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The value of molecular analysis by PCR in the diagnosis of cutaneous lymphocytic infiltrates.

The diagnosis and classification of cutaneous lymphomas remain a challenge for the clinician and dermatopathologist. This diagnostic dilemma is mainly encountered in the distinction between an early malignant lymphoma and a benign reactive lymphocytic infiltrate (pseudolymphoma). Until the beginning of the 1980s, our diagnostic tools were limited to the clinical presentation, course, and histopathology in diagnosis and classification of lymphocytic infiltrates. Advances in immunology and, in particular, in molecular genetics with the introduction of the Southern blot technique and the polymerase chain reaction (PCR) have revolutionized the diagnosis of lymphocytic infiltrates by determination of clonality. In some series, more than 90% of cutaneous T-cell lymphomas have a clonal rearrangement of the T-cell receptor gamma-chain gene, as opposed to very low percentages of rearrangement in T-cell pseudolymphomas. However, the presence of clonality does not necessarily imply malignancy. Cases of pseudolymphomas, lichen planus and pityriasis lichenoides et varioliformis acuta were reported with clonal lymphocytic proliferations. Therefore, care should be exercised in the evaluation of the results of molecular analysis, and these should always be correlated with the clinical, histological and immunophenotypic picture to arrive at the correct diagnosis. It may be expected that the molecular methods for diagnosis of lymphocytic infiltrates will be improved and refined in future, and that sensitivity and specificity will increase.

Clone Cells↗

Neutrophil gelatinase-associated lipocalin is a marker for dysregulated keratinocyte differentiation in human skin.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein initially isolated from the specific granules of human neutrophils. It is a member of the highly heterogeneous lipocalin protein family, which shares a common tertiary structure. Its synthesis is induced in gastrointestinal epithelium in association with inflammation and malignancy. To gain insight into its potential role in other epithelia we have investigated the expression of NGAL in human skin embryonic development, in normal adult skin, and in skin associated with inflammation and neoplastic transformation. In the present study we report that the embryonic expression of NGAL appears to be regulated in a spatio-temporal pattern. It was induced in the interfollicular epidermis at 20-24 weeks of gestational age but thereafter progressively receded towards the hair follicles. In normal adult skin, NGAL was detected solely in association with hair follicles. However, strong induction of NGAL in the epidermis was seen in a variety of skin disorders characterized by dysregulated epithelial differentiation such as psoriasis, pityriasis rubra and squamous cell carcinoma. In these tissues production of NGAL was confined to spatially distinct subpopulations of keratinocytes underlying areas of parakeratosis, whereas skin samples lacking parakeratotic epithelium such as lichen ruber planus, acute contact eczema and basal cell carcinoma were negative for NGAL. Consistent with being a marker for disturbed terminal differentiation, NGAL immunoreactivity showed an inverse pattern when compared with that of the differentiation marker filaggrin. The biologic functions of NGAL in epithelia are not fully known, although an immunomodulatory role in host defense has been proposed. In addition, the transient interfollicular NGAL expression during skin embryogenesis along with the induction of NGAL in adult parakeratotic epidermis suggests it play a role in epithelial differentiation pathways.

Acute-Phase Proteins↗

Corneodesmosin expression in psoriasis vulgaris differs from normal skin and other inflammatory skin disorders.

SUMMARY: Corneodesmosin (Cdsn) is a late differentiation epidermal glycoprotein putatively involved in keratinocyte adhesion. The Cdsn gene lies within the susceptibility region on chromosome 6p21.3 (PSORS1) for psoriasis, a common chronic disfiguring skin disease. A particular allelic variant of Cdsn has a strong association with psoriasis. Therefore, genetically and biologically, Cdsn is a possible candidate gene for psoriasis susceptibility. To investigate a potential role for Cdsn in psoriasis pathogenesis, protein expression studies were performed by quantitative immunohistochemistry on normal skin, psoriatic skin (lesional and nonlesional), and other skin disorders using monoclonal antibodies (G36-19 and F28-27). In normal and nonlesional skin, Cdsn was expressed in stratum corneum and one or two layers of superficial stratum granulosum. In lesional psoriasis, there was a significant increase in Cdsn expression, which was observed in multiple layers of stratum spinosum and in stratum corneum. The expression pattern varied from granular, cytoplasmic immunoreactivity to cell surface labeling with weakly immunoreactive cytoplasm. In chronic atopic dermatitis, lichen planus, mycosis fungoides, and pityriasis rubra pilaris, Cdsn immunoreactivity was confined to stratum corneum and upper stratum granulosum with no stratum spinosum immunoreactivity. Immunoelectron microscopy of normal and lesional psoriatic skin demonstrated Cdsn release concomitant with involucrin incorporation into cell envelopes and completed before mature envelope formation. Extracellular release of Cdsn occurred at a lower level of the epidermis in psoriasis than normal skin. These protein expression studies provide evidence of altered Cdsn expression in psoriasis consistent with a role of Cdsn in disease pathogenesis. Further functional and genetic studies of Cdsn are justified to determine its role as a potential psoriasis-susceptibility factor.

