Search

Le lupus érythémateux systémique (LES) est une maladie auto-immune protéiforme dont la physiopathologie, partiellement comprise, implique des facteurs génétiques et épigénétiques. La description d'un nombre croissant d'anomalies génétiques responsables de lupus monogéniques permet une meilleure compréhension de cette maladie [1]. L'haploinsuffisance en A20 (HA20) est une maladie auto-inflammatoire monogénique liée à une mutation du gène TNFAIP3 d'expression phénotypique principalement inflammatoire mais aussi auto-immune. Actuellement, 177 patients sont décrits dans la littérature, incluant des patients avec un diagnostic de lupus [2]. Cette revue a pour objectif de colliger l'ensemble des patients avec un diagnostic de LES et d'HA20 (LES-HA20). Suivant les recommandations PRISMA 2020, nous avons systématiquement analysé tous les articles publiés en anglais, espagnol et français jusqu'en février 2024 et concernant les patients LES-HA20. Parmi les 177 patients HA20 rapportés dans la littérature, un diagnostic de LES avait été retenu avant ou lors du diagnostic d'HA20 pour 16 d'entre eux (9,0 %). Les critères de classification SLICC 2012 et EULAR/ACR 2019 étaient positifs dans 92,9 % des cas. Ils présentaient généralement une atteinte multisystémique : cutanée (81,3 %) spécifique (31,3 %) ou non (62,5 %), articulaire (56,3 %), rénale (56,3 %), neuropsychiatrique (31,3 %), oculaire (25,0 %), gastro-intestinale (18,8 %), pulmonaire (18,8 %), cardiaque (12,5 %) et/ou des séreuses (12,5 %). Des cytopénies et un syndrome inflammatoire biologique étaient présents respectivement chez 75,0 % et 25,0 % de ces patients. Parmi les patients pour lesquels l'immunologie était connue (n = 14), tous avaient des anticorps anti-nucléaires, 10 des anti-ADNn (71,4 %) et 11 des anti-ECT (78,6 %). Les conséquences de l'impact du variant TNFAIP3 sur la protéine A20 étaient disponibles pour tous les patients sauf un (n = 15) : le domaine OTU N-terminal, un domaine à doigt de zinc (ZF) et une région reliant deux domaines ZF étaient impactés dans respectivement 53,3 % (n = 8), 26,7 % (n = 4) et 20,0 % (n = 3) des cas. Il n'a pas été trouvé de différences significatives de phénotype entre ces différents sous-groupes de patients. Enfin, les données thérapeutiques étaient disponibles pour 13 patients : tous avaient reçu des corticoïdes, 92,3 % un immunosuppresseur et 61,5 % de l'hydroxychloroquine. Seize patients LES-HA20 ont été identifiés parmi les 177 patients HA20 rapportés dans la littérature, rendant peu probable une association fortuite. De plus, plusieurs éléments suggèrent que cette situation est sûrement sous-diagnostiquée. Premièrement, l'HA20 est une maladie rare. Ensuite, parmi les patients HA20, huit patients supplémentaires répondaient aux critères de classification SLICC 2012, dont sept répondants également aux critères de ACR/EULAR 2019. Enfin, le polymorphisme de TNFAIP3 a été associé à la survenue du LES bien avant la première description de l'HA20 [1]. À l'instar des patients avec un LES sans HA20 (LES-non HA20), les patients LES-HA20 présentaient généralement une atteinte multisystémique et protéiforme, principalement cutanée, articulaire et rénale. Néanmoins, les patients LES-HA20 présentaient des différences notables avec ceux sans HA20 : prépondérance des lésions de lupus cutané chronique parmi les manifestations cutanées spécifiques, plus grande prévalence de l'hyperthermie, des ulcères bucco-génitaux, des manifestations neuropsychiatriques, des cytopénies auto-immunes et du syndrome inflammatoire biologique ainsi que des symptômes ophtalmologiques et digestives ou antécédents familiaux auto-immuns/inflammatoires [3]. Cette revue systématique souligne la nécessité de séquencer TNFAIP3 chez les patients lupiques associant une maladie d'apparition précoce, des antécédents familiaux de maladie auto-immune/inflammatoire et certains symptômes compatibles avec le spectre de la maladie de Behçet tels que l'aphtose buccale ou bipolaire. Reconnaître les patients HA20-SLE pourrait améliorer notre compréhension du lupus et amener à de meilleures stratégies thérapeutiques. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3) variants. Besides the mainly auto-inflammatory phenotypic expression of HA20 mimicking Behçet's disease spectrum, some of its clinical and biological manifestations are part of the spectrum of autoimmune diseases, including glomerulonephritis as well as the frequent presence of antinuclear antibodies, sometimes with anti-DNA specificity. Among all the 191 HA20 patients reported in the literature, we identified 16 patients (8.4 %) with a compatible diagnosis of SLE. When estimable, the SLICC 2012 and EULAR/ACR 2019 classification criteria were positive for 92.9 % of them. A majority had multi-system involvement, mainly cutaneous (81.3 %), musculoskeletal (56.3 %), and/or renal (56.3 %) manifestations. They also seemed to exhibit differences compared to other SLE patients: higher prevalence of fever, chronic cutaneous lupus erythematosus, oral and genital ulcers, neuropsychiatric manifestations, autoimmune cytopenia, and elevated biologic inflammatory markers. This review highlights the necessity of considering TNFAIP3 variants in SLE patients with early-onset disease, familial history, and/or specific clinical manifestations suggestive of autoinflammatory diseases. Recognizing HA20-SLE patients may improve our understanding