The course of non-infectious uveitis in pregnancy: a retrospective study of 79 pregnancies.

PURPOSE: The study aims to describe the course and management of non-infectious uveitis during pregnancy and postpartum period in European populations. METHODS: A retrospective observational study in two tertiary centers in France was performed. Pregnant patients during the follow-up of a non-infectious uveitis as well as those with new-onset uveitis were included. The medical records were analyzed with a systematic collection of the characteristics of the uveitis, the treatment and evolution of the uveitis, and the course of the pregnancy including obstetric complications. RESULTS: Seventy-nine pregnancies in 59 women were included: 48 patients (68 pregnancies) were followed for uveitis and 11 had a new-onset uveitis diagnosis. Most patients had idiopathic uveitis (32.2%) or sarcoid uveitis (27.1%). Among the patients followed for uveitis at the time of conception, there were 18 relapses (26.5%) requiring treatment escalation. Relapses occurred mainly in the two first trimester (n = 12) or during the postpartum period (n = 5) and were significantly associated with an active uveitis at the time of conception (OR = 9.2, 95% CI [1.57-48.4], p = 0.01). The characteristics of the new-onset uveitis were similar to those already existing before pregnancy. Obstetric complications occurred in 25 pregnancies (31.6%), mainly gestational hypertension and gestational diabetes. CONCLUSION: The frequency of non-infectious uveitis relapses decreases as pregnancy progresses, in agreement with data from other non-European studies. However, multidisciplinary monitoring should be advised, especially to uncontrolled patients at the time of conception.

[Parvovirus B19 infections in adults]. / Infection de l'adulte à Parvovirus.

Acute Parvovirus B19 (PVB19) infection is responsible for erythema infectiosum in children and non-specific polyarthralgias in immunocompetent adults associated with skin lesions and rarer manifestations (hepatic, neurological, cardiac or nephrological). In immunocompromised patients, cytopenias are more frequent and in some cases, viremia persists and is responsible for PVB19 chronic infection. PVB19 is responsible for pure red cell aplasia during chronic hemolytic diseases. Acute PVB19 infection is a differential diagnosis of some autoimmune diseases and has been suspected to be a trigger for some autoimmune diseases because of its ability to promote the emergence of autoimmune markers. Mechanisms of molecular mimicry, induction of apoptosis and activation of enzymes have been demonstrated, explaining in part the production of autoantibodies during infection. However, the demonstration of a causal relationship in the triggering of autoimmune disease remains to be done. This review provides a synthesis of the PVB19 infection clinical data in adults with a particular focus on these links with autoimmunity.

Murine typhus complicated by sHLH mimicking adult-onset Still's disease.

INTRODUCTION: Adult-onset Still's disease (AOSD) is a rare multisystemic disorder and a diagnostic challenge for physicians because of the wide range of differential diagnoses. Common features of AOSD and secondary hemophagocytic lymphohistiocytosis (sHLH) could favour diagnostic uncertainty, in particular in case of infection-related sHLH. OBSERVATION: A 61-year-old man was admitted to our internal medicine department for suspected AOSD. He reported a 2-week history of sudden onset fever, headaches, myalgia, sore throat, diarrhoea, and an erythematous macular rash of the trunk as well as petechial purpuric lesions on both legs on return from Reunion Island. Laboratory tests found cytopenia, hepatic cytolysis, hypertriglyceridaemia, and hyperferritinaemia. Hemophagocytosis was diagnosed on bone marrow aspiration in favour of the diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH). Subcutaneous anakinra (100mg) was initiated to treat sHLH with favourable course. Oral doxycycline was added 3days later because of atypical features for AOSD diagnosis such as diarrhoea, hypergammaglobulinaemia, and doubtful serologies for Rickettsia and Coxiella. Three weeks later, Rickettsia typhi serology was checked again and revealed an increase in IgG titer>4 times that confirmed the diagnosis of murine typhus. A diagnosis of murine typhus complicated by sHLH was retained, successfully treated by anakinra and doxycycline. CONCLUSION: Our observation shows that AOSD diagnosis has to be stringent due to the many differential diagnoses, particularly infection complicated by sHLH, which may be rare. It is important to consider murine typhus in patients returning from endemic areas, such as La Reunion or other tropical areas, when they present fever of unknown origin with non-specific clinical features. Moreover, this case illustrates the effectiveness of IL-1 blockers as a treatment for symptomatic sHLH without severity criteria, regardless of the aetiology.

