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Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation and severity are very diverse ranging from the frequent and benign exanthemas to the rare but severe CADR involving deep organs in the case of drug reaction with eosinophilia and systemic symptoms (DRESS) or leading to skin bulla and epidermal detachment in toxic epidermal necrolysis. The main differential diagnoses are infections, especially viral ones, which could give clinical symptoms identical to those occurring in CADR.

Background: Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date., Patients and Methods: We report 2 cases of acantholytic dyskeratosis, reaching the trunk and the seborrheic zones, not itchy, appeared one month after the introduction of vemurafenib. The histological analysis was typical of a "Grover-like rash" for the 2 patients., Discussion: The appearance of acantholytic dyskeratosis under vemurafenib, a BRAF inhibitor, seems related with a paradoxical activation of the MAP-kinases pathway and with a growth acceleration of lesions in which RAS mutations of keratinocytes. Theses dermatoses seem also to occur with dabrafenib., Conclusion: The patients treated by BRAF inhibitors (vemurafenib and dabrafenib) can present acantholytic dyskeratosis. The arisen of this mild dermatosis does not question, of course, the continuation of the treatment. These cutaneous manifestations can be managed with emollients., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the toxicity of liquid detergent capsules for children., Methods: Analysis of 684 consecutive cases from the Paris Poison Center (2011-2012)., Results: Most enquiries (97 %) concerned children 5 years of age or younger. The main circumstances of exposure were ingestion alone (72.4 %) or together with eye or skin contact (7.5 % and 7.3 %, respectively). The effects observed were generally due to the irritating properties of concentrated detergents: minor digestive disturbances (particularly vomiting in nearly 50 % of cases) after ingestion and conjunctivitis and/or keratitis after eye contact. The main complications were 24 cases of keratitis and one case of pulmonary toxicity after ingestion. A rash was observed in nine patients; it was delayed in two., Conclusions: The effects observed with liquid detergent capsules were very similar to those resulting from exposure to other detergents. However, exposure to these agents are very frequent and often results in eye contact, which may be responsible for keratitis, and after ingestion detergent inhalation is a possible complication. All cases with eye symptoms or cough after liquid detergent capsule exposure deserve prompt medical examination and assistance. Greater awareness of both health professionals and consumers on the dangers and risks of these laundry detergent pods is required for better treatment of exposure accidents and for their prevention., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Imatinib, an antineoplastic drug used to treat certain cancers, has many side effects such as hematologic, neurologic or cutaneous toxicity. These toxicities seem to be due to a high imatinib plasmatic concentration and are frequently controlled by a discontinuation or a dosage reduction of the drug. We report here in 2 cases of cutaneous side effects induced by imatinib in order to demonstrate the necessity of drug monitoring in such cases. In our cases, imatinib is responsible in the occurrence of these side effects. Monitoring plasma levels of imatinib allowed us to judge if levels were toxic or not and to avoid discontinuation of imatinib in some cases.

Introduction: The aim of this study was to investigate the epidemiological aspects of drug eruptions in children in hospital area in Cotonou., Patients and Method: A retrospective study was carried out in the Department of Dermatology of Cotonou (Benin) from 1998 to 2009. All cases of drug eruption occurred, during the study period, in children under 16 years old were selected for the study. The diagnosis of the drug eruption was based on clinical findings. The Identification of culprit drugs was based on the criteria as defined by the French Group of Pharmaco-vigilance., Results: From 1998 to 2009, 232 cases of drug eruption were diagnosed in the Department of Dermatology. Of this, 35 cases occurred in children under 16 years old. The patient mean age was 6.6 years with a sex ratio of 0.94. 4 patients were HIV positive. The culprit drug was identified in 21 patients (60%): sulfonamides 52.38% (11/21 cases), penicillin 9.52% (2 cases), vaccine 9.52% (2 cases), acetaminophen 9.52% (2 cases), acetyl salicylic acid 4.76% (n = 1), quinine 4.76% (n = 1), phenobarbital 4.76% (n = 1) and ceftriaxone 4.76% (n = 1). The main clinical patterns were: fixed drug eruption 45.71% (16/35), maculopapular rash 17.14% (n = 6), Stevens-Johnson syndrome 17.14% (n=6), and urticaria 8.57% (n = 3), 1 case of toxic epidermal necrolysis was seen and one patient died., Conclusion: Skin reactions caused by drug intake are a rare disorder among children and fixed drug eruption is the main clinical presentation of the disease in Cotonou (Benin).

