Association of Interleukin-1B and Interleukin-4 Gene Variants with Autoimmune Thyroid Diseases in Tunisian Population.

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Cytokines IL-1B and IL-4 play a role in the pathogenesis of AITD. This study was conducted on Tunisian patients with GD or HT to investigate the association of IL-1B and IL-4 gene polymorphisms with the risk and the prognosis of AITD. A total of 358 healthy controls and 341 patients with AITDs (249 HT and 92 GD) were genotyped for IL-1B+3953C/T and IL-4 intron 3 VNTR polymorphisms. A significant association was found between IL-1B+3953C/T polymorphism and GD or HT, both in the dominant and additive models. The IL-1B+3953T allele was associated with GD (p = 0.0003, OR = 1.93, CI = 1.34-2.78) and HT (p = 0.009, OR = 1.43, CI = 1.09-1.88). The IL-4 VNTR polymorphism was associated only with HT risk both in additive (p = 0.03, OR = 0.31, CI = 0.11-0.86) and recessive (p = 0.03, OR = 3.04, CI = 1.13-8.17) models. No significant association was found between IL-1B+3953C/T polymorphism and change in the serum concentrations of TSH and FT4 in GD and HT patients. In HT patients, the IL-1B+3953T allele (p = 0.009, OR = 0.42, CI = 0.22-0.83) and the IL-1B+3953T/T genotype (p = 0.03, OR = 0.21, CI = 0.04-1.07) were more frequent in the absence than in the presence of an anti-TPO antibody. The proportion of HT patients with the P1P2 genotype of the IL-4 gene was significantly higher in the absence than in the presence of the anti-TPO antibody (p = 0.04, OR = 0.39, CI = 0.17-0.89). These preliminary results suggest that IL-1B and IL-4 gene polymorphisms may be associated with GD and HT susceptibility and may represent prognostic factors for predicting the severity of HT.

An unusual case of Behçet's disease presenting with postpartum ovarian iliac vein thrombosis and pulmonary embolism.

Thrombosis of the ovarian vein is a rare complication which arises classically in the postpartum. We report a case of 24-year-old woman with a history of Behçet's disease, who presented with pelvic and thoracic pain, tachycardia, dyspnea and fever occurring 2 weeks after delivery. Computed tomography revealed an ascending thrombosis of the iliac and right ovarian veins complicated by bilateral pulmonary embolism. The patient responded well to the combination of anticoagulants and immunosuppressive agents. Behçet's disease should also be considered as an etiologic factor for ovarian vein thrombosis.

Pro- and anti-angiogenic VEGF mRNAs in autoimmune thyroid diseases.

The aim of this study was to assess the relationships between five different splice isoforms of VEGF mRNA and its plasma levels in individuals treated for autoimmune thyroid diseases (AITD); mainly Graves' disease (GD) and Hashimoto's thyroiditis (HT). In a population from Tunisia, levels of thyroid hormones and antibodies were quantified simultaneously with plasma VEGF and VEGF mRNA isoforms after a period of 6 months of patients' treatment. Plasma VEGF was measured in 110 AITD patients (21 GD and 89 HT patients). VEGF isoforms (VEGF121, VEGF165, VEGF145 and VEGF189 pro-angiogenic isoforms and VEGF165b anti-angiogenic isoform) in peripheral blood mononuclear cells were quantified in 71 patients (20 GD and 51 HT patients) and 86 healthy controls. Decreased levels of VEGF189 mRNA were observed in AITD compared to controls. VEGF165 was increased in GD patients compared to controls and the VEGF165b was increased in HT patients compared to GD. We observed increased levels of VEGF165b in hypothyroid AITD patients after treatment. We have also shown that the VEGF145 isoform levels were determined by FT4 in all patients and by the thyroid status after 6 months of treatment only in HT patients. An association was observed for VEGF165 mRNA levels with anti-TPO antibodies in all patients. Finally, FT4 was associated with VEGF plasma levels but only in healthy controls. In conclusion, this descriptive study highlights the specificity of VEGF mRNA isoforms in AITD, a fact underlining the need for novel clinical trials and the development of personalised theranostic approaches.

Intracardiac thrombus in Behçet's disease: two case reports.

UNLABELLED: Intracardiac thrombus in Behçet's disease is an extremely rare manifestation. We report two such cases. A 20-year-old man presented with dyspnoea, cough and haemoptysis. Right heart thrombus associated with pulmonary artery aneurysm and thromboembolism was identified by helical CT and transoesophageal echocardiography. The second case was a 29-year-old male admitted for fever and chest pain. A diagnosis of right atrial thrombosis associated with pulmonary embolism and hyperhomocysteinemia was made. Due to the absence of haemodynamic compromise, medical management consisting of immunosupressive and anticoagulation therapy was adopted which resulted in complete dissolution of the thrombus with dramatic clinical improvement in both cases of clinical status. CONCLUSION: intracardiac thrombus is a rare complication of Behçet's disease. As shown in our patients, medical treatment should be considered as the first line.

