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Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007-2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Co‐occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations. Methods: We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis‐ichthyosis‐deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method). Results: The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale‐Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively. Conclusions: The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co‐occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling. [ABSTRACT FROM AUTHOR]

Inflammatory Tinea capitis (TC) is a rare form of TC. The aim of this study was to review epidemiological, clinical and mycological profile of inflammatory TC. We present a retrospective study (1999-2010), enrolled all the cases of inflammatory TC observed at a referral hospital in the northern Tunisia. One hundred and twenty-one patients with inflammatory TC, 83 male patients (68.6%) and 38 female patients (31.4%) were enrolled. The mean age was about 8 years. A majority of TC (71.9%) were in patients lesser than 10 years of age. Positive family history and contact with animals were noted in seven and 35 cases respectively. Direct examination was positive in 110 cases (59 ectothrix, 51 endothrix) and positive cultures were obtained in 105 patients (49 Trichophyton violaceum, 31 Microsporum canis, 13 Trichophyton interdigitale complex, 12 Trichophyton verrucosum). Systemic treatment was carried out in 115 patients with griseofulvin, in one with terbinafine. A complete recovery was noted in 88 cases; and persistent alopecia in 28 cases. The inflammatory TC is rare, but more common in rural families. The disease mostly affected male genders (68.6%) and T. violaceum remains the common pathogen of inflammatory TC in northern Tunisia. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of all forms of psoriasis remains obscure. Segregation analysis and twin studies together with ethnic differences in disease frequency all point to an underlying genetic susceptibility to psoriasis, which is both complex and likely to reflect the action of a number of genes. Materials and methods In the present study, we performed a family-based association study, and a transmission dysequilibrium test using the PLINK program, in a set of seven Tunisian multiplex families using a panel of 96 single-nucleotide polymorphisms localized in several regions across the genome. Ninety-five of them were reported to be associated with psoriasis in different populations. Results Besides the confirmation of association between previous associated regions: 6p, 1p, 2p, 13q, 14q, and 20p, and cutaneous psoriasis, we identified a new association with the rs1249564 in the IL17RD gene. Conclusion Our results support the complex genetic basis of psoriasis. [ABSTRACT FROM AUTHOR]

Background Autoimmune bullous dermatoses (ABD) are a rare but significant group of cutaneous disorders posing great diagnostic and therapeutic challenges to the treating dermatologist. Few surveys have been carried out to describe the whole spectrum of ABD in a region. Objective To determine the clinicoepidemiological features of various ABD. Methods We retrospectively recruited all ABD cases seen during an 11-year period (1997-2007). Results One hundred and seventy-four patients were involved (16.3 cases/year). Pemphigus was observed to be the most common ABD (53%), with the majority being pemphigus vulgaris (61%) vs. 36% of pemphigus foliaceus (Tunisian pemphigus). Discussion Most epidemiological surveys have focused on a single or just one group of ABD. In our series, pemphigus foliaceus was relatively more prevalent than in occidental data. The frequencies of subepidermal immunobullous dermatoses in our study were in agreement with those in the literature. [ABSTRACT FROM AUTHOR]

Introduction Adverse cutaneous drug reactions (ACDR) are common, and some can be lethal. The aim of our study was to discuss the epidemiological and clinical features of severe ACDR. Materials and methods We retrospectively analyzed 100 cases of ACDR from 1981 to 2007, collected in the Department of Dermatology of the La Rabta Hospital in Tunis, which is located in the north of Tunisia. Severity was defined on three criteria: hospitalization; visceral involvement; and severity markers. Results Characteristics of the 54 included cases were: women (70%); mean age: 44.8 years; responsible drugs: anticonvulsants (28%), antibiotics (28%), and nonsteroidal anti-inflammatory drugs (15%). The most common dermatoses were maculopapular rash (50%). We observed fever (76%), lymphadenopathy (31.5%), eosinophilia (35%), and visceral involvement (50%). Twelve patients died directly related to the ACDR. Conclusion This study underlines the polymorphous clinical presentation of ACDR and the importance of researching some severity markers, which have important practical implications. [ABSTRACT FROM AUTHOR]

The article presents a study which intends to identify the clinical and epidemiological characteristics of cutaneous leishmaniasis (CL) in Tunisia. The study examined 160 CL patients divided into two groups such as the childhood and adult groups. The study used Fisher exact test and Pearson's chi-square to compare the different parameters between the groups. The study showed no observed significant difference between the groups relative to clinical forms, active lesions duration, and sex ratio.

