[Profiles of autoimmune myositis with or without pulmonary involvement: A retrospective single-center study of 40 patients]. / Profils des myosites auto-immunes avec ou sans atteinte pulmonaire : une étude monocentrique rétrospective de 40 patients.

INTRODUCTION: Idiopathic inflammatory myopathies (IMM) are rare diseases with clinico-biological heterogeneity. Pulmonary involvement is frequent and associated with some distinctive manifestations. The aim of this study was to describe the clinico-biological profile of patients with autoimmune myositis with and without pulmonary involvement. METHODS: This retrospective descriptive study included patients with idiopathic inflammatory myopathies and a positive antibody test performed at Grenoble Alpes University Hospital between 2010 and 2020. RESULTS: Forty patients were included, the majority were women. The anti-Jo1 autoantibody was the most frequently found (37.5%). The prevalence of pulmonary involvement was 70%. Mechanics' hands and Raynaud's syndrome were the extra-respiratory signs significantly more present in the group with lung involvement (P <0.05), in contrast to creatine kinase levels which were lower in this group (P <0.05). Glucocorticoids and rituximab were significantly more often used in the group with lung involvement (P <0.05). The 5-year survival rate was 76.2% in patients with lung involvement and 100% in patients without lung involvement (P=0.50). CONCLUSION: We report a high prevalence of lung involvement probably explained by the presence of many patients with anti-synthetase syndrome. Our study highlights a lower severity of muscle involvement in myositis patients with lung disease, which deserves to be confirmed in a larger study.

[Assessment of the Internal Medicine Multidisciplinary Team meetings at the Grenoble University Hospital]. / Évaluation des réunions de concertation pluridisciplinaire de médecine interne au CHU Grenoble Alpes.

INTRODUCTION: Multidisciplinary team (MDT) meetings purpose is to optimize the disease management regarding state of science. While cancer MDT has proven its effectiveness, this is not yet the case with internal medicine MDT. METHODS: We performed a descriptive monocentric retrospective study. Data were collected from 247 MDT meeting reports which took place at the Grenoble University Hospital over a 5 years period. We investigated the data related to patient, MDT features, and decision-making process and reporting. Discussions were classified as diagnostic and/or therapeutic. RESULTS: Three specialties, among which at least internal medicine, attended to meetings. While 12% of cases were considered as "complex", a specialist opinion was required in 18% of diagnostic discussions. With regards to therapeutic discussions, 35% were supported by guidelines, 50% of therapeutic implementation involved innovating and expensive drugs, with off-label prescription in 75% of them. The decision-making process was described in 6% of the reports. Treatment recommendations were actually implemented in 72% of the patients. CONCLUSION: MDT meetings in Internal medicine meets a real need of physicians, in the ultimate interest of the patient. A prospective analysis would be interesting for a better definition of the evaluation criteria of these MDT meetings, meeting the physicians' needs, in patient management best interest. Prospective analyses are needed to better define MDT meetings assessment criteria.

[Severe MDA5 dermatomyositis associated with cancer and controlled by JAK inhibitor]. / Dermatomyosite à anticorps anti-MDA5 sévère associée à un cancer et contrôlée par inhibiteur de JAK.

Dermatomyositis is an idiopathic inflammatory myopathy with various clinical and serological profiles, including poor prognosis forms for which aggressive immunosuppressive treatment is warranted. We report the case of a 60-year-old woman referred to our hospital for an anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis (MDA5 DM) with rapidly progressive interstitial pneumonia, typical cutaneous features and muscular impairment. Treatment with high-dose methylprednisolone, cyclophosphamide and gamma globulin was performed, but the patient remained corticodependant. Blood detection of positive interferon signature justified the administration of an anti-JAK1/2, leading to the clinical remission and the regression of the interferon signature. After 12 months of follow up, a small cell carcinoma was discovered, raising the question of a paraneoplastic syndrome, for which the most recent datas are quite reassuring for this kind of MDA5 DM. The presentation of this case is of twofold interest: describing one of the first report of successful treatment of intereronopathy MDA5 DM with ruxolitinib and highlighting an association with a cancer, which is not expected for this phenotype of dermatomyositis.

[Amoebosis: May sexual transmission be an underestimated way of contamination?] / Amibiase : au cours de rapports sexuels, un mode de transmission sous-estimé ?

INTRODUCTION: Amoebiasis is a cosmopolitan disease and the third most deadly of parasitic diseases. Entamoeba histolytica is the only one to be pathogenic. Its transmission is not only related to the faecal peril but also sexual, with cases described among men who have sex with men. A case of unusual sexual transmission is described in this article, aiming to discuss the impact of these ways of transmitting amoebiasis on patient management. CASE REPORT: We describe the case of an amebic liver abscess in a 27-years-old man who did not travel in endemic areas. After patient interrogation, it seems that the contamination mode was sexual, related to a heterosexual relationship with a new female partner 4 months before the diagnosis. HIV and hepatitis B serologies were negative. CONCLUSION: The diagnosis of amoebiasis should be suspected in case of dysentery or liver abscess even if there is no history of travel in endemic areas or of sexual intercourse between men.

[Use of hydroxychloroquine and prednisone in the presence of serum autoimmunity in female infertility]. / Utilisation de l'hydroxychloroquine et de la prednisone en présence d'une auto-immunité sérique dans l'infertilité féminine.

