Correspondence and Opinions surrounding the hair follicle [2]. However, this hypothesis was ruled... more Correspondence and Opinions surrounding the hair follicle [2]. However, this hypothesis was ruled out by a clinical trial which showed no efficacy of etanercept in the treatment of AA [6]. On the other hand, TNF-␣ appears to protect from hair loss since the blockade of TNF-␣-mediated effects by monoclonal antibodies resulted in the worsening of AA with infliximab in 1 patient [1] , the recurrence of AA in a patient treated with infliximab and adalimumab [cited in 2 ] and in the induction of AA in Pelivani's [2] and our present observations. That TNF-␣ blockers promote autoimmunity is known from both experimental and clinical studies [6]. In this respect, adalimumab, like other anti-TNF-␣ monoclonal antibodies, has been associated with the induction or aggravation of autoimmune diseases such as systemic lupus erythematosus and lupus-like syndrome [7]. Positive antinuclear antibody titers have been detected in patients treated with adalimumab and other anti-TNF-␣ therapies. Recent fundamental studies have shown that TNF-␣ promotes both the expansion and suppressive functions of CD4+ regulatory T cells which play an essential role in maintaining immune tolerance and preventing autoimmunity [8]. Therefore it is possible that anti-TNF-␣-induced autoimmunity is mediated by the inhibition of the suppressive functions of regulatory T cells [9] .
Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation... more 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.
Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protei... more Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protein C and S deficiencies, other types of OAC induced-skin ulcers are little known. Herein, we describe an original case of recurrent pyoderma gangrenosum (PG)-like ulcers induced by OAC. A 70-year-old female heart-transplant recipient presented deep, hyperalgesic and quickly-spreading necrotic ulceration of the right leg 6 weeks after starting oral anticoagulant therapy with fluindione. Histological analysis revealed dermal infiltrate containing polynuclear neutrophils, which accords with the histopathological diagnosis of leukocytoclastic vasculitis or PG. Infectious, autoimmune and thrombophilic causes were ruled out. Fluindione was withdrawn and the ulcer healed completely within a month. Six months later, right leg ulceration recurred two weeks after the patient resumed fluindione but healed within 1 month of discontinuation of the drug. An OAC from another chemical family (warfarin) was then introduced, with further recurrence of ulceration after 2 weeks of treatment. The chronology of events and the negativity of aetiological explorations allowed a diagnosis to be made of OAC-induced skin ulcer, a rare complication of which the pathophysiology is unclear. This is the first case of PG-like ulcers induced by OAC.
La plupart des angioedèmes sont histaminiques et correspondent à une urticaire profonde. La surve... more La plupart des angioedèmes sont histaminiques et correspondent à une urticaire profonde. La survenue d'angioedèmes histaminiques récurrents chez un malade fait le diagnostic d'urticaire chronique, y compris lorsqu'il n'existe pas d'urticaire superficielle associée. L'urticaire chronique est une maladie bénigne, et auto-immune dans 40 % des cas. La survenue d'angioedèmes au cours de l'urticaire chronique ne représente pas un signe de gravité de l'urticaire. La survenue d'angioedèmes au cours de l'urticaire chronique est associée à une durée évolutive plus longue de l'urticaire chronique. La prise d'AINS et/ou de cortisone par voie générale sont des facteurs déclenchant classiques des poussées d'angioedème dans l'urticaire chronique. Chez les patients urticariens chroniques répondeurs aux antihistaminiques, il n'y a pas lieu faire de bilan complémentaire en l'absence de signes d'orientation clinique. Key points Histaminergic angioedema and chronic urticaria Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity.
Journal of The European Academy of Dermatology and Venereology, Jul 16, 2016
Background Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthem... more Background Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. Objectives To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. Methods A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. Results The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. Limitations This was a retrospective study. Conclusions Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.