of SLE pathogenesis and lead to better therapeutic strategies for these patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Familial Mediterranean fever (FMF) is a genetic disease leading to recurrent episodes of inflammation. Two pathogenic variants are required for classical disease, but the disease can occur in heterozygous patients. Patients are treated continuously with colchicine to prevent amyloid A (AA) amyloidosis, including heterozygous patients who display a moderate form of FMF and rarely develop AA amyloidosis. The need for lifelong colchicine treatment in heterozygous FMF is therefore controversial. We aimed to characterise genotype-specific levels of inflammatory biomarkers, and to focus on heterozygous patients who discontinued colchicine., Methods: All patients with FMF from the European databases AIDnet and JIRcohort who received colchicine during follow-up were included. Demographics, C reactive protein (CRP), serum amyloid A (SAA), S100A8/A9 and S100A12 levels, leucocyte and neutrophil counts were extracted. Visits were classified as active, subclinical or inactive according to symptoms, CRP and SAA levels., Results: Data from 747 patients were extracted (233 homozygous, 201 compound heterozygous, 224 heterozygous patients, 49 heterozygous with one class III variant and 40 compound heterozygous with two class III variants). During active visits, all biomarker levels were higher compared with inactive visits (p<0.001). Heterozygous patients showed lower levels of CRP, SAA, S100A8/A9 and S100A12 during inactive and subclinical visits than patients with two class IV-V variants. Colchicine was discontinued in 52 heterozygous patients and reintroduced in 23 of them (44%)., Conclusion: S100A8/A9 and S100A12 proteins are biomarkers that can be used to assess disease activity. Heterozygous patients have lower levels of inflammatory biomarkers and some of them can sustainably discontinue colchicine treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic auto-inflammatory disease worldwide responsible for episodes of fever, serositis and musculoskeletal symptoms. Inflammatory attacks are responsible for sedentary behavior and FMF patients may be at increased cardiovascular risk. Cardiorespiratory Fitness (CRF) and physical capacities during adolescence are associated with cardiovascular mortality in adulthood. In this study, we aimed to describe the physical fitness of FMF adolescents., Methods: A monocentric retrospective study at the Versailles Hospital between January 2020 and June 2023. All FMF patients over 14-year-old who had completed a routine physical test were included. Clinical and physical data including results of the 6-minute walking test, timed unipedal stance test, Ruffier-Dickson index, 30-seconds chair-stand test and sit-and-reach test were extracted from medical records. Results were compared with previously published normative reference values and criterion-referenced standards for healthy subjects., Results: Eighteen FMF patients (12 girls, 6 boys) were included. The median age was 16 years old [14-18]. Clinical history included joint symptoms (n = 11), chest pleuritis (n = 8), and leg pain (n = 11). Estimated VO2max was below the recommended thresholds in 13 patients, which predicts cardiovascular risk. Cardiovascular adaptation was poor in 11 patients. Low VO2max was associated with CRP > 5 mg/l on test day and history of joint symptoms., Conclusion: FMF patients displayed altered physical capacities compared to normative values of healthy subjects. History of musculoskeletal pain, systemic inflammation and sedentary behavior may participate in impaired physical abilities and promote cardiovascular diseases in adulthood. Specific exercise programs could benefit patients for disease control and cardiovascular risk reduction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Transitioning from pediatric to adult care is a critical step for individuals with autoinflammatory diseases, requiring effective programs to ensure continuity of care and disease management. Despite various recommendations, the effectiveness of transition programs, particularly in monogenic autoinflammatory diseases, remains understudied., Methods: A single-center medical records review study was conducted at the French National Reference Center for Adult Autoinflammatory Diseases in Tenon Hospital from 2017 to 2023. All patients who had consulted for the first time between the ages of 15 and 30 years and had received care for an autoinflammatory disease during childhood were included. The patients were classified according to whether they had undergone a transition, defined as either no transition, simple transition (referral letter), or joint transition (pediatrician and adult physician consultation)., Results: One hundred eleven patients (median age, 18 years) were included. Patients who consulted without transition started adult follow-up and were followed up less regularly than those who underwent the transition process ( p < 0.001 and p = 0.028). In patients with familial Mediterranean fever, the absence of a formal transition was associated with poorer disease control at baseline ( p = 0.019). The type of transition did not impact disease control during follow-up., Conclusions: Participation in a transition program is associated with earlier and more regular follow-up in adulthood. Although transition type did