A posteriori diagnosis of DRESS syndrome induced by diazoxide in a patient with an insulinoma: a case report and review of the literature.

The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome can be potentially life-threatening. The diagnosis is sometimes difficult since the clinical manifestations may be incomplete or non-specific. Insulinoma is a rare functioning neuroendocrine tumor (NET) of the pancreas. Medical therapy may be needed when surgery is contraindicated, delayed or refused. Diazoxide is widely used to control hypoglycemia in patients with insulinoma. We report a clinical case of an insulinoma in a 85-year-old patient treated with diazoxide with a fatal outcome due to a delayed diagnosis of a DRESS syndrome. This is the first case of DRESS syndrome reported after using diazoxide for insulinoma treatment in our knowledge.

Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT).

OBJECTIVES: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls. METHODS: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments. RESULTS: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5 %) including 35 with short stature, 13-18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %). CONCLUSIONS: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time.

Acute adrenal crisis precipitated by thyroid storm in a patient with undiagnosed autoimmune polyglandular syndrome type 2.

Summary: Autoimmune polyglandular syndrome (APS) type 2 is characterized by the presence of Addison's disease (AD) along with autoimmune thyroid disease and/or type 1 diabetes. APS type 2 is known as Schmidt's syndrome when autoimmune adrenal insufficiency is associated with chronic lymphocytic thyroiditis. We report a very rare case of a 28-year-old female patient who had Schmidt's syndrome revealed by a thyroid storm (TS) concomitant with an acute adrenal crisis. The onset of AD resulted in a surgical emergency. The patient presented with cardiogenic shock and an acute abdomen. The precipitation factor was Hashitoxicosis presented as TS. This life-threatening condition was successfully reversed with aggressive medical therapy based on antithyroid drugs and intravenous glucocorticoids. This hyperthyroid phase lasted for a period of 8 months. The patient eventually developed hypothyroidism, suggesting that Hashimoto's thyroiditis was the most likely diagnosis. She was started on levothyroxine replacement therapy and remained euthyroid on levothyroxine. The case we describe had several diagnostic pitfalls that are discussed both at the start as well as during the evolution. Learning points: Autoimmune diseases can appear concomitantly or succeed each other over time. The clinician must be vigilant to detect these diseases in time in order to avoid a misdiagnosis of a life-threatening emergency such as adrenal insufficiency or thyroid storm. Thyroid storm is an uncommon but life-threatening manifestation of hyperthyroidism. Diagnosis is dependent on clinical symptoms, and no specific laboratory tests are available. Glucocorticoids should be used in the treatment of thyroid storm because they have an inhibitory effect on peripheral conversion of T4 to T3. In patients who have severe thyrotoxicosis, especially in conjunction with hypotension, treatment with glucocorticoids has become standard practice because of the possibility of relative adrenal insufficiency or the possibility of undiagnosed Addison's disease. The differential diagnosis of hyperthyroidism can be challenging. Graves' disease can be discussed in view of the severity of the clinical presentation and the prolonged duration of the hyperthyroid phase. Hashitoxicosis is the initial hyperthyroid phase in chronic autoimmune thyroiditis. The hyperthyroid phase is always followed by definitive resolution, with persistent euthyroidism and no hyperthyroid relapses. Synthetic antithyroid drugs may be prescribed during the hyperthyroid phase of Hashimoto thyroiditis if the clinical presentation is severe and the duration of the hyperthyroid phase is prolonged.

The use of baseline cortisol level in predicting the outcome of 1 µg Synacthen tests in an outpatient endocrinology unit.

Introduction: The clinical requirements and the indication of the Synacthen test are increasing. The objective of our study is to determine a baseline cortisol level that reliably predicts the response to Synacthen test in a low-risk group of patients. Materials and methods: We performed a cross-sectional analysis of all Synacthen tests conducted between January 2017 and June 2018. The diagnostic accuracy of basal cortisol levels as a predictor of an adequate response to Synacthen test was evaluated by ROC curve analysis. Results: One hundred and fifty-three patients were included. A baseline cortisol level <40 ng/mL had a sensitivity of 100% but a specificity of 5.8% for the failure of the Synacthen test, while a baseline cortisol level> 147.5 ng/mL showed a specificity of 100% but a sensitivity of 1.2% for an adequate response to the Synacthen test. According to the ROC curve, the optimal baseline cortisol level for predicting an adequate response to the Synacthen test was 85 ng/mL with an AUC of 0.808 (95% CI [0.738-0.877]). Conclusion: We propose a basal cortisol level assay as a first step in the evaluation of patients with suspected adrenal insufficiency.

