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Importance Indoor tanning is prevalent among young adults and women and is associated with increased risk of melanoma. Evidence suggests that indoor tanners may be more inclined to adopt poor photoprotective practices that further increase their risk of skin cancer; however, gaps in the literature exist in young adults and by indoor tanning frequency. Objective To examine the association between indoor tanning frequency and behaviors related to skin cancer prevention and to investigate whether these associations vary by age group or sex. Design, Setting, and Participants Cross-sectional population-based study of US 2015 National Health Interview Survey data including 10 262 non-Hispanic white adults aged 18 to 60 years without a history of skin cancer. Main Outcomes and Measures Rare/never use of sunscreen, protective clothing, shade; multiple sunburns within the past year; previous full-body skin examination. Results Of the 10 262 individuals in our study population (49% female; median age, 39 y), 787 (7.0%) reported having tanned indoors in the past year. Among individuals aged 18 to 34 years, frequent indoor tanners (≥10 times in the past year) were more likely to report never/rare use of protective clothing (adjusted prevalence ratio [aPR], 1.28; 95% CI, 1.10-1.49) and shade (aPR, 1.32; 95% CI, 1.03-1.70), compared with individuals who did not tan indoors. Among women aged 18 to 60 years, those who frequently tanned indoors were more likely to rarely/never use sunscreen (aPR, 1.34; 95% CI, 1.11-1.62), protective clothing (aPR, 1.27; 95% CI, 1.15-1.42), and shade (aPR, 1.54; 95% CI, 1.25-1.90) on a warm sunny day, as well as more likely to report multiple sunburns in the past year (aPR, 1.21; 95% CI, 1.00-1.45) compared with those who did not tan indoors. Individuals who tanned indoors in the past year were not significantly more likely to have undergone a previous full-body skin examination in any subpopulation examined. Conclusions and Relevance Individuals who tan indoors often exhibited a concurrent tendency to sunburn, avoid sun protection, and avoid skin cancer screening. Thus, the findings highlight that in addition to tanning bed avoidance, it is critical to emphasize sun protection and skin cancer screening in individuals who tan indoors.

Objective To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses. Design Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation. Setting Academic referral center. Patients Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment. Main Outcome Measures Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires. Results One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1β), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again. Conclusions Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.

Objective To evaluate the effectiveness of topical estradiol in stimulating collagen I and III production in naturally aged and photoaged human skin of postmenopausal women and age-matched men. Design Vehicle-controlled treatment followed by biochemical and immunohistochemical analyses of skin biopsy specimens. Setting Academic referral center. Participants Seventy healthy volunteers (40 postmenopausal women with a mean age of 75 years, and 30 men with a mean age of 75 years) with photodamaged skin. Interventions Topical application of estradiol, 0.01%, 0.1%, 1%, or 2.5% or vehicle on aged or photoaged skin, with biopsy specimens taken after last treatment. Main Outcome Measures De novo synthesis of collagen by quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Results Topical estradiol increased procollagen I and III messenger RNA and collagen I protein levels in sun-protected aged hip skin in postmenopausal women and, to a lesser extent, in age-matched men. Surprisingly, no significant changes in production were observed in women or men after 2-week estradiol treatment of photoaged forearm or face skin, despite similar expression of estrogen receptors (ER-α, ER-β, and GPR30) in aged and photoaged skin. Estradiol treatment induced the estrogen-responsive gene GREB1 , indicating that penetration of topical estradiol and genomic response to estrogen were similar in the 3 anatomic sites. Conclusions Two-week topical estradiol treatment stimulates collagen production in sun-protected hip skin, but not in photoaged forearm or face skin, in postmenopausal women and aged-matched men. These findings suggest that menopause-associated estrogen decline is involved in reduced collagen production in sun-protected skin. Interestingly, alterations induced by long-term sun exposure hinder the ability of topical 2-week estradiol to stimulate collagen production in aged skin. Trial Registration clinicaltrials.gov Identifier:NCT00113100

Objective To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. Design Randomized, double-blind, vehicle-controlled, left and right arm comparison study. Setting Academic referral center. Patients The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. Intervention Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. Main Outcome Measures Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. Results After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (−1.64 [95% CI, −2.06 to −1.22] vs −0.08 [95% CI, −0.17 to 0.01]; P P = .02 [n = 6]) and procollagen I immunostaining ( P = .049 [n = 4]) compared with vehicle. Conclusions Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance. Trial Registration clinicaltrials.gov Identifier:NCT00272610

