Failure to find evidence for deletion of LCE3C and LCE3B genes at PSORS4 contributing to psoriasis susceptibility in Tunisian families.

BACKGROUND: Recently, it has been shown that a deletion in the late cornified envelope (LCE) gene cluster (LCE3C_LCE3B-del) is associated with susceptibility to psoriasis in European and Asian populations. However, no study of this deletion has been performed in the North African population. The aim of the present study was to investigate whether this deletion is associated with familial psoriasis in Tunisian population. METHODS: A total of 34 patients and 55 healthy individuals were recruited from 7 multiplex families and a PCR assay was used to determine the association of this deletion. Its effect on susceptibility to psoriasis was assessed using the PDT program. RESULTS: We failed to detect any evidence of association between LCE3C_LCE3B-del and psoriasis in Tunisian families. No epistasic effect was found between the deletion and PSORS1 locus. CONCLUSIONS: These findings indicate that the LCE3C_LCE3B-del does not contribute in a major way to psoriasis susceptibility in Tunisian families.

Genome-wide linkage scan for psoriasis susceptibility loci in multiplex Tunisian families.

BACKGROUND: Psoriasis is a relapsing chronic inflammatory skin disease affecting all population groups, with a peak prevalence of 3% in northern European and Scandinavian caucasians. Epidemiological studies have implicated a genetic component to psoriasis. In the past 12 years multiple genome-wide linkage analyses have identified putative susceptibility loci on several chromosomes, with a major locus in the major histocompatibility complex region. OBJECTIVES: To investigate the genetic basis of familial psoriasis in the Tunisian population using a genome-wide linkage scan in seven ultiplex psoriatic families from Tunisia. METHODS: Following single nucleotide polymorphism (SNP) genotyping on the Affymetrix 10K SNP array, we performed nonparametric linkage (NPL) multipoint analyses to identify genotypes and obtain evidence for linkage with psoriasis across the genome. RESULTS: No chromosomal region gave consistent evidence for linkage, providing evidence for genetic heterogeneity in Tunisian psoriasis families. Significant evidence for linkage of psoriasis to chromosome 2p12 was seen in one family. We also identified several regions of tentative psoriasis linkage on chromosomes 2q, 4q, 6p, 11q, 12q, 9q and 13q. One family exhibiting suggestive evidence for linkage to 17q25 (PSORS2) was identified and all affected members harboured a p.Gly117Ser mutation in CARD14 (caspase recruitment domain family, member 14), recently reported to lead to psoriasis in a large family from the U.S.A. CONCLUSIONS: Our results support the genetic heterogeneity of psoriasis in the Tunisian population, provide confirmatory evidence for a novel psoriasis locus at chromosome 2p12 and reveal a psoriasis family with a mutation at PSORS2.

A multicenter, randomized, open-label, controlled study comparing the efficacy, safety and cost-effectiveness of a sequential therapy with RV4104A ointment, ciclopiroxolamine cream and ciclopirox film-forming solution with amorolfine nail lacquer alone in dermatophytic onychomycosis.

BACKGROUND: The efficacy of topical antifungals is controversial. OBJECTIVE: To compare the efficacy and safety of a sequential(SEQ) treatment with chemical nail avulsion and topical antifungals to amorolfine nail lacquer in dermatophytic onychomycosis. METHODS: This was a randomized,parallel-group, controlled study comparing a 36-week SEQ treatment with chemical nail avulsion with RV4104A ointment(class I medical device containing 40% urea) followed by ciclopirox cream for 8 weeks and ciclopirox nail lacquer for 25 weeks (SEQ group) to amorolfine nail lacquer for 36 weeks (AMO group). Patients had to have a big toenail onychomycosis,sparing the matrix. The primary efficacy criterion was complete cure at week 48. A cost-effectiveness analysis was performed. RESULTS: A total of 142 patients were randomized. The complete cure rate at week 48 was significantly higher in the SEQ group than in the AMO group (36.6 vs. 12.7%, p = 0.001). Clinical cure at week 48 was observed in 53.5% of patients in the SEQ group versus 17% in the AMO group (p < 0.01). The cost of cure per patient was 50% lower with SEQ treatment (EUR 33) compared with amorolfine(EUR 76). CONCLUSION: A treatment of onychomycosis comprising chemical avulsion of the pathological nail, ciclopirox cream and nail lacquer is significantly more effective than amorolfine nail lacquer.