Chromosomes, Human, Pair 6↗

Skin diseases associated with human herpesvirus 6, 7, and 8 infection.

Relatively recently, the discovery and analysis of three new human herpesviruses, human herpesvirus (HHV)-6, HHV-7, and Kaposi's sarcoma-associated herpesvirus (KSHV), also known as HHV-8, has contributed greatly to our understanding of the pathogenesis of several common dermatoses. HHV-6 and HHV-7 are closely related beta-herpesviruses that have been linked with roseola (mostly HHV-6), severe drug eruptions (HHV-6), and pityriasis rosea (mostly HHV-7). KSHV is a gamma-herpesvirus that is now believed to be the long sought after etiologic agent of Kaposi's sarcoma. The evidence for these skin disease associations and key findings from recent basic science investigations on viral pathogenesis are discussed in this review. In addition, possible therapeutic implications of these research studies are explored.

Herpesvirus 6, Human↗

Differentiation of Malassezia species: selectivity of cremophor EL, castor oil and ricinoleic acid for M. furfur.

In recent years, the genus Malassezia has been reclassified based on molecular data. In addition to M. furfur, M. pachydermatis and M. sympodialis, four new species, M. globosa, M. obtusa, M. restricta and M. slooffiiae, have been described. However, apart from their lipid dependence, little is known about the metabolism and nutritional requirements of all the seven species. Further to recent studies, 10 hydrophilic emulsifiers (HLB > 10) were examined in an agar diffusion test to determine their growth-promoting effect on reference strains of the different Malassezia species. Polyethylene glycol (PEG) 7 glyceryl monoalcanoate (Cetiol HE). PEG-glyceryl stearate (Tagat S2) and macrogol-50 stearate (Myrj 53) were metabolized by all strains, while PEG-35 castor oil (Cremophor EL) was metabolized only by M. furfur. The latter observation is due to a different metabolism of castor oil and its main component, ricinoleic acid (12-hydroxy oleic acid), which may also give an insight into the pathogenesis of diseases that are associated with Malassezia spp. As hydroxy fatty acids are important in maintaining the epidermal structure and function, their metabolism specifically by M. furfur might clarify some clinical aspects of pityriasis versicolor. Apart from this speculation, use of Cremophor EL, with splitting of esculin as an additional key character, improves the distinction of the species M. furfur, M. slooffiae and M. sympodialis.

Castor Oil↗

Epidermodysplasia verruciformis-like eruption complicating human immunodeficiency virus infection.

Three human immunodeficiency virus (HIV)-infected patients presented with disseminated pityriasis versicolor-like skin lesions. Histological examination showed features characteristic of epidermodysplasia verruciformis (EV). Hybridization studies demonstrated the presence of human papillomavirus (HPV) type 5 (HPV5) DNA in two patients and HPV20 in one. A relative increase in CD8+, CD57+ cells, which are known to inhibit cell-mediated cytolysis, was observed in all patients. HLA-DQB 0301 haplotype, which has been associated with EV, was detected in two patients. The findings suggest that infection with EV-associated HPV types can complicate HIV infection. Both cellular immune defects and a hitherto unknown genetic background might explain the occurrence of EV in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Lifelong severe verrucosis associated with human papillomavirus type 2: report of a case with a 38-year follow-up.

