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Biomedical subjects

A M Kligman

Publications and source records attributed to A M Kligman.

At least 19 recordsLinked to original sources

Pyoderma faciale. A review and report of 20 additional cases: is it rosacea?

BACKGROUND AND DESIGN: Pyoderma faciale was originally described by O'Leary and Kierland in 1940. It is characterized by the sudden onset of monstrous coalescent nodules and confluent draining sinuses confined to the face of young women in their early 20s. This report summarizes our results in 20 cases. The women were 15 to 46 years old (mean, 25 years). RESULTS: All women were flushers and blushers. Histopathologic examination revealed a dense perivascular and periadnexial infiltrate, including granulocytes, eosinophils with epithelioid granulomas, and septal and lobular panniculitis. No consistent laboratory abnormalities were found. After much therapeutic experimentation, we developed an effective treatment plan, based on a combination of oral isotretinoin and corticosteroids. CONCLUSION: We regard it as an extreme form of rosacea and suggest it be renamed rosacea fulminans in analogy with its counterpart, acne fulminans.

Adolescent

Agents that cause enlargement of sebaceous glands in hairless mice. I. Topical substances.

We have developed a simple murine model to measure the effects on sebaceous glands of a variety of substances commonly found in topical formulations. Applications (0.2 ml) were made daily to the flanks of hairless albino female mice, for time periods varying from 4 to 9 days. Biopsies, fixed for light microscopy, were stained with H & E. Under x400 magnification, the sebocytes comprising each gland were counted, from which the mean sebocyte count per gland was calculated. Electron micrographs were prepared to evaluate sebum production. The test substances, which included anionic and cationic surfactants, solvents and emulsifiers, almost invariably led to a rapid increase in the sebocyte count, peaking at day 5. Irritating substances, such as croton oil and benzalkonium chloride, had the greatest hyperplasiogenic effect, at least doubling the sebocyte count. Electron micrographs showed large increases in rough endoplasmic reticulum and in sebum droplets. Thus, hyperplasia appears to be a stereotypic response to diverse substances, especially if these have irritancy potential.

Administration, Topical

Agents that cause enlargement of sebaceous glands in hairless mice. II. Ultraviolet radiation.

We have developed a murine model to measure the effects on sebaceous glands of ultraviolet (UV) radiation. Hairless mice were irradiated with Westinghouse FS-40 tubes filtered to attenuate the radiation below 290 nm. Emission was mainly in the UVB range (peak, 313nm). Single and multiple exposures were given with fractions or multiples of one minimal erythemal dose (MED). Biopsies, fixed for light microscopy, were stained with H & E. Under high power, sebocytes of 30 glands per specimen were counted and the means determined. A single exposure of 1 MED caused a significant increase in sebocyte count, as did thrice-weekly exposures to 0.5 MED for 3 weeks. One 3-MED exposure produced sebocyte necrosis, yet 30 exposures at 4 MED failed to ablate the glands. In both cases there was rebound enlargement which had not returned to control levels by the end of the studies (24-30 weeks). Prolonged irradiation produced maximum enlargement in a few weeks. Thus, in a manner similar to other skin components, the response of sebaceous glands to UV radiation is one of hyperplasia.

Animals

Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis.

Hair-bearing, transitional, and alopecic scalp from three males and one female with progressive pattern alopecia were examined. Ultrastructural studies disclosed measurable thickening of the follicular adventitial sheaths of transitional and alopecic zones compared with those in the non-alopecic zones. This finding was associated with mast cell degranulation and fibroblast activation within the fibrous sheaths. Immunohistochemically, control biopsies were devoid of follicular inflammation (n = 3), while transitional regions consistently showed the presence of activated T-cell infiltrates about the lower portions of follicular infundibula. These infiltrates were associated with the induction of class II antigens on the endothelial linings of venules within follicular adventitia and with apparent hyperplasia of follicular dendritic cells displaying the CD1 epitope. Inflammatory cells infiltrated the region of the follicular bulge, the putative source of stem cells in cycling follicles. The data suggest that progressive fibrosis of the perifollicular sheath occurs in lesions of pattern alopecia, and may begin with T-cell infiltration of follicular stem cell epithelium. Injury to follicular stem cell epithelium and/or thickening of adventitial sheaths may impair normal pilar cycling and result in hair loss.