not significantly impact disease control during follow-up in familial Mediterranean fever, the potential benefit of joint consultation extends beyond consultation frequency and disease outcomes, encompassing patient perspectives and self-management abilities. This study highlights the significance of collaborative transition programs in AIDs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Autoinflammatory diseases (AIDs) are conditions characterized by dysfunction of innate immunity, causing systemic inflammation and various clinical symptoms. The field of AIDs has expanded due to improved comprehension of pathophysiological mechanisms and advancements in genomics techniques. A new emerging category of AIDs is characterized by a significant increase in interleukin 18 (IL-18), a pro-inflammatory cytokine synthesized in macrophages and activated by caspase 1 via various inflammasomes. IL-18 plays a role in the regulation of innate and adaptive immunity. IL-18 is involved in various functions, such as the proliferation, survival, and differentiation of immune cells, tissue infiltration of immune cells, polarization of immune responses, and production of other pro-inflammatory cytokines. This review analyzes the literature on IL-18 regarding its functions and its implications in the diagnosis and treatment of AIDs. IL-18-associated AIDs comprise Still's disease and diseases associated with mutations in NLRC4, XIAP, CDC42, and PSTPIP1, as well as IL-18BP deficiencies. With the exception of PSTPIP1-associated diseases, these conditions all carry a risk of macrophagic activation syndrome. Measuring IL-18 levels in serum can aid in the diagnosis, prognosis, and monitoring of these diseases. Therapies targeting IL-18 and its signaling pathways are currently under investigation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

A20 Haploinsufficiency (HA20) is a monogenic autoinflammatory disease associated with an autosomal dominant mutation in the TNFAIP3 gene. It induces a defect in the inactivation of the pro-inflammatory NF-κB pathway. Less than 200 cases have been described worldwide. The clinical picture of the disease is essentially based on the association of recurrent fever and/or biologic inflammatory syndrome, aphtosis, often bipolar, and cutaneous folliculitis. However, the clinical spectrum of HA20 is very broad, including gastrointestinal (mainly colonic ulceration), articular, cutaneous, pericardial and lymph node involvement, as well as frequent association with organ-specific or non-specific autoimmune manifestations and/or autoantibodies, including antinuclear antibodies and anti-dsDNA. As a result, the diagnosis of a number of systemic or organic disorders, most notably Behçet's disease, Crohn's disease, and sometimes even systemic lupus, has been corrected to HA20 by molecular research for a heterozygous mutation with functional deficiency of TNFAIP3. Although the first signs of the disease often appear in the first years of life, the diagnosis is often made in adulthood and requires the involvement of both paediatric and adult physicians. Treatment for HA20 is not codified and relies on conventional or biological immunomodulators and immunosuppressants adapted to the patient's symptomatology. This review highlights the enormous diagnostic challenges in this autoinflammatory disease., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 sequence variants from 2016 to August 2023 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data from 177 patients from 65 articles were retrieved (108 women). The principal features were mucosal ulcers (n = 129); fever (n = 93) followed by gastrointestinal (n = 81); skin features (n = 76); autoimmunity (n = 61), including thyroiditis (n = 25) and lupus (n = 16); and joint involvements (n = 54). Five patients had died at the time of publication. In 54 of 63 patients, CRP was significantly elevated during flares, with a median of 51 mg/l. The most commonly used treatment included corticosteroids and nonsteroidal anti-inflammatory drugs (n = 32), TNF blockers (n = 29), colchicine (n = 28), and methotrexate (n = 14). TNFAIP3 variants impacted the ovarian tumor domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, reported sex, and variant type significantly impacted phenotype. A better understanding of the wide A20 haploinsufficiency phenotype could facilitate the diagnosis process. Much remains to be elucidated about pathogenesis and treatment to improve outcome in patients with A20 haploinsufficiency., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020. Thirty-six patients were included in the analysis. Eighteen patients (50%) satisfied at least one of the MCTD classifications, 11 of whom (61%) also met 2019 ACR/EULAR criteria for SLE. Twelve other patients only met SLE without MCTD criteria, and a total of 23 patients (64%) met SLE criteria. The most frequent manifestations included Raynaud's phenomenon (RP, 91%) and arthralgia (67%). We compared the characteristics of patients meeting only the MCTD (n = 7), SLE (n = 12), or both (n = 11) criteria. Patients meeting the MCTD criteria were more likely to display SSc features, including sclerodactyly (p < 0.01), swollen hands (p < 0.01), RP (p = 0.04) and esophageal reflux (p < 0.01). The presence of scleroderma features (swollen hands, sclerodactyly, gastro-oesophageal reflux), was significantly associated with the