Familial lupus in Tunisia: a series of 14 families.

The relatively high prevalence of systemic lupus erythematosus (SLE) in familial cases supports genetic susceptibility to this disease. Although many advances have been made in the identification of new genes implicated in lupus pathogenesis, to date, there has been no large study of familial SLE. We report what we believe to be the first study of familial SLE in the North African population. The objectives of this study were to determine the main clinical and laboratory features of familial lupus and to compare them to sporadic lupus in a population of Tunisian patients. Fourteen families in which the diagnosis of lupus could be verified in at least two relatives were included in the study. All patients fulfilled four or more criteria defined by the American College of Rheumatology. Twenty-seven patients (23 females and 4 males) with familial SLE among a cohort of 253 SLE patients were found, resulting in a frequency of 10.67%. No significant differences were found between familial SLE cases and their controls in terms of sex ratio, mean age at onset and clinical and serological manifestations, which is consistent with the results of other series reported in the literature. Our results support the importance of carrying out more genetic studies within families of SLE in order to have a better understanding of the genetic and molecular mechanisms of the disease.

Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.

Toll-like receptor (TLR) genetic polymorphisms may modify their expression causing inflammatory disorders and influencing both susceptibility and severity of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene polymorphisms are implicated in the susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions and distributions in renal LN patients' biopsies. The frequencies of two SNP in the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among them 37 LN patients) and in 200 matched controls by polymerase chain reaction-restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5 expressions were assessed by reverse transcription (RT)-PCR and immunohistochemistry carried on LN renal biopsies compared to healthy renal tissue. A significant genotypic and allelic association was revealed between TLR-9-rs352140 and both SLE and LN (P < 0·05). The TLR-9 transcript level was significantly higher in LN biopsies compared to control (P < 0·05). This increase was observed histochemically in the tubulointerstitial compartment. TLR-9 was detectable in LN glomeruli patients but not in normal control glomeruli. No allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T allele and the TT genotype were raised significantly in the LN group (P < 0·05). A significant increase in TLR-5 gene expression in LN biopsies, which contrasted with normal kidneys (P < 0·05), was confirmed by an intense and diffuse staining for TLR-5 only in LN tubules (P < 0·05). Our data show that TLR-5 and TLR-9 are susceptible genes to LN and that their expression is dysregulated in LN patients' kidneys, supporting a role of these mediators in the pathogenesis of LN.

Hydroxychloroquine-induced hyperpigmentation in systemic diseases: prevalence, clinical features and risk factors: a cross-sectional study of 41 cases.

Introduction Hydroxychloroquine is an antimalarial agent widely prescribed in internal medicine, rheumatology and dermatology. Its use can be complicated by various side effects including skin pigmentation. Objectives The aim of the study is to review epidemiological, clinical features and risk factors of hydroxychloroquine-induced pigmentation. Materials and methods We performed a cross-sectional study conducted over a period of 5 months. During this period, patients who had been treated with hydroxychloroquine for over 6 months, in the internal medicine department, underwent a complete dermatological examination. All patients completed a structured questionnaire to collect demographic data, dosage and treatment duration of hydroxychloroquine, other drug intake, hydroxychloroquine indication, and presence of pigmentary changes on the skin, nail, hair, and mucosa. Results A total of 41 patients (38 women and 3 men) were included in the study. The mean age was 39.2 ± 15.4 years. The hydroxychloroquine was indicated for systemic lupus erythematosus in 73.2%, dermatomyositis in 12.2%, rheumatoid arthritis in 9.8%, actinic lichen and sarcoidosis each in 2.4%. Cutaneous pigmented lesions were found in 21 cases (51%), mucous pigmentation in 5 cases (12%) and nail pigmentation in 1 case (2.5%). In 12 of 41 (29%) of the hydroxychloroquine users, we conclude a hydroxychloroquine-induced pigmentation. There were 11 women and one man with a mean age of 43 years and all of them were systemic lupus erythematosus patients. Pigmented lesions were located on the lower limbs in seven cases, the face in two cases, lips in two cases and the gum in two cases. Pigmentation appeared after a median duration of hydroxychloroquine treatment of 32 months with a median cumulative dose of 361 g. Overall, two patients reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas following microtrauma. Significant association was found between hydroxychloroquine-induced pigmentation and treatment with oral anticoagulants and/or antiplatelet agents ( p = 0.03). Conclusion Our systematic examination of patients demonstrated that hydroxychloroquine-induced pigmentation is not rare. The imputability of hydroxychloroquine in the genesis of this discoloration is difficult to establish. Our study supports the hypothesis that ecchymosis, platelet antiaggregants and oral anticoagulants may be the main predisposing factors to hydroxychloroquine-induced pigmentation.