Adult

The hairless mouse model for assaying the atrophogenicity of topical corticosteroids.

The daily application of corticosteroids for 18 days to the dorsal skin of hairless mice resulted in loss of volume of all the cutaneous compartments. The epidermis thinned, sebaceous glands regressed, dermal thickness was reduced, horn-filled cysts shrunk, subcutaneous fat disappeared, and regression of the muscular layer occurred. The magnitude of these changes correlated strongly with the accepted potency ranking of these agents by clinical efficacy. Thus, atrophogenicity predicts anti-inflammatory activity. This model furnishes a simple screening method for assaying corticosteroid activity and for optimizing proprietary formulations.

Adipose Tissue

Age, sunlight, and facial skin: a histologic and quantitative study.

Quantitative methods were developed to assess the interrelation between age and sunlight on the facial skin of healthy women living in the same sunny area. The women were grouped into the following categories: young versus old and low versus high solar exposure. The features evaluated were perceived age, amount of facial wrinkling, skin color, and skin elasticity. A punch biopsy specimen of cheek skin was obtained and prepared histologically for evaluation of solar elastosis. The histologic examination was complemented by quantification of collagen and elastin by computer-assessed image analysis. Perceived age was estimated by untrained women viewing high quality photographs. As expected, those with greater sun exposure looked older and had more wrinkles, more severe elastosis, increased elastin, and decreased collagen.

Adult

Comparison of the kinetics of sebum secretion in young women with and without acne.

We utilized a sebum-sensitive adhesive film, Sebutape, to visualize the pore patterns of women with and without acne with computerized image analysis. In normal young women, we found a positive correlation between the number of active sebaceous follicles and total sebum excretion. When seborrhea was intense, this correlation was however lost. The situation was more complex in acne. The severity of seborrhea was positively correlated with the mean sebum excretion of individual follicles but not with the number of active follicles.

Acne Vulgaris

Rhythm of sebum excretion during the menstrual cycle.

We studied by the Sebutape technique variations in the sebum excretion and in the number of active sebaceous glands during 3 consecutive menstrual cycles. In seborrheic women we found cyclic changes with a maximum sebum excretion during the week before menstruation. In women with a low sebum production, no changes were found.

Adult

Postadolescent acne in women.

A low-grade, persistent acne is quite common in hard-working professional women in their twenties, thirties, and forties. Closed comedones are the dominant lesions, with a scattering of papulopustules. Premenstrual flares are typical. Most such patients passed through adolescence without acne. Acne cosmetica has to be ruled out. The latter is more inflammatory and the lesions are denser. It is postulated that chronic stress leads to enhanced secretion of adrenal androgens, resulting in sebaceous hyperplasia and subsequent induction of comedones. Postadolescent acne is an authentic variety of acne vulgaris; it responds well to treatment with conventional topical medicaments.

Acne Vulgaris

Postmenopausal acne.

Postmenopausal acne originates at or after menopause in darker-skinned, formerly oily-skinned, large-pored women who usually did not experience adolescent acne. It is a low-grade, long-smoldering acne in which small closed comedones are dominant, among which there is a scattering of dimunitive papulopustules. There is a seeming association with chin and upper lip hirsutism. Topical tretinoin is an effective therapy. Unopposed adrenal androgens present after ovarian failure may be the chief causes of this condition.

Acne Vulgaris

The invisible dermatoses.

The central tenet of invisible dermatology is that visible lesions represent a late stage of development. The eye is an unreliable instrument for judging the normalcy of skin. In chronic widespread dermatoses, the uninvolved skin is at least physiologically abnormal. Recently healed skin is always abnormal. Recognition of occult changes will have a substantial impact on the prevention and treatment of diseases of the skin.

Humans

Functional analyses of the superficial stratum corneum in atopic xerosis.

