Showing papers in "Archives of Dermatology in 2002"

Mechanisms of photoaging and chronological skin aging

Abstract: Human skin, like all other organs, undergoes chronological aging. In addition, unlike other organs, skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmental damage. The primary environmental factor that causes human skin aging is UV irradiation from the sun. This sun-induced skin aging (photoaging), like chronological aging, is a cumulative process. However, unlike chronological aging, which depends on the passage of time per se, photoaging depends primarily on the degree of sun exposure and skin pigment. Individuals who have outdoor lifestyles, live in sunny climates, and are lightly pigmented will experience the greatest degree of photoaging. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. This emerging information reveals that chronological aging and photoaging share fundamental molecular pathways. These new insights regarding convergence of the molecular basis of chronological aging and photoaging provide exciting new opportunities for the development of new anti-aging therapies. This article reviews our current understanding and presents new data about the molecular pathways that mediate skin damage by UV irradiation and by the passage of time.

The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.

Abstract: OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Correlations Between Clinical Patterns and Causes of Erythema Multiforme Majus, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis: Results of an International Prospective Study

Abstract: Background It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions. Objective To evaluate the validity of this clinical separation. Design Case-control study. Settings Active survey from 1989 to 1995 of 1800 hospital departments in Europe. Patients A total of 552 patients and 1720 control subjects. Methods Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome–toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups. Results Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme. Conclusions This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.

Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex.

Abstract: Background Hemangiomas of infancy vary widely in appearance, size, and depth of cutaneous involvement. There is currently no standard classification system for these lesions. While they occur in any race, an increased incidence occurs in girls, light-skinned whites, and premature infants, especially those weighing less than 1500 g. Other epidemiologic and demographic factors have not been well characterized. Objective To determine any correlations between hemangioma subtype and anatomic location with demographic factors, complications, and other associated anomalies. Design Retrospective chart review of 327 patients with hemangioma of infancy seen between 1997 and 2000 in an ambulatory referral center. Main Outcomes Measures Demographic and gestational information, lesion size, associated anomalies, complications, treatments, and outcomes were analyzed together with classification of hemangiomas into 4 groups: localized, segmental, indeterminate, and multifocal. Subtypes were correlated with race and ethnicity, the incidence of complications, and overall outcome. Results Of 472 hemangiomas (327 patients), 339 (72%) were localized, 84 (18%) were segmental, 37 (8%) were indeterminate, and 12 (3%) were multifocal (8 or more noncontiguous lesions). Segmental lesions were larger and were more frequently associated with developmental abnormalities. They also required more intensive and prolonged therapy and were associated with more complications and a poorer overall outcome ( P P P = .05), especially PHACE syndrome ( P = .05), and to have more complications ( P = .01). Increased incidence of segmental hemangiomas was the only factor in Hispanic infants associated with complications, more extensive treatment, or associated anomalies. Conclusions Hemangiomas of infancy can usually be classified as localized, segmental, indeterminate, and multifocal, based on clinical features. Segmental lesions have a higher frequency of complications and associated abnormalities, and this type of hemangioma seems to present with increased frequency in Hispanic infants.

Acne vulgaris: a disease of Western civilization.

Abstract: Background In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Ache hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. Observations Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Ache subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. Conclusions The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.

Follicular mycosis fungoides, a distinct disease entity with or without associated follicular mucinosis: a clinicopathologic and follow-up study of 51 patients.

Abstract: Objective To determine the clinicopathologic features and the disease course of patients with follicular mycosis fungoides (MF). Design A multicenter, 14-year, retrospective cohort analysis. Setting Dutch Cutaneous Lymphoma Group. Patients Fifty-one patients with the clinicopathologic features of follicular MF with (n = 49) or without (n = 2) associated follicular mucinosis. Follow-up data were compared with those of 158 patients with the classic epidermotropic type of MF, including 122 patients with generalized plaque-stage MF (T2 N0 M0) and 36 patients with tumor-stage MF (T3 N0 M0). Observations Characteristic clinical features not or rarely observed in classic MF were the preferential localization of the skin lesions in the head and neck region (45 of 51 patients), the presence of follicular papules, alopecia, acneiform lesions, mucinorrhoea, and often severe pruritus. Characteristic histologic findings were the presence of perifollicular neoplastic infiltrates with a variable degree of folliculotropism, but generally no epidermotropism, follicular mucinosis (49 of 51 cases), and often a considerable admixture of eosinophils and plasma cells. Response on initial treatment, risk of disease progression (development of extracutaneous disease and/or death from lymphoma), and disease-specific and overall survival of patients with follicular MF were worse than in classic MF patients. The actuarial disease-specific survival was 68% at 5 years and 26% at 10 years. Conclusions Follicular MF shows distinctive clinicopathologic features, is more refractory to treatment, and has a worse prognosis than the classic type of MF; it should be considered a distinct type of cutaneous T-cell lymphoma. Based on these results and those of other studies, we suggest the term follicular MF for cases with or without associated follicular mucinosis.

