Acne Vulgaris

Background

What skin disease evokes more emotional distress than acne? Pimples come in a variety of shapes and sizes and of varying severity. Fundamentally, these are folliculitis at varying stages of development.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis and Treatment

Commonly Used Terms

EPIDEMIOLOGY CHARACTERIZATION

INCIDENCE Occurs in up to 95% of the population

DISEASE ASSOCIATIONS CHARACTERIZATION

SAPHO SYNDROME

Acne with chronic recurrent multifocal osteomyelitis involving the mandible as part of the SAPHO syndrome: case report.

Roldan JC, Terheyden H, Dunsche A, Kampen WU, Schroeder JO.

Department of Oral and Maxillofacial Surgery, Christian-Albrechts-Universitat, Kiel, Germany.
Br J Oral Maxillofac Surg 2001 Apr;39(2):141-4 Abstract quote
For 12 years, a 26-year-old man had acne conglobata and a non-suppurative diffuse sclerosing osteomyelitis of the mandible as part of a chronic recurrent multifocal osteomyelitis of the sternum, the pelvic bones, and the femoral head, and aseptic arthritis of the knee, the fibulotalar, and the sternoclavicular joints.

This fulfills the formal criteria of the SAPHO syndrome. Repeated surgical and antibiotic treatment combined with hyperbaric oxygen caused partial improvement. Complete relief and partial disappearance of the scintigraphic lesions was achieved with long-term corticosteroids, non-steroidal anti-inflammatory drugs, minocycline, and isotretinoin.

PATHOGENESIS CHARACTERIZATION

DEFENSIN

Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions.

Chronnell CM, Ghali LR, Ali RS, Quinn AG, Holland DB, Bull JJ, Cunliffe WJ, McKay IA, Philpott MP, Muller-Rover S.

Centre for Cutaneous Research, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK.
J Invest Dermatol 2001 Nov;117(5):1120-5 Abstract quote
A rich residential microflora is harboured by the distal outer root sheath of the hair follicle and the hair canal - normally without causing skin diseases. Although the basic mechanisms involved in the development of inflammation during acne vulgaris remain unclear, microbial agents might play an important role in this process.

In this study we have analyzed by in situ hybridization and immunohistochemistry the expression patterns of two antimicrobial peptides, human beta defensin-1 and human beta defensin-2, in healthy human hair follicles as well as in perilesional and intralesional skin of acne vulgaris lesions such as comedones, papules, and pustules. Strong defensin-1 and defensin-2 immunoreactivity was found in all suprabasal layers of the epidermis, the distal outer root sheath of the hair follicle, and the pilosebaceous duct. Marked defensin-1 and defensin-2 immunoreactivity was also found in the sebaceous gland and in the basal layer of the central outer root sheath including the bulge region. The majority of acne biopsies displayed a marked upregulation of defensin-2 immunoreactivity in the lesional and perilesional epithelium - in particular in pustules - and a less marked upregulation of defensin-1 immunoreactivity.

The upregulation of beta-defensin expression in acne vulgaris lesions compared to controls suggests that beta-defensins may be involved in the pathogenesis of acne vulgaris.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

VIDEO MICROSCOPY

Polarized light photography and videomicroscopy greatly enhance the capability of estimating the therapeuic response to a topical retinoid (adapalene) in acne vulgaris.

Rizova E, Pagnoni PA, Stoudemayer T, Poncet M, Kligman AM.

SKIN Incorporated, Conshohocken, Pennsylvania, USA.

Cutis 2001 Oct;68(4 Suppl):25-33 Abstract quote
Assessment of improvement in acne lesions following treatment is often based on clinical evaluation and photographs. However, limitations are associated with this sublective evaluation, making it difficult to accurately review individual acne lesions and to observe early response to therapy. Conventional photographs do not allow us to visualize small lesions, and it can be difficult to differentiate inflammatory lesions as papules or small nodules.

Our objective was to evaluate a new standardized method for tracking individual acne lesions based on photographs. The effect of adapalene gel 0.1% on both inflammatory and noninflammatory acne lesions was evaluated using this technique. Polarized light photography and videomicroscopy were used to record the evolution of acne lesions over a 16-week period in 5 volunteers with moderate acne vulgaris. During the first 4 weeks before treatment, acne lesions were evaluated on a 3-times weekly basis to establish a pattern of progression and determine the length of time to resolution. Sebum secretion rates were monitored using Sebutape adhesive patches applied to the forehead and both cheeks for 1 hour. After 4 weeks, adapalene gel 0.1% was used once daily at bedtime for 8 weeks; polarized light photography, videomicroscopy, and assessment of sebum production followed treatment response. This treatment period was followed by a further 4-week phase, after which acne lesions and sebum secretion rates were evaluated.

Our results showed that the new methodology was appropriate to track acne lesions and allowed an accurate and more oblective evaluation of individual lesions. Using this methodology demonstrated that adapalene gel 0.1% causes rapid resolution of inflammatory and noninflammatory lesions. The probability of clearing inflammatory and noninflamma tory lesions during the treatment period increased, and the probability of new lesions appearing decreased. Sebum secretion rates declined in patients while on study drug, returning to near pretreatment levels following therapy cessation.

Using sophisticated photography and videomicroscopy every other day proved to be a valuable, noninvasive, and reliable method of following response to adapalene treatment in patients with moderate acne vulgaris.

LABORATORY MARKERS

LIPID ABNORMALITIES

Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne.

Bershad S, Rubinstein A, Paterniti JR, Le NA, Poliak SC, Heller B, Ginsberg HN, Fleischmajer R, Brown WV.
N Engl J Med 1985 Oct 17;313(16):981-5 Abstract quote
Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne.

