Treatment of psoriasis with adalimumab.

BACKGROUND: Adalimumab is an anti-tumour necrosis factor agent of use in psoriatic arthritis. AIM: The objective of this study was to assess the efficacy and safety of adalimumab in patients with plaque psoriasis unresponsive to previous therapies. METHODS: We present nine patients with psoriasis and psoriatic arthropathy treated with adalimumab, including a woman with a history of breast cancer and a man with hepatitis C virus-related liver disease. RESULTS: After 12 weeks, 66.6%, 55.5% and 11.1% of the patients showed a Psoriasis Assessment and Severity Index response of 50%, 75% and 90%, respectively. After 20 weeks, these levels had increased to 75%, 62.5% and 37.5%, respectively. After 12 weeks, the Psoriasis Global Assessment (PGA) score was clear or almost clear in 33.3% of the patients. By week 20, this clearance rate had almost doubled (62.5%). In two patients, the treatment was prolonged for 52 weeks, with a sustained response. One patient presented nonspecific colitis and died as a result of in-hospital pneumonia; any implication of adalimumab in the death is not clear. No other serious adverse effects were observed. CONCLUSION: In this series adalimumab was found to be effective for psoriasis refractory to other treatments including infliximab and etanercept.

[Atypical pigmented penile macules]. / Máculas atípicas pigmentadas del pene.

Two patients with pigmented lesions of the penis are described. The lesions consisted of asymptomatic, multifocal, irregular macules, with variegated pigmentation. The main differential diagnostic problem was with mucocutaneous melanoma. Histologic examination of the lesions showed basal layer hyperpigmentation. No cytologic atypia of melanocytes was detectable. The diagnosis in both cases was melanotic macules. Because of their atypical clinical appearance, genital melanotic macules are often misinterpreted as mucocutaneous melanoma. However histopathologic study solves the problem because genital melanotic macules show no melanocytic proliferation nor melanocytic atypia.

Máculas atípicas pigmentadas del pene / Atypical pigmented penile macules

Describimos los casos de dos pacientes con lesiones hiperpigmentadas localizadas en el pene que se presentaban como máculas asintomáticas, multifocales, heterocrómicas, de bordes irregulares. El principal problema diagnóstico era diferenciarlas de un melanoma mucocutáneo. El estudio histopatológico mostró hiperpigmentación de la basal en ausencia de atipia melanocítica. El diagnóstico en ambos casos fue de máculas melanóticas del pene. En ocasiones, estas lesiones presentan una apariencia clínica atípica pudiendo confundirse con un melanoma mucocutáneo. Sin embargo, los hallazgos de la biopsia confirman la benignidad de la lesión

Two patients with pigmented lesions of the penis are described. The lesions consisted of asymptomatic, multifocal, irregular macules, with variegated pigmentation. The main differential diagnostic problem was with mucocutaneous melanoma. Histologic examination of the lesions showed basal layer hyperpigmentation. No cytologic atypia of melanocytes was detectable. The diagnosis in both cases was melanotic macules. Because of their atypical clinical appearance, genital melanotic macules are often misinterpreted as mucocutaneous melanoma. However histopathologic study solves the problem because genital melanotic macules show no melanocytic proliferation nor melanocytic atypia

Positive margins in basal cell carcinoma: relationship to clinical features and recurrence risk. A retrospective study of 248 patients.

BACKGROUND: Incomplete resection of a basal cell carcinoma does not necessarily imply tumour recurrence. OBJECTIVE: The purpose of our study was to determine the clinical features most often associated with positive surgical margins and to establish whether positive margins effectively imply tumour recurrence. METHODS: We did a retrospective evaluation of 273 basal cell carcinomas in a total of 248 subjects. For each case, data regarding tumour location, sex, histological type and the presence or absence of affected surgical margins were collected. Follow-up was available in 151 cases. RESULTS: Positive margins were most often observed in facial lesions, particularly in the nasal and perioral areas, and for morphoeic histological types. Tumours with margin involvement exhibited a higher recurrence rate (26%) than those with free margins (14%) over a 5-year follow-up period. CONCLUSIONS: Individualized management, with special considerations depending on tumour location and histological type, is needed to treat basal cell carcinomas and cases with affected margins. Re-excision, preferably with Mohs' surgery, is advised in the latter as recurrences are much more complicated to treat. Furthermore, all cases need adequate follow-up, even in cases with unaffected surgical margins.

Molecular genetic analysis of HLA-DR and -DQ alleles in Spanish patients with melanoma.

