CUTANEOUS MANIFESTATIONS OF PRIMARY IMMUNODEFICIENCY DISEASES IN TUNISIAN CHILDREN

Abstract. Skin manifestations are frequent among patients with primary immunodeficiency diseases (PIDs). Their prevalence varies according to the type of immunodeficiency. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of PIDs among Tunisian children. We conducted a prospective study on two hundred and ninety children with immune deficiency. Demographic details (including age, sex, and consanguinity) with personal and family history were recorded. Special attention was paid to cutaneous manifestations. Dermatological involvements were grouped according to the etiology of their most prominent sign. Cutaneous manifestations were found in 164 patients (56.5%). They revealed the diagnosis of PIDs in 71 patients (24.5 %). The mean age at presentation was 21 months. Overall the most prominent cutaneous alterations were infectious. They accounted for 106 cases (36.55%). The most prevalent causes of cutaneous infections were bacterial: 93 cases (32.06%). Immuno-allergic skin diseases were among the common findings in our study. These include eczematous dermatitis found in 62 cases (21.38%). Malignancy related PIDs was seen in a boy with Wiskott Aldrich syndrome. He developed Kaposi’s sarcoma at the age of 14 months. Cutaneous changes are common among children with PIDs. In pediatric patients with failure to thrive, chronic refractory systemic manifestations often present in other family members, recurrent cutaneous infections unresponsive to adequate therapy, atypical forms of eczematous dermatitis or unusual features should arouse the suspicion of PIDs and prompt specialized immunologic consultation should be made

Oral HPV infection and MHC class II deficiency (A study of two cases with atypical outcome)

<p>Abstract</p> <p>Background</p> <p>Major histocompatibility complex class II deficiency, also referred to as bare lymphocyte syndrome is a rare primary Immunodeficiency disorder characterized by a profondly deficient human leukocyte antigen class II expression and a lack of cellular and humoral immune responses to foreign antigens. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections. The infections begin in the first year of life and involve usually the respiratory system and the gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood. Bone marrow transplantation is the curative treatment.</p> <p>Case reports</p> <p>Here we report two cases with a late outcome MHC class II deficiency. They had a long term history of recurrent bronchopulmonary and gastrointestinal infections. Bone marrow transplantation could not be performed because no compatible donor had been identified. At the age of 12 years, they developed oral papillomatous lesions related to HPV (human papillomavirus). The diagnosis of HPV infection was done by histological examination. HPV typing performed on the tissue obtained at biopsy showed HPV type 6. The lesions were partially removed after two months of laser treatment.</p> <p>Conclusions</p> <p>Viral infections are common in patients with MHC class II and remain the main cause of death. Besides warts caused by HPV infection do not exhibit a propensity for malignant transformation; they can cause great psychosocial morbidity.</p

BETA THALASSEMIA MAJOR IN A DEVELOPING COUNTRY: EPIDEMIOLOGICAL, CLINICAL AND EVOLUTIONARY ASPECT

Beta-thalassemia major (TM) remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months- 31 years) were included in the study.The majority were originated from the north west of the country .A moderate overload between 1501 and 2500ng/ml was found in 61patients, while 81 patients (26.9%) had ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%). 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social benefits and health benefits

Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases.

Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. We sought to investigate the incidence of gene mosaicism in patients with PIDs. The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs