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• The effects of topically applied spironolactone on the sebaceous glands of flank organs in adult male golden hamsters were investigated. Daily treatment with spironolactone (0.3 mg and 3 mg) on one side only significantly reduced the size of the treated flank organs, while the contralateral flank organs remained unchanged. Lower doses of spironolactone and the vehicle had no effect. Cyproterone acetate therapy resulted in the bilateral reduction of flank organ sizes. In vivo measurement of the palpable bulk of the flank organs correlated with flank organ volumes as determined by computer-assisted planimetry of serial histologic sections. Dry weights of seminal vesicles in animals treated with spironolactone did not differ significantly from those of the control group, while topically applied cyproterone acetate significantly reduced seminal vesicle weight. Topically administered spironolactone appears to have only local antiandrogenic effects, as indicated by the lack of changes in the untreated contralateral flank organs and in the weights of seminal vesicles.(Arch Dermatol 1985;121:57-62)

• A study was performed to determine the effect of UV-B radiation on the sensitization of patients to topically applied mechlorethamine hydrochloride. Patients with widespread psoriasis were randomized into two groups. One group was given six daily treatments of one minimal erythemal dose (MErD) prior to starting daily applications of a 0.02% mechlorethamine ointment and, thereafter, one MErD weekly; the other group was given daily applications of mechlorethamine but received no UV-B. The improvement of psoriasis was monitored by a severity score system and patients were treated for 30 days, or until contact dermatitis occurred. The addition of UV-B to topical applications of mechlorethamine reduced the incidence of allergic contact dermatitis to mechlorethamine from 64% to 22%. In those sensitized to mechlorethamine, the time required for sensitization to develop was increased from 14 to 23 days by UV-B therapy.(Arch Dermatol 1983;119:117-121)

On the basis of clinical, histological, and cellular kinetic observations, a separation of the major ichthyosiform dermatoses into four groups is proposed.Ichthyosis vulgaris patients have dry skin and fine scales on their trunk and extremities, but gross changes in the skin of their legs may be more severe. A granular layer is histologically absent.Lamellar ichthyosis patients have large, coarse scales. The granular layer is prominent in this condition.Epidermolytic hyperkeratosis consists of a clinical spectrum of disorders; generalized forms may be bullous, and localized forms may resemble linear nevi. Intracellular and intercellular edema gives the epidermis a characteristic reticular pattern in histological sections.Psoriasiform erythroderma is clinically and histologically indistinguishable from universal psoriasis.Increased mitotic activity and consequent increased scale formation appear to be important pathogenetic features in these disorders, except for ichthyosis vulgaris in which mitotic counts were actually lower than in the control specimens.

Several commonly used emollients were studied as to their effectiveness in absorbing and filtering erythema-causing ultraviolet radiation in the 280 to 315 nm range (UVB). Planter's Peanut Oil (Standard Brands) and Mazola Corn Oil (Best Foods Inc) had no effect; Alpha Keri Bath Oil (Westwood Pharmaceuticals), mineral oil, and Johnson's Baby Oil (Johnson & Johnson Co) had minimal effects. Vaseline Petroleum Jelly (Chesebrough-Ponds Inc), petrolatum, and hydrophilic ointment substantially reduced the erythema that was induced by exposure to low doses of UVB radiation. Therefore, these emollients may interfere with the therapeutic effects of the ultraviolet radiation component of the Goeckerman treatment when it is administered in low doses to patients with psoriasis.(Arch Dermatol 115:1188-1191, 1979)

To determine the efficacy of suberythemogenic ultraviolet phototherapy in conjunction with administration of a tar gel (SEUV TG), patients with widespread psoriasis were treated by application of a tar gel preparation followed after 12 hours by suberythemogenic doses of fluorescent sunlamp irradiation. In paired comparison studies, therapeutic effects of the following treatments were evaluated: SEUV-TG, a more conventional erythemogenic tar gel phototherapy regimen (modified Goeckerman), the tar gel alone, and SEUV irradiation following application of gel vehicle. Response to therapy was monitored with a severity score system. In patients with psoriasis responsive to phototherapy, smaller quantities of UV energy administered in combination with a tar gel were at least as effective as larger erythemogenic doses. Production of erythema with fluorescent sunlamp radiation does not appear to be necessary to improve psoriasis. Both UV radiation and tar gel have beneficial effects on psoriasis, but the combination is superior.(Arch Dermatol 115:840-846, 1979)