Journal of The European Academy of Dermatology and Venereology, Sep 9, 2015
BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adve... more BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement.ObjectivesTo describe the dermatopathological features in a large series of DRESS and their possible association with clinical features and the severity of the disease.MethodsA retrospective analysis of the clinicobiological and dermatopathological features in a monocentric cohort of patients with DRESS.ResultsFrom January 2005 to January 2013, 45 patients were validated as probable or definite cases of DRESS. The median age was 64 years (range 3–87). The most frequent clinical and biological features included: fever ≥38.5°C (95%), facial oedema (72%), enlarged lymph nodes (51%), visceral involvement (75%), blood eosinophilia (97%) and atypical lymphocytes (82%). Severe DRESS occurred in 24% and a fatal outcome in 6% of patients. Histopathological analysis showed that no specific histopathological pattern was characteristic for DRESS. However, several changes in different cutaneous compartments were observed in 2 of 3 of cases. Spongiosis (55%) and keratinocyte damage (53%) were the most common epidermal changes. Spongiosis was associated with non‐severe DRESS (P = 0.041) whereas confluent keratinocyte necrosis correlated with severe DRESS (P = 0.011). Vascular changes were frequent (88%). A moderate dermal perivascular lymphocytic infiltrate was invariably present, containing eosinophils, neutrophils and/or atypical lymphocytes in 57% of cases.ConclusionsEpidermal changes are indicative for the severity of DRESS.
British Journal of Clinical Pharmacology, Jan 4, 2019
Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontan... more Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODS Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTS Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with
Annales de dermatologie et de vénéréologie, FMC, Apr 1, 2021
Résultats Lymphocytes, monocytes, macrophages sont réservoirs d'herpes virus latents. Pour obteni... more Résultats Lymphocytes, monocytes, macrophages sont réservoirs d'herpes virus latents. Pour obtenir des particules HHV6 les virologues stimulent par PHA ou PMA des cellules mononuclées d'adultes sains. La réactivation virale par stimulation lymphocytaire a fondé un test (« virus plaque assay ») pour compter les lymphocytes spécifiques d'antigène. Une couche de cellules sensibles à la lyse virale est couverte de lymphocytes préalablement infectés par un virus cytolytique et stimulés par l'antigène à tester. Le nombre de plaques de lyse quantifie les lymphocytes spécifiques. Tests épi-cutanés, et tests in vitro sont plus souvent et plus fortement positifs dans les DRESS, expliquant la réactivation virale plus fréquente. Discussion Ces faits oubliés montrent que le DRESS est primitivement une hypersensibilité médicamenteuse dont découle parfois une réactivation virale. Cette réactivation est-elle pathogène ? Chez l'adulte sain les réactivations virales sont réputées non rares et asymptomatiques. Chez les immunodéprimés des manifestations graves (encéphalites, colites ulcérées.. .) peuvent en résulter. Ces complications sont exceptionnelles dans les DRESS. Deux séries rétrospectives de « tailles » limitées comparant DRESS avec et sans réactivation ont suggéré que fièvre, évolution prolongée, adénopathies, lymphocytes atypiques et hépatite étaient plus fréquents en cas de réactivation. Une étude prospective de large taille pourra seule évaluer l'impact réel des réactivations virales du DRESS. Conclusion Le DRESS est primitivement une manifestation sévère d'hypersensibilité médicamenteuse. La réactivation virale n'est qu'un marqueur de cette l'intensité. Sa possible contribution aux symptômes et à la sévérité des DRESS reste à évaluer. Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.
Introduction L’eczema tete et cou est une topographie frequente de l’eczema de l’adulte jeune. Ma... more Introduction L’eczema tete et cou est une topographie frequente de l’eczema de l’adulte jeune. Malassezia est une levure connue depuis plusieurs annees comme residant normalement sur la peau humaine et egalement comme agent de diverses maladies cutanees comme le Pityriasis versicolor. Resultats Nous rapportons le cas d’un homme de 39 ans, atopique (asthme et rhino-conjonctivite) suivi pour un eczema de la tete et du cou sans aucune autre lesion d’eczema sur le corps. La biopsie cutanee etait compatible avec un eczema. Les IgE Malassezia spp etaient elevee a 20,40 kU/L (n Discussion Des etudes anterieures ont montre que l’ITRACONAZOLE a la dose de 200 mg ou 400 mg pendant une semaine ameliorent le SCORAD. Une autre equipe a demontre les memes resultats avec l’ITRACONAZOLE pendant 8 a 10 mois. Dans un sous-groupe de patients atteints de DA refractaire aux dermocorticoides, la sensibilite a Malassezia doit etre suspectee, en particulier chez les patients souffrant de lesions de la tete et du cou. La physiopathologie reste peu connue mais certaines equipes ont evoque une sensibilisation accrue aux levrues (P ovale ou malassezia) chez les patients atopiques. Chez ces patients, P. ovale in vitro est responsable d’une reponse Th2 en relargeant des cytokines comme l’IL 4 et l’IL 10. Conclusion Le traitement minute par FLUCONAZOLE 300 mg pourrait ameliorer les eczema de la tete et du cou resistant aux dermocorticoides associe a des IgE Malassezia eleves.
