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PubMed2003

Localized epidermolytic hyperkeratosis of the female external genitalia.

BACKGROUND: Epidermolytic hyperkeratosis (EH) is most commonly associated with the diffuse involvement of congenital ichthyosiform erythroderma, but can also be found in a localized pattern. Localized EH is rare, but mucocutaneous lesions have been been identified, most commonly in the mouth. METHODS: We observed a 58-year-old African-American female who noted spots on her genitalia for approximately 2 years. The lesions were increasing in size, darkening, and had become pruritic and sore over the past 6 months. RESULTS: Physical examination revealed seven scattered, tan to brown, verrucoid papules on the labia and mons pubis, resembling condylomata acuminata or Bowenoid papulosis. Biopsy of a single labial papule revealed epidermal acanthosis, compact hyperkeratotic papillomatosis, perinuclear clear zones, granular keratohyalin clumping, hypergranulosis, and dyskeratosis resulting in intracellular eosinophilic globules, all characteristic of EH. CONCLUSIONS: Because of the rarity of localized genital EH and similar appearance to common diagnoses, clinical confusion may occur without biopsy.

Biopsy↗
PubMed2000

A novel in vivo model in guinea pigs for dry skin syndrome.

BACKGROUND/AIMS: The lack of a suitable, validated animal model for the comparison of the pharmacological effectiveness of known and potential moisturizers in the treatment of "dry skin syndrome" led us to develop such an in vivo model. METHODS: "Dry skin syndrome" was induced in guinea pigs by daily application of 2% sodium lauryl sulphate (SLS) in deionized water on one of the two shaved flanks for three consecutive days. After ascertaining skin dryness, that side was treated with an agent for 6 days. The in vivo humectant effect was measured by a Corneometer CM 825(R), erythema was measured by a Mexameter MX 16(R). In some cases histological studies were carried out. RESULTS: The treatment with the 2% SLS led to a consistent "dry skin syndrome" for 2 weeks. Glycerol, Vaseline, urea and ammonium lactate treatments validated the model, since the Corneometer CM 825(R) readings of the treated dry side was equal to that of the control untreated side after 1 week of treatment. Mexameter MX 16(R) measurements showed abolishment of the erythema by glycerol only. Histological study showed that SLS treatment creates acanthosis that is partially reversed by Vaseline and fully reversed by glycerol treatment. CONCLUSION: The guinea pig dry skin model is a relevant model of the human "dry skin syndrome". The instrumental results combined with the histological findings indicate that erythema measurements are relevant for the determination of curative effect.

Journal Article↗
PubMed2002

Instrumental evaluation of retinoid-induced skin irritation.

BACKGROUND/PURPOSE: Retinoids like tazarotene are approved for the treatment of chronic plaque psoriasis. In the beginning of topical retinoid therapy, 15-20% of the patients suffer from mild to moderate adverse reactions with burning and erythema. The aim of the study was to find predicative parameters of the individual irritative potential and to suggest options to reduce these initial irritations. METHODS: Twenty in-patients with different skin types (1 + 2: 11, 3 + 4: 9), with chronic plaque psoriasis were included in this open study. In each patient, 7 randomized plaques on the forearm were treated for 14 days on different ways: test area 1: morning (m) and evening (e) placebo, test area 2: placebo (m) and tazarotene 0.05% (e), test area 3: placebo (m) and tazarotene 0.1% (e), test area 4: calcipotriol (m) and calcípotriol (e), test area 5: mometasone furoate (m) and tazarotene 0.05% (e), test area 6: mometasone furoate (m) and tazarotene 0,1% (e), test area 7: placebo (m) and tazarotene in increasing concentrations (e), test area 8: healthy skin for control. Before and after therapy, skin barrier function, blood flow and plaque thickness in 20-MHz sonography were assessed in different test areas intraindividually by non- invasive biophysical measurements. RESULTS: After 14 days of therapy, tazarotene 0.05% and 0.1% produced a stronger increase of laser Doppler flow in patients with skin type 1 and 2 than in patients with skin type 3 and 4. When using the combination therapy of tazarotene and mometasone, the laser Doppler flow was significantly lower than in tazarotene as monotherapy. 20-MHz-ultrasound showed a significant decrease in the thickness of the echo-poor band in all topical therapy regimens compared to placebo. Patients of skin type 1 and 2 reached a higher density of the dermis than patients of skin type 3 and 4, meaning a stronger decrease of inflammatory infiltration and acanthosis. CONCLUSION: Adapting retinoid therapy to the patient's skin type can reduce the initial irritative side-effects. During the first days, patients with skin type 1 or 2 should add a medium potency corticosteroid. Stronger skin irritation caused by tazarotene therapy increases therapy effects.

