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AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future. [ABSTRACT FROM AUTHOR]

Summary: Background: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome'). Objectives: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. Methods: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow‐up, were recorded. Results: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow‐up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild‐to‐moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C‐reactive protein levels and less frequent chondritis). The 5‐year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. Conclusions: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation. Whatis already known about this topic? VEXAS syndrome is a recently described autoinflammatory disease related to UBA1 mutation. The clinical phenotype includes patients with thrombosis, fever, chondritis, neutrophilic dermatosis and MDS. What does this study add? The main clinical features of VEXAS patients remain recurrent fever (64.7% vs. 72%, in original description by Beck et al.), skin lesions (83.6% vs. 88%), lung infiltrates (49.1% vs. 72%), unprovoked thrombosis (35.5% vs. 44%), with new features such as arthralgia (28.4%), ocular involvement (40.5%) or lymph node enlargement (34.5%), expanding the previous clinical phenotype of VEXAS syndrome.We identified 3 clusters of VEXAS syndrome, including an MDS‐related phenotype; mild‐to‐moderate disease with less fever, chondritis and thromboembolism, and one with more 'inflammatory' profile characterized by cutaneous vasculitis lesions and relapsing profile.A phenotype–genotype association was observed for UBA1 p.Met41Leu which was associated with less 'inflammatory' and mild‐to‐moderate phenotype and better overall prognosis. Linked Comment: L.T. Nicholson and L.M. Madigan. Br J Dermatol 2022; 186:392–393. Plain language summary available online [ABSTRACT FROM AUTHOR]

Objectives: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease. It is associated with MEFV mutations. Its main features are recurrent episodes of fever and serositis. Patients can display dermatological manifestations such as erysipelas-like erythema, generally considered as a neutrophilic dermatosis (ND). It has been suggested that FMF can be associated with other types of ND. Our aim was to perform a systematic review of the literature to assess the link between ND and FMF. Method: A systematic review of the literature was performed using MEDLINE from 1946 to 2018. Three independent investigators identified reports of non-erysipelas-like erythema neutrophilic dermatosis (NEND) associated with FMF, selected the criteria to establish the diagnosis of FMF and ND, and evaluated the link between the two conditions. FMF-associated NEND was supported by confirmation of both diagnoses and exclusion of other causes of ND. Results: Eighteen articles were selected. Nine articles reported FMF patients with the following NEND: neutrophilic panniculitis (n = 4), Sweet syndrome (n = 6), and pyoderma gangrenosum (n = 1). None of these cases was supported by histological confirmation, fulfilled diagnostic criteria for definitive or probable FMF, or confirmed the exclusion of all the most frequent diseases associated with NEND. As a result, there is insufficient evidence to support a potential relationship between NEND and FMF. Conclusions: The association between FMF and NEND remains unclear. In FMF patients with NEND, every differential diagnosis and alternative cause of NEND should be excluded before drawing any conclusions about a potential causal relationship. [ABSTRACT FROM AUTHOR]

