A. Bigot’s research while affiliated with University of Tours and other places

Introduction Acute hepatic porphyria (AHP) comprises a group of rare genetic diseases caused by mutations in genes encoding enzymes involved in heme biosynthesis. AHP is characterized by acute neurovisceral crises including violent abdominal pain, dysautonomia, central and peripheral neurological symptoms. This disease remains underdiagnosed. Identifying AHP is therefore a major challenge for early and appropriate care of patients and their families. The primary objective was to determine the prevalence of patients with AHP from different hospital departments and referred to an internist referent for a suggestive clinical picture with a first negative etiological assessment. The secondary objective was to define and characterize the profile of patients according to their initial symptomatology. Patients et methods This was an observational, multicenter, and ambispective study. 160 patients from 13 French hospital centers were included in the study between 09/2021 and 12/2023. The diagnosis of AHP was based on the urinary dosage of the neurotoxic precursors of heme: delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). A patient was diagnosed with AHP (AHP+) if: ALA ≥ 3 µmol/mmol of creatinine and/or PBG ≥ 1 µmol/mmol of creatinine. In all other cases, the patient was considered not to suffer from AHP (AHP-). Results Among the 152 patients included in the analyses, 9 (5.9%) patients were diagnosed AHP+. All were female, mean age was 34.3 years and they were referred by a neurologist (2), an internist (2), an emergency physician (1), a gastroenterologist (1), a gynecologist (1) or another physician (1). One third of AHP+ patients had a family history of AHP. The factors triggering attacks were stress (6), menstrual cycle (4), medications (4), infections (1), alcohol or tobacco consumption (1+1). The mean delay between inclusion and first severe, diffuse and apyretic abdominal pain was 28.4 months. Eight patients had dysautonomia (nausea, vomiting, constipation and/or tachycardia), 5 patients had peripheral neurological symptoms and 6 patients had central neurological symptoms. Conclusion This study found a 5.9% prevalence of AHP in patients with suggestive clinical picture in France. It confirms the main symptoms of AHP including severe, diffuse abdominal pain over several days, without fever, and possibly associated with neurological symptoms.

Introduction IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. Objective We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. Methods We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. Results Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. Conclusion To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.

Introduction Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors. Methods Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models. Results Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV- 2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5–7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections. Conclusion VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.