Administration, Cutaneous↗
PubMed2002

Mechanisms of expression of HHV8, EBV and HPV in selected HIV-associated oral lesions.

Opportunistic DNA viruses, particularly members of the herpesvirus family, are frequently the aetiological agents of HIV-associated oral lesions. Oral lesions common to the early phase of the AIDS epidemic, including Kaposi's sarcoma (KS), oral aphthous ulceration, AIDS-associated oral lymphoma, and oral hairy leukoplakia (OHL), have been tested for the prevalence of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). While EBV DNA is detected by PCR in all of these lesions, abundant viral replication can only be detected in OHL. In OHL, a novel state of EBV infection has been discovered with concurrent expression of replicative and transforming proteins, with all of these proteins contributing to the development of the lesion. Activation of signalling pathways and up-regulation of the viral receptor, proliferative and antiapoptotic genes by these proteins induce several of the histological features common to OHL, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected OHL tissue enables epithelial cell survival and may enhance viral replication. Detection of KSHV in these HIV-infected individuals has been localized only to their saliva. Replicative and latent KSHV gene products have been detected in association with the development of oral KS lesions. EBV, but not human cytomegalovirus (HCMV), has been detected by PCR in minor salivary gland biopsies of HIV-associated salivary gland disease. Human papillomaviruses (HPV) are associated with oral warts in HIV-positive individuals; a diagnosis that appears to be increasing in frequency in the era of highly active antiretroviral therapy. To date, there appears to be little increase in the incidence of HPV-associated oral cancer. The mechanisms of interaction between HIV and HPV are not fully understood. Expression of viral gene products is clearly important and necessary for the development of multiple AIDS-associated oral lesions.

AIDS-Related Opportunistic Infections↗
PubMed1971

The mitotic values for the epithelium in oral keratoses and lichen planus.

In biopsies from the oral mucosa of 235 cases in which the diagnosis was lichen planus, keratosis or leukoplakia, mitotic values were calculated for the stratum basale (M.V. basal) and the stratum spinosum (M.V. spinous). The mean M.V. basal was significantly different from the mean M.V. spinous in the keratosis and leukoplakia groups, but not in the lichen planus group. Within the keratosis and leukoplakia groups, M.V. basal and M.V. spinous were significantly correlated. When each of the mean M.V.s was compared with the M.V.s for the other diagnostic groups, various significant differences were found. The M.V.s were examined in relation to the type of keratinization, the presence of acanthosis or atrophy, and the patient's age, but the M.V.s were not significantly related to these features.

Acantholysis↗
PubMed1998

Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21-22.

Obesity is strongly implicated in the pathophysiology of insulin resistance, diabetes mellitus and dyslipidemia. The mechanisms, however, by which obesity causes these complications are not known. The study of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus, dyslipidemia and acanthosis nigricans. The genetic basis of FPLD is unknown. We carried out a genome-wide scan with a set of highly polymorphic short tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21-22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at theta(max)=0 was 5.84. Multipoint-linkage analysis yielded a peak lod score of 8.25 between D1S305 and D1S1600. There was no evidence for genetic heterogeneity (alpha=1) in the pedigrees.

Chromosomes, Human, Pair 1↗
PubMed1995

A mutation in the mucosal keratin K4 is associated with oral white sponge nevus.

