In vivo fluorescence spectroscopy of nonmelanoma skin cancer.

In vivo and ex vivo tissue autofluorescence (endogenous fluorescence) have been employed to investigate the presence of markers that could be used to detect tissue abnormalities and/or malignancies. We present a study of the autofluorescence of normal skin and tumor in vivo, conducted on 18 patients diagnosed with nonmelanoma skin cancers (NMSC). We observed that both in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) the endogenous fluorescence due to tryptophan residues was more intense in tumor than in normal tissue, probably due to epidermal thickening and/or hyperproliferation. Conversely, the fluorescence intensity associated with dermal collagen crosslinks was generally lower in tumors than in the surrounding normal tissue, probably because of degradation or erosion of the connective tissue due to enzymes released by the tumor. The decrease of collagen fluorescence in the connective tissue adjacent to the tumor loci was validated by fluorescence imaging on fresh-frozen tissue sections obtained from 33 NMSC excised specimens. Our results suggest that endogenous fluorescence of NMSC, excited in the UV region of the spectrum, has characteristic features that are different from normal tissue and may be exploited for noninvasive diagnostics and for the detection of tumor margins.

Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The Doxepin Study Group.

BACKGROUND: Atopic dermatitis is associated with severe pruritus for which effective topical treatment is lacking. As a potent H1 and H2 antagonist, the antipruritic effect of topical doxepin was first demonstrated in histamine-induced itch in nonatopic volunteers. OBJECTIVE: The current study was undertaken to compare the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. METHODS: A total of 270 patients with atopic dermatitis who had daily moderate to severe pruritus for at least 1 week were enrolled in the double-blind, vehicle-controlled, multicenter study. Treatment was randomly assigned: 5% doxepin cream or vehicle cream was applied twice on the day of the baseline visit and four times daily for the remainder of the 7-day trial. RESULTS: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57% of vehicle-treated patients by day 7; a majority of these positive responses occurred during the first 24 hours. Pruritus severity scores demonstrated significantly greater improvement with topical doxepin at each study visit (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvement in the doxepin-treated group. At each of three visits, the physician's global evaluation for relief of pruritus also showed significant improvement in the doxepin treatment group (p < 0.01). The physician's global evaluations of eczema significantly favored topical doxepin on day 7 (p < 0.01). Nineteen patients withdrew from the study because of adverse effects (doxepin, n = 16; vehicle, n = 3). The most commonly reported were localized stinging or burning (doxepin group, n = 39; vehicle group, n = 34) and drowsiness (doxepin group, n = 37; vehicle group, n = 3), all of which decreased in frequency and severity over time. CONCLUSION: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has an apparent short-term low risk of major side effects or sensitization.

Perianal pseudoverrucous papules and nodules in children.

BACKGROUND: Pseudoverrucous papules and nodules were originally described as a reaction to irritation in association with urostomies. These changes have not been described as occurring on the perianal skin or around colostomies. OBSERVATIONS: Five children had remarkably similar-appearing papules and nodules of the perianal and suprapubic skin. The rash consisted of more than a dozen 2- to 8-mm shiny, smooth, red, moist, flat-topped, round lesions. This peculiar and striking reaction appears to be the result of encopresis or urinary incontinence. Biopsy specimens reveal reactive acanthosis or psoriasiform spongiotic dermatitis. The lesions regress when the irritating factor is removed. CONCLUSIONS: Recognition of this entity is important because pseudoverrucous papules and nodules may mimic more serious dermatoses and unnecessary workup may be initiated. Although this reaction involving perianal skin has not been reported previously, we believe it is not uncommon.

Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro.

Certain arachidonic metabolites may play a pathogenic role in psoriasis. Platelets are rich sources of 12-hydroxy-eicosatetraenoic acid (12-HETE) and thromboxane A2, mediators of skin inflammation and platelet aggregation, respectively. We have studied untreated psoriatic patients without a history of diabetes mellitus and smoking. In psoriatics, platelet aggregation elicited by thrombin, ADP, and ristocetin was significantly enhanced as compared with healthy adult volunteers. Enhancement of platelet aggregation was detected in patients with both minimal and widespread disease. The formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), a cyclooxygenase product, and 12-HETE, a 12-lipoxygenase product, was increased in psoriatics with widespread disease but not in those with minimal disease. Formation of 12-HETE was stimulated to a higher degree (125%) than HHT (98%) in psoriasis (P less than 0.05). Addition of platelet-derived 12-HETE to cultured human epidermal keratinocytes resulted in a stimulation of the DNA synthesis (68% at 10(-7) M). These data suggest that platelet activation occurs in psoriasis, and that release of inflammatory and mitogenic compounds by activated platelets may play a role in the pathophysiology of psoriasis. Whether enhanced platelet aggregation in psoriasis is associated with occlusive vascular disease needs further investigation.

Topical application of nonsteroidal anti-inflammatory drugs prevents vehicle-induced improvement of psoriasis.

In a double-blind fashion, we compared the effect of topical application of 1% indomethacin cream or 1% meclofenamate cream with the effect of vehicle therapy alone in thirty patients with psoriasis. After 4 weeks' treatment of bilaterally symmetric psoriatic plaques, the indomethacin-treated sides were worse than the vehicle-treated sides in fourteen of twenty patients (p less than 0.01); the meclofenamate-treated sides were worse than the vehicle-treated sides in seven of ten patients (p less than 0.05). We suspect that the nonsteroidal anti-inflammatory drugs contributed to the maintenance of our patients' psoriasis by altering the arachidonic acid transformation cascade.