Background: Risk factors for erysipelas (cellulitis) were rarely evaluated in controlled studies. Regional variations of these risk factors have never be assessed. Objective: To assess risk factors for erysipelas of the leg in Tunisia. Subjects and Methods: Case-control study in seven hospital centers in Tunisia. Cases were 114 consecutive patients with erysipelas of the leg [sudden onset (<24 h) of a well-demarcated dermo-hypodermatitis with fever or chills]. Two controls were matched to each case for age, sex, and hospital (n = 208). Main outcome measures are local and general suspected risk factors for erysipelas of the leg. Results: In multivariate analysis, disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0–31) and 7.0 (1.3–38). No association was observed with diabetes, alcoholism, or smoking. Conclusions: We confirmed the major role of local risk factors and the minor role of general risk factors for erysipelas of the leg, in a setting different than the one previously studied. Detecting and treating toe-web intertrigo and traumatic wounds should be considered in the prevention of erysipelas of the leg. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Xeroderma pigmentosum is an autosomal recessive disease characterized by a high sensitivity to UV radiations. The disease is clinically and genetically heterogeneous, thus making accurate early clinical diagnosis difficult. Although the disease is considered rare worldwide, previous studies have shown that it is more frequent in Maghreb countries. So far, no genetic study has been published on Libyan patients, except three reports limited to clinical descriptions., Methods: Our study, which represents the first genetic characterization of XP in Libya, was conducted on 14 unrelated families including 23 Libyan XP patients with a consanguinity rate of 93%. Blood samples were collected from 201 individuals including patients and their relatives. Patients were screened for founder mutations already described in Tunisia., Results: The two founder Maghreb XP mutations, XPA p.Arg228* associated with the neurological form and XPC p.Val548Alafs*25 in patients with only cutaneous manifestations, were homozygously identified. The latter was predominant (19 of 23 patients). In addition, another XPC homozygous mutation (p.Arg220*) has been identified in only one patient. For the remaining patient, the absence of founder XPA, XPC, XPD, and XPG mutations suggests mutational heterogeneity of XP in Libya., Conclusion: Identification of common mutations with other Maghreb populations is in favor of a common ancestor in North-African populations., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Competing Interests: Drs. Charlotte Bernigaud and Olivier Chosidow act as unpaid scientific advisors for Medicines Development for Global Health. Olivier Chosidow is a member of the International Alliance for the Control of Scabies (IACS) steering committee and Charlotte Bernigaud is a member of the IACS. The authors have declared that no other competing interests exist.

A possible etiological link between the onset of endemic pemphigus in Tunisia and bites of Phlebotomus papatasi, the vector of zoonotic cutaneous leishmaniasis, has been previously suggested. We hypothesized that the immunodominant P. papatasi salivary protein PpSP32 binds to desmogleins 1 and 3 (Dsg1 and Dsg3), triggering loss of tolerance to these pemphigus target autoantigens. Here, we show using far-Western blot that the recombinant PpSP32 protein (rPpSP32) binds to epidermal proteins with a MW of approximately 170 kDa. Coimmunoprecipitation revealed the interaction of rPpSP32 with either Dsg1 or Dsg3. A specific interaction between PpSP32 and Dsg1 and Dsg3 was further demonstrated by ELISA assays. Finally, mice immunized with rPpSP32 twice per week exhibited significantly increased levels of anti-Dsg1 and -Dsg3 antibodies from day 75 to 120. Such antibodies were specific for Dsg1 and Dsg3 and were not the result of cross-reactivity to PpSP32. In this study, we demonstrated for the first time to our knowledge a specific binding between PpSP32 and Dsg1 and Dsg3, which might underlie the triggering of anti-Dsg antibodies in patients exposed to sand fly bites. We also confirmed the development of specific anti-Dsg1 and -Dsg3 antibodies in vivo after PpSP32 immunization in mice. Collectively, our results provide evidence that environmental factors, such as the exposure to P. papatasi bites, can trigger the development of autoimmune antibodies.

