Biomedical subjects
Publications and source records attributed to N J Lowe.
The awareness of sun-induced skin damage has increased in both the lay public and physician. Coincidentally, there has been progress in the development of new ultraviolet-(UV) radiation protecting sunscreens. In this review and update on sunscreens, sunscreen classification, UVB and UVA protection, sunscreen vehicle, and substantivity will be addressed.
The persistence of facial telangiectasis and erythema in patients with rosacea frequently presents a major cosmetic problem. It may also contribute to relapses of papular and pustular lesions. This study of 27 patients treated for their telangiectasia and erythema with a flash lamp pumped dye laser tuned at 585 nm is described. The laser gave good or excellent reduction of telangiectasia and erythema and overall appearance in 24 of the patients with between one and three treatments. In addition, papule and pustule activity was decreased in 59.2% of the patients, with those with the most severe pre-treatment activity having the most significant improvement. It is suggested that this is a useful additional form of treatment that may improve the telangiectasia and erythematous component of rosacea.
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We have evaluated the in vivo effects of 13-cis retinoic acid (13-cis RA) on human antibody responses to immunization with tetanus toxoid (TT) and keyhole limpet hemocyanin (KLH). Subjects with severe cystic acne were immunized with suboptimal doses (10 micrograms) of KLH 7 d and 3 months after starting retinoid therapy (13-cis RA, 1 mg/kg/day for 4 mo). A standard booster immunization with TT was given along with the initial KLH sensitization. A control group of acne patients received identical immunization regimens, but no 13-cis RA. Plasma retinoid levels were evaluated by reverse-phase HPLC and confirmed that blood-level concentrations of 13-cis RA and metabolites in these acne patients reached values previously demonstrated to be immunomodulatory in vitro. The retinoid had no effect on responses to TT as reflected by the characteristics of increased anti-TT IgG levels or the isotype distribution of the antibody. In contrast, the anti-KLH response was significantly enhanced in the 13-cis-RA-treated group. Whereas anti-KLH antibody was detected in only 4 of 13 control subjects after the secondary immunization, 10 of 13 retinoid-treated subjects had measurable levels of anti-KLH IgG (p less than 0.05). Among the responders, no differences were noted in the isotype distribution of anti-KLH antibody. These results showing enhanced anti-KLH responses induced by 13-cis RA therapy represent the first demonstration in humans that in vivo administration of a retinoid can modulate antigen-specific immune responses.
It has been well established in both human and animal skin that ultraviolet radiation from both ultraviolet B (UVB) (290 nm-320 nm) and ultraviolet A (UVA) (320 nm-420 nm) can produce profound changes in the skin that with recurrent exposure, cause it to become what we recognize as photoaged skin. Experimental studies in animals have confirmed that some sunscreen chemicals are capable of providing protection against ultraviolet-induced photoaging. It is presumed that regular use of these effective sunscreens will also reduce skin aging changes in humans.
Sunscreens are agents that attenuate the effects of ultraviolet radiation on the skin by absorption or reflection of part of the incident radiation or by interception of harmful products of its interaction with the Sunscreens may be applied topically or ingested; however, topical agents are by far the more common and effective and only they will be discussed in this report. Topical sunscreens are formulated as creams or lotions and are characterized by their sun protection factor, a measure of their efficacy against sunburning and their substantivity, their resistance against removal after application.
We report a retrospective review of 18 patients with pityriasis rubra pilaris treated with isotretinoin or etretinate, or both. Of patients treated with only isotretinoin, 60% have achieved sustained resolution. Of four patients treated with etretinate, three have cleared completely and the other patient has shown substantial improvement. Our data suggest that etretinate may be superior to isotretinoin in the treatment of adult-onset pityriasis rubra pilaris.
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The use of 8-methoxypsoralen water soaks plus ultraviolet A was evaluated retrospectively in 11 patients with moderate to severe palmoplantar psoriasis that had been resistant to previous topical therapies. Patients received twice- or thrice-weekly 30-minute hand and/or foot soaks in 8-methoxypsoralen, 2.5 mg/L, followed by UVA irradiation. The condition of one patient cleared completely, and seven showed good improvement. The range of treatments required for maximal improvement was 14 to 43 with a mean of 28. The range of maximum UVA dosage per treatment was 3.5 to 17.5 joules/cm2, and the range of cumulative UVA required for maximal improvement was 45 to 388 joules/cm2 with a mean of 165 joules/cm2. The mean serum level of 8-methoxypsoralen 60 minutes after completion of hand and foot soaks was 2.5 +/- 0.5 ng/ml compared with 95.75 +/- 10.43 ng/ml after oral 8-methoxypsoralen, 0.5 mg/kg. In our experience this treatment has been a safe and relatively effective form of therapy for resistant palmoplantar psoriasis.