• The effect of topical application of halcinonide cream and betamethasone valerate cream on plasma cortisol was studied in an acute usage study as well as a subacute study, which more closely approximated common clinical usage. In the acute study, halcinonide cream caused a marked decrease in plasma cortisol, both with and without occlusion, in patients with extensive psoriasis, but only with occlusion in normal subjects. Betamethasone valerate cream decreased plasma cortisol levels in patients with extensive psoriasis when applied with occlusion and, to a lesser extent, without occlusion. In a double-blind subacute usage study without occlusion, two of 23 patients treated with halcinonide cream showed decreased plasma cortisol levels during the treatment period, while none of the 21 patients treated with betamethasone valerate cream showed such decreases. Three patients in the halcinonide group developed striae. Clinical response to halcinonide was superior to that with betamethasone valerate cream, but a similar number of patients were resistant to treatment with each medication.(Arch Dermatol 113:1196-1202, 1977)

• Fifty hospitalized dermatology patients participated in a study to evaluate the transfer of topically applied tetracycline hydrochloride-containing fluorescent ointments, creams, lotions, and tinctures from various sites of application. Patients were examined with a Wood's lamp 24 hours after application to determine the sites and areas of transfer. The topically applied medications did not remain confined to sites of initial application. The anatomic sites of initial application determined the pattern of transfer. Certain patterns of transfer were characteristic among groups of patients and for specific patients. The vehicle of the topical preparation greatly influenced the extent and sites of transfer.(Arch Dermatol 1983;119:660-663)

• A patient with psoriasis is described who had an abnormal response to the glucose tolerance test without other evidence of diabetes and then developed postprandial hyperglycemia and glycosuria during a period of topical administration of a corticosteroid cream, halcinonide cream 0.1%, under occlusion. A second patient with a similar glucose tolerance test result showed postprandial hyperglycemia when treated similarly with betamethasone valerate cream 0.1%. Two additional patients with mildly abnormal responses to glucose tolerance tests showed no evidence of altered glucose metabolism when treated with halcinonide cream in a similar manner.(Arch Dermatol 112:1559-1562, 1976)

• A newly designed cabinet can be used for the treatment of psoriasis with fluorescent ultraviolet (UV) lamps. The new design provides more uniform distribution of UV radiation in both the horizontal and vertical axes, and several safety features have been added. The distribution and uniformity of UV output in this and in a previously described cabinet are compared. The UV output at the vertical center of the older UV light cabinet was six times greater than that at either the top or bottom, while the design of the present cabinet provides uniform UV radiation except for a slight increase at head height and at the level of the lower legs compared with the middle third of the cabinet. The variation in output of the older cabinet may, in part, explain the commonly encountered difficulty in the phototherapy of psoriasis of the scalp and lower extremities.(Arch Dermatol 1981;117:469-473)

Pemphigus is a disease associated with a high death rate if untreated and a high morbidity rate when treated with corticosteroids administered systemically for a prolonged period. Parenterally administered gold sodium thiomalate was evaluated in 18 patients as an alternate means of therapy. Fourteen of these patients (three of whom had never received systemic corticosteroids for this condition) have been successfully managed for variable periods with this drug.

Therapy of patients with severe psoriasis has been facilitated in recent years by the use of systemic methotrexate. Several common schedules for drug administration include small daily oral doses and weekly intramuscular or oral doses. These schedules were empirically designed and have had reasonably good results. A new schedule of methotrexate administration is recommended for the treatment of psoriasis, based on current knowledge concerning the epidermal cell proliferation kinetics of psoriasis and chemotherapy with cell-cycle specific drugs. Methotrexate was administered orally in small doses (2.5 to 7.5 mg) at 12-hour intervals for a total of three doses at weekly intervals. Of 26 patients with severe psoriasis, 20 attained 75% to 100% improvement with administration of methotrexate. Side effects were minimal. The pharmacologic rationale for this drug schedule and its value relative to other commonly used schedules is discussed. Consideration of potential long-term risks with methotrexate must still be considered when evaluating patients for therapy.