White sponge nevus (WSN) is a benign autosomal dominant disorder which affects non-cornifying stratified squamous epithelia (MIM 193900) (ref. 1). Phenotypically it presents as white 'spongy' plaques (oral leukokeratoses), most commonly in the mouth but also reported in the esophagus and anogenital mucosa. Histologically, the plaques show evidence of hyperproliferation, acanthosis and tonofilament aggregation. These types of pathogenic changes are characteristic of many of the epidermal keratin disorders. Keratins are expressed in pairs by epithelial cells in a tissue and cell specific manner. The major differentiation specific keratins of the buccal mucosa, nasal, esophageal and anogenital epithelia are K4 and K13 (ref. 7). The tissue distribution and nature of the lesions in patients affected by WSN suggested that mutations in K4 and/or K13 might be responsible for this disorder. We have now confirmed this hypothesis and report here a three base-pair (bp) deletion in the helix initiation peptide of K4 in affected members from two families with this condition.

Amino Acid Sequence↗
PubMed2006

High frequency of FGFR3 mutations in adenoid seborrheic keratoses.

FGFR3 germline mutations cause autosomal dominant skeletal disorders including achondroplasia, thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, and Crouzon syndrome. Somatic mutations of FGFR3 have been identified in bladder cancer, multiple myeloma, and other neoplasms. FGFR3 mutations have also been detected in 40% of seborrheic keratoses (SKs) of the hyperkeratotic and acanthotic subtype, which are very common benign skin tumors. Using a multiplex SNaPshot assay that covers 11 activating FGFR3 mutations, we investigated a series of 27 SKs of the adenoid subtype. Mutations were detected in 23 of 27 (85%) adenoid SKs. R248C mutations were the most frequent mutation type. In two SKs, the A393E mutation was found, which has not been described in acanthotic and hyperkeratotic SKs so far. Three adenoid SKs displayed two simultaneous FGFR3 mutations. Adenoid SKs seem to be characterized by a higher frequency of FGFR3 mutations than hyperkeratotic and acanthotic SKs. The mechanism for the high rate of somatic FGFR3 mutations in these benign skin tumors remains elusive, but UV light exposure may play a potential role, especially in the R248C mutations.

Aged↗
PubMed2003

Expression of enhancing factor/phospholipase A2 in skin results in abnormal epidermis and increased sensitivity to chemical carcinogenesis.

Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A(2). EF exhibits growth-promoting activity in vitro, in the presence of epidermal growth factor, and also brings about phenotypic transformation of normal cells. In order to ascertain the role of EF in vivo, a human keratin-14 promoter was used to drive the expression of EF ectopically to squamous epithelial cells. The founder mouse and its progeny showed abnormal whiskers and a scaly, beaded tail. In these mice, keratinization pattern of the epidermis was disturbed and parakeratosis and acanthosis were noted. The transgenic mice, TgK14-EF, expressed EF in the suprabasal layers of tail epidermis as well as in the epithelial cells of hair follicle and sebaceous glands of skin. Expression of EF along with hyperplasia was also observed in other squamous epithelia such as buccal mucosa, tongue and oesophagus. TgK14-EF mice homozygous for the transgene showed delayed and scanty hair growth although the mice were healthy and fertile. The hemizygous TgK14-EF mice were sensitive to a two-stage chemical carcinogenesis and developed a higher number of papillomas than their normal littermates over the course of the experiment. The conversion rate of papilloma to carcinoma was two fold higher in the transgenic mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings.

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.

Adult↗
PubMed2003

Human papillomavirus-negative ileostomal chronic papillomatous dermatitis.

BACKGROUND: Papillomatous stoma-related skin lesions may result from irritant reactions or infection with epidermodysplasia verruciformis human papillomavirus (HPV) types. METHODS: We report upon a papillomatous lesion at the ileostoma of a 63-year-old male with familial adenomatous polyposis and colorectal adenocarcinoma. We thoroughly tested the lesion for HPV using immunohistochemistry, transmission electron microscopy, and polymerase chain reaction analyses. RESULTS: The lesion was a fleshy, multilobulated, and verrucous plaque, with hyperkeratosis, hypergranulosis, acanthosis and marked papillomatosis. The clinical and light microscopic features were suggestive of a condyloma. However, no HPV was detected. CONCLUSIONS: We suggest that the lesion most likely represents chronic papillomatous dermatitis, a reaction to mechanical and/or chemical irritation usually associated with urostomies and only rarely observed with ileostomies. This case highlights the clinical, diagnostic and therapeutic aspects of an unusual cutaneous morbidity associated with ileostomies.

