No Correlation between Anti-drug Antibodies and Therapeutic Response in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF Blockers.

INTRODUCTION: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response. METHODS: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA). RESULTS: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity. CONCLUSION: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.

Intestinal pseudo-obstruction: Unusual presentation of systemic lupus erythematous.

Systemic diseases should be always considered when managing unexplained intestinal pseudo-obstruction. Intestinal pseudo-obstruction related to systemic lupus erythematosus is often responsive to corticosteroid therapy when promptly treated.

Evaluation of students' motivation during the gamification of electrocardiogram interpretation learning.

INTRODUCTION: The quality of the training of medical students is one of the guarantors of the proper functioning of our health system. Gamification is an innovative educational pedagogical method that stimulates the pleasure of learning and encourages learner motivation. AIM: To evaluate the subjective and external motivations and academic self-efficacy of DCEM1 students by playing with TD sessions designed to learn the systematic interpretation of rhythm disorders on surface ECGs using playing cards. METHODS: It was a descriptive, cross-sectional study. Three successive groups of 25 students each took part in this study which took place at the Faculty of Medicine of Tunis. Each group was subdivided into 5 subgroups. During the TD session, the same 18 playing cards are distributed to each subgroup, and various wide and thin QRS tachycardia ECG plots are projected successively. Each subgroup should collect playing cards related to the methodical interpretation of each ECG trace and establish the final diagnosis of rhythm disorder. At the end of the pedagogical training, an anonymous self-assessment questionnaire to measure the types of motivation and academic self-efficacy was submitted to the students. RESULTS: Seventy-five students participated in our study. They were mostly female (sex ratio = 4). Gamification learning using playing cards has generated learners' intrinsic motivation (5.89 ± 0.97), allowing them to feel more confident in themselves, capable of acquiring new skills. Regarding extrinsic motivation, having good results on the exam was not their main concern (4.34 ± 1.23). This learning method has created a feeling of self-efficacy among our learners (5,004 ± 0,98). Indeed, they proved to be able to assimilate the fundamental notions of the course (5.86 ± 1.26), to understand the most complex material of the course (5 ± 1.55) and to acquire the competences targeted by this course (5.41 ± 0.5 ). Finally, all learners were satisfied with the method of gamification learning using playing cards. They recommended that this method be generalized throughout all ECG sessions. CONCLUSION: Gamification learning seems to be an effective and appropriate approach to teaching in the medical field since it allows to associate the notion of pleasure and the act of learning and stimulating motivation and self-efficacy learners.

Bilateral Sub-deltoid Bursitis in a Patient Receiving Infliximab for Crohn's Disease.

BACKGROUND: Infiximab has been shown to be effective in inducing and maintaining remission of intestinal bowel diseases. Infiximab has been associated with many adverse events. Articular manifestations are commonly reported, but they are of variable clinical expression and aetiology. Among them, inflammatory bursitis has rarely been described. OBJECTIVE: Herein a case of inflammatory bursitis in a patient with Crohn's disease after switching to biosimilar infliximab is reported. CASE REPORT: A 41-year-old man with Crohn's disease evolving from 3 years was referred to infliximab therapy at a dose of 5mg/kg because of an aggressive resistant perineal fistula. After 14 infusions of infliximab, the treatment was switched to infliximab biosimilar using the same dose and frequency of administration. Forty-eight hours after the second infusion, he developed an acute onset of muscle pain and stiffness on both of his shoulders. A musculoskeletal ultrasound was performed and revealed a hypoechoic widening of both subacromial bursae. It was more severe on the left side. DISCUSSION: The diagnosis of non-infective sub-acromial bursitis secondary to infliximab infusion was made as the patient's symptoms resolved rapidly without any antibiotics. Infliximab was definitively stopped and adalimumab was introduced. CONCLUSION: Musculoskeletal side effects of infliximab infusion are uncommonly reported. Among them, bursitis has been reported in only a few cases. Ultrasonography can help early diagnosis of bursitis. The time of occurring of this reaction regarding infliximab infusion, screening of Antibodies to Infliximab (ATI) and clinical outcome after drug discontinuation are the main helpful arguments.

A Stiff Person Syndrome Misdiagnosed as a Psychiatric Illness: A Case Report.