Nine patients with a familial type of diffuse hyperkeratosis of the palms and soles are reported. Skin biopsies (and, in one case, epidermal kinetic studies) showed the changes of epidermolytic hyperkeratosis. It is suggested that the category of epidermolytic hyperkeratosis be expanded to include this variety of keratoderma palmaris et plantaris.

Liver status in 29 psoriatic patients, eight before methotrexate treatment and 21 after methotrexate therapy (three weeks to ten years), was evaluated by performing routine liver function tests, a test for sulfobromophthalein (Bromsulphalein) (BSP) retention, and liver biopsy. Results from liver function tests were normal in all but four patients but the BSP retention was elevated above 6% in ten patients. Among 21 patients treated with methotrexate, liver specimens from 16 showed fatty metamorphosis; from four, focal necrosis. Three of the patients treated with methotrexate, two of whom were heavy alcohol consumers, demonstrated portal fibrosis or cirrhosis. Of the control patients who had not received methotrexate, half had abnormal liver biopsy findings, which suggested that the overall evaluation of methotrexate damage to the liver will be complicated. Presence or absence of other liver disease, or history of exposure to potential hepatotoxins such as alcohol must be considered in evaluating patients for methotrexate therapy.

The location of the proliferative pool of cells in normal epidermis, ichthyosis vulgaris, lamellar ichthyosis, X-linked ichthyosis, epidermolytic hyperkeratosis, and psoriasis was examined using autoradiographic and projection techniques.A significant number of thymidine-labeled cells (deoxyribonucleic acid-synthesizing cells) were found above the basal cell layer in all conditions examined. Cell proliferation in the epidermis is not limited to the basal layer but also occurs in more superficial cells.

1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU) (NSC 409962), an agent being tested for antitumor activity, may cause hyperpigmentation of skin. This darkening follows topical application but not systemic administration. Although evident erythema does not always precede hyperpigmentation caused by BCNU, histologic changes in the epidermis suggest that this increased melanogenesis occurs as a postinflammatory event.

Examination of the eyes of a series of patients with four distinct types of ichthyosis disclosed that ectropion secondary to involvement of the skin of the lower eyelid was found only in patients with lamellar ichthyosis. Deep corneal dystrophy was present in all patients with X-linked ichthyosis and in most of the female carriers of this disorder. No deep corneal changes were noted in patients with lamella ichthyosis or epidermolytic hyperkeratosis. The examination of the cornea is useful in distinguishing males with X-linked ichthyosis from those with lamellar ichthyosis and ichthyosis vulgaris and in identifying female carriers of X-linked ichthyosis.

Therapeutic responses to topical administration of preparations containing 0.1% to 0.3% vitamin A acid and control bases applied to contralateral areas of involvement were compared in 26 patients with psoriasis, 8 with ichthyosis vulgaris, 8 with X-linked ichthyosis, 17 with lamellar ichthyosis, and 10 with epidermolytic hyperkeratosis. Topical administration of vitamin A acid was most effective in psoriasis, lamellar ichthyosis, and epidermolytic hyperkeratosis, disorders associated with epidermal cell hyperplasia; it did not appear to be effective in ichthyosis vulgaris. Irritation with higher concentrations of vitamin A acid, which subsided rapidly when the medication was withheld, was the only adverse effect noted.

The human cervical and vaginal cell generation cycle (Tc) and its component parts (Tg1, Ts, Tg2, Tm) have been defined in normal tissues using in vivo autoradiographic techniques. The most active proliferative compartment is composed of the first and second parabasal layers and accounts for about 90 per cent of reproductive capacity. The single basal layer probably exists primarily as a reserve cell compartment for the parabasal compartment and can be activated by an appropriate stimulus, such as exogenous estrogen stimulation. For example, Tcis about 3 days for the parabasal cell and 30 days for the basal cell in normal ovulatory and postmenopausal women; estrogen stimulation can accelerate Tcto 1.7 and 11 days, respectively, which is apparently due to shortening of Tg1. Initial studies indicate marked acceleration of Tcin squamous cell carcinoma of the cervix. Clinically, knowledge of normal and abnormal cell proliferation kinetics should provide insight into selective chemotherapeutic programs and dose-time relationships.