Les maladies auto-immunes et auto-inflammatoires (MAI2) forment un groupe hétérogène de maladies dont certaines sont d'origine génétique. Elles peuvent se manifester dès l'enfance et entraîner une morbidité et une mortalité non négligeables. Le transfert des adolescents de la pédiatrie vers la médecine adulte constitue une étape parfois difficile pour les patients et leur famille et peut ainsi entraîner une rupture du suivi médical, des soins, et l'apparition de complications. Des recommandations existent pour la réussite de la transition des patients atteints de maladies chroniques mais peu sont adaptées spécifiquement aux MAI2 de l'enfant et de l'adulte (Suris et al., 2015–Solau-Gervais, 2012). Le groupe de travail sur la transition de la filière française des maladies auto-immunes et auto-inflammatoires rare (FAI2R) présente ses réflexions et recommandations pour une transition réussie. La préparation à la transition doit être anticipée et avoir pour objectif l'autonomie des adolescents en les responsabilisant et leur fournissant les connaissances pour gérer eux-mêmes leurs soins, savoir comment réagir de manière appropriée en cas de changement de leur état et comment évoluer au sein du système de santé des adultes. Cela exige la participation active et coordonnée du patient, de sa famille et des équipes de soins pédiatriques et adultes. La transition implique une prise en charge pluridisciplinaire et des programmes d'éducation thérapeutique dédiés. Enfin, l'identification de médecins spécialistes par région, formés aux MAI2 rares, accompagnés par des patients experts, pourrait améliorer la prise en charge des patients atteints de MAI2 rares de l'adolescence à l'âge adulte. Autoimmune and autoinflammatory diseases (AIDs) are a heterogeneous group of diseases. They can occur in childhood and account for significant morbidity and mortality. Transitioning from pediatric to adult healthcare can be difficult for patients and their families. It can interfere with patient follow-up and management, and eventually lead to complications. Although recommendations exist for the successful transition of patients with chronic diseases, few are specifically adapted to children and adults with AIDs (Suris et al., 2015–Solau-Gervais, 2012). The French working group on transition of the rare autoimmune and autoinflammatory diseases presents its reflections and recommendations for a successful transition. Preparation for transition should start early. Its goals are to empower adolescents by providing them with the knowledge to manage their own care, respond appropriately to changes in their condition, and evolve within the adult healthcare system. This requires the active participation of the patient, his or her family, as well as the pediatric and adult medical teams. The transition process involves multidisciplinary care and dedicated therapeutic education programs. Finally, the identification of medical specialists by region, trained in rare AIDs and accompanied by expert patients, may improve the management of patients with rare AIDs from adolescence to adulthood. [ABSTRACT FROM AUTHOR]

All patients were not opposed for inclusion of their medical data in the JIR cohort and were informed that collected data might be used for research studies in compliance with privacy rules. The authors are grateful to all the patients who took time to participate in this study. When tattooing was performed, most patients were under colchicine (69.7%) and only two patients reported minor transient adverse events. [Extracted from the article]

LMD-MS/MS analysis of several dermal microdissected amyloid deposits demonstrated high spectra for KRT5/14 heterodimers, along with the amyloid signature proteins. Spectra of other known amyloid proteins were not detected; notably, no spectra for light chain immunoglobulins were detected, ruling out AL amyloidosis. gl The Chinese family included three symptomatic members (II.8, II.9 and II.10), who complained of pruritic lesions, highly suggestive of lichen amyloidosis, over arms, legs and back. LC-MS/MS and immuno-electron subtyping combined with genetics show that OSMR mutations cause amyloid deposition of keratins 5/14 in familial primary localized cutaneous amyloidosis. [Extracted from the article]

Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. The prevalence of AAA in AOSD was 0.88% (95%CI [0.49–1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ± 12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies. [ABSTRACT FROM AUTHOR]

