Alopecia areata: a review of disease pathogenesis.

BACKGROUND: Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation. Objectives In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion. METHODS: We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis. RESULTS: The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune-cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon-γ, interleukin-15, MICA and NKG2D, have been identified as contributing to the autoimmune process. CONCLUSIONS: Alopecia areata remains incurable, although it has been studied for years. Available treatment options at best are beneficial for milder cases, and the rate of relapse is high. Understanding the exact mechanisms of hair loss in alopecia areata is therefore of utmost importance to help identify potential therapeutic targets.

Multiplex PCR allows simultaneous detection of pathogens in ships' ballast water.

There is enormous potential for global transfer of microorganisms, including pathogens, in ships' ballast water. We contend that a major advancement in the study of ballast-water microorganisms in particular, and of aquatic pathogens in general, will be expedited sample analysis, such as provided by the elegant technology of DNA microarrays. In order to use DNA microarrays, however, one must establish the appropriate conditions to bind target sequences in samples to multiple probes on the microarrays. We conducted proof-of-concept experiments to optimize simultaneous detection of multiple microorganisms using polymerase chain reaction (PCR) and Southern hybridization. We chose three target organisms, all potentially found in ballast water: a calicivirus, the bacterium Vibrio cholerae, and the photosynthetic protist Aureococcus anophagefferens. Here, we show simultaneous detection of multiple pathogens is possible, a result supporting the promising future use of microarrays for simultaneous detection of pathogens in ballast water.

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

The impact of onychomycosis on quality of life: development of an international onychomycosis-specific questionnaire to measure patient quality of life.

BACKGROUND: Onychomycosis is a widespread refractory disease deleteriously affecting quality of life via social stigma and disrupting daily activities. Many physicians perceive onychomycosis as a cosmetic rather than a medical problem. OBJECTIVE: Our purpose was to develop a questionnaire-based instrument to quantify the impact of onychomycosis on patients' quality of life. METHODS: The questionnaire was developed and validated in a multinational cross-sectional study. Completed questionnaires from 532 patients were analyzed: 284 toenail, 248 fingernail (onychomycosis or paronychia). RESULTS: The degree of quality of life impairment from onychomycosis varied by country studied, possibly reflecting cross-national health perception differences. Longer duration of disease, greater involvement of individual nails, and greater number of nails involved were associated with more serious adverse effects. Many physicians underestimated the associated degree of pain. CONCLUSION: The study confirms that onychomycosis physically and psychologically affects patients' lives. The questionnaire may be a valuable tool in evaluating the effect of therapeutic agents on quality of life of patients with onychomycosis.

Pharmacokinetics of doxepin in subjects with pruritic atopic dermatitis.

BACKGROUND: Doxepin applied topically by itself or in combination with triamcinolone acetonide is a safe and effective treatment for atopic dermatitis. OBJECTIVE: We evaluated the pharmacokinetic profile of doxepin and desmethyldoxepin after topical application of doxepin hydrochloride 5% cream alone or in combination with 0.025% triamcinolone acetonide (doxepin/TAC). METHODS: Twenty-four subjects with atopic dermatitis received either doxepin or doxepin/TAC cream 4 times daily for 7 days in a randomized, double-blind, controlled trial. Serum samples were obtained and pharmacokinetic parameters estimated from the dose-normalized serum concentrations of doxepin and desmethyldoxepin. Efficacy and adverse experiences were determined by physician and subject evaluations. RESULTS: Pharmacokinetic parameters (K(e ), t(1/2 ) and AUC) calculated in 9 subjects (doxepin/TAC = 4 subjects, doxepin = 5 subjects) with detectable serum concentrations were similar for both groups. Pruritus relief and lessening of pruritus severity were significantly greater with doxepin/TAC than doxepin alone. CONCLUSION: Topically applied doxepin is safe and effective therapy for pruritus.

Effect of onychomycosis on quality of life.

BACKGROUND: Onychomycosis impairs normal nail functions, causes considerable pain, interferes with daily activities, and has negative psychosocial effects. OBJECTIVE: Our purpose was to determine patients' perception of onychomycosis on the quality of life. METHODS: A total of 258 patients with confirmed onychomycosis were surveyed by telephone at three centers. Responses to a standardized quality-of-life questionnaire were analyzed for patient demographics, physical and functional impact, psychosocial impact, and economic impact. RESULTS: Highest positive responses were nail-trimming problems (76%), embarrassment (74%), pain (48%), nail pressure (40%), and discomfort wearing shoes (38%). Ability to pick up small objects was impaired in 41% of subjects with fingernail involvement. More than 58 onychomycosis-related sick days and 468 medical visits (1.8 per subject) were reported during a 6-month period. CONCLUSION: Onychomycosis has significant social, psychologic, health, and occupational effects. Relevance of quality-of-life issues to overall health, earning potential, and social functioning should prompt reconsideration of the value of aggressive treatment of and financial coverage for onychomycosis.

A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea.

The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low.

The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis.

OBJECTIVE: To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques. DESIGN: Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study. SETTING: Medical center outpatient dermatology services. PARTICIPANTS: One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms. INTERVENTIONS: Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B). MAIN OUTCOME MEASURES: Treatment success and plaque elevation, scaling, and erythema vs time. RESULTS: The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily. CONCLUSION: The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.

