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.

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.

[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).

[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.

[Primary Sjögren syndrome in a child]. / Syndrome de Goujerot-Sjögren primitif de l'enfant : à propos d'un cas.

Sjögren syndrome is uncommon in children and occurs most often in association with autoimmune diseases (secondary Sjögren syndrome). We describe the clinical and biological features of a 7-year-old girl with primary Sjögren syndrome revealed by recurrent parotiditis. CASE REPORT: A 7-year-old girl was referred for investigation of multiple episodes of parotid swelling since age 4 years, without systemic symptoms. The examination was unremarkable except for enlarged and painless parotid glands. Laboratory investigations and labial salivary gland biopsy revealed Sjögren syndrome without associated disease. Hydroxychloroquine was prescribed with clinical improvement. CONCLUSION: Recurrent parotiditis in children is an uncommon condition. The onset of parotid swelling at 5 years or over deserves screening for disimmune disorders, sarcoidosis, or Sjögren syndrome. Diagnosis of Sjögren syndrome is based on diagnostic criteria.

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.

[Surgical and endoluminal management of the inflammatory aortitis: A Tunisian center experience]. / Traitement chirurgical et endovasculaire des atteintes aortiques inflammatoires : expérience d'un centre tunisien.

Non-infectious aortitis is usually due to giant-cell arteritis, Takayasu disease or Behçet disease. The main aortic lesions are stenoses, occlusions and aneurysms in the Takayasu disease and aneurysms in the Behçet disease and giant-cell arteritis. Treatment is based on corticosteroid therapy and surgery. Endoluminal management is now the rule. We report a retrospective descriptive study of 10 patients who underwent surgical or endoluminal management of inflammatory lesions of the aorta between January 2000 and December 2015. There were 4 cases of Takayasu disease and 6 cases of Behçet disease. The aortic lesions were aneurysmal in all of the patients with Behçet disease. In the patients with Takayasu disease, aortic occlusions predominated, associated with other arterial lesions. Four patients with Behçet disease were managed surgically, and 2 patients underwent endovascular repair. All of the patients with Takayasu disease underwent surgery. Two patients died in the postoperative period, and two patients died during long-term follow-up. Systematic screening, as well as regular monitoring of the entire aorta during the follow-up, is necessary due to the frequency of aortic aneurysms.

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.

[TAFRO syndrome and monoclonal gammapathy: Uncommon association!]. / Syndrome de TAFRO et gammapathie monoclonale : association inhabituelle !

Castleman's disease is a lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia. Recently, a new variant of multicentric Castleman's disease has been identified in Japan called TAFRO syndrome. It is characterized by a constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction and organomegaly (TAFRO). It is usually associated with polyclonal hyperimmunoglobulinemia. Here, we report the first and unique case of TAFRO syndrome with monoclonal gammapathy.

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.

[Neonatal lupus and maternofetal transmission of anti-SSA/Ro and anti-SSB/La antibodies]. / Lupus néonatal et transmission materno-fœtale des anticorps anti-SSA/Ro et anti-SSB/La.

Neonatal lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro (60 and 52kDa) or anti-SSB/La antibodies. The aim of this study was to evaluate the clinical and biological profile of NL at the neonatal unit of Sfax, Tunisia, over a 10-year period. Six mother-NB pairs (two sets of twins and two sisters) had positive ANA by transplacental transmission during the study period. The ANA pattern was speckled and the NBs' sera titer was half that of their mothers'. Anti-SSA, anti-Ro52, and anti-SSB were found in 100%, 33%, and 50% of the mothers' sera, respectively. The transmission of anti-SSA was observed in four pregnancies out of six, anti-Ro52 in two pregnancies out of two, and anti-SSB in one pregnancy out of three. The patients' clinical records showed that two NBs had a congenital heart block: one with anti-SSA, whose mother had Sjögren syndrome, and another with anti-SSA, anti-SSB, anti-Ro52, and anti-mitochondrial antibodies (M2 type), whose mother had no diagnosis at the child's birth (cutaneous erythema and positive ANA with the same profile). Cutaneous signs (erythema, petechia) were described in three NBs out of six. The two sets of fraternal twins had cutaneous signs with the same ANA titer and profile (no anti-SSA transmission from their mother with lupus and anti-phospholipid syndrome). The two sisters' (two pregnancies 3 years apart) mother had Sjögren syndrome, one of them had heart block with positive anti-SSA, and the other was asymptomatic with anti-SSA and anti-Ro52. The same mother had a history of three pregnancies with two NBs who died of heart block.

Causes and outcome of hospitalisations in Tunisian patients with systemic lupus erythematosus.

OBJECTIVE: To describe the most common reasons of admission of Tunisian patients with systemic lupus erythematosus (SLE) and the outcomes of these hospitalisations. METHOD: The charts of patients with SLE who were hospitalised at our Department of Internal Medicine during a 2-year period from January 2011 to December 2012 were retrospectively reviewed, and the demographic characteristics, clinical and laboratory features, as well as all comorbidities, were collected. RESULTS: There were 128 episodes of hospitalisation of 87 patients with SLE. 25 patients (28.7%) were admitted twice or more. The median length of stay for all admissions was 11 days (2-76). The total number of days of hospitalisation was 1896 days, which represent 10.7% of the total number of days of hospitalisation in our department. The most common overall reason for hospitalisation was active SLE (55 events, 43%). In 29 patients, SLE was newly diagnosed during hospitalisation. Other causes of hospitalisation included assessment of the disease, infections (9.4%) and associated autoimmune disease (6.25%). Adverse drug reaction (3.1%) and thromboembolic events (1.25%) were uncommon causes of hospitalisations. There was a significant difference in length of stay between patients admitted with SLE flare and those admitted for non-SLE flare reasons (p<0.01). Four hospitalisations (3%) resulted in death. The principal cause of death was active SLE. CONCLUSIONS: Hospitalisation of patients with SLE is common in our department. Our study of this North African SLE population confirms the findings of previous studies suggesting that active SLE and infection remain the most common causes of hospitalisation of patients with SLE.

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.

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.