Dermatologists universally recognize that the unaffected skin of patients with atopic dermatitis tends to be dry and slightly scaly. To characterize the functional properties of the superficial stratum corneum in atopic xerosis, we studied the forearms of 28 patients with atopic dermatitis, aged 14 to 30 years, and 18 age-matched controls, with the use of mainly noninvasive methods. Patients with atopic xerosis showed markedly higher transepidermal water loss and markedly lower skin surface hydration levels than did the controls. The corneocytes in atopic xerosis tended to desquamate in clumps of cell aggregates instead of as individual cells. They contained a substantially lower amount of water-soluble amino acids, which play a role in the water-retaining capacity of stratum corneum, than did those of controls. Although the number of stratum corneum cell layers in atopic xerosis (21 +/- 4) was substantially larger than that in controls (15 +/- 1), its turnover time (7 +/- 2 days) was appreciably shorter than that for controls (14 +/- 2 days). Like those noted in the skin with increased epidermal proliferation, the size of superficial corneocytes in patients with atopic xerosis was substantially smaller than in controls. Histopathologic examination revealed acanthotic epidermis, mild perivascular mononuclear cell infiltrate, and pigment incontinence. Atopic xerosis, the dry skin of patients with atopic dermatitis, shows various stratum corneum functional impairments, probably reflecting increased epidermal proliferation due to a low-level ongoing dermatitis.

Adolescent

Contact dermatitis to neomycin sulfate.

The prevalence of contact allergic dermatitis and nonallergic irritant reactions to neomycin sulfate was determined in a large group of young adults who had a noteworthy exposure to topical antibiotics. Only two subjects (0.09%) had contact allergy proved by closed patch testing, while 20 (0.9%) had nonallergic irritant reactions to 20% neomycin sulfate and 17 (0.78%) had nonallergic reactions to one of the hydrophilic ointment bases. In a separate population of 653 children referred for diagnostic patch testing, only one subject had contact allergy to neomycin. All three subjects who had reactions had a history of repeated use of neomycin on chronically damaged skin. These results support the conclusion that intermittent use of neomycin on minor cuts and wounds is not associated with an excessive rate of sensitization.

Adolescent

The soap chamber test. A new method for assessing the irritancy of soaps.

The chamber test for assessing the irritancy of soaps entails five weekday exposures to 8% solutions with readings of scaling, redness, and fissuring on the following Monday. Eighteen well-known toilet soaps were evaluated. Great differences were noted. Most had an appreciable irritancy potential. These results contrast with a number of studies which failed to show differences among soaps or which concluded that soaps were innocuous.

Erythema

Photoprotection by melanin--a comparison of black and Caucasian skin.

The photoprotective role of melanin was evaluated by comparing the transmission of ultraviolet (UV) radiation through skin samples of blacks and Caucasians, using both biologic and spectroscopic techniques. UVA transmission was measured using fluoranthene, which causes a phototoxic response to UVA wavelength. UVB was measured by monitoring erythema produced by either a 150-watt xenon arc or FS-20 sunlamps. It was found that on the average, five times as much ultraviolet light (UVB and UVA) reaches the upper dermis of Caucasians as reaches that of blacks. Differences in transmission between the stratum corneum of blacks and of Caucasians were far less striking. The main site of UV filtration in Caucasians is the stratum corneum, whereas in blacks it is the malpighian layers. Melanin acts as a neutral density filter, reducing all wavelengths of light equally. The superior photoprotection of black epidermis is due not only to increased melanin content but also to other factors related to packaging and distribution of melanosomes. Not only are these data consistent with epidemiologic evidence, but they also may indicate why blacks are less disposed to phototoxic drug responses as well as less susceptible to acute and chronic actinic damage.

Adult

The influence of longwave ultraviolet radiation on sunburn cell production by UVB.

The potentiation of sunburn by longwave ultraviolet radiation (photoaugmentation) has been examined with regard to the influence of these waves on sunburn cell production in human skin. It was found that UVA did not enhance sunburn cell production. Photoaugmentation is limited to the erythemal component of the sunburn reaction.

Adolescent