Background: Bortezomib (Velcade) is a proteasome used in the treatment of myeloma. It is associated with a number of adverse cutaneous effects, often described as papulonodular rash on the upper half of the body. We report a new case characterised by the presence of CD30+ lymphocytic infiltrate in the lesions., Patients and Methods: A 62-year-old woman receiving six courses of bortezomib for stage IIIA IgA myeloma presented a skin eruption during the second course of treatment that involved rounded papular or papulonodular elements on the upper body. Histopathological examination of a skin biopsy sample showed clinical picture reminiscent of Sweet's syndrome but including a significant number of CD30+ lymphocytes. The skin rash recurred to a greater or lesser degree during subsequent courses of therapy, but it was not necessary to discontinue the treatment. Symptoms subsided after the final course of bortezomib., Discussion: Skin eruptions with bortezomib are a common occurrence but generally do not prevent continuation of treatment. While they have given rise to a variety of histopathological pictures, clinical settings such as those seen with our patient appear common. In terms of histopathology, the rash is reminiscent of Sweet's syndrome but our case differed in terms of the presence of CD30+ infiltrate. The latter may be compared with reactional infiltrates of the same type seen during use of other treatments for malignant blood diseases. The underlying mechanism is poorly understood.

Background: Fluindione is an oral anticoagulant belonging to the vitamin K antagonist class. Although fluindione is very widely prescribed in France, few cases of cutaneous drug reactions have been reported. Below we describe a case of acute generalised exanthematous pustulosis due to fluindione as confirmed by patch-testing., Patients and Methods: A 70-year-old woman was hospitalised for diffuse erythematous and pustular rash 48hours after initiation of fluindione treatment for cardiac arrhythmia. A diagnosis of fluindione-induced acute generalised exanthematous pustulosis was made. After withdrawal of fluindione, the eruption cleared up within eight days. Warfarin was then used without skin reaction. Subsequent patch-tests were positive for fluindione., Discussion: These signs were consistent with fluindione-induced acute generalised exanthematous pustulosis. A causative role of fluindione is very likely in view of the rapid onset after initiation, improvement after withdrawal and positive patch tests. Skin patch-testing, which is easily performed, can be extremely helpful in determining a causal relationship with medication.

Background: For the first time, 2 cases highlight the fact that, in the event of cutaneous adverse drug reactions under treatment associating 2 drugs, a positive test with one of the 2 does not authorize further readministration of the remaining drug without hospital surveillance., Patients and Methods: A man had urticaria during treatment with pristinamycin subsequently replaced by ceftriaxon. All the patch-tests with synergistins were positive, whereas patch-tests, prick-tests and intradermal tests with betalactams were negative. The oral challenge with ceftriaxon was positive. A woman taking spiramycin developed a maculopapular rash which was slowly regressive despite substitution with cefixim and corticotherapy. Patch-tests, prick-tests and intradermal tests with macrolides and betalactams were negative. An oral challenge with spiramycin was positive., Discussion: Sensitization to two antibiotics without shared chemical structures can occur during the same episode of a cutaneous adverse drug reaction, even without prior indication of sensitization to these drug classes. The mechanisms at play in this phenomenon are still debated, but this highlights the fact that reintroduction of any drug suspected at the time of a cutaneous adverse drug reaction must be performed under hospital surveillance, whatever the degree of imputability and even if skin tests with other drugs taken simultaneously were positive.

