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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 19 recordsLinked to original sources

A follow-up study in 28 patients treated with infliximab for severe recalcitrant psoriasis: evidence for efficacy and high incidence of biological autoimmunity.

BACKGROUND: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis. OBJECTIVES: To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment. METHODS: Twenty-eight patients, 15 men and 13 women (median age 39.4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively. RESULTS: The mean number of infliximab infusions was 5.5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus. CONCLUSIONS: The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.

Adult↗

[Dermatosis and depressive symptoms].

BACKGROUND: Dermatological diseases modify and impair patients' self-image and can result in considerable psychological suffering. The purpose of this study was to determine the prevalence of depressive symptoms in patients consulting for dermatological diseases. PATIENTS AND METHODS: A prospective study was carried out on 5 successive days at the dermatology department of the Saint-Louis Hospital in Paris. A questionnaire designed to assess depressive symptoms, the CES-D, was given to all patients consulting throughout the study period. This self-assessment scale for depression was devised by the National Institute of Mental Health and has been validated over more than 20 years by means of hundreds of large-scale epidemiological studies in both general and selected patient populations. RESULTS: On completion of the 5-day study, 879 questionnaires had been collected. The sex-ratio was 53.4% women to 46.6% men. The prevalence of depressive symptoms as evaluated by the questionnaire was 23.6% for a total of 774 evaluable dossiers. Patients consulting without an appointment (n = 172) represented 22% of study subjects versus 78% attending a scheduled visit (n = 602). Depressive symptoms were found in 31.4% of patients consulting without an appointment versus 21.4% of patients with an appointment (p<0.01). Male patients consulting without an appointment constituted the most fragile group, with depressive symptoms being seen in 38.8% of this population. DISCUSSION: The prevalence of depressive symptoms among patients seen at a hospital dermatology department was 23.6% in this study. This figure was significantly higher among patients consulting without an appointment, and among men in particular. It was equal to or higher than that seen among patients considered as having more incapacitating or painful conditions as assessed using the same questionnaire. The incidence of concomitant depression should prompt dermatologists to investigate for its existence and to take appropriate therapeutic measures in order to reduce the mental suffering of their patients.

Adolescent↗

[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].

BACKGROUND: Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis. Its clinical and hematological safety is usually good. Hypersensitivity in hepatic failure patients is the most serious side effect described. PATIENTS AND METHODS: This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003. Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values). Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded. RESULTS: Twenty patients were included, 11 women and 9 men of median age 58.6 years (22-82 years) with multiple metastases in all cases. DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status. Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group. In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment. In 2 patients, treatment was stopped after the second course because of disease progression. In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment. Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively. In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology. Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment. DISCUSSION: Hypersensitivity with DTIC seems to be frequent, being observed in 20% of our patients, with early onset (after the first or second course) and absence of dose-dependence. We describe for the first time two cases of medullar aplasia occurring in association with DTIC hypersensitivity. During phase I studies, the hematologic toxicity of DTIC was moderate, rarely affecting red cells, and was observed with higher doses than those used in metastatic malignant melanoma. We suggest that this aplasia forms part of the signs of hypersensitivity because of the bone marrow morphology, the existence of anemia and concomitant resolution with all the others signs of hypersensitivity. CONCLUSION: Laboratory monitoring (NFS, liver enzymes) is thus justified, particularly after the first and second courses of DTIC. In case of fever and hypereosinophilia without liver dysfunction, DTIC may be continued together with symptomatic treatment. In the event of hepatic dysfunction, and of course severe hematological disorders, potentially fatal complications can occur and treatment must be stopped.

Adult↗

CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial.

BACKGROUND: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. OBJECTIVES: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. PATIENTS/METHODS: Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P<0.0001). RESULTS: for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. CONCLUSIONS: The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.

Adult↗

European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey.