The Journal of Allergy and Clinical Immunology: In Practice, Dec 1, 2022
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially ... more Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially fatal drug-induced systemic hypersensitivity response characterized by erythematous eruption, fever, leukocytosis with eosinophilia, and internal organ involvement. Antitubercular agents are potential causative agents for DRESS syndrome but difficult to verify as a culprit drug, since antitubercular agents are coadministered as a combination regimen. A 42-year-old female with endobronchial tuberculosis was diagnosed with DRESS syndrome after 4-week treatment of isoniazid, rifampicin, ethambutol, and pyrazinamide with prednisolone 50 mg. All the antitubercular agents were stopped and replaced with levofloxacin, cycloserine, p-aminosalicylic acid, and kanamycin. However, severe exacerbation of DRESS syndrome compelled the patient to discontinue the administration of the second-line antitubercular agents. Two months later, the patient underwent a patch test for all the antitubercular agents which had been used, and the results showed positivity to isoniazid and cycloserine. We report a rare case of DRESS syndrome that reacted to cycloserine as well as isoniazid. Development of coreactivity to other drugs should be differentiated with a flare-up reaction in the management of DRESS syndrome.
Introduction Les individus de plus de 50 ans peuvent developper des eruptions cutanees diffuses, ... more Introduction Les individus de plus de 50 ans peuvent developper des eruptions cutanees diffuses, prurigineuses, eczematiformes d’etiologie incertaine qui peuvent representer des difficultes therapeutiques car resistance aux differentes lignes therapeutiques. Resultats Nous presentons le cas d’un patient de 87 ans. Debut de la dermatose en 2008 de maniere progressive. Traite initialement par dermocorticoide sans remission complete. Hyper eosinophilie oscillant jusqu’a 4,9 G/L en janvier 2016. L’anatomopathologie est en faveur d’un eczema. Pas d’argument pour une pemphigoide bulleuse, ni un lymphome cutane. SCORAD 52. Lymphopenie predominant sur les lymphocytes T CD8 et CD4. TARC/CCL17 plasmatique eleve a > 2000 en faveur d’une origine lymphoide de l’eosinophilie. Le scanner thoraco-abdomino-pelvien ne retrouve pas de neoplasie sous-jacent. Les causes parasitaires, medicamenteuses, tumorales et virales ont ete eliminees. Le methotrexate, pris entre 2016–2019 a la dose de 25 mg a eu une efficacite relative sur le plan cutane avec diminution neanmoins de l’hyper eosinophilie et du TARCC. La recherche de transcrit FIP1L1PDGFRA etait negative ainsi que la recherche d’une anomalie du phenotype lymphocytaire. Le diagnostic d’eczema severe du avec eosinophilie etait suspecte. Devant cette dermatose resistant aux traitements locaux et systemiques, le Dupixent a ete introduit a la dose de 300 mg toutes les deux semaines. La reponse clinique a ete complete des l’instauration du Dupixent avec sevrage en dermocorticoides. Discussion Le syndrome hyper eosinophilique (SHE) lymphoide est une maladie chronique du a une polarisation de la reponse immunitaire vers un profil Th2. En effet il existe un dysfonctionnement des LT (Th2) producteur de l’IL 4 et IL13 qui sont des cytokines majeures favorisant la differentiation medullaire en polynucleaires eosinophiles. Le Dupixent est utilise dans la dermatite atopique de l’adulte et son implication dans la physiopathologie de la dermatite atopique est clairement demontree. Conclusion Du fait de leurs similitudes clinique, notre cas illustre que le DUPILUMAB pourrait etre utile dans les dermatoses eczematiformes des patients âges, avec eosinophilie, non etiquetees.
Journal of The European Academy of Dermatology and Venereology, Jul 21, 2021
IntroductionThe distinction between epidermal necrolysis [EN; including Stevens–Johnson syndrome ... more IntroductionThe distinction between epidermal necrolysis [EN; including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities.Materials and methodsThis French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow‐up.ResultsWe included 62 children [43 boys, median age 10 years (range 3–18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM.ConclusionClinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work‐up in such situation. Sequelae affected both EN and EMM.