Summary: Background: Mastocytosis is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells. The adult and paediatric forms differ in their clinical and genetic features and outcomes. Objectives: To describe the clinical evolution of a well‐characterized cohort of paediatric mastocytosis (PM), and to analyse the relationship between KIT mutation and the clinical course. Methods: This was a prospective cohort study performed at the National Clinical Reference Center for Mastocytosis. Diagnosis was confirmed by identification of KIT mutation on lesional skin biopsy. Mastocytosis subtype, mast cell mediator‐related symptoms (MC MRS) and clinical course were recorded. Fifty‐three patients with PM and > 4 years of disease course were enrolled. The mean ± SD age at the final evaluation was 13·2 ± 4·8 years. The main outcome was the type of KIT mutation as a predictor of evolution and clinical characteristics. Results: Patients presented with maculopapular cutaneous mastocytosis (n = 44), diffuse cutaneous mastocytosis (n = 6) or mastocytoma (n = 3). The mean duration of disease was 12·1 years. Substantial or partial cutaneous regression (18 of 53 and 16 of 53), stabilization or aggravation (16 of 53) and complete cutaneous regression (three of 53) were noted. MC MRS mainly regressed (21 of 53). For 22 patients, evolution of MC MRS and evolution of cutaneous lesions were different. No significant association between evolution and KIT mutation or between evolution and type of cutaneous mastocytosis was found. A late onset of the disease (after 2 years) is associated with worse evolution. Conclusions: PM is not systematically self‐regressive. MC MRS manifestations and cutaneous lesions can persist or increase overtime. KIT mutation is not a predictor of evolution. What's already known about this topic? The clinical and genetic features and outcomes of mastocytosis differ between the adult and paediatric forms.Paediatric mastocytosis is also a clonal disease.Spontaneous regression occurs in the majority of cases and no predictive factors have been identified. What does this study add? This prospective study of 53 patients shows that KIT mutation is not a predictor of evolution. However, characteristics such as age at disease onset could be predictors.Paediatric mastocytosis evolution is not systematically regressive, and adolescents can experience only partial regression or aggravation, including both cutaneous and mast cell mediator‐related symptoms.A long‐term follow‐up study of paediatric patients with mastocytosis is needed. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Background. There are few data on anakinra use after failure of conventional medications for crystal-induced peripheral arthritis and/or crowned dens syndrome among complex hospitalized patients. Methods. We retrospectively analyzed the outcome of six patients affected with subacute crystal-induced arthritis who had received anakinra in second or third line therapy, including three patients with crowned dens syndrome and three others with gouty arthritis. Patients’ comorbidities, reasons for anakinra use and associated drugs, and outcomes were recorded. Results. All patients presented with elevated inflammatory syndrome, systemic symptoms with poly/oligoarthritis. Except for absolute contraindications, all patients were previously treated with full or decreased dose of NSAID, colchicine, and/or glucocorticoids, with unsatisfactory response. All three gouty patients exhibited complete responses in all acute involvements under anakinra within 3 to 5 days, including one of them who needed the reintroduction of colchicine treatment that was previously unsuccessful. Crowned dens syndrome patients, including two with pseudogout and one with subacute hydroxyapatite deposition disease, needed 9 to 11 days to achieve complete response. Tolerance to anakinra was good. Conclusion. In case series of complex hospitalized patients, anakinra showed good activity in crowned dens syndrome and associated crystal-induced peripheral arthritis, with longer treatment duration than in gouty arthritis. [ABSTRACT FROM AUTHOR]

When anti-SSA/Ro antibodies are present in sera of mothers with connective tissue diseases, the incidence of congenital heart block (CHB) has been reported to be 1–2% in live births. The risk of recurrence of CHB in a subsequent child remains limited to 10–16%. CHBs are usually complete but CHB of the first or second degree can also be observed. In some cases, CHB is associated with endocardial fibroelastosis. Late-onset cardiomyopathy may occur later in life in these children. The mortality of CHB, which is predominant in utero and in the first months of life, is an estimated 16–19%. A pacemaker is required in about 66% of cases. Curative treatment of CHB is based on fluorinated steroids (dexamethasone or betamethasone) that do cross the placenta in an active form. Guidelines are available but further studies are needed to optimize treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Aside from congenital heart block (CHB), sinus bradycardia and prolongation of the corrected QT (QTc) interval have been reported in infants born to mothers with anti-SSA antibodies. To assess the pathologic nature of these manifestations, this study focused on electrocardiographic (EKG) variations in these children, comparing them with findings in a control group. METHODS: We studied 165 consecutive pregnancies in 106 anti-SSA-positive women with connective tissue diseases (CTDs). EKGs obtained on 58 children of this group were compared with those obtained on 85 infants born to mothers with CTD who were negative for both anti-SSA and anti-SSB. RESULTS: No statistically significant difference was seen between the 2 study groups with regard to gestational age, prematurity, birth weight, age of the children at the time of EKG, age of the mothers, or treatments received by the mothers during their pregnancies. Seven of 137 children developed cutaneous neonatal lupus syndrome; 1 child developed CHB (CHB risk of 1 in 99 [1%] if only the first prospectively observed pregnancy in women without a history of CHB is included in the analysis). For EKGs recorded during the first 2 months of life, the mean +/- SD PR interval was 96 +/- 16 msec in the anti-SSA-positive group and 96 +/- 13 msec in the anti-SSA-negative group (P = 0.84), with mean QTc values of 397 +/- 27 and 395 +/- 25 msec (P = 0.57) and mean heart rates of 141 +/- 23 and 137 +/- 21 beats per minute (P = 0.20), respectively. No difference in the PR interval, QTc interval, or heart rate was observed for EKGs obtained between 2 and 4 months of life. When EKGs obtained at 0-2 months were compared with those obtained at 2-4 months, a physiologic prolongation of the QTc interval was observed in both study groups. No sudden infant death or symptomatic arrhythmia occurred during the first year of life. CONCLUSION: The EKG findings in children of anti-SSA-positive and anti-SSA-negative mothers were not significantly different. Our results suggest that the prolongation of the QTc interval and sinus bradycardia that have recently been reported in children of mothers with anti-SSA antibodies occur independently of the anti-SSA antibodies. The pathologic nature of these EKG variations was not confirmed by our controlled study. Copyright 2004 American College of Rheumatology [ABSTRACT FROM AUTHOR]

