Atrophic and hypertrophic photoaging: Clinical, histologic, and molecular features of 2 distinct phenotypes of photoaged skin.

BACKGROUND: Exposure to the sun causes premature skin aging, known as photoaging. Clinical features of photoaging vary widely among individuals. In one form, skin appears thin with telangiectasia, and in another form, skin appears thickened with coarse wrinkles. Etiologic, clinical, and therapeutic distinctions among different forms of photoaging remain largely unknown. OBJECTIVE: To characterize the clinical, histologic, and molecular features of hypertrophic and atrophic photoaging. METHODS: In total, 53 individuals were clinically classified as having primarily atrophic or hypertrophic photoaging or neither (controls). Participants' demographic and sun exposure-related lifestyle data were captured by questionnaire. Fifteen clinical features of participants were qualitatively or quantitively scored. Facial biopsies were analyzed for gene expression and histologic characteristics. RESULTS: Actinic and seborrheic keratosis, telangiectasia, and prior incidence of skin cancers were statistically significantly greater and photoaging scale severity, coarse wrinkles, thickness, and sallowness were significantly reduced in atrophic versus hypertrophic groups. Histology also revealed significantly less elastotic material in atrophic photoaging. Gene expression of matrix metalloproteinases and collagens did not differ between the 2 forms of photoaging. LIMITATIONS: The study was not designed to identify other possible subtypes of photoaging. CONCLUSION: Systematic, categorical, and quantitative clinical and histologic assessments distinguish atrophic and hypertrophic photoaging.

Eccrine sweat glands are major contributors to reepithelialization of human wounds.

Eccrine sweat glands are skin-associated epithelial structures (appendages) that are unique to some primates including humans and are absent in the skin of most laboratory animals including rodents, rabbits, and pigs. On the basis of the known importance of other skin appendages (hair follicles, apocrine glands, and sebaceous glands) for wound repair in model animals, the present study was designed to assess the role of eccrine glands in the repair of wounded human skin. Partial-thickness wounds were generated on healthy human forearms, and epidermal repair was studied in skin biopsy samples obtained at precise times during the first week after wounding. Wound reepithelialization was assessed using immunohistochemistry and computer-assisted 3-dimensional reconstruction of in vivo wounded skin samples. Our data demonstrate a key role for eccrine sweat glands in reconstituting the epidermis after wounding in humans. More specifically, (i) eccrine sweat glands generate keratinocyte outgrowths that ultimately form new epidermis; (ii) eccrine sweat glands are the most abundant appendages in human skin, outnumbering hair follicles by a factor close to 3; and (iii) the rate of expansion of keratinocyte outgrowths from eccrine sweat glands parallels the rate of reepithelialization. This novel appreciation of the unique importance of eccrine sweat glands for epidermal repair may be exploited to improve our approaches to understanding and treating human wounds.

A gender-based comparison of pain tolerance during pulsed dye laser therapy.

BACKGROUND: Cosmetic laser treatments are frequently performed without anesthesia in the clinic setting and there is a need to better understand the factors that may impact patient pain levels during these procedures. There has been prior research suggesting that there are significant gender-based differences in pain experiences with a variety of interventions. AIMS: We sought to examine the influence of gender and specific emotional factors on pain perception during pulsed dye laser treatments. PATIENTS/METHODS: We conducted a questionnaire-based study of 84 adult patients (42 males and 42 females) who underwent facial pulsed dye laser treatments in our clinic for cosmetic purposes. Questionnaires were completed by each patient after his or her initial laser treatment and patients were queried as to their perceived levels of pain during the procedure. Additional information regarding quality of life measures and patient motivation was also collected. RESULTS: Contrary to prior research suggesting lower pain thresholds for women in other clinical or experimental settings, we found no statistically significant differences in mean pain levels reported between patients of each gender. There was a trend toward females being somewhat more likely than males to see the pain of the treatment as justified for an improvement in appearance. CONCLUSIONS: Patient motivation and pain tolerance levels may be similar between genders among patients undergoing non-invasive cosmetic procedures. Clinicians may, therefore, expect patients of either gender to tolerate such treatments equally well.