Correspondence and Opinions surrounding the hair follicle [2]. However, this hypothesis was ruled... more Correspondence and Opinions surrounding the hair follicle [2]. However, this hypothesis was ruled out by a clinical trial which showed no efficacy of etanercept in the treatment of AA [6]. On the other hand, TNF-␣ appears to protect from hair loss since the blockade of TNF-␣-mediated effects by monoclonal antibodies resulted in the worsening of AA with infliximab in 1 patient [1] , the recurrence of AA in a patient treated with infliximab and adalimumab [cited in 2 ] and in the induction of AA in Pelivani's [2] and our present observations. That TNF-␣ blockers promote autoimmunity is known from both experimental and clinical studies [6]. In this respect, adalimumab, like other anti-TNF-␣ monoclonal antibodies, has been associated with the induction or aggravation of autoimmune diseases such as systemic lupus erythematosus and lupus-like syndrome [7]. Positive antinuclear antibody titers have been detected in patients treated with adalimumab and other anti-TNF-␣ therapies. Recent fundamental studies have shown that TNF-␣ promotes both the expansion and suppressive functions of CD4+ regulatory T cells which play an essential role in maintaining immune tolerance and preventing autoimmunity [8]. Therefore it is possible that anti-TNF-␣-induced autoimmunity is mediated by the inhibition of the suppressive functions of regulatory T cells [9] .
Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation... more 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.
Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protei... more Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protein C and S deficiencies, other types of OAC induced-skin ulcers are little known. Herein, we describe an original case of recurrent pyoderma gangrenosum (PG)-like ulcers induced by OAC. A 70-year-old female heart-transplant recipient presented deep, hyperalgesic and quickly-spreading necrotic ulceration of the right leg 6 weeks after starting oral anticoagulant therapy with fluindione. Histological analysis revealed dermal infiltrate containing polynuclear neutrophils, which accords with the histopathological diagnosis of leukocytoclastic vasculitis or PG. Infectious, autoimmune and thrombophilic causes were ruled out. Fluindione was withdrawn and the ulcer healed completely within a month. Six months later, right leg ulceration recurred two weeks after the patient resumed fluindione but healed within 1 month of discontinuation of the drug. An OAC from another chemical family (warfarin) was then introduced, with further recurrence of ulceration after 2 weeks of treatment. The chronology of events and the negativity of aetiological explorations allowed a diagnosis to be made of OAC-induced skin ulcer, a rare complication of which the pathophysiology is unclear. This is the first case of PG-like ulcers induced by OAC.
La plupart des angioedèmes sont histaminiques et correspondent à une urticaire profonde. La surve... more La plupart des angioedèmes sont histaminiques et correspondent à une urticaire profonde. La survenue d'angioedèmes histaminiques récurrents chez un malade fait le diagnostic d'urticaire chronique, y compris lorsqu'il n'existe pas d'urticaire superficielle associée. L'urticaire chronique est une maladie bénigne, et auto-immune dans 40 % des cas. La survenue d'angioedèmes au cours de l'urticaire chronique ne représente pas un signe de gravité de l'urticaire. La survenue d'angioedèmes au cours de l'urticaire chronique est associée à une durée évolutive plus longue de l'urticaire chronique. La prise d'AINS et/ou de cortisone par voie générale sont des facteurs déclenchant classiques des poussées d'angioedème dans l'urticaire chronique. Chez les patients urticariens chroniques répondeurs aux antihistaminiques, il n'y a pas lieu faire de bilan complémentaire en l'absence de signes d'orientation clinique. Key points Histaminergic angioedema and chronic urticaria Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity.
Journal of The European Academy of Dermatology and Venereology, Jul 16, 2016
Background Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthem... more Background Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. Objectives To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. Methods A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. Results The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. Limitations This was a retrospective study. Conclusions Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.