The article presents a 2019 case study of a 71-year-old man who had on-and-off spontaneous diffuse cutaneous lesions and has had cutaneous vasculitis. Biopsy showed leucocytoclastic vasculitis (LV) and ultrasonography led to a thyroid transcription factor 1-positive pulmonary adenocarcinoma diagnosis. This was assessed to be a case of extensive ecchymoses and palpable purpura due to vitamin C deficiency and LV heralding lung adenocarcinoma which were resolved by vitamin doses and chemotherapy.

L'haploinsuffisance de A20 (HA20) est une maladie auto-inflammatoire monogénique, associée à des mutations de transmission autosomique dominante du gène TNFAIP3. Elle entraîne un défaut d'inactivation de la voie pro-inflammatoire du NF-κB. Moins de 200 cas ont été décrits dans le monde. Le tableau clinique de la maladie repose essentiellement sur un triptyque constitué par une fièvre et/ou un syndrome inflammatoire biologique récurrents, une aphtose volontiers bipolaire et une folliculite cutanée. Cependant, le spectre clinique du HA20 est très large et inclut des atteintes digestives, articulaires, cutanées, péricardiques ou ganglionnaires. Il existe également une association fréquente à des manifestations et/ou des marqueurs auto-immuns, dont les anticorps anti-nucléaires et anti-ADN natifs. Ainsi, le diagnostic de nombres d'affections systémiques ou organiques et principalement la maladie de Behçet, la maladie de Crohn, voire le lupus systémique, a pu être redressé en diagnostic de HA20 par la recherche moléculaire d'une mutation hétérozygote avec déficit fonctionnel de TNFAIP3. Si les premières manifestations de la maladie surviennent souvent dans les premières années de vie, son diagnostic n'est souvent fait qu'à l'âge adulte et requiert une implication des médecins pédiatres et adultes. Les traitements du HA20 ne sont pas codifiés, reposant sur immunomodulateurs et immunosuppresseurs conventionnels ou biologiques adaptés à la symptomatologie du patient. Cette revue met ainsi la lumière sur les vastes challenges diagnostiques de cette maladie auto-inflammatoire rare mais probablement sous-diagnostiquée. 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. [ABSTRACT FROM AUTHOR]

Summary: This study from Paris, France, followed 53 children with mastocytosis as they grew up. In mastocytosis there are increased numbers of mast cells (best known for their role in allergy) in the body, especially in the skin. In the childhood sub‐types, mast cell numbers are usually increased only in the skin and the condition is generally said to improve around puberty. Symptoms include itch, swelling and blistering in the skin but occasionally, if a lot of chemical messengers are released from huge numbers of mast cells, general ('systemic') symptoms such as flushing, abdominal pain, diarrhoea and headache occur. Most children improved, particularly if they had had mastocytosis for more than 12 years or had reached 16 years of age; in six the condition worsened, and in only three children did the mastocytosis clear completely from the skin. In 11 children the condition had started after two years of age and this was the only factor that predicted what would happen over time: the outcome was worse in this group. Systemic symptoms tended to improve, though they resolved completely in only five children and frequently persisted even if the skin changes improved. Three cases went on to develop more generalised mastocytosis, with involvement of bone in one case, bone and liver in the second case, and gut in the third. Forty‐six children showed a mutation in a gene called KIT, which is already known to be associated with mastocytosis, but there was no relationship between this, the type of mastocytosis, or whether or not the mastocytosis improved, persisted or worsened. Linked Article: Meni et al. Br J Dermatol 2018; 179:925–932 [ABSTRACT FROM AUTHOR]

