Biomedical subjects
S Boulinguez
Publications and source records attributed to S Boulinguez.
[Acquired bullous epidermplysis].
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[Tissue diffusion of fucidine tablets: new study of pharmacokinetics].
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[Aphthae or painful ulcers induced by nicorandil].
A RECOGNIZED CAUSE OF BUCCAL APHTHOSIS: Nicorandil is the leading drug in a new pharmacology class of well tolerated anti-angina products with vasodilating action. The first cases of buccal aphthosis or ulcerations induced by nicorandil were reported in 1996. Among drugs inducing buccal aphthosis or ulcerations, the largest body of information available on reported cases concern nicorandil. CHARACTERISTIC LESIONS: Forty cases of painful buccal lesions induced by nicorandil have been recorded. Among the 8 publications in the literature, 7 were reported by French groups. The prevalence of this adverse effect is an estimated 5%. Patient age varies from 60 to 90 years with an even gender distribution. A history of aphthosis is noted in 23% of the cases. The lesions vary in size from 0.5 cm to 3 cm and in number from 1 to 10, generally localized on the inner aspect of the cheeks or on the tongue. The lesions develop for about 3 to 36 before diagnosis and the delay to onset of signs after initiating nicorandil treatment is 15 days to 24 months (generally 2 months). Lesions basically develop after high-dose treatments and, for a few cases, after increasing the dosage. Cure is obtained in all cases after 1 to 12 weeks. OPEN QUESTIONS: The probability that nicorandil is the cause of these ulcerations or aphthae is very high. Certain terms do however need to be defined with precision. Are we talking about aphthae or ulcerations? The term painful ulceration would appear to be preferable because it includes both ulcerations and aphthae in cases lacking further information. The wide variability in the geographical distribution could likely be linked to underreporting. The notion of a dose effect suggests a toxic mechanism that could develop in predisposed populations (ethnic origin...) and would be directed against buccal targets (salivary glands...) via the active drug or its metabolites or via drug interactions. This new adverse effect of nicorandil is quite spectacular and very painful. However, no life-threatening event has been observed.
Adverse effects associated with EMLA cream used as topical anesthetic for the mechanical debridement of leg ulcers.
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[Cutaneous reactions or necrosis from interferon alpha: can interferon be reintroduced after healing? Six case reports].
PURPOSE: Alpha, beta or gamma interferon (INF) are cytokines produced by cells in response to antigenic stimulation. They are used to treat various hepatic, hematological, oncological and neurological diseases. Cutaneous reactions (rash, alopecia, labial herpes, erythema, or induration at the site of injection, and more rarely cutaneous necrosis) represent 5 to 12% of side-effects observed in patients receiving INF. The authors report six cases of local cutaneous reactions to alpha INF, five of which corresponded to cutaneous necrosis. This makes them question the relevance of INF reintroduction. METHODS: The study included 5 male and 1 female patients (mean age: 59.1 years; range: 42 to 74 years old). Three patients had chronic hepatitis C, while three others presented a blood disease. RESULTS: Cutaneous necrosis occurred after 1 to 10 months of treatment. The mean time to healing was 16.2 weeks. Reintroduction of the drug including injection in other sites did not lead to recurrence of necrosis in five out of the six cases. CONCLUSION: INF-induced cutaneous necrosis does not depend on the type of INF, the site of injection, the dose and may occur 2 months to 9 years after treatment implementation. The exact mechanisms involved in cutaneous necrosis remain unknown. Morbidity is due to a very long time to healing (4 to 6 months). Futhermore, healing sometimes requires prior surgery. Physicians should be aware of the potential occurrence of erythema in patients treated by INF, as it is the first sign of necrosis. The site of injection should then be modified. In case of necrosis, risk factors for thrombophilia, factors reducing microcirculation (DHE, beta-blockers, cigarette smoking) should be investigated. INF injections should be cautiously reintroduced in other sites with the help of a nurse in case of self-injections prior to the occurrence of necrosis. Regarding self-injections patients' training should be emphasized.