Relevance of Brain MRI in Patients with Uveitis: Retrospective Cohort on 402 Patients.

AIM: To assess the diagnostic value of brain magnetic resonance imaging (bMRI) for the etiological diagnosis of uveitis and to establish predictive factors associated with its advantageous use. METHODS: Retrospective study on all patients with de novo uveitis who were referred to our tertiary hospital and who underwent a bMRI between 2003 and 2018. RESULTS: bMRI was contributive in 19 out of 402 cases (5%), among patients with a contributive bMRI, 68% had neurological signs. Univariate analysis established that neurological signs (p < .001), granulomatous uveitis (p = .003), retinal vasculitis (p = .002), and intermediate uveitis (p < .001) were all significantly associated with a contributive bMRI. Multivariate analysis confirms the significant association of neurological signs (p < .001) and intermediate uveitis (p = .01). CONCLUSION: bMRI appears to be a relevant exam in specific cases; intermediate/posterior uveitis or panuveitis accompanied by neurological signs, retinal vasculitis, or in patients older than 40, to rule out an oculocerebral lymphoma. ABBREVIATIONS: ACE: Angiotensin-Converting Enzyme; bMRI: Magnetic Resonance Imaging; CBC: Complete Blood cell Count; BMRI: Brain Magnetic Resonance Imaging; CT: Computerized Tomography; MS: Multiple Sclerosis; NS: Neurological Signs; OCL: Oculocerebral Lymphoma; RIS: Radiologically Isolated Syndrome.

[Spontaneous adrenal hematomas. Retrospective analysis of 20 cases from a tertiary center]. / Hématomes surrénaliens non traumatiques : série rétrospective de 20 cas.

INTRODUCTION: Spontaneous adrenal hemorrhages (AH) are a rare condition with no consensus about their management. METHODS: Patients were identified using the Medicalization of the Information System Program database, imaging software and a call for observations to internists, intensivists and obsetricians working at our institution. Adult patients whose medical records were complete and whose diagnosis was confirmed by medical imaging were included. RESULTS: From 2000 to 2007, 20 patients were identified, including 15 were women. The clinical onset of AH was non-specific. In five cases, AH occurred during pregnancy; four of them were unilateral and right sided. The etiology of the other fifteen (bilateral adrenal hemorrhage in 11) were as follows: antiphospholipid syndrome (n=8), heparin-induced thrombocytopenia (n=4), essential thrombocythemia (n=3), spontaneous AH due to oral anticoagulants (n=1), complication of a surgical act (n=3), and sepsis (n=3). In seven cases, two causes were concomitant. The diagnosis of AH was often confirmed by abdominal CT. An anticoagulant treatment was initiated in 16 cases. Ten of the eleven patients presenting with bilateral adrenal hematomas were treated using a long-term substitute opotherapy. One patient died because of a catastrophic antiphospholipid syndrome. CONCLUSION: The clinical onset of HS is heterogeneous and non-specific. The confirmatory diagnosis is often based on abdominal CT. The search for an underlying acquired thrombophilia is essential and we found in this study etiological data comparable to the main series in the literature. Adrenal insufficiency is most of the time definitive in cases of bilateral involvement.

Sarcoidosis diagnosed in the elderly: a case-control study.

