Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome.

BACKGROUND: Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. OBJECTIVES: We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. METHODS: Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. RESULTS: We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon-intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype-phenotype correlation, as seen in relatives carrying similar mutations. CONCLUSIONS: This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.

Outpatient dermatology major surgery: a 1-year experience in a Spanish tertiary hospital.

INTRODUCTION: The constant increase in the incidence of skin cancer together with the requirement for maximum exploitation of available medical resources has meant that dermatological major surgery on an outpatient basis has greatly increased in recent years. OBJECTIVE: This article reviews the practice of dermatological surgery in an outpatient setting over a 1-year period. Its purpose is to analyse the number of surgical procedures, the type of cutaneous processes treated and the kind of surgical intervention and anaesthesia used. We also assessed the percentage of cancellations, postsurgical hospital admission and postsurgical complications. Clinicopathological correlation and complete tumour removal were also evaluated. MATERIAL AND METHODS: Our clinical experience of major surgery of outpatients at the dermatology department of the Hospital Juan Canalejo in A Coruña (Spain), analysing 565 patients in a non-randomized pilot study running from January to December 2003, is presented. RESULTS: Six hundred and forty-four surgical procedures were performed on a total of 565 patients. The three main cutaneous processes treated were basal cell carcinoma (240), squamous cell carcinoma (117) and melanoma (77). The most frequent type of procedure was direct closure (346), followed by exeresis and flap (133) and partial- or full-thickness skin graft (29), nail apparatus surgery (56) and lip surgery (33). Twelve patients were admitted to hospital after surgery owing to the complexity of their operations or to complications arising during surgery. Five hundred and fifty-three patients were discharged after being kept under observation for a few hours. Seventeen patients (3%) suffered complications following surgery, which consisted of partial implant failure (six cases), infection of the surgical wound (six cases), intense pain (four cases) and haemorrhage (one case). There was a good clinicopathological correlation in 90.78% of non-melanoma skin cancers, of which 92.03% were completely removed. CONCLUSIONS: Medium and high complexity operations for dermatological processes, traditionally performed on hospitalized patients, can be conducted on an outpatient basis. This allows hospitalization costs and waiting lists to be reduced and affords the possibility of achieving better morbidity rates and medical care than in the standard hospital setting.

Acne in Apert's syndrome: treatment with isotretinoin.

Apert's syndrome is an uncommon disease characterized by synostosis of extremities, vertebrae and skull. A clear association between Apert's syndrome and acne vulgaris with resistance to usual acne treatments has been described. A case of Apert's syndrome treated with oral isotretinoin with good results is reported and the pathogenic mechanisms of acne in this syndrome are discussed.

Cutaneous ulceration as a sign of methotrexate toxicity.

Methotrexate (MTX) inhibits DNA synthesis by competition with dihydrofolate reductase. Adverse cutaneous reactions to MTX are usually dose-related and have been mainly reported in patients receiving extremely large doses of chemotherapy. Painful erosion of psoriatic plaques has been often reported as an early sign of MTX toxicity, but cutaneous ulceration as a sign of MTX toxicity in patients without psoriasis has only been described in one case. We report a patient with rheumatoid arthritis and without psoriasis who developed cutaneous ulceration on the knuckles as a sign of MTX toxicity. Cutaneous ulceration by MTX toxicity is an exclusion diagnosis and its pathogenic mechanism may be multifactorial, including direct toxicity of the drug in addition to local factors.

Linear immunoglobulin A bullous dermatosis induced by gemcitabine.

OBJECTIVE: To report a case of linear immunoglobulin (Ig) A bullous dermatosis (LABD) induced by gemcitabine. CASE SUMMARY: A 59-year-old man was diagnosed with squamous-cell carcinoma of the lung in T4N2M0 stage and treated with cisplatin, vinorelbine, and gemcitabine. Twenty-four hours after the administration of gemcitabine, a symmetric, bullous, herpetiform eruption appeared on his trunk and upper limbs. Histopathologic examination and direct immunofluorescence test were consistent with IgA bullous dermatosis. Cutaneous lesions resolved two weeks after the drug was withdrawn and topical steroid treatment was instituted. DISCUSSION: Drug-induced LABD is a variant of classic or idiopathic LABD. Vancomycin is the most frequently implicated drug, but other agents have been reported to cause LABD. According to the Naranjo probability scale, the relationship of gemcitabine treatment with cutaneous eruption in our patient is possible. CONCLUSIONS: We report the first case of gemcitabine-induced LABD. Clinicians should monitor patients receiving this drug for signs of LABD.