[Drug-induced hypersensitivity syndrome in internal medicine: diagnostic and therapeutic traps. Eight observations].
PURPOSE: Drug-induced hypersensitivity syndrome (DIHS) is an acute and severe drug reaction. Manifestations include severe skin lesions, fever, nodal enlargement, blood eosinophilia and multisystemic involvement. The severe systemic manifestations of DIHS are responsible for a 10% mortality rate. The pertinence of corticosteroid therapy is discussed. METHODS: The authors report eight retrospective cases of DIHS obtained from the PMSI (Programme de Médicalisatiopn des Systèmes d'Information) between November 1991 and November 1998. RESULTS: The series consisted of five male and three female patients (mean age: 52.6 years; range: 23-83 years). The interval between the introduction of the drug and the onset of the reaction varied from two to eight weeks. Due to severe systemic manifestations, three patients were given corticosteroid therapy. Healing of skin and systemic disorders resolved with a mean delay of 4.4 weeks (range: 1 to 56 weeks). CONCLUSION: DIHS can be a diagnostic trap, as there are no diagnostic criteria for DIHS. Only the association of multiple arguments such as the time to the occurrence of symptoms, clinical similarity to many infectious illnesses, hypereosinophilia, atypical lymphocytosis, etc. may help guide diagnosis. DIHS can also be a therapeutic trap, as prompt withdrawal of the offending drug is essential to minimize morbidity. Although still controversial in the literature, the pertinence of corticosteroid therapy may be discussed in case of severe systemic effects. Patch testing can be a valuable tool to determine the responsibility of a drug; however it proves to be useful only when positive.
Role of drug exposure in aphthous ulcers: a case-control study.
BACKGROUND: Drug-induced aphthous ulcers have been the subject of several isolated and heterogeneous case reports for the last three decades. OBJECTIVES: To perform a case-control study to evaluate the risks linked to drug exposure in aphthous ulcers. METHODS: Eighty patients with typical clinical patterns of aphthous ulcers and 152 control patients who had had consultations for skin tumours were studied. A standardized questionnaire, concerning clinical features, life-style and medications taken during the last month, was completed for each patient. RESULTS: Case patients had a much higher intake of medications than control patients, respectively, 5.1 and 2. 8 medications per patient (P < 0.0001). Multivariate paired analysis showed an association between aphthous ulcers and two classes of drugs: non-steroidal anti-inflammatory drugs (P < 0.001) and beta-blockers (P = 0.002). Smoking could have a protective effect against aphthous ulcers (P < 0.001). CONCLUSIONS: Previous case reports and the results of this study suggest a real link between beta-blockers and aphthous ulcers. Our study did not confirm a role of other drugs but a few interesting case reports with positive reintroduction have to be considered. These results could be beneficial for patients, as healing may occur when the incriminated drug is discontinued.
[Analysis of the literature about drug-induced aphthous ulcers].
OBJECTIVES: Analysis of the literature on drug-induced aphthous ulcers and mucosal ulcerations and evidence-based grading. MATERIAL AND METHODS: Four literature sources were analyzed. Three groups of key words were used: 1) oral, buccal, genital, mucosal; 2) ulcer, ulceration, aphthous, aphthosis; 3) induced, drug, adverse-effects, with cross-overs. Four grading patterns were used: presence of aphthous term or synonym, typical clinical description of aphthous ulcer, presentation suggesting diagnosis of aphthous ulcer, criteria defining likelihood of drug causality. RESULTS: We examined 66 of the 220 publications responding to our selection criteria. Typical clinical description of aphthous ulcer and/or clinical presentation suggesting the diagnosis of aphthous ulcer were noted for 8 compounds with likely or palausible patterns of causality. For 21 compounds, we found only aphthous term or synonym without a clinical description or presentation. DISCUSSION: Our review of the literature individualized a group of 8 compounds where the diagnosis of aphthous ulcers was plausible and another group of 21 compounds where the diagnosis of aphthous ulcers requires confirmation. The clinical relevance and limitations of this analysis are discussed. CONCLUSION: Drug-induced aphthosis is probably a real phenomenon. Causality of the 8 compounds in the first group is simply more fully documented than for the 21 compounds in the second group. A low evidence level may not confirm these hypotheses. Some drugs may have been incorrectly ruled out due to lack of information.