We describe a 67-year-old woman with disseminated warts which she had had for more than 38 years. The lesions consisted of common and plane warts, wart-like plaques and red-brownish macules similar to those in pityriasis versicolor. Furthermore, during follow-up, several solar keratoses, plaques of Bowen's disease and invasive squamous cell carcinomas were excised. The patient also had T-cell immunodeficiency of unknown aetiology. Histopathology demonstrated that all the warts showed the cytopathological features of common warts, but not those of the warts in epidermodysplasia verruciformis (EV). We investigated the presence of human papillomavirus (HPV) DNA in the warts by blot hybridization and molecular cloning and found that the lesions harboured HPV 2, but not EV-HPVs or other HPVs. In addition, the histopathological distribution of the viral DNA was confirmed in paraffin sections of warts from the patient at different ages by in situ hybridization. However, these investigations yielded negative results in specimens of Bowen's disease and invasive squamous cell carcinoma. These results demonstrated that the patient had been infected with HPV 2 from childhood, but the negative results for detection of DNA of HPV 2 in carcinomas from the patient do not support an oncogenic potential for HPV 2. In conclusion, HPV 2, an aetiological agent of common warts in the general population, may induce a lifelong severe verrucosis in some immunosuppressed patients.

Adult↗

A study of the spectrum of skin disease occurring in a black population in south-east London.

We recorded the diagnosis made in 461 black patients (187 children and 274 adults) attending a dermatology clinic between January and March 1996. In the childhood population, atopic eczema and tinea capitis were the most frequent dermatoses, comprising 63% of diagnoses recorded. In the adult population, acne and acne keloidalis nuchae were seen most frequently. Other conditions observed commonly were eczema, psoriasis, keloid scarring, pityriasis versicolor and postinflammatory changes. Our study demonstrates a wide spectrum of skin disease and includes disorders more common in black skin, disorders unique to black skin, those which present a greater cosmetic disability, and normal findings which have been mistaken for pathological disease.

Acne Vulgaris↗

Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/METHODS: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 DNA, while the tonsillar carcinoma harboured 'genital' HPV16 DNA. In addition, in situ hybridization localized the respective viral DNA in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.

Adult↗

The prevalence and descriptive epidemiology of atopic dermatitis in Singapore school children.

BACKGROUND: Atopic dermatitis is a common disease that appears to be increasing in frequency during recent decades. Most of the studies are based on the Western population, and there are few data in the Asian population. OBJECTIVES: To determine the prevalence and descriptive epidemiology of atopic dermatitis among school children in the general community in Singapore. METHODS: This is a questionnaire study of 12 323 students done over a 1-year period, comprising 7 year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and 17 secondary schools randomly selected in Singapore. All children had a complete cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K. Working Party diagnostic criteria. The questionnaire was translated into Chinese and both the English and Chinese versions were issued simultaneously to the students. RESULTS: The 1-year period prevalence of atopic dermatitis was 20.8%. Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and 21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18 : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the 16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset of the disease occurred before the age of 10 years in 49.5% of the 16 year olds. "Pure" atopic dermatitis without concomitant respiratory allergies was noted in 788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3% having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory allergies whereas more girls were affected with "pure" atopic dermatitis alone (1.4 : 1). At least one first-degree family member with atopy was noted in 1435 children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis (68%). Among siblings with one parent with atopic dermatitis, 37% had either a father or a mother with atopic dermatitis. Common aggravating factors reported included exercise, heat and sweating, grass intolerance, thick clothing and stress. Pityriasis alba was noted in 25% of the study population, keratosis pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to moderate atopic dermatitis that could be controlled with a fairly simple regimen of moisturizers, topical steroids, antihistamines and antibiotics. CONCLUSIONS: The high prevalence of atopic dermatitis in Singapore is similar to that observed in developed countries, suggesting that environmental factors may be important in determining the expression of the disease.

Adolescent↗

Guttate morphoea in human T-cell lymphoma/lymphotrophic virus type-1 (HTLV-1) infection.

A 62-year-old Japanese man presented with multiple small atrophic macules on the trunk and extremities. The lesions were discrete, oval in shape and enclosed by lilac ring. They were distributed in a Christmas tree distribution, reminiscent of pityriasis rosea. Skin biopsy showed increased collagen fibres in the dermis and invading subcutaneous tissue. The clinico-pathological features were consistent with guttate morphoea, a rare variant of localized scleroderma. Serological tests revealed a positive reaction to human T-cell lymphoma/lymphotropic virus type-1 infection.

Biopsy↗

Antibodies from patients with psoriasis recognize N-acetylglucosamine terminals in glycoproteins from Pityrosporum ovale.