Lesion features in cutaneous leishmaniasis (CL) depend on the infecting Leishmania species as well as on host immune reponse. In this study, we evaluated the histological and immunological differences between two forms of CL described in Tunisia: zoonotic cutaneous leishmaniasis (ZCL) caused by L. major and sporadic cutaneous leishmaniasis (SCL) caused by L. infantum. Histological analysis showed a mild to moderate infiltrate within ZCL lesions. In contrast, massive infiltration of the dermis was observed within SCL lesions. Contrary to ZCL, infiltrates within SCL lesions were organized and showed granuloma composed of macrophages and lymphocytes. In addition, immunohistochemical analysis showed a predominance of CD4 + T cells within both CL forms. Furthermore, expression of interferon-γ, interleukin (IL)-10, IL-8, IL-13 and monocyte chemotactic protein (MCP)-1 was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR). MCP-1 and IL-10 were expressed at comparable levels in ZCL and SCL lesions. Interestingly, IL-8 mRNA levels were significantly higher in ZCL lesions compared to SCL lesions, but interferon-γ was significantly higher in SCL lesions than in ZCL lesions., (© T. Boussoffara et al., published by EDP Sciences, 2019.)

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major infection is characterized by different clinical presentations which depend in part on the host factors. In attempt to investigate the impact of the host's immune response in the outcome of the disease, we conducted a prospective study of 453 individuals living in endemic foci of L. major transmission in Central Tunisia. Several factors were assessed at the baseline including (i) the presence of typical scars of ZCL, (ii) in vivo hypersensitivity reaction to leishmanin, and (iii) the in vitro release of granzyme B (Grz B) by peripheral blood mononuclear cells (PBMC) in response to stimulation with live L. major promastigotes. After one season of parasite's transmission, repeated clinical examinations allowed us to diagnose the new emerging ZCL cases. Heterogeneity was observed in terms of number of lesions developed by each individual as well as their size and spontaneous outcome, which led us to establish the parameter "severity of the disease." The efficacy of the presence of typical ZCL scar, the leishmanin skin test (LST) positive reactivity and the high levels of Grz B (≥2 ng/ml), in the protection against the development of ZCL were 29, 15, and 22%, respectively. However, these factors were more efficient against development of intermediate or severe forms of ZCL. Levels of Grz B >2 ng/ml showed the best efficacy of protection (equals to 72.8%) against development of these forms of ZCL. The association of such parameter with the positivity of the LST exhibited a better efficacy (equals to 83.6%). In conclusion, our results support the involvement of Leishmania -specific cytotoxic cellular immune response in host protection against Leishmania -infection. This factor could be of great interest in monitoring the success of vaccination against human leishmaniasis.

Background: Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease. It represents one of the symptoms of atopic diathesis. DA affects usually infants and children. aim : The aim of our study is to draw up the epidemiological, clinical features, treatment and outcome of severe childhood AD through a hospital series. methods: A retrospective study of 24 cases of severe childhood AD hospitalized in the Dermatology Department of La Rabta hospital of Tunis was conducted during a 28 year-period (1981 - 2009). results: The hospital incidence of severe childhood AD was 0,085‰. Patient's mean age at the beginning was 14 months. The sex ratio H/F was 1.66. Cutaneous manifestations occurred preferentially in face (75%). Generalized eczema was observed in 37.5% of cases. Pruritus and xerosis were constant. The mean duration of hospitalization was 11 days. Topical corticosteroids was the most effective method of treating severe DA, associated with antiseptic solutions emollient and antihistaminic drugs. Infectious complications were noted in 50% of cases. Ocular complications were observed in 16.7% of cases. Recurrences were reported in 9 cases. Conclusion :AD is an inflammatory, chronically relapsing, and pruritic skin disorder developing in a xerotic skin. Severe AD in childhood is rare in Tunisia. It requires a good understanding of therapeutic modalities by the patient and his family. It is a cause of important morbidity and it may have a bad impact on quality of life.

Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG&#95;009252.1: g.36847&#95;40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.

Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner-Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the present study, we report clinical features and molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in two young patients, both born to consanguineous unions between first-degree cousins. These two unrelated families originated from Northern and Southern Tunisia. The clinical diagnosis was based on the observation of several complications related to Richner-Hanhart syndrome: recurrent eye redness, tearing and burning pain, photophobia, bilateral pseudodendritic keratitis, an erythematous and painful focal palmo-plantar hyperkeratosis and a mild delay of mental development. The diagnosis was confirmed by biochemical analysis. Sequencing of the TAT gene revealed the presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs 6). Early diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and the severity of long-term complications of hypertyrosinemia such as intellectual disability., (© 2013 Elsevier B.V. All rights reserved.)

Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

Background: To assess the ten-year cardiovascular risk for coronary heart disease (CHD) in psoriatic patients and to test the impact of psoriasis severity and duration on cardiovascular risk., Methods: A case-control study included 202 adult psoriatic patients and 202 controls., Results: Risk CHD was estimated using the Framingham risk score algorithm. Patients had a higher ten-year Framingham risk score (13.62 +/- 11.86 vs. 9.23 +/- 8.04; p = 0.002) than controls. In addition, a high risk score and a very high risk score (> 40%) were more frequent in psoriatic patients compared with controls (p = 0.043 and p < 0.001, respectively). According to the severity of psoriasis, the ten-year cardiovascular risk increases progressively and significantly (11.84 +/- 10.08; 15.59 +/- 11.79 and 16.92 +/- 14.13 for mild, moderate and severe psoriasis, respectively)., Conclusions: Psoriatic patients have significantly greater risks of developing coronary heart disease than controls in relationship with psoriasis comorbidities such as hypertension, diabetes, dyslipidemia, inflammation and probably with psoriasis itself.

Xeroderma Pigmentosum (XP) is a rare recessive autosomal cancer prone disease, characterized by UV hypersensitivity and early appearance of cutaneous and ocular malignancies. We investigated four unrelated patients suspected to be XP-C. To confirm linkage to XPC gene, genotyping and direct sequencing of XPC gene were performed. Pathogenic effect of novel mutations was confirmed by reverse Transciptase PCR. Mutation screening revealed the presence of two novel mutations g.18246G>A and g.18810G>T in the XPC gene (NG&#95;011763.1). The first is present in one patient XP50NEF, but the second is present in three unrelated patients (XP16KEB, XP28SFA, and XP45GB). These 3 patients are from three different cities of Southern Tunisia and bear the same haplotype, suggesting a founder effect. Reverse Transciptase PCR revealed the absence of the XPC mRNA. In Tunisia, as observed in an other severe genodermatosis, the mutational spectrum of XP-C group seems to be homogeneous with some clusters of heterogeneity that should be taken into account to improve molecular diagnosis of this disease.