Polymorphism of interleukin 6 -174 G/C in Behcet disease: case series and review of literature.

To assess the association between polymorphisms of the IL-6 -174 G/C and Behçet's disease (BD) in Tunisian patients. DNA was extracted from blood samples taken from 43 Tunisian patients and 43 healthy controls. The polymorphisms were analyzed by PCR with the PCR-RFLP. No significant association was found between patients and controls concerning polymorphism of IL6 -174 G/C between the (allelic frequency: C (17.44 vs 8, 13%; P=0.17) et G (82,55 vs 91,86%; P= 0.21). Neither age of onset of BD nor sex appears to be influenced by allelic variation of SNP-174 G / C of IL6. Disease duration of BD was longer in patients having the form 174 G-allele. SNP -174G/C was more frequent in patients without significant association (32.5 vs 16,26% ; P=0.07). SNP -174 G/C was not associated with the HLA B51. Neither age of onset of BD nor sex appears to be influenced by SNP-174 G / C of IL6. Disease duration of BD was longer in the absence of the SNP-174 G/C IL6, with no significant difference (79.2 + / -45.095 vs.70.28 + / - 47.034 months, P=0.59). The polymorphism of IL6 -174 G/C does not modulate clinical expression of BD. The single nucleotide polymorphisms of the IL-6 do not appear to be associated with BD reconstruction.

Polymorphisms in TSHR and IL1RN genes and the risk and prognosis of Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a complex genetic autoimmune thyroid disease (AITD). Thyroid-stimulating hormone receptor (TSHR) is considered as candidate gene in AITD. IL1RN gene is involved in the pathogenesis of a number of autoimmune diseases. These findings prompted us to investigate the association of TSHR and IL1RN genes polymorphism with the risk and the prognosis of HT in Tunisia. A total of 249 healthy controls and 202 patients with HT were genotyped for TSHR D727E and IL1RN(VNTR) polymorphism. No significant difference was found for D727E polymorphism between HT patients and healthy controls. For IL1RN gene, we found an association between HT and IL1RN(VNTR) polymorphism. The A1A3 genotype was more prevalent in HT patients than in controls. However, the A1A4 genotype was associated with HT as a protective factor. Significant association of the TSHR polymorphism with lower plasma TSH level in HT patients has been detected. We found for the first time an association of IL1RN(VNTR) polymorphism with the production of anti-thyroid peroxidase antibody at the onset of disease. These preliminary results suggest that only the IL1RN(VNTR) polymorphism may be associated with HT susceptibility and that TSHR and IL1RN(VNTR) polymorphisms may represent prognostic factors for predicting the severity of HT.

Managing the risk of cancer in Cowden syndrome: a case report.

INTRODUCTION: Cowden syndrome is a rare cancer predisposition syndrome inherited in an autosomal-dominant fashion. The syndrome is characterized by hamartomatous polyps that affect multiple organs: skin, mucous membranes, thyroid, breast, gastrointestinal tract, endometrium and brain. It is also associated with an increased risk of developing malignancy in many tissues but especially breast, thyroid and endometrium. CASE PRESENTATION: We present the case of a 30-year-old Tunisian woman with mental retardation who presented to our facility with rectal hamartomatous polyps. Her medical history included fibrocystic disease of the breast over the last three years. A physical examination revealed macrocephaly, hyperkeratotic papules on the mid-facial skin, palmoplantar keratosis and oral mucosal papillomatosis. A breast examination revealed nodular breast tissue bilaterally and a diffuse thyroid goiter. Our patient was clinically euthyroid. A total thyroidectomy was performed. A histopathologic examination revealed thyroid papillary carcinoma. A gastrointestinal evaluation revealed esophageal and gastric polyps. Biopsies showed hyperplastic and adenomatous lesions associated with Helicobacter pylori. A final diagnosis of Cowden syndrome was made according to the syndrome testing criteria adapted by the US National Comprehensive Cancer Network. A prophylactic bilateral mastectomy was proposed but refused by our patient. Our patient was kept under surveillance for breast and colorectal malignancies. CONCLUSIONS: Early and accurate diagnosis of Cowden syndrome is essential because it is a cancer predisposition syndrome that carries an increased risk for developing malignancy in many tissues, especially breast and thyroid. For this reason, education regarding the signs and symptoms of cancer is important. All patients must be screened for malignancies and options for prophylactic mastectomy should be discussed. Guidelines for cancer screening including surveillance and management plans for these patients should be distinguished from those of the general population, and may lead to a more timely diagnosis and treatment of cancers associated with this syndrome.

Thymic hyperplasia in a patient with Grave's disease.

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

Gastrointestinal involvement revealing Henoch Schonlein purpura in adults: Report of three cases and review of the literature.

The diagnosis of Henoch-Schonlein purpura (HSP) is difficult, especially when abdominal symptoms precede cutaneous lesions. We report three cases of adult HSP revealed by gastrointestinal (GI) involvement.