Controversial data have been reported about HLA alleles and susceptibility to melanoma. The relationship between distribution of HLA alleles in patients with melanoma and susceptibility to tumour was analysed, to study the possible correlation between HLA class II DQA1, DQB1 and DRBI genes and melanoma in a Spanish population. Genomic DNA from 82 patients with melanoma and 367 random healthy donors, from the same geographic area, were typed by PCR-SSP (sequence specific primers). The patients were also divided into different groups according to the age and presence of cancer relatives, and compared with the controls. None of these HLA class II alleles showed significant positive or negative associations with either the overall population of patients with melanoma or the considered subgroups. Moreover, values for relative risk of DQB1*0301, DQB1*0302, DQB1*0303, DQB*05, DQA1*0401, DQA1*0101/0104 and DRB*08, which have been reported to be increased or decreased in patients with melanoma, were very low and of no statistical significance. Our results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Spanish population, although further studies on larger series are needed to corroborate this. Key words:

Primary cutaneous melanoma in hidden sites is associated with thicker tumours - a study of 829 patients.

The aim of this study was to determine if primary cutaneous melanomas in hidden anatomical sites were associated with thicker tumours. Retrospective medical data of 829 patients with melanomas diagnosed at our centre between January 1976 and July 1998 were recorded from our database. Three groups were defined according to the anatomical site of the primary melanoma: (1) visible areas (group 1: 493 patients); (2) visible areas only to the patients or to their partners in privacy (group 2: 281 patients); and (3) hidden areas (group 3: 55 patients). Univariate analysis indicated that patients with melanoma in hidden regions presented significantly thicker tumours (median for group 3: 2.25 versus 1.17 for group 1 and 1.42 for group 2). This group were also more commonly males (group 3: 58% men versus group 1: 38% and group 2: 51%), in a more advanced stage (metastatic disease at diagnosis in 16% of patients in group 3 versus 6% in groups 1 and 2) and at a more advanced age (median group 3: 66 years versus group 1: 59 years and group 2: 51 years), than patients in the other two groups. The association between tumour thickness and body site remained statistically significant after a multivariate analysis. As a delay in diagnosis may be responsible for the thicker size of melanoma in the hidden areas, preventive programmes should stress the importance of not forgetting these locations in self-examination and screening. Special attention should be given to educating elderly men.

Detection of Epstein-Barr virus DNA in a patient with Kimura's disease.

An 80-year-old man, with a past medical history of senile dementia, presented with a 6-month history of a solitary, gradually enlarging tumor, located on his chin. A squamous cell carcinoma had been surgically excised 30 years previously in the same location. Physical examination revealed an erythematous, well-defined plaque of 3 cm in diameter, located on the chin (Fig. 1). The submandibular lymph nodes were enlarged. Squamous cell carcinoma and primary cutaneous lymphoma were considered. Relevant laboratory findings were as follows: white blood cell count, 5.600/microL; eosinophils, 1000/microL; gammaglobulin, 2.4 g/dL; lactate dehydrogenase, 343 IU/L; and immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) positive (at 1 : 128 serum dilution), with negative IgM. Skin and lymph node biopsies were performed. Histopathologic study of the cutaneous specimen revealed a heavy lymphoid infiltrate with numerous lymphoid follicles, with prominent germinal centers involving the subcutaneous fat as well as the deep dermis and muscular fascia. Some germinal centers showed folliculolysis. The lymphoid follicles were surrounded by fibrous tissue. The interfollicular infiltrate was rich in plasma cells and eosinophils that formed scattered eosinophilic microabscesses. Thin-walled vessels were numerous and prominent, but with no epithelioid or vacuolated endothelial cells (Fig. 2). Histopathology of a lymph node biopsy specimen showed reactive lymphoid follicle hyperplasia, with prominent eosinophilic infiltrates in both follicular and interfollicular areas. Eosinophilic deposits and polykaryocytes of Warthin-Finkeldey type were seen in the germinal centers. The paracortical area showed vascular proliferation. Polymerase chain reaction (PCR) for the detection of specific sequences of EBV from routinely processed paraffin-embedded material was carried out under the conditions and with the same set of primers as described previously in detail (Tenorio A, Echevarría JE, Casas E et al. J Virol Methods 1993; 44: 261-269). DNA samples were confirmed to be amplifiable with PCR primers specific for a conserved region of the human beta-globin gene. Every sample was tested at least twice for EBV DNA and beta-globin gene. One sample from one skin lesion of the patient, with confirmed diagnosis of Kimura's disease, and 10 samples from normal skin biopsies retrospectively collected from other patients in archival files of our department were tested. Only the patient's specimen tested positive to EBV. The amplified product of EBV was analyzed using DNA sequencing and confirmed the results obtained. The patient received radiotherapy at doses of 35 Gy. Nevertheless, the tumor enlarged to reach twofold its original size 1 month later. Due to the physical status of the patient, no further treatments were considered, but the disease remained stable over the following 3 years.

Analysis of the CDKN2A and CDK4 genes and HLA-DR and HLA-DQ alleles in two Spanish familial melanoma kindreds.