We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug.

If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease.

Dyslipidemia and a reversible decrease in insulin sensitivity induced by therapy with 13-cis-retinoic acid.

Koistinen HA, Remitz A, Gylling H, Miettinen TA, Koivisto VA, Ebeling P.

Department of Medicine, Division of Geriatrics, Helsinki University Central Hospital, Helsinki, Finland.
Diabetes Metab Res Rev 2001 Sep-Oct;17(5):391-5 Abstract quote
BACKGROUND: 13-cis-Retinoic acid (Roaccutan) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity.

METHODS: We studied 11 men [aged 24+/-2 years (mean+/-SEM), body mass index (BMI) 22.1+/-0.9 kg/m(2)] who received Roaccutan treatment for acne for a period averaging 5 months but who were otherwise healthy. The insulin sensitivity of the subjects was measured before, during and 1-3 months after the end of treatment using the euglycaemic hyperinsulinaemic clamp technique.

RESULTS: Treatment with 13-cis-retinoic acid reduced total (59+/-4 vs 55+/-4 micromol/kg/min, p<0.02), oxidative (25+/-1 vs 22+/-2 micromol/kg/min, p<0.05) and non-oxidative (36+/-3 vs 33+/-3 micromol/kg/min, p=0.05) glucose disposal rate, and there was a 4% increase in HbA(1c) (from 5.2+/-0.07 to 5.4+/-0.07%, p<0.02). After treatment cessation these values returned to baseline. 13-cis-Retinoic acid treatment also resulted in increased very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phospholipid concentrations.

CONCLUSION: Treatment of acne with 13-cis-retinoic acid reduces insulin sensitivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

ACNE FULMINANS

The treatment of acne fulminans: a review of 25 cases.

Seukeran DC, Cunliffe WJ.

Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U K.
Br J Dermatol 1999 Aug;141(2):307-9 Abstract quote
The treatment of acne fulminans has been difficult. It is difficult to perform a controlled treatment trial due to the rarity of the complication. However, it is possible to compare four different therapeutic regimens which have evolved with time in the management of 25 patients over a period of 25 years. Oral antibiotics produced a slow response in the resolution of acne and systemic symptoms. The addition of a systemic steroid produced a quick resolution of systemic features, but the time until resolution of the acne was longer than when it was used in combination with oral isotretinoin.

The protocols which used a combination of prednisolone and isotretinoin led to faster control of systemic features as well as clearance of acne when compared with other protocols. This was particularly so if the oral steroid was used sooner rather than later.

We conclude that the preferred treatment of acne fulminans is oral prednisolone 0.5-1 mg/kg daily for 4-6 weeks (thereafter slowly reduced to zero) with oral isotretinoin being added to the regimen at the fourth week, initially at 0.5 mg/kg daily and gradually increased to achieve complete clearance.

CHLORACNE

Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

Pelclova D, Fenclova Z, Dlaskova Z, Urban P, Lukas E, Prochazka B, Rappe C, Preiss J, Kocan A, Vejlupkova J.

Department of Occupational Medicine, Charles University, Prague, Czech Republic.

Arch Environ Health 2001 Nov-Dec;56(6):493-500 Abstract quote
Presented herein are the results of follow-up examinations of 13 workers performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in a herbicide production plant. In these workers, the current mean plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high-resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid).

This mean value corresponded to an estimated concentration of approximately 5,000 pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level indicates that this group was one of the most heavily exposed groups to 2,3,7,8-TCDD described in the literature. Patients with persistent chloracne had significantly higher plasma levels of 2,3,7,8-TCDD than persons without chloracne. A significant, positive correlation was found between plasma levels of 2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed since 1974. During 1996, there was a significant positive correlation between 2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides. Also in 1996, significant correlations were found between neuropsychological variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were observed between neuropsychological variables and (1) the highest levels of triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996, (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest level of cholesterol since the year 1969, and (5) cholesterol levels in 1996. Such correlations are biologically plausible, and they provide evidence of impaired cognitive performance (i.e., memory first), with a concurrent increase of plasma lipid levels. Abnormal electromyography, electroencephalography, and visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of former workers.

Abnormal electroencephalography findings occurred more frequently in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p < .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the 1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was statistically significant (p < .05).

HISTOPATHOLOGY CHARACTERIZATION

CHLORACNE

Chloracne: histopathologic findings in one case.

Pastor MA, Carrasco L, Izquierdo MJ, Farina MC, Martin L, Renedo G, Requena L.

Departments of Dermatology and Pathology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.
J Cutan Pathol 2002 Apr;29(4):193-9 Abstract quote
BACKGROUND: : Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder.

METHODS: : We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae.

RESULTS: Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs.

CONCLUSIONS: Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT

GENERAL

Acne therapy: A methodologic review.

Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN.

Departments of Pediatrics, Dermatology, Oncology, and Epidemiology, Johns Hopkins School of Medicine and Bloomberg School of Public Health.
J Am Acad Dermatol 2002 Aug;47(2 Pt 1):231-40 Abstract quote
BACKGROUND: Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies.

OBJECTIVE: We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities.

METHODS: This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers.

RESULTS: Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons.

CONCLUSION: Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided.

COMBINATION THERAPIES

A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris.

Zouboulis CC, Derumeaux L, Decroix J, Maciejewska-Udziela B, Cambazard F, Stuhlert A.

Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany.
Br J Dermatol 2000 Sep;143(3):498-505 Abstract quote
BACKGROUND: A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris.

