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PubMed1985

Acquired (digital) fibrokeratoma.

Histologic examination of fifty cases of acquired digital fibrokeratoma discloses three histologic variants of these lesions, viz: a tumor composed of thick dense and closely packed collagen bundles, a variant with an increased number of fibroblasts in the cutis, and a type with an edematous and poorly cellular structure. The acquired digital fibrokeratoma is considered as resulting from a neoformation of collagen by the fibroblasts. The acanthosis of the epidermis is probably secondary to the dermal alteration.

Adolescent↗
PubMed1986

Epidermal effects of retinoids: supramolecular observations and clinical implications.

Retinoids, synthetic vitamin A analogs, stimulate mucous metaplasia and gap-junction proliferation in embryonic and neoplastic epidermis. Such effects demonstrate that vitamin A has potent effects on epidermal differentiation. Oddly, however, retinoid action in normal postnatal tissues, where these drugs are used clinically, appears to be quite different. In animals and humans, both topical and systemic retinoids produce acanthosis, hypergranulosis, and a relative (but not absolute) decrease in the thickness of the stratum corneum. These changes reflect the distinct boost in cell turnover that results from retinoid treatment. On the ultrastructural level, desmosomes are actively shed by cells of the spinous layer, resulting in many fewer attachment points along the cell membranes of the outer epidermis. Loss of desmosomes, coupled with decreased tonofilaments, enhanced keratinocyte autolysis, and intercellular deposition of glycoconjugates (not mucin), cause loosening and fragility of the stratum corneum (so-called anti-keratinizing effects). The biochemical basis of retinoid activity, in addition to stimulating increased cell turnover, appears to be a global enhancement of glycoconjugate synthesis and the generation of less mature keratins. The epidermal effects of retinoids can be exploited therapeutically: to cause loosening of thickened stratum corneum, for example in psoriasis or ichthyosis; to enhance penetration of pharmacologic agents such as 5-fluorouracil across hypertrophic actinic keratoses; and to normalize differentiation in neoplastic epidermis involving mucous metaplasia and gap-junction proliferation.

Animals↗
PubMed1988

Sulfur revisited.

Sulfur is a time-honored therapeutic agent useful in a variety of dermatologic disorders. Its keratolytic action is due to formation of hydrogen sulfide through a reaction that depends upon direct interaction between sulfur particles and keratinocytes. The smaller the particle size, the greater the degree of such interaction and the greater the therapeutic efficacy. When applied topically, sulfur induces various histologic changes, including hyperkeratosis, acanthosis, and dilatation of dermal vasculature. One study showed that sulfur was comedogenic when applied onto human and rabbit skin, findings that were not reproduced in other studies. About 1% of topically applied sulfur is systemically absorbed. Adverse effects from topically applied sulfur are uncommon and are mainly limited to the skin. In infants, however, fatal outcome after extensive application has been reported.

Acne Vulgaris↗
PubMed1988

Acantholytic acanthoma.

This article describes 31 examples of acantholytic acanthoma, a newly recognized, solitary, benign cutaneous tumor. Acantholytic acanthoma was typically an asymptomatic, keratotic papule or nodule. Patients ranged in age from 32 to 87 years (median 60 years); the ratio of men to women was 2:1; the most frequent clinical diagnosis was keratosis; and half of the growths were on the trunk of the body. Histologically, the lesions showed hyperkeratosis, papillomatosis, and acanthosis. Acantholysis was an outstanding finding in all cases; the patterns resembled pemphigus vulgaris, pemphigus vegetans, superficial pemphigus, or Hailey-Hailey disease, but no patient had evidence of any of these disorders. The term acantholytic is used because acantholysis is the outstanding histologic feature in these neoplasms; acanthoma was chosen because the growths are benign tumors of epidermal keratinocytes. The relationship of acantholytic acanthoma to acantholytic blistering disease is similar to that of solitary lichen planus-like keratosis to lichen planus and epidermolytic acanthoma to bullous congenital ichthyosiform erythroderma.

Acantholysis↗
PubMed1989

Lichenoid epidermal nevus: "linear lichen planus".