Chronic Disease↗
PubMed2000

Ichthyosis follicularis with alopecia and photophobia in a mother and daughter.

A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non-inflammatory follicular hyperkeratosis, generalized non-scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. Skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.

Adult↗
PubMed2000

Longitudinal erythronychia with distal subungual keratosis: onychopapilloma of the nail bed and Bowen's disease.

We biopsied longitudinal erythronychia in 16 subjects, and found an onychopapilloma in 14 cases and Bowen's disease in the remaining two. Shared clinical features in addition to erythronychia (or sometimes an interrupted line made up of splinter haemorrhages) were typically a longitudinal marked ridge of the nail bed expanded at the distal nail bed as subungual keratosis, and associated localized onycholysis. The presentation of Bowen's disease in this pattern has not been previously reported. In all cases of onychopapilloma of the nail bed, acanthosis and papillomatosis were evident, and were associated with a keratogenous zone identical to the nail matrix. In addition, we found multinucleate giant cells in two onychopapillomas. We have therefore suggested that the term 'localized, distal, subungual keratosis with multinucleate cells' should be replaced by 'onychopapilloma' (nail-producing papilloma).

Adolescent↗
PubMed2002

Protean manifestations of human papillomavirus type 60 infection on the extremities.

BACKGROUND: Human papillomavirus type 60 (HPV-60) induces a ridged wart or an epidermal cyst on the sole of the foot, exhibiting identical pathological changes, with a single refractile eosinophilic intracytoplasmic inclusion body in infected cells. However, there is no information on the role of HPV-60 in the development of cutaneous lesions on other anatomical sites. OBJECTIVES: To perform the clinicopathological analysis of various cutaneous lesions of a patient in relation to HPV genotype. PATIENT: A 50-year-old male patient developed multiple papules, plaques and nodules on his hand, arm and legs. RESULTS: Clinicopathologically, the lesions were classified into three categories. A common wart on the finger showed papillomatosis and acanthosis characterized by numerous keratohyalin granules. Plane warts on the arm showed perinuclear vacuolization of the cells in the upper Malpighian layer. On the other hand, a pigmented papillomatous nodule on the finger, and the other lesions on the hands and legs exhibited similar histological features with a unique cytoplasmic eosinophilic inclusion body. All the three categorized lesions were equally positive for HPV capsid antigen by immunohistochemistry. By blot hybridization analysis for HPV sequences, it was revealed that a common wart on the finger and plane warts on the arm harboured HPV-27 and HPV-3, respectively, while all the other lesions harboured HPV-60. The histological localization of each viral DNA was confirmed in the corresponding lesions by in situ hybridization. CONCLUSIONS: HPV-60 is able to induce papular and nodular lesions on the extremities.

Arm↗
PubMed2003

Histopathological and immunohistochemical assessment of acquired ichthyosis in patients with human T-cell lymphotropic virus type I-associated myelopathy.