Treatment response of keloidal and hypertrophic sternotomy scars: comparison among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped pulsed-dye laser treatments.

Abstract: Objective To compare the clinical response of keloidal and hypertrophic scars after treatment with intralesional corticosteroid alone or combined with 5-fluorouracil (5-FU), 5-FU alone, and the 585-nm flashlamp-pumped pulsed-dye laser (PDL). Design Prospective, paired-comparison, randomized controlled trial. Setting A private ambulatory laser facility. Patients Ten patients with previously untreated keloidal or hypertrophic median sternotomy scars at least 6 months after surgery that were considered problematic by the patients. Interventions Five segments were randomly treated with 4 different regimens: (1) laser radiation with a 585-nm PDL (5 J/cm 2 ); (2) intralesional triamcinolone acetonide (TAC) (20 mg/mL); (3) intralesional 5-FU (50 mg/mL); and (4) intralesional TAC (1 mg/mL) mixed with 5-FU (45 mg/mL). One segment of each scar received no treatment and served as a control. Main Outcome Measures Scar height, erythema, and pliability were evaluated before and every 8 weeks after treatment. Patients' subjective evaluations were tabulated. Histologic sections of segments were examined in 1 biopsy sample per segment at week 32. Results There was a statistically significant clinical improvement in all treated segments. No significant difference in treatment outcome vs method of treatment was noted. However, intralesional formulas resulted in faster resolution than the PDL: scar induration responded better to intralesional formulas, scar texture responded better to the PDL, and scar erythema responded the same as the control with all treatments. Adverse sequelae, including hypopigmentation, telangiectasia, and skin atrophy, were observed in 50% (5/10) of the segments that received corticosteroid intralesionally alone. No long-term adverse sequelae were demonstrated in the segments treated with other modalities. Conclusions Clinical improvement of keloidal and hypertrophic scars after treatment with intralesional corticosteroid alone or combined with 5-FU, 5-FU alone, and PDL seemed comparable, with the exceptions of the incidence of adverse reactions, which were most common with intralesional corticosteroid. Intralesional 5-FU is comparable to the other therapies.

Dermoscopic examination of nail pigmentation

Abstract: Background: Diagnosis of longitudinal melanonychia is usually difficult, and neither a single clinical criterion nor a combination of symptoms currently can be used to clearly distinguish malignant from benign bandlike pig- mented nail lesions. Biopsy is painful and often leaves definitive dystrophic scars. Objectives: To describe and evaluate dermoscopic pat- terns associated with longitudinal nail pigmentation. Patients and Methods: A total of 148 unselected con- secutive cases of longitudinal melanonychia were included over a period of 4 years (20 melanoma, 37 nevi, 16 drug- induced nail pigmentation, 45 nail apparatus lentigo of vari- ous types, 8 ethnic-type nail pigmentation, and 22 subun- gual hemorrhages). All patients were recruited from the dermatology unit outpatient clinic of the Hotel Dieu de Lyon. All cases were photographed in vivo under oil im- mersion (dermoscopy). Patterns were recorded prior to fi- nal pathologic diagnosis. An independent biostatistics unit performed statistical evaluation using 7 semiologic patterns. Results: Melanoma cases were significantly associated with a brown coloration of the background and the pres- ence of irregular longitudinal lines (P=.001). Blood spots were mostly observed in subungual hemorrhages (P = .001); however, their presence could not rule out melanoma. Micro-Hutchinson sign was observed only in melanoma, but its rare occurrence did not allow any statistical evaluation of its specificity. Nail apparatus nevi were significantly associated with a brown coloration of the background and the presence of regular lines (P=.001). Nail apparatus lentigo, ethnic-type pigmen- tation, and drug-induced pigmentation were signifi- cantly associated with homogeneous longitudinal thin gray lines and gray coloration of the background (P=.001). Microscopic longitudinal grooves were unspecific, oc- curred in several conditions, and were associated with any type of ungual discoloration. Conclusions: We believe that dermoscopic examina- tion of the nail plate in cases of longitudinal melano- nychia provides useful information that could help cli- nicians to more accurately decide if a nail apparatus biopsy should be performed; however, histopathologic diagno- sis remains the gold standard in doubtful cases. Arch Dermatol. 2002;138:1327-1333

Herbal Therapy in Dermatology

Abstract: Herbal therapy is becoming increasingly popular among patients and physicians. Many herbal preparations are marketed to the public for various ailments including those of the skin. Herbal therapies have been used successfully in treating dermatologic disorders for thousands of years in Europe and Asia. In Germany, a regulatory commission oversees herbal preparations and recommended uses. In Asia, herbal treatments that have been used for centuries are now being studied scientifically. Currently, the United States does not regulate herbal products, as they are considered dietary supplements. Therefore, there is no standardization of active ingredients, purity, or concentration. There are also no regulations governing which herbs can be marketed for various ailments. This has made learning about and using these treatments challenging. Information compiled in a practical fashion may enable more patients to benefit from these treatments currently used worldwide. We reviewed the herbal medications that show scientific evidence of clinical efficacy, as well as the more common herbs shown to be useful in the treatment of dermatologic disorders. The safety of each herb has been addressed to better enable the physician to know which herbal therapies they may want to begin to use in practice. Common drug interactions and side effects of herbal medicines that may be seen in the dermatologic setting were also studied.

Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance.

Abstract: Design: Longitudinal study. Quality of life and psychological well-being were measured before the dermatologic visit with a self-completed questionnaire. Telephone interviews were performed 3 days and 4 weeks after the visit to evaluate patient satisfaction and medication adherence, respectively. Setting: Outpatient clinics of a large dermatologic hospital in Rome, Italy. Patients: A total of 1389 outpatients were contacted and 722 (52%) agreed to participate. Among them, 424 responded to the inclusion criteria and were enrolled in the study. Of these, 396 (93%) completed the telephone interviews. Results: The dermatologists’ prescriptions were not exactly followed by 44% of patients. In multiple logistic regression analysis, treatment adherence was strongly associated with complete satisfaction. Poor quality of life on the emotions scale (indicating mainly high levels of shame and embarrassment) was also associated with medication adherence. On the contrary, a strong negative association was observed between psychiatric morbidity and compliance. Conclusions: This is the first longitudinal study on dermatologic patients showing that dissatisfaction with care and psychiatric morbidity are significantly and independently associated with poor medication adherence. To improve medication adherence, particular attention should be dedicated to the physician’s interpersonal skills, which emerged as a major component of patient satisfaction. Moreover, our results highlight the need for a timely identification and appropriate management of psychiatric disorders in everyday dermatologic practice. Arch Dermatol. 2002;138:337-342

Interferon alfa-2a in the treatment of Behcet disease : a randomized placebo-controlled and double-blind study

Abstract: Objective To determine the therapeutic efficacy of interferon alfa-2a in the treatment of Behcet disease. Design A randomized placebo-controlled and double-blind study. Setting University referral center. Patients Fifty patients with Behcet disease were involved in the study. Intervention The patients were given interferon alfa-2a, 6 × 10 6 IU, subcutaneously 3 times per week or placebo for 3 months, and examined clinically at weekly intervals. Main Outcome Measures For each mucocutaneous lesion and articular symptom, the mean frequency and duration were evaluated during the 3-month pretreatment, treatment, and follow-up periods. Pain for oral and genital ulcers was scored on a scale of 0 to 3. The ocular inflammatory score, the frequency of attacks, and changes in visual acuities for patients with ocular involvement were assessed before the study, at the end of treatment, and during the follow-up periods. In addition, overall responses at the end of the treatment period were graded as follows: complete remission, disappearance of all clinical signs and symptoms during treatment; partial remission, greater than a 50% decrease in the frequency, duration, and severity of pain for oral and genital ulcers and/or a decrease in the severity and frequency of ocular attacks; stable disease, less than a 50% change in the clinical signs and symptoms; and no effect or deterioration, ineffectiveness or worsening of clinical signs and symptoms. Results Twenty-three interferon alfa-2a– and 21 placebo-treated patients, ranging in age from 16 to 55 years (mean ± SD age, 32.38 ± 7.94 years), were evaluable for efficacy. Interferon alfa-2a treatment significantly decreased the duration ( P = .02) and pain ( P = .01) of oral ulcers and the frequency of genital ulcers ( P = .03) and papulopustular lesions ( P = .01). The mean frequency and duration of erythema nodosum–like lesions ( P = .77 and .27, respectively), thrombophlebitis ( P = .29 and .61, respectively), and articular symptoms ( P = .92 and .74, respectively) also decreased. But there were no statistically significant differences. An improvement in the severity and the frequency of ocular attacks occurred in 5 of 6 patients in the interferon alfa-2a–treated group and in 1 of 3 patients in the placebo-treated group. Of the 23 patients in the interferon alfa-2a–treated group, 15 responded to treatment (2 complete and 13 partial responses); and of the 21 patients in the placebo group, 3 responded to treatment (3 partial responses) ( P Conclusion Interferon alfa-2a is an effective alternative treatment for Behcet disease, particularly for the management of the mucocutaneous lesions of the disease.

Cancer Screening: A Practical Guide for Physicians

Abstract: New to this fourth edition are chapters on dermatocosmetic vehicles, surface film, causes and measurement of skin aging, make-up products, skin healing, cosmetics in sports, cosmetotextiles, nutricosmetics, natural ingredients, cosmeceuticals, and regulatory vigilance.Key Features:Authors drawn from universities, clinical practice, and industryAuthors drawn from Dermatology, Toxicology, and PharmacologyInternational authorshipLatest hot topics

Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody.