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

Direct quantitative comparison of molecular responses in photodamaged human skin to fractionated and fully ablative carbon dioxide laser resurfacing.

BACKGROUND: Fractionated ablative laser resurfacing has become a widely used treatment modality. Its clinical results are often found to approach those of traditional fully ablative laser resurfacing. OBJECTIVE: To directly compare the molecular changes that result from fractionated and fully ablative carbon dioxide (CO(2)) laser resurfacing in photodamaged human skin. METHODS AND MATERIALS: Photodamaged skin of 34 adult volunteers was focally treated at distinct sites with a fully ablative CO(2) laser and a fractionated CO(2) laser. Serial skin samples were obtained at baseline and several time points after treatment. Real-time reverse transcriptase polymerase chain reaction technology and immunohistochemistry were used to quantify molecular responses to each type of laser treatment. RESULTS: Fully ablative and fractionated CO(2) laser resurfacing induced significant dermal remodeling and collagen induction. After a single treatment, fractionated ablative laser resurfacing resulted in collagen induction that was approximately 40% to 50% as pronounced as that induced by fully ablative laser resurfacing. CONCLUSIONS: The fundamental cutaneous responses that result from fully ablative and fractionated carbon dioxide laser resurfacing are similar but differ in magnitude and duration, with the fully ablative procedure inducing relatively greater changes including more pronounced collagen induction. However, the molecular data reported here provide substantial support for fractionated ablative resurfacing as an effective treatment modality for improving skin texture.

Overview of skin aging and photoaging.

Aging skin is an issue of concern to many patients. In this review aging and photoaging are defined, mechanisms which underlie these processes explored, and available treatment options discussed.

Patient interest in and familiarity with anti-aging therapies: A survey of the general dermatology clinic population.

BACKGROUND: The appearance of aging skin is a common complaint among dermatology patients. There is an expanding market for anti-aging therapies, but little information is available regarding which patients utilize these treatments and patient preferences regarding treatment. AIMS: To describe the patient population utilizing anti-aging therapies, assess patient familiarity with treatment options, and learn where treatment information is most often obtained. PATIENTS/METHODS: Three hundred patients were surveyed in the University of Michigan General Dermatology Clinic. RESULTS: Fifty-three percent of the general dermatology patient population has used an anti-aging treatment in the past; 66% reported interest in the future use. Interest is high among all genders, ages, and incomes. Most subjects obtained treatment information from magazines, but subjects were more likely to pursue treatment if information was obtained from a dermatologist. CONCLUSION: Demographics of anti-aging therapy are changing, and a wide variety of patients pursue treatment. Patients are largely unfamiliar with most treatment options and are more likely to pursue treatment after receiving treatment information from a dermatologist. The information presented in this study is helpful to both dermatologists and marketers of anti-aging products.

A randomized, controlled, split-face clinical trial of 1320-nm Nd:YAG laser therapy in the treatment of acne vulgaris.

BACKGROUND: There is a need for additional effective treatments for acne vulgaris. Laser therapy has been explored as a therapeutic option for acne, but rigorously designed studies in this area have been limited. OBJECTIVE: We sought to examine the efficacy of an infrared laser in the treatment of acne. METHODS: We conducted a randomized, controlled, single-blind, split-face clinical trial of 46 patients with facial acne. Patients received a series of 3 nonablative laser treatments using a novel neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to half of the face. Serial blinded lesion counts and global acne severity rating of standardized bilateral patient photographs were performed. Sebum production was measured, and patient self-assessment surveys were administered. RESULTS: A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin. There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts. Grading of serial photographs revealed no significant differences between treated and untreated skin. Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness. LIMITATIONS: The current study only addresses the efficacy of a single laser system employing a specific treatment regimen. CONCLUSIONS: Infrared laser therapy may improve comedonal acne. Additional work is needed to better define the degree and duration of the effect. Patients appear to positively view such therapy for both acne and oily skin.

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.

Cutaneous reactions to chemotherapy and their management.

