Dacryoadenitis: do not forget ANCA vasculitis.

Objective: This paper aimed to describe another form of aggressive limited Granulomatosis with polyangiitis (GPA) revealed by dacryoadenitis. Methods and results: We report an unusually limited GPA in a 48-year-old man presenting with bilateral proptosis. She had never presented kidney or pulmonary manifestations, but her disease was persistently active including oto-rhino-laryngological manifestations, dacryoadenitis, and neurological manifestations unresponsive to corticosteroids and immunosuppressors. Discussion: Granulomatosis with polyangiitis (GPA) is an auto-immune inflammatory vasculitis. Involvement of lacrimal glands as the first presentation is uncommon. It is characterized by the development of granulomas. Patients with orbital mass without lacrimal gland involvement have a higher rate of systemic disease, a severe clinical course, and a higher rate of recurrences. A patient with dacryoadenitis seems to be with a good prognosis. Eye manifestations were significantly more common in patients with pachymeningitis. MPO-ANCA-positive pachymeningitis was more frequent in older female patients. PR3-ANCA-positive pachymeningitis had more severe neurological damage. Induction treatment consists of intravenous methylprednisolone (IV) associated with cyclophosphamide. Conclusion: Faced with dacryoadenitis, it is important to screen for ANCA-associated vasculitis. Abbreviations: GPA = Granulomatosis with polyangiitis, ANCA = Antineutrophil Cytoplasmic Antibodies.

Recurrent intra-cardiac thrombosis: A rare manifestation of Behçet's disease.

Behçet's disease is a systemic vasculitis characterized by recurrent bipolar aphtosis and ophthalmic disorders. Cardiac involvement is rarely reported and could be associated to poor prognosis. Intracardiac thrombosis is exceptional and represents a therapeutic issue. We report the case of a young man admitted in internal medicine department for management of prolonged fever and recurrent mouth ulcers.

[Aspirin and prevention of the recurrence of venous thromboembolism]. / Aspirine et prévention de la récidive de la maladie veineuse thromboembolique.

After a first episode of unprovoked vein thrombosis, the risk of recurrence persists for many years. Long term of anticoagulant therapy prevents the recurrence of vein thrombosis but is associated with a major risk of bleeding. As platelets play a role in the initiation and propagation of venous thromboembolism as well, antiplatelet agents, may play a role in the treatment and prevention of this disease. This review summarizes available evidence on effect of aspirin in the prevention of recurrent deep vein thrombosis.

Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

Central retinal vein occlusion : an uncommon complication in sarcoidosis.

Sarcoidosis is a multi-system granulomatosis of unknown etiology, defined by the presence of epithelioid and gigantocellular granulomas, without caseous necrosis. Ocular sarcoidosis manifests mainly as bilateral granulomatous anterior uveitis. Occlusion of the central retinal vein in sarcoidosis is a rare manifestation, which is the particularity of our observation. We report the case of a patient presenting with unilateral central retinal vein occlusion associated with granulomatous anterior uveitis on the same side. Systemic manifestations and further investigations led to the diagnosis of sarcoidosis.

Pulmonary vasculitis in Behçet's disease: reference atlas computed tomography pulmonary angiography (CTPA) findings and risk assessment-management proposal.