[Primary cutaneous osteosarcoma]. / Ostéosarcome cutané primitif.

BACKGROUND: Osteosarcoma is a malignant tumor of mesenchymatous origin that chiefly affects the metaphysis of long bones. The extraskeletal form of the disease is rare, and even rarer is a cutaneous site, whether metastatic or primary. Herein, we report a new case of primary cutaneous osteosarcoma. PATIENTS AND METHODS: A 54-year-old woman presented a hard subcutaneous nodular tumor on her left arm noted 1 year earlier. The diagnosis of cutaneous osteosarcoma was made on the basis of histological analysis of the lesion, which showed a sarcomatous dermal-hypodermal proliferation secreting osteoid. Clinical and radiological staging ruled out any extra-cutaneous spread, particularly to bone, thus confirming the primary cutaneous nature of the osteosarcoma. DISCUSSION: Primary cutaneous osteosarcoma is a rare tumor, diagnosis of which is normally based on histopathological features.

Acute generalized exanthematous pustulosis induced by the essential oil of Pistacia lentiscus.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular eruption characterized by small nonfollicular pustules on an erythematous background, sometimes associated with fever and neutrophilia. Over 90% of cases are drug-induced; however, it can be caused in rare cases by other agents. We report two cases of AGEP secondary to ingestion of Pistacia lentiscus essential oil, the first two such cases to our knowledge. The cutaneous morphology, disease course and histological findings were consistent with a definite diagnosis of AGEP, based on the criteria of the EuroSCAR study group. These two cases highlight the need to consider herbal extracts as a potential rare cause of AGEP and to ensure the safety of herbal medicines.

[Erythematous type scaly papule on the abdomen: chromoblastomycosis due to Fonsecaea pedrosoi]. / Plaque érythémato-squameuse papuleuse et atrophique de l'abdomen: chromomycose à Fonsecaea pedrosoi.

Chromoblastomycosis is a chronic subcutaneous fungal infection caused by dematiaceous saprophytic moulds. We report a case of chromoblastomycosis due to Fonsecaea pedrosoi observed in man from the Baja region of Tunis. He presented since one year an erythemato-squamous atrophic plaque localised at the abdomen area. Clinical remission was obtained after cryotherapy and terbinafine.

[Mycetoma in Tunisia: a 15-case series]. / Les mycétomes en Tunisie: 15 observations.

BACKGROUND: Mycetoma is a chronic infection of cutaneous and subcutaneous tissue that can be caused by fungi or bacteria. It is endemic in tropical and subtropical areas but rare in Tunisia. PURPOSE: The purpose of this report is to describe epidemioclinical features, treatment and outcomes in patients presenting mycetoma in Tunisia. PATIENTS AND METHODS: The files of all patients treated for mycetoma in the Dermatology Department of La Rabta Hospital in Tunisia from 1982 to 2006 were retrospectively reviewed. RESULTS: A total of 15 cases of mycetoma were recorded during the study period. There were 6 men and 9 women with a mean age of 53.2 years. The most common clinical presentation was infiltrated erythematous plaques with sinus tracts (fistulas). Lesions were located on the foot in 12 cases. Thirteen patients reported the presence of grains in fluid discharging from fistulas. The cause of mycetoma was actinomycetes, i.e., Actinomadura madurae, in 9 cases and fungus in 6 cases including 3 due to Madurella mycetomi and 2 to Pseudallesheria boydii. Treatment was based on oral antibiotics for actinomycetoma and oral antifungals for eumycetoma. CONCLUSIONS: Mycetoma in Tunisia is still uncommon with a slight female predominance. The foot is the most frequent location. Diagnosis can be accomplished by direct mycologic examination, culture, and histololgy. There is no consensus on treatment that is often prolonged with numerous relapses.

