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• BACKGROUND AND DESIGN.— To avoid systemic side effects, topical and intralesional administration of cyclosporine has been used; however, only intralesional administration has been successful. To understand more about the dosing requirements and resultant tissue levels of intralesional cyclosporine, we injected psoriasis plaques in a double-blind fashion with three different concentrations of cyclosporine (17 mg/mL in seven patients, 10 mg/mL in 13 patients, and 2.5 mg/mL in 11 patients) or matching vehicle three times weekly for 4 weeks. RESULTS.— Statistically significant improvement was observed in plaques treated with 17 mg/mL (P =.003) compared with vehicle-treated plaques; the improvements in plaques treated with 10 mg/mL (P=.078) and 2.5 mg/mL (P=.054) achieved marginal statistical significance compared with vehicle treatment. Four weeks after discontinuation of ther

• In an 8-week double-blind trial of sulfasalazine for the treatment of moderate-to-severe psoriasis, 23 and 27 patients received the active and placebo tablets, respectively. At the end of the double-blind phase, there were 17 assessable patients receiving sulfasalazine; 7 (41%) had marked improvement, 7 (41%) had moderate improvement, and 3 (18%) demonstrated minimal change. Only 1 patient receiving placebo demonstrated moderate improvement, whereas the rest had minimal improvement or worsening of psoriasis. When the randomization code was broken, patients receiving sulfasalazine were allowed to continue therapy for an additional 4 weeks in an open manner, while those using placebo left the study. Six of 23 patients discontinued sulfasalazine therapy during the double-blind phase because of side effects, 4 due to the development of a cutaneous eruption and 2 due to nausea. Fourteen of 17 patients, who were assessable at the end of the 8-week double-blind phase, completed the additional 4 weeks of sulfasalazine therapy. Of these 14 patients, marked improvement occurred in 8 (57%), moderate improvement in 2 (14%), and minimal improvement in 4 (29%), compared with pretherapy. The low incidence of severe side effects makes sulfasalazine a consideration for oral therapy in patients whose disease severity does not justify use of methotrexate, etretinate, or psoralen plus UV-A, but whose disease severity is too widespread for safe and practical use of topical corticosteroids.(Arch Dermatol. 1990;126:487-493)

BACKGROUND AND DESIGN: The ability of superficial dermabrasion to improve clinical features of photoaged skin is well known, but the specific biological mechanisms involved are poorly understood. The so-called repair zone, as visualized by routine histologic examination, has been attributed to new collagen formation within the papillary dermis and may be responsible for clinical improvement following dermabrasion. We investigated molecular and histologic events occurring in dermabraded skin and correlated them with clinical improvement. Ten photoaged patients (mean age, 59 years) underwent facial dermabrasion to the level of the papillary dermis. Clinical severity of photoaging was graded in a blinded manner at baseline and 12 weeks after dermabrasion. Biopsy specimens obtained at baseline and 3 and 12 weeks after dermabrasion were analyzed histologically and by in situ hybridization for fibroblast procollagen I mRNA, immunohistologically and by Western blotting with a monoclonal antibody specific for the aminoterminal cleavage site of procollagen I. RESULTS: Masson's trichrome staining demonstrated an increase in collagen from baseline (as an upper dermal band in the dermabrasion ''repair zone'') at 3 and 12 weeks' postdermabrasion. Immunohistologic examination demonstrated papillary dermal fibroblast staining for procollagen I at baseline that increased by threefold at 3 weeks' postdermabrasion and by 1.5-fold at 12 weeks' postdermabrasion. Western blotting demonstrated an average-fold increase in pN collagen I of 4.2± 1.5 at 3 weeks and of 2.7±0.7 at 12 weeks. By in situ hybridization, baseline levels of procollagen I mRNA in papillary dermal fibroblasts increased sixfold at weeks 3 and 12 postdermabrasion. Increase in procollagen I mRNA correlated with clinical improvement, ie, reduction in wrinkling. CONCLUSION: Superficial dermabrasion clinically improves photoaged skin, and this improvement correlates strongly with increased collagen I gene expression.(Arch Dermatol. 1994;130:1136-1142)

BACKGROUND AND DESIGN: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. RESULTS: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild ''retinoid dermatitis'' occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution.Conclusions: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.(Arch Dermatol. 1994;130:727-733)