Association study of MICA-TM and HLA-class I polymorphism with uveitis in South Tunisian population.

BACKGROUND: Uveitis refers to intraocular inflammation. The pattern of uveitis is largely influenced by a multitude of factors including genetic background. AIM: The purpose of our study was to identify the association between the polymorphism of the transmembrane region of MICA (MICA-TM) and uveitis in Tunisian patients with intraocular inflammation. PATIENTS AND METHODS: A total of 79 Tunisian patients and 123 healthy controls were enrolled in our study. HLA-class I phenotyping was performed by microlymphocytotoxicity complement dependent and MICA-TM was genotyped by a semiautomatic fluorescent-labelled PCR method, amplicons were analysed on ABI Prism 310 genotyper. Comparisons of allele frequencies between patients and controls, and between patients' subgroups were performed using SPSS 20.0. RESULTS: In our 79 patients, HLA-B27 showed a significant increased frequency when compared with healthy controls (P=0.003, 7.88 [95% IC=2.17-28.65]). The association was more significant when considering idiopathic anterior uveitis (P=0.00002, OR=11.65 [95% IC=3.06-45.17]). No MICA allele was significantly increased in uveitis groups compared to controls. In the idiopathic uveitis group, MICA-A4 was associated with late age of onset of disease (P=0.04). HLA-B51 and MICA-A6 were associated respectively with severe tyndall (P=0.008) and with the presence of synechiae (P=0.007). CONCLUSION: Some clinical features of uveitis may be influenced by specific MICA-TM alleles. In our South Tunisian population, MICA plays a disease modifying role, rather than being an important gene in the susceptibility for developing of uveitis.

Association study of MICA gene polymorphisms with rheumatoid arthritis susceptibility in south Tunisian population.

The aim of this study was to investigate the role of major histocompatibility complex (MHC) class I chain-related gene A (MICA) polymorphisms, important in natural killer (NK) cell function, in patients with rheumatoid arthritis (RA). A transmembrane (TM) alanine-encoding GCT repeats, termed A4, A5, A5.1, A6 and A9 in the MICA gene, and single-nucleotide polymorphisms (SNPs): the Met129Val polymorphism (rs1051792) and the nonsynonymously coding SNP (rs1051794) were genotyped in 142 patients with RA and 123 unrelated healthy individuals using, respectively, PCR fluorescent method, nested PCR-RFLP and allele specific PCR (ASP). Association was assessed based on the χ2 test, genotype relative risk (GRR) and odds ratio (OR) with 95% confidence intervals (CIs). Our results show a trend of association of the different MICA genotypes G/G, G/A and A/A (P = 0.029) which did not attain the significance after Bonferroni's correction (pc = 0.08). Although, we revealed a significant association of the genotype A/A of MICA-250 in patients with RA compared to healthy controls (pc = 0.033). In contrast, no significant differences between alleles and genotypes frequencies were found either with MICA-TM or MICA met129 val (P > 0.05) in our sample. Moreover, stratification of patients with RA according to clinical and immunological data for the different polymorphisms studied shows a significant association of both MICA-250 G allele (pc = 0.0075) and MICA-250 GG genotype (pc = 0.008) and both allelic (val) (pc = 0.021) and genotypic (val/val) distribution (pc = 0.0095) for MICA met129 val in the RF-positive subgroup compared to RF-negative patients with RA. In contrast, we found a strong association of the MICA-TM A9 allele in RF-negative patients with RA (pc = 0.0003). This study indicates the involvement of the MICA-250 polymorphism in the genetic susceptibility and severity to RA and suggests that variations in MICA-TM and MICA met129 val may have an effect on RA severity in our south Tunisian sample.