[Profuse subcutaneous nodules in a Tunisian patient: Kaposi sarcoma revealing AIDS]. / Nodules sous cutanés profus chez un Tunisien: maladie de Kaposi révélatrice de SIDA.

The purpose of this report is to describe a case involving Kaposi sarcoma as the inaugural manifestation of HIV infection at the full-blown AIDS stage. The patient was a 59-year-old Tunisian man who presented with profuse subcutaneous nodules and multiple lymph nodes. Treatment was based on antiretroviral therapy in association with radiotherapy.

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles.

BACKGROUND: Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes. OBJECTIVES: The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form. METHODS: Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped. RESULTS: Firstly, when the whole patient population was studied, DRB1*03, DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03. In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles. CONCLUSIONS: These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.

Histological characterization of Darier's disease in Tunisian families.

BACKGROUND: Darier's disease (OMIM 124200) is an autosomal-dominant skin disorder characterized by warty papules and plaques in seborreheic areas, palmo-plantar pits and distinctive nail abnormalities. The disease has complete penetrance in adults and variable expressivity. It is caused by mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase type 2 isoform (SERCA2). OBJECTIVE: We report histological investigations of six unrelated Tunisian families including 15 affected individuals with Darier's disease mutations. RESULTS: The typical histological features of Darier's disease have been observed in the 15 patients. Variable histological features have been observed among Tunisian patients ranging from mild to moderate lesions of Darier's disease. A significant correlation has been observed between the clinical presentation of the Darier's disease (mild or moderate) and the intensity of the histological features. Isolated acral form of Darier's disease was seen in one case. Two distinct original associations have been observed: Darier's disease/pemphigus vulgaris in one patient and Darier's disease/ichtyosis in the other patient. CONCLUSION: Our findings confirmed the clinical heterogeneity of Darier's disease on the basis of histological study. The intensity of the histological features could be closely correlated to the severity of Darier's disease clinical presentation.

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia.

BACKGROUND: Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1. AIM: To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus. METHODS: We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients. Results Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1-positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions. CONCLUSION: These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

[Darier's disease: an evaluation of its neuropsychiatric component]. / Les manifestations neuropsychiatriques de la maladie de Darier : résultat préliminaire d'une étude epidémioclinique et génétique de huit familles.

BACKGROUND: Darrier's disease is a rare genodermatosis with a dominant autosomic penetrating variable transmission. The association between Darier's disease and neuropsychiatric disorders has been reported since 1996. Moreover, associations with mental retardation, schizophrenia, mood disorders and suicide have been reported. The discovery in 1999 of the ATP2A2 gene of Darier's disease, localised on chromosome 12, allowed significant advances notably in understanding the pathogenicity of these symptoms. MATERIAL AND METHODS: In this article, we present the preliminary results of a clinical and genetic study of eight Tunisian families, involving dermatologists, psychiatrists and geneticians. Eight patients with Darier's disease and their first degree relatives were included in the study after they had given their written consent. Thirty-five subjects were examined, 23 of them had Darier's disease. All patients were submitted to a complete clinical examination; notably dermatological screening, genetic inquiry and blood tests for haplotype analysis. Only 13 of them underwent a psychiatric examination. RESULTS: The psychiatric examination was carried out only in 13 patients with Darier's disease, who revealed neuropsychiatric symptoms with a frequency of 61.1% (8/13). Two patients presented mild mental retardation; six patients had mood disorders, three of them belonged to the same family (two had recurrent depression, four belonged to the bipolar spectrum [2 bipolar disorder type 2, 2 cyclothymia]). The coexpression of the two distinct phenotypes (Darier's disease and bipolar disease), within the same three members' of the family of our study, suggests the existence of a genetic linkage between the two diseases, as has been reported in the literature.