† BACKGROUND AND DESIGN.— The assessment of the severity of cutaneous photodamage and its response to treatment is an impractical consideration for most practitioners without extensive experience or recourse to high-quality, standardized, baseline photographs. To address this problem, a ninepoint photonumeric standard scale was developed using photographs of subjects representing grades of photodamage from none to severe. This scale was formally tested in a side-by-side comparison with a conventional and widely used written descriptive scale. A panel of seven graders used both scales to score two sets of 25 photographs of photodamaged individuals, and the intergrader agreement and repeatability for the scales were calculated. RESULTS.— The photonumeric scale demonstrated significantly greater agreement between graders than did the descriptive scale (chance-corrected agreements of 0.31 and 0.11, respectively, P<.0001) with no significant difference in repeatability between the two methods. CONCLUSIONS.— This study demonstrates that the photonumeric standard scale is superior to existing methodology in the accurate assessment of cutaneous photodamage and would be a useful adjunct to studies of the efficacy of skin repair agents for this indication.(Arch Dermatol. 1992;128:347-351)

• A histologic study was designed to evaluate the pilosebaceous unit of the scalp in nonpustular patch- and plaque-stage psoriasis. Punch biopsy specimens from involved and uninvolved areas of 28 patients were sectioned in a horizontal plane for qualitative and quantitative study. All samples were evaluated in a blind mode, and data were analyzed for statistical significance. There was no evidence for alopecia of any type. Sebaceous gland atrophy was a frequent concomitant in the psoriatic lesion, with probable down-sizing of the hair follicle and thinner hair shafts. Paradoxical sebaceous gland atrophy and down-sized hair follicles in psoriasis may be due to possible inhibiting effects of yet unidentified factors produced by the epidermal lesion.(Arch Dermatol. 1989;125:639-642)

† Findings from an eight-week fish oil-supplemented diet given to 13 psoriatic patients demonstrated that eicosapentaenoic acid (20:5,n3 [EPA]) and docosahexaenoic acid (22:6,n3 [DCHA]) are rapidly incorporated into the sera, neutrophils, and epidermis of participating patients, and that the incorporation of EPA and DCHA into epidermal lipids increased with weeks of supplementation with minimal alteration of arachidonic acid (AA) in the epidermal lipids. Global clinical evaluation showed that eight patients demonstrated mild to moderate improvement in their psoriatic lesions. Improved clinical response correlated with high EPA/DCHA ratios attained in epidermal tissue specimens. These findings underscore the need for further investigations into the role of dietary n3 fatty acids, particularly the possibility of pentaenoic acid as a potential protective agent and/or therapeutic adjunct for the clinical management of psoriasis.(Arch Dermatol 1986;122:1277-1282)

• The HLA type of patients with various kinds of immune reactions to bovine collagen implants were evaluated to determine a possible genetic basis for such responses. All patients suffering adverse clinical reactions to bovine collagen implants were lacking the HLA-DR4 antigen. All patients who received multiple bovine collagen injections without having adverse clinical reactions were lacking HLA-B5 and HLA-DR5 and had a significantly increased incidence of HLA-DR4. Combinations of histocompatibility antigens may influence immune response to bovine collagen implants.(Arch Dermatol 1986;122:650-654)

Long-term sun exposure (UV-A and -B light) results in characteristic clinical changes of the skin (eg, wrinkles, lentigines, elastosis, roughness, and sallowness) collectively known as photodamage.1 We observed that a number of our patients have asymmetrical facial photodamage, with the left side of the face appearing more severely photodamaged than the right side. We postulated that this perceived left-sided predominance of severe photodamage may have arisen from exposure to UV light while driving a left-hand-drive automobile. We performed a study designed to test this hypothesis. METHODS. A total of 120 patients (age range, 43 to 81 years; mean, 62 years; 105 female and 15 male subjects) were recruited through the mail using a questionnaire that obtained the following information: age, sex, occupation, percentage of time spent as an automobile driver, number of years as a driver, number of hours driven per week, and the percentage of time driving with

TO THE EDITOR.— In the July 1985 issue of the Archives, we reported reduction of antibody-dependent cell-mediated cytotoxicity (ADCC) of polymorphonuclear leukocytes obtained from patients during etretinate therapy for psoriasis.1 To further examine the immunomodulatory effect of the retinoid, we also monitored natural killing (NK) activity of lymphocytes and ADCC of monocytes obtained from the same study patients, comparing the activities with those of control subjects.Lymphocytes for the NK cell cytotoxicity assay were isolated by collecting nonadherent monocytes after Ficoll-Hypaque density centrifugation. A human myeloid cell line (K562) was used as the target cell. Radioactive labeling of K562 cells by sodium chromate Cr 51 was accomplished as previously described.2 For the assay, lymphocyte effector cells were incubated with the K562 target cells at three effector-to-target ratios (10:1, 5:1, and 2:1). The rest of the assay procedure and calculation of the percent of cytotoxicity were identical to methods