Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Multiple Biologics for Multiple T2 Diseases: A Pharmacoepidemiological Algorithm for Sorting Out Patients by Indication.

Background: Several biologics (Bx) and targeted synthetic drugs (TSD) exist to treat T2 diseases, including chronic spontaneous urticaria (CSU), severe asthma (SA), chronic rhinosinusitis with nasal polyposis (CRSwNP) or atopic dermatitis (AD). Objective: To identify patients treated with Bx/TSD from a dynamic dispensing database using an algorithm-based methodology. Methods: We used the LRx database (Lifelink Treatment dynamics, IQVIA) which covers nearly 45% of the French retail pharmacies. Patients who had at least one Bx/TSD dispensing from April 2021 to March 2022 were included. An algorithm was designed to determine the indication of the Bx/TSD prescription analyzing all previous drug dispensation since March 2012 following a 3-steps procedure. Results: A total of 21,677 patients received at least one Bx/TSD between March 2021 and April 2022. The algorithm identified 91.7% (n = 19,884) patients with a T2 disease (AD = 18.4%, CRSwNP = 1.5%, SA = 59.5%, and CSU = 12.4%), the rest having either an association of diseases (1%) or an undetermined one (7.3%). SA was the main reason for Bx/TSD initiation (52%), followed by AD (29%), CSU (14%) and CRSwNP (5%). For SA patients already under biologic at entry, omalizumab was the most frequently prescribed (48%) followed by benralizumab, mepolizumab (22% each) and dupilumab (8%). Dupilumab was mostly prescribed for AD patients (89% for patient-initiated vs 96% for patient-renewed) followed by baricitinib. Conclusion: The algorithm was able to identify patients with T2 diseases under Bx/TSD treatments. This tool may help to follow the evolution of prescription patterns in the future.

Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients.

Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3-93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Genital Pseudotumor as a Manifestation of Mpox Virus Infection.

This case report describes a 37-year-old man with a 1-week history of a genital nodule that rapidly ulcerated and with concomitant fever 2 days after anal intercourse.

Histological Features Associated With Human Mpox Virus Infection in 2022 Outbreak in a Nonendemic Country.

Skin histology of papules and pustules from 5 men having sex with men with mpox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and perivascular and periadnexal deep lymphocytes. Histologic description of mpox lesions improves our understanding about clinical presentations and may have some therapeutic implications.

Which first-line treatment for cutaneous sarcoidosis? A retrospective study of 120 patients.

Sarcoidosis is a systemic disease that affects the skin in about 25% of patients. The treatment of cutaneous sarcoidosis is guided by the extent of lesions, associated symptoms and organ involvement. To evaluate rates of response to various potential first-line treatments for cutaneous sarcoidosis during the year following treatment initiation. This retrospective multicentre study included 120 patients with cutaneous sarcoidosis. Treatment response was assessed retrospectively from the patients' medical records. Univariate logistic regression analysis, with an estimation of unadjusted odds ratios (OR) and their 95% CI ,was performed to identify factors associated with complete cutaneous remission (CR), followed by multivariate logistic regression analysis. At one year, 43 of the 120 (36%) included patients had CR. The best response rates were obtained with oral corticosteroids (12/21, 57%), followed by a combination of hydroxychloroquine and topical steroids (6/13, 46%). In multivariate analysis, lupus pernio was the only predictor of a poor cutaneous response. We suggest the use of a combination of hydroxychloroquine and topical steroids as an optimal first-line treatment for cutaneous sarcoidosis, given the known adverse effects of systemic corticosteroids.

Chemical characterization of inks in skin reactions to tattoo.

Skin reactions are well described complications of tattooing, usually provoked by red inks. Chemical characterizations of these inks are usually based on limited subjects and techniques. This study aimed to determine the organic and inorganic composition of inks using X-ray fluorescence spectroscopy (XRF), X-ray absorption spectroscopy (XANES) and Raman spectroscopy, in a cohort of patients with cutaneous hypersensitivity reactions to tattoo. A retrospective multicenter study was performed, including 15 patients diagnosed with skin reactions to tattoos. Almost half of these patients developed skin reactions on black inks. XRF identified known allergenic metals - titanium, chromium, manganese, nickel and copper - in almost all cases. XANES spectroscopy distinguished zinc and iron present in ink from these elements in endogenous biomolecules. Raman spectroscopy showed the presence of both reported (azo pigments, quinacridone) and unreported (carbon black, phtalocyanine) putative organic sensitizer compounds, and also defined the phase in which Ti was engaged. To the best of the authors' knowledge, this paper reports the largest cohort of skin hypersensitivity reactions analyzed by multiple complementary techniques. With almost half the patients presenting skin reaction on black tattoo, the study suggests that black modern inks should also be considered to provoke skin reactions, probably because of the common association of carbon black with potential allergenic metals within these inks. Analysis of more skin reactions to tattoos is needed to identify the relevant chemical compounds and help render tattoo ink composition safer.

