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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. [ABSTRACT FROM AUTHOR]

Among the six patients who stopped treatment owing to AD remission, the median duration of treatment was 57 weeks (IQR 44-25-65-25). From a total of 968 patients treated with dupilumab during the study period, 150 patients (15-5%) discontinued treatment after a median treatment duration of 5 months [interquartile range (IQR) 3-10]. Dear Editor, Dupilumab, an anti-interleukin-4 monoclonal antibody, has shown a positive benefit-risk ratio when treating moderate-to-severe atopic dermatitis (AD) in clinical studies.1 High persistence for patients on dupilumab has recently been reported in a clinical practice setting, with 77% of patients remaining in treatment for 12 months in a retrospective study that included 1963 patients with AD; however, reasons for discontinuation were not investigated.2 Investigating the reasons for treatment discontinuation in chronic diseases permits the assessment of both the safety and the effectiveness of a given treatment in a clinical practice setting. [Extracted from the article]

We included all patients who underwent allergological tests including skin tests (ST): patch tests (PT), skin prick tests (SPT), intradermal test (IDT); and/or oral provocation test (OPT), and who were under treatment with IT. PT were performed in 18 patients (29-5%), SPT in 52 patients (85%), IDT in 57 patients (93%) and OPT in 38 patients (62%). [Extracted from the article]

Concerning the patients ( I n i = 70/152, 46.1%) followed by a dermatologist, a past medical history of allergy was found in 32.9% corresponding to 11 respiratory allergy, 16 drug allergy (but none to previous vaccination), and three food allergy. Data were collected from dermatologists for 70 patients (Table 1), and from vaccination centres for 82 patients. The patients in this manuscript have given written informed consent for the publication of their case details. [Extracted from the article]

Trials assessing dupilumab in atopic dermatitis (AD) showed transient eosinophilia in less than 2% of patients.1 The frequency of hypereosinophilia (HE), defined as eosinophil blood count (EBC) >=1500/mm SP 3 sp ,2 was higher (15.8%) in our previous real-life cohort of AD patients treated with dupilumab.3 Since symptomatic HE was reported in asthma trials, we aimed to assess the clinical impact of HE in AD patients receiving dupilumab. Dupilumab-associated hypereosinophilia in patients treated for moderate-to-severe atopic dermatitis Fifty-nine patients with HE were included among a total of 653 patients receiving dupilumab from 12 hospital centres (Table 1), allowing us to estimate a mean prevalence of HE under dupilumab of 9% {95% CI [7.0-11.6]}. [Extracted from the article]

This study aimed to retrospectively determine the efficacy and safety of dupilumab treatment within a French multicentric cohort of 16 adult patients with chronic PN refractory to multimodal treatment regimens (April 2017-August 2019). After 3 months of dupilumab treatment, three patients (18.8%) had a CR of lesions, 12 (75%) had a PR of lesions (Fig. a), and one patient had NR. Evolution of the number of prurigo nodularis lesions at baseline and after 3 months of dupilumab treatment (patients were divided into groups depending on the number of lesions: 0, <10, 10-50, >50) (b). [Extracted from the article]

Atopic Dermatitis (AD) is a chronic, relapsing inflammatory skin disease that carries a significant burden of disease and patient quality-of-life impairment. Several disorders known or supposed to be associated with AD were collected: atopic manifestations, cardiometabolic diseases, neuropsychiatric disorders, auto-immune or inflammatory diseases, addictions, neoplasia and patient-reported past skin infections. [Extracted from the article]

We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral GSK2586184 50–400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes in Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index score, and number/severity of adverse events. A pre-specified interim analysis was performed when ≥ 5 patients per group completed 2 weeks of treatment. In total, 84–92% of patients were high baseline expressors of the interferon transcriptional biomarkers evaluated. At interim analysis, GSK2586184 showed no significant effect on mean interferon transcriptional biomarker expression (all panels). The study was declared futile and recruitment was halted at 50 patients. Shortly thereafter, significant safety data were identified, including elevated liver enzymes in six patients (one confirmed and one suspected case of Drug Reaction with Eosinophilia and Systemic Symptoms), leading to immediate dosing cessation. Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index scores were not analysed due to the small number of patients completing the study. The study futility and safety data described for GSK2586184 do not support further evaluation in patients with SLE.Study identifiers: GSK Study JAK115919; ClinicalTrials.gov identifier: NCT01777256. [ABSTRACT FROM AUTHOR]

