Hamida Turki

Interleukin-36-Receptor Antagonist Deficiency and Generalized Pustular Psoriasis

BACKGROUND Generalized pustular psoriasis is a life-threatening disease of unknown cause. It is characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein, which may be associated with plaque-type psoriasis. METHODS We performed homozygosity mapping and direct sequencing in nine Tunisian multiplex families with autosomal recessive generalized pustular psoriasis. We assessed the effect of mutations on protein expression and conformation, stability, and function. RESULTS We identified significant linkage to an interval of 1.2 megabases on chromosome 2q13-q14.1 and a homozygous missense mutation in IL36RN, encoding an interleukin-36-receptor antagonist (interleukin-36Ra), an antiinflammatory cytokine. This mutation predicts the substitution of a proline residue for leucine at amino acid position 27 (L27P). Homology-based structural modeling of human interleukin-36Ra suggests that the proline at position 27 affects both the stability of interleukin-36Ra and its interaction with its receptor, interleukin-1 receptor-like 2 (interleukin-1 receptor-related protein 2). Biochemical analyses showed that the L27P variant was poorly expressed and less potent than the nonvariant interleukin-36Ra in inhibiting a cytokine-induced response in an interleukin-8 reporter assay, leading to enhanced production of inflammatory cytokines (interleukin-8 in particular) by keratinocytes from the patients. CONCLUSIONS Aberrant interleukin-36Ra structure and function lead to unregulated secretion of inflammatory cytokines and generalized pustular psoriasis. (Funded by Agence Nationale de la Recherche and Société Française de Dermatologie.).

Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans.

Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis.

Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo

Background  The pathogenetic mechanisms in vitiligo have not been clarified completely. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. The active and stable phases of vitiligo are defined as the progression or appearance of new lesions in the last 3 months and the absence of new lesions or progression in the last 6 months, respectively.

Old World cutaneous leishmaniasis: diagnosis and treatment

Cutaneous leishmaniasis is a major world health problem. Diagnosis is suspected on evocative clinical presentation in patients living in or coming from endemic areas. Several methods have been used. The smear is a simple investigation used in endemic regions. The culture enables to identify the specimen. PCR has a high sensitivity. Montenegros reaction is used in the epidemiological study. Pentavalent antimony derivatives remain the mainstay of systemic treatment. Their efficiency is well established. Their toxicity should be researched. Other treatments can be utilized, such as miltefosine. Local therapy is used in uncomplicated lesions. Injections of the pentavalent antimony derivate, cryotherapy and paromomycin ointmentsis are important options and should be used more frequently in Old World leishmaniasis.

Epidemiology of dermatophytoses in Sfax, Tunisia.

The distribution of dermatophytes varies in different countries and geographical areas depending on several factors. To determine the frequency of aetiological agents and the clinical variants of dermatophytoses, we carried out a study between 1998 and 2007. Out of 25 432 subjects suspected to have superficial mycoses, 9960 (39.2%) were affected with dermatophytoses; 14957 positive samples were obtained. The mean age was 35.7 years (range: 21 days to 97 years). Sex ratio was 0.9. Our patients were from urban regions in 81.9% of cases. The most common type of infection was onychomycosis (30.3%), followed by tinea pedis (24.8%), intertrigo (21.7%), tinea corporis (11.4%) and tinea capitis (9.6%). Fifteen patients had generalised dermatophytosis. Hadida and Schousboe disease was diagnosed in one case with lethal evolution. The most isolated dermatophyte was Trichophyton rubrum (74.5%), followed by T. violaceum (7.9%), T. mentagrophytes (7.5%), Microsporum canis (3.8%), Epidermophyton floccosum (0.7%) and T. verrucosum (0.54%). Other species were occasionally isolated: T. schoenleinii, T. tonsurans, M. audouinii and M. ferrugineum. The prevalence of dermatophytoses remains high in our country (996 cases/year). Trichophyton rubrum is the predominant causal agent. However, zoophilic agents become more prevalent. Epidemiological surveys are an essential tool for developing strategies for infection control.

Novel Synthesis of 2‐Oxo‐2H‐Benzopyrano[2,3‐d]Pyrimidines

Abstract The synthesis of novel substituted 3‐cyanoiminocoumarins and corresponding N‐ethoxycarbonyl iminocoumarins is described. The condensation of N‐ethoxycarbonyl‐3‐cyano‐7‐diethylamino iminocoumarin with amines as N‐nucleophiles yields substituted 2‐oxo‐2H‐benzopyrano‐[2,3‐d]pyrimidines having promising optical properties.