A 3-year-old girl had an eruption that showed clinical and histologic evidence of both a verrucous epidermal nevus and a lichenoid tissue reaction. Linear plaques had been present on her right lower limb for 2 years. Microscopic features included hyperkeratosis, papillomatosis, acanthosis, a bandlike lymphohistiocytic infiltrate that obscured the dermoepidermal junction, Civatte bodies, and melanophages. Lichenoid epidermal nevus is a new variant of linear verrucous epidermal nevus. At least some of the cases previously diagnosed as linear lichen planus probably represent lichenoid epidermal nevus. There is a parallel between lichenoid epidermal nevus and the entity described as inflammatory linear verrucous epidermal nevus, which frequently was misinterpreted as linear psoriasis before it was recognized as a linear verrucous epidermal nevus with psoriasiform features.

Child, Preschool↗
PubMed1998

Hereditary epidermolytic palmoplantar keratoderma (Vörner type) in a family with Ehlers-Danlos syndrome.

We describe a kindred in whom epidermolytic palmoplantar keratoderma occurred in association with Ehlers-Danlos syndrome type III (benign hypermobility syndrome). This kindred consisted of 27 members of four generations, 14 of whom had palmoplantar keratoderma (PPK). Of those who had palmoplantar keratoderma, 6 had Ehlers-Danlos type III (EDS II). The proband presented with diffuse, symmetrical hyperkeratotic plaques that were yellow and sharply demarcated, covering the entire palms and soles, in addition to marked large and small joint flexibility and skin hyperextensibility. A biopsy specimen from the palm revealed features of epidermolytic hyperkeratosis with acanthosis. To our knowledge, this is the first report of PPK in a family with Ehlers-Danlos syndrome. Linkage analysis of these two clinical traits showed that the genes responsible for PPK and EDS III are not closely linked, and therefore are not immediately adjacent. However, linkage at greater genetic distances could not be excluded.

Adult↗
PubMed1998

Transglutaminase 1 expression in a patient with features of harlequin ichthyosis: case report.

Harlequin ichthyosis (HI) is a life-threatening disorder characterized clinically by massive generalized hyperkeratosis and ultrastructurally by an absence of lamellar bodies. However, infants who survive the perinatal period develop a phenotype resembling the nonbullous ichthyosiform erythrodermic (CIE) form of autosomal recessive ichthyosis. We studied a child with a severe hyperkeratotic skin disorder present at birth that developed into a CIE-like phenotype. Electron microscopy demonstrated an absence of lamellar bodies consistent with HI. Abnormalities of filaggrin and involucrin expression by immunostaining were evident. However, transglutaminase 1 (TGase1) was expressed in the epidermis in a pattern consistent with other diseases that involve epidermal acanthosis. Analysis of patient keratinocytes grown in vitro demonstrated expression of normal amounts of TGase1 mRNA and full length TGase1 protein, as well as normal levels of transglutaminase enzymatic activity.

Biomarkers↗
PubMed2002

Toxicity and pharmacokinetics of 2-(2-dimethylaminoethoxy)ethanol following cutaneous dosing.

A 9-day repeated cutaneous toxicity study in the New Zealand White rabbit was conducted using 6-h occluded contact with 0 (water control), 50, 250 and 500 mg dimethylaminoethoxyethanol (DMEE)/kg. There were no clinical signs, and no effects on body weight, food consumption or serum chemistry. Hematological effects were limted to increased leukocyte count due to heterophil leukocytosis, increased platelet count, and decreased hemoglobin and hematocrit at the high dose. These findings are typical of the response of cutaneous inflammation. Histopathological findings were limited to the DMEE-treated skin, and consisted of acanthosis and ulcerative/necrotizing dermatitis. Thus, there was no evidence for cumulative percutaneous systemic toxicity for DMEE. The pharmacokinetics of DMEE was investigated in the Fischer 344 rats. Rats were given an intravenous dose of 15 or 150 mg/kg, or an occluded cutaneous dose of 150 mg/kg [14C]DMEE, and its fate was followed for 48-72 h. DMEE was readily absorbed through the skin (bioavailability=72-80%). Concentration in plasma rose steadily to a maximum at about 3.5 h after dosing, and then declined in a biphasic manner. 14C-DMEE-derived radioactivity was distributed throughout the body, with no apparent sequestration in any particular organ. The highest concentrations were observed in the kidney, liver and lung, and the lowest concentrations were found in the brain and fat. Urine was the major route of excretion, with minor amounts eliminated in the feces and as expired CO(2). The rate of excretion was moderate, with about 30% of the applied dose eliminated in the first 12 h, and by 72 h after dosing, less than 4% of the dose remained in the carcass. Unchanged DMEE was the principal component detected in the urine. This observation, together with the less than 1% of the dose excreted as CO(2), showed that metabolism was not an important process in the elimination of DMEE in the rat.

