Immunohistological study of tight junction protein expression in mal de Meleda.

Mal de Meleda (MdM, MIM: 248300) is a rare autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis with onset in early infancy. The gene responsible for MdM, ARS, encodes for Secreted Lys6/Plaur domain-containing protein 1 which is essential for epidermal homeostasis. Tight junctions have been proposed to have two mutually exclusive functions: a fence function which prevents the mixing of membrane proteins between the apical and basolateral membranes; and a gate function which controls the paracellular passage of ions and solutes between cells. In this study we report immunohistochemical investigations of tight junction proteins claudin-1 and occludin in MdM Tunisian families. Nine skin biopsies from patients with MdM were analyzed. The control group was formed by skin biopsies belonging to healthy individuals. Immunohistochemical study was performed on fixed sections from biopsies of four microns with the following polyclonal antibodies: anti-claudin-1 and anti-occludin. In control skin, claudin-1 exhibited membrane expression throughout the epidermis with increasing and upward intensity, whereas occludin was detected in the cell membrane of keratinocytes of the stratum granulosum. In MdM skin, claudin-1 was expressed throughout the thickness of the spinous layers with membrane staining, and occludin had cytoplasmic staining in the granular layer. The immunohistochemical expression of TJ proteins in MdM patients harbors premature expression of occludin and decreased expression of claudin-1, highlighting further evidence for disorders in epidermal homeostasis.

Vesiculobullous eruption revealing lipoid proteinosis: A potential diagnostic pitfall. A case report and a brief review.

We describe a new case of lipoid proteinosis (LP) in a child and discuss its different clinical presentations, especially in its early erosive stage, as well as its prognosis and therapy. A 3.5-year-old healthy girl presented with a chronic and recurrent vesiculobullous skin eruption since early childhood. She had developed hoarseness of the voice during the first few months of life. Cutaneous examination revealed the presence of multiple non-pruritic tense vesicles and erosions on a non-erythematous base on her face, hands and elbows with a waxy thickening of the skin on her face. Histologic examination confirmed the diagnosis of LP. The patient was then regularly followed in our department for therapy for her disease.

Erratum to "Bullous eruption in an infant, what's your diagnosis?" [Int J Pediatr Adolesc Med 1 (2) (2014) 104-106].

[This corrects the article DOI: 10.1016/j.ijpam.2014.11.004.].

[Severe childhood atopic dermatitis]. / La dermatite atopique severe de I'enfant.

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.

Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome.

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.

[Cutaneous carcinoma induced by radiotherapy: a report of 31 cases]. / Carcinomes cutanés induits par la radiothérapie: a propos de 31 cas.

BACKGROUND: Depilatory radiotherapy was used in the sixties as a treatment for ringworm in Tunisia. Subsequently some of these patients developed radio-induced carcinomas of the scalp. AIM: To present the epidemiological, clinical, pathological,therapeutic features and out come of radio-induced cutaneous carcinomas. METHODS: We conducted a retrospective study performed in the dermatology department of the La Rabta hospital of Tunis over a 6- year-period recording all histologically confirmed carcinomas in patients irradiated in childhood for tinea capitis. RESULTS: Thirty one patients were included with 49 tumors: 47 basal cell carcinomas and 2 squamous cell carcinomas. The average latent period between the irradiation and the appearance of the carcinomas was of 35.7 years. The average age was 53 years. A male predominance was noted, with a sex ratioM/F of 6.75. Clinically, basal cell carcinomas were nodular in all cases. Surgery was indicated in 90% of cases. Cryosurgery and radiotherapy were used respectively in 1 and 2 patients. CONCLUSION: Our study shows that radio-induced cutaneous carcinomas are widely dominated by basal cell carcinoma. They arise, approximately, ten years earlier than carcinoma in patients with no history of scalp irradiation. However X-ray exposure does not seem to influence clinical or histological presentation, therapeutic modalities nor prognosis of these tumors. The prognosis of radioinduced cutaneous carcinomas was globally similar to that of other cutaneous carcinomas with same histological type and equivalent degree of invasion.

Simvastatin-induced dermatomyositis in a 50-year-old man.

Dermatomyositis (DM) is a rare inflammatory autoimmune disease for which an iatrogenic origin has been described in a few cases. The authors report a case of DM occurring after simvastatin intake. A 50-year-old male sought medical attention for a photodistributed rash and considerable muscular weakness present for 3 months. One year earlier, simvastatin had been introduced. Serum creatine kinase levels were elevated. Histological examination of a muscle biopsy was consistent with a diagnosis of DM. Investigation for neoplasia and associated autoimmune disease proved negative. All clinical and laboratory abnormalities diminished corticosteroid therapy (1 mg/kg/day). Case reports have suggested that lipid-lowering drugs, especially statins, could induce or reveal chronic muscle diseases. In statins myopathy, reduction of coenzyme Q has been discussed as a key mechanism. Our case of DM in a patient receiving simvastatin adds to the previous reported cases in the literature and highlights the potential role of statins as triggers of immune systemic diseases.

Clinical and mutational heterogeneity of Darier disease in Tunisian families.

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.

Immunohistological study of involucrin expression in Darier's disease skin.

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder characterized by acantholysis and abnormal keratinization. The gene responsible for DD, ATP2A2 encodes for the sarco/endoplasmic reticulum (ER) Ca2+-ATPase isoform 2 protein. Involucrin, considered as a marker of terminal epidermal differentiation, could be altered in some keratinization disorders including DD. PATIENTS AND METHODS: An immunohistochemical staining using anti-involucrin antibody was carried out on 16 DD patients epidermis. Involucrin staining was compared with biopsies from cutaneous lesions of three healthy individuals and of patients with Hailey-Hailey disease (five cases) and Mal de Meleda (four cases). A semi-quantitative analysis was performed in order to evaluate involucrin immunostaining on the basis of intensity, extension and epidermal distribution. The involucrin expression was examined afterward with confocal laser scanning microscopy. RESULTS: In contrast to normal skin, all DD cases showed premature expression of involucrin in the lower epidermal layers in four cases with a strong labeling in both keratinocytes cell membrane and cytoplasm. Other keratinization disorders share premature expression of involucrin but displayed differences in cytoplasm/cell membrane labeling. CONCLUSIONS: DD skin displayed a constant immunohistochemical involucrin pattern characterized by both premature expression and a particular cytoplasmic/cell membrane localization distribution.

[Cryosurgery for nose basal cell carcinoma. Series of 17 tumors]. / Place de la cryochirurgie dans le traitement des carcinomes basocellulaires du nez. A propos d'une série de 17 tumeurs.

UNLABELLED: Basal cell carcinoma (BCC) is the most common malignant tumour of the skin frequently located on the head and chiefly on the nose. Cryosurgery is one of the methods to treat BCC. OBJECT: To determine the efficacy of cryosurgery of 17 BCC of the nose in terms of recurrence rates and cosmetic results. RESULTS: 15 patients were included with a median age of 73 years and a photo type III or IV in 86% of cases. Mean size of tumours was 12 mm. Lesions were chiefly located on the alae nasi (70.5%). Complications were few and minor. After an average follow-up of 13.5 months, recurrence rate was about 5.8% (one case). Cosmetic results were good or excellent in 14 cases/17; only one patient had developed a notch of the nose. CONCLUSION: Cryosurgery is a rapid, of a low cost technique and chiefly with good oncological and cosmetic results.

Further evidence of the clinical and genetic heterogeneity of recessive transgressive PPK in the Mediterranean region.

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.