Drug-induced psoriasis: an evidence-based overview and the introduction of psoriatic drug eruption probability score.

Psoriasis is a common skin disorder that needs a long-term management, not only because, of its prevalence but also because of the profound impact it can have on patients quality of life. Drugs may result in exacerbation of a preexisting psoriasis, in induction of psoriatic lesions on clinically uninvolved skin in patients with psoriasis, or in precipitation of the disease in persons without family history of psoriasis or in predisposed individuals. The knowledge of the drugs that may induce, trigger, or exacerbate the disease is of primary importance in clinical practice. By reviewing the literature, there are many reports on drug-induced psoriasis, but the data are not univocal. We propose, when possible, the use of a probability score from the authors to obtain a better classification and further understanding of drug-induced psoriasis.

Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.

Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.Peculiar dermatologic manifestations are present in several heritable gastrointestinal disorders. Muir-Torre syndrome (MTS) is a genodermatosis whose peculiar feature is the presence of sebaceous gland tumors associated with visceral malignancies. We describe one patient in whom multiple sebaceous gland tumors were associated with early onset colon and thyroid cancers and attenuated polyposis coli. Her family history was positive for colonic adenomas. She had a daughter presenting with yellow papules in the forehead region developed in the late infancy. Skin and visceral neoplasms were tested for microsatellite instability and immunohistochemical status of mismatch repair (MMR), APC and MYH proteins. The proband colon and skin tumors were microsatellite stable and showed normal expression of MMR proteins. Cytoplasmic expression of MYH protein was revealed in colonic cancer cells. Compound heterozygosity due to biallelic mutations in MYH, R168H and 379delC, was identified in the proband. The 11-year-old daughter was carrier of the monoallelic constitutional mutation 379delC in the MYH gene; in the sister, the R168H MYH gene mutation was detected. This report presents an interesting case of association between MYH-associated polyposis and sebaceous gland tumors. These findings suggest that patients with MTS phenotype that include colonic polyposis should be screened for MYH gene mutations.

Presence of high-risk mucosal human papillomavirus genotypes in primary melanoma and in acquired dysplastic melanocytic naevi.

BACKGROUND: Some studies have shown that cutaneous and mucosal melanoma biopsy specimens harbour human papillomavirus (HPV), suggesting that this virus may play a role in development and progression of the tumour. OBJECTIVES: To investigate the presence of HPV DNA and the prevalence of different high-risk mucosal HPV genotypes in primary melanoma (PM) and in acquired dysplastic melanocytic naevi (ADMN). METHODS: Fifty-one PMs from 18 men and 33 women (median age 55.5 years), 33 ADMN from 15 men and 18 women (median age 35.1 years) and 20 control skin samples from nine men and 11 women (median age 43.5 years) were studied. All diagnoses were made after histological analysis. HPV DNA analysis was made using two different polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) methods, namely MY-PCR and GP-PCR. RESULTS: Using GP-PCR, mucosal HPVs were detected in 14 PMs (27%; P = 0.0166) and eight ADMN (24%; P = 0.0367), while with MY-PCR, mucosal HPVs were found in 11 PMs (22%; P = 0.04) and five ADMN (15%; P not significant). All control skin samples were negative for mucosal HPVs with both DNA amplification procedures. CONCLUSIONS: Using our PCR-ELISA methods, the detection of mucosal high-risk HPV genotypes in 24% of precursor lesions (ADMN) and in 27% of PMs adds to the body of evidence indicating a colocalization of mucosal HPV and tumoral melanocytic pathologies.

Sexually-transmitted infections in adolescents and young adults in a large city of Northern Italy: a nine-year prospective survey.