An association between a common deletion comprising the late cornified envelope LCE3B and LCE3C genes (LCE3C&#95;LCE3B-del) and psoriasis has been reported in Caucasian and Asian populations. To investigate whether this deletion plays a role in the genetic of psoriasis in Tunisian population, we determined the LCE3C&#95;LCE3B-del genotype in 180 Ps patients and 208 healthy controls from different regions of Tunisia. The LCE3B and LCE3C gene variant was determined in the patients through PCR amplification and the SPSS software package. The frequency of the LCE3C&#95;LCE3B-del was similar between patients and healthy controls. Subanalyses by family history revealed that the frequency of LCE3C&#95;LCE3B-del was significantly higher in patients with a positive family history than in control individuals, as well as in individuals with a positive family history versus those without in the case cohort. However, no significant difference was observed between psoriatic patients with no family history and controls. We also evaluated the relationship between LCE3C&#95;LCE3B-del and PSORS1. No significant epistatic effect was observed suggesting that there was no significant epistasis of the two loci in the Tunisian population. Our findings indicate that the LCE3C&#95;LCE3B-del might play a role in familial psoriasis in the Tunisian population.

Background: Cutaneous manifestations are the most common extra intestinal manifestations associated with inflammatory bowel disease (IBD)., Aim: To assess the epidemio-clinical profile of skin manifestations in IBD., Methods: A prospective and descriptive study was conducted. We have examined skin, mucosa, hair and nails, of all patients with an IBD during one year., Results: One hundred-ninety-five patients were included. Crohn's disease (CD) was noted in 154 cases (79.8%), ulcerous rectocolitis (UC) in 39 cases (21.2%) and inclassable IBD in 2 cases. Cutaneous manifestations were found in 91% of Crohn's patients and in 92% of UC patients. Granulomatous perianal skin lesions were the main cutaneous manifestations of CD (53%). The most common affected sites were ano-perineal fistulae, perianal and perineal fissures and oedematous and infiltrated perianal and genital plaques. Reactive lesions (Erythema nodosum, Pyoderma gangrenosum, Aphthous stomatitis) were noted in 14 cases. Skin manifestations due to malabsorption were also frequently observed (101 cases: 51.7%).Other dermatoses implicating various mechanisms such as psoriasis, alopecia areata, vitiligo, rosacea, lichen planus, were also noted. Adverse skin manifestations due to treatment (folliculitis, acne, macula-papular rash and DRESS syndrome) were present in 16 cases., Conclusion: Our series is characterized by a high frequency of cutaneous manifestations associated to IBD. A better recognition of these skin manifestations by the physician may improve their management.

Background: Kaposi's sarcoma (KS) is a mutifocal angiogenic process characterized by cellular and vascular proliferation., Aim: To identify the epidemio-clinical, histological and therapeutic features of KS., Methods: Retrospective study of 75 cases of KS at the dermatology department of Rabta hospital in Tunis during a period of 25 years (1982-2007)., Results: Three epidemio-clinical forms of KS were observed in our study: the classic KS (70 cases), the AIDS-related KS (4 cases) and the iatrogenic KS (1 case). The mean age of our patients at diagnosis was 69.16 years with a sex ratio of 2.33. Elective site of cutaneous lesions in the classic KS was the limbs (87.1%). The cephalic part was concerned in 17.1% of cases. Mucosal involvement was found in 28.5% of patients. Extra dermatological localizations of KS were observed in 32.9%., Conclusion: Our study identified some epidemio-clinical features of the classic KS especially the high frequency of mucosal and cephalic involvement as well as extra dermatological localizations. Thus further exploration is required even without alarm signs.

Background: the erythrodermic psoriasis (EP) is a rare but severe form of psoriasis that may be potentially life-threatening., Aim: To study the characteristics of this severe form of psoriasis., Methods: We present a retrospective study, including all cases of EP followed in the dermatology department of the La Rabta hospital of Tunis over a 31-year-period from January, 1980 to June, 2010., Results: sixty patients were included, concerning 46 men and 14 women, with an average age of 53.7. A history of psoriasis was reported in 78 % of the cases. A triggering factor was found in 53 % of the cases. Systemic treatments were required in 55 % of cases. An improvement was noted in 69.4 % of the cases. A recurrence of the EP was observed in 15% of the cases. Three cases of sepicemia and one of stroke were noted., Conclusion: Erythrodermic psoriasis is the most common etiology of erythroderma. It represents more than half of severe psoriasis. As shown in our study it affects mainly adults' males. It complicates usually a common psoriasis. Septic and thromboembolic complications ones justify a close follow up.

