Progressive decreases in nuclear retinoid receptors during skin squamous carcinogenesis.

Retinoids are essential for normal skin growth, differentiation, and apoptosis and are active pharmacologically in the prevention and treatment of skin cancers and other lesions. Retinoid effects are mediated mainly by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as transcription factors to alter gene expression. Using in situ hybridization, we analyzed the expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) were moderate to very strong in normal skin, with higher expressions in spinous and granular layers than in the basal layer. RAR-beta expression was weak or absent in normal and lesion samples. All five receptors expressed in the skin were suppressed progressively from normal skin to premalignant skin (AK) to invasive skin SCC. Specific receptor decreases in lesions relative to normal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the two predominant retinoid receptors in skin, was relatively less for RXR-alpha (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be an earlier event and expression of RAR-gamma may be a later event of multistep squamous skin carcinogenesis. Our results indicate that suppressed expression of retinoid receptors occurs early (in AK) and is associated with progression of squamous skin carcinogenesis to SCC.

Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts.

OBJECTIVE: To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts. DESIGN: Double-blind, randomized, multicenter, vehicle-controlled investigation. SETTING: Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations. PATIENTS: Three hundred twenty-six patients with anogenital warts. MAIN OUTCOME MEASURE: Number of patients with clearing of all treated warts (treatment success). RESULTS: The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions. CONCLUSIONS: The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.

Evaluation of the American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program.

BACKGROUND: Increasing incidence and mortality rates from cutaneous melanoma are a major public health concern. As part of a national effort to enhance early detection of melanoma/skin cancer, the American Academy of Dermatology (AAD) has sponsored an annual education and early detection program that couples provision of skin cancer information to the general public with almost 750,000 free skin cancer examinations (1985-1994). OBJECTIVE: To begin to evaluate the impact of this effort, we determined the final pathology diagnosis of persons attending the 1992-1994 programs who had a suspected melanoma at the time of examination. METHODS: We directly contacted all such persons by telephone or mail and received pathology reports from those who had a subsequent biopsy. RESULTS: We contacted 96% of the 4458 persons with such lesions among the 282,555 screenings in the 1992-1994 programs. We obtained a final diagnosis for 72%, and the positive predictive value for melanoma was 17%. Three hundred seventy-one melanomas were found in 364 persons. More than 98% had localized disease. More than 90% of the confirmed melanomas with known histology were in situ or "thin" lesions (< or = 1.50 mm thick). The median thickness of all melanomas was 0.30 mm. The 8.3% of AAD cases with advanced melanoma (metastatic disease, regional disease, or lesions > or = 1.51 mm) is a lower proportion than that reported by the 1990 Surveillance, Epidemiology and End Result Registry. The rate of thickest lesions (> or = 4 mm) and late-stage melanomas among all participants was 2.83 per 100,000 population. Of persons with a confirmed melanoma, 39% indicated (before their examination) that without the free program, they would not have considered having a physician examine their skin. CONCLUSION: The 1992-1994 free AAD programs disseminated broad skin cancer educational messages, enabled thousands to obtain a free expert skin cancer examination, and found mostly thin, localized stage 1 melanomas (usually associated with a high projected 5-year survival rate). Because biases impose possible limitations, future studies with long-term follow-up and formal control groups should determine the impact of early detection programs on melanoma mortality.

The Texas Skin Cancer/Melanoma Project.

The Texas Skin Cancer/Melanoma Project, cosponsored by the Texas Dermatological Society and the Texas Division of the American Cancer Society, was organized to promote awareness of skin cancer. Through a well-orchestrated effort, the citizens of Texas were educated about prevention and early detection. On one day, statewide screening was conducted at 55 sites and 11,151 patients were screened. Polls conducted before and after the project show that the level of knowledge and concern about skin cancer increased following the project. Skin cancer is ideal for such a public education and screening project.

Skin cancer: a primer for the nondermatologist.

The rising incidence of skin cancer in the United States has become a significant public health concern. The morbidity and mortality associated with these conditions can be reduced significantly by earlier detection and treatment. All physicians, not just dermatologists, can play a role in this regard. This article is intended to alert practicing physicians to the extent of the problem and to familiarize them with the various forms of skin cancer.

Granuloma inguinale.

An unusual American epidemic consisting of twenty cases of granuloma inguinale is chronicled. Evidence from this series supports the venereal transmission of the disorder. Trimethoprim/sulfamethoxazole proved to be a safe and effective therapy.

Unusual appearance of Crohn's disease.

The association of perianal fistulas and Crohn's disease is well recognized. The appearance of lesions distant from the anal area is, however, uncommon. A young girl appeared with a history of weight loss and extensive mucocutaneous ulcerations. Diarrhea subsequently developed. Colonoscopy revealed friability, edema, and ulcerations. A crypt abscess was found in colonic biopsy specimens. Treatment with prednisolone acetate and sulfasalazine resulted in prompt improvement. A skin biopsy done initially and repeated colon biopsy three months later demonstrated granulomas, consistent with Crohn's disease. The literature regarding skin lesions in association with Crohn's disease is reviewed and the importance of recognizing the cutaneous manifestations of Crohn's disease is emphasized.

Disciform erythrasma.

A case of disciform erythrasma is presented. This unusual manifestation of a common cutaneous infection may mimic other dermatologic disorders, including lichen sclerosus et atrophicus and plaque-type parapsoriasis. The condition is characterized by an atrophic appearing surface, located in nonintertriginous areas. Appropriate diagnostic procedures easily differentiate disciform erythrasma. These include Wood's light examination, potassium hydroxide preparation, and skin scrapings or tissue sections stained with Gram stain, periodic acid-Schiff, Giemsa, or methylene blue.

Eosinophilic fasciitis: an early variant of scleroderma.

Eosinophilic fasciitis, originally reported as a syndrome distinct from scleroderma, appears now to be an early inflammatory variant of scleroderma. No less than one half of the cases reported as eosinophilic fasciitis have convincing features of scleroderma, including Raynaud's phenomenon, esophageal dysmotility, restrictive lung disease, diffuse hyperpigmentation, synovitis, flexion contractures, dermal sclerosis, colonic diverticula, scleroderma kidney, positive latex fixation test, and the presence of serum antinuclear antibodies (ANA). Clinical presentations of scleroderma range from isolated acrosclerosis to rapidly progressive systemic sclerosis. As clinical experience and long-term follow-up data on eosinophilic fasciitis accumulate, it appears that the syndrome may well represent another variant in the scleroderma spectrum. Reported here is a case which presented clinically and histologically as eosinophilic fasciitis, but which progressed over 3 years to diffuse, histologically confirmed scleroderma.

Bullous disease of childhood.

Bullous disease of childhood (BDC) is a persistent or recurrent blistering skin disease characterized by large, tense bullae in a generalized distribution, but with a predilection for the scalp, trunk, pubis, and inner thighs. It usually begins in the first decade of life and spontaneously remits after several months to three years of activity. Sulfapyridine or dapsone therapy usually controls the disease. Administration of corticosteroids for systemic effects should be avoided.

Infantile acropustulosis.

Infantile acropustulosis is a syndrome that is characterized by recurrent crops of 1- to 2-mm, intensely pruritic vesicopustules on the distal extremities. The eruption is unresponsive to topical steroids, and pruritus is relieved only by soporific doses of antihistamines.