To determine demographic, epidemiological, clinical features and risk factors of sexually-transmitted diseases (STD) in adolescents and young adults referring to a STD centre in Northern Italy, patients diagnosed with a STD and aged 13-20 years, were prospectively evaluated from the year 1991. Teenagers showed an appreciable and increasing risk of a broad spectrum of STD, and represented 3.6-13.3% of patients yearly diagnosed with a STD in a nine-year period. More than 10% of patients were under the age of 18, and did not report condom use in the six months preceding diagnosis in 96.7% of cases. A significant increase in the female gender was found since 1993 (but our series was massively influenced by the recent immigration of female sex workers, who declared frequent condom use), while male homosexuals and drug addicts represented a minority. When excluding subjects engaged in prostitution, over 50% of patients declared only 0-1 sexual partners during the last six months, but a significant increase in sexual promiscuity was observed over time (1997-1999 versus 1991-1996) (p<.02). Over two thirds of our teenagers never used a condom prior to the diagnosis of STD, and the apparently increased temporal trend to condom utilization proved related only to the recent immigration of sex workers; lack of condom use proved significantly related to the male gender, and a lower education. Non-gonococcal STD and human Papillomavirus infection accounted for over 60% of overall diseases, while the frequency of molluscum contagiosum, gonorrhea, HSV genital ulcer, and Chlamydia disease ranged from 6.1 to 7.4%, and that of syphilis, phthiriasis, trichomoniasis, and HIV infection varied from 1.3 to 4.7%. Non-gonococcal STD and syphilis were increasingly diagnosed over time, especially in immigrant prostitutes (and despite their frequent condom use). According to our surveillance study of teenagers, a number of demographic, epidemiological, and clinical features of STD showed significant variations over time: recent immigration, spread of prostitution, increased sexual promiscuity, and infrequent condom use, are relevant and/or persisting risk factors. A permanent monitoring of STD in young adults and adolescents is strongly warranted, to allow a timely diagnosis and an appropriate treatment, and to plan preventive strategies specifically addressed to this target population, with special attention to immigrants and sex workers.

Evaluation of efficacy and tolerance of neuramide in the treatment of herpes zoster and postherpetic neuritis.

Ninety-two patients suffering from herpes zoster were enrolled in a double-blind controlled study aimed at evaluating the efficacy and tolerance of the drug neuramide. Neuramide (N) and placebo (P) were administered to patients intramuscularly twice daily for 28 days as follows: group N + N (patients always treated with neuramide); group N + P (patients treated with neuramide for 1 week, then with placebo); group P + N (patients treated with placebo for 1 week, then with neuramide); group P + P (patients always treated with placebo). During the first week, all patients were also treated with standardized doses of acyclovir. The presence and extent of clinical symptoms were evaluated during the first 4 weeks, while the appearance, degree and duration of postherpetic neuralgia were evaluated both during treatment and over a 6-month follow-up period. There were no significant differences between the four groups of patients when subjective parameters (such as pain and paresis at the lesion site) were examined. However, clinical examination at the end of treatment showed that treatment with neuramide was therapeutic. Indeed, the times for recovery and for regeneration of epithelium were significantly shorter when neuramide was administered for 3 weeks of the treatment period. Furthermore, the change from vesicles to crusts was significantly faster in the neuramide group than in the placebo group. Postherpetic neuritis occurred in the first months of follow-up. However, in groups N + P and P + P, the symptoms lasted throughout the 6-month observation period, while in the other groups this period was shorter. Indeed, there were significant differences (p < 0.05) in terms of the above complications between the following groups: N + N and N + P; N + N and P + P; N + P and P + N; P + N and P + P. No significant differences were observed between the N + N and P + N, or N + P and P + P groups. Taken together, these data demonstrate that neuramide treatment for at least 3 weeks significantly reduces the risk of postherpetic neuritis development.

[Sexually transmitted diseases (STD) and their relationship with sexual behaviour and condom use, in a cohort of teenagers referring to a STD centre. A nine-year, prospective study]. / Malattie a trasmissione sessuale (MTS) e loro correlazione con il comportamento sessuale el'utilizzo del preservativo In una coorte di giovani adulti afferenti ad un centro per MTS. Nove anni di osservazione prospettica.

In order to assess the relationship between a diagnosis of sexually-transmitted disease (STD), sexual behaviour, condom use, and other social, demographic, and epidemiological variables in a cohort of young adults who referred to a STD centre during a 9-year period, all patients aged 13-20 years were prospectively evaluated, with special attention paid to sexual behaviour, and use of condom or other contraceptive techniques. The 284 assessed young adults represented 6.1% of all patients with a diagnosis of STD: an increasing temporal trend was noticed (from 3. % in 1991, up to 10.4% nel 1999: p<.0001). On the whole, 70.1% of subjects aged 20 years or less never used a condom during the 6 months preceding the diagnosis of STD: only 21.8% of patients reported regular condom use, and 4.9% more subjects referred occasional use, while in the remaining 3.2% of cases other contraceptive methods were employed. Among under age patients (10.6% of study population), the rate of condom use was 3.3% only, while male homosexuals always denied the use of barrier methods. Although a progressive increase in condom use was observed through the study time (from 0% encountered in 1991-1994, to 57.6% of 1999: p<.0001), this phenomenon proved linked only to the massive increase of immigrant sex workers, which occurred since 1997. When excluding from analysis any probable female prostitutes, lack of condom use tested related to the male gender (p<.05), and a low education (p<.04). Over 50% of patients reported 0-1 partners during the last 6 months, even though an increase in sexual promiscuity was observed during the last three years, compared with 1991-1996 (p<.02). Among the 297 different STD episodes (mostly nongonococcal cervicitis-vaginitis and urethritis, and HPV infection), an increasing incidence of nongonococcal STD and syphilis was found, but no correlation was observed between the spectrum of diagnosed STD, sexual behaviour, and condom use. In particular, in 69.9% of the 103 episodes nongonococcal disease occurred despite regular (65 cases), or occasional (7 episodes) condom use. Moreover, no significant relationship was disclosed between STD occurrence, condom use, and other analyzed social, demographic, epidemiological, and clinical variables. According to our survey, an increased risk of STD seems to involve young adults, and to be related to the variation of multiple demographic, epidemiological, and behavioral features. While immigration and prostitution had the major impact during the last three years, sexual promiscuity and infrequent condom use represent persistent; risk factors in this age population. Besides their diagnostic and therapeutic role, STD centres are able to carry out permanent monitoring of STD, as a starting point to plan adequate information campaigns and specific prevention strategies.