A cost-effectiveness analysis of PHiD-CV compared to PCV13 in a national immunization program setting in Tunisia.

BACKGROUND: In response to the substantial clinical and economic burden of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) in Tunisia, the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was recently introduced into the national immunization program. However, there has yet to be a full-scale health economic analysis comparing currently available pneumococcal conjugate vaccines (PCVs) in Tunisia. METHODS: A Markov model that simulated the disease processes of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) over a newborn cohort lifetime was used to evaluate the cost-effectiveness/utility of PHiD-CV and the 13-valent pneumococcal conjugate vaccine (PCV13) from payer's perspective, using 3% discounting. Vaccine effects were considered for up to 9 years of age. RESULTS: Vaccination with PHiD-CV or PCV13 was estimated to avert approximately 700 cases of IPD (200 meningitis, 500 bacteremia), and around 5,000 cases of all-cause pneumonia. However, PHiD-CV vaccination was estimated to avert around 4,000 additional AOM cases (18,000) versus PCV13 (14,000). Both PCVs were demonstrated to be cost-effective interventions, but PHiD-CV was estimated to generate additional cost savings of almost $1 million US dollars (USD) with similar levels of clinical benefits. An additional scenario which incorporated serotype-specific vaccine efficacy found no significant change in overall results. CONCLUSION: PCVs are a cost-effective strategy to relieve the burden associated with diseases caused by S. pneumoniae and NTHi in Tunisia. PHiD-CV is more cost-effective than PCV13, generating similar health benefits, at a reduced net cost of almost $1 million USD per vaccinated cohort.

Parental self-medication with antibiotics in a Tunisian pediatric center.

INTRODUCTION: Self-medication of antibiotics among children is a very common problem in Tunisia. Its prevalence isn't well established. The aims of this study are to evaluate parents' knowledge concerning antibiotic use, and identify the factors associated with this problem. PATIENTS AND METHODS: We conducted a cross-sectional study over a one year period (between August 2019 and July 2020). Data collection was performed using a questionnaire guided interview. We included parents of children consulting or hospitalized in the pediatric department of the university hospital Taher Sfar in Mahdia. RESULTS: A total of 354 parents were included with an average age of 36.4±9.2 years. The average knowledge score was 2±1.3 points. In fact, 61.6% of the parents had poor knowledge about antibiotics. The frequency of non-prescription antibiotics use among children was 20.6%. Amoxicillin was the most used antibiotic (72.6%). Sore throat, important fever and flu-like symptoms were the main symptoms justifying non-prescription antibiotic use among our pediatric population in 60.3%, 34.2% and 23.3% of cases respectively. The main reason of self-medication was the fact that the same antibiotic was once prescribed to treat the same symptoms (58.9%). The used antibiotic came from an old prescription for the same child in 57.5% of the cases and was recommended by the pharmacist in 39.7% of the cases. After multivariate analysis, the factors associated with parental self-medication with antibiotics were: the advanced parent's age, the ability to name an antibiotic and knowledge's score>2. CONCLUSION: Our study confirmed that parental knowledge about antibiotic use is low. In fact, the government should from one hand, organize antibiotic delivery and prohibit off the counter sells and in the other hand promote the education of the public through different procedures to stop this major health problem.

Combined sclerosis of the spinal cord revealing Biermer's anemia: about a case.