Background: TNFalpha blockers have recently extended the therapeutic arsenal available in dermatology. However, dermatologists must be informed of their potential adverse dermatological effects. While the chief adverse effect of TNFalpha blockers is risk of infection, cutaneous adverse effects have not yet been clearly elucidated and publications on this topic are few and far between. The aim of our study is to report various dermatological problems noted during treatment with TNFalpha blockers., Patients and Methods: This was a retrospective study of patient files. The study population comprised patients receiving TNFalpha blockers and presenting cutaneous reaction, and seen in the dermatology department between August 2001 and December 2004., Results: Eleven patients were included. The following cutaneous reactions were seen: delayed skin rash (1 case), lupus syndrome (1 case), cutaneous vasculitis (2 cases), palmoplantar pustulosis (2 cases), psoriasis vulgaris (1 case), atopic dermatitis (1 case), lichenoid rash (1 case), purpuric capillaritis (1 case) and melanoma (1 case)., Discussion: The cutaneous manifestations seen represented a wide range of different clinical pictures. Dermatologists must be aware of these potential adverse effects. Future improvement of knowledge of the physiopathological mechanisms as well as the institution of prospective cohort studies should provide clearer guidance on the management of such symptoms.

Background: Imatinib (Gleevec) is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia. We describe a case of drug reaction with eosinophilia and systemic symptoms (DRESS) after institution of treatment with imatinib., Patient and Methods: A 78-year-old woman was treated with low-dose imatinib for chronic myeloid leukemia since November 2003. A macular and pruritic eruption appeared on the patient's trunk after 7 weeks of treatment and gradually worsened. After 1 month, she was admitted for generalized skin eruption with fever and diffuse lymphadenopathy. Laboratory data showed hypereosinophilia and blood cultures positive for Staphylococcus aureus. Imatinib was stopped and replaced with hydroxyurea (Hydrea). Improved clinical and laboratory results were seen with antibiotics and topical steroids., Discussion: To our knowledge, this is the first case of DRESS following treatment with imatinib. Cutaneous reactions to imatinib are frequent and are usually mild, comprising maculopapular eruption, pruritus and facial edema. Few cases of serious skin reactions have been reported until now. Several authors suggest that the prevalence and severity of cutaneous manifestations are related to a pharmacologic effect of imatinib. Our observation cannot rule out an underlying immunologic mechanism. Septicemia may also play a part in the development of DRESS.

The DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) corresponds to a drug reaction generally including cutaneous eruption, fever, hematologic abnormalities such as eosinophilia and atypical lymphocytosis and one or more specific visceral lesions specially in the liver. We report a case of drug hypersensitivity syndrome or DRESS associated with intra and extra-hepatic biliary lesions. This syndrome was associated with sulfasalazine and naproxene therapy. A reactivation of HHV6 was documented in the continuations of the DRESS and could play a role in the symptomms.

The authors undertook a retrospective study of the modes of prescription, the tolerance and efficacy of prostaglandin E1 in 62 consecutive neonates with congenital heart disease (average Age 1.6 days: 35 boys: weight: 3.1 +/- 0.6 Kg) admitted to the paediatric intensive care unit of Nancy University Hospital between 1998 and 2002. The infusion time and cumulative dosage were 134 +/- 112 (6-480) hours and 111 +/- 94 (4-396) microg/Kg respectively. The side effects that were observed were: Apnoea (19%), abdominal distension (16%), bradycardia (13%), enterocolitis (6.5%), hypotension (6.5%), vomiting (5%), fever (1.6%) and skin rash (1.6%). Gastrointestinal disturbances are associated with a low body weight (p<0.04), to prolonged treatment (p<0.02) with no influence of initial or cumulative dosages (P=NS), with respiratory assistance (p<0.03) and longer hospital stay (p<0.01). Hypotension was commoner in cases of poor neonatal adaptation. Mortality was correlated with severe initial acidosis (p<0.02), a low Apgar score, the initial prolonged use of high doses of prostaglandin (p<0.04), and the presence of severe valvular aortic stenosis or hypoplasia of the left heart (p<0.002). The authors conclude that treatment with prostaglandin is effective in the majority of cases despite the use of low maintenance doses (0.01 microg/Kg/min). Gastrointestinal disturbances favourised by the perinatal context, the cardiac disease, and prolonged treatment are significant factors for morbidity and mortality. The beneficial role of early neonatal enteral feeding was not demonstrated in this high risk population.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also called hypersensitivity reaction, is a severe idiosyncratic reaction to drugs, especially to anti-epileptic drugs. Clinical features associate cutaneous eruption, fever, multiple peripheral ganglions, and potentially life-threatening damage of one or more organs. DRESS syndrome is well described in adults treated with aromatic anti-epileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, but also with other drugs. The new anti-epileptic drugs, such as oxcarbazepine also induce various cutaneous eruptions, but with less report of DRESS syndrome. In children, DRESS syndrome is rare and probably underdiagnosed. We report on the case of a 11-year-old girl hospitalised with an acute severe hepatitis revealing an oxcarbazepine-induced DRESS syndrome.

