A founder large deletion mutation in Xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy.

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_009252.1: g.36847_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.

Further evidence of mutational heterogeneity of the XPC gene in Tunisian families: a spectrum of private and ethnic specific mutations.

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_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.

Histiocytosis X revealed by diabetes insipidus and skin lesions.

Langerhans cell histiocytosis is part of a larger group of syndromes described as histiocytoses. The disease may involve single or multiple systems including skin and nervous system. Here we report an adult case where Langerhans cell histiocytosis presented with diabetes insipidus and cutaneous ulcers.

A case of multiple epithelioid angiomatous nodules.

Cutaneous epithelioid angiomatous nodule (CEAN) is a distinct type of epithelioid vascular tumor that is usually solitary. Herein we present a 31-year-old man with multiple, rapidly growing nodules on the scalp.

[Treatment of psoriasis by methotrexate in the era of biotherapies: a study in 21 Tunisian patients]. / Traitement du psoriasis par méthotrexate à l'ère des biothérapies : étude chez 21 patients tunisiens.

INTRODUCTION: We present here results of methotrexate, in term of efficacy and tolerance, administrated in 21 Tunisian patients with severe psoriasis. METHODS: It was a retrospective study conducted between january 2002 and december 2009 in the department of dermatology of Charles Nicolle Hospital of Tunis. We have included 21 patients with severe psoriasis treated by methotrexate. RESULTS: Patients were 53 year-middle aged with a sex-ratio = 6. Psoriasis evolved for a mean of 10 years (1month-60 years). Patients had: plaque psoriasis (n = 18, 85.8%) with 63% body surface involvement, erythrodermic psoriasis (n = 2, 9.5%) and psoriatic arthritis (n = 1, 4.7%). Methotrexate was orally administrated at an initial dose of 5-7.5 mg/week. The maximum dose was of 7.5 mg-12.5 mg/week. Complete remission was achieved in 62% of cases and partial remission in 28.5% of cases. Haematological and hepatic toxicities were observed in 2 patients (9.5%). Mean remission period was of 14 months (3 months-3 years). Seven patients had severe relapses. CONCLUSION: Our study concluded to the efficacy of methotrexate in severe psoriasis with a high rate and long term remission, despite lower doses than those classically used in the literature.

Cutaneous adverse drug reactions in children. A series of 90 cases.

BACKGROUND: Cutaneous adverse drug reactions (CADR) are frequent in children. They have different clinical presentations and may be caused by several drugs. AIM: To evaluate the epidemioclinical features of cutaneous adverse drug reactions (CADR) and the different causative drugs in a Tunisian paediatric series. METHODS: We have retrospectively included 90 children (under 16 years old) with a well documented cutaneous drug reaction, seen in the Department of Dermatology of Charles Nicolle hospital of Tunis over 18 years (1991-2008). Age, gender, duration of skin disorders, type of cutaneous lesions, incriminated drugs, delay between drug consumption and eruption, validation by the national pharmacovigilance centre, treatment and outcome were recorded. RESULTS: Our patients were 6.9 year-aged (sex-ratio M/F 1.19). They had maculopapular eruption (MPE) (57.7%), acute urticaria (16.6%), fixed drug eruption (14.4%), erythema multiform (2.2%), photosensitization (1.1%) or severe cutaneous drug reactions (10%).Incriminated drugs were: Antibiotics (55.5%), non-steroidal antiinflammatory drugs (18.8%), antiepileptics (11.1%), and analgesics (5.5%). Betalactamins were the most commonly incriminated antibiotics (32 out of 50 patients; 64%). Barbiturates were the most commonly incriminated anti-epileptics (7/90 cases, 7.7%). Favourable outcome was noted in all patients, even those with severe drug reactions. CONCLUSION: MPE to antibiotics were the most common kinds of CADR in children. Drug responsibility should be based on solid criteria given the frequency of MPE of infectious origin and the frequent prescription of antibiotics in paediatric population.

Postvaccination morphea profunda in a child.

We report a new case of postvaccination morphea profunda (MP) in a child and discuss its different clinical presentations, prognosis, and therapy and its relationship with "solitary morphea profunda." A 2-year-old healthy girl presented with an induration of the anterior aspect of the left thigh of 9 months duration. The lesion had appeared 3 months after a third dose of diphtheria-tetanus-pertussis vaccine. Cutaneous examination showed an induration of 7 × 7 cm with an "orange peel" texture after pinching the skin. Histologic examination confirmed the diagnosis of MP. Systemic steroids (1 mg/kg/day) led to the stabilization of the lesion. After 4 months of treatment, we began the concomitant use of oral methotrexate (10 mg/wk) for 2 months. Methotrexate was then continued alone for 10 months, leading to a significant regression of the induration with no relapse.

[Not Available]. / Traitement du psoriasis par méthotrexate à l'ère des biothérapies : étude chez 21 patients tunisiens.

INTRODUCTION: We present here results of methotrexate, in term of efficacy and tolerance, administrated in 21 Tunisian patients with severe psoriasis. METHODS: It was a retrospective study conducted between january 2002 and december 2009 in the department of dermatology of Charles Nicolle Hospital of Tunis. We have included 21 patients with severe psoriasis treated by methotrexate. RESULTS: Patients were 53year-middle aged with a sex-ratio=6. Psoriasis evolved for a mean of 10years (1month-60years). Patients had: plaque psoriasis (n=18, 85.8%) with 63% body surface involvement, erythrodermic psoriasis (n=2, 9.5%) and psoriatic arthritis (n=1, 4.7%). Methotrexate was orally administrated at an initial dose of 5-7.5mg/week. The maximum dose was of 7.5mg-12.5mg/week. Complete remission was achieved in 62% of cases and partial remission in 28.5% of cases. Haematological and hepatic toxicities were observed in 2 patients (9.5%). Mean remission period was of 14months (3months-3years). Seven patients had severe relapses. CONCLUSION: Our study concluded to the efficacy of methotrexate in severe psoriasis with a high rate and long term remission, despite lower doses than those classically used in the literature.