[Pretibial epidermolysis bullosa and hypothyroidism].
BACKGROUND: We report a case of primary non-autoimmune hypothyroidism causing pretibial epidermolysis bullosa. CASE REPORT: A 70-year-old man with primary non-autoimmune hypothyroidism developed blisters of different ages on the lateral aspect of both legs. Pathology reported blisters with subepidermal cleavage. Direct immunofluorescence was negative. Electron microscope examination showed a variable cleavage level and diffuse infiltration of a granulous and amorphous microfibrillar substance. After hormone replacement therapy, euthyroidism was associated with a reduction in the number of bullae and finally complete remission. After 12 months follow-up, the patient has not experienced recurrence. DISCUSSION: Recurrence-free clinical improvement after hormone replacement therapy suggests the diagnosis of hypothyroidism pretibial epidermolysis bullosae. Mochizuki et al. described a similar case which rapidly regressed after hormone therapy but where the electron microscope showed a different cleavage level. These bullae appear to result from a mechanical mechanism due to their localization in areas exposed to friction and also to the presence of bullae of different ages. This hypothesis is confirmed by the presence of a variable level of cleavage and a substance dense to electrons at electron microscopy as well as by the skin weakness. Our case confirms the reality of hypothyroidism pretibial epidermolysis bullosa. Thyroid hormones should be assayed in patients presenting pretibial bullae.
[Scurvy presenting with ecchymotic purpura and hemorrhagic ulcers of the lower limbs].
INTRODUCTION: The risk of vitamin C deficiency is underestimated in industrialized countries and is only disclosed in rare cases of severe scurvy. CASE REPORT: We report three cases of scurvy presenting with ecchymotic purpura and hemorrhagic ulcerations of the lower limbs. Vitamin C supplementation led to rapid improvement of the skin lesions. DISCUSSION: Clinical diagnosis of low-grade deficiency can be difficult. Biological diagnosis requires special care in sample taking and transport.
[The levels of quality of life].
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Photosensitivity with sulfasalazopyridine hypersensitivity syndrome.
Five weeks after the start of treatment with an association of sulfasalazopyridine and piroxicam, a 30-year-old woman presented with an eczematous eruption in light-exposed areas, hepatomegaly and fever (38 degrees C). Laboratory studies showed leukocytosis, eosinophilia and hepatic cytolysis. Treatment consisted of withdrawing the two drugs and topical steroids. The clinical signs regressed in 6 days. An increase in eosinophilia and hepatic cytolysis was observed until the tenth day, after which the trend reversed. Laboratory parameters were normal on the twentieth day. One month later, photopatch testing was performed. A patch test with sulfanilamide irradiated with UVA was positive. Clinical and laboratory findings were highly suggestive of drug hypersensitivity syndrome. The positive result from the UVA photopatch test with sulfanilamide suggests that sulfasalazopyridine was involved in the occurrence of hypersensitivity syndrome in our patient. We conclude that photodistributed eruptions can be observed in drug hypersensitivity syndrome with photosensitizing drugs.
[Tolerance and feasibility of adjuvant treatment of stage II malignant melanoma with high-dose interferon-alpha].
