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 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.

[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.

[Infectious complications in systemic lupus erythematosus: a series of 146 patients]. / Complications infectieuses au cours du lupus érythémateux systémique: étude de 146 patients.

PURPOSE: The objective of this study was to analyse the incidence and characteristics of infection in systemic lupus erythematosus (SLE) and to determine the related risk factors. METHODS: A retrospective review of a well documented population of 146 Tunisian patients with SLE was undertaken. All patients fulfilled four or more criteria defined by the American College of Rheumatology. RESULTS: Sixty-five patients (44.5%) suffered at least one infection. Skin, urinary tract and lung were the most affected localizations. Bacterial infections (67.5%) were the most common. In the univariate analysis, nephritis, neuropsychiatric, leucopenia, lymphopenia, decreased complement (CH50, C3 and C4), SLE activity, ever use of steroids and cyclophosphamide were significantly associated with infection. In the multivariate analysis, nephritis, neuropsychiatric and lymphopenia were found to be significant. CONCLUSION: SLE has an increased overall risk for infection and they are especially prone to develop urinary, cutaneous and pulmonary infections. Infectious complications seem to be more associated with major organ damage than with steroid or immunosuppressive therapy.

[Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases]. / Maladie de Kikuchi-Fujimoto et connectivite: à propos de trois observations.

INTRODUCTION: Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. EXEGESIS: This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. CONCLUSION: Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.

[Osteomalacia revealing Sjögren's syndrome: a case report]. / Ostéomalacie révélatrice d'un syndrome de Gougerot-Sjögren : à propos d'un cas.

INTRODUCTION: The most common renal disease in Sjögren's syndrome is tubulo-interstitial nephritis, responsible for tubular acidosis in around 20 % of patients. Osteomalacia exceptionally occurs as the first manifestation of a renal tubule disorder due to a Sjögren's syndrome. EXEGESIS: We report a case of a 20-year-old woman with tubular acidosis induced osteomalacia secondary to primary Sjögren's syndrome. Improvement was obtained with bicarbonates, vitamin D, calcium and high-dose steroid therapy. CONCLUSION: During Sjögren's syndrome, osteomalacia can complicate the distal renal tubular acidosis. In spite of the rare cases of osteomalacia revealing Sjögren's syndrome, this auto-immune disease must appear in the list of the aetiologies of osteomalacia.

[Benzylthiouracil induced ANCA-positive vasculitis: study of three cases and review of the literature]. / Vascularite à anticorps anticytoplasme des polynucléaires neutrophiles induite par le benzylthiouracile: étude de trois observations et revue de la littérature.

INTRODUCTION: Vasculitis with antineutrophilic cytoplasmic antibodies (ANCA) have been reported in patients treated with anti-thyroid drugs, especially propylthiouracil. Benzylthiouracil, which exhibits similar structural likeness with propylthiouracil, has been recently observed to be associated with Anca-positive vasculitis. CASES REPORT: We present a study of three women with Grave's disease aged 21, 37 and 40 years, who were treated with benzylthiouracil. These patients developed vasculitis characterized by constitutional symptoms (two patients), joint pain (two patients), renal involvement (two patients), pulmonary hemorrhage (one patient) and multiple neuropathy (one patient). All patients presented p-ANCA with anti-MPO pattern. Discontinuation of benzylthiouracil and treatment with corticosteroids improved systemic involvement in all patients. CONCLUSION: Much like other anti-thyroid drugs, benzylthiouracil can be associated with ANCA-positive vasculitis. Because of the gravity of this complication, clinical monitoring is recommended in patients taking benzylthiouracil. If vasculitis develops, the anti-thyroid drug should be discontinued and corticosteroid treatment, with immunosuppressors in some cases, is initiated.

[Pleural effusion revealing Horton's disease]. / Pleurésie révélatrice d'une maladie de Horton.

Pulmonary involvement is rare in Horton's disease. Only few cases have been reported presenting as interstitial infiltration, pulmonary artery vasculitis, pulmonary nodules and granulome formation. Pleural effusion was rarely reported. A 65-year-old male patient presented with a right pleural effusion. Horton's disease was evoked in the presence of cephalgias, an ocular involvement and general signs. Temporal artery biopsy showed giant cell arteritis. After negative etiologic work up, pleural effusion was attributed to Horton's disease. Outcome was favourable with systemic corticosteroid therapy. Pleural involvment in Horton's disease is rare and characterized the absence of specific biological and histological findings. However, pleural effusion may be a presenting manifestation of Horton's disease.

[Portal thrombosis complicating an acute cytomegalovirus infection in an immunocompetent patient]. / Thrombose portale compliquant une infection à cytomégalovirus aiguë chez un sujet immunocompétent.