To determine whether endogenous synthesis of new extracellular matrix may contribute to the degree and duration of clinical benefits derived from cross-linked hyaluronic acid dermal filler injections.In vivo biochemical analyses after filler injections.Academic referral center.Eleven healthy volunteers (mean age, 74 years) with photodamaged forearm skin. Interventions Filler and vehicle (isotonic sodium chloride) injected into forearm skin and skin biopsy specimens taken 4 and 13 weeks later.De novo synthesis of collagen, the major structural protein of dermal extracellular matrix, was assessed using immunohistochemical analysis, quantitative polymerase chain reaction, and electron microscopy.Compared with controls, immunostaining in skin receiving cross-linked hyaluronic acid injections revealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and N-terminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (P.05). Gene expression for types I and III procollagen as well as several profibrotic growth factors was also up-regulated at 4 and 13 weeks compared with controls (P.05). Fibroblasts in filler-injected skin demonstrated a mechanically stretched appearance and a biosynthetic phenotype. In vitro, fibroblasts did not bind the filler, suggesting that cross-linked hyaluronic acid is not directly stimulatory.Injection of cross-linked hyaluronic acid stimulates collagen synthesis, partially restoring dermal matrix components that are lost in photodamaged skin. We hypothesize that this stimulatory effect may be induced by mechanical stretching of the dermis, which in turn leads to stretching and activation of dermal fibroblasts. These findings imply that cross-linked hyaluronic acid may be useful for stimulating collagen production therapeutically, particularly in the setting of atrophic skin conditions.

Objective To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO 2 ) laser resurfacing of photodamaged human skin. Design Serial in vivo biochemical analyses after laser therapy. Setting Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO 2 laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment. Main Outcome Measures Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1β and tumor necrosis factor α; and profibrotic cytokine transforming growth factor β1. Results Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1β, tumor necrosis factor α, and transforming growth factor β1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold), and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment. Conclusions The biochemical changes seen after CO 2 laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.

Objective To quantitatively examine changes in p53 tumor suppressor gene immunostaining after carbon dioxide (CO 2 ) laser resurfacing of photodamaged skin to assess the potential value of this treatment in reducing the risk of progression to cutaneous carcinoma. Design Serial in vivo immunohistochemical analyses after laser therapy. Setting Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Other Participants Volunteer sample of 11 adults, 51 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO 2 laser resurfacing of photodamaged forearms and serial biopsies at baseline, 3 weeks, and 6 months after treatment. Main Outcome Measures Because keratinocytes with mutations in p53 or altered p53 expression stain via immunohistochemical techniques, image analysis of immunohistochemically stained sections was used to quantify p53 expression. Results Positive immunostaining for p53 in the interfollicular epidermis was noted in 8 of 11 subjects at baseline, with an average staining density of 250 cells/mm 2 . Average staining decreased to 3 cells/mm 2 3 weeks after treatment. This decrease was sustained at 5 cells/mm 2 6 months after resurfacing. Conclusions There was a consistent decrease in p53 immunostaining in the interfollicular epidermis lasting for at least 6 moths after CO 2 laser resurfacing of photodamaged skin. Since p53 mutation or overexpression is observed in a majority of cases of cutaneous carcinoma, the posttreatment repopulation of the epidermis with p53-negative keratinocytes should theoretically decrease the risk of malignant progression. Further study of laser resurfacing as a prophylactic procedure in patients at high risk for skin cancer development appears warranted.

A 47-year-old woman presented with a 2-month history of progressive tightening of the skin on her legs. The tightening of her skin had begun 2 weeks after she was hospitalized for acute renal failure precipitated by therapy with nonsteroidal anti-inflammatory drugs. She had no history of renal disease or medical conditions that would predispose her to the organ failure. During her hospitalization, she was treated with supportive therapy only and did not require hemodialysis or peritoneal dialysis. Her renal function normalized, but the skin fibrosis continued to worsen. We initially examined her approximately 2 months after the onset of her skin disease. At the time, she had orangered indurated plaques on both thighs and the lower part of her legs. The range of motion of her knees was diminished so much that ambulation had become difficult. She denied any signs or symptoms of photosensitivity, Raynaud symptom, or esophageal dysfunction. Serologic evaluation includedanti-Scl70, anti-Sm,anti-ribonucleoprotein, anti-Ro, anti-La, and serum protein electrophoresis, the results of which were all negative. A skin biopsy specimen from an affected area revealed diffuse fibroblastic proliferation, with increased collagen and mucin in the dermis. These changes were consistent with nephrogenic fibrosing dermopathy (NFD). THERAPEUTIC CHALLENGE