[Familial psoriasis: descriptive report of 9 families]. / Le psoriasis familial: etude descriptive à propos de 9 familles.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. The familial nature of psoriasis has long been recognized. Aim of our study was to describe the epidemiological, clinical and genetic features of familial psoriasis. METHODS: Through a prospective study we investigated during a study period of lyear (2006-2007) 9 Tunisian unrelated multiplex families. Patients with psoriasis and their available family members were examined by the same dermatologist. RESULTS: Thirty nine individual presented psoriasis (25 men and 4 women), with a mean age at onset about 19.8 years. With the systematic exam of member's family we discover 11 cases of unknown psoriasis. The common form of psoriasis was the preponderant one (37 cases). The nails, the scalp, the mucous membranes were involved respectively in 21, 12 and 13 cases. The psoriasis was severe in 11 cases. CONCLUSION: Through this study we find similar epidemiological and clinical features of those reported previously. The intra and inter-familial variability was evident in our patients.

Involvement of granzyme B and granulysin in the cytotoxic response in lichen planus.

BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the main suspected mechanism of this dermatosis. Granzyme B and granulysin are components of the cytoplasmic granules of cytotoxic T lymphocytes and natural killers. They are involved in cell-mediated apoptosis. This work studies the possible implication of granzyme B and granulysin in the cell-mediated cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B and granulysin was studied by real-time reverse transcriptase polymerase chain reaction in 15 biopsies of lichen planus. The distribution and the phenotype of the inflammatory infiltrate and the expression of granzyme B were studied by immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme B and granulysin mRNA expression was one to two hundred times greater than in biopsies of normal skin. Immunohistochemical study revealed that the lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes. Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our results suggest a central role for cell-mediated cytotoxicity by the granule exocytosis pathway probably because of auto-cytotoxic T-cell clones in the pathogenesis of lichen planus.

[Erythema nodosum: profile in a Tunisian teaching hospital]. / Erythemes noueux: etude d'une serie hospitaliere.

BACKGROUND: Erythema nodosum (EN) is the most frequent acute nodular hypodermatitis. Etiologies of EN are varied although a similar clinical presentation. The aim of our study is to establish epidemio-clinical characteristics of EN in 103 patients. METHODS: (62 in care (january 1980-december 2005) and 41 consultants (january 1991-december 2005) were seen on the dermatology unit of the Rabta hospital. We have only included patients that had done: blood count, chest X-Ray, ASLO, tuberculin intradermoreaction, transaminase, inflammation marker. RESULTS: We had 86 women and 17 men with a mean age of 36,5 years. Lesions were located in lower limbs in 88 cases. The main etiologies were: post streptococcal infections (42 cases), tuberculosis (8 cases), Crohn disease (8 cases), Behçet disease (7 cases) and sarcoidosis (5 cases). EN was idiopathic in 23 patients. The most common provoking agent of EN varies from a country to another and even in the same country from a study to another. In Tunisia, post streptococcal infections and Behçet disease still frequent etiologies for EN, sarcoidosis and inflammatory colites are more and more found unlike tuberculosis which is less incriminated than before. In case of EN it is reasonable to begin etiological enquiry by common causes.

[Three cases of cutaneous blastomycosis]. / La blastomycose cutanée: trois cas.

Blastomycosis is a rare mycotic infection in Africa. Isolated cutaneous disease is extremely rare. We report three cases of cutaneous blastomycosis confirmed by istologic and mycologic examination. No visceral involvement was found. Blastomycosis is rare in Tunisia. The most common site of involvement is the lung. The three cases reported presented with skin involvement only, suggesting a cutaneous inoculation of Blastomyces dermatitidis. The diagnostic criteria of cutaneous blastomycosis are discussed.