Abstract: Background Leukocyte function–associated antigen 1 (LFA-1), consisting of CD11a and CD18 subunits, plays an important role in T-cell activation and leukocyte extravasation. Objective To test whether blocking CD11a decreases immunobiologic and clinical activity in psoriatic plaques. Design Open-label, multicenter, dose escalation study. Patients Thirty-nine patients with moderate-to-severe psoriasis. Intervention Intravenous infusions of efalizumab, a humanized anti-CD11a monoclonal antibody, for 7 weeks at doses of 0.1 mg/kg every other week or 0.1 mg/kg weekly (category 1), 0.3 mg/kg weekly (category 2), and 0.3 increasing to 0.6 or 1.0 mg/kg weekly (category 3). Skin biopsies were performed on days 0, 28, and 56. Main Outcome Measures Serum efalizumab levels, levels of total and unoccupied T-cell CD11a, T cell counts, epidermal thickness, cutaneous intercellular adhesion molecule 1 (ICAM-1) and keratin 16 (K16) expression, Psoriasis Area and Severity Index (PASI) scores. Results Dose-response relationships were observed for pharmacokinetics and pharmacodynamic measures. Category 1 failed to maintain detectable serum efalizumab or T cell CD11a down-modulation between doses. Category 2 achieved both. Category 3 achieved both and additionally maintained sustained T-cell CD11a saturation between doses. A dose-response relationship was also observed clinically and histologically. The mean decrease in the PASI score was 47% in category 3, 45% in category 2, and 10% in category 1 ( P Conclusions At doses of 0.3 mg/kg or more per week, intravenous efalizumab produced significant clinical and histologic improvement in psoriasis, which correlated with sustained serum efalizumab levels and T-cell CD11a saturation and down-modulation.

Efficacy of Topical 5% Imiquimod Cream for the Treatment of Nodular Basal Cell Carcinoma: Comparison of Dosing Regimens

Abstract: Objective To establish a safe and efficacious dosing regimen for the treatment of primary nodular basal cell carcinoma (BCC) using 5% imiquimod cream. Design Two phase 2 studies were conducted: a 6-week, randomized, open-label, dose-response study evaluating 4 dosing regimens and a 12-week, randomized, vehicle-controlled, double-blind, dose-response study evaluating 4 dosing regimens. Setting Twenty-four public and private dermatology clinics in Australia and New Zealand (6-week study) and the United States (12-week study) participated. Patients The study populations comprised 99 patients enrolled in the 6-week study and 92 patients in the 12-week study. Patients were at least 18 years old and had a biopsy-confirmed diagnosis of nodular BCC. Interventions In the 6-week study, imiquimod was applied once daily for 3 or 7 days per week or twice daily for 3 or 7 days per week. In the 12-week study, imiquimod or placebo cream (vehicle) was applied once daily for 3, 5, or 7 days per week, or twice daily for 7 days per week. The entire tumor area was excised 6 weeks after treatment and examined histologically for evidence of remaining BCC. Main Outcome Measure The proportion of patients having no histologic evidence of BCC in the posttreatment excision specimen. Results Dosing once daily for 7 days per week resulted in the highest clearance rate, with 25 (71%) of 35 and 16 (76%) of 21 patients showing clearance of their tumor in the 6- and 12-week studies, respectively. Conclusions Topical 5% imiquimod cream is well tolerated and most effective in treating nodular BCC when applied once daily for 7 days per week for either 12 or 6 weeks.

A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses.

Abstract: Background Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK. Objective To assess the efficacy and safety of imiquimod for the treatment of AK. Design Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary. Setting A specialized outpatient dermatology clinic within a state-funded hospital in Germany. Patients The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers. Main Outcome Measures The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded. Results Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported. Conclusion Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.

Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age.

Abstract: Background Although bullous pemphigoid (BP) is the most frequent autoimmune bullous disease and is associated with a considerable case-fatality rate, little is known about factors that influence its prognosis. Objective To identify prognostic factors for lethal outcome in the first year after the initial hospitalization in patients with BP. Design A multicenter retrospective cohort study. Setting Seven dermatologic university hospitals in Germany. Participants A total of 369 patients diagnosed as having BP between January 1, 1987, and December 31, 1997. Statistics Univariate (Kaplan-Meier) and multivariate (Cox regression) analysis. Results Of the 369 patients with BP, 209 (57%) died, 106 (29%) within the first year after hospitalization. Fifty-four percent were women. The mean ± SD age at entry was 77.3 ± 11.1 years. The patients with BP were followed up to 10.5 years, with a median time of 1.8 years to death or interview (25th and 75th quartiles, 0.5 and 4.0 years). The major risk factors for lethal outcome in the first year after hospitalization were an increased age, with a multivariate risk estimate of 3.2 (95% confidence interval [CI], 1.9-5.2) for age greater than 80.4 years (median); a daily glucocorticosteroid dosage of more than 37 mg (75th quartile) at discharge, with a multivariate risk estimate of 2.5 (95% CI, 1.5-4.3); serum albumin levels of 3.6 g/dL or less (25th quartile), with a multivariate risk estimate of 2.6 (95% CI, 1.5-4.4); and an erythrocyte sedimentation rate greater than 30 mm/h (75th quartile), with a multivariate risk estimate of 1.7 (95% CI, 1.1-2.8). Conclusions There is a considerable case-fatality rate in patients with BP. Older patients who require a higher dosage of oral glucocorticosteroids at hospital discharge and who have low serum albumin levels are at greater risk of death within the first year after hospitalization. These prognostic factors should be considered in the care of patients with BP as well as in the design of future clinical trials.

Follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and Sézary syndrome.

Abstract: Context Beginning in 1957, patients have been described with localized alopecia characterized histopathologically by mucin deposition within hair follicles (follicular mucinosis [FM]). At least 2 distinct diagnostic entities have been proposed: one occurring in children and young adults without association with other diseases ("idiopathic" FM), the other occurring in elderly patients and associated with mycosis fungoides or Sezary syndrome ("lymphoma-associated" FM). Objective To determine whether idiopathic and lymphoma-associated FM are distinct or related entities. Design Case series. Setting Department of Dermatology, University of Graz, Graz, Austria. Patients Forty-four patients with FM were divided into 2 groups. Group 1 comprised 16 patients (mean age, 37.5 years) with no associated mycosis fungoides or Sezary syndrome; group 2 was made up of the other 28 (mean age, 52.2 years), who had clinicopathologic evidence of cutaneous T-cell lymphoma. Results Mean age was lower in patients with idiopathic FM, but a considerable overlapping among the 2 groups was present. Location on the head and neck region was common in both groups, but most patients with lymphoma-associated FM had lesions also on other body sites. In fact, solitary lesions at presentation were common in patients with idiopathic FM (11 [68.8%] of 16 patients), but uncommon in those with lymphoma-associated FM (2 [7.1%] of 28 patients). Histopathologic findings did not allow clear-cut differentiation of the 2 groups. Finally, a monoclonal rearrangement of the T-cell receptor γ gene was demonstrated by polymerase chain reaction analysis in about 50% of tested cases from each group. Conclusions Criteria previously reported to differentiate idiopathic from lymphoma-associated FM proved ineffective. In analogy to localized pagetoid reticulosis (Woringer-Kolopp disease), small-plaque parapsoriasis, and so-called solitary mycosis fungoides, idiopathic FM may represent a form of localized cutaneous T-cell lymphoma.

Histological characteristics of metastasizing thin melanomas: a case-control study of 43 cases.

Abstract: Objective To study clinical and histological features associated with metastasizing thin melanomas (MTMs). Design Case-control study of clinicopathological features of patients with MTMs by a panel of 10 dermatopathologists. Setting Members of the North American Melanoma Pathology Study Group selected the cases from the melanoma databases at 8 academic institutions. Patients Forty-three patients with MTMs ( Intervention None. Main Outcome Measures Clinical (age, sex, site of lesion, stage at diagnosis, metastasis site, disease-free survival, and outcome) and histological (Breslow thickness, Clark level, growth phase, regression, and inflammatory response) features of patients with MTMs vs controls. Results There was an overrepresentation of axial tumors among patients with MTMs. Extensive regression was present in 18 patients (42%) with MTM vs 2 matched control subjects (5%) (95% confidence interval, 21%-53%;P= .001). Other histological variables were not significantly different. Two patients had melanomas in situ with subsequent metastasis. Conclusions Thin melanomas with extensive regression represent a group at higher risk for the development of metastasis. Furthermore, the risk of metastasis cannot be dismissed in cases of melanoma in situ.

Viral disease transmitted by laser-generated plume (aerosol).

Abstract: Objective To evaluate the possibility of disease transmission through liberated plume from virally infected tissue that is exposed to the carbon dioxide laser. Design Bovine papillomavirus–induced cutaneous fibropapillomas were exposed to the carbon dioxide laser. Laser settings were within the range of clinically used settings. The laser plume (aerosol) was suctioned and collected and then reinoculated onto the skin of calves. Setting University laboratory research center. Main Outcome Measures Laser plume viral content and postinoculation tumor growth were analyzed and documented. Results Collected laser plume contained papillomavirus DNA in all tested laser settings. The viral DNA was most likely encapsulated. Tumors developed at laser plume–inoculated sites for all laser parameter settings. Histological and biochemical analyses revealed that these tumors were infected with the same virus type as present in the laser plume. Conclusions Laser plume has been shown, for the first time to our knowledge, to actually transmit disease. Strict care must be maintained by the laser practitioner to minimize potential health risks, especially when treating viral-induced lesions or patients with viral disease.