Moderate Psoriasis in Clinical Practice: French Expert Consensus Using a Modified Delphi Method.

INTRODUCTION: Despite the existence of multiple assessment scores for psoriasis severity, skin disease with limited skin lesions but significant impairment of quality of life can be difficult to classify, leading to under- or overtreatment. Our objective was to obtain consensus on clinical criteria to classify psoriasis severity in French clinical practice, with a focus on moderate disease, using a modified Delphi method. METHODS: A steering committee (SC) formulated a 22-item questionnaire to classify moderate psoriasis. An independent panel of French dermatologists indicated their level of agreement for each item using a 9-point Likert scale (round 1). Items without a strong consensus were modified and included in round 2. For each item, strong consensus was defined as at least 75% of scores ≥ 7 and median score ≥ 8; good consensus was defined as at least 75% of scores ≥ 7 or median score ≥ 8. RESULTS: Of 80 dermatologists who agreed to participate, 47 (59%) responded in round 1. All participants from round 1 responded in round 2. Fifteen (68%) items achieved strong consensus and four (18%) achieved good consensus. For psoriasis severity, several clinical dimensions assessed both by the physician (location, symptoms, temporality, previous treatments) and the patient (perception, physical and psychological impairment) obtained consensus. The following were considered sufficient to confirm that psoriasis is at least at a moderate stage: limited involvement but with an impact on patient/family quality of life; involvement of a special area; presence of uncontrolled symptoms (scaling, bleeding, pruritus, insomnia); accumulation of mild intensity symptoms; presence of burdensome onychodystrophy; failure of well-applied topical treatments. There was strong consensus that recognition of moderate psoriasis should lead to reassessment of topical treatments. CONCLUSION: Our modified Delphi panel suggests detailed criteria to help physicians classify patients with psoriasis which is at least at a moderate stage, which could, in turn, improve treatment in these patients.

Autoantibodies against IFNα in patients with systemic lupus erythematosus and susceptibility for infection: a retrospective case-control study.

IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients [female 87.2%, median age of 44.4 (34-54.2) years] were included. The median disease duration was 10 years [4-20] with a median SLEDAI score of 2 [0-4] at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections-mostly bacterial and viral-were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%, p = 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis.

Evaluation of Thalidomide Treatment of Patients With Chronic Erythema Multiforme: A Multicenter Retrospective Cohort Study.

IMPORTANCE: Erythema multiforme (EM) may become long term, with a recurrent or persistent course. First-line treatment for chronic EM is valaciclovir. There is no consensus for selection of second-line treatment of chronic EM. OBJECTIVE: The aim of this study was to assess the effectiveness of treatment with thalidomide for patients with chronic EM. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective national multicenter cohort study, among 68 French hospital dermatology departments contacted by e-mail, 10 reported having eligible cases. All adults aged 18 years or older under dermatology care for chronic EM (including recurrent and persistent forms) who had received thalidomide between 2010 and 2018 were included. Analyses were conducted from June 24, 2019, to December 31, 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who did not experience an EM flare within 6 months of initiating thalidomide treatment for recurrent EM or with complete clearance at 6 months for persistent EM (complete remission). RESULTS: Overall, 35 patients with chronic EM (median [range] age, 33 [15-65] years; 20 [57%] female) experienced failure of at least 1 previous treatment prior to initiating treatment with thalidomide. After 6 months of continuous thalidomide treatment, 23 (66%) were in complete remission, 5 (14%) had stopped the treatment, and 7 (20%) experienced at least 1 flare. The median (IQR) initial dose followed by remission was 50 (50-100) mg/d. Main adverse effects were asthenia (16 [46%]) and neuropathy (14 [40%]). Twenty-five (71%) of patients stopped thalidomide treatment after a median (IQR) of 12 (8-20) months owing to lack of effect (7/25 [28%]), neuropathy or another adverse effect (14/25 [56%]), or long-term complete remission (4/25 [16%]). Low-dose thalidomide, less than 50 mg every other day was sufficient in 9 of 23 (39%) of responders and was associated with less neuropathy and longer treatment duration. CONCLUSIONS AND RELEVANCE: In this cohort study, second-line therapy with thalidomide was associated with complete remission in two-thirds of the 35 patients with chronic EM. However, adverse events were a common cause of thalidomide withdrawal. In the long term, dose reduction when possible may allow for continuation by improving tolerance.