Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

[Correctly adDRESS the cause of hemophagocytic lymphohistiocytosis]. / Pièges diagnostiques d'un syndrome d'activation macrophagique.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe syndrome usually associated with a cytotoxicity deficiency, which leads to an excess of immune response driven by activated macrophages and cytotoxic T cells. In children, HLH can be genetic, as part of a familial lymphohistiocytosis, or secondary: the most frequent causes are systemic-onset juvenile idiopathic arthritis, hematological malignancies, and severe infections, especially with Ebstein-Barr virus or leishmaniosis. We report on the case of a 3-year-old girl with no past medical history, who presented inaugural Pseudomonas aeruginosa maxillary osteitis, with secondary HLH. The rarity of this osteitis, the characteristics of the pathogen, and the onset of HLH oriented the diagnosis toward primary immunodeficiencies, malignancies, or systemic diseases. Steroids were initiated at 2mg/kg/day and were very effective in improving the systemic symptoms. Antibiotic therapy was continued unchanged. A few days after discontinuation of steroids, while the patient was still under antibiotics, she presented with erythroderma. Skin biopsy revealed eosinophil infiltrate in line with the diagnosis of a drug reaction with eosinophilia and systemic symptoms (DRESS), even though we only observed very transient eosinophilia, up to 0.98G/L, during HLH. Stopping antibiotics normalized the symptoms without using systemic corticosteroids. Patch tests confirmed an allergy to piperacillin. These atypical manifestations of DRESS underline that causative diagnosis of HLH is challenging, and DRESS syndrome should be considered.

[Fixed drug eruption to clarithromycin: The importance of challenge tests in diagnosis]. / Érythème pigmenté fixe à la clarithromycine : importance des tests de provocation pour le diagnostic.

BACKGROUND: Determining the substance responsible for recurrent fixed drug eruption (FDE) may be difficult in the case of patients on multiple medication. Allergy testing may prove invaluable in such situations, as we demonstrate herein with an original case. PATIENTS AND METHODS: A 49-year-old man presented a rash on the seventh day of treatment with esomeprazole, clarithromycin and amoxicillin prescribed for gastritis involving Helicobacter pylori. The condition regressed spontaneously within a few days, but left three areas of hyperpigmentation. The patient subsequently reported four further episodes consisting of stereotypical reactivation in the areas of the three initial lesions and occurring 24hours after use of clarithromycin (2 episodes) and amoxicillin (2 episodes). The patient resumed proton pump inhibitor therapy (esomeprazole) without incident. Based on history taking, an initial diagnosis was made of multiple fixed drug eruption involving amoxicillin and clarithromycin. The initial skin allergy investigations were negative (patch-tests for amoxicillin and clarithromycin on healthy skin on the patient's back and on the affected area). After discussion, we decided to reintroduce the suspected drugs in succession. Beginning with clarithromycin, 12h after a single dose of 250mg, we noted an erythematous reaction on the pigmented areas, together with a burning sensation. In an identical challenge test with amoxicillin (500mg), the latter drug was perfectly well tolerated, ruling out the diagnosis of FDE to amoxicillin and thus the diagnosis of multiple FDE suggested by the patient history. DISCUSSION: FDEs to macrolides are rare, and herein we report a new case. Our observation confirms the diagnostic value of challenge tests in FDE. These tests should only be performed in the event of non-severe FDE, in other words not in bullous or systemic reactions, and they often constitute the only diagnostic approach possible, since skin tests are rarely positive during investigation for FDE.

[Recurrent pyoderma gangrenosum-like ulcers induced by oral anticoagulants]. / Ulcérations récidivantes à type de pyoderma grangrenosum induites par les antivitamines K.

BACKGROUND: 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. PATIENTS AND METHODS: 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. DISCUSSION: 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.

[Management of drug reaction with eosinophilia and systemic symptoms (DRESS)]. / Prise en charge du drug reaction with eosinophilia and systemic symptoms (DRESS).

OBJECTIVE: The management of drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is not codified. Demonstration of the reactivation of Herpesviruses illustrates the specific pathophysiology of this syndrome. Proposals for the management of DRESS were elaborated by the cutaneous adverse drug reaction working group of the French Society of Dermatology to help with its management. METHODS: From a review of literature and the experience of the members of this group, consensual proposals were written about diagnostic criteria, tests, treatment options, and follow-up. These proposals will need to be validated in prospective studies. RESULTS: A decisional tree of treatment options is proposed, based on the severity of visceral manifestations. The importance of a rapid withdrawal of the culprit drug and of a long-term follow-up is underlined. Treatment will be adapted to the clinicobiological status (topical corticosteroid, systemic corticosteroid, intravenous gammaglobulins, antivirals).

[Hypercalcemia-hyperleukocytosis paraneoplastic syndrome complicating cutaneous squamous cell carcinoma. Report of two cases]. / Syndrome paranéoplasique hypercalcémie-hyperleucocytose au cours des carcinomes épidermoïdes cutanés. A propos de deux observations.

INTRODUCTION: We report two cases of hypercalcemia-hyperleucocytosis paraneoplastic syndrome complicating cutaneous squamous cell carcinoma. CASE REPORTS: The first patient, a 50-year-old man, suffering for hidradenitis suppurativa for the past 20 years, was admitted for squamous cell carcinoma. Laboratory findings showed marked hypercalcemia and hyperleucocytosis. PTHrP serum level was increased. Bone scintigraphy was normal. There was evidence of pulmonary metastasis. Despite treatment the patient died of agranulocytosis. The second patient was a 60-year-old man who presented with several months enlarging left axillary tumour. He has been treated by surgery for a squamous cell carcinoma of the left hand, 6 months ago. Serum calcium and white cell bloods count were elevated. The diagnosis of metastatic lymph node of cutaneous squamous cell carcinoma was confirmed. There was evidence of pulmonary metastasis. Despite chemotherapy the patient died rapidly. CONCLUSION: Hypercalcemia-hyperleucocytosis paraneoplastic syndrome is rarely described during the course of cutaneous squamous cell carcinoma. This syndrome seems to be related to hormones or cytokines secretion by the neoplasic cells including PTHrP and G-CSF. Some authors ascribe it a poor prognostic significance.