Summary: 这项来自法国巴黎的研究追踪了 53 名患有肥大细胞增多症的儿童。在肥大细胞增多症中,体内肥大细胞(最为人所知的是它们在过敏中的作用)的数量增加,特别是在皮肤中。在儿童亚型中,肥大细胞数通常仅在皮肤中增加,并且通常认为该状况在青春期前后改善。症状包括瘙痒、皮肤肿胀和水疱,但偶尔情况下,如果大量化学信使从大量肥大细胞中释放出来,会出现全身("系统")症状,如潮红、腹痛、腹泻和头痛。大多数儿童都有所改善,特别是如果他们患有肥大细胞增多症超过 12 年或已达到 16 岁;6 名儿童病情恶化,只有 3 个儿童的肥大细胞增多症完全从皮肤中清除。在 11 名儿童中,这种疾病在两岁后开始,这是预测随着时间推移会发生什么的唯一因素:该组的结果更糟。全身症状趋于改善,尽管它们仅在五个孩子中完全消退,并且即使皮肤改变改善也经常持续存在。3 例病例继续发展为更广泛的肥大细胞增多症,其中一例累及骨,第二例累及骨和肝脏,第三例累及肠道。46 名儿童表现出一种名为 KIT 的基因突变,已知这种基因与肥大细胞增多症有关,但这与肥大细胞增多症的类型、或者肥大细胞增多症是否改善、持续或恶化并没有关系。 Linked Article: Meni et al. Br J Dermatol 2018; 179:925–932 [ABSTRACT FROM AUTHOR]

Les maladies auto-inflammatoires (MAI) sont des maladies aboutissant à une activation inadaptée de l'immunité innée en dehors de toute infection. Le champ des MAI monogéniques est en constante expansion, avec la découverte de nouvelles pathologies et mécanismes physiopathologiques grâce à notamment l'accès facilité aux séquençages pangénomiques. Les actinopathies avec manifestations auto-inflammatoires sont un nouveau groupe émergent de MAI, lié à des défauts dans la régulation de la dynamique du cytosquelette d'actine. Ces maladies débutent le plus souvent en période néonatale, et associent à des degrés variables un déficit immunitaire primitif plus ou moins sévère, des cytopénies (en particulier thrombopénie), des manifestations auto-inflammatoires notamment cutanéodigestives, des manifestations atopiques et auto-immunes. Le diagnostic est à évoquer essentiellement devant un tableau d'auto-inflammation cutanéodigestif de début précoce, associé à un déficit immunitaire primitif et à une thrombopénie ou à une tendance aux saignements. Certaines de ces maladies présentent des spécificités, notamment un risque de syndrome d'activation macrophagique ou une tendance à l'atopie ou à la lymphoprolifération. Nous proposons ici une revue de la littérature sur ces nouvelles maladies, avec une proposition d'approche pratique en fonction des principales anomalies biologiques associées et quelques particularités cliniques. Le diagnostic demeure cependant génétique, et plusieurs diagnostics différentiels sont à évoquer. La physiopathologie de ces maladies n'est pas encore entièrement élucidée, et des études sont nécessaires afin de mieux éclaircir les mécanismes inhérents pouvant guider le choix des thérapeutiques. Dans la plupart des cas, la sévérité du tableau indique l'allogreffe de moelle. Auto-inflammatory diseases (AIDs) are diseases resulting from an inappropriate activation of innate immunity in the absence of any infection. The field of monogenic AIDs is constantly expanding, with the discovery of new pathologies and pathophysiological mechanisms thanks to pangenomic sequencing. Actinopathies with auto-inflammatory manifestations are a new emerging group of AIDs, linked to defects in the regulation of the actin cytoskeleton dynamics. These diseases most often begin in the neonatal period and combine to varying degrees a more or less severe primary immune deficiency, cytopenias (especially thrombocytopenia), auto-inflammatory manifestations (especially cutaneous and digestive), atopic and auto-immune manifestations. The diagnosis is to be evoked essentially in front of a cutaneous-digestive auto-inflammation picture of early onset, associated with a primary immune deficiency and thrombocytopenia or a tendency to bleed. Some of these diseases have specificities, including a risk of macrophagic activation syndrome or a tendency to atopy or lymphoproliferation. We propose here a review of the literature on these new diseases, with a proposal for a practical approach according to the main associated biological abnormalities and some clinical particularities. However, the diagnosis remains genetic, and several differential diagnoses must be considered. The pathophysiology of these diseases is not yet fully elucidated, and studies are needed to better clarify the inherent mechanisms that can guide the choice of therapies. In most cases, the severity of the picture indicates allogeneic marrow transplantation. [ABSTRACT FROM AUTHOR]