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3bright γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3bright γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1+ T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1β. Finally, we demonstrated that IL-17-producing CD3bright γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1+ T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders. [ABSTRACT FROM AUTHOR]

Nevertheless, this therapeutic class can promote immune dysbalance, since two recent cases of baricitinib-induced paradoxical psoriasis have been reported.13 The mechanisms of psoriasis' development during dupilumab treatment in AD patients are unknown. Atopic dermatitis (AD) and psoriasis are T cell-mediated inflammatory diseases: a Th2-component with interleukin (IL)-4 and IL-13 production in AD, a Th17/IL-23 and TNF response in psoriasis. [Extracted from the article]

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman. [ABSTRACT FROM AUTHOR]

Background Psoriasis is frequently associated with overweight and obesity. Anti-TNF-α therapies are effective in the treatment of psoriasis. TNF-α is highly involved in body weight regulation. Objective Our objective was to evaluate the increase in weight throughout the treatment with infliximab and the association of weight gain with the body mass index (BMI). Methods Thirty-five patients affected with severe plaque psoriasis receiving infliximab were included. A control group consisted of 16 patients affected with severe plaque psoriasis and treated with cyclosporine, methotrexate, or acitretin. Assessment of PASI score, body weight and BMI were performed at a 1 and 3-year follow-up. Results We observed a body weight increment of 2.5 ± 4.4 kg (mean ± SD) (i.e. + 3.6% of baseline) and 0.1 ± 5 kg (i.e. + 1.2%) in patients treated with infliximab and the control group, respectively ( P = 0.046), after 1 year of treatment. After 3 years of infliximab administration, weight gain was 4.8 ± 5 kg ( n = 16) (i.e. + 6%) ( P = 0.005). Moreover, as classified by BMI, normal weight patients experienced a 4 ± 3.7 kg weight gain (i.e. + 6%) whereas overweight and obese patients had gained 1.3 ± 4.8 kg (i.e. + 1.2%) ( P = 0.039) after 1 year of anti-TNF-α therapy. Percentual changes in body weight were larger in normal weight patients at baseline than in overweight/obese counterparts ( P = 0.0149). Conclusion All patients, including normal weight patients, should receive a dietary intervention. [ABSTRACT FROM AUTHOR]

Background: Few data are available concerning the efficiency of pulse corticosteroids in alopecia areata (AA). Objective: Our purpose was to assess the long-term outcomes of patients treated with methylprednisolone bolus. Methods: This study included 60 patients treated between 1995 and 2000. The short-term outcomes were analyzed in 2000. The long-term assessment of 30 patients was performed in 2010 by phone questionnaire. Results: Significant hair regrowth was observed in 10/30 patients at 6 months after the bolus treatment. Half of the plurifocalis AA patients were responders at 6 months, but less than one quarter of alopecia totalis (AT) and alopecia universalis (AU) patients responded. Long-term outcomes were assessed after a mean duration of 12.3 years; 8/10 initial responders had mild or no disease, and 14/20 initial nonresponders had severe AA. Conclusions: This study confirmed the low efficiency, both short- and long-term, of this treatment for AT and AU. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Acute generalized exanthematous pustulosis ( AGEP) is a severe adverse cutaneous reaction, which is mostly due to drugs, but which has also been described as occurring after infections. We report a case of severe AGEP with extensive blistering mimicking toxic epidermal necrolysis ( TEN) in a 47-year-old woman. This was associated with a life-threatening primary mumps infection, complicated by perimyocarditis and encephalitis. The recent increase in the incidence of mumps should lead physicians to be aware of the uncommon clinical features and complications of this disease. [ABSTRACT FROM AUTHOR]

Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about DRESS syndrome and reversible liver function abnormalities in patients with systemic lupus erythematosus treated with the highly selective JAK-1 inhibitor GSK2586184 that was published in the previous issue.

The article presents information on the systemic treatment of psoriasis with immunomodulatory therapies. It discusses the data of the patients from Northern France with severe psoriasis between January 2005 and May 2010. A table representing patient and treatment characteristics including obesity, hypertension and diabetes is also shown.