International data from 2002 report 10.9 million new cases of cancer and 6.7 million cancer deaths. Chemotherapy is an essential component in the multidisciplinary management of most cancers. Cutaneous reactions to chemotherapeutics are common and may contribute significantly to the morbidity, and rarely to the mortality, of patients undergoing such treatments. Recognition and management of these reactions is important to provide optimal care. This article aims to present the most common cutaneous reactions to frequently used chemotherapies and provides management guidelines. A MEDLINE search from 1966 through June 2005 was conducted to identify reports of common cutaneous toxicities with systemic chemotherapy and their appropriate management. An analysis of our literature search is presented in review form outlining common chemotherapy-related cutaneous reactions and their management, as well as the chemotherapeutics responsible for the cutaneous toxicity. Chemotherapy-related cutaneous toxicity includes generalized rashes such as the spectrum between erythema multiforme and toxic epidermal necrolysis, and site-specific toxicity such as mucositis, alopecia, nail changes, extravasation reactions, or hand-foot syndrome. Most of the toxicity is reversible with chemotherapy dose reductions or delays. Certain toxicities can be effectively treated or prevented, allowing optimal delivery of chemotherapy (e.g. premedications to prevent hypersensitivity, prophylactic mouthwashes to prevent mucositis). Newer non-chemotherapeutic targeted therapies such as epidermal growth factor receptor inhibitors (e.g. gefitinib, cetuximab) may also be associated with cutaneous toxicity and can be distressing for patients. Recent data suggest that skin toxicity associated with these agents may correlate with efficacy. Cutaneous toxicity occurs frequently with chemotherapy and non-chemotherapeutic biologic therapies. Early recognition and treatment of the toxicity facilitates good symptom control, prevents treatment-related morbidity, and allows continuation of anti-cancer therapy.

Prevalence of psychotropic medication use among cosmetic and medical dermatology patients: a comparative study.

BACKGROUND: Little is known about the psychologic status of cosmetically oriented dermatology patients. OBJECTIVE: We sought to determine the prevalence of psychotropic medication use among such patients to offer insight into the rates of psychopathology in this group. METHODS: We conducted a retrospective chart review of patients seeking consultation at a cosmetic dermatology practice, recorded patients' use of psychotropic medicines, and compared this with data from a control group of medical dermatology patients. RESULTS: Both groups reported rates of psychotropic medication use above those expected in the general population. There was no statistically significant difference in the prevalence of psychotropic drug use between cosmetic (18%) and medical (17%) dermatology patients. LIMITATIONS: There is not a one-to-one correspondence between psychotropic medication use and the presence of psychopathology. Data are based on patient health histories and, thus, may be subject to underreporting. CONCLUSIONS: There is a relatively high rate of psychotropic drug use among all patients seeking care from dermatologists, but this does not appear to be more common among patients interested in undergoing cosmetic procedures.

Treatment of Acne in Pregnancy.

Acne vulgaris is a common disease of the pilosebaceous unit and affects adolescents and adults. Because high-quality guidelines regarding treatment of acne in pregnancy are scarce, management of this condition can be challenging. We describe the safety profile of common therapies and outline approaches based on available evidence. Topical azelaic acid or benzoyl peroxide can be recommended as baseline therapy. A combination of topical erythromycin or clindamycin with benzoyl peroxide is recommended for inflammatory acne. Oral erythromycin or cephalexin is generally considered safe for moderate to severe inflammatory acne when used for a few weeks. A short course of oral prednisolone may be useful for treating fulminant nodular cystic acne after the first trimester. In general, topical and oral antibiotics should not be used as monotherapy, but combined with topical benzoyl peroxide to decrease bacterial resistance. Oral retinoids are teratogenic and absolutely contraindicated for women who are pregnant or considering pregnancy. Although some complementary therapies including micronutrients and nonpharmacologic treatments seem to be well tolerated, limited data exist regarding their safety and efficacy, and they are not currently recommended during pregnancy. The risk-to-benefit ratio, efficacy, acceptability, and costs are considerations when choosing a treatment for acne in pregnancy.

Virus-associated trichodysplasia spinulosa.

