[Sequential histological and immunohistochemical assessment of proliferation and apoptotic markers during treatment of psoriasis with antitumor necrosis factor alpha (infliximab)]. / Evaluación histológica e inmunohistoquímica secuencial de marcadores de proliferación y apoptosis durante el tratamiento de la psoriasis con anti-factor de necrosis tumoral alpha (infliximab).

BACKGROUND AND OBJECTIVES: Psoriasis is an inflammatory skin disease of immunologic nature that is mediated by T-helper-1 cytokines. Clinical response to treatment with antitumor necrosis factor (TNF) alpha antibodies (infliximab) has been significant; however, the mechanisms for clearance of lesions have not been elucidated. The aim of the present study was to assess variations in the histology and expression of proliferation and apoptotic markers in sequential skin biopsies of patients with psoriasis treated with infliximab. MATERIAL AND METHODS: We studied skin biopsies (of lesioned and healthy skin) from 3 patients with extensive moderate-to-severe psoriasis (mean psoriasis area and severity index [PASI] score, 35) treated with intravenous infliximab infusions (5 mg/kg) at weeks 0, 2, and 6. Biopsies were taken on days 0, 14, and 28, and were processed for conventional histological and immunohistochemical study. The apoptotic markers used were TP53, B-cell lymphoma 2 protein, anticaspase 3, and anticaspase 8. The cell proliferation marker used was Ki67. RESULTS: Treatment with infliximab was associated with a significant clinical improvement in 3 patients (mean PASI score, 21.6 at 14 days and 13.9 at 6 weeks), which correlated with the progressive disappearance of histological lesions with a decrease in epidermal proliferation. However, apoptosis was not observed, and the samples tested negative for anticaspase antibodies. Expression of TP53 decreased 2 weeks after starting treatment, and was similar to that in normal skin at 28 days. CONCLUSIONS: Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed.

[Trichothiodystrophy: PIBIDS syndrome]. / Tricotiodistrofia: síndrome PIBIDS.

Trichothiodystrophy comprises a heterogeneous group of autosomal recessive entities. This fact gives rise to different interrelated neuroectodermal disorders. From a structural point of view these features are the result of the low tissue sulfur content. We report a case of trichothiodystrophy initially classified as Tay syndrome that based on clinical features, complementary exams as well as on the disease evolution was labelled as PIBIDS syndrome.

[Narrow band UVB therapy in early stage mycosis fungoides. A study of 23 patients]. / Tratamiento con UVB de banda estrecha de los estadios iniciales de la micosis fungoide. Estudio de 23 pacientes.

INTRODUCTION: Phototherapy is effective for mycosis fungoides. Narrow band UVB (UVB1) therapy is being used as an alternative to PUVA therapy for its efficacy and less adverse events. The objective of the study was to determine the efficacy of narrow band UVB therapy in early stage mycosis fungoides. METHODS: It is a retrospective study of 23 patients with stage IB mycosis fungoides that have received UVB1 therapy following the phototherapy protocol of the Spanish Photobiology Group. RESULTS: Thirteen patients (57 %) had a complete response, eight patients (35 %) had a partial response and two patients (8 %) did not respond. Half of the patients with complete response (n = 6) relapsed after one year of follow-up. CONCLUSIONS: We consider that UVB1 therapy is a good alternative for treatment of early stage mycosis fungoides, although the disease-free period is short.

[Ofujis papuloerythroderma. Presentation of 3 cases and review of its concept and etiology]. / Papuloeritrodermia de Ofuji. Presentación de tres casos y revisión de su concepto y etiología.

Ofuji's papuloerythroderma is not a specific clinical entity, but a concequence of numerous inflammatory dermatoses and neoplasms. Some authors advocate that it is possible to find this erupcion in elderly patients with different types of erythroderma of known or unknown origin. It is necessary to recognize this condition since these patients can develop a lymphoma in the future. In this article three atopic patients are described with clinical lesions of papuloerythroderma respecting the cutaneous folds, with eosinophilia, increase of the IgE levels and histological characteristics of atopic eczema. We think that atopic dermatitis should be considered in the etiologic study of patients with papuloerythroderma.

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

[Study of urethritis in males using Papanicolaou smear]. / Estudio de las uretritis masculinas mediante la tinción de Papanicolaou.

Sexual pathogens, cell types and morphologic alterations of urethral epithelial cells were investigated by means of the Papanicolaou smear in 110 heterosexual men. Seventy-five patients with urethritis were included: 17 (22.6%) with gonococcal urethritis (GU) and 58 (77.3%) with non-gonococcal urethritis (NGU). Thirty-five males without symptoms or signs of urethritis comprised the control group. An increase in epithelial cell dissociation was observed in patients with urethritis. Non-specific inflammatory changes were statistically more common in patients with urethritis than in controls, and more severe in GU (65%) than in NGU (15.5%). Nuclear atypia was a common finding (43.5%) in infections due to C. trachomatis. Mucus was associated with the presence of urethritis although no differences regarding etiology were found. No polimorphonuclear neutrophils were observed in the exudate of three patients (5%) with NGU. There was a statistically significant presence of lymphocytes in patients with urethritis, particularly in GU (45%), more frequent than in NGU (15.5%). Erythrocytes were also significantly more frequent in urethritis, with a greater proportion in GU (94%) than in NGU (64%). Plasma cells, eosinophils, and histiocytes were only observed in a few patients with urethritis. The Papanicolaou smear had a sensitivity of 47% and a specificity of 90% in Chlamydia trachomatis infections.