Bilateral ptosis as a presenting feature of primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report.

Pachydermoperiostosis is a rare hereditary disorder, which affects both bones and skin. It is characterized by a combination of dermatologic changes (pachydermia or thickening of the skin) and rheumatologic manifestations (periostosis and finger clubbing). Eyelid ptosis which is caused by thickened eyelids (blepharoptosis) is a less common symptom. We report the case of a patient with a complete form of pachydermoperiostosis with bilateral ptosis as presenting feature.

Multiple cranial nerve palsy revealing hypertrophic pachymeningitis with positive myeloperoxidase-antineutrophil cytoplasmic antibody.

Pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. Here, we report the case of a 60-year old man who had a progressive sensorineural hearing loss, visual disturbance and others cranial nerve involvement with an accompanying headache over several months. Brain magnetic resonance imaging showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody titers. After empirical steroid and cyclophosphamide therapy, the neurological problems were partially improved. Therefore, in the case of atypical sensorineural hearing loss accompanied by cranial nerve palsy or headache, pachymeningitis should be considered in the differential diagnosis.

Screening for toxic retinopathy due to antimalarial drugs in Tunisia.

INTRODUCTION: Toxic retinopathy due to antimalarial drugs is characterized by structural anomalies associated with severe, irreversible visual loss. The advantage of ophthalmologic monitoring is to detect these anomalies at an asymptomatic, preclinical stage, so that the recommended dose can be adjusted before the ophthalmologic manifestations appear. MATERIAL AND METHODS: Cross-sectional study carried out in the ophthalmology department of Habib Bourguiba University Hospital, Sfax, between August 2016 and February 2018. All patients treated in the internal medicine department of Hedi Chaker University Hospital with synthetic antimalarial drugs for at least 1 year were included. A complete ophthalmologic examination and specialized retinal testing (fundus autofluorescence, 10-2 automated visual field and swept source OCT) were performed for all patients. RESULTS: Fifty-six patients treated with antimalarial drugs were analyzed. The main indication was systemic lupus erythematosus (80.3%). Fifty-three patients (94.64%) were treated with hydroxychloroquine, and 3 patients (5.4%) with chloroquine. Thirteen patients (23.2%) exhibited signs of retinal toxicity, with fundus autofluorescence alterations in 8% of cases, fundus anomalies in 12.5% of cases, 10-2 automated visual field defects in 16% of cases, and SS-OCT alterations in 23.2% of cases. We did not find a statistically significant association between retinal toxicity, weight, age, sex and renal insufficiency (p values of 0.8, 0.6, 0.66 and 0.7 respectively). Furthermore, the association between the cumulative dose and retinal toxicity was statistically significant (p=0.02). The prevalence of toxic retinopathy was identified as 5% at 5 years, 25% at 10 years and 70% at 20 years. CONCLUSIONS: A better understanding of the risk factors for retinal toxicity is necessary when prescribing synthetic antimalarial drugs. Screening should be systematic. It should be based on a combination of functional and anatomic tests. The frequency of screening depends on the associated risk factors.

Clinical implications and prognostic significance of thrombocytopenia in Tunisian patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to determine the role of thrombocytopenia in terms of disease manifestations, disease activity and prognostic impact in a cohort of Tunisian systemic lupus erythematosus (SLE) patients. METHODS: The charts of 182 SLE patients diagnosed between 1996 and 2009 were retrospectively reviewed. The clinical manifestations, immunological profiles, disease activity, SLE relapses and survival rate at the time of follow-up were recorded. RESULTS: Thrombocytopenia (<100,000/mm(3)) and severe thrombocytopenia (<20,000/mm(3)) was observed in 19.2% and 4.4%, respectively. Hemorrhagic manifestations were observed in 11 patients (31.4%). Thrombocytopenia was significantly associated with splenomegaly, renal disorders, neurologic manifestations, arterial thrombosis, leucopenia, low C3 level at SLE diagnosis, SLE relapses and infectious complications. Using multivariate logistic regression, thrombocytopenia was independently associated with splenomegaly (odds ratio [OR] = 9.36, p = 0.001), neurologic manifestations (OR = 4.6, p = 0.006) and renal disease (OR = 4.15, p = 0.02). By multivariable Cox proportional hazard regression analyses, thrombocytopenia was associated with the occurrence of mortality after adjusting for variables known to influence it (hazard ratio [HR] = 1.79, p = 0.045). The cause of death was unrelated to hemorrhagic complications in all patients. CONCLUSION: Our results, concerning North-African SLE patients, confirm the findings of previous studies which suggest that thrombocytopenia correlates with more severe disease and has a negative impact on the survival of lupus patients.