Journal of The European Academy of Dermatology and Venereology, Sep 9, 2015
BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adve... more BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement.ObjectivesTo describe the dermatopathological features in a large series of DRESS and their possible association with clinical features and the severity of the disease.MethodsA retrospective analysis of the clinicobiological and dermatopathological features in a monocentric cohort of patients with DRESS.ResultsFrom January 2005 to January 2013, 45 patients were validated as probable or definite cases of DRESS. The median age was 64 years (range 3–87). The most frequent clinical and biological features included: fever ≥38.5°C (95%), facial oedema (72%), enlarged lymph nodes (51%), visceral involvement (75%), blood eosinophilia (97%) and atypical lymphocytes (82%). Severe DRESS occurred in 24% and a fatal outcome in 6% of patients. Histopathological analysis showed that no specific histopathological pattern was characteristic for DRESS. However, several changes in different cutaneous compartments were observed in 2 of 3 of cases. Spongiosis (55%) and keratinocyte damage (53%) were the most common epidermal changes. Spongiosis was associated with non‐severe DRESS (P = 0.041) whereas confluent keratinocyte necrosis correlated with severe DRESS (P = 0.011). Vascular changes were frequent (88%). A moderate dermal perivascular lymphocytic infiltrate was invariably present, containing eosinophils, neutrophils and/or atypical lymphocytes in 57% of cases.ConclusionsEpidermal changes are indicative for the severity of DRESS.
British Journal of Clinical Pharmacology, Jan 4, 2019
Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontan... more Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODS Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTS Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with
Annales de dermatologie et de vénéréologie, FMC, Apr 1, 2021
Résultats Lymphocytes, monocytes, macrophages sont réservoirs d'herpes virus latents. Pour obteni... more Résultats Lymphocytes, monocytes, macrophages sont réservoirs d'herpes virus latents. Pour obtenir des particules HHV6 les virologues stimulent par PHA ou PMA des cellules mononuclées d'adultes sains. La réactivation virale par stimulation lymphocytaire a fondé un test (« virus plaque assay ») pour compter les lymphocytes spécifiques d'antigène. Une couche de cellules sensibles à la lyse virale est couverte de lymphocytes préalablement infectés par un virus cytolytique et stimulés par l'antigène à tester. Le nombre de plaques de lyse quantifie les lymphocytes spécifiques. Tests épi-cutanés, et tests in vitro sont plus souvent et plus fortement positifs dans les DRESS, expliquant la réactivation virale plus fréquente. Discussion Ces faits oubliés montrent que le DRESS est primitivement une hypersensibilité médicamenteuse dont découle parfois une réactivation virale. Cette réactivation est-elle pathogène ? Chez l'adulte sain les réactivations virales sont réputées non rares et asymptomatiques. Chez les immunodéprimés des manifestations graves (encéphalites, colites ulcérées.. .) peuvent en résulter. Ces complications sont exceptionnelles dans les DRESS. Deux séries rétrospectives de « tailles » limitées comparant DRESS avec et sans réactivation ont suggéré que fièvre, évolution prolongée, adénopathies, lymphocytes atypiques et hépatite étaient plus fréquents en cas de réactivation. Une étude prospective de large taille pourra seule évaluer l'impact réel des réactivations virales du DRESS. Conclusion Le DRESS est primitivement une manifestation sévère d'hypersensibilité médicamenteuse. La réactivation virale n'est qu'un marqueur de cette l'intensité. Sa possible contribution aux symptômes et à la sévérité des DRESS reste à évaluer. Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.
Introduction L’eczema tete et cou est une topographie frequente de l’eczema de l’adulte jeune. Ma... more Introduction L’eczema tete et cou est une topographie frequente de l’eczema de l’adulte jeune. Malassezia est une levure connue depuis plusieurs annees comme residant normalement sur la peau humaine et egalement comme agent de diverses maladies cutanees comme le Pityriasis versicolor. Resultats Nous rapportons le cas d’un homme de 39 ans, atopique (asthme et rhino-conjonctivite) suivi pour un eczema de la tete et du cou sans aucune autre lesion d’eczema sur le corps. La biopsie cutanee etait compatible avec un eczema. Les IgE Malassezia spp etaient elevee a 20,40 kU/L (n Discussion Des etudes anterieures ont montre que l’ITRACONAZOLE a la dose de 200 mg ou 400 mg pendant une semaine ameliorent le SCORAD. Une autre equipe a demontre les memes resultats avec l’ITRACONAZOLE pendant 8 a 10 mois. Dans un sous-groupe de patients atteints de DA refractaire aux dermocorticoides, la sensibilite a Malassezia doit etre suspectee, en particulier chez les patients souffrant de lesions de la tete et du cou. La physiopathologie reste peu connue mais certaines equipes ont evoque une sensibilisation accrue aux levrues (P ovale ou malassezia) chez les patients atopiques. Chez ces patients, P. ovale in vitro est responsable d’une reponse Th2 en relargeant des cytokines comme l’IL 4 et l’IL 10. Conclusion Le traitement minute par FLUCONAZOLE 300 mg pourrait ameliorer les eczema de la tete et du cou resistant aux dermocorticoides associe a des IgE Malassezia eleves.