Long-term Effectiveness of Treatment With Terbinafine vs Itraconazole in Onychomycosis: A 5-Year Blinded Prospective Follow-up Study

Abstract: microscopy and culture at the end of follow-up and no requirement of second intervention treatment. Secondary efficacy criteria included clinical cure without second intervention treatment and mycological and clinical relapse rates. Results: Median duration of follow-up was 54 months. At the end of the study, mycological cure without second intervention treatment was found in 34 (46%) of the 74 terbinafine-treated subjects and 10 (13%) of the 77 itraconazole-treated subjects (P.001). Mycological and clinical relapse rates were significantly higher in itraconazolevs terbinafine-treated patients (53% vs 23% and 48% vs 21%, respectively). Of the 72 patients who received subsequent terbinafine treatment, 63 (88%) achieved mycological cure and 55 (76%) achieved clinical cure. Conclusion: In the treatment of onychomycosis, continuous terbinafine provided superior long-term mycological and clinical efficacy and lower rates of mycological and clinical relapse compared with intermittent itraconazole. Arch Dermatol. 2002;138:353-357

Phase 1 and 2 Trial of Bexarotene Gel for Skin-Directed Treatment of Patients With Cutaneous T-Cell Lymphoma

Abstract: Objective To evaluate the safety, dose tolerance, and efficacy of topical bexarotene gel in patients with early-stage cutaneous T-cell lymphoma (CTCL). Design Phase 1 and 2, open-label, dose-escalation clinical trial of bexarotene gel. Setting Three university-based clinics. Participants Sixty-seven adults with early-stage (TNM stages IA-IIA) CTCL. Interventions Bexarotene gel, 0.1%, 0.5%, and 1.0%, applied in incremental dose adjustments from 0.1% gel every day to 1.0% gel 4 times daily or the maximal tolerated dose. Main Outcome Measures Patients were followed for efficacy and safety, and treatment continued as long as they benefited. Response (≥50% improvement) was evaluated by the Physician's Global Assessment of cutaneous disease and by an overall severity assessment of cutaneous disease, including signs of CTCL and area involved. Results Most patients tolerated topical bexarotene at 1% gel twice daily for routine use. Adverse events were generally mild to moderate in severity and were confined to treatment sites. Treatment-limiting toxic effects were associated with skin irritation and increased with gel exposure. Patients achieved an overall response rate of 63% and a clinical complete response rate of 21%. Median projected time to onset of response was 20.1 weeks (range, 4.0-86.0 weeks), and the estimated median response duration from the start of therapy was 99 weeks. Patients with no previous therapy for mycosis fungoides responded at a higher rate (75%) than those who previously underwent topical therapies (67%). Conclusions Bexarotene gel was well tolerated, was easily self-applied, and had a substantial response rate in treating patients with early-stage CTCL.

Necrotizing fasciitis: report of 39 pediatric cases.

Abstract: Background Necrotizing fasciitis (NF) is a severe, life-threatening soft tissue infection. General features and risk factors for fatal outcome in children are not well known. Objective To characterize the features of NF in children and the risk factors for fatal outcome. Design Retrospective, comparative, observational, and longitudinal trial. Setting Dermatology department of a tertiary care pediatric hospital. Patients All patients with clinical and/or histopathological diagnosis of NF seen from January 1, 1971, through December 31, 2000. Main Outcome Variables Incidence, age, sex, number and location of lesions, preexisting conditions, initiating factors, clinical and laboratory features, diagnosis at admission, treatment, evolution, sequelae, and risk factors for fatal outcome. Results We examined 39 patients with NF (0.018% of all hospitalized patients). Twenty-one patients (54%) were boys. Mean age was 4.4 years. Single lesions were seen in 30 (77%) of patients, with 21(54%) in extremities. The most frequent preexisting condition was malnutrition in 14 patients (36%). The most frequent initiating factor was varicella in 13 patients (33%). Diagnosis of NF at admission was made in 11 patients (28%). Bacterial isolations in 24 patients (62%) were polymicrobial in 17 (71%). Pseudomonas aeruginosa was the most frequently isolated bacteria; gram-negative isolates, the most frequently associated bacteria. Complications were present in 33 patients (85%), mortality in 7 (18%), and sequelae in 29 (91%) of 32 surviving patients. The significant risk factor related to a fatal outcome was immunosuppression. Conclusions Necrotizing fasciitis in children is frequently misdiagnosed, and several features differ from those of NF in adults. Immunosuppression was the main factor related to death. Early surgical debridement and antibiotics were the most important therapeutic measures.