Pemphigus is a severe autoimmune blistering disorder, in which immunoglobulin G autoantibodies are directed against desmosomal glycoproteins. The antibodies against desmogleine1 are prevalent in normal subjects living in Tunisia, that suggests the role of environment in the pathogenesis of this endemic type of pemphigus and the need for additional factors to switch from a subclinical form to a clinical form of the disease. The aim of this study was to investigate explanatory environmental factors. We tested the hypothesis that normal subjects whom presented staphylococcal infections have antibodies against desmoglein. We recruited 29 patients with staphylococcal infections from the dermatology department of the university hospital of Tunis. 29 controls healthy subjects are used to compare the prevalence of anti-desmoglein1 and 3 between these two groups. We used a specific and sensitive enzyme linked immunosorbent assay to detect autoantibodies against Dsg1. (10.3% versus 7% in healthy Tunisian blood donors: p < 0.05). Conversely, we observed a significant association with antibodies against Dsg3 (20.78% versus 3% in healthy Tunisian blood donors: p < 0.05). Subclasses analysis of anti-desmoglein antibodies showed that they were almost exclusively the IgG 1, 2 and 3 subclasses in positive normal sera. The antibodies against desmogleins binding activity of these positive sera were confirmed by indirect immunofluorescence analysis and by immunobloting using human epidermal extract. In conclusion, we detected autoantibodies in the sera of patients with staphylococcal infections and found elevated levels of autoantibodies against Dsg 3.

Background: Behçet's disease (BD) is a systemic inflammatory disease involving many systemic lesions characterized by vasculitis as a common basic pathologic process. Mucocutaneous (MC) features are considered as the diagnostic hallmarks., Aim: To retrospectively determine the epidemiological and clinical aspects of BD mucocutaneous symptoms in Tunisia compared to those found in the literature., Methods: Twenty-eight patients were involved in a single-center dermatological recruitment for a 27-year period (1980-2007) on the basis of international BD criteria., Results: Our series included 19 males and 9 females. The mean age at onset was 28 years and the mean age at diagnosis was 37.9 years. The frequency of MC manifestations was as follows: oral ulcers (100%), genital ulcers (92.8%), other cutaneous signs (82.1%) such as papulopustular lesions (53.5%), and dermohypodermal nodes (11.53%), aphthous cutaneous ulcers (17.8%), and other lesions (leg ulcer: three cases, erythema multiform: one case, and infected pyodermatitis: one case). Systemic manifestations were present in 18 patients., Conclusions: MC manifestations are hallmarks of the disease and usually the onset symptoms. The frequencies of the various MC signs seen in our study broadly match those found in the literature.

Background: hidradenitis suppurativa (HS) is a chronic inflammatory, suppurating, fistulizing, and scar-producing disease of apocrine gland-bearing skin. The diagnosis is primarily clinical, based on the presence of both sinus tracts and abscesses with a characteristic distribution., Objective: Review of epidemiological, clinical, and prognostic characteristics of HS and discussion of the etiopathogenic aspects of this chronic problem., Patients and Methods: We retrospectively report all cases of HS followed at the Department of Dermatology between January 1985 and December 2008., Results: Eleven patients (10 male and 1 female), with a mean age of 35.2 years (range 21 dash, vertical53 years) at HS diagnosis were followed for HS. The average age of disease onset was 23.9 years. The median delay between onset of symptoms and diagnosis was 144 months (range 1 dash, vertical408 months). Clinical features showed inflamed discharging papules or nodules, painful tender erythematous nodules, and double-ended comedones. The disease mainly affected the axillary, anal, perineal, and genital areas. Histologically, dermal features showed active folliculitis or abscess, sinus tract formation, fibrosis, and granuloma formation. Pathological associations (Darier's disease and Down syndrome) were noted in two patients. Treatment consisted of antibiotics in eight patients, retinoids (1 mg/kg/ day) in three patients, and surgery in three patients. The mean follow-up was 13 months (range 2 dash, vertical30 months). Recurrence of lesions was observed in all patients approximately 1 month after treatment withdrawal. The Down syndrome patient developed vaginal hydrocele of the testis as a complication of his staphylococcic ulcers. In all cases healing occurred with substantial scarring., Discussion: An obvious male predominance was noted in our patients as well as a delay in the diagnosis of HS, which could be explained by non-recognition of the disease by non-specialists that see the patients at the primary-care level.