BACKGROUND: The use of high-dose interferon alpha as adjuvant therapy has been shown for the first time to improve recurrence-free and overall survival in stage II malignant melanoma. The aim of our work was to evaluate the toxicity of this therapeutic scheme during a 1-year period in 13 patients with malignant melanoma. PATIENTS AND METHODS: Thirteen patients, mean age 56 years, with stage II melanoma were included. Interferon alpha was administered at the dose of 20 MU per m2 body surface area five days per week for four weeks during the induction phase and at the dose of 10 MU subcutaneously three times a week for 48 weeks in the maintenance phase. Patients underwent clinical assessment daily and had blood tests twice a week during the induction phase. Weekly blood tests and monthly examinations were then performed during the maintenance phase. Clinical and biological toxicity was evaluated in accordance with the WHO scores. Grade 3 toxicity led to a 30 p. 100 dose reduction and treatment was interrupted in case of grade 4 toxicity. RESULTS: A flu-like syndrome (grade 1-2) and digestive disorders, nausea, anorexia related to dysgeusia or dry mouth were observed in most of the patients during the induction phase and persisted in 30% of the patients during the maintenance phase. Six patients developed a state of depression (grade 2-3) which persisted during the maintenance phase, inciting us to prescribe an antidepressor regimen for all our patients. One patient developed major reversible alopecia at dose reduction. Nine patients had grade 1 or grade 2 neutropenia and four had grade 3 neutropenia. Seven patients developed grade 1-2 thrombocytopenia, six had elevated transaminase levels (grade 1-2) and two moderately elevated CPK. CONCLUSION: At the end of the induction phase of interferon alpha therapy in 13 patients with malignant melanoma, 8/13 had received 100 p. 100 of the theoretical dose and 11/13 had received 80 p. 100. At the end of the treatment protocol, 5/10 patients had received 100 p. 100 of the theoretical dose and 8/10 more than 80 p. 100. The proposed protocol appears to be feasible without major risk. Rigorous clinical and biological surveillance is mandatory.
[Penile lichen sclerosus: follow-up study].
INTRODUCTION: The aim of this work was to study the long-term course of patients with penile lichen sclerosus and atrophicus. PATIENTS AND METHODS: We reviewed the files of 16 patients followed at our university center from 1982 to 1997 for pathologically proven penile lichen sclerosus and atrophicus. Age at disease onset, duration of the disease course, presence of a triggering factor, initial localization, signs and symptoms, treatment given and its efficacy were recorded. RESULTS: Mean age at diagnosis was 52 years. Inaugural prepuce localizations were observed in 6 cases, involving the distal part of the penis and the glan in 3 cases. Concomitant involvement of the glan and the balanopreputial groove were seen in 6 cases. The localization was limited to the glan in one case. Six patients underwent posthectomy and one had dorsal plasty of the prepuce. The 9 other patients were treated medically with topical corticosteroids and/or androgens. One patient had died prior to evaluation. Among the 9 patients given medical treatment, lichen sclerosus persisted in 7, one developed a squamous cell carcinoma of the penis and one was cured. Among the 6 cases of surgical treatment, 5 were cured and 1 had persistent lesions. Considering the initial localization, long-term course showed that 7 of the 8 patients with a prepuce localization (alone or in association with glan involvement) were cured while the 7 patients with a lesion of the balanopreputial groove (alone or in association with glan involvement) or a lesion of the glan alone still had lichen sclerosus and atrophicus. The non parametric Fischer test showed that the chances of cure were better for preputial localizations than for balanopreputial localizations (p = 0.001) and that surgical treatment was more effective than medical treatment. DISCUSSION: This study of a small number of patients highlighted two points: prepuce localizations of lichen sclerosus and atrophicus cure better than balanopreputial localizations, and that medical treatment is partially effective in balanopreputial localizations. One patient developed squamous cell carcinoma of the penis. As the level of the cancer risk remains unknown, it would be important to provide the most effective treatment in all cases of penis lichen sclerosus and atrophicus.
Bullous pemphigoid induced by bumetanide.
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