HLA DRB1/DQB1 alleles and DRB1-DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: a population-based case-control study.

Rheumatoid arthritis (RA) is an inflammatory disease, which affects synovial joints, and is influenced by environmental and genetic factors, in particular the human leucocyte antigen (HLA) system. In our study, we investigated the association of HLA class II DRB1 and DQB1 alleles and DRB1-DQB1 haplotypes with RA susceptibility in Tunisian subjects. Therefore, HLA class II low-resolution genotyping was done in 110 RA patients and 116 controls, with a HLA-DRB1*04 high-resolution typing. Our results showed a strong association between HLA-DRB1*04/DRB1*04:05 alleles and RA presence, which persisted after correcting for multiple comparisons (Pc < 10-3, Pc = 0.020, respectively), in contrast to the protective effect of HLA-DRB1*04:03 allele (Pc = 15.2 × 10-4). However, increased frequency of DQB1*05 (Pc = 0.020) and decreased frequency of DRB1*04:03 subtype (Pc = 0.032) were seen in RF+ patients than controls. Moreover, when RA patients were compared to controls, DRB1*04-DQB1*03 haplotype was associated with RA susceptibility in Tunisians (Pc = 16.8 × 10-5), independently of RF status. Conversely, DRB1*01 allele and DRB1*01-DQB1*05 haplotype was highly present in RF+ vs RF- groups (Pc < 10-3, Pc = 5.6 × 10-3, respectively) and seems to be linked to seropositivity. Investigation of HLA class II alleles and haplotypes association with RA susceptibility with secondary Sjögren's syndrome (sSS) showed a predisposing effect of DRB1*04 (Pc < 10-3) and DRB1*04-DQB1*03 haplotype when RA with sSS/without sSS groups were compared to healthy controls. Our results confirms the association of HLA-DRB1*04, specifically HLA-DRB1*04:05 subtype, and DRB1*04-DQB1*03 haplotype with RA susceptibility in Tunisians, independently of seropositivity or the sSS presence.

Interleukin-1ß, Interleukin1-Ra, Interleukin-10, and tumor necrosis factor-α polymorphisms in Tunisian patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study was to investigate the role of IL-1ß (-511C>T), TNFα (-308 G>A), IL-10 (-1082 G>A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians. PATIENTS AND METHODS: Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF). RESULTS: IL1-RN VNTR A1A3 genotype is associated with higher risk of RA (P=0.012, OR=4.31). Among the cases, males who carry this genotype were more exposed to RA (P=0.044, OR=8, 47). For IL1- ß gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls (P=0.013, OR=2.45). This higher frequency was especially observed in women (P=0,003, OR=3.42). In contrast, IL10-1082G/G genotype was less common in patients (P=0.046, OR=0.46). According to EF, men carrying IL1-RN VNTR A1A3 (P=0.005 OR=5.28) and IL1-ß-511C/C (P=0.015 OR=2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele (P=0.024, OR=1.84) and A/A genotype (P=0.033, OR=3.1) were positively associated to EF of RA. However, G allele (P=0.024, OR=0.31) and GG genotype (P=0.31, OR=0.031) of the TNFα-308 were protectors. CONCLUSION: Our results indicated that IL-1RN VNTR, IL-1ß (-511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1ß (-511C>T) and TNFα (-308 G>A) are associated with severity of RA.

[Unusual presentation of Wegener's granulomatosis]. / Présentation inhabituelle d'une granulomatose de Wegener.

We report an unusual case of Wegener's granulomatosis revealed by spleen infarction and complicated by reno-vascular hypertension. A 33-year-old man with a history of spleen infraction and cerebral venous thrombosis was admitted for malignant hypertension, renal failure and nephritic syndrome. On Doppler renal ultrasonography, ostial stenosis of the right renal artery was evidenced. Right kidney was non functional on scintigraphy and the patient underwent a right nephrectomy. Granulomatous vasculitis of the right renal artery was found but anti-neutrophilic cytoplasmic antibodies were absent. The diagnosis of Wegener's granulomatosis was suspected. The patient was treated with cyclophosphamide, corticosteroids and plasma exchanges, and renal function markedly improved.

[Liver involvement in sarcoidosis: study of seven cases]. / L'atteinte hépatique au cours de la sarcoïdose: à propos de sept cas.