BACKGROUND AND AIM:  Pulmonary artery aneurysms (PAAs) are the most well-defined type of pulmonary vascular complication in Behçet's disease (BD).The aim of this study is to analyze which CT pulmonary angiography (CTPA) signs are associated with serious morbidity and mortality. METHODS: The study included 42 BD patients with pulmonary vascular complications. All patients' medical records were reviewed retrospectively in terms of demographics, disease characteristics, laboratory investigations, pulmonary manifestations, arterial and/or venous thrombosis and CTPA vascular and parenchymal findings. RESULTS: Deep venous thrombosis was observed in 31(73.8%) patients, arterial thrombosis in 13(31%), peripheral arterial aneurysms in 12(286%), haemoptysis in 38 (90.5%), and fatal haemoptysis in 8(19 %) patients. CTPA revealed: in situ thrombosis in 14(33.3%) patients, true stable PAAs in 13(31), true unstable PAAs in 11(26.2%), stable pulmonary artery pseudoaneurysms (PAPs) in 7(16.7%), unstable PAPs in 17(40.5%), the latter were associated with perianeurysmal leaking in 26(61.9%) and bronchial indentation in 19(45.2%).In regression analysis, fatal outcomes were associated with age in years (p=0.035), arterial thrombosis (p=0.025), peripheral arterial aneurysms (p=0.010), intracardiac thrombosis (p=0.026) and positively associated with haemoptysis severity (p<0.001). CONCLUSION: Peripheral arterial thrombosis and/or aneurysms, intracardiac thrombosis and haemoptysis severity are predictor of fatal outcomes in BD pulmonary vasculitis. PAPs with perianeurysmal alveolar haemorrhage and/or bronchial indentation are serious CTPA signs that require prompt identification and aggressive treatment. PAPs are a more serious aneurysmal pattern than true PAAs because they are a contained rupture of a PA branch in the context of pulmonary vasculitis.

Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study.

OBJECTIVES: In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients. METHODS: We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019. RESULTS: A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab. CONCLUSION: In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months.

Granulomatous gingival manifestation in Melkersson Rosenthal syndrome: a case report.

Melkersson-Rosenthal syndrome is a rare condition of unknown etiology. It is characterized by a classical triad of symptoms: relapsing facial and lip swelling, facial palsy and a fissured tongue. We report the case of a 29-year-old female patient who presented with the above-mentioned symptoms of Melkersson-Rosenthal syndrome. However, clinical examination revealed an exceptional manifestation, which is the gingival hyperplasia. The symptoms were partially managed with systemic steroids and surgical resection of gingival hyperplasia. The most significant finding to emerge from our case is that gingival enlargement can be identified as a rare clinical feature of the MRS disease, which is confirmed difficult to be managed.

Acquired hemophilia A in a patient with adult-onset Still's disease: Successful treatment with steroids.

Acquired hemophilia A (AHA) is a potentially life-threatening hemorrhagic disorder with many etiologies. We report the first case in the literature describing the association of AHA with adult-onset Still's disease (AOSD).

Biclonal Gammopathies in South Tunisia: Clinical and Biological Characteristics.

OBJECTIVE: Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. METHODS: We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. RESULTS: A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ±â€…10.87 years [range, 45-90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. CONCLUSION: BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM.

Orbital inflammatory pseudotumor revealing multi-organ immunoglobulin G4-related disease.

Relatively recently, the concept that immunoglobulin G4 (IgG4)-related disease is a distinct chronic inflammatory disorder rather than a subset of Sjögren's syndrome has been accepted. IgG4-related disease (IgG4-RD) is a fibro-inflammatory systemic immune-mediated condition that can affect the pancreas, salivary glands, and lymph nodes. Almost every organ may be impacted synchronously or metachronously by this illness, which causes the development of sclerotic masses of varying sizes. Numerous other rheumatic diseases can present with characteristics of IgG4-RD, making it difficult to distinguish between them. However, cases of IgG4-RD involving the bilateral orbits, and pancreas with biological abnormalities are rare. We present a case of an 18-year-old female with vitiligo since the age of 3 years who presented with acute pancreatitis and acalculous cholecystitis, bilateral orbital masses, palpebral edema, and eosinophilia. The patient was diagnosed with IgG4-RD in keeping with clinical presentation and the elevated serum IgG4 level and after elimination of other differential diagnoses. The patient's symptoms gradually relieved after glucocorticoid therapy. This case presents an uncommon combination of clinical features infrequently reported in the literature. Multi-organ IgG4-RD is a multisystemic mass, commonly creating diagnostic challenges for clinicians. Furthermore, and more importantly, it highlights the need to keep a differential of IgG4-RD in mind, to aid in the early and correct treatment of the disease.

About a rare association: Guillain-Barré Syndrome and polymyositis.