Biermer's anemia is an auto immune disease that can lead to neurological manifestations. Medullary combined sclerosis accounts for only 10% of neurological complications. There are few reports of documented bone marrow involvement by magnetic resonance imaging (MRI). Observation: We report a case of combined sclerosis of the cervical spinal cord assessed by cerebro-medullary MRI in a context of vitamin B12 deficiency in a 36-year-old patient who was hospitalized in the intensive care unit for septic shock with respiratory starting point, requiring the use of mechanical ventilation for 13 days and the discovery in post-extubation of pancytopenia with macrocytic anemia and flasquo-spasmodic tetraparesis prompting an emergency MRI showing combined sclerosis of the spinal cord , with vitamin B12 deficiency and megaloblastic anemia at the myelogram. The patient had benefited of vitamin therapy combined with a physical rehabilitation and the evolution was marked by a recovery of walking and normalization of biology after 2 months. Conclusion:    The advantage of medullary MRI in a severe clinical form with neurological impairment of vitamin B12 deficiency to guide the diagnosis. The treatment is based on vitamin therapy with a good evolution.

Preliminary national report on cystic fibrosis epidemiology in Tunisia: the actual state of affairs.

AIM: To establish a preliminary national report on clinical and genetic features of cystic fibrosis (CF) in Tunisian children as a first measure for a better health care organization. METHODS: All children with CF diagnosed by positive sweat tests between 1996 and 2015 in children's departments of Tunisian university hospitals were included. Data was recorded at diagnosis and during the follow-up from patients' medical records. RESULTS: In 12 departments, 123 CF children were collected. The median age at diagnosis was 5 months with a median diagnosis delay of 3 months. CF was revealed mostly by recurrent respiratory tract infections (69.9%), denutrition (55.2%), and/or chronic diarrhea (41.4%). The mean sweat chloride concentration was 110.9mmol/L. At least one mutation was found in 95 cases (77.2%). The most frequent mutations were Phe508del (n=58) and E1104X (n=15). Fifty-five patients had a Pseudomonas Aeruginosa chronic colonization at a median age of 30 months. Cirrhosis and diabetes appeared at a mean age of 5.5 and 12.5 years respectively in 4 patients each. Sixty-two patients died at a median age of 8 months. Phe508del mutation and hypotrophy were associated with death (p=0.002 and p<0.001, respectively). CONCLUSION: CF is life-shortening in Tunisia. Setting-up appropriate management is urgent.

Torsion of otherwise healthy ovary Has a worse prognosis than torsion of pathologic ovary in children.

INTRODUCTION: To evaluate if torsion of an otherwise healthy ovary (THO) has a different prognosis than torsion with an underlying ovarian mass (TUOM) in children. MATERIAL AND METHODS: Children with an ovarian torsion who were treated in our department from 1997 to 2016 were studied retrospectively. Patients with prenatal ovarian torsion and isolated oviduct torsion were excluded. Trophicity of the ovary was assessed by ultrasonography at the end of follow-up. RESULTS: Fifty-four girls were included. Twenty-seven presented a TUOM; the others had a THO. Beside the deleterious effect of late surgical management, another prognostic factor was identified. THO was more prone to an ovarian hypotrophy or atrophy than TUOM (n = 20 vs n = 5, p < 0.01). This was confirmed by logistic regression analysis (OR = 5.08, p = 0.01). To explain this finding, we further compared TUOM and THO. The diagnosis of TUOM was more frequently suspected on US at the first visit (p = 0.005). TUOM also occurred more often after puberty (>12 years, 52.9% vs 11.1%, p < 0.001) than THO. CONCLUSION: THO is more frequently associated with an ovarian atrophy or hypotrophy than TUOM. A less obvious diagnosis at US and the early occurrence of THO before puberty with a less favorable hormonal climate may explain this finding. LEVEL OF EVIDENCE: III.

Hospital cost of invasive pneumococcal disease in children aged under 15 years old in Tunisia.