Les épreuves classantes nationales informatisées (ECNi) s'appuient actuellement sur une évaluation des connaissances des étudiants et non des compétences cliniques, pourtant déterminantes dans la performance professionnelle. Pour évaluer l'impact potentiel de cette absence de considération, nous avons évalué la concordance entre les rangs des étudiants aux épreuves facultaires cliniques et leur rang aux ECNi. Nous avons inclus les étudiants de 6e année de médecine à Sorbonne Université des promotions 2017 à 2021 et récupéré leurs notes et rangs aux épreuves facultaires théoriques et cliniques et aux ECNi. Les épreuves théoriques sont au même format que les ECNi. Les épreuves cliniques comprennent une évaluation sémiologique au lit du malade et une évaluation des compétences relationnelles lors de deux entretiens cliniques simulés. Nous avons étudié la concordance entre les épreuves facultaires et les ECNi par le coefficient de corrélation intraclasse (CCI). Nous avons inclus 1806 étudiants. La concordance entre le rang aux épreuves facultaires théoriques et le rang aux ECNi est bonne (CCI 0,83; IC 95 % 0,81–0,85) alors que la concordance entre le rang aux épreuves facultaires cliniques et le rang aux ECNi est médiocre (CCI 0,13; IC 95 % 0,09–0,17). L'accord entre le rang de classement aux ECNi et les compétences cliniques évaluées par une épreuve facultaire spécifique est actuellement faible. Incorporer une évaluation pratique dans le classement national, comme le prévoit la réforme du deuxième cycle, motivera l'ensemble des étudiants à investir des efforts dans l'acquisition des compétences cliniques et valorisera les plus performants dans cette dimension. Before attending residency, 6th-year French medical students must validate a final examination including a practical clinical test in their faculty. However, the national ranking that determines their future specialty and region solely relies on a computerized knowledge test. Our goal was to investigate the association between the final faculty test and the national ranking test. In our faculty, the final examination includes a computerized theoretical test (similar to the national one) and a practical test: a standardized evaluation of semiology skills at the bedside and a standardized assessment of relational skills with role plays. The agreements between the national test and faculty computerized and practical tests were analyzed by intraclass correlation coefficients (ICC). Data from 1806 students who underwent the three examinations from 2017 to 2021 were analyzed. There was a good agreement between the ranks in the faculty and national computerized tests: ICC 0.83 (95% CI 0.81–0.85). By contrast, the agreement between the ranks in the faculty practical test and the national computerized test was poor: ICC 0.13 (95% CI 0.08–0.17). Results were stable over the years. The agreement between the ranking of the current national test and the clinical skills assessed by a specific faculty test is poor. This could relate to a true independence or to different levels of motivation to perform well. Indeed, the result of the national test is the most important one as it determines their career. Incorporating a clinical assessment into the national ranking test will motivate students to acquire clinical skills and value those who perform well this practical dimension. [ABSTRACT FROM AUTHOR]