Some confusion exists in the literature about which criteria should be used to define familial melanoma. This could explain the different reported frequencies of mutations in predisposing genes, mostly CDKN2A, in these patients. This study evaluated the human leucocyte antigen (HLA) class II genotype and the presence of mutations in CDKN2A and CDK4 genes in 2 families with very different clinical features. The family with a germinal mutation in exon 2 of CDKN2A (Gly101Try) presented the following clinical features: 3 first-degree affected members, 1 of whom had 2 melanomas, and all the melanomas appearing before 35 years of age. In contrast, the second family did not present any mutation in the studied genes and included 2 first-degree affected members diagnosed at over 45 years of age. Neither family showed an association with HLA genotype. Other genes are also involved in familial melanoma but, when the CDKN2A gene is affected, some clinical features seem to be uniform.

Follicular mycosis fungoides: presentation of a case and review of the literature.

Follicular mycosis fungoides is a rare variant of mycosis fungoides (MF). Structural-wise there are several acneiform lesions made up of comedones, cysts and hyperkeratosis. The main histological finding is atypical lymphocytic infiltration around follicular structures, without epidermotropism. The association with follicular mucinosis is widely discussed in the literature. We report a case of follicular (MF) and review the cases published to date.

Widespread angiokeratomas and tuberous sclerosis.

We report a 29-year-old woman who had prominent cutaneous markers of tuberous sclerosis, with subependymal nodules and renal cysts on computerized tomographic scan, who also showed multiple angiokeratomas widely distributed on the buttocks and posterior thighs. Enzymatic studies ruled out Fabry's disease and other lysosomal storage disorders. This is the first reported association of widespread angiokeratomas and tuberous sclerosis.

Pleomorphic angioleiomyoma.

A 72-year-old man presented with a single nodule in the right thigh of 12 years' evolution. Histopathology confirmed the diagnosis of angioleiomyoma. However, unlike other tumors of this type reported in the literature, marked nuclear pleomorphism without mitotic figures was noted.

Erythema elevatum diutinum associated with celiac disease: response to a gluten-free diet.

An 11-year-old girl with a history of insulin-dependent diabetes mellitus had erythema elevatum diutinum (EED) associated with a celiac disease related to a possible kidney disease. Dapsone did not improve the skin manifestations. However, the lesions disappeared after a gluten-free diet was begun. To our knowledge, this report describes the first case of EED in a patient with celiac disease.

Photosensitivity induced by fibric acid derivatives and its relation to photocontact dermatitis to ketoprofen.

BACKGROUND: Photosensitivity reactions to fibric acid derivatives are not well understood and have been rarely reported. OBJECTIVE: The aim of this study was to describe two cases of photosensitivity, one induced by fenofibrate and one by bezafibrate; to study the in vivo photosensitizing potential of these drugs; and to evaluate the possibility of cross-reactivity between fenofibrate and ketoprofen. METHODS: Patch and photopatch tests with fibric acid derivatives and ketoprofen were performed in the patients, in 12 normal volunteers, and in 7 patients with photopatch-proven photocontact dermatitis to ketoprofen. Phototesting studies were performed both while the patients were taking the drugs and after withdrawal of them, as well as in a group of 18 hyperlipemic volunteers without history of photosensitivity who were taking therapeutic doses of fenofibrate or bezafibrate for 2 to 3 months. RESULTS: Positive photopatch test responses to ketoprofen and to fenofibrate were obtained only in the first patient, who also had a weaker positive ordinary patch test response to the latter. Five patients photosensitized to ketoprofen also had a positive patch test to fenofibrate. Phototesting studies were abnormal in both patients but normal in all volunteers. CONCLUSION: An association between systemic photosensitivity to fenofibrate and photocontact sensitivity to ketoprofen seems to exist. The structural similarities of these chemicals favor cross-reactivity.

Oxicam-induced photosensitivity. Patch and photopatch testing studies with tenoxicam and piroxicam photoproducts in normal subjects and in piroxicam-droxicam photosensitive patients.

BACKGROUND: The mechanism of piroxicam-induced photosensitivity is unknown. It was first attributed to metabolites of the drug produced in vivo but further photochemical studies disclosed that piroxicam was not stable to light, forming at least two photoproducts. Photosensitivity reactions to droxicam and tenoxicam have been not reported. OBJECTIVE: The aim of this study was to determine whether piroxicam photoproducts contribute to the light reactions induced by this drug, to describe a case of droxicam-induced photosensitivity and to study the in vivo photosensitizing potential of tenoxicam. METHODS: Patch and photopatch tests with two major photoproducts of piroxicam, with different preparations of UVA-preirradiated piroxicam, and with low and high concentrations of tenoxicam were performed in normal volunteers and in piroxicam-photosensitive patients. Phototesting studies were also performed before and after the oral administration of tenoxicam in both groups of subjects. RESULTS: Positive patch test responses were obtained in piroxicam-photosensitive patients only with the preirradiated piroxicam preparations. Phototesting studies with tenoxicam were normal in both groups. CONCLUSION: Minor or intermediate piroxicam photoproducts are more likely to be responsible for the photosensitivity reactions induced by this drug.