BACKGROUND: Pneumococcal infections are an important cause of morbidity and mortality in the world and in Tunisia. Data on the economic burden of these infections are needed to inform decision-making to include pneumococcal vaccinations in routine childhood immunization. AIMS: This study aimed to estimate the medical cost of hospitalizations due to invasive pneumococcal disease (pneumonia and meningitis) among children aged under 15 years old in Tunisia. METHODS: A prospective multicentre study was conducted in 15 paediatric departments, across different socio-economic areas of Tunisia, from June 2014 to May 2015. All children aged under 15 years old who were hospitalized for pneumococcal pneumonia or confirmed bacterial meningitis were enrolled. A case report form was completed for every eligible case. Activity Based Costing method was used to estimate the hospital cost. Data entry and statistical analysis were conducted using SPSS, version 20.0. RESULTS: During the study period, 727 children were hospitalized for pneumococcal pneumonia and 60 children were hospitalized for bacterial meningitis, among them 21(35%) had confirmed pneumococcal meningitis. The median hospital cost for pneumococcal pneumonia was 353.910 Tunisian Dinars (TND) and TND 1680.632 for pneumococcal meningitis. Using overall data extrapolation, it was estimated that nearly 1091 hospitalizations for pneumococcal pneumonia and 69 hospitalizations for pneumococcal meningitis occurred each year in Tunisian children aged under 15 years of age, incurring total costs of TND 502 079.408. CONCLUSION: The economic burden of pneumococcal infections seems to be substantial in Tunisia. The estimated costs does not reflect the real costs of this infection. Cost-effectiveness studies would be helpful to inform policy-makers to take appropriate decisions.

Phenotypic variability in Tunisian PFIC3 patients harboring a complex genotype with a differential clinical outcome of UDCA treatment.

INTRODUCTION: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a chronic autosomal recessive disorder characterized by a wide spectrum of clinical severity generally related to the degree of pathogenicity of the causal sequence variation in ABCB4 gene. PATIENTS AND METHODS: The present study reports the molecular investigation by Next Generation Sequencing (NGS) of five related patients with PFIC3 disease followed by bioinformatic analysis. A biochemical follow-up is also performed to assess the response of the ursodeoxycholic acid treatment. RESULTS: The molecular results revealed complex genotype in homozygous state in all patients including a pathogenic c.1436C > T (P479L) variation in the ABCB4 gene and two well-known polymorphisms, the V444A in ABCB11 gene and the D19H in the ABCG8 gene. Although the presence of the same genetic background, all patients present the disease at different ages and clinical signs with a variable degree of clinical severity at diagnosis. Additionally, a differential outcome to the treatment has been pointed out. CONCLUSION: Our results provide evidence regarding the putative intervention of modifier factors in the phenotypic variability reported for the first time in the PFIC3 disease and highlight the importance of an early administration of the UDCA as a good solution to ovoid the disease progression.

Poikiloderma with neutropenia in a Tunisian patient with a novel C16orf57 gene mutation.

Poikiloderma with neutropenia (PN) is a genodermatosis characterized by poikiloderma, permanent neutropenia, recurrent infections, nail abnormalities, and palmoplantar hyperkeratosis. We report the case of a Tunisian patient with PN. Skin lesions started from the face and spread to the extremities and trunk. Neutropenia was initially periodic and concomitant with infections periods. DNA analysis identified a novel homozygous deletion of a 1-bp (c.161delC, p.P54RfsX60) in the C16orf57gene, presumed to be causative. This report presents the variability of the clinical manifestations and evolution of PN and emphasizes the importance of studying other patients with PN to better delineate mutations profile among populations.

[Corticosurrenaloma: an exceptional cause of primary hyperaldosteronism]. / Le corticosurrénalome: une cause exceptionnelle d'hyperaldostéronisme primaire.

Corticosurrenaloma is a rare malignant tumor of the adrenal gland that often secretes corticosteroids, sex steroids and precursors. Aldosterone-producing corticosurrenaloma is very rare, accounting for 1 case/10million inhabitants. We report the case of a 38-year old man presenting with severe arterial hypertension associated with deep hypokalaemia (2.2 mmol/L). Exploration showed primary hyperaldosteronism (aldosterone = 2645 pmol/l, aldosterone/renin ratio = 327 pmol/MUI), with hypersecretion of glucocorticoids. Abdominopelvic CT scan revealed left poorly differentiated and heterogeneous adrenal mass measuring 9cm, infiltrating into the surrounding adipose tissue and the diaphragm, extending into the left renal vein, with regional adenopathy and hepatic nodule measuring 4cm. The patient underwent radical nephrectomy followed by right hepatectomy two months after resulting in remission. A year after the patient developed lung metastases. This study highlights that corticosurrenaloma should be suspected in patients with primary aldosteronism despite its rarity.

Enterovirus meningitis in Tunisia (Monastir, Mahdia, 2011-2013): identification of virus variants cocirculating in France.