Introduction: Fluindione (Previscan) is an oral anti-vitamin K anticoagulant, widely prescribed in France. Contrary to phenindione, which is also an indanedione derivative, very few cases of immunoallergic reactions have been described., Case Report: A 68 year-old man, treated with fluindione for cardiac arrhythmia, presented with a pustular eruption and erythema twenty days after initiation of treatment. The eruption was associated with hyperthermia, arthralgia, neutrophilia (11,000/mm2), hepatic cytolysis and renal involvement including acute renal failure, hematuria and proteinuria. In view of the absence of any earlier case in the literature, we did not impute fluindione and the drug was reintroduced and led to the rapid recurrence of all the same manifestations., Discussion: These manifestations were consistent with an immunoallergic reaction to fluindione (probable intrinsic imputability I3) and acute interstitial nephritis (probable intrinsic imputability I3). We believe this is the first case of acute generalized exanthematous pustulosis induced by fluindione (intrinsic imputability Bo). A few rare cases of fluindione-induced hypersensitivity reactions and acute interstitial nephritis, however, have been described.

CIRCUMSTANCES AND CHARACTERISTICS: The risk of toxiderma is greater in patients infected by the human immunodeficiency virus (HIV). The most common toxidermas are maculopapular exanthema and drug hypersensitivity reactions. These toxidermas are predominantly observed with non-nucleoside reverse transcriptase analogs (nevirapine, efavirenz) and abacavir. Toxiderma has also been observed with other nucleoside reverse transcriptase analogs (zalcitabine) and protease inhibitors. REGARDING SEVERITY: The toxidermas observed are usually benign (maculopapular exanthema) and do not always require suspension of the treatment. However, certain toxidermas (Stevens-Johnson syndrome, Lyell syndrome and drug hypersensitivity syndrome) may be life-threatening and therefore contraindicate the continuation of treatment and also its sudden reintroduction. PREVENTION AND PRACTICAL APPROACH: Several studies have assessed the risk factors for toxiderma induced by nevirapine and hypersensitivity reactions to abacavir. The practical approach varies depending on the drug responsible, the clinical form of the toxiderma and the possible alternatives.

Introduction: Our objective was to characterize adverse cutaneous reactions to celecoxib, a new non steroidal anti-inflammatory drug., Patients and Methods: A retrospective study of 6 consecutive patients., Results: The average delay before the onset of the reaction was 10.2 days for patients taking the medication for the first time and 48 hours for one patient taking the drug for the second time. Two patients had fever. Patients presented with an exanthema and in most cases an edema of the face. Buccal mucosa was involved in two patients, and one patient had minimal blister lesions. In five of the six patients, minor and transitory biological abnormalities were found. The intrinsic imputability of the celecoxib was I3 (C3S2) in all the cases., Discussion: Our cases are similar to those reported by the French drug regulatory agency (Pharmacovigilance). Usually the adverse cutaneous reactions were not too severe, with maculo-papulo exanthema and edema of the face. The reactions due to celecoxib are more frequent than those due to other non steroidal anti-inflammatory drugs (7.5% versus 4.1%), but severe cases are rarely reported. Besides, an allergic history to sulphonamide contraindicates celecoxib. However celecoxib does not have the aromatic amine common to antibacterial sulphonamides, and there is no proof of cross reactions between these two families. Furthermore, this amine is usually associated with drug reaction severity, which could explain why severe cases due to celecoxib are rare.