Superficial white onychomycosis in a 3-year-old human immunodeficiency virus-infected child.

BACKGROUND: Superficial white onychomycosis is exceptional in children, although a few anecdotal cases have been reported in the literature. On the other hand, superficial white onychomycosis and proximal subungual onychomycosis, while unusual in the general population, often appear in adult human immunodeficiency virus (HlV)-infected persons. CASE REPORT: A 3-year-old girl with vertically acquired HIV-1 infection presented superficial white onychomycosis involving the second, third, fourth and fifth toes of her left foot, caused by Trichophyton rubrum. She was treated with topical amorolfine once a week, with a good response within 4 weeks. CONCLUSIONS: We report a case of superficial white onychomycosis associated with HIV infection in a 3-year-old girl. To our knowledge, this type of onychomycosis has not been previously reported in HIV-infected prepubertal children.

Dermatomyositis and mucinosis.

BACKGROUND: Mucin deposition is a common feature in autoimmune collagen diseases including dermatomyositis. Nevertheless, clinical manifestations of mucinosis are uncommon in patients with dermatomyositis. Two cases of mucinosis associated with dermatomyositis are reported. PATIENTS: A 53-year-old woman presented with symmetrical plaques on the upper limbs formed by the coalescence of small, violaceous papules. In addition, she showed the typical cutaneous and muscle features of dermatomyositis. A 44-year-old woman with dermatomyositis of 5 years' evolution developed linear, flesh-colored papules across the flexural creases of her palms and fingers. RESULTS: Skin biopsy of the upper limb lesions in the first patient showed epidermal changes compatible with dermatomyositis and dermal mucin deposition. Histopathologic examination of the palmar lesions of the second patient showed less intense epidermal changes of dermatomyositis and dermal mucin deposition. CONCLUSIONS: Mucin deposition in patients with dermatomyositis may have an unusual clinical presentation, and it should be considered in the differential diagnosis of atypical cutaneous lesions in these patients.

Multiple apocrine hidrocystomas: treatment with carbon dioxide laser vaporization.

BACKGROUND: Apocrine hidrocystoma is a benign cystic tumour with apocrine differentiation. Although most cases are solitary tumours, multiple tumours may occur. Surgical removal is the usual treatment for apocrine hidrocystoma, but it may be troublesome and disfiguring in cases with multiple tumours. OBJECTIVE: To determine the efficacy and cosmetic outcome of carbon dioxide laser vaporization in the treatment of multiple apocrine hidrocystomas. PATIENTS AND METHODS: A total of 11 lesions in three adult patients were treated with carbon dioxide laser vaporization using a continuous and defocused mode, with a power density of 5 J/cm(2). The lesions were localized lateral to the outer canthus, on the free edge of the eyelids, and on the ear. Only a single session of treatment was performed for each lesion. Photographic controls were taken before and after treatment. RESULTS: The lesions cleared after laser treatment without residual changes, and a successful cosmetic result was obtained. CONCLUSION: Carbon dioxide laser is an efficient method of the treatment for multiple apocrine hidrocystomas.

Two cases of segmental multiple glomangiomas in a family: type 1 or type 2 segmental manifestation?

Several autosomal dominant skin diseases may manifest cutaneous mosaicism. Two types of segmental arrangement can be distinguished: type 1 is characterized by segmental lesions with similar severity to that observed in the diffuse phenotype, the remaining skin being normal; type 2 is characterized by segmental lesions showing a major degree of severity and milder lesions diffusely arranged. Multiple glomus tumours have recently been included in the group of genodermatoses showing type 2 segmental involvement. A family with 2 cases of multiple glomangiomas arranged in a segmental fashion is reported. A 12-year-old girl presented multiple nodular glomangiomas on her right buttock and thigh, in a band-like distribution. A sister of her paternal grandfather showed plaque-like multiple glomangiomas on her left thigh and various glomangiomas on her right buttock and arm. No other family members were known to be affected. Two new cases of familial segmental multiple glomangiomas are reported, with the particularity that one of these exhibited type 2 segmental manifestation and the other type 1 from a clinical point of view.