THE PURPOSE of this paper is to report skin findings not previously described in Fabry's disease and to call to the attention of physicians a simple method of diagnosis which distinguishes the disorder from another more benign condition which may have similar skin lesions.The classical skin lesions of angiokeratoma corporis diffusum are 0.1-3.0 mm diameter red to purple macules and papules on the scrotum and other areas of the body. Some have a hyperkeratotic surface. As first described by Fabry in 1898,1 the disorder was considered to be of dermatologic importance only. Anderson, reporting another case at about the same time, suggested that renal lesions similar to those in the skin might have accounted for his patient's hematuria.2 This condition is now known to be a systemic disease in which a glycolipid, ceramide-trihexoside,3,4 is stored in many kinds of cells, including renal and bronchial epithelium, cardiac

On the basis of clinical, histological, and cellular kinetic observations, a separation of the major ichthyosiform dermatoses into four groups is proposed.Ichthyosis vulgaris patients have dry skin and fine scales on their trunk and extremities, but gross changes in the skin of their legs may be more severe. A granular layer is histologically absent.Lamellar ichthyosis patients have large, coarse scales. The granular layer is prominent in this condition.Epidermolytic hyperkeratosis consists of a clinical spectrum of disorders; generalized forms may be bullous, and localized forms may resemble linear nevi. Intracellular and intercellular edema gives the epidermis a characteristic reticular pattern in histological sections.Psoriasiform erythroderma is clinically and histologically indistinguishable from universal psoriasis.Increased mitotic activity and consequent increased scale formation appear to be important pathogenetic features in these disorders, except for ichthyosis vulgaris in which mitotic counts were actually lower than in the control specimens.

Methotrexate is extremely effective for control of severe psoriasis; however, its mode of action is not yet fully understood. Deoxyribonucleic acid synthesis and its inhibition by methotrexate in normal and psoriatic epidermis was studied autoradiographically. Intradermally given methotrexate inhibits DNA synthesis for 12 to 16 hours in normal and psoriatic skin. Intramuscularly it causes complete inhibition in psoriasis but only partial inhibition in normal epidermis. Psoriatic epidermis is more sensitive to the action of methotrexate than normal epidermis. This may be due to increased drug sensitivity of the individual abnormal cell, as well as to increased percentage of psoriatic cells in the methotrexate-susceptible part of the cell cycle (S period). The local (cutaneous) effect of methotrexate to inhibit DNA synthesis suggests the further investigation of a topically administered form of methotrexate or its analogues for the treatment of psoriasis.

Normal skin and actinic keratoses were exposed to fluorouracil in order to study its effect on deoxyribonucleic acid (DNA) synthesis. Using intradermally injected tritiated deoxyuridine and autoradiography, we have demonstrated that fluorouracil blocks DNA synthesis in vivo by inhibiting thymidylate synthetase activity. Fluorouracil administered intradermally blocks DNA synthesis in both normal skin and actinic keratoses. Applied topically, and topically with occlusion, fluorouracil inhibits DNA synthesis for two and four hours respectively in actinic keratoses. An estimated minimum tissue concentration of 10-4 to 10-5 M of fluorouracil was required to inhibit thymidylate synthetase activity in human skin. Possible correlation of this biochemical effect with the clinical action of fluorouracil on actinic keratoses is discussed.

Transepidermal water loss (TWL) measurements in subjects having one of four distinct forms of ichthyosis were determined hygrometrically. The observed TWL was highest in epidermolytic hyperkeratosis but was significantly elevated above normal in all forms. The increased TWL rates through greatly thickened horny layers as compared to normal layers imply inefficient water barrier function of the stratum corneum in these disorders.

In a study of subjects who took two tetracycline congeners or a placebo for one week and were then exposed to sunlight, abnormal reactions to sun occurred in 12 of 13 subjects who took demeclocycline, 1 of 14 who took methacycline hydrochloride, and 1 of 16 who took the placebo.