Retrospective study on the association of human herpesvirus reactivation with severe DRESS: A description of blood and skin reactivations.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse event (mortality of 10%). Its pathophysiology involves herpesviruses, particularly HHV-6, but the exact mechanisms are still poorly understood. OBJECTIVE: To describe severe cases of DRESS and especially their association with herpesvirus reactivation. METHODS: This study was a multicentre case series conducted between 2007 and 2021 at five University Hospital Centres in France. The study included patients who had severe DRESS, which was defined as death, transfer to the intensive care unit (ICU), or severe damage to internal organs. We excluded patients without blood PCR sample, without a drug formally attributed or with RegiSCAR score < 6. We collected data on severity, causative drug, associated visceral damage and results of viral blood PCRs. HHV-6 reactivation was studied in skin biopsies by detection of small non-coding transcripts (HHV-6 miR-aU14) and a late viral protein (GP82/105). RESULTS: Fifty-two patients were included (29 female, median age 62, interquartile range (IQR) [37;72]). Eight patients (15%) died, 13 (27%) were admitted to ICU. Most patients (n = 34; 65%) had multisystem involvement: most frequent was liver (n = 46; 88%), then renal failure (n = 24; 46%). Forty patients (77%) had at least one blood viral reactivation among HHV-6, EBV or CMV, of which 21 (53%) had at least two. Median time of blood HHV-6 reactivation was 24 days (IQR [20;35]). HHV-6 reactivation was demonstrated in 15 out of 20 skin biopsies, with a median time of 11 days [9;17]. CONCLUSIONS: We confirmed the high rate of HHV-6 reactivation in severe DRESS and demonstrated cutaneous HHV-6 reactivation using small non-coding transcripts (HHV-6 miR-aU14), which preceded viral PCR positivity in blood. These results suggest that HHV-6 reactivation during DRESS may start in skin. Furthermore, search for miR-aU14 in skin biopsy could become a useful diagnostic tool for early detection of HHV-6 reactivation.

[Combined Intense Pulsed Light and low-level light therapy in the treatment of Meibomian gland dysfunction]. / Traitement combiné par lumière intense pulsée et thérapie par lumière de faible niveau dans le dysfonctionnement des glandes de Meibomius.

INTRODUCTION: Meibomian gland dysfunction (MGD) is the most common cause of dry eye syndrome. The goal of this study was to evaluate the efficacy of combined intense pulsed light (IPL) and low-level light therapy (LLLT) in symptomatic MGD. MATERIALS AND METHODS: This retrospective study analyzed data from 30 patients with MGD causing dry eye symptoms not relieved by medical therapy and managed with combined IPL and LLLT. The primary endpoint was the Ocular Score Disease Index (OSDI) score at 1 month and 1 year. Secondary endpoints were visual acuity, intraocular pressure, tear film break-up time, Schirmer's test, Oxford score, and infrared meibographic score at 1 month after the conclusion of treatment. RESULTS: The mean OSDI score decreased from 43±19 to 17±12 (1 month; p<0.0001) and then to 29±11 (12 months; p=0.013); 63% of patients were meibographic grade 2 before versus 7% after treatment (range, 1-4) (p=0.009); 75% of patients were Oxford grade 1 before versus 41% after treatment (p=0.004) (range, 1-3). No significant difference in the other secondary endpoints was noted. CONCLUSION: Over time, IPL therapy in combination with LLLT appears to improve patients with symptomatic MGD resistant to medical therapy.

Childhood epidermal necrolysis and erythema multiforme major: a multicentre French cohort study of 62 patients.

INTRODUCTION: The 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 METHODS: This 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. RESULTS: We 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. CONCLUSION: Clinical 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.

Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

BACKGROUND: Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). OBJECTIVE: We sought to better describe adult IEN and understand the aetiology. METHODS: This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. RESULTS: IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. CONCLUSIONS: IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

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.

[Severe immediate hypersensitivity reaction with generalized contact urticaria after cutaneous application of topical permethrin]. / Réaction d'hypersensibilité immédiate sévère avec urticaire de contact généralisée secondaire à l'application cutanée de perméthrine topique.

BACKGROUND: Permethrin is a synthetic pyrethroid used as a chemical insecticide that obtained an MA in the management of human scabies in 2014. We report a case of severe immediate hypersensitivity (IH) reaction with generalized contact urticaria secondary to the cutaneous application of 5% permethrin cream (Topiscab®). OBSERVATION: A 44-year-old woman with no personal history of atopy was treated with oral ivermectin, Topiscab® and levocetirizine for suspected scabies. Eight hours after taking a levocetirizine tablet and five hours after the application of a tube of Topiscab® together with oral ivermectin, she presented generalized urticaria, nausea and diarrhoea, followed by loss of consciousness. Skin prick-tests for ivermectin and levocetirizine were negative. We noticed non-significant erythema with permethrin. The open application test with Topiscab® was strongly positive at 20min with the appearance of an urticaria plaque in the area of application. The open test with sorbic acid was positive at 2h. Accidental exposure to permethrin spray caused dyspnoea and recurrence of urticaria. DISCUSSION: Mild and transient symptoms are regularly described after cutaneous application (burning, paraesthesia or increased itching). Delayed hypersensitivity reactions such as contact dermatitis have been reported in the literature. Exceptional cases of severe IH reactions have been described following occupational exposure to airborne pyrethroid insecticides. No cases of severe IH reaction secondary to application of topical permethrin have been reported.

[Tacrolimus ointment in the management of atopic keratoconjunctivitis]. / Tacrolimus pommade dans la prise en charge de la kératoconjonctivite atopique.

INTRODUCTION: Atopic keratoconjunctivitis is associated with eyelid eczema. It may require the use of local corticosteroids which if prolonged can be a source of ocular complications. Tacrolimus is an immunosuppressant used in cutaneous application in atopic dermatitis. The aim of this study was to measure the efficacy and tolerance of tacrolimus 0.1% ointment in palpebral application in atopic keratoconjunctivitis. PATIENTS AND METHODS: This retrospective, single-center study was conducted between June 2014 and February 2017. Patients with atopic keratoconjunctivitis not controlled by first-line medical treatments were included. The primary endpoint was the evolution of functional signs as assessed by the NEI-VFQ25 and OSDI quality of life scores. Secondary endpoints were visual acuity and local corticosteroid use. RESULTS: Among the 18 patients included, the mean age was 37.9±16.8 years. The first follow-up visit was on average 68.3±55.3 days after initiation of treatment. The NEI-VFQ25 score was significantly improved for seven of its sub-scores (P<0.05) and the mean OSDI decreased significantly from 52.3±26.2 to 22.0±27.0 (P<0.001) showing a decrease in eye discomfort. A significant reduction was observed in the number of patients using local corticosteroids. There was no significant change in visual acuity. CONCLUSION: Tacrolimus ointment 0.1% in palpebral application appears to be an effective treatment for the management of atopic keratoconjunctivitis.