Pigmented lesion in the inguinal region.

Pigmented Bowen disease (PBD) is a rare tumor characterized by increased melanin pigment in the epidermis or papillary dermis in addition to the typical findings of Bowen disease. We report the case of a 60-year-old woman who presented with a 6-month history of a gradually enlarging solitary dark brown plaque in her right inguinal region. Histopathology showed hyperkeratosis with parakeratosis, acanthosis, disorganization of epidermal architecture, atypical keratinocytes, and increased melanin pigment of the papillary dermis. Considering the clinical and the histological evidence, a diagnosis of PBD was established. Complete resection confirmed the diagnosis. Pigmented Bowen disease is an unusual form of squamous carcinoma in situ. Other tumors in the differential diagnosis include pigmented basal cell carcinoma and superficial spreading melanoma.

A delayed diagnosis of lepromatous leprosy: pitfalls and clues to early recognition.

PURPOSE: To remind special attention to atypical symptoms of Hansen's disease, we report a case of an atypical case due to a delayed diagnosis. BACKGROUND: Clinical features of leprosy are well known, cutaneous lesions and involvement of the peripheral nerves being the cardinal clinical signs. Among these presentations, systemic involvement, including mucous membranes of the upper respiratory tract and eyes, is rarely reported even if it is still commonly seen in endemic areas, in particular lepromatous leprosy. CASE REPORT: We describe here a new case of Hansen's disease in a 51-year-old Tunisian woman with an atypical presentation and a delayed diagnosis. The early symptoms of the disease were different from the main clinical signs of Hansen's disease since they involved the upper respiratory tract and the eyes. A nasal smear was positive for acid-fast bacilli, thus confirming the diagnosis of bacilliferous leprosy. Histological findings suggested the diagnosis of leprosy and were somewhat more characteristic of the borderline lepromatous type. CONCLUSION: Diagnosis of Hansen's disease in patients with neither apparent skin lesions nor neurological signs is still problematic. Clinicians should not only pay attention to the more obvious signs in their own fields of expertise but should be aware of the possible systemic involvement of leprosy.

Chronic actinic dermatitis: two patients with successful management using narrowband ultraviolet B phototherapy with systemic steroids.

BACKGROUND: Chronic actinic dermatitis (CAD) is a debilitating photodermatosis with characteristic clinical, histological and photobiological features (reduced minimal erythema dose: MED). Its management involves various therapeutic approaches, among them there is phototherapy. Efficacy of psoralen ultraviolet therapy (PUVA therapy) was previously demonstrated but there are no current data on the use of narrowband ultra violet B (UVB) therapy (NB-UVB) in CAD. NB-UVB has already been proven to be effective and safe in several other photodermatoses. CASE REPORTS: We report here two dark-skinned patients (skin type IV and V) with CAD, successfully treated with an incremental regimen of NB-UVB phototherapy coupled to a 3 month-course of systemic steroids (1mg/Kg/day). CONCLUSION: Our protocol of NB-UVB with steroids seems to be effective for the management of CAD with a good short term safety profile.

Erythema elevatum diutinum: an "idiopathic" case.

Erythema elevatum diutinum (EED) is a rare condition with an unclear pathogenesis. Initially classified within neutrophilic dermatoses, it is now considered as a leukocytoclastic vasculitis accordingly to its histopathologic pattern. Several clinical presentations as well as many associated diseases are reported in the literature. We report a new case of EED in a 58-year-old man who presented with a three-month history of plaques and nodules on the extensor surfaces of hands, elbows, knees, ankles, forearms, and buttocks. Histology showed a leucocytoclastic vasculitis, suggestive of the diagnosis of EED. Screening for an associated pathology, namely a paraproteinemia or a solid cancer, was negative. Treatment with dapsone leads to amelioration within few weeks.

[Kindler syndrome: clinical and ultra-structural particularities, a propos of three cases]. / Le syndrome de Kindler, particularités cliniques et ultrastucturales à travers trois nouvelles observations familiales.

INTRODUCTION: Kindler's syndrome is a rare type of genetic skin condition belonging to the class of bullous poikilodermia. We report three new sibling cases of this rare syndrome. CASES REPORTS: The condition was seen in three sisters aged 12, 16 and 20 years, born of a first-degree consanguineous marriage with no family history of Kindler's syndrome. The three patients presented spontaneously regressive bullous eruptions, poikilodermia of gradual onset, major cutaneous atrophy on the back of the hands and the feet, photosensitivity and gingival hypertrophy. Electron microscopy examination of poikilodermic skin showed normal anchoring filaments and intraepidermal cleavage. DISCUSSION: Diagnosis of Kindler's syndrome is based upon clinical evidence. Kidler's syndrome is a well defined clinical entity. Ultra-structural studies show intraepidermal, junctional, and dermal cleavage. This syndrome must be differentiated from congenital epidermolysis bullosa, Weary's syndrome, and other bullous hereditary poikilodermas.