Dermoscopy of Pigmented Seborrheic Keratosis: A Morphological Study

Abstract: Objectives To describe morphological features of seborrheic keratosis as seen by dermoscopy and to investigate their prevalence. Design Prospective cohort study using macrophotography and dermoscopy for the documentation of seborrheic keratosis. Settings Seborrheic keratoses were prospectively collected in 2 sites: a private practice in Plantation, Fla (site 1), and the Department of Dermatology at the University Hospital Geneva in Switzerland (site 2). Patients A total of 203 pigmented seborrheic keratoses (from 192 patients) with complete documentation were collected (111 from site 1 and 93 from site 2). Interventions Screening for new morphological features of seborrheic keratosis and evaluation of all lesions for the prevalence of these criteria. Main Outcome Measures Identification of new morphological criteria and evaluation of frequency. Results A total of 15 morphological dermoscopic criteria were identified. Standard criteria such as milialike cysts and comedolike openings were found in a high number of cases (135 and 144, respectively). We found network and networklike structures to be present in 94 lesions (46%). Using standard diagnostic criteria for seborrheic keratosis, 30 lesions would not have been diagnosed as such. Conclusions The classic dermoscopic criteria for seborrheic keratosis (milialike cysts and comedolike openings) have a high prevalence but the use of additional dermoscopic criteria such as fissures, hairpin blood vessels, sharp demarcation, and moth-eaten borders improves the diagnostic accuracy. The proper identification of pigment network and networklike structures is important for the correct diagnosis.

Pain Associated With Injection of Botulinum A Exotoxin Reconstituted Using Isotonic Sodium Chloride With and Without Preservative: A Double-blind, Randomized Controlled Trial

Abstract: Context Botulinum A exotoxin is used for various indications, including the treatment of dynamic forehead lines. Objective To determine whether injection with botulinum A exotoxin reconstituted with preservative-containing normal saline (isotonic sodium chloride) is less painful than injection with exotoxin that has been reconstituted with preservative-free saline. Design Two arms: (1) retrospective study; (2) double-blind, randomized controlled trial. Setting A multiple-physician dermatology practice. Patients (1) Retrospective study—20 consecutive adult patients presenting for treatment of upper-face dynamic lines; (2) prospective study—15 consecutive adult patients presenting for treatment of upper-face dynamic lines. Intervention In prospective study only, one side (left or right) of the face was treated with exotoxin reconstituted with preservative-containing saline, and the other side, with exotoxin reconstituted with preservative-free saline. Main Outcome Measures (1) Retrospective study—discomfort at current treatment (with preservative-containing saline) compared with discomfort with most recent prior treatment (with preservative-free saline); (2) prospective study—discomfort on the side treated with preservative-containing saline compared with discomfort on the side treated with preservative-free saline. Results (1) Retrospective study—18 (90%) of 20 patients reported that treatment with exotoxin reconstituted with preserved saline was less painful than prior treatment with exotoxin reconstituted with preservative-free saline; (2) prospective study—15 (100%) of 15 patients reported less pain in the side of their face treated with exotoxin reconstituted with preservative-containing saline (P Conclusion Use of preservative-containing saline to reconstitute botulinum A exotoxin can significantly decrease patient discomfort on injection.

Awareness of the risks of tanning lamps does not influence behavior among college students.

Abstract: Hypothesis Awareness of the risks of artificial tanning influences tanning behavior among college students. Objective To correlate the prevalence of tanning lamp use, the perceived benefits and risks associated with UV exposure, and knowledge about skin cancer among university students. Design A survey was designed and administered to college students seeking "walk-in" care at a university student health center from September 7, 1999, through September 30, 1999. Setting A large midwestern public university student health center. Participants Undergraduate and graduate students attending the student health center for any medical condition. Intervention None. Main Outcome Measure Completion of the survey. Results Of the surveyed students, 47% had used a tanning lamp during the preceding 12 months. Female students were more common users than male students. Of the students surveyed, 39% reported never having used tanning lamps. More than 90% of users of tanning lamps were aware that premature aging and skin cancer were possible complications of tanning lamp use. Conclusions Despite adequate knowledge of the adverse effects of UV exposure, university students freely and frequently use tanning lamps, primarily for desired cosmetic appearance. To alter this risky behavior will require a fundamental change in the societal belief that tans are attractive and healthy.

Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery.

Abstract: Background: In nonmelanoma skin cancer, the clinically visible portion may represent a small fraction of microscopic tumor spread. Previous studies have examined individual risk factors for subclinical spread based on patient and tumor characteristics. However, these risk factors have not been prioritized or studied in combination. Objective: To identify the most predictive risk factors for extensive subclinical tumor spread. Design: Retrospective analysis of 1131 Mohs micrographic surgical cases. Variables analyzed included patient age, sex, and immune status and lesion size, location, histologic subtype, and recurrence. Logistic regression was applied to identify important combinations of tumor characteristics and to quantify relative odds of spread. Setting: Academic referral center. Patients: Consecutive sample of all referred patients treated by a single Mohs micrographic surgeon in a 3-year period. Main Outcome Measure: Number of Mohs micrographic surgical layers required to clear a tumor, with 3 or more layers defined as extensive subclinical spread. Results: The highest-risk tumors, with odds ratios greater than 6.0, were basosquamous and morpheaform basal cell carcinoma (BCC) on the nose, morpheaform BCC on the cheek, and those with a preoperative size greater than 25 mm. Other important risk factors were recurrent and nodular BCC on the nose; location on the eyelid, temple, or ear helix; neck tumors and recurrent BCC in men; and tumor size greater than 10 mm. Patients younger than 35 years were at lower risk. Increasing age and immunocompromise were not significant predictors. Conclusion: Identification of lesions likely to exhibit extensive subclinical spread can help guide management to ensure complete tumor eradication and thereby reduce the risk of recurrence and its associated morbidity and cost.