Les maladies auto-inflammatoires liées à des mutations du gène RIPK1 ont été décrites récemment. Il existe deux phénotypes cliniques distincts en fonction du type et de la localisation des variants. Lorsque la mutation est récessive induisant une perte de fonction, les patients présentent un tableau mixte de déficit immunitaire avec des infections bactériennes et fungiques à répétition et des signes de maladie auto-inflammatoire à type d'inflammation chronique et précoce du tube digestif, de polyarthrites non érosives et de retard de croissance. En revanche, lorsque la mutation est dominante, gain de fonction, les manifestations sont uniquement auto-inflammatoires avec une lymphoprolifération diffuse, des lésions buccales à type d'aphtose ou d'ulcérations, des douleurs abdominales ainsi qu'une hépato-splénomégalie. Les mutations dominantes affectent uniquement le site de clivage de la caspase 8 et le phénotype clinique est appelé CRIA pour Cleavage-Resistant RIPK1-Induced Autoinflammatory syndrome. La forme autosomique récessive est sévère, engageant le pronostic vital avec une nécessité d'allogreffe de mœlle osseuse tandis que la forme dominante répond bien aux antagonistes du récepteur de l'interleukine-6. Ainsi, les mutations de RIPK1 peuvent induire des manifestations cliniques variées avec deux phénotypes distincts. Bien qu'encore rares, car de description récente, ces maladies peuvent être évoquées par un interniste devant un tableau digestif récurrent et vont être de plus en plus diagnostiquées à l'avenir grâce à l'intégration de ce gène dans les puces de diagnostic dédiées aux maladies auto-inflammatoires et inflammatoires précoces du tube digestif, en séquençage de nouvelle génération. Autoinflammatory diseases related to RIPK1 mutations have been recently described. Two distinct clinical phenotypes have been reported and depend on the type and location of the mutation. When the mutation is recessive with loss of function, patients develop a combined phenotype of immune deficiency with recurrent bacterial and fungal infections and signs of early inflammatory bowel disease, non-erosive polyarthritis and growth retardation. On the other hand, when the mutation is dominant, gain of function, the manifestations are only auto-inflammatory with extensive lymphoproliferation, oral lesions such as aphthosis or ulcers, abdominal pain and hepatosplenomegaly. The mutations described for the dominant form affect only the cleavage site of caspase 8 and the clinical phenotype is called CRIA for Cleavage-Resistant RIPK1-Induced Autoinflammatory syndrome. The recessive form is severe and life-threatening requiring hematopoietic stem cell transplantation while the dominant form responds well to interleukin-6 receptor antagonists. Thus, RIPK1 mutations can induce various clinical manifestations with two distinct phenotypes. Although still rare, because of their recent description, these diseases can be suspected by an internist, in front of recurrent digestive features and will be increasingly diagnosed in the future through the integration of this gene in the diagnostic chips dedicated to autoinflammatory diseases and early inflammatory bowel diseases, using next generation sequencing. [ABSTRACT FROM AUTHOR]

Le syndrome périodique associé aux mutations du récepteur du facteur de nécrose tumorale de type 1 (TRAPS) est une maladie auto-inflammatoire autosomique dominante rare associée à des mutations du gène du récepteur de type 1 du TNF (TNFRSF1A). Elle se caractérise par des douleurs abdominales fébriles récurrentes relativement longues accompagnées d'arthromyalgies. Le principal diagnostic différentiel est la fièvre méditerranéenne familiale (FMF). Étude observationnelle rétrospective sur les patients d'origine Méditerranéenne suivis pour TRAPS et inclus dans la cohorte observationnelle « Juvenile Inflammatory Rheumatism » (JIR) L'âge du début des symptômes, l'âge du diagnostic, le nombre d'années d'errance et les traitements reçus ont été recueillis pour chaque cas index. Neuf patients issus de 6 familles ont été inclus ; un diagnostic moléculaire avait confirmé le TRAPS chez tous. L'âge médian au diagnostic était de 26 ans, le nombre moyen d'année d'errance était de 17 ans. Le diagnostic de FMF avait été porté en premier lieu chez tous les patients. L'amylose AA a révélé le TRAPS chez 2 patients. La colchicine a été débutée sans aucune efficacité dans tous les cas. Cinq patients ont été traités par une biothérapie inhibant l'interleukine-1 avec une efficacité de 100 %. Chez un patient d'origine méditerranéenne présentant des douleurs abdominales fébriles récurrentes plus ou moins compliquées d'amylose AA, le premier diagnostic à évoquer est la FMF. Des poussées longues, une transmission d'allure dominante, un parent non méditerranéen, et l'inefficacité de la colchicine doivent faire évoquer le TRAPS. Tumor Necrosis Factor Type 1 Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autosomal autoinflammatory disease associated with mutations in the TNF type 1 receptor gene (TNFRSF1A). It is characterized by relatively long recurrent febrile seizures with an average duration of 7 days accompanied by arthralgia, myalgia, and usually a rash. In a patient of Mediterranean origin with recurrent fever, familial Mediterranean fever is the first diagnosis to be suspected by argument of frequency. A retrospective observational study was conducted on patients from Mediterranean origin followed for TRAPS and included in the "Juvenile Inflammatory Rheumatism" (JIR) observational cohort in the national French autoinflammatory center. The age of onset of symptoms, age of diagnosis, number of years of wandering and treatments received were collected for each index case. Nine patients from 6 families of Mediterranean origin were included. A molecular diagnosis confirmed TRAPS in all patients. The median age at diagnosis was 26 years, the mean number of years of wandering was 17 years. The diagnosis of FMF was made first in all patients. AA amyloidosis revealed TRAPS in 2 patients. Colchicine was started without any efficacy in all cases. Five patients were treated with interleukin-1 inhibitory biotherapy with 100% efficacy. In a patient of Mediterranean origin presenting with recurrent febrile abdominal pain of AA amyloidosis, the first diagnosis to be suspected is FMF. Long relapses, dominant transmission, a non-Mediterranean relative, and the ineffectiveness of colchicine should evoke TRAPS. [ABSTRACT FROM AUTHOR]