OBJECTIVES: We aimed to follow up this study.

METHODS: The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris.

RESULTS: At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated.

CONCLUSIONS: A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.

ADAPALENE

Randomized, controlled, bilateral (split-face) comparison trial of the tolerability and patient preference of adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne vulgaris.

Egan N, Loesche MC, Baker MM.

International Research Services, Inc, Rockland, Maine, USA.

Cutis 2001 Oct;68(4 Suppl):20-4 Abstract quote
Poor patient compliance is one of the main reasons for treatment failure in acne. Our objective was to evaluate the tolerability and patient preference of adapalene gel 0.1% compared with tretinoin microsphere gel 0.1% using a randomized, controlled, investigator-masked, bilateral (split-face), 4-week comparative study of the 2 products when applied once daily in 40 patients.

We found that adapalene produced less stinging/burning than tretinoin at weeks 1 and 4 and, overall, more patients felt more skin irritation on the side of the face treated with tretinoin than on the side treated with adapalene (P<.05). At week 4, a significantly greater number of patients preferred adapalene gel 0.1% to tretinoin microsphere gel 0.1% (72.5% vs 27.5%, respectively, P<.01).

CLINDAMYCIN

Comparison of the efficacy and safety of a combination topical gel formulation of benzoyl peroxide and clindamycin with benzoyl peroxide, clindamycin and vehicle gel in the treatments of acne vulgaris.

Leyden JJ, Berger RS, Dunlap FE, Ellis CN, Connolly MA, Levy SF.

Department of Dermatology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Am J Clin Dermatol 2001;2(1):33-9 Abstract quote
BACKGROUND: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris. When used in combination, they promise greater efficacy than either individual agent used alone and the combined use of benzoyl peroxide with topical antibacterial has been shown to decrease the emergence of antibacterial resistant species.

OBJECTIVE: The objective was to determine the efficacy and safety of a combination benzoyl peroxide plus clindamycin in a gel formulation compared with each of its 2 active constituents in gel vehicle, and gel vehicle given alone in the treatment of acne vulgaris.

METHODS: In this 10-week, multicenter, double-blind trial, 480 patients with moderate to moderately severe acne were randomized to receive twice-daily treatment with 5% benzoyl peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clindamycin, or vehicle.

RESULTS: Significantly greater reductions in the number of inflammatory and total lesions were demonstrated in patients using combination therapy compared with those using any of its 3 individual components. Likewise, both physicians' and patients' global evaluations showed significantly greater improvements with the combination therapy than with its individual components. The most frequent adverse effect, dry skin, occurred to a similar extent in the combination and benzoyl peroxide treatment groups.

CONCLUSION: The improved efficacy obtained with the combination therapy was accompanied by a tolerability profile similar to that of benzoyl peroxide alone, making this new combination product an alternative antimicrobial therapy for acne vulgaris.

LASER RESURFACING

Laser resurfacing for facial acne scars.

Jordan RE, Cummins CL, Burls AJ, Seukeran DC.

Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.
Cochrane Database Syst Rev 2001;(1):CD001866 Abstract quote
BACKGROUND: Most people have acne at some stage during their life, with about one per cent being left with permanent acne scars. Recent laser techniques are thought to be more effective than chemical peels and dermabrasion.

OBJECTIVES: To assess the effects of laser resurfacing for treating facial acne scars.

SEARCH STRATEGY: We searched MEDLINE (1966 to April 1999), EMBASE (1980 to April 1999), Science Citation Index (1981 to April 1999), the Cochrane Controlled Trials Register (April 1999), DARE (April 1999), INAHTA (April 1999), NHS HTA Internet site (April 1999). Dermatological Surgery (1995 to March 1999) and the British Journal of Dermatology (1995 to September 1999) were handsearched. We searched the reference lists of relevant articles and contacted experts and commercial laser manufacturers.

SELECTION CRITERIA: Randomised controlled trials which compare different laser resurfacing techniques for treating patients with facial acne scars, or compare laser resurfacing with other resurfacing techniques or no treatment.

DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies, assessed the quality of studies and extracted data.

MAIN RESULTS: No randomised controlled trials where laser treatment was compared to either placebo or a different type of laser were found. Most of the 27 studies uncovered were poor quality case series with small numbers of acne-scarred patients.

REVIEWER'S CONCLUSIONS: The lack of good quality evidence does not enable any conclusions to be drawn about the effectiveness of lasers for treating atrophic or ice-pick acne scars. Well designed randomised controlled comparisons of carbon dioxide versus Erbium:YAG laser are urgently needed.

MINOCYCLINE

Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy.

Pierard-Franchimont C, Goffin V, Arrese JE, Martalo O, Braham C, Slachmuylders P, Pierard GE.

Department of Dermatopathology, University Medical Center Sart Tilman, Liege, Belgium.

Skin Pharmacol Appl Skin Physiol 2002 Mar-Apr;15(2):112-9 Abstract quote
BACKGROUND: Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare. AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages.

METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings.

RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria.

CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.

PHOTOTHERAPY

Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris.

Papageorgiou P, Katsambas A, Chu A.

Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K.
Br J Dermatol 2000 May;142(5):973-8 Abstract quote
In this study we have evaluated the use of blue light (peak at 415 nm) and a mixed blue and red light (peaks at 415 and 660 nm) in the treatment of acne vulgaris. One hundred and seven patients with mild to moderate acne vulgaris were randomized into four treatment groups: blue light, mixed blue and red light, cool white light and 5% benzoyl peroxide cream.

Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min. Comparative assessment between the three light sources was made in an observer-blinded fashion, but this could not be achieved for the use of benzoyl peroxide. Assessments were performed every 4 weeks. After 12 weeks of active treatment a mean improvement of 76% (95% confidence interval 66-87) in inflammatory lesions was achieved by the combined blue-red light phototherapy; this was significantly superior to that achieved by blue light (at weeks 4 and 8 but not week 12), benzoyl peroxide (at weeks 8 and 12) or white light (at each assessment). The final mean improvement in comedones by using blue-red light was 58% (95% confidence interval 45-71), again better than that achieved by the other active treatments used, although the differences did not reach significant levels.

We have found that phototherapy with mixed blue-red light, probably by combining antibacterial and anti-inflammatory action, is an effective means of treating acne vulgaris of mild to moderate severity, with no significant short-term adverse effects.

ORAL CONTRACEPTIVES

Efficacy of a low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for the treatment of moderate acne: A randomized, placebo-controlled trial.

Leyden J, Shalita A, Hordinsky M, Swinyer L, Stanczyk FZ, Weber ME.

Department of Dermatology, University of Pennsylvania Hospital, Philadelphia, USA.
J Am Acad Dermatol 2002 Sep;47(3):399-409 Abstract quote
BACKGROUND: Acne is a multifactorial disease in which androgens appear to play an important role. A low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel (EE/LNG) has been shown to improve biochemical markers of androgenicity. Lowering bioavailable androgens may improve acne.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a low-dose oral contraceptive containing 20 microg of EE and 100 microg of LNG for the treatment of moderate acne.

METHODS: In a randomized, double-blind, placebo-controlled clinical trial, healthy female subjects (n = 371; >/=14 years old) with regular menstrual cycles and moderate facial acne were randomly assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts and clinician global assessment were performed at the end of each cycle. Patient self-assessments were collected and biochemical markers of androgenicity were also measured.

RESULTS: At the end of the study, the number of inflammatory and total lesions was significantly lower with EE/LNG compared with placebo (P <.05). Patients in the EE/LNG group also had significantly better scores for clinician global and patient self-assessments than those in the placebo group (P <.05). Biochemical markers of androgenicity improved during EE/LNG treatment compared with placebo and baseline values.

CONCLUSION: A low-dose oral contraceptive containing EE/LNG is effective and safe for the treatment of moderate acne.

RETINOIDS

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

Strauss JS, Leyden JJ, Lucky AW, Lookingbill DP, Drake LA, Hanifin JM, Lowe NJ, Jones TM, Stewart DM, Jarratt MT, Katz I, Pariser DM, Pariser RJ, Tschen E, Chalker DK, Rafal ES, Savin RP, Roth HL, Chang LK, Baginski DJ, Kempers S, McLane J, Eberhardt D, Leach EE, Bryce G, Hong J.

Department of Dermatology, University of Iowa Health Care, Iowa City, IA 52242-1090, USA.

J Am Acad Dermatol 2001 Aug;45(2):187-95 Abstract quote
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.

Use of isotretinoin (Accutane) in the United States: Rapid increase from 1992 through 2000.

Wysowski DK, Swann J, Vega A.

Office of Post-Marketing Drug Risk Assessment, Food and Drug Administration.

J Am Acad Dermatol 2002 Apr;46(4):505-9 Abstract quote
BACKGROUND: Isotretinoin, a drug approved to treat severe recalcitrant nodular acne, has been marketed in the United States since 1982. The drug is an effective treatment for acne that is refractory to other therapies, but it is a teratogen and can cause serious side effects.

OBJECTIVE: Our purpose was to describe trends in the use of isotretinoin in the United States from marketing through year 2000 and summarize characteristics of patients and prescribers.

METHODS: Data from 2 pharmaceutical marketing research databases, the National Prescription Audit Plus and the National Disease and Therapeutic Index, and from 2 health plan networks were obtained and analyzed.

RESULTS: Retail pharmacies dispensed 19.8 million outpatient prescriptions for isotretinoin from marketing in 1982 through 2000. From 1983 through 1993, the median annual number of prescriptions was just over 800,000; between 1992 and 2000, the number of prescriptions increased 2.5-fold (250%) to nearly 2 million in year 2000. The increases registered in the health plans were somewhat larger: about 275% increases from 1995 through 1999. There is no ICD-9 code for nodulocystic acne; consequently, the type of acne treated with isotretinoin is not determinable from these data. However, between 1993 and 2000, the proportion of isotretinoin treatment for severe acne declined from 63% to 46%, whereas the proportion of treatment for mild and moderate acne increased from 31% to 49%. Data also indicated that the sex distribution of patients was nearly even, and that 63% of male patients prescribed isotretinoin were 15 to 19 years old, whereas 51% of female patients were 15 to 24 years old.

CONCLUSION: In the last 8 years, there has been a 2.5-fold (250%) increase in the number of dispensed prescriptions for isotretinoin in the United States. Data also reveal an increasing proportion of isotretinoin use for mild and moderate acne

TAZAROTENE

Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial.

Webster GF, Berson D, Stein LF, Fivenson DP, Tanghetti EA, Ling M.

Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Cutis 2001 Jun;67(6 Suppl):4-9 Abstract quote
Tazarotene 0.1% gel and tretinoin 0.025% gel are both effective in the treatment of acne vulgaris.