BACKGROUND: EUROPSO (European Federation of Psoriasis Patient Associations) undertook a Europe-wide survey examining quality of life and patients' perspectives on treatment and their disease. OBJECTIVES: To explore patients' perspectives of psoriasis on their lifestyle and well-being and to gain insight into the effectiveness of and satisfaction with currently available therapies for psoriasis. METHODS: Self-administered questionnaires (n = 50,500) were mailed to members of psoriasis patient associations in Belgium, the Czech Republic, Finland, France, Germany, Italy and the Netherlands. RESULTS: Responses were received from 18,386 patients (36%), of whom 17,990 had psoriasis. Mean age at onset of psoriasis was 30.5 years, 59% of respondents had self-reported moderate to severe psoriasis (3% or greater body surface area involvement) and 30% had been diagnosed with psoriatic arthritis. The mean Psoriasis Disability Index score was 12.2 (25% of the maximum score), increasing to 21 (44%) in patients with more than 10% body surface area involvement. The greatest impact was on activities of daily living, especially affecting clothing choice, bathing routine and sporting activities. Overall, 77% replied that psoriasis was a problem or a significant problem. While patients were satisfied with the information and care from their dermatologist (40% highly satisfied), available treatment options were less satisfactory, with over 70% reporting only low to moderate satisfaction. CONCLUSIONS: This is the largest survey of people with psoriasis in Europe and shows that psoriasis has a profound impact on quality of life.

Activities of Daily Living↗

Evidence of a marked 25-hydroxyvitamin D deficiency in patients with congenital ichthyosis.

BACKGROUND: Vitamin D is essential for bone mineralization, and its deficiency may be the cause of skeletal fractures and osteomalacia. Geographical or ethnic factors may modulate the cutaneous synthesis of vitamin D. We hypothesized that major changes in keratinization may similarly alter the cutaneous synthesis of vitamin D. OBJECTIVES: To explore calciotrophic hormones, parameters of bone remodelling and bone mineral density (BMD) in nine patients with non-bullous congenital ichthyosis. PATIENTS AND METHODS: Six patients were European, three were North African. Four had received acitretin over a long period of time. A complete biological investigation, including serum and urinary calcium and phosphorus, calciotrophic hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)], bone formation and resorption markers, was performed on all patients during the winter season and repeated among four patients after summer. BMD was measured in all patients. RESULTS: All patients had a marked 25-(OH)D deficiency, clearly below the deficiency threshold of 25 nmol/L. Patients from North Africa had a greater deficiency than European patients, perhaps because of the difference in skin pigmentation. iPTH remained normal in European patients but was elevated among the North Africans. After sun exposure, an improvement in vitamin status was visible in only one patient. Bone formation and resorption markers remained normal. Femoral neck osteodensitometry indicated values near the osteopaenic threshold in two young North African females. No deleterious effect of retinoids on vitamin D metabolism was observed. CONCLUSION: Patients, and in particular pigmented patients, with congenital ichthyosis present a severe deficiency in vitamin D. Care provided to protect the skeletal future of these patients involves measuring BMD and prescribing supplementation.

Adolescent↗

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.

Adolescent↗

[Cicatricial pemphigoid: treatment with mycophenolate mofetil].