We have previously reported the finding of circulating antibodies recognizing two proteins of 100 and 120 kD (PO100 and PO120) from Pityrosporum ovale in patients with psoriasis. These antibodies were specific, since they were not detected in normal sera nor in other diseases linked to P. ovale such as seborrhoeic dermatitis or pityriasis versicolor. The present study aimed at further characterizing the specificity of these antibodies. Enzyme-labelled lectins were used to determine the carbohydrate composition of PO120 and PO100. BSII, a lectin that recognizes terminal N-acetylglucosamine (GlcNAc), showed the same banding pattern as sera from patients. Reactivity against these proteins was inhibited after mild oxidation of the carbohydrate moieties of the extract. Treatment of the extracts with lyticase altered the immune reactivity against the PO120 band as seen in Western blot assays. PO100 was not detected after lyticase digestion. Digestion with lysozyme did not alter the immune reactivity of the PO100 and PO120 bands, although the protein pattern in SDS-PAGE was modified. To examine the relevance of anti-GlcNAc antibodies in the immune response to P. ovale in psoriasis, we performed a binding inhibition ELISA. Psoriatic sera that were positive in the ELISA against a heat-denatured extract of P. ovale were rendered negative only by pre-incubation with GlcNAc in a concentration-dependent manner. Our results are indicative that the antibody response to PO100 and PO120 in patients with psoriasis is directed towards terminal GlcNAc residues.

Acetylglucosamine↗

Drugs causing fixed eruptions: a study of 450 cases.

BACKGROUND: Drug eruptions are among the most common cutaneous disorders encountered by the dermatologist. Some drug eruptions, although trivial, may cause cosmetic embarrassment and fixed drug eruption (FDE) is one of them. The diagnostic hallmark is its recurrence at previously affected sites. OBJECTIVE: We evaluated 450 FDE patients to determine the causative drugs. RESULTS: The ratio of men to women was 1:1.1. The main presentation of FDE was circular hyperpigmented lesion. Less commonly FDE presented as: nonpigmenting erythema, urticaria, dermatitis, periorbital or generalized hypermelanosis. Occasionally FDE mimicked lichen planus, erythema multiforme, Stevens-Johnson syndrome, paronychia, cheilitis, psoriasis, housewife's dermatitis, melasma, lichen planus actinicus, discoid lupus erythematosus, erythema annulare centrifugum, pemphigus vulgaris, chilblains, pityriasis rosea and vulval or perianal hypermelanosis. Cotrimoxazole was the most common cause of FDE. Other drugs incriminated were tetracycline, metamizole, phenylbutazone, paracetamol, acetylsalicylic acid, mefenamic acid, metronidazole, tinidazole, chlormezanone, amoxycillin, ampicillin, erythromycin, belladonna, griseofulvin, phenobarbitone, diclofenac sodium, indomethacin, ibuprofen, diflunisal, pyrantel pamoate, clindamycin, allopurinol, orphenadrine, and albendazole. CONCLUSIONS: Cotrimoxazole was the most common cause of FDE, whereas FDE with diclofenac sodium, pyrantel pamoate, clindamycin, and albendazole were reported for the first time. FDE may have multiform presentations.

Adolescent↗

Skin diseases in Bamako (Mali).

BACKGROUND: Skin diseases have only recently been considered as a possible public health problem in developing countries. Data supporting this matter are scarce. The aim of this study is to report the experience of a specialized dermatologic center in Bamako (Mali) in order to complete two previous studies conducted in the Bamako area: a prevalence study in the general population and a study in nonspecialized health centers of Bamako. It is our intention to provide a comprehensive picture of the problem of skin diseases in an African developing country. METHODS: We retrospectively collected all cases of skin diseases diagnosed during consultations provided at the Institut Marchoux in Bamako, the only center specializing in dermatology in Mali, during the year 1993. RESULTS: A total of 10,575 new outpatients were seen with 10,889 skin diseases. The main skin diseases registered were as follows: infectious dermatoses (41% of all diagnoses, including scabies (16.6%), superficial mycoses (13.6%), and primary pyoderma (5.6%)), dermatitis (20.4%), papular urticaria (4.4%), acne (4.2%), pityriasis alba (3.6%), keratoderma (3.6%), and urticaria (3%). Typical tropical infectious diseases accounted for only 1% of all diagnoses. CONCLUSIONS: It appears that certain skin diseases (mainly scabies and pyoderma) are an important health problem for the population of the Bamako area. Public health policies should be implemented in order to manage this problem rationally.

Acquired Immunodeficiency Syndrome↗

The profile of atopic dermatitis in a tertiary dermatology outpatient clinic in Singapore.