Results of a multicenter, double-blind, randomized, parallel-group study that compared the efficacy and tolerability of these drugs are presented here. A total of 143 patients with mild-to-moderate facial acne vulgaris were randomized to receive tazarotene 0.1% gel or tretinoin 0.025% gel once daily for 12 weeks. Tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in reducing the open comedo count (P < or = .05), the total noninflammatory lesion count (P < or = .05), and the total inflammatory lesion count (not statistically significant). At some time points, tazarotene was associated with increased irritation, but peeling, erythema, dryness, burning, and itching never exceeded trace levels.

We conclude that tazarotene 0.1% gel is more effective than tretinoin 0.025% gel in reducing noninflammatory lesions and similarly effective in reducing inflammatory lesions.

Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel.

Bershad S, Singer GK, Parente JE, Tan MH, Sherer DW, Persaud AN, Lebwohl M.
Arch Dermatol 2002 Apr;138(4):481-9 Abstract quote
CONTEXT: Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown.

OBJECTIVES: To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control.

DESIGN: A randomized, masked, vehicle-controlled trial.

SETTING: Outpatient facilities at an urban medical school and an affiliated suburban office practice.

PARTICIPANTS: Ninety-nine volunteers with facial acne were enrolled; 81 completed the study.

INTERVENTION: Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application.

MAIN OUTCOME MEASURES: Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe.

RESULTS: By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P<.001), and reduction in overall disease severity (30% and 29% vs 3%; P<.001). Local adverse effects did not differ significantly among the 3 groups after week 4.