Administration, Topical↗
PubMed1994

Effects of sustained low-level muscarinic agonism in rats.

Sustained, low level muscarinic activity was induced in rats by feeding the muscarinic agonist and experimental drug candidate CI-969 at 50, 100 and 200 mg/kg body weight/day for 4 wk. Except for urine staining, clinical signs typical of acute high-dose exposure to muscarinic agonists were not observed. A dose-related suppression of body weight gain approached 60% at the high dose, but no significant effects on haematology or clinical chemical parameters were observed after 4 wk of exposure. Corneal opacities with histopathological features including neovascularization, acanthosis and stromal proliferation were observed in a dose-related fashion in both sexes at 100 and 200 mg/kg/day. Hypertrophy of the Harderian and lacrimal glands also occurred, probably as an adaptive response to sustained muscarinic activity. Lacrimal gland concentrations of the muscarinic agonist were in the range of pmol/mg tissue and therefore significant direct exposure of cornea to the compound through the tears was discounted. The presence of corneal muscarinic receptors was investigated to determine whether opacities could be related to direct, receptor-mediated events in the cornea; however, no specific binding of the muscarinic receptor radioligand [3H]quinuclidylbenzilate was detected. Because muscarinic agonist-induced opacities can be inhibited by scopolamine, the apparent lack of muscarinic receptors in the cornea indicates that the opacities are not a direct effect, but are instead secondary to muscarinic events at another site. To our knowledge, this is the first report of corneal opacities induced by a muscarinic agonist.

Animals↗
PubMed1999

Chronic toxicity and carcinogenicity testing in the Sprague-Dawley rat of a prospective insect repellant (KBR 3023) using the dermal route of exposure.

The chronic toxicology and carcinogenic potential of 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine (KBR 3023), a prospective new insect repellent intended for human use, was studied in rats using the dermal route of application. Relying upon the toxicology profile that emerged in the subchronic rat bioassay that was conducted using dermally applied dosages of 0, 80, 200, 500 and 1000 mg KBR 3023/kg body wt/day, it was determined, in concert with the Environmental Protection Agency (EPA), that dermally applied dosages of 0, 50, 100 or 200 mg KBR 3023/kg body wt/day would be used in the conduction of all definitive forms of subchronic, chronic, and lifetime descriptive testing performed with the chemical. Using this testing approach, the specific results of this 2-year study are as follows. All in-life parameters, which included body weight, food consumption, clinical observations, survival, ophthalmology, clinical chemistry, hematology, and urinalysis, were unaffected by exposure to KBR 3023. Similarly, postmortem analyses, which included organ weights and gross pathology, were also unchanged following exposure to KBR 3023. Histopathology at the dose site/skin was characterized by a pattern of acanthosis and/or hyperkeratosis across all doses in 1- and 2-year rats. Beyond the dosing site, cystic degeneration of the liver was described in 2-year 200-mg KBR 3023/kg body wt/day males. No other compound-related non-dosing site lesion was identified at any dose tested. No evidence of a compound-induced neoplasia was suggested in this bioassay.

Administration, Cutaneous↗
PubMed1977

Leukokeratosis nicotina glossi-smokers' tongue.

"Leukokeratosis nicotina glossi" or "smokers' tongue" is a homogeneous leukoplakia with evenly distributed pin-point hemispherical depressions. Histologically, there is a loss of glossal papillae, hyperkeratosis, acanthosis and the formation of large drop-shaped rete pegs with central clefting and occasional parakeratotic plugging. Mitotic activity and atypia are not marked and there is no evidence of Candida species infection. In some respects the lesion histologically resembles verrucous carcinoma but, unlike that condition, papillomatosis is not clinically noticeable and an invasive "leading edge" is not apparent. All but one of the subjects in which the lesion was seen were men, all had concurrent leukokeratosis nicotina palati and two gave histories of laryngeal carcinoma.

Adult↗
PubMed2002

Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience.