INTRODUCTION: Sarcoidosis is a systemic disorder of unknown aetiology that may involve many organs including the liver. METHODS: This is a monocentre retrospective and descriptive study over 12 years of patients with systemic sarcoidosis who presented with liver involvement. RESULTS: Amongst 21 patients with systemic sarcoidosis, seven presented a liver involvement (five males and two females; mean age 42.5 years). The liver involvement was the presenting manifestation in three. Liver enlargement was noted in five patients and abnormal liver function tests in four. In one patient, abdominal computed tomographic scan showed a nodular hepatomegaly. Liver histology demonstrated typical granulomatous lesions in six. One patient developed a Budd-Chiari syndrome that responded favourably to corticosteroids. Six out of the seven patients were treated with corticosteroids. CONCLUSION: Liver involvement in common in sarcoidosis and commonly asymptomatic. Treatment is not systematic.

[Interstitial pneumonia complicating amyopathic dermatomyositis: a case report]. / Pneumopathie interstitielle compliquant une dermatopolymyosite amyopathique : à propos d'un cas.

Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, characterized by the absence of motor weakness and the presence of normal muscle enzyme levels. ADM is sometimes accompanied by neoplasm or interstitial pneumonia that shows a rapid progressive course both of them are associated with a poor prognosis. A 56-year-old woman with no medical history was referred to the department of medicine because of arthralgia with a remarkable weight loss. She also complained of rapidly progressive dyspnea, cough and photosensitivity. Physical examination on admission showed scaly erythema on the dorsum of the hands (Gottron sign) and periorbital edema with a purplish appearance (heliotropic rash), arthritis, but no muscle weakness. Auscultation of the chest identified audible fine crackles on the lower aspects of both lungs. Results of laboratory findings on admission revealed a lymphopenia. The serum creatine kinase and serum lactate dehydrogenase concentration were normal. IRM muscle and electromyography were normal. Antinuclear antibody was positive 1:80 and anti-Jo-1 antibody and other autoantibodies to specific antigens were all negative. High resolution computed tomographic chest scans also revealed diffuse ground-glass opacities in both lungs with basilar predominance. Arterial blood gas analysis revealed hypoxia and hypocapnia. LBA was not performed because of the deterioration of respiratory symptoms. There was no neoplasm associated. The diagnosis of ADM complicated with ADM rapidly progressive interstitial pneumonia was made. Despite of IV methylprednisolone pulse therapy (1g*day-1 for 3 days) and cyclophosphamide, she died by respiratory failure.

[Estrogen use in systemic lupus erythematosus]. / Rôle des estrogènes dans le lupus érythémateux systémique.

The role of exogenous estrogen in the initiation and maintenance of human systemic lupus erythematosus (SLE) remains very controversial. To review the current literature of the safety of using exogenous estrogens in patients with SLE, a Medline search for articles published between 1970 et 2004 regarding this relationship was performed. Although cohort studies suggest an increase in the incidence of SLE with both oral contraceptives and hormone replacement therapy, recent retrospective studies suggest that the risk of flares is not increased with hormone replacement therapy. Large prospective double blind placebo controlled studies inclusive of all ethnic groups such as the Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) trial had to provide the basis for definitive recommendations but it had been interrupted after WHI study results.

[Systemic manifestations of chronic hepatitis C]. / Les manifestations systemiques des hépatites virales C chroniques.

It's well known that hepatitis C virus (HCV) related chronic liver disease may be associated with various extra hepatic disorders. These manifestations can revealed the hepatic disease. We review the available data on the conditions and asses their clinical implications: vascular, cutaneous, articular, neurological or renal disorders. There is no correlation between these extra hepatic manifestations and the severity of liver disease. Several recent studies have established a strong link between HCV infection and essential mixed cryoglobulinemia but some other extra hepatic associations are just fortuitous. Others datas are necessary to better analyze these extra hepatic disorders and to offer the beneficial treatment of patients with chronic hepatitis C.

[Synovitis caused by plant thorn and chronic polyarthritis. Apropos of a case and review of the literature]. / Synovite à piquant végétal et polyarthrite chronique. A propos d'un cas et revue de la littérature.

A 54 year old male developed plant thorn synovitis of the knee followed five months later by nonerosive seronegative polyarthritis. The occurrence of chronic inflammatory joint disease shortly after plant thorn synovitis is exceedingly rare. The relationship between the two events remains to be clarified.

Bronchoalveolar lavage and transbronchial biopsy in spondyloarthropathies.

Fourteen patients (12 men, 2 women) with spondyloarthropathies underwent bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and other respiratory investigations. BAL revealed lymphocytosis and increased nonaltered neutrophil polynuclears in a smoker and an isolated lymphocytosis in one patient with restrictive syndrome and radiographic apical fibrosis. TBB showed interstitial fibrosis in the 2 patients and in 3 others who are all nonsmokers and among whom 2 had a restrictive syndrome. Subclinical alveolitis in spondyloarthropathies is absent. Interstitial fibrosis is not rare and its frequent association in a restrictive syndrome suggests a mechanical origin.