Guillain-Barré syndrome (GBS) and polymyositis (PM) are two rare autoimmune diseases, one of which affects the peripheral nervous system and other the muscle. We report the case of a young woman with no previous medical history who was hospitalized with an ascending paralysis associated with acute respiratory failure due to a GBS. The patient was treated with plasmapheresis with unfavorable outcome and permanent proximal muscular disability. The diagnosis of an associated PM was retained based on biological myolysis and the results of electromyography and muscular biopsy. To our knowledge, this association of GBS and PM has been reported only once in the literature. The search for syndromic associations in the presence of an autoimmune helps to avoid diagnostic errors.

Agranulocytosis in systemic lupus erythematosus: A case report.

Agranulocytosis is a rare acute condition characterized by severe a < gft (neutropenia in which the neutrophils count is less than 100/mm3. It can be classified into two categories, inherited, and acquired. Acquired agranulocytosis is not commonly caused by auto-immune diseases such as systemic lupus erythematosus (SLE). We report a case of a patient suffering from agranulocytosis related to SLE at disease onset, associated with other rare disease involvements.

Cavitary lung opacity of unusual cause during Behçet disease.

Pulmonary artery aneurysm must be evoked in front of any hemoptysis in a patient with Behçet disease as it requires urgent immunosuppressive therapy and often surgery.

Coexistence of thrombotic thrombocytopenic purpura and adult-onset Still's disease.

The association of Thrombotic thrombocytopenic purpura (TTP) and adult-onset Still's disease (AOSD) is very uncommon. Hereby, we present a case of TTP occurring in patient with a known AOSD and the successful outcome after plasma exchanges.

Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicentre retrospective study of 209 patients.

OBJECTIVE: To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). METHODS: A total of 209 patients with TAK [median age 29 years (interquartile range 7-62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. RESULTS: A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. CONCLUSION: This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.

INTRODUCTION: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. OBJECTIVES: The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. METHODS: The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. RESULTS: This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. CONCLUSION: The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas  classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

Pure extra-thoracic sarcoidosis: about 24 cases.

Introduction. Pure extra-thoracic sarcoidosis is rare and poorly characterized in the literature. Herein we present features of pure extra-thoracic sarcoidosis, in comparison with sarcoidosis with intra-thoracic involvement, in a population from the south of Tunisia. Methods. Retrospective, descriptive and comparative study of the patients presenting systemic sarcoidosis and attending the Department of Internal Medicine at the Hedi Chaker University Hospital, Sfax, Tunisia, for 21 years, from January 1996 to December 2016. Results. Twenty-four patients presented pure extra-thoracic sarcoidosis (30% of the cases of systemic sarcoidosis). There was a female predominance (79%). The mean age was 50 years. The main features were polyadenopathies (10 patients: 41.7%), cutaneous involvement (10 patients: 41.6%), inflammatory polyarthralgia (8 cases: 33.3%), general symptoms (6 patients: 25%), uveitis (6 cases: 25%), cholestasis (3 cases) and kidney involvement (2 cases). Lymphopenia, hypercalcemia, and hypercalciuria were observed each one in 12.5% of the cases, and high angiotensin converting enzyme (ACE) level in 38.5% of the cases. The histological proof was required in all the patients. Statistically significant associations identified were mainly hepatic involvement with general symptoms (p=0.035), peripheral lymphadenopathies (p=0.035) and kidney damage (p=0.022), and cutaneous involvement with articular manifestations (p=0.032). Systemic corticosteroids were used in half of the cases, with a good outcome in 21 cases, and recurrence in two cases. One patient was lost to follow up. The comparison to the form with mediastino-pulmonary involvement showed less lymphadenopathies (p=0.001), less lymphopenia (p=0.006), and less frequent use of corticosteroids (p=0.044). Conclusion. Our series was characterized by the frequency of the pure extra-thoracic form and the diversity of the systemic manifestations.

A critical analysis of 57 cases of Hughes-Stovin syndrome (HSS). A report by the HSS International Study Group (HSSISG).

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.