ContextThe high prevalence of acne vulgaris and its significant morbidity underscore the need for convenient, low-risk, and efficacious therapy. Treatment with various lasers has been reported to improve acne.ObjectiveTo evaluate the clinical efficacy of pulsed dye laser therapy in the treatment of acne.Design, Setting, and PatientsRandomized, single-blind, controlled, split-face clinical trial of a volunteer sample of 40 patients aged 13 years or older with facial acne conducted at an academic referral center from August 2002 to September 2003.InterventionOne or 2 nonpurpuric pulsed dye laser treatments to half of the face (fluence of 3 J/cm2), serial blinded clinical assessments (lesion counts), and grading of acne severity using standardized bilateral serial photographs.Main Outcome MeasuresComparison of the changes in lesion counts from baseline to 12 weeks between treated and untreated sides of the face and changes in photographic evidence of acne severity as graded by a panel of dermatologists blinded to treatment assignment.ResultsAfter 12 weeks, using intent-to-treat analysis with last observation carried forward, there were no significant differences between laser-treated and untreated skin for changes in mean papule counts (−4.2 vs −2.2; P = .08), mean pustule counts (0 vs −1.0; P = .12), or mean comedone counts (2.9 vs 1.6; P = .63). Grading of serial photographs confirmed the clinical assessments, showing no significant mean (SE) differences in Leeds scores (range, 1-12) for treated skin (3.98 [0.32] at baseline and 3.94 [0.27] at week 12) compared with untreated skin (3.83 [0.32] at baseline and 3.79 [0.28] at week 12) (P>.99).ConclusionsIn this study, the nonpurpuric pulsed dye laser therapy did not result in significant improvement of facial acne. More research is needed before this laser therapy may be recommended as an acne treatment.

To determine safety and efficacy of monotherapy with etanercept.Randomized, double-blind, placebo-controlled, multicenter study.Outpatient, ambulatory; private practice and university dermatology research centers.Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug.Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study.Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures.After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups.Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

Khafif et al1and Selye2describe calciphylaxis as an acute local calcification affecting several organ systems, including the skin, kidney, and, less commonly, the lung, heart, and gastrointestinal tract. Cutaneous lesions characteristically begin as tender, violaceous, livedoid discolorations on the proximal aspect of the extremities and on the lower part of the abdomen. The lesions become indurated plaques and nodules that progress to necrotic deep ulcerations with eschar formation. Microscopic assessment reveals calcium deposition in the small and intermediate dermal vasculature with resultant epidermal ischemia and necrosis. While the pathogenesis is uncertain, the majority of cases of calciphylaxis have occurred in patients with chronic renal failure and secondary hyperparathyroidism. We report on a rare presentation of calciphylaxis in the absence of renal failure. Report of a Case. A 58-year-old white woman with alcoholic cirrhosis was admitted for management of ascites and skin ulcers and evaluation of a hepatic

Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth and differentiation. Hegemann et al 1 tested various PKC inhibitors in an immortalized keratinocyte cell culture. They showed that the degree of inhibition of cell proliferation was proportional to the potency of PKC inhibition. The authors speculated that PKC inhibitors might be effective for treatment of psoriasis. Hegemann et al showed that polymyxin B is a relatively potent inhibitor of PKC; however, unlike the other PKC inhibitors tested, polymyxin B caused little inhibition of cell proliferation in their culture system. Hegemann et al suspected that the polar polymer structure of polymyxin B prevented its penetration through keratinocyte cell membranes. Polymyxin B is in common use in over-the-counter preparations with an excellent safety record. Despite its poor inhibition of cell proliferation in culture, we performed a double-blind, randomized, bilateral, vehicle-controlled study comparing the effectiveness of topical polymyxin

REPORT OF A CASE We were asked to evaluate a ''pressure sore'' on the back of a 65-year-old white man admitted to the intensive care unit. The patient had a history of alcoholic cirrhosis for several years, and he was transferred from an outside hospital for persistent gastric variceal bleeding. A transjugular intrahepatic portosystemic shunt was performed. Postoperatively, aspiration pneumonia developed that necessitated ventilatory support. An ulceration on the middle of the patient's back was noted during the physical examination performed on admission to our institution. The ulceration did not improve after a week of local wound care, and the dermatology service was consulted. The patient was cachectic but comfortable and responsive. A 2.5-cm dark-red nodule with a central 1-cm ulceration was noted overlying the fifth thoracic vertebra (Figure 1). Intubation precluded obtaining a complete history, but it was ascertained that the lesion was asymptomatic and had been present for

Background and Design: The efficacy of topical tretinoin (all- trans -retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n=32), 0.025% tretinoin (n=35), or vehicle (n=32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. Results: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. Conclusions: Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoininduced repair of photoaging in humans. (Arch Dermatol. 1995;131:1037-1044)

Background and Design: A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole . The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this sub-specialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study. Results: A total of 155 such individuals were identified. The mean(±SEM) age of the patients at first evaluation was 26± 1 years. The group was followed for 7± 1 years. The male-female ratio was 1:1. A