CONCLUSION: Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

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LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
VIDEO MICROSCOPY
Polarized light photography and videomicroscopy greatly enhance the capability of estimating the therapeuic response to a topical retinoid (adapalene) in acne vulgaris. Rizova E, Pagnoni PA, Stoudemayer T, Poncet M, Kligman AM. SKIN Incorporated, Conshohocken, Pennsylvania, USA.	Cutis 2001 Oct;68(4 Suppl):25-33 Abstract quote Assessment of improvement in acne lesions following treatment is often based on clinical evaluation and photographs. However, limitations are associated with this sublective evaluation, making it difficult to accurately review individual acne lesions and to observe early response to therapy. Conventional photographs do not allow us to visualize small lesions, and it can be difficult to differentiate inflammatory lesions as papules or small nodules. Our objective was to evaluate a new standardized method for tracking individual acne lesions based on photographs. The effect of adapalene gel 0.1% on both inflammatory and noninflammatory acne lesions was evaluated using this technique. Polarized light photography and videomicroscopy were used to record the evolution of acne lesions over a 16-week period in 5 volunteers with moderate acne vulgaris. During the first 4 weeks before treatment, acne lesions were evaluated on a 3-times weekly basis to establish a pattern of progression and determine the length of time to resolution. Sebum secretion rates were monitored using Sebutape adhesive patches applied to the forehead and both cheeks for 1 hour. After 4 weeks, adapalene gel 0.1% was used once daily at bedtime for 8 weeks; polarized light photography, videomicroscopy, and assessment of sebum production followed treatment response. This treatment period was followed by a further 4-week phase, after which acne lesions and sebum secretion rates were evaluated. Our results showed that the new methodology was appropriate to track acne lesions and allowed an accurate and more oblective evaluation of individual lesions. Using this methodology demonstrated that adapalene gel 0.1% causes rapid resolution of inflammatory and noninflammatory lesions. The probability of clearing inflammatory and noninflamma tory lesions during the treatment period increased, and the probability of new lesions appearing decreased. Sebum secretion rates declined in patients while on study drug, returning to near pretreatment levels following therapy cessation. Using sophisticated photography and videomicroscopy every other day proved to be a valuable, noninvasive, and reliable method of following response to adapalene treatment in patients with moderate acne vulgaris.
LABORATORY MARKERS
LIPID ABNORMALITIES
Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne. Bershad S, Rubinstein A, Paterniti JR, Le NA, Poliak SC, Heller B, Ginsberg HN, Fleischmajer R, Brown WV.	N Engl J Med 1985 Oct 17;313(16):981-5 Abstract quote Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne. We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug. If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease.
Dyslipidemia and a reversible decrease in insulin sensitivity induced by therapy with 13-cis-retinoic acid. Koistinen HA, Remitz A, Gylling H, Miettinen TA, Koivisto VA, Ebeling P. Department of Medicine, Division of Geriatrics, Helsinki University Central Hospital, Helsinki, Finland.	Diabetes Metab Res Rev 2001 Sep-Oct;17(5):391-5 Abstract quote BACKGROUND: 13-cis-Retinoic acid (Roaccutan) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity. METHODS: We studied 11 men [aged 24+/-2 years (mean+/-SEM), body mass index (BMI) 22.1+/-0.9 kg/m(2)] who received Roaccutan treatment for acne for a period averaging 5 months but who were otherwise healthy. The insulin sensitivity of the subjects was measured before, during and 1-3 months after the end of treatment using the euglycaemic hyperinsulinaemic clamp technique. RESULTS: Treatment with 13-cis-retinoic acid reduced total (59+/-4 vs 55+/-4 micromol/kg/min, p<0.02), oxidative (25+/-1 vs 22+/-2 micromol/kg/min, p<0.05) and non-oxidative (36+/-3 vs 33+/-3 micromol/kg/min, p=0.05) glucose disposal rate, and there was a 4% increase in HbA(1c) (from 5.2+/-0.07 to 5.4+/-0.07%, p<0.02). After treatment cessation these values returned to baseline. 13-cis-Retinoic acid treatment also resulted in increased very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phospholipid concentrations. CONCLUSION: Treatment of acne with 13-cis-retinoic acid reduces insulin sensitivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
GENERAL
Acne therapy: A methodologic review. Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN. Departments of Pediatrics, Dermatology, Oncology, and Epidemiology, Johns Hopkins School of Medicine and Bloomberg School of Public Health.	J Am Acad Dermatol 2002 Aug;47(2 Pt 1):231-40 Abstract quote BACKGROUND: Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies. OBJECTIVE: We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities. METHODS: This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers. RESULTS: Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons. CONCLUSION: Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided.
COMBINATION THERAPIES
A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris. Zouboulis CC, Derumeaux L, Decroix J, Maciejewska-Udziela B, Cambazard F, Stuhlert A. Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany.	Br J Dermatol 2000 Sep;143(3):498-505 Abstract quote BACKGROUND: A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris. OBJECTIVES: We aimed to follow up this study. METHODS: The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris. RESULTS: At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated. CONCLUSIONS: A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.
ADAPALENE
Randomized, controlled, bilateral (split-face) comparison trial of the tolerability and patient preference of adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne vulgaris. Egan N, Loesche MC, Baker MM. International Research Services, Inc, Rockland, Maine, USA.	Cutis 2001 Oct;68(4 Suppl):20-4 Abstract quote Poor patient compliance is one of the main reasons for treatment failure in acne. Our objective was to evaluate the tolerability and patient preference of adapalene gel 0.1% compared with tretinoin microsphere gel 0.1% using a randomized, controlled, investigator-masked, bilateral (split-face), 4-week comparative study of the 2 products when applied once daily in 40 patients. We found that adapalene produced less stinging/burning than tretinoin at weeks 1 and 4 and, overall, more patients felt more skin irritation on the side of the face treated with tretinoin than on the side treated with adapalene (P<.05). At week 4, a significantly greater number of patients preferred adapalene gel 0.1% to tretinoin microsphere gel 0.1% (72.5% vs 27.5%, respectively, P<.01).
CLINDAMYCIN
Comparison of the efficacy and safety of a combination topical gel formulation of benzoyl peroxide and clindamycin with benzoyl peroxide, clindamycin and vehicle gel in the treatments of acne vulgaris. Leyden JJ, Berger RS, Dunlap FE, Ellis CN, Connolly MA, Levy SF. Department of Dermatology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.	Am J Clin Dermatol 2001;2(1):33-9 Abstract quote BACKGROUND: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris. When used in combination, they promise greater efficacy than either individual agent used alone and the combined use of benzoyl peroxide with topical antibacterial has been shown to decrease the emergence of antibacterial resistant species. OBJECTIVE: The objective was to determine the efficacy and safety of a combination benzoyl peroxide plus clindamycin in a gel formulation compared with each of its 2 active constituents in gel vehicle, and gel vehicle given alone in the treatment of acne vulgaris. METHODS: In this 10-week, multicenter, double-blind trial, 480 patients with moderate to moderately severe acne were randomized to receive twice-daily treatment with 5% benzoyl peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clindamycin, or vehicle. RESULTS: Significantly greater reductions in the number of inflammatory and total lesions were demonstrated in patients using combination therapy compared with those using any of its 3 individual components. Likewise, both physicians' and patients' global evaluations showed significantly greater improvements with the combination therapy than with its individual components. The most frequent adverse effect, dry skin, occurred to a similar extent in the combination and benzoyl peroxide treatment groups. CONCLUSION: The improved efficacy obtained with the combination therapy was accompanied by a tolerability profile similar to that of benzoyl peroxide alone, making this new combination product an alternative antimicrobial therapy for acne vulgaris.
LASER RESURFACING
Laser resurfacing for facial acne scars. Jordan RE, Cummins CL, Burls AJ, Seukeran DC. Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.	Cochrane Database Syst Rev 2001;(1):CD001866 Abstract quote BACKGROUND: Most people have acne at some stage during their life, with about one per cent being left with permanent acne scars. Recent laser techniques are thought to be more effective than chemical peels and dermabrasion. OBJECTIVES: To assess the effects of laser resurfacing for treating facial acne scars. SEARCH STRATEGY: We searched MEDLINE (1966 to April 1999), EMBASE (1980 to April 1999), Science Citation Index (1981 to April 1999), the Cochrane Controlled Trials Register (April 1999), DARE (April 1999), INAHTA (April 1999), NHS HTA Internet site (April 1999). Dermatological Surgery (1995 to March 1999) and the British Journal of Dermatology (1995 to September 1999) were handsearched. We searched the reference lists of relevant articles and contacted experts and commercial laser manufacturers. SELECTION CRITERIA: Randomised controlled trials which compare different laser resurfacing techniques for treating patients with facial acne scars, or compare laser resurfacing with other resurfacing techniques or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies, assessed the quality of studies and extracted data. MAIN RESULTS: No randomised controlled trials where laser treatment was compared to either placebo or a different type of laser were found. Most of the 27 studies uncovered were poor quality case series with small numbers of acne-scarred patients. REVIEWER'S CONCLUSIONS: The lack of good quality evidence does not enable any conclusions to be drawn about the effectiveness of lasers for treating atrophic or ice-pick acne scars. Well designed randomised controlled comparisons of carbon dioxide versus Erbium:YAG laser are urgently needed.
