Generalized pruritus without primary lesions. Differential diagnosis and approach to treatment.

A 65-year-old man presented with recurrent generalized pruritus and excoriations of many years' duration. He had been treated with antihistamines, topical corticosteroids, and antibiotics for secondary wound infections, but improvement was only temporary. He had also been hospitalized for leg ulcers complicated by cellulitis. Examination revealed multiple oval and linear red papules and nodules measuring 0.5 to 2 cm in diameter. Some of the lesions were eroded and had a central crater and yellowish crust. The patient also had hypopigmented linear scars localized to the posterior scalp, neck, upper back, chest, abdomen, arms, and legs with sparing of the middle and lower back (figures 1 and 2). An ulcer measuring 1.5 x 2 cm that was surrounded by indurated skin was present on the medial aspect of his right ankle. The ulcer was partially covered by yellow exudate. There was no evidence of cellulitis. Liver enzyme, serum creatinine, and thyrotropin levels, as well as a chest roentgenogram, were normal. Wound cultures for bacteria and fungi were nonsignificant. A punch biopsy from a representative lesion showed an abrupt epidermal defect with sparse superficial lymphocytic infiltrate in the dermis. The patient was admitted to the hospital to isolate him from his home environment. He received a 10-day course of systemic cephalexin, topical clobetasol propionate ointment for the affected skin areas, and oral hydroxyzine for pruritus. Ultraviolet light therapy was instituted once daily and was to continue for 2 months. His lesions had improved moderately by the time he was discharged from the hospital. On follow-up 2 weeks later, his lesions were flat and had resulted in hypopigmented scars. Three months later, however, he had persistent, intense pruritus, and new excoriations had developed on his forearms and back. He improved after receiving treatment with oral doxepin hydrochloride.

Wavelength and fluence effect on vascular damage with photodynamic therapy on skin.

Normal skin phototoxicity is clinically predictable during photodynamic therapy with light at 690 and 458 nm wavelengths, in the first 5 h after intravenous bolus infusion of benzoporphyrin derivative mono-acid ring A. This study goal was to determine histologic milestones that lead to tissue necrosis with exposure to red (690 nm) and blue (458 nm) light. The threshold doses for skin necrosis on rabbits were equal at both wavelengths. Lower, equal to, and higher than threshold fluences were delivered in duplicates at hourly intervals, with 40% increments, at constant irradiance. Pathology specimens from irradiated and control sites, were collected at 0, 2, 7, 24, 48 h, and 2 wk after treatment and were paired to equivalent treated sites for clinical evaluation. Immediately after irradiation, at 690 and 458 nm thresholds, light microscopy showed stasis and inflammatory infiltrate in the papillary dermis, respectively; electron microscopy demonstrated pericyte and endothelial cell damage - greater at 690 than 458 nm. At day 1, vascular stasis in the dermis showed a steeper dose-response with red than blue light, and led to necrosis of skin appendages (day 1) and epidermis (days 1-2) at both wavelengths. Sub-threshold fluences induced similar, but significantly milder (p < 0.05) changes and epidermis recovered. Skin necrosis, at threshold fluences in photodynamic therapy with benzoporphyrin derivative mono-acid ring A, was primarily due to vascular compromise to a depth potentially reaching the subcutaneous muscle at 690 nm, whereas at 458 nm vascular damage was confined to upper dermis. This system facilitates selective destruction of skin vasculature, sparing normal epidermis.

Predictive dosimetry for threshold phototoxicity in photodynamic therapy on normal skin: red wavelengths produce more extensive damage than blue at equal threshold doses.

The goal of this investigation was to establish methodology to determine and prevent phototoxic responses of normal skin to photodynamic therapy (PDT). The drug used was a second-generation photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA). The dependence of skin phototoxicity on drug dose (0.5-2.0 mg/kg), fluence (1.2-390 J/cm2), and wavelength (690 nm and 458 nm) was studied in the New Zealand albino rabbit in the first 5 h after injection. Skin responses were recorded for 2 wk after irradiation. Noninvasive measurements of drug fluorescence were made on unexposed skin sites during the first 5 h after drug injection. Immediate responses to PDT included erythema induced by 458 nm light and blanching induced by 690 nm light. Delayed reactions included edema on the day of exposure, purpura at 24 h, eschar by day 2 or 3, and scar by the end of follow-up. The threshold fluence for immediate responses correlated strongly with the threshold fluence for delayed reactions. The induction of threshold purpura on day 1 was a reliable index for skin phototoxicity that led to necrosis. The minimum purpura dose on day 1 after irradiation increased exponentially with the interval between drug injection and irradiation, independent of irradiation wavelength, for all drug doses. The action spectrum for threshold purpura mimics closely the absorption spectrum of BPD-MA. The in vivo drug fluorescence correlated with skin phototoxicity, thus allowing predictive dosimetry. This model system defines the safety limits for skin phototoxicity of PDT with BPD-MA.

Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is increasingly employed for skin cancer, yet ALA dosing is crude. Using iontophoresis, we developed a rapid and quantifiable system for topical ALA delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy volunteers. Six doses of ALA were delivered with a series of charges varying from 3-120 milliCoulombs (mC); four additional doses were given with a charge of 60 mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow-red light, the series of six ALA doses receiving 100 J/cm2, while the four identical doses received 6.25, 12.5, 25, and 50 J/cm2, respectively. Resultant erythema was measured by reflectance spectroscopy. The time course of PpIX fluorescence was ALA-dose-dependent. With charge < or = 24 mC, PpIX fluorescence peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre-irradiation and fall in PpIX fluorescence post-irradiation correlated with erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent, and phototoxicity can be predicted from ALA dose, irradiation dose, and photobleaching of PpIX. This reproducible system allows accurate dosimetry in topical PDT and facilitates study of ALA metabolism.

Dietary and other risk factors in the aetiology of cholelithiasis: a case control study.

We studied the effect of dietary factors and a variety of other risk factors on the development of cholelithiasis through a case control study. The study involved 96 cases and 118 age and sex matched controls. All cases and controls were interviewed with regard to a variety of risk factors and frequency of consumption of over 100 food items. Analysis was done both by chi square and a multiple logistic regression model. From all the dietary factors the only ones that showed a positive statistically significantly (p less than 0.05) association was consumption of animal fat as expressed by eating all visible fat on the meat and using butter on the table. Interestingly high consumption of olive oil had a negative (protective) association with the disease. A negative association was also found with smoking and holding a job demanding hard labor.