The suitability of quality-of-life questionnaires for psoriasis research: a systematic literature review.

Abstract: Objective To critically appraise the suitability of current quality-of-life (QOL) questionnaires for psoriasis research. Data Sources Computerized searches of 5 bibliographic databases. Questionnaire Selection Predefined criteria were used to identify QOL questionnaires in dermatologic studies. Two investigators independently assessed and agreed on multidimensional generic, dermatology-specific, and psoriasis-specific QOL questionnaires for inclusion. Data Extraction Data were extracted on the internal structure, reliability, and validity of the included questionnaires. Data Synthesis Three generic, 3 dermatology-specific, and none of the psoriasis-specific questionnaires met the inclusion criteria: the Nottingham Health Profile (NHP), the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the Sickness Impact Profile (SIP), the Dermatology Quality of Life Scales (DQOLS), the Dermatology-Specific Quality of Life Instrument (DSQL), and the Skindex-29. The generic NHP, SF-36 and SIP are well established, reliable, and valid. Although the data are not conclusive, the SF-36 was useful to assess effects of psoriasis on its component scales. The dermatology-specific DQOLS, DSQL, and Skindex-29 are relatively new and, therefore, less widely tested. Available psychometric data demonstrated the reliability and validity of all 3 dermatology-specific questionnaires. The Skindex-29 was also useful to assess change. Conclusions None of the identified psoriasis-specific questionnaires met the inclusion criteria. Data on the suitability of the included questionnaires for psoriasis research were relatively sparse. The included generic questionnaires allow comparisons with nondermatologic diseases but do not allow assessment of relevant dermatology-specific aspects and are not sensitive to subtle effects of psoriasis on QOL. On the basis of the psychometric data of the present review, we find the Skindex-29 to be the most valuable dermatology-specific questionnaire for psoriasis research. Combination of the Skindex-29 with the generic SF-36 combines the merits of both types of questionnaires and we therefore recommend this combination.

Nodular Type and Older Age as the Most Significant Associations of Thick Melanoma in Victoria, Australia

Abstract: Objectives To explore the clinical associations of thick melanoma and to compare the clinicopathological variables of nodular and superficial spreading types. Design Cross-sectional study of all invasive primary melanomas recorded by the Victorian Cancer Registry for 1998 and those reviewed by the Victorian Melanoma Service between October 1, 1994, and April 31, 1999. Setting Population-based cancer registry and public hospital–based multidisciplinary melanoma clinic. Patients This study included 1422 patients recorded by the Victorian Cancer Registry and 674 patients who had attended the Victorian Melanoma Service; unclassifiable tumor types were excluded, leaving 1144 and 645 patients, respectively, eligible for analysis. Main Outcome Measures Melanomas were categorized by thickness into thin (≤1 mm), intermediate (>1-3 mm), and thick (>3 mm) and compared according to patient age, sex, and tumor type and site. Superficial spreading and nodular types were also compared in this manner. Use of the Victorian Melanoma Service database enabled a more comprehensive analysis of historical and phenotypic characteristics. Results Thick melanoma was predominantly nodular, occurring in older men, mostly on the head and neck and associated with fewer nevi. Nodular melanoma was thicker and found mostly on the lower limbs or head and neck; it had a greater association with a history of solar keratoses than did superficial spreading melanoma. Conclusion Nodular type and older age are the most significant associations of thick melanoma.

Relative contribution of intrinsic vs extrinsic factors to skin aging as determined by a validated skin age score.

Abstract: Objective To assess the relative contribution of intrinsic aging vs lifestyle factors to facial skin age. Design Prospective analysis of a cohort. Setting Skin research institute. Study subjects A cohort of 361 white women (age range, 18-80 years) with apparently healthy skin. Measurements Visual and tactile assessment of facial skin features. Results Twenty-four skin characteristics were used to build a skin age score (SAS). The relationship between the SAS and chronological age followed a linear model with 2 plateaus--1 before age 30 years and 1 after age 71 years. An analysis was performed to determine whether certain lifestyle habits known to have effects on skin aging were related to the discrepancies between chronological age and the SAS. Significant effects were identified for phototype, body mass index, menopausal status, degree of lifetime sun exposure, and number of years of cigarette smoking. However, these factors accounted for only 10% of the discrepancies. Moreover, most skin characteristics used reflected changes understood to represent intrinsic aging rather than photodamage or other extrinsic factors. Conclusions An SAS can be generated from multiple discrete signs evaluated on facial skin and is an informative tool for quantifying skin aging. The SAS is influenced by factors already recognized to affect the aging phenotypes; however, factors related to the rate of intrinsic aging, presumably genetic in character, seem to play a larger role than previously suspected.