BACKGROUND: The severity of cicatricial pemphigoid (CP) varies. First-intent treatment of mild or moderate cases is dapsone. In life or sight-threatening cases, intravenous cyclophosphamide pulses are efficient but may have digestive side effects and imply repeated hospitalizations. Mycophenolate mofetil (MMF) is an oral and well tolerated immunosuppressant agent which has proved its efficacy in pemphigus and some bullous pemphigoid. In CP, encouraging case reports have been previously published. We report herein a retrospective study about 14 patients who have received MMF since 2000. PATIENTS AND METHODS: There were 5 men and 9 women, with a mean age of 69 years. MMF was introduced in 3 different clinical situations: immediately in relay to cyclophosphamide in 7 patients with severe CP (group I); in case of a mild-severe relapse at distance from with dranal of cyclophosphamide in 3 patients (group II); as first-intent immunosuppressant agent in 4 patients whose disease was not under control with high-dose dapsone, but not life - or sight-threatening (group III). In all these patients, the disease was invalidating and not controlled by dapsone +/- sulfasalazine, but did not threaten life or sight. The aim was to achieve satisfying control of the disease with an oral and well tolerated immunosuppressant agent, and to maintain good quality of life. The dose of MMF was 1.5 or 2 g per day. The criteria of MMF efficacy was the healing of previous lesions and the absence of new progressive lesions. RESULTS: MMF was efficient in obtaining or maintaining a good control of the disease in 10/14 patients, as long as the underlying treatment with dapsone (2 mg/kg/d) was maintained. In 7/10 cases, it was possible to decrease the dapsone dose in order to improve hematological tolerance. In the 3 other cases, a relapse occurred when the dose of dapsone was decreased. MMF was inefficient in controling the disease in 4/14 patients (29 p. 100). Clinical and biological tolerance of MMF was good in 13/14 patients. DISCUSSION: In this series, MMF was proposed to heterogenous patients, who presented at that time a mild-moderate disease and for whom we wanted in improve the quality of life. MMF seems to be an interesting drug, capable of obtaining or maintaining satisfactory control of the disease and permitting the decrease of dapsone doses in some mild-severe CP. However MMF must not replace cyclophosphamide in severe sight or life-threatening forms of CP.

Administration, Oral↗

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum.

Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Administration, Topical↗

[Particular histological features of a case of Sweet's syndrome induced by G-CSF].

BACKGROUND: Sweet's syndrome may occur during medullar aplasia, especially after treatment with exogenous growth factors such as G-CSF. In this context, Sweet's syndrome presents particular histological features that we detail in this observation. CASE REPORT: A 50 year-old man was treated for multiple myeloma with a mobilizating chemotherapy prior to autologous stem cell transplantation. Four days after the onset of G-CSF, he presented with a febrile generalized eruption of erythematous infiltrated lesions. Histological examination of a skin biopsy showed a neutrophilic infiltrate associated with atypical xanthomized histiocytes and vascular hyperplasia with marked endothelial turgescence. Treatment with a short cause of oral corticosteroids was efficient. DISCUSSION: The classical histological features of Sweet's syndrome consist in a dermal neutrophilic infiltrate with edema. In our patient, we noticed the presence of atypical histiocytes among the dermal neutrophilic infiltrate. These histiocytes are described in maculo-papular eruptions induced by G-CSF, and should not be confused with a malignant infiltrate associated with a hemopathy. Vascular hyperplasia may be related to the angiogenic properties of G-CSF. Knowledge of these histological features would enable clinicians and histologists to recognize the appropriate diagnosis.

Granulocyte Colony-Stimulating Factor↗

[Recessive dystrophic epidermolysis bullosa (Hallopeau-Siemens) with IgA nephropathy: 4 cases].

BACKGROUND: The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe hereditary dermatosis, associated with a collagen VII deficiency. A chronic inflammatory syndrome, secondary to recurrent cutaneous infections, may be the cause of AA amyloidosis, with chronic renal failure, involving life prognosis. Less frequently, an IgA glomerulonephritis may occur and induce renal failure. Only two cases have been previously described. We report herein four new cases. CASE REPORT: We report four cases of HS-RDEB associated with IgA glomerulonephritis. A renal biopsy confirmed the diagnosis in all four cases. Later on, two patients had a second renal biopsy, indicated for deterioration of renal function. One of these patients showed AA type renal amyloidosis on the second biopsy. None of these six biopsies, conducted in our four patients led to local cutaneous complications. Subsequently three patients presented with terminal renal failure. Hemodialysis was set up, with good tolerance and improvement in quality of life. DISCUSSION: IgA glomerulonephritis should be suspected if a patient with HS-RDEB presents with hematuria. Renal biopsy is not contraindicated, confirms the diagnosis and helps to specify the prognosis. Hemodialysis is possible and well tolerated in the terminal stage of renal failure. There is not enough evidence for a genetic link between HS-RDEB and IgA glomerulonephritis, but repeated skin infections may be involved in the pathophysiology of the renal disease.