BACKGROUND: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder which is often misdiagnosed. We report here a case of SPS with a long diagnosis delay. CASE: A 36-year-old man presented with an 11-year history of progressive stiffness and painful spasms of his both legs, with recent worsening of his condition over the last year resulting in a considerable difficulty of standing up and walking. As the patient developed phobic symptoms, he was considered as having a psychiatric illness and treated with antianxiety and antidepressant drugs. As no real improvement was observed, the patient was referred to internal medicine. Neurological examination showed paraspinal, abdominal and lower limbs muscle contraction with lumbar rigidity. These symptoms were associated to adrenergic symptoms: profuse sweating, tachycardia and high bloodpressure. Initial routine investigations revealed high blood glucose level. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles showed continuous motor unit activity in agonist and antagonist muscle. Electroencephalography and brain magnetic resonance imaging were normal. Immunologic tests according to radio immune assay technique revealed high level of serum anti-glutamic acid decarboxylase (anti-GAD65) antibodies. Diagnosis of autoimmune SPS was retained based on clinical, electrophysiological, and immunological findings. Pregabalin at the dose of 150 mg, three times a day was prescribed with satisfying response. CONCLUSION: SPS is supported by an autoimmune pathogenesis and anti-GAD antibodies seems to be very helpful when SPS is clinically suspected. Treatment of SPS is a challenge, given the scarcity of the syndrome and the absence of established recommendations.

Iron deficiency anemia: clinical and etiological features.

BACKGROUND: Iron deficiency is the most common nutritional deficiency worldwide and its resulting anemia appears as a public health problem. Iron deficiency anemia is rather a symptom than a disease in itself, and the identification of its etiology is of paramount importance. AIM:   to study the clinical and etiological features of iron deficiency anemia in an Internal Medicine department. METHODS: We conducted a retrospective descriptive study between 2001 and 2015 at an internal medicine department including patients presenting with iron deficiency anemia and having at least one etiological investigation. RESULTS: The average age was 45.6  16,3 years. Three main mechanisms of iron deficiency anemia were noted: repeated blood loss (94.4%), digestive malabsorption of iron (17.8%) and lack of dietary iron intake (6.6%). The digestive origin dominated the etiologies of iron deficiency anemia with a leading frequency of gastritis (32.2%). An underlying cancer was discovered in six cases. The average duration of follow-up was 9.1 months. An unfavorable outcome (persistence or recurrence of iron deficiency anemia) was associated with an absence or insufficiency of etiological treatment (p << 10-3) and with a duration of iron treatment inferior to 4 months (p = 0.034). CONCLUSION: In case of iron deficiency anemia, the prognosis depends on the quality of the etiological investigation. It can allow the discovery of an underlying cancer. The management of iron deficiency anemia relies on a well-led iron supplementation and an optimal treatment of the incriminated cause.

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review.

OBJECTIVE: To describe safety and efficacy of rituximab in patients with systemic sclerosis. METHODS: We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. RESULTS: Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8; 18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). CONCLUSION: Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases.

Characteristics of neurological manifestations of Behçet's disease: a retrospective monocentric study in Tunisia.

OBJECTIVE: The aim of the present study was to analyze demographic, clinical and genetic features of Behçet's disease patients with neurological involvement through a monocentric study of a homogenous group of hospitalized patients observed in the same department and to compare them with those of other ethnic and geographic groups. METHODS: Four hundred and thirty Behçet's disease (BD) patients were retrospectively studied. Diagnosis of BD was made according to the international study group for Behçet's disease criteria. Patients with neurological findings suggestive of involvement of the nervous system by BD were further studied according to clinical examination, laboratory tests and neuroradiological investigations. RESULTS: Neurological involvement was observed in 121 patients (28.1%). The mean age at neuro-Behçet's disease (NBD) onset was 29.7 years. Average disease duration of BD before neurological manifestations onset was 6.4 years. Male to female ratio was 1.8. Of the 121 NBD patients, parenchymal involvement occurred in 74 patients (61%). Among them 26 (21.4%) presented with brainstem involvement, 24 (19.8%) with hemispheric involvement and 2 (1.6%) with spinal cord involvement. Non-parenchymal NBD occurred in 47 patients (39%). Involvement of the main vascular structures (Vasculo-NBD) was the most common non-parenchymal NBD lesion found in 35 patients (28.9%) consisting of cerebral vein thrombosis (CVT) in 24 cases and cerebral arterial thrombosis in 11 cases. Forty-nine (40.5%) patients with NBD have been followed-up for a median of 3 years (range 1-19 years). Forty-one of them recovered well without significant residual disability, 5 patients made no improvement and are left with severe neurological impairments and 3 died. Male gender and CNS parenchymal lesions occurrence were significantly associated with a poorer prognosis. CONCLUSION: Clinical and epidemiological features of NBD are various. In our Tunisian cohort of NBD patients the main characteristic features were male predominance, a relatively high prevalence of CVT, a low prevalence of intra-cranial hypertension and a significant lower frequency of HLA-B51 haplotype.