BACKGROUND: Studies on sarcoidosis in elderly patients are scarce and none have specifically evaluated patients aged ≥75 at onset. AIM: We aimed to analyse the characteristics of patients with sarcoidosis diagnosed after 75 and to compare them with those of younger patients. DESIGN: Multicenter case-control study comparing elderly-onset sarcoidosis (EOS) with young-onset sarcoidosis (YOS) seen at Lyon University Hospitals between 2006 and 2018. METHODS: Using our institutional database, we included 34 patients in the EOS group and compared them with 102 controls from the YOS group in a 1:3 ratio. Demographic characteristics, medical history, clinical presentation, laboratory and imaging findings, sites of biopsies, histological analyses, treatments and outcomes were recorded using a comprehensive questionnaire. RESULTS: There were more Caucasians in the EOS group (94.1% vs. 59.8%; P < 0.001), who had significantly more comorbidities (mean, 3.1 ± 2 vs. 1.1 ± 1.6; P < 0.001). In the EOS group, there was less pulmonary involvement (26.5% vs. 49%; P = 0.022), less lymphadenopathy (2.9% vs. 16.7%; P = 0.041), no erythema nodosum (0% vs. 12.8%; P = 0.029) and no arthralgia (0% vs. 25.5%; P = 0.001). Conversely, uveitis was more common in the EOS group (55.9% vs. 20.6%; P < 0.001). Pathological confirmation was obtained significantly less frequently in the EOS group (67.7% vs. 85.3%; P = 0.023). Corticosteroid-related side effects were significantly more common in the EOS group (100% vs. 75.9%; P = 0.030). CONCLUSION: Epidemiology and clinical presentation of EOS differs from YOS, including more comorbidities and more uveitis. Elderly patients are more prone to corticosteroid side effects.

Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients.

BACKGROUND: East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies have described the clinical features and treatment of this disease, especially in France. METHODS: This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers. RESULTS: Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women. CONCLUSION: We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients' ethnicity.

[Adult-onset Still's disease complications]. / Complications de la maladie de Still de l'adulte.

Adult-onset Still's disease (AOSD), first described in 1971 by Bywaters, is a rare systemic auto-inflammatory disorder of unknown etiology, characterized by a symptomatic triad associating prolonged fever, polyarthritis and rash. The management of this disease has significantly improved since its first description, and, although the overall prognosis of the AOSD is good, with a low attributable mortality, below 3% (but up to 18% depending on the series), some rare complications are still possible, can be life-threatening and change the prognosis of the disease. A literature search was performed to review AOSD's complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiovascular (pericarditis, myocarditis, HTAP) or pulmonary complications, neurologic, renal complications, and AA amyloidosis. For most of AOSD-related complications, corticosteroids remain the first-line treatment, in association with supportive care measures in case of severe complications. In case of inadequate response, multidisciplinary care with concil from a referral center is advised, and IL-1 or IL-6 blockers, but also ciclosporine, are the molecule to use in second intention.

[JAK inhibitors: Perspectives in internal medicine]. / Les inhibiteurs de JAK : perspectives pour la médecine interne.

In the past ten years, the better understanding of the pathophysiological mechanisms underlying inflammatory and autoimmune diseases has led to the emergence of many targeted therapies. Among them, the Janus kinase inhibitors are acting upstream in the inflammatory cascade of several key cytokines in disorders such as rheumatoid arthritis, ulcerative colitis or psoriasis. At the moment, these three diseases represent the only indications validated by the FDA and the EMA of the use of JAK inhibitors apart from hematology. Preclinical data and therapeutic trials indicate their efficacy in other autoimmune or inflammatory conditions, such as lupus, dermatomyositis, ankylosing spondylitis, sarcoidosis and giant cell arteritis. This review provides a summary of current use and advancement of knowledge in the use of JAK inhibitors in pathologies faced by internists.

Clinical and etiologic characteristics of de novo uveitis in patients aged 60 years and above: experience of a French tertiary center.

