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.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

Treatment of Eosinophilic Annular Erythema: Retrospective multicenter study and literature review.

BACKGROUND: Eosinophilic annular erythema (EAE) is a rare eosinophil-related skin disease which typically manifests with annular erythematous plaques and severe pruritus. Besides the diagnosis, the treatment of EAE is challenging since relevant published data are sparse. METHODS: The aim of this study was to assess the underlying diseases, treatments and outcomes of patients with EAE. To this end, we conducted a retrospective multicenter study and a systematic review of the MEDLINE database. RESULTS: We included 18 patients with EAE followed in 8 centers. The MEDLINE database search yielded 37 relevant publications reporting 55 cases of EAE with 106 treatment sequences. The most common and efficient treatments included topical or systemic corticosteroids, hydroxychloroquine and dapsone. In refractory patients, a combination of systemic corticosteroids with hydroxychloroquine was associated with 88% of complete clinical response. DISCUSSION: To improve the management of EAE patients, we discuss the following treatment strategy: in topical steroid-resistant patients, hydroxychloroquine can be given as first-line systemic treatment. Dapsone, hydroxychloroquine or systemic corticosteroids are second-line options to consider. Last, monoclonal antibodies or JAK inhibitors targeting type 2 inflammation could represent promising last-resort options in refractory patients.

[Impact of disease on daily activities, emotions and quality of life of patients with hereditary angioedema]. / Impact de l'angiœdème héréditaire sur les activités de la vie quotidienne, la sphère émotionnelle et la qualité de vie des patients.

INTRODUCTION: Hereditary angioedema (HAE) is characterized by recurrent attacks of swelling of various locations and severity. An impaired quality of life of patients with HAE has been reported by several studies. We aimed at examining the overall impact of the disease in patients followed for type I HAE, particularly its impact on daily life activities, emotions and quality of life. METHODS: A questionnaire was distributed to patients consulting for type I HAE, collecting demographics, disease characteristics, impact on professional life, Hospital Anxiety and Depression score (HAD), SF-36 score and the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR). RESULTS: The 33 patients included reported an average of 5.17 attacks over the last year. Stress was the main trigger A long-term treatment was reported by 58% of patients, 72% received specific treatment in the event of a serious attack. Sick days were reported by 33% of patients during their studies, and by 34% during work. One patient suffered from depressive symptoms and ten from anxious symptoms, according to the HAD score. The areas most impacted on the SF-36 score were general health and vitality. The mean score for MACTAR was low. CONCLUSION: HAE still has a significant impact on the daily and emotional lives of patients, despite the availability of prophylactic and crisis treatments.

[Bacterial acute non necrosing cellulitis (erysipelas) in adult]. / Prise en charge de la dermo-hypodermite aiguë non nécrosante bactérienne de l'adulte.

Erysipelas is defined by a sudden onset (with fever) preceding the appearance of a painful, infiltrated, erythematous plaque, accompanied by regional lymphadenopathy. It is usually localized on the lower limbs, but it can occur on the face. It is due to ß-hemolytic streptococcus A and more rarely to staphylococcus aureus. It is important to establish the diagnosis and eliminate the non-bacterial causes of inflammatory edema. The other diagnoses frequently found are contact eczema, acute arthritis, bursitis, inflammatory flare-up of chronic dermohypodermitis of venous origin, flare-up of chronic multifactorial eczema (venous insufficiency, vitamin deficiencies, senile xerosis and/or contact eczema), rare familial periodic fevers, rare neutrophilic dermatoses or eosinophilic cellulitis. It is necessary to identify signs of severity that would justify hospitalization. In front of a typical acute bacterial dermohypodermitis and in the absence of comorbidity, no additional investigation is necessary. Systematic blood cultures have low profitability. Locoregional causes must be identified in order to limit the risk of recurrence which remains the most frequent complication. In uncomplicated erysipelas, amoxicillin is the gold standard; treatment with oral antibiotic therapy is possible if there is no sign of severity or co-morbidity (diabetes, arteritis, cirrhosis, immune deficiency) or an unfavorable social context. In case of allergy to penicillin, pristinamycin or clindamycin should be prescribed. Prophylactic antibiotic therapy with delayed penicillin is recommended in the event of recurrent erysipelas.

[Pemetrexed-induced cutaneous sclerosis of the lower limbs]. / Œdèmes inflammatoires et scléreux des membres inférieurs sous pémétrexed.

BACKGROUND: Pemetrexed is an antifolate used to treat intrathoracic cancers. We report a rare case of cutaneous toxicity of pemetrexed with inflammatory cutaneous sclerosis of the lower limbs. PATIENTS AND METHODS: A 63-year-old man diagnosed with metastatic adenocarcinoma of the lung was treated with pemetrexed. Fourteen months after undergoing this chemotherapy, he developed inflammatory and fibrotic edema of the lower limbs with functional consequences on knee bending. Cardiac, renal, hepatic, thrombotic and infectious causes were ruled out. Pemetrexed was suspended and partial remission was obtained using super-potent topical corticosteroids. With the approval of the oncologist, nivolumab was introduced as a follow-on therapy after pemetrexed. DISCUSSION: Often misdiagnosed by physicians, this form of toxicity due to pemetrexed is rare but classically described. To limit cutaneous side effects, dexamethasone may be proposed the day before, the same day as and the day after the infusion. Suspension of chemotherapy is not routine but depends on the risk-benefit ratio of the functional impact of the dermatosis and on the therapeutic alternatives available for the cancer.

[Hemorrhagic bullous dermatosis (HBD): A rare side-effect of heparins]. / Dermatose bulleuse hémorragique (DBH) : un effet indésirable rare des héparines.

BACKGROUND: Bullous haemorrhagic dermatosis (BHD) induced by heparin is a rare and benign side effect of which we report two cases. PATIENTS AND METHODS: Case 1: an 81-year-old man presented haemorrhagic bullae on the limbs and trunk 7 days after starting enoxaparin. The laboratory haemostasis assessment was normal. A diagnosis was made of BHD induced by enoxaparin and the patient's treatment was switched to apixaban, resulting in a favourable outcome with resolution of the lesions within 15 days. Case 2: a 71-year-old woman hospitalised for pulmonary embolism was given tinzaparin. At two months of treatment, haemorrhagic bullae were observed on her forearms at distance from the injection sites. A diagnosis of BHD induced by tinzaparin was made. Treatment with tinzaparin was continued and the lesions resolved within 15 days. DISCUSSION: Heparin-induced BHD is a rare entity initially described in 2006. Ninety-five cases of heparin-induced BHD have been reported. It is characterized by multiple haemorrhagic bullae at a distance from the injection sites. Time to onset of lesions after heparin initiation ranges from 24h to 4 months. Laboratory assessment should be routinely performed to rule out any haemostasis disorders. Lesions subside within 15 days whether heparin is continued or withdrawn. CONCLUSION: Heparin-induced BHD is a rare but benign side effect of heparins. In the absence of recommendations, therapeutic management should be adapted to the individual situation.