Association study of CARD8 (p.C10X) and NLRP3 (p.Q705K) variants with rheumatoid arthritis in French and Tunisian populations.

The objective of the study was to investigate the association of caspase activating and recruitment domain 8 (CARD8) and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) polymorphisms with rheumatoid arthritis (RA) in Tunisian and French populations. CARD8 (c.30T>A, rs2043211) and NLRP3 (c.2113C>A, rs35829419) single nucleotide polymorphisms (SNPs) were genotyped in 100 French RA trio families and 141 Tunisian patients with RA and 191 unrelated healthy controls, using TaqMan(®) allelic discrimination assay. The genetic analyses for the association and linkage in French families were performed using the comparison of allelic frequencies (AFBAC), the genotype relative risk (GRR) and the transmission disequilibrium test (TDT). Data for case and control samples were analysed by chi-square-test, GRR and odds ratio (OR). No significant differences between alleles and genotypes frequencies were detected in French trio and Tunisian patients with RA and controls, either with CARD8 or with NLRP3 SNPs both in French and in Tunisian populations. Moreover, stratifying patients according to the presence of rheumatoid factor (RF), anti-cyclic peptides antibodies (ACPA), erosion, nodules, other autoimmune disease or HLA-DRB1*04-positive subgroups did not show any significant association with CARD8 or NLRP3 (P ≥ 0.05). This study suggests that variations in the innate immunity genes CARD8 (p.C10X) and NLRP3 (p.Q705K) have no effect on RA susceptibility either in the Tunisian or in the French population.

[Association of HLA class I antigens with Behçet disease in South Tunisia]. / Étude d'association des antigènes HLA classe I avec la maladie de Behçet dans le Sud tunisien.

PURPOSE: To study antigen HLA class I association with different clinical forms of Behçet's disease in South Tunisian population. PATIENTS AND METHODS: We retrospectively reviewed 129 clinical case patients. All of the patients fulfilled the criteria of the international study group for Behçet's disease, and were followed at the department of internal medicine of the university hospital of Sfax. HLA class I phenotyping was performed by microlymphocytotoxicity complement dependent for our 129 patients and for 123 healthy controls. We used the program SPSS 11.0 to analyse clinical data and to compare HLA class I antigen distribution between these two populations. RESULTS: The study group concerned a total of 129 patients (81 males and 48 females). The mean age at disease onset was of 32 years. HLA-B51 antigen was the only antigen significantly more frequent among patients (24.81%) than controls (9.76%, p=0.002). HLA-B44 was significantly more frequent among patients having familial history of recurrent buccal aphthosis or Behçet disease. HLA-A11 antigen was associated with early disease onset, and HLA-A1 was negatively associated with severe form of the disease (neurological, vascular or ocular manifestations). CONCLUSION: Our study confirmed the HLA-B51 association with Behçet disease. Nevertheless, B51 frequency in South Tunisian patients was lower than that found in other studies regardless of the clinical manifestation.

Optic neuropathy as a presenting feature of systemic lupus erythematosus: two case reports and literature review.

Systemic lupus erythematosus (SLE) may affect the eyes and/or visual system in up to a third of patients; however, optic nerve involvement has been rarely reported. SLE presenting as optic neuropathy is exceptional. We report two new cases of optic neuropathy as a presenting feature of SLE. The first patient presented with an ischemic optic neuropathy and antiphospholipid antibodies, and the second presented with optic neuritis. A literature review for previous cases of SLE presenting as optic neuropathy was performed. Early diagnosis of SLE-associated optic neuropathy is warranted and leads to a better prognosis.

Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders.