Manifestations cutanées chez les hémodialysés chroniques: Étude prospective de 363 cas

Resume Objectif Les manifestations cutanees chez les hemodialyses chroniques sont frequentes et variees. Leur pathogenie est souvent hypothetique. Le but de ce travail est d’evaluer la prevalence et la nature de ces lesions cutanees et de discuter certains mecanismes pathogeniques. Methodes Cette etude prospective a ete realisee du 1erfevrier au 30 avril 1996. Elle a interesse 363 patients hemodialyses dans 7 centres. Chaque patient a eu un interrogatoire et un examen dermatologique. Resultats Il y avait 210 hommes et 153 femmes. L’âge moyen etait de 50,6 ans. La duree totale de l’hemodialyse a varie de 1 a 192 mois avec une moyenne de 52,4 mois. Quatre-vingt huit pour cent des patients etudies avaient des manifestations cutanees et 44,9 % un prurit. Il est apparu apres le debut de l’hemodialyse chez 82,1 % d’entre eux. La xerose cutanee a ete trouvee chez 69 % des patients. Les alterations de la pigmentation cutanee ont ete observees dans 17 % des cas, representees essentiellement par une hyperpigmentation des zones photoexposees. Chez 6 patients, un blondissement de la peau, des cheveux et des phaneres est survenu 10 mois a 8 ans apres le debut de l’hemodialyse. L’hyperkeratose folliculaire a ete constatee chez 15 % des patients. Une seule patiente avait une pseudomaladie de Kyrle confirmee. Les troubles des phaneres representes essentiellement par les ongles amincis et les hemorragies sous-ungueales ont ete notes dans 18,5 % des cas. Les autres manifestations cutanees ont ete les petechies ou les ecchymoses (66 %), les infections cutanees a type de folliculite (9 %), les calcifications sous-cutanees (2 cas), une pseudoporphyrie cutanee (2 cas), un eczema en regard de la fistule (11,5 %) du essentiellement aux produits appliques localement. Conclusion Les manifestations cutanees chez les hemodialyses chroniques sont frequentes et polymorphes. Si la plupart sont connues de longue date, certaines, en particulier le blondissement, sont de connaissance plus recente. Leur pathogenie est le plus souvent mal elucidee. Le traitement est souvent symptomatique. La dialyse et la greffe renale constituent le meilleur traitement. Voir aussi dans ce numero l’editorial de Gerard Guillet, Les signes cutanes chez les hemodialyses: des marqueurs predictifs de morbidite ou de mortalite?.p 377-8.OBJECTIVE Chronic hemodialysis patients experience frequent and varied cutaneous manifestations, of often hypothetical pathogenesis. The aim of this work is to assess the prevalence and nature of these cutaneous lesions and discuss some pathogenic mechanisms. METHODS This prospective study was conducted from 1 February through 30 April 1996. It included 363 hemodialysis patients in seven centers. Each patient was interviewed and examined. RESULTS There were 210 men and 153 women. Their mean age was 50.6 years. The total duration of hemodialysis ranged from 1 to 192 months, with a mean of 52.4 months. 88% of the patients had cutaneous manifestations. Pruritus was reported by 44.8%. It appeared after hemodialysis began for 82.1% of them. Cutaneous xerosis was observed in 69%. Changes in pigmentation were observed in 17% of cases, primarily involving hyperpigmentation of photo-exposed areas. In 6 patients, skin, hair, and exoskeleton began to turn lighter 10 months to 8 years after hemodialysis. Follicular hyperkeratosis was observed in 15%. One patient had a confirmed case of perforating follicular dermatosis. Disorders of the exoskeleton (18.5% of cases) were represented mainly by thin nails and subungual hemorrhages. Other cutaneous manifestations included petechiae and ecchymoses (66%), folliculitis-type infections (9%), subcutaneous calcifications (2 cases), cutaneous pseudoporphyria (2 cases), and eczema around the fistula (11.5%), due essentially to locally-applied products. CONCLUSION Cutaneous manifestations in chronic hemodialysis patients are frequent and polymorphous. While most have long been known, lightening of skin, in particular, others have been discovered more recently. Their pathogenesis is most often poorly elucidated. Treatment is often symptomatic. Dialysis and renal transplantation constitute the best treatment.

The relationship between alopecia areata and alexithymia, anxiety and depression: A case-control study

Background: Alopecia areata (AA) is a skin disease characterized by the sudden appearance of areas of hair loss on the scalp and other hair-bearing areas, but its aesthetic repercussions can lead to profound changes in patients psychological status and relationships. Aim: The goal was to investigate a possible relationship between AA and alexithymia as well as two other emotional dimensions, anxiety and depression. Materials and Methods: Fifty patients with AA seen in the Department of Dermatology of Hedi Chaker University Hospital, Sfax were included in this study. Anxiety and depression were evaluated by Hospital Anxiety and Depression scale questionnaire, alexithymia was assessed by Toronto Alexithymia scale 20, and severity of AA was measured by Severity of Alopecia Tool. Results: Patients mean age was 32.92 years. 52% of patients were females. Depression and anxiety were detected respectively in 38% and 62% of patients. There was statistically significant difference between patients and control group in terms of depression (P = 0.047) and anxiety (P = 0.005). Forty-two percent of patients scored positive for alexithymia. No significant difference was found between patient and control groups (P = 0.683) in terms of alexithymia. Anxiety was responsible for 14.7% of variation in alexithymia (P = 0.047). Conclusions: Our study shows a high prevalence of anxiety and depressive symptoms in AA patients. Dermatologists should be aware of the psychological impact of AA, especially as current treatments have limited effectiveness.

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.

Sweet's syndrome: a retrospective study of 90 cases from a tertiary care center.

Sweets syndrome (SS) is a neutrophilic dermatosis characterized by the abrupt onset of cutaneous, systemic and histopathological alterations in response to different stimuli.