Introduction: Fluconazole (Triflucan(R)), a systemic triazole antifungal agent is largely prescribed and some cutaneous side effects have already been described. We report the first case of acute generalized exanthematous pustulosis due to this molecule in a patient with cutaneous candidosis., Case Report: A 65 year-old-woman was treated with fluconazole (200 mg/day) for a persistent cutaneous candidosis infection on the buttocks. After the third dose, the patient presented with a pustular eruption with erythema located on her trunk and in her large skin folds. The eruption was associated with fever at 39 degrees C, asthenia and neutrophilia (9,000/mm(3)). The histologic examination and the negativity of microbiological cultures were consistent with the diagnosis of acute generalized exanthematous pustulosis. The eruption cleared with local steroids in about ten days. Nineteen days later, the same pustular eruption occurred but without fever nor neutrophilia., Discussion: Clinical, biological and histological manifestations were consistent with the diagnosis of acute generalized exanthematous pustulosis due to fluconazole. According to the imputability criteria of Begaud et al., intrinsic imputability of fluconazole was possible (I2). According to the classification of the EuroSCAR study, it was certain. No similar case of recurrence had already been described after the withdrawal of the molecule. We believe this is the first case of acute generalized exanthematous pustulosis due to fluconazole (extrinsic imputability: B0).

Introduction: To better individualize drug hypersensitivity reaction, Bocquet et al. have recently called this adverse drug reaction DRESS (Drug Rash with Eosinophilia and Systemic Symptoms)., Exegesis: We report two cases of DRESS and highlight the main characteristics of this syndrome. Two patients presented severe febrile skin eruption following drug intake (carbamazepine or sulfazalazine), with hypereosinophilia and hepatitis. All symptoms resolved after drug withdrawal and corticosteroid therapy. DRESS syndrome is an idiosyncratic reaction characterised by febrile eruption, occurring 2 to 6 weeks after the beginning of the treatment, accompanied by systemic symptoms and biological abnormalities (hypereosinophilia, hepatitis). Some complications can occur. This syndrome can be fatal. Numerous drugs can be responsible for this reaction to medication. The physiopathology has not yet been elucidated, and the treatment is not codified, but the triggering agent must immediately be stopped. Corticotherapy is sometimes used., Conclusion: It is important to recognize this entity recently named DRESS syndrome because it can mimic other pathologies, is potentially serious, and because withdrawal of the incriminating drug is imperative.

Background: Acute generalized exanthematous pustulosis is a rare drug allergy. Generalized reactions to systematically administrated corticosteroids are even rarer. We report the first case of acute generalized exanthematous pustulosis due to methylprednisolone., Case Report: A thirty year-old-woman presented, a few hours after intravenous administration of methylprednisolone indicated for multiple sclerosis, a maculopapulous rash predominant in the folds rapidly becoming pustulous with malaise, fever and neutrophilia. The histologic examination and negativity of microbiological cultures were consistent with the diagnostic of acute generalized exanthematous pustulosis. The rash cleared spontaneously in one week with normalization of the biology. One month later, epicutaneous tests, confirmed the allergy to group A corticosteroids. The treatment of multiple sclerosis was pursued with dexamethasone., Discussion: Clinical and histological manifestations were consistent with the diagnostic of acute generalized exanthematous pustulosis to methylprednisolone. Generalized reaction to systematically administered corticosteroids are very rare. Immediate reactions are the most frequently reported reactions, only about thirty delayed-type generalized skin eruptions have been reported to date. Group A corticosteroids are the most frequent causal agent. Epicutaneous tests have good sensitivity for acute generalized exanthematous pustulosis, for allergy to corticosteroids, delayed results are very important.

Drug-induced exanthemas are probably the most frequent cutaneous adverse drug reaction. Outcome of the isolated forms are usually favourable. However, exanthemas may be part of a more severe form, as hypersensitivity syndrome, Lyell syndrome, Stevens-Johnson syndrome or acute generalized exanthematic pustulosis. The mechanism is essentially immunologic. Antibiotics (aminopenicillins, antibacterial sulfamides, antituberculosis drugs) must be considered high risk drugs. Treatment is only symptomatic. Corticosteroids must be avoided.