diagnosis of MCTD. Conversely, the absence of those manifestations suggested the diagnosis of another definite connective tissue disease, especially SLE., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Mevalonate kinase deficiency (MKD) is a monogenic auto-inflammatory disease. Its manifestations range from partial MKD to mevalonic aciduria (MVA). All patients display a periodic fever, and MVA patients additionally exhibit severe neurological involvement. The objective of this work was to describe neurological manifestations of MKD., Methods: A systematic literature review was performed from January 1990 to January 2022. Forty-five patients from 18 case reports and five cohort studies were included in the analysis., Results: In cohort studies, the most-reported manifestations were headaches (41%) and fatigue (31%). Serious involvements including ataxia and developmental delay were described less than 1% of patients but 22-31% of case reports. They consistently appeared in the first years of life. Retinal dystrophy was frequently reported (31%) in case reports. Other manifestations, including uveitis, aseptic meningitis, and stroke remained rare., Discussion: Severe neurological manifestations are rare in MKD but are responsible for major functional disabilities. They are present at onset and never appear at follow-up of patients with mild MKD. Conversely, headaches and fatigue are frequent symptoms that should be investigated. Visual examinations should be performed on the appearance of visual symptoms. The efficacy of anti-IL-1β therapy on neurological manifestations should be further investigated., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients., Methods: Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020., Results: Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group., Conclusion: FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Immunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis., Methods: We conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS)., Results: Twenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, P < 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, P = 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, P = 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12-84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV., Conclusion: We report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse., (Copyright © 2021 by the Journal of Rheumatology.)

Multiple myeloma (MM) is a rare cancer. Cutaneous involvement is uncommon with fewer than 100 cases described in the literature. We report herein a patient with MM, subtype IgA kappa, with unusual clinical presentation including the lower lip.

Emergence of antibiotic resistance put an end to the antibiotic miracle. According to recent review data, the number of cases of multiresistant bacteria, which are resistant to all antibiotics available, is increasing as well in the developed countries as in the developing countries. To face the emergence of these bacteria, it is necessary to evaluate the situation in Tunisian hospitals and act consequently. This review provide recent data on antibiotic resistance in Gram negative bacilli in Tunisian hospitals by focusing on some emergent resistances, which represent a daily challenge for the medical profession, such as extended spectrum beta-lactamases, carbapenem resistance, and fluoroquinolone resistance.

Background: We sought to compare the prevalence of exclusive breastfeeding throughout at least the first 6 months of life in patients presenting atopic dermatitis (AD) with a control group, and to check for a correlation between the duration of exclusive breastfeeding and the severity of AD., Patients and Methods: We conducted a case-control study with prospective inclusion over a period of 3 years. The study group consisted of 114 patients aged less than 15 years, from an urban area, presenting AD but with no personal or family history of atopy. Each patient was compared with two controls from the same town, matched for age and gender, with no personal or family history of atopy, and free of AD. Data analysis was performed using the SPSS software package, version 15.0. A P-value of less than 0.05 was considered as statistically significant., Results: The prevalence of exclusive breastfeeding for at least the first 6 months of life in the patient group was significantly lower than in the control group (P=0.0413). On the other hand, AD was significantly less severe in patients exclusively breastfed for longer than 9 months (P=0.0079)., Conclusion: The correlations recorded in our study do not allow us to draw any definite conclusions about a protective effect of exclusive breastfeeding with regard to AD. However, other benefits of extended exclusive breastfeeding justify supporting breastfeeding in a community with an existing sociocultural predisposition for this feeding method., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Fixed drug eruption (FDE) is characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. We report here a case of multiple FDE induced by atenolol in a 48-year-old woman confirmed by positive patch test in previously affected sites. Beta-blockers-induced FDE are very rare. Only two cases had been reported in the literature. To the best of our knowledge, this is the first case reported of atenolol-induced FDE confirmed by a positive patch test.