Adult↗

High-dose therapy and autologous stem cell transplantation in relapsing cutaneous lymphoma.

Treatment of cutaneous T-cell and B-cell lymphomas is difficult and relapses are frequent. To evaluate the efficiency of high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) on relapsing cutaneous lymphomas, we conducted a retrospective study of 14 patients. We investigated the clinical and histological parameters of the lymphoma, previous treatments to ASCT, short-term complications of ASCT, and occurrence of a relapse. There were 11 males and three females, with a median age of 42 years. Most often, the skin disease was disseminated without extracutaneous involvement. Four patients had a B-cell lymphoma and 10 a T-cell lymphoma. CD30 was negative in 8/10 T-cell lymphomas. Before ASCT, 13 patients had chemosensitive disease; one had refractory disease. The conditioning regimen included TBI in nine cases. No toxic death occurred. Relapse of the lymphoma occurred in eight cases (T-cell lymphoma in seven cases), within 4 months after ASCT in six cases. Relapses were treated with local treatment, interferon or classical chemotherapy. At the end of the study, 11 patients were alive and three patients had died. HDT and ASCT do not benefit patients with T-cell lymphomas. For patients with disseminated relapsing cutaneous B-cell lymphomas, this procedure should be considered.

Adult↗

Ciclosporin in psoriasis clinical practice: an international consensus statement.

The main recommendations for the use of ciclosporin in the management of psoriasis are: (i) intermittent short courses (average of 12 weeks duration) of ciclosporin are preferable; (ii) ciclosporin should be given in the dose range 2.5-5.0 mg kg(-1) day(-1) (doses greater than 5.0 mg kg(-1) day(-1) should only be given in exceptional circumstances); (iii) treatment regimens should be tailored to the needs of each patient; (iv) selection of patients should take into account psychosocial disability, as well as clinical extent of disease and failure of previous treatment; (v) each patient's renal function (as measured by serum creatinine) should be thoroughly assessed before and during treatment; (vi) each patient's blood pressure should be carefully monitored before and during treatment; (vii) adherence to treatment guidelines substantially reduces the risk of adverse events; (viii) long-term continuous ciclosporin therapy may be appropriate in a subgroup of patients; however, duration of treatment should be kept below 2 years whenever possible; and (ix) when long-term continuous ciclosporin therapy is necessary, annual evaluation of glomerular filtration rate may be useful to accurately monitor renal function.

Consensus↗

Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosa.

BACKGROUND: In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. OBJECTIVE: In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. METHODS: Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. RESULTS: Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36-70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. CONCLUSION: Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood.

Adolescent↗

Validation of a morphometric method for evaluating fibroblast numbers in normal and pathologic tissues.

The aim of this work was to validate an image analysis method, based on cell nuclei form factor determination, for counting fibroblasts within human dermis. We first used reconstructed dermal equivalents in which fibroblasts can also be counted directly after lysis of the collagen matrix. We found a good correlation between the results of direct counting and those of image analysis from day 10 to day 28 of culture. When applied to young normal donors' skin biopsies fixed in Bouin's solution and embedded in paraffin, the image analysis method yielded mid-dermis fibroblast counts of between 2100 and 4100 per mm3 of fresh tissue. A nuclear form factor (FF) comprised between 0.35 and 0.84 was found to be a biologic marker of fibroblasts. This was confirmed after fibroblast discrimination from other cell types, which had rounder nuclei (FF >/= 0.85) and were identified either by their location (e.g. endothelial cells) or by labeling with specific antibodies (e.g. lymphocytes and monocytes/macrophages). Similar results were obtained with seven healthy donors' skin biopsies that had been frozen in nitrogen liquid and cryostat-sectioned, showing that this counting method is independent of the histologic procedure. Finally, analysis of samples of hypertrophic scars from two patients revealed that fibroblast density in some parts of the dermis was more than twice the value found in other parts presenting a fibroblast density almost normal, showing that this cell counting method can also be used to assess fibroblast heterogeneity within a given tissue.

Cell Count↗