Background: Manifestations similar to DRESS syndrome (drug rash with eosinophilia and systemic symptoms) may be induced by nevirapine., Case Reports: Three patients developed skin rash and general signs of liver dysfunction during the first 5 weeks after starting nevirapine. Laboratory tests showed elevated eosinophil counts and signs of inflammation simulating severe infection., Discussion: The incidence of DRESS syndrome is probably underestimated. No standard treatment has been proposed. In our 3 patients, parenteral corticosteroid therapy was successful, leading to a rapidly favorable clinical course although liver tests took longer to return to normal.

Generalised acute exanthematic pustuloses are severe skin reactions that are induced by drugs. These toxidermies are characterised by sudden appearance of a diffuse area of erythema, covered with a scattering of superficial pustules, starting most often on the face and in the folds. Most often, the inducing drugs are the antibiotics, more rarely carbamapezine.

Unlabelled: We report 3 cases of rash after the first dose of antituberculosis polytherapy, thus raising questions concerning the procedures to be followed., Case Report: Three patients developed a pruritic rash 1 hour after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol given simultaneously. The eruption did not recur after readministration of isoniazide and rifampicine successively. Pyrazinamide, which was readministered last (at the full dose in one case and at progressive doses in the two others), induced a recurrence in two of them. Pyrazinamide was definitively withdrawn in one patient with recurrence and slower pyrazinamide readministration allowed continuation of treatment in the other two patients., Conclusion: Since pyrazinamide appeared to be responsible for rash following the first administration of antituberculosis polytherapy, a protocol for readministration of the 4 drugs is suggested. If the responsibility of pyrazinamide is confirmed it should be readministered very slowly.

Unlabelled: We report a rash after the first dose of antituberculosis polytherapy which raises questions concerning procedures to be followed., Case Report: An 8-year-old child presented with a pruritic rash 1.5 hours after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol was simultaneously administered, which did not recur after successive re-administration of isoniazide and rifampicine. Pyrazinamide, which was re-administered last, induced a recurrence. Slower pyrazinamide re-administration allowed continuation of treatment., Conclusion: A protocol for re-administration of the four drugs is suggested.

Background: Acute generalized exanthematic pustulosis is a severe adverse drug reaction which occurs after taking antibiotics. Rare cases implicating psychotrops have been observed., Case Report: A 71-year old women with schizophrenia was given closapine for six weeks when she developed an erythematopustular skin reaction and fever typical of acute generalized exanthematic pustulosis. The skin disease regressed one week after withdrawing clozapine., Discussion: This is the first case of acute generalized exanthematic pustulosis observed after taking the neuroleptic drug, clozapine, used in severe schizophrenia.

Introduction: Acute generalized exanthematous pustulosis usually occurs as a typical skin reaction to drugs. We observed a case with a photodistribution induced by hydroxychloroquine and/or PUVA., Case Report: A male subject had been treated for actinic pseudolymphoma since 1988. General corticosteroids had been given initially and were followed by PUVA and azathioprine. A new episode with erythema involving the trunk and the proximal portion of the limbs was treated with corticosteroids and hydroxychloroquine. The symptomatology regressed but pustular erythema developed in exposed areas two days after a PUVA session on the upper part of the body. The eruption did not involve the zones of the phototests one month earlier. The lesions resolved rapidly after withdrawal of hydroxychloroquine and PUVA., Discussion: Photo-induced acute generalized exanthematous pustulosis with a photodistribution has not been reported previously. The imputability of hydroxychloroquine and PUVA, and their association is suggested. The appearance of pustular lesion on exposed areas and the protection resulting from the phototests would lead to several hypotheses. General corticosteroids were ineffective in preventing and in treating acute generalized exanthematous pustulosis.

Toxidermia is a well-known complication of antidepressor therapy, often related to photosensitization. The authors report an original case of amoxapine-related acute generalized exanthematous pustulosis which regressed at drug withdrawal.

The authors report the case of a young patient who developed an eruption resembling an acute generalized pustular dermatitis after amoxicillin therapy for a tonsillitis. The nosological distinctions between this clinical entity and pustular psoriasis are discussed.