Altered expression of immunoreactive involucrin in lamellar ichthyosis.

In some cases of lamellar ichthyosis, mutations in the epidermal transglutaminase gene and a reduction in the thickness of the cornified envelope have been documented. Involucrin is a major component of the cornified envelope and a substrate for epidermal transglutaminase. The aim of the present work was to analyse the expression of involucrin in lamellar ichthyosis. An ultrastructural study and/or immunohistochemical and biochemical techniques with anti-involucrin antibody were carried out on the epidermis of fifteen patients (12 families) suffering from lamellar ichthyosis. The effect of in vivo retinoid treatment on the involucrin epidermal expression was also investigated. Four cases with normal skin, seventeen cases of other ichthyoses and ten cases of psoriasis were used as controls. In all these cases of lamellar ichthyosis, a thin or absent cornified envelope, electron-dense granules inside corneocytes and a decrease of the epidermal involucrin expression were observed. In the patients receiving treatment with retinoids, western blot and ELISA revealed an increase in the involucrin expression. The decreased expression of involucrin in lamellar ichthyosis could contribute to the altered desquamation process accompanying the disease, since the clinical improvement associated with retinoid treatment is accompanied by an increase in the expression of involucrin.

Differential patterns of filaggrin expression in lamellar ichthyosis.

Lamellar ichthyosis (LI) is a rare genetic and congenital disturbance of keratinization that is phenotypically and genotypically heterogeneous. Filaggrin is one of the major components of the stratum corneum situated in the protein matrix and the cornified envelope. In view of the heterogeneity of LI, this study aimed at exploring filaggrin expression in the skin of patients suffering from the disease. Epidermal filaggrin expression was determined using immunohistochemical techniques and Western blot in 12 patients with LI and the findings were compared with those observed in four normal controls and eight patients with ichthyosis vulgaris. With Western blot, six different patterns of filaggrin expression were detected. The patients with similar clinical manifestations showed a similar pattern, as did members of the same family. Overall, higher filaggrin expression in scales correlated with a better prognosis. In patients receiving retinoids no variations in filaggrin expression during treatment were detected. Our results suggest that LI is heterogeneous as regards filaggrin expression. Filaggrin could therefore be used as a prognostic marker as well as being a marker of the basic defect involved in LI.

Basal cell carcinoma in a girl after cobalt irradiation to the cranium for acute lymphoblastic leukemia: case report and literature review.

A 12-year-old girl had a lesion located on the upper part of the scalp that was clinically interpreted as a melanocytic nevus and corresponded histologically to a basal cell carcinoma. At age 2 years she had been diagnosed as having acute lymphoblastic leukemia L1, for which she was treated with systemic chemotherapy. She also received telecobalt therapy to the whole cranium for prophylaxis of meningeal leukosis. Having rejected other possible causes that can favor the appearance of basal cell carcinoma during childhood (basal cell nevus syndrome, nevus sebaceus, albinism, etc.), we believe that this case should be added to the five previously reported in the literature as basal cell carcinoma developing at an early age in cranial radiation portals with megavoltage radiotherapy. We draw attention to the need to explore radiated areas of skin as part of the long-term follow-up of these patients, and to the advisability of obtaining a biopsy from any persistent lesion in these areas.

Benign cephalic histiocytosis: case report and literature review.

A 3-year-old boy had maculopapules on his face and neck since age 6 months. These were yellow-brown, asymptomatic, and clinically similar to flat warts. Histopathologic study revealed a fibrohistiocytic infiltrate in the superficial dermis. Ultrastructurally, comma-shaped bodies, desmosome-like junctions, and coated vesicles were seen; there were no lipid droplets or Birbeck granules. With these data, a diagnosis of benign cephalic histiocytosis was made. Twenty-five cases are reported in the literature: 17 males and 8 females (male:female ratio 2:1). Sixteen patients had lesions on parts of the body other than the head, neck, and shoulders.

Primary syphilis with multiple chancres and porphyria cutanea tarda in an HIV-infected patient.

A 51-year-old promiscuous heterosexual man with no history of venereal diseases or porphyria had a large genital chancre and deep erosions on the hands. The HIV serology was positive; the CD4 lymphocyte count was 187/mm3, but the patient did not fulfill the CDC criteria for AIDS. Five months later he developed a clinical and biochemically typical porphyria cutanea tarda.