The efficacy of a new hydrocolloid dressing occlusion, alone or with 0.1% triamcinolone cream, was compared with triamcinolone acetonide alone or under plastic film occlusion in the treatment of localized plaque-type psoriasis. Thirty-eight patients were randomly assigned to one of four bilateral, paired-comparison treatment groups. Patients underwent 3 weeks of treatment, after which they were followed up for an additional week. After 3 weeks hydrocolloid occlusion with triamcinolone acetonide yielded a significantly better response than the cream alone or the hydrocolloid dressing alone, but the new dressing was comparable to a plastic film occlusive dressing of triamcinolone acetonide. After discontinuation of treatment, however, the sites that had been treated with hydrocolloid-occluded triamcinolone acetonide retained the better results. Topical steroids under hydrocolloid occlusive dressing may be a useful alternative to steroids alone for treatment of localized recalcitrant psoriasis.
Mucocutaneous side-effects from etretinate are common and are usually dose-dependent, whereas hypersensitivity drug eruptions are rare. Two patients are described in whom erythema multiforme-like eruptions appeared several days after oral intake of etretinate. In one patient etretinate rechallenge again produced the skin eruption. A brief review of the less common skin manifestations of etretinate therapy is provided.
A patient with Darier's disease was discovered to have persistent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. The spinal abnormalities have remained asymptomatic but have now progressed following 4 years of etretinate therapy. The development of skeletal abnormalities, in particular spinal hyperostosis, is well-documented in patients receiving the synthetic retinoid, isotretinoin (Accutane, Roaccutane). The occurrence of extraspinal tendon and ligament calcification has been emphasized following long-term therapy with etretinate (Tegison, Tigason), but the relationship between etretinate and spinal hyperostosis is less certain, there being a need for a long-term, prospective, appropriately controlled investigation of patients receiving etretinate. We report a patient with Darier's disease who was discovered to have prominent, asymptomatic cervical and thoracic spinal hyperostoses after receiving isotretinoin for 7 years. Subsequent treatment with etretinate for 4 years did not prevent progression of the spinal abnormalities.
Nineteen patients with severe or recalcitrant rosacea were treated twice daily with 0.75 percent metronidazole topical gel in an open label study. Sixteen of the patients (84 percent) showed 50 percent or greater reduction in inflammatory lesions, while fifteen (79 percent) demonstrated a reduction in erythema severity and an improvement when evaluated by the investigator global assessment. No positive response was recorded for any patient prior to topical medication, whereas six of nine patients previously treated with tetracycline/minocycline demonstrated improvement. Seven of these nine patients responded to topical metronidazole treatment. One additional patient who did not respond to minocycline or desonide treatment showed a good response to topical metronidazole. Only one patient reported local irritation after using metronidazole. These results demonstrate that topical metronidazole gel is safe and effective for the treatment of severe or recalcitrant rosacea.
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Comparison in ultraviolet (UV) dosimetry is reported for three different phototherapy machines. Two of the machines used UV-emitting fluorescent tubes in a standard upright cabinet formation. One of these machines was equipped with predominantly UVB-emitting fluorescent tubes and the other with predominantly UVA-emitting tubes. The third machine consisted of a series of vertically mounted high-pressure mercury halide lamps equipped with two different filters for selection of wavelengths between 295 and 400 nm or 320 and 400 nm. The horizontal UV output of the mercury halide and UVB fluorescent units was reduced between the UV-emitting areas, and it is advised that patients rotate when using these units. It was determined that the vertical uniformity and intensity of UV emission was superior in the mercury halide unit compared with the fluorescent tubed units.
Although retinoid derivatives are an effective treatment for severe psoriasis, they result in systemic toxicity, including hyperlipidemia. In an attempt to reverse this retinoid-related hyperlipidemia in patients with psoriasis, a prospective 4-week pilot study of fish oil supplementation was carried out in 25 patients with psoriasis vulgaris receiving etretinate (Ro-10-9359) or acitretin (Ro 10-1670). Daily fish oil supplements containing 3 gm of omega-3 fatty acids (1.8 gm of eicosapentaenoic acid 20:5 omega 3, and 1.2 gm of docosahexaenoic acid 22:6 omega 3) were found to be effective in reducing hypertriglyceridemia, with a significant mean reduction from 215.6 +/- 92.5 to 156.9 +/- 58.5 mg/dl (-27%) when compared with controls (203.6 +/- 46.9 to 204.1 +/- 54.3 mg/dl). High-density lipoprotein cholesterol levels increased from 41.4 +/- 10.5 to 46.1 +/- 10.8 mg/dl (+11%), and the ratio of total cholesterol to high-density lipoprotein cholesterol decreased from 6.6 +/- 1.9 to 5.9 +/- 1.7 (-11%). It is concluded that fish oil supplementation may prove a valuable adjunct to ameliorate the lipid changes secondary to retinoids.
Retinoids are potent therapuetic agents that have been found to be effective in a variety of skin diseases. They are of benefit in various forms of severe psoriasis. With severe plaque psoriasis, they are used most effectively in combination with other forms of therapy, such as phototherapy. With generalized pustular psoriasis, they are effective monotherapy and are frequently helpful for the control of exfoliative psoriasis. A variety of new retinoid analogs have been studied in clinical investigations. This article discusses important aspects of the use of etretinate, isotretinoin, acitretin, and arotinoid ethyl ester in the treatment of severe forms of psoriasis.