MINOCYCLINE
Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy. Pierard-Franchimont C, Goffin V, Arrese JE, Martalo O, Braham C, Slachmuylders P, Pierard GE. Department of Dermatopathology, University Medical Center Sart Tilman, Liege, Belgium.	Skin Pharmacol Appl Skin Physiol 2002 Mar-Apr;15(2):112-9 Abstract quote BACKGROUND: Some antibiotics represent a mainstay in acne treatment. However, studies comparing their efficacies are rare. AIM: To evaluate the clinical and in vivo antibacterial effect of lymecycline and minocycline at different dosages. METHOD: Eighty-six patients with moderate to severe acne were enrolled in a randomized, double-blind, intent-to-treat study comparing in three parallel groups the effect of (1) lymecycline 300 mg daily for 12 weeks, (2) minocycline 50 mg daily for 12 weeks and (3) minocycline 100 mg daily for 4 weeks followed by 50 mg daily for 8 weeks. Evaluations were made at the screening visit and at five on-treatment visits. They consisted of clinical counts of acne lesions and evaluations of bacterial viability using dual flow cytometry performed on microorganisms collected from sebaceous infundibula by cyanoacrylate strippings. RESULTS: Patients receiving minocycline 100/50 mg had the best clinical outcome, particularly in the reduction of the number of papules. By the end of the trial, the microbial response to minocycline 100/ 50 mg was also superior to either of the other two treatments. There were less live and more dead bacteria. CONCLUSION: In this trial, minocycline 100/50 mg was superior for the treatment of inflammatory acne when compared to lymecycline 300 mg and minocycline 50 mg.
PHOTOTHERAPY
Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris. Papageorgiou P, Katsambas A, Chu A. Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K.	Br J Dermatol 2000 May;142(5):973-8 Abstract quote In this study we have evaluated the use of blue light (peak at 415 nm) and a mixed blue and red light (peaks at 415 and 660 nm) in the treatment of acne vulgaris. One hundred and seven patients with mild to moderate acne vulgaris were randomized into four treatment groups: blue light, mixed blue and red light, cool white light and 5% benzoyl peroxide cream. Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min. Comparative assessment between the three light sources was made in an observer-blinded fashion, but this could not be achieved for the use of benzoyl peroxide. Assessments were performed every 4 weeks. After 12 weeks of active treatment a mean improvement of 76% (95% confidence interval 66-87) in inflammatory lesions was achieved by the combined blue-red light phototherapy; this was significantly superior to that achieved by blue light (at weeks 4 and 8 but not week 12), benzoyl peroxide (at weeks 8 and 12) or white light (at each assessment). The final mean improvement in comedones by using blue-red light was 58% (95% confidence interval 45-71), again better than that achieved by the other active treatments used, although the differences did not reach significant levels. We have found that phototherapy with mixed blue-red light, probably by combining antibacterial and anti-inflammatory action, is an effective means of treating acne vulgaris of mild to moderate severity, with no significant short-term adverse effects.
ORAL CONTRACEPTIVES
Efficacy of a low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for the treatment of moderate acne: A randomized, placebo-controlled trial. Leyden J, Shalita A, Hordinsky M, Swinyer L, Stanczyk FZ, Weber ME. Department of Dermatology, University of Pennsylvania Hospital, Philadelphia, USA.	J Am Acad Dermatol 2002 Sep;47(3):399-409 Abstract quote BACKGROUND: Acne is a multifactorial disease in which androgens appear to play an important role. A low-dose oral contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel (EE/LNG) has been shown to improve biochemical markers of androgenicity. Lowering bioavailable androgens may improve acne. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a low-dose oral contraceptive containing 20 microg of EE and 100 microg of LNG for the treatment of moderate acne. METHODS: In a randomized, double-blind, placebo-controlled clinical trial, healthy female subjects (n = 371; >/=14 years old) with regular menstrual cycles and moderate facial acne were randomly assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts and clinician global assessment were performed at the end of each cycle. Patient self-assessments were collected and biochemical markers of androgenicity were also measured. RESULTS: At the end of the study, the number of inflammatory and total lesions was significantly lower with EE/LNG compared with placebo (P <.05). Patients in the EE/LNG group also had significantly better scores for clinician global and patient self-assessments than those in the placebo group (P <.05). Biochemical markers of androgenicity improved during EE/LNG treatment compared with placebo and baseline values. CONCLUSION: A low-dose oral contraceptive containing EE/LNG is effective and safe for the treatment of moderate acne.
RETINOIDS
A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne. Strauss JS, Leyden JJ, Lucky AW, Lookingbill DP, Drake LA, Hanifin JM, Lowe NJ, Jones TM, Stewart DM, Jarratt MT, Katz I, Pariser DM, Pariser RJ, Tschen E, Chalker DK, Rafal ES, Savin RP, Roth HL, Chang LK, Baginski DJ, Kempers S, McLane J, Eberhardt D, Leach EE, Bryce G, Hong J. Department of Dermatology, University of Iowa Health Care, Iowa City, IA 52242-1090, USA.	J Am Acad Dermatol 2001 Aug;45(2):187-95 Abstract quote 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.
Use of isotretinoin (Accutane) in the United States: Rapid increase from 1992 through 2000. Wysowski DK, Swann J, Vega A. Office of Post-Marketing Drug Risk Assessment, Food and Drug Administration.	J Am Acad Dermatol 2002 Apr;46(4):505-9 Abstract quote BACKGROUND: Isotretinoin, a drug approved to treat severe recalcitrant nodular acne, has been marketed in the United States since 1982. The drug is an effective treatment for acne that is refractory to other therapies, but it is a teratogen and can cause serious side effects. OBJECTIVE: Our purpose was to describe trends in the use of isotretinoin in the United States from marketing through year 2000 and summarize characteristics of patients and prescribers. METHODS: Data from 2 pharmaceutical marketing research databases, the National Prescription Audit Plus and the National Disease and Therapeutic Index, and from 2 health plan networks were obtained and analyzed. RESULTS: Retail pharmacies dispensed 19.8 million outpatient prescriptions for isotretinoin from marketing in 1982 through 2000. From 1983 through 1993, the median annual number of prescriptions was just over 800,000; between 1992 and 2000, the number of prescriptions increased 2.5-fold (250%) to nearly 2 million in year 2000. The increases registered in the health plans were somewhat larger: about 275% increases from 1995 through 1999. There is no ICD-9 code for nodulocystic acne; consequently, the type of acne treated with isotretinoin is not determinable from these data. However, between 1993 and 2000, the proportion of isotretinoin treatment for severe acne declined from 63% to 46%, whereas the proportion of treatment for mild and moderate acne increased from 31% to 49%. Data also indicated that the sex distribution of patients was nearly even, and that 63% of male patients prescribed isotretinoin were 15 to 19 years old, whereas 51% of female patients were 15 to 24 years old. CONCLUSION: In the last 8 years, there has been a 2.5-fold (250%) increase in the number of dispensed prescriptions for isotretinoin in the United States. Data also reveal an increasing proportion of isotretinoin use for mild and moderate acne
TAZAROTENE
Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Webster GF, Berson D, Stein LF, Fivenson DP, Tanghetti EA, Ling M. Jefferson Medical College, Philadelphia, Pennsylvania, USA.	Cutis 2001 Jun;67(6 Suppl):4-9 Abstract quote Tazarotene 0.1% gel and tretinoin 0.025% gel are both effective in the treatment of acne vulgaris. Results of a multicenter, double-blind, randomized, parallel-group study that compared the efficacy and tolerability of these drugs are presented here. A total of 143 patients with mild-to-moderate facial acne vulgaris were randomized to receive tazarotene 0.1% gel or tretinoin 0.025% gel once daily for 12 weeks. Tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in reducing the open comedo count (P < or = .05), the total noninflammatory lesion count (P < or = .05), and the total inflammatory lesion count (not statistically significant). At some time points, tazarotene was associated with increased irritation, but peeling, erythema, dryness, burning, and itching never exceeded trace levels. We conclude that tazarotene 0.1% gel is more effective than tretinoin 0.025% gel in reducing noninflammatory lesions and similarly effective in reducing inflammatory lesions.
Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel. Bershad S, Singer GK, Parente JE, Tan MH, Sherer DW, Persaud AN, Lebwohl M.	Arch Dermatol 2002 Apr;138(4):481-9 Abstract quote CONTEXT: Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown. OBJECTIVES: To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control. DESIGN: A randomized, masked, vehicle-controlled trial. SETTING: Outpatient facilities at an urban medical school and an affiliated suburban office practice. PARTICIPANTS: Ninety-nine volunteers with facial acne were enrolled; 81 completed the study. INTERVENTION: Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application. MAIN OUTCOME MEASURES: Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe. RESULTS: By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P<.001), and reduction in overall disease severity (30% and 29% vs 3%; P<.001). Local adverse effects did not differ significantly among the 3 groups after week 4. CONCLUSION: Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	Occurs in up to 95% of the population