OBJECTIVES: The signal transducer and activator of transcription 4 (STAT4) gene localised on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. The aim of this study was to investigate the role of the STAT4 gene in susceptibility to rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) in Tunisian case control studies. METHODS: Genotyping of STAT4 rs7574865 single nucleotide polymorphism (SNP) was performed in 140 patients affected with RA, 159 patients affected with AITDs and 200 healthy controls using TaqMan® allelic discrimination assay. Data were analysed by χ2-test, genotype relative risk (GRR) and odds ratio (OR). RESULTS: Our results revealed that frequencies of the T allele and the T/T genotype were significantly higher among RA patients compared to controls (p=0.008; p=0.003, respectively). However, no significant associations with the risk of autoimmune thyroid diseases were detected. Moreover, the stratification of RA patients subgroups revealed a significant association of both T allele and T/T genotype in patients presented erosion (p=0.003; p=0.004, respectively) as well as anti-cyclic peptides-negative RA (ACPA-) (p=0.002; p=0.0003, respectively). Furthermore, genotypic association was found according to the absence of rheumatoid factor antibody (RF) (p=0.0014). But, no significant differences in allele and genotype frequencies of STAT4 rs7574865 polymorphism were detected according to the presence of another autoimmune disease, nodules and in HLA-DRB1*04 and HLA-DRB1*0404 positive subgroups. CONCLUSIONS: Our results support involvement of the STAT4 gene in the genetic susceptibility to RA but not to AITDs in the Tunisian population.

Enhanced reactivity to malondialdehyde-modified proteins by systemic lupus erythematosus autoantibodies.

OBJECTIVE: Evaluation of the reactivity of autoantibodies of systemic lupus erythematosus (SLE) patients directed against malondialdehyde (MDA)-modified catalase, superoxide dismutase (SOD), and different Hep2 protein fractions (hydrophobic, hydrophilic, and nuclear). METHOD: Thiol groups and MDA-protein adducts were first assessed among 65 SLE patients and 60 healthy controls. Then, the reactivities of SLE immunoglobulin (Ig)G autoantibodies towards MDA-modified and unmodified proteins were compared using a standard enzyme-linked immunosorbent assay (ELISA). RESULTS: An increase in the levels of MDA-modified proteins and a decrease in the concentration of thiol groups among SLE patients (p < 0.05) were observed. IgG circulating autoantibodies in the sera of SLE patients exhibited a significant enhanced reactivity (p < 0.05) against catalase and SOD-modified proteins. The same data were observed in the different protein fractions extracted from cultured cells (p < 0.05). CONCLUSION: These data reinforce the role of oxidative stress and especially lipid peroxidation products in the progression of SLE disease.

[Optic neuropathy in Behçet's disease: a series of 18 patients]. / Les neuropathies optiques au cours de la maladie de Behçet : à propos de 18 cas.

INTRODUCTION: The objective of this study was to analyse the incidence and the main characteristics of optic neuropathy in Behçet's disease. METHODS: A retrospective review of a well-documented population of 376 Tunisian patients with Behçet's disease was performed. All patients fulfilled three or more criteria defined by the International Study Group for Behçet's Disease. The diagnosis of optic neuropathy was based on the clinical examination, visual field, visual evoked potentials and retinal angiography. RESULTS: Eighteen patients (4.7 %) presented an optic nerve involvement. The mean age at presentation of these patients (10 men and nine women) was 39.11+/-12.9 years (range 17 to 73). The mean vision at presentation was 4.2/10+/-2.9, the vision was less than 1/10 in 34.5 % of eyes. The optic neuropathy was anterior in 89 % cases (26 eyes, 90 %), posterior in one case (2 eyes, 7 %); one patient (1 eye, 3 %) presented an optic atrophy. The optic neuropathy was associated with other ocular lesions in 13 cases (72.2 %). It was an inflammatory neuropathy in four cases (22.3 %) and a stasis papilledema complicating a benign intracranial hypertension in five cases (27.8 %). Corticosteroids were administrated in 17 cases (94.4 %), cyclophosphamide in six cases (33.3 %) and anticoagulant therapy in one patient (5.6 %). After a mean duration of 79 months (range: three months to 12 years), a third of the patients (8 eyes, 27.5 %) have a visual loss. CONCLUSION: Optic neuropathy is a rare ocular involvement in Behçet's disease. It can be related to an inflammatory neuropathy, a stasis papilledema complicating a benign intracranial hypertension or an ischemic neuropathy. The association of optic neuropathy with other ocular lesions could be responsible for a diagnostic delay. Its treatment relies on systemic corticosteroids and immunosuppressive drugs. The prognosis remained poor, with a third of the patients having lost their sight.