Management of androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is the most frequent cause of hair loss affecting up to 50% of men and 40% of women by the age of 50. METHODS: This paper outlines the current status of diagnosis and offers guidelines for optimal management of AGA in both men and women. RESULTS: The diagnosis of AGA can usually be confirmed by medical history and physical examination alone. A trichogram can be useful to assess the progression of the hair loss. A scalp biospy is diagnostic but usually not required. In women with signs of hyperandrogenism, investigation for ovarian (polycystic ovarian disease) or adrenal (late-onset congenital adrenal hyperplasia) disorders is required. Mild to moderate AGA in men can be treated with oral finasteride or topical minoxidil. Oral finasteride at the dosage of 1 mg/day produced clinical improvement in up to 66% of patients treated for 2 years. The drug is effective for both frontal and vertex hair thinning. Medical treatment with finasteride or minoxidil should be continued indefinitely since interruption of therapy leads to hair loss with return to pretreatment status. Mild to moderate AGA in women can be treated with oral antiandrogens (cyproterone acetate, spironolactone) and/or topical minoxidil with good results in many cases. Hair systems and surgery may be considered for selected cases of severe AGA both in men and in women. CONCLUSIONS: Patients with AGA should be informed about the pathogenesis of the condition. If used correctly, available medical treatments arrest progression of the disease and reverse miniaturization in most patients with mild to moderate AGA.

Sexually transmitted diseases in 1161 HIV-positive patients: a 38-month prospective study in southern Spain.

BACKGROUND: HIV infection is primarily a sexually transmitted disease (STD), but intravenous drug use (IDU) is the main risk factor for HIV infection in certain areas, including southern Europe. A number of prospective studies of dermatological findings in HIV-1 infected patients have been published, almost all from countries where homosexuality is the main risk factor of HIV infection and without correlation with CD4 cell counts. No STD data is included in those studies. OBJECTIVE: To determine the incidence of STDs in a cohort of 1161 HIV-1-positive patients from Spain, in the previous medical history and during the prospective study. METHODS: We prospectively examined 1161 HIV-1-positive patients for 38 months, 986 men and 175 women. IDU was the risk factor in 74%, while homosexuality was a risk factor in only 9%. CDC stage II was predominant (51%), while stage IV was less frequent (39%). The mean CD4 cell count was 353/mm3. Patients' past and present medical history of STDs was obtained. CD4 cells/mm3 counts were measured at each visit. RESULTS: Six hundred and eighty-four patients had a past history of STD, whilst new infections were diagnosed in 258 individuals (22%) during the 38-month study. Pediculosis pubis (26%), gonorrhoea (22%), syphilis (13%), genital candida infection (11%) and condyloma acuminatum (10%) were the commonest previous STDs, followed by non-gonococcal urethritis (NGU) (5%), genital herpes (4%) and trichomoniasis (2%). During the 38-month study period and with strong recommendation of condom use for sexual intercourse, condyloma acuminatum (7%), scabies (6%), syphilis (4%) and genital herpes (3%) were commonly diagnosed, followed by gonorrhoea (1.8%), NGU (1.6%), genital candida infection (1.5%), pediculosis pubis (0.6%) and trichomoniasis (0.3%). Only genital herpes had a statistically significant association with advanced stage (P = 5.12 x 10(-6)) and low CD4 cell counts (180 +/- 166 cells/mm3). CONCLUSION: Despite the predominance of the IDU factor among our patients, the incidence of STDs in the past medical history was surprisingly high. The incidence of STD during the study was also high, despite the advice of using condoms after the diagnosis of HIV infection. STDs may accelerate the course of HIV infection and be a poor prognostic indicator in these patients. If an HIV-1-positive patient can acquire an STD, he/she can also transmit HIV infection. This indicates that new publicity campaigns are still needed to stop HIV and STDs infection among HIV-positive patients as well as in the general population.

The history and contributions of the Spanish dermatosurgical school.

The origin of dermatologic surgery in Spain may be traced to the efforts of Professor Felipe de Dulanto, Initially the specialty encompassed only simple direct closure, local flaps, and skin grafts. As the field evolved, distant flaps and other techniques, including dermabrasion, cryosurgery, Mohs' surgery, and laser surgery, were added to the armamentarium. The close, interdepartmental relationships between Dermatology and Otolaryngology, Ophthalmology, Pediatrics, and Gynecology allowed Spanish dermatologic surgery to expand and encompass lymph node dissections, complex reconstructions of the neck, eyelid, vulvar area, breasts, and abdomen.