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
ACNE FULMINANS
The treatment of acne fulminans: a review of 25 cases. Seukeran DC, Cunliffe WJ. Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U K.	Br J Dermatol 1999 Aug;141(2):307-9 Abstract quote The treatment of acne fulminans has been difficult. It is difficult to perform a controlled treatment trial due to the rarity of the complication. However, it is possible to compare four different therapeutic regimens which have evolved with time in the management of 25 patients over a period of 25 years. Oral antibiotics produced a slow response in the resolution of acne and systemic symptoms. The addition of a systemic steroid produced a quick resolution of systemic features, but the time until resolution of the acne was longer than when it was used in combination with oral isotretinoin. The protocols which used a combination of prednisolone and isotretinoin led to faster control of systemic features as well as clearance of acne when compared with other protocols. This was particularly so if the oral steroid was used sooner rather than later. We conclude that the preferred treatment of acne fulminans is oral prednisolone 0.5-1 mg/kg daily for 4-6 weeks (thereafter slowly reduced to zero) with oral isotretinoin being added to the regimen at the fourth week, initially at 0.5 mg/kg daily and gradually increased to achieve complete clearance.
CHLORACNE
Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Pelclova D, Fenclova Z, Dlaskova Z, Urban P, Lukas E, Prochazka B, Rappe C, Preiss J, Kocan A, Vejlupkova J. Department of Occupational Medicine, Charles University, Prague, Czech Republic.	Arch Environ Health 2001 Nov-Dec;56(6):493-500 Abstract quote Presented herein are the results of follow-up examinations of 13 workers performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in a herbicide production plant. In these workers, the current mean plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high-resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid). This mean value corresponded to an estimated concentration of approximately 5,000 pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level indicates that this group was one of the most heavily exposed groups to 2,3,7,8-TCDD described in the literature. Patients with persistent chloracne had significantly higher plasma levels of 2,3,7,8-TCDD than persons without chloracne. A significant, positive correlation was found between plasma levels of 2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed since 1974. During 1996, there was a significant positive correlation between 2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides. Also in 1996, significant correlations were found between neuropsychological variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were observed between neuropsychological variables and (1) the highest levels of triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996, (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest level of cholesterol since the year 1969, and (5) cholesterol levels in 1996. Such correlations are biologically plausible, and they provide evidence of impaired cognitive performance (i.e., memory first), with a concurrent increase of plasma lipid levels. Abnormal electromyography, electroencephalography, and visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of former workers. Abnormal electroencephalography findings occurred more frequently in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p < .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the 1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was statistically significant (p < .05).