BACKGROUND: Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy frequently display cutaneous alterations such as acquired ichthyosis. OBJECTIVES: Elucidation of the pattern of acquired ichthyosis in HTLV-I-associated myelopathy. METHODS: Skin fragments from 10 patients with HTLV-I-associated myelopathy presenting with acquired ichthyosis were assessed by histopathological and immunohistochemical tests. We used anticytokeratin antibodies related to normal keratinization (K1/K10), and others related to cutaneous conditions such as activation, migration and hyperproliferation of keratinocytes (K6/K16), and involucrin, a precursor protein in the formation of the protein envelope in keratinocytes. For quantification of the proliferating basal and parabasal cells the anti-Ki-67 antibody was employed. RESULTS: On light microscopy, all skin specimens displayed orthokeratotic hyperkeratosis and hypogranulosis. Three of them presented focal parakeratosis. A slight to moderate perivascular infiltrate of mononuclear lymphocytes was observed in seven cases, three of which showed discrete spongiosis with epidermotropism of lymphocytes. All fragments displayed coexpression of K1, K10 and K16 in the suprabasal layers. Expression of involucrin was also observed in all cases, in the upper spinous and granular layers. Focal expression of K6 was observed in three cases, under a parakeratotic area. The mean number of Ki-67+ basal and parabasal cells was 3.5 cells per mm, similar to that in control skin. CONCLUSIONS: In acquired ichthyosis related to HTLV-I-associated myelopathy, histopathology revealed orthokeratotic hyperkeratosis and a perivascular inflammatory infiltrate of mononuclear lymphocytes, with areas of parakeratosis and foci of epidermotropism in rare cases. The expression profiles of K1, K10 and involucrin were similar to those in normal skin. The diffuse coexpression of K16 with K1 and K10 throughout the analysed epidermis, as well as the occurrence of restricted areas of parakeratosis expressing K6, indicate the presence of keratinocyte activation with induction of the alternative keratinization pathway, probably dependent on the cytokines liberated by the mononuclear cells of the dermal inflammatory infiltrate infected with HTLV-I. The absence of acanthosis and of increased cellular kinetics, as shown by the low rate of Ki-67 antigen expression, allow the inference that the pattern of acquired ichthyosis related to HTLV-I-associated myelopathy may be retentional. The observation of foci of parakeratosis expressing K6 in three specimens suggests that, at least in certain areas and in some cases, interference with epidermal differentiation and maturation occurs.

Cell Division↗
PubMed1999

Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects.

The outbreak of HIV infection introduced a new phenomenon in varicella zoster virus (VZV) pathology, namely the long-standing wart-like skin lesions that are frequently associated with resistance to thymidine kinase (TK)-dependent antiviral agents. This paper reviews the clinical, histological, and molecular aspects and the therapeutic management of these verrucous lesions. The majority of lesions are characterized by chronically evolving, unique or multiple wart-like cutaneous lesions. The main histopathological features include hyperkeratosis, verruciform acanthosis and VZV-induced cytopathic changes with scant or absent cytolysis of infected keratinocytes. The mechanism that establishes the chronic nature of the lesions appears to be associated with a particular pattern of VZV gene expression exhibiting reduced or nondetectable gE and gB synthesis. Drug resistance to TK-dependent antiviral agents is a result of nonfunctional or deficient viral TK. This necessitates alternative therapeutic management using antiviral agents that target the viral DNA polymerase.

Acyclovir↗
PubMed2000

Cutis verticis gyrata of the scalp in a patient with autosomal dominant insulin resistance syndrome.

Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp which becomes raised to form ridges and furrows resembling the cerebral gyri. We report a case of CVG associated with the autosomal dominant insulin resistance syndrome. This syndrome is characterized by obesity, mild mental retardation, delayed puberty, acanthosis nigricans and hyperinsulinaemia. The association of CVG and autosomal dominant insulin resistance has not been previously described.

Adult↗
PubMed2002

Amicrobial pustular dermatosis in two patients with immunological abnormalities.

We report two patients with severe amicrobial pustular dermatosis with immunological abnormalities: a 63-year-old woman with a 30-year-history of discoid lupus erythematosus and sicca syndrome, and a 35-year-old woman with high levels of gamma-globulinemia and positive antinuclear antibodies. Both patients presented with crusty and eroded erythematous plaques studded with aseptic pustules on the back, face, and scalp. Histological examination showed acanthosis, neutrophilic exocytosis to the epidermis, and neutrophilic and lymphocytic infiltration with nuclear dust in the dermis. These patients were diagnosed as having "amicrobial pustulosis associated with autoimmune diseases". The eruptions improved with combination treatment of oral prednisolone with cyclosporin A or diaminodiphenylsulphone. Although the pathogenesis remains unclear, amicrobial pustular dermatosis might be one of the cutaneous complications in autoimmune diseases.

Administration, Oral↗