The Journal of Allergy and Clinical Immunology: In Practice, Dec 1, 2022
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially ... more Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially fatal drug-induced systemic hypersensitivity response characterized by erythematous eruption, fever, leukocytosis with eosinophilia, and internal organ involvement. Antitubercular agents are potential causative agents for DRESS syndrome but difficult to verify as a culprit drug, since antitubercular agents are coadministered as a combination regimen. A 42-year-old female with endobronchial tuberculosis was diagnosed with DRESS syndrome after 4-week treatment of isoniazid, rifampicin, ethambutol, and pyrazinamide with prednisolone 50 mg. All the antitubercular agents were stopped and replaced with levofloxacin, cycloserine, p-aminosalicylic acid, and kanamycin. However, severe exacerbation of DRESS syndrome compelled the patient to discontinue the administration of the second-line antitubercular agents. Two months later, the patient underwent a patch test for all the antitubercular agents which had been used, and the results showed positivity to isoniazid and cycloserine. We report a rare case of DRESS syndrome that reacted to cycloserine as well as isoniazid. Development of coreactivity to other drugs should be differentiated with a flare-up reaction in the management of DRESS syndrome.
Introduction Les individus de plus de 50 ans peuvent developper des eruptions cutanees diffuses, ... more Introduction Les individus de plus de 50 ans peuvent developper des eruptions cutanees diffuses, prurigineuses, eczematiformes d’etiologie incertaine qui peuvent representer des difficultes therapeutiques car resistance aux differentes lignes therapeutiques. Resultats Nous presentons le cas d’un patient de 87 ans. Debut de la dermatose en 2008 de maniere progressive. Traite initialement par dermocorticoide sans remission complete. Hyper eosinophilie oscillant jusqu’a 4,9 G/L en janvier 2016. L’anatomopathologie est en faveur d’un eczema. Pas d’argument pour une pemphigoide bulleuse, ni un lymphome cutane. SCORAD 52. Lymphopenie predominant sur les lymphocytes T CD8 et CD4. TARC/CCL17 plasmatique eleve a > 2000 en faveur d’une origine lymphoide de l’eosinophilie. Le scanner thoraco-abdomino-pelvien ne retrouve pas de neoplasie sous-jacent. Les causes parasitaires, medicamenteuses, tumorales et virales ont ete eliminees. Le methotrexate, pris entre 2016–2019 a la dose de 25 mg a eu une efficacite relative sur le plan cutane avec diminution neanmoins de l’hyper eosinophilie et du TARCC. La recherche de transcrit FIP1L1PDGFRA etait negative ainsi que la recherche d’une anomalie du phenotype lymphocytaire. Le diagnostic d’eczema severe du avec eosinophilie etait suspecte. Devant cette dermatose resistant aux traitements locaux et systemiques, le Dupixent a ete introduit a la dose de 300 mg toutes les deux semaines. La reponse clinique a ete complete des l’instauration du Dupixent avec sevrage en dermocorticoides. Discussion Le syndrome hyper eosinophilique (SHE) lymphoide est une maladie chronique du a une polarisation de la reponse immunitaire vers un profil Th2. En effet il existe un dysfonctionnement des LT (Th2) producteur de l’IL 4 et IL13 qui sont des cytokines majeures favorisant la differentiation medullaire en polynucleaires eosinophiles. Le Dupixent est utilise dans la dermatite atopique de l’adulte et son implication dans la physiopathologie de la dermatite atopique est clairement demontree. Conclusion Du fait de leurs similitudes clinique, notre cas illustre que le DUPILUMAB pourrait etre utile dans les dermatoses eczematiformes des patients âges, avec eosinophilie, non etiquetees.
Journal of The European Academy of Dermatology and Venereology, Jul 21, 2021
IntroductionThe distinction between epidermal necrolysis [EN; including Stevens–Johnson syndrome ... more IntroductionThe distinction between epidermal necrolysis [EN; including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities.Materials and methodsThis French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow‐up.ResultsWe included 62 children [43 boys, median age 10 years (range 3–18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM.ConclusionClinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work‐up in such situation. Sequelae affected both EN and EMM.
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