Les patients atteints de troubles psychiatriques souffrent de problèmes somatiques nombreux et souvent mal pris en charge. Cette étude vise à établir le profil des patients avec comorbidités psychiatriques hospitalisés en médecine interne depuis les urgences et à comparer leurs durées de séjour avec celles des patients sans comorbidité psychiatrique. Cette étude observationnelle rétrospective sur données de soins collectées dans l'Entrepôt de Données de Santé de l'Assistance publique–Hôpitaux de Paris a inclus les patients hospitalisés après passage aux urgences, au cours de l'année 2017, dans 9 services de médecine interne. L'existence d'une comorbidité psychiatrique et le poids des comorbidités somatiques (score de Charlson) étaient déterminés par le codage diagnostique. Le score de Charlson et la durée moyenne de séjour étaient comparés entre les patients avec et sans comorbidités psychiatriques. Au total, 8981 séjours étaient inclus (8001 patients), dont 1867 (21 %) avec comorbidité psychiatrique. Après ajustement sur l'âge, le sexe, le service et le diagnostic principal, le score de Charlson moyen était supérieur de 0,68 chez les patients avec comorbidités psychiatriques (p < 0,001) et leur durée moyenne de séjour était supérieure de 30 % après ajustement supplémentaire sur le score de Charlson (p < 0,001). Ces différences étaient similaires dans les analyses restreintes à chacune des dix catégories majoritaires de diagnostic principal. Les patients avec comorbidités psychiatriques sont nombreux en hospitalisation d'aval des urgences. Ils ont des durées de séjour plus longues, incomplètement expliquées par des comorbidités somatiques plus lourdes. Une attention particulière doit être portée à cette population vulnérable. Patients with psychiatric disorders suffer from a higher rate of somatic disorders than those without psychiatric disorder, often inappropriately managed. Our study aimed to describe patients with psychiatric comorbidity in post-emergency internal medicine units and to compare their length of hospital stay to patients without psychiatric disease. This French cross sectional study used the data warehouse of the greater Paris hospitals. It included, all patients hospitalized through the emergency department in 9 internal medicine departments during the year 2017. Psychiatric disorders and the burden of somatic disorders (Charlson score) were determined through diagnostic coding. Charlson score and hospital length of stay were compared between patients with and without psychiatric comorbidity. In total, 8981 hospital stays (8001 patients) were included, 1867 (21%) with psychiatric comorbidity. After adjusting for age, gender, hospital and main diagnosis, the Charlson score was on average 0.68 higher in the psychiatric comorbidity group (P < 0.001) and the length of hospital stay was 30% higher after further adjustment on the Charlson score (P < 0.001). These differences were consistent for each main diagnosis. Patients with psychiatric comorbidity are frequent in post-emergency internal medicine wards. They experience longer hospital stays, only partly related with a higher burden of somatic disorders. Special attention should be paid to this vulnerable population. [ABSTRACT FROM AUTHOR]