[Recurrent inflammatory myofibroblastic tumor with renal, retroperitoneal and lymph node involvement]. / Tumeur myofibroblastique inflammatoire récurrente avec triple localisation, rénale, rétropéritonéale et ganglionnaire.

Inflammatory myofibroblastic tumors are uncommon and benign tumors with unknown aetiology. First reported in the lungs, the inflammatory myofibroblastic tumors have been observed in other locations, especially in the abdomen and the pelvis. We report a 14-year-old adolescent female, who presented sequentially an inflammatory pseudotumor of lymph node, the left kidney and the retroperitoneum. Extrapulmonary inflammatory myofibroblastic tumors are mesenchymal solid tumors. They are frequently circumscribed and confined to a single organ. The recurrence of some inflammatory myofibroblastic tumors and their expression of chromosomal abnormalities found in some types of lymphoma suggest that some of these lesions constitute a true neoplastic process.

[Neutrophilic dermatosis associated with anti-neutrophilic cytoplasmic antibodies (ANCA) after benzylthiouracil therapy]. / Dermatose neutrophilique associée à des anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) après prise de benzylthiouracile.

BACKGROUND: We report the case of a female patient who developed polymorphic expressions of neutrophilic dermatosis associated with p-ANCA while receiving benzylthiouracil for hyperthyroidism. CASE REPORT: A 41-year-old-woman was treated with benzylthiouracil for Basedow's disease. After 21 months of therapy, she developed fever with different expressions of neutrophilic dermatosis: pyoderma gangrenosum of feet, Sweet's syndrome of the forearms and the face. Biopsies confirmed the diagnosis of neutrophilic dermatosis. The histological examination of a skin specimen taken from the developing border of a foot lesion showed polynuclear neutrophilic infiltration with leucocytoclastic vasculitis and the presence of anti-myeloperoxydase p-ANCA. Abdominal ultrasound showed multiple splenic microabscesses. The myelogram, gastroscopy and colonoscopy findings were normal. Benzylthiouracil was stopped and systemic corticosteroid therapy resulted in regression of the skin lesions and splenic microabscesses. DISCUSSION: Different types of neutrophilic dermatosis were described in our case, confirming the notion of neutrophilic dermatosis continuum. The occurrence of neutrophilic dermatosis and p-ANCA after benzylthiouracil therapy suggests the involvement of polynuclear neutrophils in a common pathogenic mechanism. However, to date there have been no other reports analogous to ours, and inclusion of neutrophilic dermatosis as a benzylthiouracil-induced adverse effect would require confirmation by other instances of such associations.

[Rendu-Osler disease and recurrent thromboembolic venous disease]. / Maladie de Rendu-Osler et maladie veineuse thromboembolique récidivante.

Rendu-Osler-Weber syndrome is a rare systemic fibrovascular dysplasia, recognized by mucocutaneous telangiectasias, arteriovenous malformations, epistaxis and family history. Venous thromboembolic disease is a poor prognostic factor in this disease given the risk of increased bleeding caused by anticoagulant therapy. We report a new case of a 56-year-old patient with Osler disease who developed recurrent thromboembolic venous disease when anticoagulants were discontinued. According to a review of the literature, this association does not appear to be fortuitous and is a factor of disease severity.

[Tocilizumab for refractory Takayasu arteritis with aortic aneurysm]. / Traitement par tocilizumab d'une artérite de Takayasu réfractaire avec anévrysme aortique.

Takayasu arteritis (TA) is a form of large vessel vasculitis (LVV) which affects the aorta and the main arteries. Many reports showed efficacy of biologic drugs (TNF α inhibitors and interleukin 6 inhibitors) in refractory TA cases. We report the case of a 46-year-old woman with refractory TA complicated by giant aortic aneurysm (AA) and severe hypertension, treated efficacy with tocilizumab (anti-interleukin 6 receptor monoclonal antibody).