Zouhir Bahloul

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 IRF5 gene polymorphisms with rheumatoid arthritis in a Tunisian population

Objective: A strong genetic association of rheumatoid arthritis (RA) with the interferon regulatory factor 5 (IRF5) gene has been described previously in a Swedish population, although this result was not confirmed in a French population. We undertook an association study between IRF5 and the RA phenotype, as well as a study with serological markers of RA, in a Tunisian population. Methods: A single‐nucleotide polymorphism (SNP; rs2004640) was genotyped using a Taqman 5′ allelic discrimination assay on an ABI 7500 real‐time polymerase chain reaction (PCR) instrument in 140 RA patients and 185 controls. Rheumatoid factor (RF) and anti‐citrullinated protein/peptide antibodies (ACPA) were determined by enzyme‐linked immunosorbent assay (ELISA). Association was assessed based on the χ2 test and odds ratios (ORs) with 95% confidence intervals (CIs). Results: The frequency of the TT genotype of the IRF5 SNP rs2004640 differed significantly between patients and controls (p = 0.01). This difference was greater when a subgroup of patients with another ‘autoimmune’ disorder was considered (p = 0.007). A weak but significant association was also found in a subgroup of patients who were positive for ACPA (p = 0.04) or erosion (p = 0.01). Conclusions: Our results indicate that the TT genotype of the IRF5 (rs2004640) dimorphism is associated with RA in a Tunisian population.

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.

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.

Acute pancreatitis as initial manifestation of adult Henoch-Schönlein purpura: report of a case and review of literature

Abdominal pain observed in Henoch-Schönlein purpura (HSP) is usually attributed to edema and hemorrhage in the small bowel wall, secondary to a small-vessel vasculitis. Pancreatitis secondary to HSP is extremely rare. Here we report a 53-year-old man presented with acute pancreatitis that developed into characteristic rashes seen during HSP at the second day of the clinical onset, together with arthritis and glomerulonephritis. HSP is a rare and benign cause of acute pancreatitis. This complication can occur as an initial manifestation of HSP. Elevated serum amylase level can be considered as the early diagnostic tool for HSP pancreatitis. The patients with HSP who have abdominal pain as their chief complaint should be evaluated for pancreatitis, by routine serum amylase and abdominal computed tomography scan, to plan the specific treatment and avoid unnecessary surgery.

Association purpura rhumatoïde de l'adulte et carcinome épidermoïde du poumon

INTRODUCTION Association between Schönlein-Henoch purpura and neoplasm can suggest the responsibility of tumour antigens in the genesis of the vasculitis. We report a new case of squamous cell carcinoma associated with Schönlein-Henoch purpura and we discuss the reality of this association. CASE REPORT We report the case of a 50-year-old man who presents Schönlein-Henoch purpura with a purpura of lower limbs, joint involvement, gastrointestinal lesions and IgA renal mesangial deposits. The patient received three intravenous methylprednisolone pulses followed with oral corticosteroids. Six months later, while the vasculitis was in remission, the patient presented a squamous cell lung carcinoma. He was treated by chemotherapy and local radiotherapy. At the late follow-up, the neoplasm was incompletely resolved. CONCLUSION The neoplasm could be responsible of the development of the Schönlein-Henoch purpura. The discovery of this systemic vasculitis in an elderly patient should warrant a deep screening for an occult neoplasm.

Anticyclic citrullinated peptide antibody and rheumatoid factor in south Tunisian patients with rheumatoid arthritis: association with disease activity and severity.

To explore relationships between immunological status, clinical features, radiographic damage, disease activity, and functional disability in Tunisian patients with rheumatoid arthritis (RA).

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 Bonferronis 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.

Systemic lupus erythematosusmyositis overlap syndrome: report of 6 cases

The incidence of myositis in patients with systemic lupus erythematosus (SLE) is low among different series. Here we attempt to describe the main features of SLE/myositis overlap syndrome. We retrospectively reviewed the medical records of 174 patients with SLE seen over 15-year period. All the patients fulfilled the revised American Rheumatology Association criteria for SLE. Patients who met The Bohan and Peter criteria for definite myositis were included in this study. Among those patients, six patients had an associated myositis (3.4% overall). They were 6 women with a mean age of 29 years (20–41 years). At the initial evaluation, 3 patients (50%) were complained from myalgia, and all patients had symmetrical muscle weakness (proximal muscle weakness in 6 cases with distal muscle weakness in 2 cases). The muscle disease was severe in 1 case. Involvements of muscles of the pharynx and upper esophagus were noted in 4 patients (66.6%). The creatine kinase (CK) levels were elevated in 4 cases with a mean rate of 2153.5 UI/L. The electromyogram (EMG) revealed signs of myositis in 5 cases. Muscle biopsy, performed in 5 patients, revealed an inflammatory myopathy changes in 4 cases. Antinuclear antibodies (ANA) were positive in all cases. All our patients were treated with high doses of corticosteroids with favorable outcome. Relapse of SLE disease had occurred in 2 patients. The association SLE-myositis is rare with heterogeneous presentation. Through our observations and literature data we will specify the characteristics of this association.

Wegener’s granulomatosis presenting as multiple bilateral renal masses: case report and literature review

Wegener’s granulomatosis (WG) is a disease of unknown etiology characterized by necrotizing granulomatous vascularitis. The upper and lower respiratory tract and kidney involvements are very common; however, its presentation as bilateral renal masses is unusual. We report a case of a 59-year-old female patient who presented with multiple bilateral renal masses. The patient presented with sinusal and ocular symptoms suggestive of WG, and positive antineutrophil cytoplasmic antibodies (c-ANCA) with an anti-PR3 pattern. Histopathologic examination of the renal biopsy specimen revealed granulomatous inflammation with vasculitis and fibrinoid necrosis. The patient management, including prednisone and cyclophosphamid, induced a marked improvement of the renal masses. This case illustrates that WG should be considered in the differential diagnosis of renal masses.