Necrobiotic xanthogranuloma without periorbital involvement: an ultrastructural investigation.

A case of necrobiotic xanthogranuloma without typical periorbital involvement is described at the ultrastructural level. The patient, a 58-year-old Italian man, presented in 1995 with a brief history of nodulo-papular lesions commencing on the lower limbs, and mild paraproteinemia. During 6 years of follow-up, anemia, neutropenia with marked lymphopenia, and increased ESR were found, while serum cholesterol and triglyceride levels decreased from hyper to hypo values. Systemic diseases, such as diabetes, malignancy, or extracutaneous lesions, often associated with NXG, have not developed. Conventional histology was distinctive for NXG, and immunohistochemistry confirmed that dermal histiocytes were not of Langerhans cell lineage. At ultrastructure, regeneration and degeneration ("regen-degen") features were observed in some individual deep dermal histiocytes, which have not been previously documented in the literature. Identification of giant histiocytes showing 'regen-degen'' aspects might prove to be a useful ultrastructural diagnostic marker for NXG.

Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing.

Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant PEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by PEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-alpha1(VII) polypeptide chain. As a consequence, procollagen VII failed to be processed to mature collagen VII and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody. The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified. This represents the first report of a recessive deletion mutation in PEB and extends the range of EBD phenotypes associated with mutation 33563del14.

Mid-dermal elastolysis: a pathological and ultrastructural study of five cases.

The aim of this study was to evaluate the presence of inflammatory phenomena and elastic fiber phagocytosis in mid-dermal elastolysis. The pathological and ultrastructural features of 5 Caucasian female patients (ranging from 26 to 40 years) with acquired diffuse asymptomatic areas of skin wrinkling have been reviewed. The clinical features of all cases were characteristic of this condition and only in one patient were erythematous urticaria-like, non pruriginous patches also observed. In 4 cases a history of prolonged sun bathing was present and in 3 cases there was a short history of oral contraception. The pathological study confirmed the typical absence of elastic fibers in the midreticular dermis. In two cases elastic fibers were still detectable in the periadnexal dermis. Hematoxylin and eosin sections showed a mild perivascular infiltrate in two cases, while in three patients histiocytes were scattered among collagen bundles. Multinucleated giant cells containing fragmented elastic fibers were detectable in one patient. Ultrastructural analysis revealed large mononuclear cells with phagocytic aspects toward elastic fibers in all cases.

The various clinical patterns of xanthoma disseminatum. Considerations on seven cases and review of the literature.

BACKGROUND: Xanthoma disseminatum (XD) is a rare mucocutaneous xanthoma nowadays classified as a benign non-Langerhans cell histiocytosis. OBJECTIVE: We studied 7 cases of XD with a long follow-up and reviewed the literature in order to compare and discuss previous reports. METHODS: We studied clinical manifestations, course, histopathologic, ultrastructural and immunohistochemical findings of 7 cases of XD followed for 1-20 years. RESULTS: We report our findings and compare our cases with those described in the literature. CONCLUSIONS: XD and Langerhans cell histiocytosis were distinguished by clinical differences, as well as ultrastructural and immunohistochemical methods. Three clinical patterns of XD appeared to emerge in our group of patients and in the cases reviewed from the literature.

Keratosis lichenoides chronica: a pediatric case.