Co-existing sarcoidosis and Takayasu arteritis: report of a case.

INTRODUCTION: Takayasu arteritis (TA) is a chronic vasculitis of unknown origin, affecting mainly the aorta and its main branches. As a result of the inflammation, stenosis, occlusion or dilatation of the involved vessels may occur and cause a wide range of symptoms. It has been described in association with various auto-immune disorders (mainly inflammatory digestive tract diseases). However, only few cases of TA associated with sarcoidosis have been reported, raising the question of an association by chance. CASE REPORT: We report a case of a 34 year-old woman, with one year history of sarcoidosis, who presented with asymmetric high hypertension revealing inflammatory humeral, axillary and subclavian arteritis related to TA, successfully treated by steroid and immunosuppressive therapy(MethotrexateR). CONCLUSION: TA and sarcoidosis may be related, rising the hypothesis that TA or Takayasu arteritis-like granulomatous vasculitis may be, in fact, a complication of sarcoidosis.

Hyperhomocysteinaemia in Behçet's Disease.

Objectives. The aim of this study was to investigate if hyperhomocysteinaemia is a contributive risk factor for the pathogenesis and the activity of Behçet's disease (BD). Design and Methods. Fifty four patients fullfiling the criteria of the International Study Group for BD were enrolled. Fifty healthy volunteers matched for age and sex with the BD group were included as a negative control group. Patients, with any condition that might affect plasma homocysteine concentration, were excluded. Results. Mean serum homocysteine concentration was significantly higher in patients with BD than in the healthy controls (P < .001), in patients with active disease (P = .04), and in masculine gender (P = .05). There was no significant difference between homocysteine level and clinical involvement. Conclusions. We demonstrated that plasma total homocysteine level (tHcy) is increased in BD and correlated with disease activity. No association was found between homocysteine levels and clinical involvement.

Escherichia coli osteomyelitis of the ischium in an adult.

Osteomyelites, bone infections of a hematogenous origin, are rare in the pelvis (2.3%) and are extremely rare in the ischium. Ischiatic osteomyelitis is usually found in children and adolescents, but has rarely been described in adults. The clinical presentation varies and the diagnosis is based on magnetic resonance imaging (MRI). The most frequently isolated germ is the staphylococcus, while Escherichia coli has been found in a few cases. We report a case of osteomyelitis from E. coli in a 46-year-old woman revealed by persistent fever. The point of entry was a septicemia from gastrointestinal origin, related to colon polyps. The clinical picture was also complicated by an antiphospholipid antibody syndrome (superior mesenteric vein and splenomesenteric branch thrombosis). The course was favorable thanks to appropriate antibiotic treatment and surgical debridment of the infection.

Oxidative stress: correlation with Behçet's disease duration, activity and severity.

OBJECTIVE: To study the oxidant/antioxidant status in Behçet's disease (BD) patients and the potential link between antioxidant enzymatic defences impairment and the disease duration, activity and severity. METHODS: 40 BD patients (27 males, 13 females; mean age: 38.8 years) were prospectively enrolled in the study and compared to a sex and age matched control group. Plasma malondialdehyde (MDA), the reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio, erythrocyte superoxide dismutase, catalase and glutathione peroxidase (GSH-PX) were analysed in both groups. A correlation analysis was performed between these parameters and disease duration, activity and severity. Activity and severity of BD were assessed meaning two respective clinical scores. RESULTS: When compared to controls MDA was increased and GSH/GSSG reduced in BD patients (respectively p<0.005). Superoxide dismutase (SOD) was significantly lower while catalase was significantly higher in BD than in controls. Correlation analysis showed that SOD activity was significantly and negatively correlated to disease duration and activity but not to severity. Other oxidant/antioxidant markers were not significantly linked to neither disease duration nor activity and severity. CONCLUSION: Our study confirm the existence of an oxidative stress (OS) state in BD as shown by the increase of MDA and the diminution of GSH/GSSG ratio which can be used as another index of OS. Despite this OS state, the activity of antioxidant enzymes and especially of SOD is impaired and negatively correlated to the disease duration and activity. We think that a rational strengthening of antioxidant defences should be part of an optimal treatment strategy.

Secondary Amyloidosis, a Fatal Complication of Behcet's Disease: Three Case Reports.

Renal amyloidosis (RA) is known to be one of the many complications of Behcet's disease (BD) but its frequency has been often underestimated. In this paper, we report on three cases of RA in a series of 105 patients with BD. RA was clinically suspected in our patients by the presence of edema and/or hypotension. The nephrotic syndrome was present in all of them and one patient had associated renal failure. Renal biopsy showed amyloid deposits type AA in all cases.Our patients received Colchicine at doses of 1 mg per day but with disappointing results. Their prognosis was significantely impaired with our three patients dying at ten years, six months and four weeks after diagnosis of RA. We will try, through this clinical experience and based on the relevant literature to better understand this kind of morbid association.