BACKGROUND: Atopic dermatitis is a common, chronic, relapsing, pruritic, eczematous skin condition occurring in patients with a personal or family history of atopy. The aim of this study is to describe the profile of atopic dermatitis seen at a tertiary referral skin center in a tropical multiracial country. METHODS: A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994. RESULTS: There were 492 patients, age range from 1 month to 74 years, with an equal sex ratio. The prevalence was 2%. The onset of the disease occurred before the age of 10 years in 61.2% of patients. In 13.6% of patients, the onset was after the age of 21 years. Two hundred and fifty four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies; 238 patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma, and 13% having both asthma and allergic rhinitis; 231 patients (47%) had at least one first-degree family member with atopy: atopic dermatitis (17%), asthma (15%), and allergic rhinitis (15%). Most of the patients, 416 (84.5%), had subacute dermatitis at presentation. Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%). The most common infective complication was bacterial infection (impetiginized dermatitis, folliculitis, cellulitis) present in 95 patients (19%), followed by viral infections (dermatitis herpeticum, viral warts, and molluscum contagiosum) in 17 patients (3%). Allergies were noted in 43 patients (9%). The most common was drug allergy (penicillin and cotrimoxazole) in 28 patients, followed by food allergy in 11 patients. Common aggravating factors reported included heat, sweating, stress, thick clothing, and grass intolerance. Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids, and antibiotics for acute flares. Short courses of systemic steroids were used in 78 patients (16%). Three patients were treated with phototherapy: two on combined UVA and UVB (UVAB) and one on oral psoralen photochemotherapy (PUVA). CONCLUSIONS: The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature, except for a lower prevalence and a significant proportion of adult-onset atopic dermatitis.

Adolescent↗

Demodex folliculorum in pregnancy.

BACKGROUND: Demodex folliculorum (DF), which is a resident in human pilosebaceous follicles, has been implicated in rosacea, blepharitis, pityriasis folliculorum, pustular folliculitis, and skin lesions of immunosuppressed patients on chemotherapy or with acquired immunodeficiency syndrome (AIDS). OBJECTIVE: We aimed to determine the influence of pregnancy on the carriage of DF. METHODS: Mite density in 40 pregnant women was compared with that of age- and sex-matched controls. Two standardized skin surface biopsies were taken from each subject. Results In pregnant women, DF was found at 0.55/cm2, compared with a mean value of 1.2/ cm2 in nonpregnant controls. The difference between the two groups was not statistically significant (Mann-Whitney test, P = 0.22). CONCLUSIONS: Our findings indicate that pregnancy may not have a direct effect on mite density.

Adolescent↗

Prevalence of skin diseases in rural areas of Assiut Governorate, Upper Egypt.

BACKGROUND: Few epidemiological surveys have been carried out to determine the prevalence of skin diseases in the population of Egypt, particularly "Upper Egypt". So it is a pressing necessity to conduct such a study in rural Assiut. OBJECTIVES: To determine the prevalence of various skin diseases in rural Assiut. SUBJECTS AND METHODS: A cross-sectional community-based survey was followed. The survey included 8008 rural inhabitants of all ages and both sexes from a representative of three villages of Assiut Governorate, Upper Egypt. The data were collected through personal interview and examination at homes from December 1994 to December 1996. RESULTS: They showed that 6961 (86.93%) of the studied population had one or more skin diseases. The group with parasitic skin infestations had the highest prevalence rate (27.40%) of the total sample, of which pediculosis capitis (19.37%) was the commonest. Eczema/dermatitis group had a rate of 19.82%, with pityriasis alba forming the majority (13.49%). Pigmentary disorders were 17.68%, followed by fungal skin infections (16.17%), then naevoid disorders (16.10%), hair and scalp disorders (12.07%), bacterial skin infections (10.10%), sweat gland disorders (6.16%), acne vulgaris (5.37%). Leprosy constituted 1.6/10,000. Other various skin disorders were recorded. CONCLUSIONS: Infective-parasitic diseases were a major problem particularly among the younger age-group and those of low socio-economic status.

Adolescent↗

Ciclopirox for the treatment of superficial fungal infections: a review.

Ciclopirox is a broad-spectrum antifungal agent that also exhibits anti-inflammatory and antibacterial activity. The lotion and cream formulations of ciclopirox are effective in many types of infection, including tinea corporis/cruris, tinea pedis, cutaneous candidiasis, pityriasis (tinea) versicolor, and seborrheic dermatitis. The new ciclopirox gel 0.77% formulation is also indicated for the treatment of seborrheic dermatitis of the scalp, interdigital tinea pedis and tinea corporis.

Administration, Topical↗