Objective: To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients., Design: Case series., Setting: Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia., Patients: Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members., Main Outcome Measure: Patients were investigated at the clinical, histological, and genetic levels. Families were genotyped with 5 microsatellite markers spanning the ATP2A2 gene. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene., Results: Typical clinical features of DD were constantly present. Phenotypic variation within and between the studied families was observed. Different neuropsychiatric disorders were seen in 5 families, and various cutaneous and extracutaneous original clinical associations were observed. The haplotype analysis led to the identification of different haplotypes cosegregating with the disease in the studied families. Mutation screening of the ATP2A2 gene revealed 3 recurrent mutations (119-120delAG, R677X, and D702N) and 4 novel variations: 2 missense mutations (G217A and L900R), one microinsertion (2772-2779 ins C), and one microdeletion (1747-1749 del 2T)., Conclusions: Our findings provide evidence for clinical and mutational heterogeneity of Tunisian families with DD. No obvious phenotype-genotype correlation was established. To our knowledge, this is the first molecular investigation of DD in the North African population.

Transgressive palmoplantar keratoderma (PPK) is the phenotypic hallmark of Mal de Meleda (MDM, MIM 24300). It is characterized by erythema and hyperkeratosis that extend to the dorsal face of the hands and feet. The disease is distributed worldwide and includes the Mediterranean population. The gene responsible for MDM, ARS (component B) mapped on chromosome 8qter, encodes for the SLURP-1 protein (Ly-6/uPAR related protein-1). A variety of mutations within the ARS gene have been shown to underlie MDM in different populations. Genetic heterogeneity of MDM is suspected. We have recently shown that three different homozygous mutations (82delT, C77R, C99Y) were responsible for MDM in 17 patients from Northern Tunisia belonging to eight unrelated consanguineous families. We report here a Tunisian family with three siblings presenting with recessive transgressive PPK closely resembling the MDM phenotype that excludes linkage to the ARS gene.

To accurately quantify the different outcomes of Leishmania major infection and to evaluate the fraction of zoonotic cutaneous leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin skin test (LST) reactivity, a cohort of 470 children was followed up in 2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997, before the ZCL emergence season, LST was performed, and results were reassessed 12 months later. Active case detection during the ZCL emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity increased proportionally with the reaction size before the emergence season, revealing a dose-response effect of approximately 70%. In addition, asymptomatic L. major infection appeared to be a significant form of natural immunization, particularly in the context of relatively low transmission. These findings may help in the design and evaluation of vaccines.

Discoid lupus erythematosus (DLE) is uncommon in children. The clinical features of childhood DLE are similar to those of adult DLE in presentation and chronic course. However, children have a particularly high level of transition to systemic disease. We undertook a retrospective study of 16 children with DLE ranging in age from 2 to 15 years, seen over a 9-year period. Six were less than 10 years old at the onset of the disease. The sex ratio was equal. The frequency of childhood DLE was about 7% of the total number of DLE patients seen in our department. Photosensitivity was defined as a clinical history of induction or exacerbation of discoid lesions following sun exposure, and was present in 81% of patients. There was no progression to systemic lupus erythematosus (SLE); an average follow-up time was 10.5 months (2-30 months). We would like to emphasize the increased frequency of childhood DLE in our country and the importance of photosensitivity. However, follow-up data regarding transition to SLE is lacking, therefore we are unable to offer a prognosis to our patients.