OBJECTIVE: To review our experience of keratinising squamous metaplasia of the bladder as a predictor for the development of cancer and other complications, and formulate a policy for its management. MATERIALS AND METHODS: A retrospective review (1945-1999) identified 34 patients with histologically proven keratinising squamous metaplasia (27 males and 7 females, average age 50 years, range 13-80 years). The histological criteria used to diagnose keratinising squamous metaplasia were squamous metaplasia of the urothelium with keratinisation and/or hyperkeratosis and/or acanthosis. Female patients with non-keratinising squamous metaplasia (vaginal metaplasia) were excluded. RESULTS: Four patients had synchronous bladder carcinoma (three advanced with early death; one localised, cured by cystectomy). Another 14 patients had extensive metaplasia (Group A, >50% of mucosal involvement). Three cases had cystectomy and cure. Six cases (out of 11) developed subsequent cancer (4 advanced and early death, two localised and cured by cystectomy). One other case died of obstructive uropathy secondary to squamous metaplasia. Two cases died of unrelated causes. Sixteen patients had limited squamous metaplasia (Group B, <50% involvement mucosal surface). Twelve patients had endoscopic resection, extraction bladder calculus etc. with no further complications. Another two patients underwent urinary diversion. Two patients (out of 16) developed subsequent cancer both with advanced disease and early death. CONCLUSION: Keratinising squamous metaplasia of the bladder is a significant risk factor for vesical carcinoma and complications, such as bladder contracture and ureteral obstruction. This risk of complications increases with more extensive bladder mucosal involvement. The wide variation in lag time to the development of complications necessitates indefinite follow-up. Selected patients with extensive bladder involvement and long life expectancy should be offered cystectomy.

Adolescent↗
PubMed1996

Coexistence of an unusual form of scabies and lepromatous leprosy. A case report.

A case of unusual crusted (Norwegian) scabies involving the entire skin of a 26 year old Brazilian patient with lepromatous leprosy is reported. The more prominent histopathological findings were acanthosis, hyperkeratosis and crusting with many mites of Sarcoptes scabiei. In the dermis, numerous foamy histiocytes filled with abundant acid-fast bacilli were seen.

Adult↗
PubMed1984

Pachydermodactyly: a case report and discussion of the pathologic entity.

Numerous case reports have described idiopathic hypertrophy of the skin on the dorsum of the hands. Many different and confusing names have been assigned to these conditions. A case report of a patient with pachydermodactyly is presented, with a discussion of the literature, in an effort to clarify the identification, treatment, and nomenclature of idiopathic hyperkeratosis and acanthosis of the dorsum of the hands.

Adult↗
PubMed2003

Non-cytocidal infection of keratinocytes by canine distemper virus in the so-called hard pad disease of canine distemper.

A late, but not uncommon sequel to canine distemper virus (CDV) infection of dogs is thickening of footpads and nasal planum, the so-called hard pad disease, originally described as vacuolar degeneration of epidermal keratinocytes with inclusion body formation and massive hyperkeratosis. However, in a recent study of footpads of naturally CDV-infected dogs only hyperkeratosis was observed without any of the other changes. Instead, acanthosis was frequently noticed. CDV nucleoprotein was present in the suprabasal keratinocytes and eccrine epithelial glands only. No CDV nucleoprotein was present in basal keratinocytes. This observation in combination with lack of obvious cytocidal changes strongly suggested the possibility of a restricted viral infection with presence of viral mRNA but without protein expression. Therefore, the presence of CDV nucleoprotein mRNA was investigated using in situ hybridization and compared to the localization of the nucleoprotein in footpads of clinically healthy and distemper dogs. Viral nucleoprotein and nucleoprotein mRNA in nearly all cases co-localized to the same compartments and basal keratinocytes did not contain nucleoprotein mRNA. These findings dispute the idea of a restricted viral infection of footpad keratinocytes in dogs with natural CDV infection. Instead, a migration of the virus to the epidermal surface along with the proliferating and differentiating epithelium is the most likely explanation for the lack of virus antigen in basal keratinocytes.

Animals↗
PubMed1996

Health hazards of obesity.