INTRODUCTION: The cytomegalovirus (CMV) infection is most often asymptomatic. The grave forms concern the immunocompromised patients. We report a new case pf acute CMV hepatitis complicated with portal thrombosis in an immunocompetent patient. EXEGESIS: A 29 year old man has presented a CMV hepatitis proved by the presence of pp65 protein and the viral DNA in serum. This infection was complicated by a portal thrombosis and the evolution was rapidly favourable under anticoagulant treatment. Eleven cases of major thrombosis complicating acute CMV infection in immunocompetent patients were previously reported in the English and French literature. The absence of local and general cause, the remission without anticoagulation, the elevated risk of thrombosis in both HIV and CMV seropositive patients, and in CMV seropositive renal transplant patients suggest a causal relation. Various pathogenic hypotheses were raised: presence of antiphospholipid antibodies, absent in our case, procoagulant phenotype induction of infected endothelial cells, proliferation induction of smooth cells. CONCLUSION: The acute CMV infection can be considered such as a possible cause of major thrombosis.

[Risk factor for deep venous thrombosis in internal medicine: A retrospective study of 318 cases]. / Profil étiologiques des thromboses veineuses profondes en milieu de médecine interne : une étude rétrospective de 318 cas.

OBJECTIVE: Venous thromboembolic disease is a common condition. Deep vein thrombosis (DVT) and pulmonary embolism are the most common manifestation but other locations may also occur. The objectives of the study were to estimate the incidence and determine the epidemiologic, topographic and associated conditions of venous thromboembolic disease in a department of internal medicine. METHODS: A retrospective study of a series of 318 cases of DVT was conducted in Internal Medicine CHU Hedi Chaker, Sfax, during a period of 15 years (1996-2010). RESULTS: DVT of the lower limbs was the most common location (87%). Other sites of DVT was noted in 16.35% of cases including upper limbs (19 cases), vena cava (16 cases), cerebral veins (10 cases), portal vein (10 cases) and hepatic vein (3 cases). A risk factor of VTE was found in 274 patients (86.1%). A state of thrombophilia was retained in 203 patients (63.5%). It was a hereditary thrombophilia (22.6%), an antiphospholipids syndrome (19.1%), Behçet's disease (16.4%) and neoplasia (7.2%). The study of the distribution of venous thrombosis as the seat and etiology showed that: the antiphospholipid syndrome was the most associated conditions with the upper extremity DVT (31.7%) whereas Behçet's disease was the most frequent etiology of vena cava thrombosis (7 cases) and the cerebral vein thrombosis especially in young males.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, multi-systemic inflammatory disorder of unknown causes. This disease is mainly characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The aim of this study is to investigate the associations between C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the plasma homocysteine (Hcy), folate, and B12 levels in a relatively large cohort of Tunisian patients with BD. METHODS: The study included 142 patients with BD and 172 healthy controls. The C677T and A1298C polymorphisms were genotyped using PCR-RFLP. Serum Hcy level was determined using a fluorescence polarization immunoassay. Serum folate and vitamin B12 levels were measured by electrochemiluminescence immunoassay. RESULTS: Genotype and allele frequencies of the two studied MTHFR polymorphisms did not show any significant differences among BD patients compared to controls. Patient carriers of the 677TT variant and the 677T allele displayed significantly higher Hcy concentration. Moreover, no significant association was found between neither A1298C polymorphism nor the C allele and Hcy, folate, and B12 levels. In multivariate analyses, we reported that 677T allele, male gender, and creatinine level were independent risk factors for hyperhomocysteinemia (HHC). CONCLUSIONS: In the present study, we report the absence of any significant differences between genotype and allele frequencies for both studied polymorphisms among BD patients compared to healthy controls. Besides, we showed that the T allele of MTHFR C677T polymorphism influenced the Hcy level which is an independent risk factor for HHC in Tunisian BD patients.

Destructive arthritis in Behçet's disease: a report of eight cases and literature review.

Behçet's disease (BD) is a multisystemic disease with typically non-erosive and non-deforming joint manifestations. The occurrence of destructive arthritis in Behçet's disease has rarely been reported. Here we attempt to define the epidemiological, clinical and radiological features of this unusual type of osteoarticular manifestation of BD. We retrospectively reviewed the medical records of 553 patients with Behçet's disease seen over 25-year period in our department of Internal Medicine (Sfax-Tunisia). All the patients fulfilled The International Study Group of Behçet's Disease criteria. Patients with destructive arthritis (defined by radiological changes: erosions and/or geodes and/or global narrowing of the joint space and/or ankylosis) were included in this study. Rheumatologic manifestations were observed in 71.1% patients. Eight patients (1.4% overall, 2% among patients with rheumatologic manifestations) had presented with destructive arthritis. The joint symptoms involved the knee in two cases, the wrist in one case, the elbow (one case), the sternoclavicular joint in two cases, the foot in one case and the tarsal scaphoïd in one case. There was recurrent arthritis at the same joint in the majority of cases. X-ray examinations revealed radiological changes: global narrowing of the joint in one case (knee), narrowing of the joint with geodes in three cases (knee, sternoclavicular), isolated geodes in two cases (tarsal scaphoid, foot) and severe lesions with ankylosis in two cases (two elbows, right wrist). Joint manifestations are common in patients with BD, but destructive arthritis is rare.