Impact of onychomycosis on quality of life.

The author reviews the current knowledge of the impact of onychomycosis on quality of life. Like other visible disorders of the integumentary system, onychomycosis affects many aspects of life, including physical functioning, interpersonal interactions, and emotional state. After examining the nature of quality of life and the study instruments used to measure it, the author reviews several studies that have examined the relationship between onychomycosis and quality of life. The author concludes that onychomycosis is a significant medical problem that has a great impact on patients' lives and should therefore be treated as definitively as possible.

Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.

BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options. OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.

American Academy of Dermatology guidelines of care. Development and process.

Medical practice guidelines are being developed at an accelerating pace, in all areas of medicine, for a wide range of uses. The field of practice guideline development is not new, but a number of important economic and health care issues have renewed interest in their creation. In 1987, in response to many of these issues, the American Academy of Dermatology took a leadership role and began a process designed to develop guidelines for disease entities treated by dermatologists. The result was a set of clinical practice guidelines and the most comprehensive dermatology guideline development processes to date. Herein we describe the guideline development process in its current, refined form and discuss some of its unique and important characteristics. New applications of guidelines, outside of clinical practice improvement, have made their development controversial. Nevertheless, it is important for the medical profession to lead in this effort, and the American Academy of Dermatology continues to explore ways to refine and update its guidelines to reflect the latest medical science and technology.

Fluorescence photography in the evaluation of hyperpigmentation in photodamaged skin.

BACKGROUND: Treatment-related changes in hyperpigmentation are difficult to quantify with visible light photography, especially when the changes are subtle. OBJECTIVE: Our purpose was to determine the utility and reliability of fluorescence photography to measure changes in mottled and diffuse hyperpigmentation. METHODS: Thirty-two subjects, with mildly to moderately photodamaged skin, completed a 36-week, double-blind, vehicle-controlled study of tretinoin cream 0.025%. Clinical evaluation of hyperpigmentation as well as standard flash photographs and fluorescence photographs were obtained at baseline and week 36. RESULTS: The fluorescence photographs were evaluated blindly and yielded macule counts that decreased significantly from baseline in tretinoin-treated subjects compared with vehicle-treated subjects (31% vs 11% decrease; p = 0.02). Diffuse hyperpigmentation, as evaluated from the fluorescence photographs, decreased 16% from baseline for tretinoin-treated subjects and increased 5% for vehicle-treated subjects (p < 0.01). No significant differences in mottled or diffuse hyperpigmentation were observed between groups through clinical evaluation. CONCLUSION: Fluorescence photography is a noninvasive method that is sensitive in the evaluation and quantification of distribution and changes of mottled and diffuse hyperpigmentation.

Oxyhemoglobin is a quantifiable measure of experimentally induced chronic tretinoin inflammation and accommodation in photodamaged skin.

Chronic exposure to a weak irritant leads to inflammatory changes which may be followed by pigmentary changes and accommodation. The inflammatory responses to acute exposure to an irritant have been extensively studied. This study investigated quantitatively the inflammatory reactions produced in photodamaged skin with chronic application of a weak chemical irritant (tretinoin cream 0.025%) over a period of 9 months (36 weeks). Forty-eight subjects with moderately to severely photodamaged skin were enrolled in a 36-week, double-blind placebo-controlled study. Tretinoin cream was applied nightly on the distal two thirds of one dorsal forearm and placebo on the other. The proximal third of each dorsal forearm received no treatment and served as control. Clinical assessments and diffuse reflectance measurements were made at 7 time points during treatment. Apparent concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and melanin were estimated by analysis of the diffuse reflectance spectra. No changes were observed in the apparent HbO2 or the Hb concentration of the placebo-treated or control sites, thus establishing a reliable baseline. The apparent HbO2 concentration of the tretinoin-treated sites increased significantly from baseline to a maximum at 12-18 weeks of treatment, then returned to baseline with continued applications. The changes in HbO2 concentration agreed closely with clinical assessments of erythema. The apparent melanin concentration, corresponding to diffuse hyperpigmentation, showed a large seasonal decrease in both the control and the treated sites, with an additional decrease in the treated sites between 12 and 18 weeks. Erythema appeared after repeated applications and eventually resolved under continuous treatment. The maximum decrease in hyperpigmentation occurred simultaneously with the maximum increase in erythema.

Polarized light photography enhances visualization of inflammatory lesions of acne vulgaris.

BACKGROUND: Polarized light photography has been used to selectively differentiate surface from subsurface features of photoaged skin. OBJECTIVE: Our purpose was to compare acne assessments obtained from clinical evaluations with assessments from photographs obtained with flash photography and with perpendicular polarized light photography. METHODS: Assessments of acne with the Cunliffe scale were made of 32 subjects. Retrospective evaluations of standard and perpendicular polarized light photographs were made in a blinded fashion by a panel of evaluators. RESULTS: Visualization of inflammatory acne lesions was enhanced with perpendicular polarized light photography, with clear delineation of erythematous borders. Acne assessments with the use of a Cunliffe scale were significantly higher (p = 0.001) from perpendicular polarized light photographs than for clinical evaluations. CONCLUSION: Polarized light photography enhances visualization of inflammatory acne lesions in a manner not possible with conventional flash photographs, permitting accurate evaluation of the extent of disease and the effectiveness of therapy.