Several health hazards and social disabilities are associated with obesity. Increased mortality is associated with increased body weight. A high rate of mortality results from heart disease, diabetes mellitus, gallbladder disease, high blood pressure, and cancer. Physiologic cardiovascular changes occur, leading to left ventricular hypertrophy and lipid abnormalities. Hypertension, stroke, and venous stasis are increased. Pulmonary abnormalities include obstructive sleep apnea, which can be associated with secondary polycythemia and right ventricular hypertrophy. Gallstones, gallbladder disease, and accumulation of fat on the liver are significantly increased. Gout and reproductive abnormalities in women are common. Osteoarthritis of the knees and spine occur, although osteoporosis is rare. Risk for endometrial and breast cancer is increased, particularly in the presence of increased central fat. Changes in the skin include stretch marks, acanthosis negricans, hirsutism, intertrigo, and multiple papillomas. Impaired psychosocial function is manifested as social isolation, loss of job mobility, increased employee absenteeism, and economic and social discrimination.

Female↗
PubMedDate not supplied

The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat--a case study with KBR 3023 (a prospective insect repellent).

KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine, a prospective insect repellent being developed by the Bayer Corporation, was evaluated for reproductive toxicity in the Sprague-Dawley rat. As the intended human use of the test compound is topical, the test system was also exposed to the compound via the dermal route. Specifically, the adult rats (P generation) were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 100, or 200 mg KBR 3023/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Clinical signs and changes in body weight and food consumption were assessed throughout the study. All adults and neonates underwent a gross necropsy examination. Tissues retained for microscopic examination from all adult animals included the kidney, liver, pituitary, reproductive organs, and samples of skin from the shaved dose site. In addition to the parameters noted above, the animals were evaluated for the effect of the test compound on estrous cycling, mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. There were no test compound-related clinical signs or effects on body weight or food consumption observed in either the adults or the pups during any phase of the study. There were no compound-related effects on any reproductive or litter parameters. Dermal findings at the dose site (acanthosis and hyperkeratosis) were noted in both generations. Other than the dermal findings, no compound-related necropsy findings were seen in either the adults or the pups. No compound-related histopathologic findings were noted in the reproductive tissues of either the males or females. Based on these results, KBR 3023, administered as described in this study at dose levels as high as 200 mg/kg body weight (the physical limit of dermal application for this compound), did not demonstrate any reproductive toxicity.

Administration, Topical↗
PubMed2000

Possible contribution of stem cell factor in psoriasis vulgaris.

It is suggested that mast cell is implicated to play a role in the pathogenesis of psoriasis. In this study, to determine the role of stem cell factor (SCF), which is a growth factor of mast cells, we have examined the immunohistochemical localization and serum level of SCF in patients with psoriasis vulgaris. Immunohistochemical analysis revealed diffuse staining for SCF on keratinocytes in acanthotic epidermis in psoriasis, along with endothelial cells and fibroblasts. Serum SCF level, which was measured by enzyme-linked immunosorbent assay (ELISA), was significantly increased in patients with psoriasis vulgaris (1033+/-334 pg/ml) (n=24) than that of normal subjects (666+/-196 pg/ml) (n=15) (P<0.05). However, serum SCF did not show a correlation with the disease severity assessed by psoriasis activity and severity index (PASI) score. As patients with psoriasis vulgaris occasionally complain itching, next we divided 20 patients into two groups, those with itching (Group I) (n=8) and those without (Group II) (n=12), and compared the mast cell number located in the papillary dermis between thickened psoriatic epidermis, serum SCF and plasma histamine levels. Results showed that mast cell numbers (56.3+/-22.3/mm(2) in Group I vs 31.5+/-10. 3/mm(2) in Group II, P<0.05) and plasma histamine level (1.5+/-0.59 ng/ml vs 0.39+/-0.15 ng/ml, P<0.01) were significantly higher in patients of Group I than those of patients of Group II, however, the difference of serum SCF level (1132+/-368 pg/ml vs 890+/-373 pg/ml) did not reach a statistical significance. Finally, in a separate experiment, we examined whether exogenous SCF is capable of inducing psoriatic architecture on the transplanted uninvolved psoriatic skin onto severe combined immunodeficient (SCID) mice. SCF injection for 2 weeks could not induce a psoriasiform architecture such as acanthosis on the transplanted uninvolved psoriatic skin, although mast cells were increased in number. These results raised a possibility that keratinocyte-derived SCF plays a role, in part, in the increased number of mast cells in the papillary dermis of psoriasis, which may lead pruritus associated with psoriasis. Elevated serum SCF level may also be responsible for increment of mast cells in psoriasis vulgaris. Mast cell-derived factor stimulated by exogenous SCF could not induce psoriatic epidermis, suggesting that other factors such as activated lymphocytes or macrophages are further required for the development of psoriatic lesions.

Animals↗