Acute enterovirus (EV) meningitis is a frequent cause of hospitalisation, and over 100 EV serotypes may be involved. A total of 215 patients of all ages with meningitis signs were investigated in 2 Tunisian hospitals. Their cerebrospinal fluid (CSF) was analysed retrospectively for EVs with a TaqMan real-time RT-qPCR. The virus strains were typed, and their evolutionary relationships were determined by Bayesian phylogenetic methods. An EV genome was detected in 21/215 patients (9.8%). The CSF viral loads ranged from 3.27 to 5.63 log10 genome copies/mL. The strains were identified in 13/21 patients and assigned to EV-B types. Viruses identified in Tunisian patients were genetically related to variants detected in France. The viral loads were similar in Tunisian and French patients for most EV types. The phylogenetic data and viral loads determined in Tunisian and French patients suggest that close EV variants were involved in aseptic meningitis in the 2 countries over a same period.

History of settlement of villages from Central Tunisia by studying families sharing a common founder Glycogenosis type III mutation.

Glycogen storage disease type III (GSD III; Cori disease; Forbes disease) is an autosomal recessive inherited metabolic disorder resulting from deficient glycogen debrancher enzyme activity in liver and muscle. In this study, we focused on a single AGL gene mutation p.W1327X in 16 Tunisian patients from rural area surrounding the region of Mahdia in Central Tunisia. This constitutes the largest pool of patients with this mutation ever described. This study was performed to trace the history of the patients' ancestries in a single region. After extraction of genomic DNA, exon 31 of AGL gene was sequenced. The patients were investigated for the hypervariable segment 1 of mitochondrial DNA and 17 Y-STR markers. We found that the p.W1327X mutation was a founder mutation in Tunisia Analysis of maternal lineages shows an admixture of autochthonous North African, sub-Saharan and a predominance of Eurasian haplogroups. Heterogeneity of maternal haplogroups indicates an ancient settlement. However, paternal gene flow was highly homogeneous and originates from the Near East. We hypothesize that the p.W1327X mutation was introduced into the Tunisian population probably by a recent migration event; then the mutation was fixed in a small region due to the high rate of consanguineous marriages and genetic drift. The screening for this mutation should be performed in priority for GSD III molecular diagnosis, for patients from the region of Mahdia and those from regions sharing the same settlement history.

Primary Hyperparathyroidism and Hyperthyroidism in a Patient with Myotonic Dystrophy: A Case Report and Review of the Literature.

Various endocrine manifestations are commonly described in myotonic dystrophy (MD), including primary hypogonadism, diabetes mellitus, and thyroid and parathyroid dysfunction. We describe a 46-year-old woman with a family history of MD with her son. She was diagnosed with cardiac arrhythmia and required the implantation of a pacemaker. She was noted to have a bilateral cataract. She complained of muscle weakness, diffuse myalgia, and palpitation. The electromyography (EMG) showed myotonic discharges. Laboratory tests showed high serum calcium 2.83 mmol/L, serum phosphate 1.2 mmol/L, parathormone 362.5 pg/mL, thyroid stimulating hormone TSH 0.02 mIU/L (normal range: 0.34-5.6 mIU/L), FT4 21.17 ng/mL, and negative anti-thyroperoxidase antibodies. Cervical ultrasound revealed a multinodular goiter. The 99mTc-MIBI scintigraphy localized a lower right parathyroid adenoma. The clinical data, the family history of MD, EMG data, and endocrine disturbances were strongly suggestive of MD associated with hyperthyroidism and primary hyperparathyroidism.

Seizures and movement disorders induced by hyperglycemia without ketosis in elderly.

BACKGROUND: Non-ketotic hyperglycemia (NKHG) may increase the probability of seizures and movement disorders. METHODS: We describe a series of 14 elders admitted for seizures and movement disorders linked to NKHG. RESULTS: Twelve patients developed motor seizures and two others movement disorders. Glucose levels varied 9.28 to 32 mmol/l, while osmolarity values varied from 302.28 to 328 mosmol/l. All patients responded well to insulin therapy and four of them needed anti-epileptic drugs. CONCLUSION: Seizures or movement disorders in elderly with NKHG could be misdiagnosed as neurological diseases. Blood glucose must be audited whenever patients with seizures or movement disorders are encountered, as the condition may quickly resolve when NKHG is controlled.