PURPOSE: To describe the characteristics of de novo uveitis in patients ≥ 60 years old. METHODS: Retrospective review of patients with uveitis followed in our tertiary center over a 14-year period. Patients aged 60-70 years and patients aged > 70 years were compared. RESULTS: A total of 283/1044 (27.1%) patients with uveitis were ≥ 60 years of age. Idiopathic uveitis (36.1%) and sarcoidosis (31.5%) were the most frequent etiologies. Sarcoidosis was significantly more frequent (31.5% vs. 13.7%, p < 0.0001) after the age of 60 years. Intraocular lymphoma (5.0% vs. 1.1%) and herpes virus infection (5.0% vs. 0.9%) were also more common in this age group, unlike HLA B27-related uveitis and spondyloarthritis (4.6% vs. 14.9%). Pure ophthalmologic entities: birdshot retinochoroidopathy (2.8%) or Fuchs uveitis (0.4%), were rare in patients ≥ 60 years of age and Posner Scholssman, Pars planitis, White dots syndrome, Behçet's disease, and Multiple Sclerosis were never reported. In patients > 70 years old, idiopathic uveitis (41.1% vs. 31.7%) and presumed sarcoidosis (56.5% vs. 25.6%) were more frequent than in the 60-70-year age group. CONCLUSION: In our center, sarcoidosis is the leading cause of non-idiopathic uveitis in older patients. Idiopathic uveitis and other entities account for less than two-thirds of cases. Ophthalmologic entities are rare after 60 years of age. We also report for the first time the characteristics of uveitis after 70 years of age.

[Interleukin-1, inflammasome and autoinflammatory diseases]. / Interleukine-1, inflammasome et maladies auto-inflammatoires.

Interleukin-1 is a major cytokine of innate immunity and inflammation. It exerts various systemic effects during the inflammatory response, such as fever induction, thrombopoiesis and granulopoiesis, or leukocyte recruitment. Its involvement has been demonstrated in many inflammatory-mediated diseases, such as diabetes or gout. Moreover, interleukin-1 plays a pivotal role in some autoinflammatory diseases, such as cryopyrinopathies or familial Mediterranean fever. In these diseases, a constitutional defect of the inflammasome, a protein complex responsible for the activation of interleukin-1, explains the hypersecretion of interleukin-1. Other autoinflammatory diseases have a more complex pathophysiology involving deregulation of the interleukin-1 pathway, upstream or downstream of the inflammasome, or through more complex mechanisms. In this review, we are detailing the synthesis, the activation, the signalling, and the regulation of interleukin-1. We then describe the autoinflammatory diseases or related-diseases where the pathological role of interleukin-1 has been demonstrated.

[Opportunistic infections and sarcoidosis]. / Les infections opportunistes au cours de la sarcoïdose.

Opportunistic infections (OI) are uncommon in sarcoidosis (1 to 10%) and mostly occur in patients with previously diagnosed disease or can rarely be the presenting manifestation. The most common OIs are, in descending order: aspergillosis, cryptococcosis, and mycobacterial infections. Treatment with corticosteroids is the most frequent risk factor for OI occurrence during sarcoidosis but immunosuppressive drugs and therapy with anti-TNFα are also risk factors. Overall, clinical presentation, treatment, and outcome are identical to that occur in other conditions complicated with the occurrence of OIs. However, some atypical presentations of OIs can mimic sarcoidosis exacerbation and misdiagnosis may lead clinicians to increase immunosuppression, causing worsening of the OI. The meticulous collection of patient's history along with factors differentiating OI from sarcoidosis exacerbation is key factor to optimally manage these patients.

[Clinical efficacy of eculizumab as treatment of gemcitabine-induced thrombotic microangiopathy: A case report]. / Efficacité de l'éculizumab comme traitement de la microangiopathie thrombotique induite par la gemcitabine : à propos d'un cas.

INTRODUCTION: Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest. CASE REPORT: A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900 mg per week 4 times, then 1200 mg every 2 weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7 intravenous injections. CONCLUSION: Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy.

[Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update]. / Données actualisées sur la physiopathologie, les phénotypes et les traitements de la maladie de Still de l'adulte.

Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.