was established. Inclusion criteria were suspected cutaneous allergic reactions induced by systemic drugs responsible for hospitalization or developed during hospitalization. A physical examination was done by a dermatologist who completed a standardized questionnaire. Requested information included patient characteristics (associated disorders, severity score), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). A group comprising dermatologists and pharmacologists evaluated the drug imputability and preventability. RESULTS: Forty-eight cases were collected. A prevalence of 3.6/1000 among hospitalized patients was estimated. The prevalence rate was higher in patients hospitalized in medical departments (0.5%) than in surgical departments (0.01%) (P < 0.001). The cases were mostly recruited in departments of infectious diseases and dermatology. The most frequent associated disorders were: human immunodeficiency virus (HIV) infection (19%), connective tissue disease (10%) and viral or autoimmune hepatitis (12%). Of these patients, 31% had had a previous immunological drug reaction. Adverse cutaneous drug reactions were principally exanthematous (56%). Reactions were considered severe in 34% of cases because they were responsible for hospitalization (18%), increased the duration of hospitalization (14%) or were life threatening (2%). Principal imputable drugs were antibiotics, mainly penicillins. An imputability score was likely in 56% of cases, but it was only possible to conclude definitively in 44% of patients. In 15% of the cases, the side-effect was considered to be preventable. CONCLUSIONS: This study finds a lower incidence than other studies that reported an incidence of 2% of cutaneous drug reactions in hospitalized patients, but only allergic adverse cutaneous reactions induced by systemic drugs were collected in this study. The previous studies were principally done in selected patients hospitalized only in general internal medicine or medical divisions. Our results confirm some data already known about skin drug reactions: HIV infection as a risk factor (P < 0.0001), high prevalence of adverse cutaneous reactions due to antibiotics, and difficulty in ascertaining the imputability of a drug. A high proportion (34%) of these reactions was severe and 15% were avoidable; these two facts justify the development of an intensive programme of clinical pharmacology.
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INTRODUCTION: Interferon alpha has many side effects. Among them the risk of occurrence of seizures is not well known by dermatologists. We report three cases of seizures that occurred in patients treated with interferon alpha in two dermatological diseases: mycosis fungoides and melanoma. OBSERVATIONS: A 68 year-old man, treated for mycosis fungoides, and two men aged 47 and 52 years, treated for melanoma, were under interferon alpha. After 11 months, 3 weeks and 9.5 months, respectively, the three patients had seizures without any past history of epilepsy. Anamnesis and assessment of each patient (brain CT, biological results) suggested the responsibility of interferon alpha. After withdrawal of the treatment, no relapse was observed after 3 months, 6 months and 1 year later, respectively. DISCUSSION: Seizures during treatment with interferon alpha have already been reported. According to the series their prevalence would be of 1 to 4 p. 100. Their pathophysiology is not well known, but apparently interferon alpha lowers the epileptogenic threshold by affecting the central nervous system either directly or through cytokines or neuromediators. The risk of occurrence of seizures must be known by the prescribing physician who must systematically search for past history of epilepsy or risk factors for seizures. This rare but existing side effect raises the problem of information to be supplied to the patient by the prescribing physician.
INTRODUCTION: Adult dermatomyositis is associated with cancer in 15 p. 100 to 50 p. 100 of cases and, hence, investigations should be systematically performed to search for cancer. A number of predictive factors have been reported. The aim of our study was to search for predictive factors of cancer, among adults with dermatomyositis. METHODS: We prospectively assessed 26 adults presenting with dermatomyositis, hospitalised in our department of dermatology from January 1993 to June 2000. The parameters assessed were: association with a cancer, age, gender, cutaneous necrosis, muscular weakness, electromyographic abnormalities, erythrocyte sedimentation rate, and muscular enzyme levels. RESULTS: Mean age was of 52 years and sex ratio (M/F) was of 0.53. Cancers were diagnosed in eight cases (31 p. 100) (mean age: 59.5 years; sex ratio=1; cancer localization: lung (2), breast (2), ovary, endometrium, bladder, and melanoma). Five patients in the cancer group had cutaneous necrosis and only 2 in the without cancer (p=0.01; PPV=71.4 p.100). Elevation of muscular enzyme was also associated with cancer. CONCLUSION: Our report demonstrates that cutaneous necrosis is closely associated with cancer and it suggests that in selected patients with dermatomyositis and cutaneous necrosis, more exhaustive and repeated investigations should be performed to search for cancer. The interest of elevation in muscular enzyme as a predictive factor of cancer is discussed.
BACKGROUND: Prostatic adenocarcinoma is exceptionally associated with cutaneous lesions. We describe a patient with cutaneous lymphangitis and paraneoplastic ichtyosis related to prostatic cancer. CASE REPORT: A 92 year-old man had been treated for five years for a prostatic carcinoma. An angiomatous lesion developed with in 3 months near the right breast. Physical examination revealed axillary node enlargement, a large skin angiomatous lesion, and ichtyosis. The skin biopsy of the angiomatous skin lesion demonstrated its prostatic origin with carcinomatous metastases in the lymphatic vessels. The ichtyosis was considered as paraneoplastic. DISCUSSION: Cutaneous metastases from prostatic carcinoma are rare. Less than 1 p. 100 of cutaneous metastases are of prostate origin despite the high frequency of this cancer in the general population. The clinical aspects - angiomatous lesion and paraneoplastic ichtyosis - are exceptional.
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