Keratosis lichenoides chronica (KLC) is a rare chronic disorder of keratinization characterized by lichenoid hyperkeratotic papules arranged in a linear pattern, erythematosquamous plaques and seborrhea-like dermatitis on the face. Adults between 20 and 50 years of age are usually affected, but the disease is very uncommon in childhood. Our purpose was to study the clinical and histopathologic findings and course of KLC in one pediatric case. Detailed clinical data were studied. Two punch biopsies were performed and histopathologic features were compared with those of other reported cases of KLC. In our patient, a 4-year-old boy, the clinical features of the lesions did not deviate notably from those of other cases of KLC. The histologic pattern of the papules was typical of KLC, while that of the erythematosquamous plaques showed some dyskeratotic keratinocytes. The histologic pattern of the erythematosquamous lesions is peculiar in our case, whereas only a nonspecific pattern is reported in the literature. The papular and erythematosquamous lesions showed similar histopathologic features suggesting that they could be different degrees of evolution of the same lesion.

Nail matrix hypergranulosis.

Nail pathology shares some common features with skin pathology, but it also has its own peculiar aspects. The anatomical and physiological characteristics of the nail unit probably play a major role in determining these pathological differences. Although the presence of keratohyaline granules is a normal feature of the skin, there is no granular layer in the normal nail matrix. As a consequence, nail matrix hypergranulosis should be considered a separate entity from skin hypergranulosis. In our review of 150 longitudinal nail biopsy specimens, keratohyaline granules were seen in the nail matrix of 24 cases of lichen planus, 29 cases of spongiotic trachyonychia, 10 cases of psoriasis, and three cases of Hallopeau acrodermatitis. In all cases, the presence of keratohyaline granules was associated with the absence of the normal keratogenous zone. Similar nail matrix features were detectable in three cases of malignant melanoma, two cases of primary systemic amyloidosis, and one case of histiocytoid hemangioma compressing the nail matrix. Our data suggest that inflammatory and compressive insults to the nail matrix cause both disappearance of the keratogenous zone and matrix keratinization with the formation of keratohyaline granules. Skin hypergranulosis reflects a hyperplasia of a normal skin component. In the nail matrix, however, hypergranulosis represents the appearance of structures not normally present. Nail matrix hypergranulosis should be considered a pattern of nail matrix reaction to different inflammatory insults. It is therefore more analogous to epidermal parakeratosis than to epidermal hypergranulosis.

Intermittent cyclosporin A treatment of severe plaque psoriasis. Long-term follow-up of 26 patients.

The aim of this study was to evaluate the long-term effects of intermittent Cyclosporin A treatment of severe plaque psoriasis. For this purpose we considered the clinical records of 26 patients who had been intermittently treated with Cyclosporin A for 2 to 4 years. All 26 patients had severe plaque-type psoriasis (PASI score > 18) that was unresponsive to conventional treatment. The initial Cyclosporin A dosage was 5 mg/kg/day in 8 cases and 3 mg/kg/day in 18 cases. In all patients, Cyclosporin A treatment was prolonged until complete or nearly complete remission of psoriasis (mean 2 months; range 1-4 months). All patients subsequently underwent a 2-4 months maintenance treatment with Cyclosporin A dosages that were gradually reduced until tapering off. In order to maintain clinical improvement after Cyclosporin A withdrawal, patients were treated with topical steroids, topical tar, emollients and UVA exposure and/or eliotherapy. Cyclosporin A treatment (2.5-3 mg/kg/day) was reintroduced only when clinical relapses reached a PASI score of 12 or more. Duration and dosages of Cyclosporin A cycles were always adapted for the purpose of obtaining an improvement acceptable to the patient (PASI < 8) rather than total clearance of psoriasis. So far, the 26 patients have undergone 3-5 cycles of therapy with low doses of Cyclosporin A. None of these 26 patients interrupted Cyclosporin A treatment because of side effects. In conclusion, in our experience cyclic CyA treatment is effective for the long-term treatment of psoriatic patients.

Progressive hyperpigmentation: case report with a clinical, histological, and ultrastructural investigation.

A clinical, histological and ultrastructural study of a 38-year-old woman with generalized progressive hyperpigmentation is reported. Hyperpigmentation started in early infancy, progressed during childhood and has increased to a dark bronze-brown color with 'mottling' in the last 8 years. Histology and electron microscopy revealed epidermal hypermelanosis and 'negroid' distribution of melanosomes in keratinocytes. In our family, autosomal dominant phenotype transmission with 'variable expression' is suggested. The literature on the entity has been reviewed. This case is another rare example of familial progressive hyperpigmentation.