Virus-associated trichodysplasia spinulosa (VATS) is a cutaneous eruption of spiny papules predominantly affecting the face that is associated with a distinctive histologic picture of abnormally maturing anagen follicles with excessive inner root sheath differentiation and hyperkeratotic infundibula. Ultrastructurally, intranuclear viral particles consistent with polyoma virus are found. Only 2 patients have thus far been reported. Both had developed the eruption after a kidney transplant. We report 2 additional cases of VATS. One is an 8-year-old boy who presented with facial papules after a kidney transplant. The other is a 19-year-old man with a history of acute lymphocytic leukemia who never had a transplant. He developed a papular facial eruption as well as alopecia. Light microscopic and ultrastructural examinations revealed a spectrum in the severity of the histologic alterations as well as the number of intranuclear viral particles. This report expands the range of pathologic alterations associated with VATS and documents for the first time that it can affect patients without a solid organ transplant. The similarity of the clinical and histologic features of VATS with those previously reported by others as cyclosporine-induced "follicular dystrophy" or "pilomatrix dysplasia" raises the possibility that the described phenomena may reflect the same entity. Increased awareness of the distinct histologic picture associated with VATS will likely lead to more frequent diagnosis of this underrecognized entity.

Hypo-collagenesis in photoaged skin predicts response to anti-aging cosmeceuticals.

BACKGROUND: Chronic sun exposure causes photoaging, the appearance of prematurely aged skin. This phenomenon is characterized by progressive alteration of the dermal extracellular matrix, including elastin and collagen fibers. While many cosmeceuticals claim to improve the appearance of photoaged skin, data are lacking regarding their ability to induce molecular responses associated with wrinkle effacement, particularly increased collagen production. AIMS: To conduct a meta-analysis to determine whether there was a factor(s) that could predict response to various cosmeceuticals. PATIENTS/METHODS: Hundred subjects enrolled in five separate studies of cosmeceuticals containing: L-ascorbic acid, pentapeptide, α-lipoic acid, yeast extract, or 1% idebenone. Five groups consisting of 16-20 volunteers applied one cosmeceutical to their photodamaged forearms for several weeks. Punch biopsies were obtained pretreatment and post-treatment and analyzed for type I procollagen by ELISA. RESULTS: Analysis of basal collagenesis reinforced the notion that hypo-collagenesis is associated with photoaging severity, independent of age or gender. Treatment outcome varied greatly among subjects, ranging from no improvement to a 7-fold increase in collagenesis. Retrospective statistical meta-analysis was conducted to determine whether age, gender, type of cosmeceutical, or evidence of hypo-collagenesis in untreated skin could predict responsiveness to cosmeceuticals. Our analysis revealed that subjects with hypo-collagenesis responded 6.4 times more often than subjects with normo-collagenesis. DISCUSSION: Hypo-collagenesis was the only factor that influenced treatment outcome. This study therefore identifies hypo-collagenesis as the unique parameter predicting anti-aging cosmeceutical treatment outcome. These findings provide a basis for future cosmetic testing and the potential development of custom formula skin care.

Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy.

BACKGROUND: There remains the need for more effective therapeutic options to treat acne vulgaris. Interest in light-based acne treatments has increased, but few randomized, controlled clinical trials assessing the value of photodynamic therapy (PDT) for acne have been reported. AIMS: We sought to examine the efficacy of PDT using 5-aminolevulinic acid (ALA) and pulsed dye laser therapy in the treatment of acne. PATIENTS/METHODS: We conducted a randomized, controlled, split-face, single-blind clinical trial of 44 patients with facial acne. Patients were randomized to receive three pulsed dye laser treatments to one side of the face after a 60-90 min ALA application time, while the contralateral side remained untreated and served as a control. Serial blinded lesion counts and global acne severity ratings were performed. RESULTS: Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin. Erythematous macules (remnants of previously active inflammatory lesions) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin. There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion. Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts, while only 7% of patients responded in terms of noninflammatory lesion counts. CONCLUSIONS: PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne.

Molecular analysis of aggressive microdermabrasion in photoaged skin.