REPORT OF A CASE A 42-year-old white man with human immunodeficiency virus (HIV) infection of 4 years' duration was admitted to Massachusetts General Hospital, Boston, for debilitating exacerbation of psoriasis. The skin condition, present for 3 years, had been reasonably controlled with UV-B phototherapy. For several weeks before admission, the patient had difficulty getting to the light therapy unit on a regular basis because of ambulatory problems. Progressively enlarging ''warts'' on his toes were becoming too painful for the patient to walk very far. Oxycodone with acetaminophen, morphine sulfate, and amitriptyline prescribed for his alcoholic neuropathy, manifested as leg pain, were being used for control of his toe pain. Except for HIV-associated hematologic changes, he had no other significant medical problems. In addition to the pain control medications, he was receiving zidovudine and ranitidine. He had no prior therapy for lesions on his toes. Findings from his physical examination revealed

• Background and Design.— Epiluminescence microscopy (ELM) is a clinical technique that permits in vivo visual inspection of pigmented anatomic structures of the epidermis, dermoepidermal junction, and papillary dermis. A protocol is proposed for systematic visual inspection of pigmented lesions. Seventy pigmented lesions were imaged with a digital ELM camera system. Images were visually inspected for eight "global" ELM features, 23 "local" ELM features, and 18 network features. An atlas of the most clinically significant ELM features is presented with pilot estimates of their sensitivity and specificity for detecting melanoma. Results.— Preliminary data suggest that ELM features that may be most specific for melanoma include multicomponent pattern, nodular pattern, pseudopods, radial streaming, blue-gray areas, whitish veil (milky way), and sharp network margins. Epiluminescence microscopic features that may be most sensitive for melanoma include pigment dots, peripheral erythema, peripheral dark network patches, marked mean network irregularity, network line thickness variability, radial streaming, blue-gray areas, and whitish veil (milky way). Epiluminescence microscopic features that may be most sensitive for severe melanocyte atypia include pigment dots, peripheral erythema, hypopigmented network patches, peripheral dark network patches, marked mean network irregularity, and focal absence of network. In addition, features that may have a very high specificity for benign lesions include saccular pattern (suggests hemangioma), globular pattern (suggests a compound or dermal nevus), and multiple comedolike openings (suggests seborrheic keratosis). Conclusions.— Features most sensitive for severe atypia and melanoma could form the basis for a screening test for considering biopsy. Features most specific for melanoma then could be applied to further triage management of pigmented lesions that meet initial screening criteria. In addition, features with very high specificity for benign lesions may help develop ELM criteria to avoid unnecessary surgery. ( Arch Dermatol. 1993;129:157-174)

• We reviewed 231 patients who developed recurrent disease 1 to 218 months after surgical therapy for clinical stage I cutaneous melanoma. Metastatic lesions amenable to surgery, including visceral recurrences, were resected. Adjuvant systemic chemotherapy/immunotherapy or regional hyperthermic perfusion was added in patients with unresected disease. Local irradiation was employed for nonresectable brain or other isolated symptomatic metastases. The overall 5-year survival rate after initial recurrence was 36%. In patients with soft tissue or nodal recurrence, the 5-year survival rates were 49% and 38%, respectively; six (11%) of 53 patients whose initial recurrence was in a visceral organ achieved prolonged remission. Primary lesion anatomic site, thickness, pathologic type, and interval from initial therapy to recurrence were unrelated to survival. Significant prognostic factors included the site of initial metastasis, stage of primary disease, and the successful complete eradication of gross disease by surgical excision or intensive chemotherapy. (Arch Surg.1991;126:703-708)

Since lipemia is commonly induced by retinoid therapy, we investigated the effects of etretinate administration on glucose metabolism by obtaining five-hour oral glucose tolerance tests in 23 patients before and after 20 weeks of etretinate therapy for psoriasis. Compared with pretreatment values, peak and aggregate levels for serum glucose and aggregate levels for serum insulin were significantly lower during therapy. The changes were not associated with obesity, weight loss during treatment, or pretherapy glucose tolerance or insulin secretion level. Of 11 patients with impaired or diabetic glucose tolerance prior to therapy, eight patients had improved glucose tolerance after 20 weeks of etretinate treatment. Despite inducing hypertriglyceridemia in most patients, etretinate therapy is associated with a reduction in glucose levels in response to a glucose load.

• We monitored the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from 14 patients with psoriasis before and during etretinate therapy. Neutrophils obtained from the patients with psoriasis at pretherapy demonstrated significantly greater cytotoxic activity than control cells. After four weeks of etretinate therapy, the cytotoxicity of neutrophils from the psoriatic patients decreased significantly and was no longer significantly different from the control value (at a 1:1 effector-to-target ratio). The decline in neutrophil cytotoxicity preceded significant clearing of our patients' psoriasis. The reduction in the antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes from patients with psoriasis occurs early during therapy and may represent one of the mechanisms of action of etretinate. (Arch Dermatol1985;121:877-880)

To the Editor.— In the July 1985 issue of theArchives, 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