OBJECTIVE: Presence of non-specific autoimmunity (antinuclear antibodies without antigenic specificities and/or antiphospholipid antibodies without criteria of antiphospholipid syndrome) seems to be associated with unexplained female infertility. The objective is to study the characteristics of patients who undergone treatment for non-specific antibodies in Medically Assisted Procreation (MAP). METHODS: Ten patients were prospectively followed at MAP center of Grenoble University Hospital. Patient characteristics were collected and evaluated. All patients had a consultation in internal medicine unit as well as an autoimmune assessment (antinuclear antibodies, APL especially) in search of defined autoimmune disease (exclusion criterion). The treatments undertaken were at clinician' discretion. RESULTS: One patient received quadritherapy (heparin, platelet antiaggregant, prednisone and hydroxychloroquine), 5 received triple therapy, 3 had dual therapy, and one patient had prednisone only. The 10 patients had a pregnancy under treatment, 8 of which were completed without complications. The control of autoimmunity under treatment appears to show a decrease in serum antibody levels. Tolerance was good (delayed hypersensitivity to hydrochloroquine resulted in discontinuation of therapy in only one patient). CONCLUSION: The presence of non-specific serum autoimmunity in a context of infertility appears to be pathogenic and immunomodulatory treatments are clinically and/or biologically effective. A prospective and interventional study with a larger number of patients is needed to assess the efficacy of such treatments in patients with unexplained infertility.

Hereditary angioedema with normal C1 inhibitor and factor XII mutation: a series of 57 patients from the French National Center of Reference for Angioedema.

Hereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene. Fifty-seven patients were identified from 24 different families. In most cases they were young women (mean age at diagnosis: 31 years, mean age at first symptom: 21 years, female/male ratio: 76%). Twenty-one per cent of the patients experienced angioedema attacks only during pregnancy or when on oestrogen contraception. Sixty-three per cent had attacks at all times, but they were more severe during these same periods. Male carriers of the mutation were more frequently asymptomatic than females (P = 0·003). C1-INH concentrate and icatibant were both effective for treating attacks. The prophylactic use of tranexamic acid led to a 64% decrease in the number of attacks. This is one of the largest series reported of HAE patients with FXII mutation. The therapeutic management appeared to be identical to that of HAE with C1-INH deficiency.

Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ±â€Š14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ±â€Š1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

Idiopathic histaminergic angioedema without wheals: a case series of 31 patients.

Idiopathic histaminergic acquired angioedema (IH-AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell-mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH-AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH-AAE). Thirty-one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH-AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti-histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three-fourfold in 16·1% (five patients). IH-AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1-anti-histamines may be necessary to control symptoms.

[Macrophage activation syndrome secondary to tocilizumab: Myth or reality?]. / Syndrome d'activation macrophagique sous tocilizumab : mythe ou réalité ?

INTRODUCTION: Some authors have reported macrophage activation syndrome (MAS) secondary to infusion of tocilizumab, a monoclonal antibody that blocks interleukin-6 (IL-6). The pathophysiology of MAS is however linked to uncontrolled activation of innate immunity, mediated in part by IL-6. We conducted a study for macrophage activation biomarkers in a cohort of patients treated with tocilizumab. RESULTS: Twenty-seven patients were included prospectively in our center. Levels of neutrophils, platelets, CRP and fibrinogen were lower at the end of treatment than at initiation (P<0.05); other biomarkers were stable. There was neither clinical sign of SAM nor hemophagocytosis in myelogram. CONCLUSION: Laboratory abnormalities are related to direct blockade of IL-6 by tocilizumab and decrease hepatic protein synthesis. Tocilizumab is not responsible for MAS and associations described are more likely to be related to the autoimmune underlying disease, rather than treatment.

[Management of thrombotic thrombocytopenic purpura in two French centers: A series of 27 patients]. / Prise en charge du purpura thrombotique thrombopénique dans deux centres français : à partir de 27 patients.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems associated with multiple organ dysfunctions and often severe disease course. METHODS: In order to enhance the understanding of TTP, the clinical features, laboratory characteristics, treatment and outcome of 27 patients with TTP were retrospectively analyzed and investigated in two centres (Annecy and Grenoble). RESULTS: All the 27 patients presented with haemolytic anemia and decreased platelet counts. Eight patients had fever. Thirteen patients had kidney involvement including proteinuria and renal function abnormalities. Eighteen patients had neurological manifestations. Association of the 5 characteristic features of TTP was rarely found (11%) which could lead to diagnosis delay. The von Willebrand factor-cleaving protease (ADAMTS13) activity was less than 10% in all patients. At the same time, plasma ADAMTS13 inhibitors were detected in 20 patients out of the 27. After treatment with plasma exchange, glucocorticoid and rituximab, 23 patients (85%) achieved complete remission. Four patients died, in which two cases were secondary to late diagnosis. CONCLUSION: TTP is a thrombotic microangiopathy often associated with multiple organ dysfunctions. Salvage therapy, based on some studies experiences and discussed with the Reference Center, could help getting answers in most severe cases. Awareness of physicians is an important step to further limit any delay in medical care, and to further improve the prognosis of patients with TTP.

Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients.

OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).

[Severe pneumonia due to cytomegalovirus in chronic obstructive pulmonary disease]. / Pneumopathies sévères à Cytomégalovirus et broncho-pneumopathie chronique obstructive.

UNLABELLED: Severe pneumonia due to cytomegalovirus in chronic obstructive pulmonary disease. INTRODUCTION: We describe two cases of immunocompetent patients with chronic obstructive pulmonary disease (COPD) who developed severe cytomegalovirus (CMV) pneumonia. The clinical and radiological context and CMV replication in broncho-alveolar lavage suggested a diagnosis of CMV pneumonia. CASE HISTORIES: We report two cases in patients with moderate chronic obstructive pulmonary disease not treated with long-term steroid therapy who developed bilateral pneumonia with hypoxaemia. The only pathogen identified was CMV with replication of the virus in the broncho-alveolar lavage. Investigation failed to detect any associated immune deficiency. CONCLUSION: Severe cytomegalovirus pneumonia could be encouraged by the existence of chronic obstructive pulmonary disease due to local inflammatory changes.