OBJECTIVE: To investigate dermal remodeling effects of crystal-free microdermabrasion on photodamaged skin. DESIGN: Biochemical analyses of human skin biopsy specimens following microdermabrasion treatment in vivo. SETTING: Academic referral center. PARTICIPANTS: Volunteer sample of 40 adults, aged 50 to 83 years, with clinically photodamaged forearms. Intervention Focal microdermabrasion treatment with diamond-studded handpieces of varying abrasiveness on photodamaged forearms and serial biopsies at baseline and various times after treatment. MAIN OUTCOME MEASURES: Quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay were used to quantify changes in inflammatory, proliferative, and remodeling effectors of normal wound healing. Type I and type III procollagen served as the main outcome marker of dermal remodeling. RESULTS: Coarse-grit microdermabrasion induces a wound healing response characterized by rapid increase in induction of cytokeratin 16 and activation of the AP-1 transcription factor in the epidermis. Early inflammation was demonstrated by induction of inflammatory cytokines, antimicrobial peptides, and neutrophil infiltration in the dermis. AP-1 activation was followed by matrix metalloproteinase-mediated degradation of extracellular matrix. Consistent with this wound-healing response, we observed significant remodeling of the dermal component of the skin, highlighted by induction of type I and type III procollagen and by induction of collagen production enhancers heat shock protein 47 and prolyl 4-hydroxylase. Dermal remodeling was not achieved when microdermabrasion was performed using a medium-grit handpiece. CONCLUSIONS: Microdermabrasion using a coarse diamond-studded handpiece induces a dermal remodeling cascade similar to that seen in incisional wound healing. Optimization of these molecular effects is likely the result of more aggressive treatment with a more abrasive handpiece.

Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.

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 1beta), 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.

Molecular effects of photodynamic therapy for photoaging.

OBJECTIVE: To quantitatively examine the epidermal and dermal cellular and molecular changes that occur after photodynamic therapy of photodamaged human skin. DESIGN: Serial in vivo biochemical and immunohistochemical analyses after photodynamic therapy using topical 5-aminolevulinic acid (5-ALA) and pulsed-dye laser treatment. SETTING: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. PATIENTS: A volunteer sample of 25 adults, 54 to 83 years old, with clinically apparent photodamage of the forearm skin. INTERVENTIONS: Three-hour application of 5-ALA followed by pulsed-dye laser therapy using non-purpura-inducing settings to focal areas of photodamaged forearms and serial biopsy specimens taken at baseline and various times after treatment. MAIN OUTCOME MEASURES: Immunohistochemical analysis was used to assess levels of markers of epidermal proliferation (Ki67), epidermal injury (cytokeratin 16), and photodamage (p53), as well as various markers of dermal collagen production (including prolyl 4-hydroxylase and heat shock protein 47, and type I procollagen). Real-time reverse transcriptase-polymerase chain reaction technology was used to quantify type I and type III collagen. Type I procollagen protein was quantified with enzyme-linked immunosorbent assay. RESULTS: Epidermal proliferation was stimulated as demonstrated by increases in Ki67 (more than a 5-fold increase; P < .05) and epidermal thickness (more than a 1.4-fold increase; P < .05). Epidermal injury was produced with increased cytokeratin 16 levels demonstrated (to nearly 70-fold of baseline levels; P < .05). Upregulation of collagen production was demonstrated with increases in procollagen I messenger RNA (2.65-fold; P < .05), procollagen III messenger RNA (3.32-fold; P < .05), and procollagen I protein (2.42-fold; P < .05) levels detected. The baseline epidermal p53 level correlated with cytokeratin 16 levels at acute time points, and the latter were found to correlate with peak collagen production. CONCLUSIONS: Photodynamic therapy with the specific treatment regimen employed produces statistically significant quantitative cutaneous molecular changes (eg, production of types I and III collagen) that are associated with improved appearance of the skin. Baseline epidermal p53 immunostaining levels may be predictive of dermal responses to this therapy. Comparison with historical data using pulsed-dye laser therapy alone suggests that use of the photosensitizer may enhance dermal remodeling. The quantitative in vivo molecular data presented herein are in keeping with an evolving model to potentially predict the efficacy of new techniques for the treatment of photoaging.