Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum.
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To better define the role of bacteria in inflammatory acne vulgaris, we have investigated the ability of four strains of Propionibacterium acnes and three strains of Propionibacterium granulosum to activate complement. Complement activation was assayed by incubating normal human serum with varying concentrations of each strain and measuring residual total hemolytic complement activity. When serum was tested unaltered, P. acnes strains were approximately threefold more potent than an equal weight of P. granulosum in consuming complement, which could reflect classical and/or alternative pathway activation. All strains also consumed complement in serum chelated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, which selectively assays alternative pathway activation. Incubation of unaltered serum with both P. acnes and P. granulosum resulted in immunoelectrophoretic conversion of C4, C3, and factor B of the alternative pathway. Incubation of chelated serum resulted in conversion of C3 and factor B. These data taken together suggest that both species can activate complement through either pathway. Serum incubated with P. acnes was chemotactic for polymorphonuclear leukocytes, and this chemotactic activity was largely C5 dependent as shown by antibody inhibition. It is suggested that complement activation may occur in vivo in acne, and the inflammatory response may be contributed to by the generation of C5-dependent chemotactic factors. (+info)
Psychosocial impact of acne vulgaris: evaluating the evidence.
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This paper reviews current evidence presented by recent studies on the impact of acne on psychosocial health. Study methodologies, including case-control and cross-sectional surveys, have demonstrated psychological abnormalities including depression, suicidal ideation, anxiety, psychosomatic symptoms, including pain and discomfort, embarrassment and social inhibition. Effective treatment of acne was accompanied by improvement in self-esteem, affect, obsessive-compulsiveness, shame, embarrassment, body image, social assertiveness and self-confidence. Acne is associated with a greater psychological burden than a variety of other disparate chronic disorders. Future studies with a longitudinal cohort design may provide further validation of the causal inference between acne and psychosocial disability provided by the current literature. (+info)
Antibody response to crude cell lysate of propionibacterium acnes and induction of pro-inflammatory cytokines in patients with acne and normal healthy subjects.
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Propionibacterium acnes (P. acnes) plays an important role in the disease pathogenesis of acne vulgaris, a disorder of pilosebaceous follicles, seen primarily in the adolescent age group. In the present study, the presence of antibodies against P. acnes (MTCC1951) were detected in acne patient (n=50) and disease free controls (n=25) using dot-ELISA and Western blot assay. The ability of P. acnes to induce pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs), obtained from acne patients and healthy subjects, were also analysed. The patients (n=26) who were culture positive for skin swab culture, were found to have a more advanced disease and higher antibody titres (1:4000 to > 1:16000) compared to the P. acnes negative patients (n=24) and normal controls (n=25). An analysis of patients' sera by western blot assay recognized a number of antigenic components of P. acnes, ranging from 29 to 205 kDa. The major reactive component was an approximately 96 kDa polypeptide, which was recognised in 92% (24 of 26) of the patients sera. Further, the P. acnes culture supernatant, crude cell lysate and heat killed P. acnes whole cells, obtained from 72-h incubation culture, were observed to be able to induce significant amounts of IL-8 and tumor necrosis factor alpha (TNF-alpha) by the PBMCs in both the healthy subjects and patients, as analysed by cytokine-ELISA. The levels of cytokines were significantly higher in the patients than the healthy subjects. A major 96 kDa polypeptide reactant was eluted from the gel and was found to cause dose dependent stimulation of the productions of IL-8 and TNF-alpha. Thus, the above results suggest that both humoral and pro-inflammatory responses play major roles in the pathogenesis of acne. (+info)
The pustular skin lesions in Behcet's syndrome are not sterile.
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BACKGROUND: The pustular skin lesions of Behcet's syndrome (BS) are clinically and histopathologically similar to ordinary acne, but BS patients get lesions at sites not commonly involved in acne, such as the legs and arms. The microbiology of these lesions has not been studied adequately. OBJECTIVE: To make a detailed study of the microbiology of BS lesions. METHODS: Subjects were patients with BS and acne vulgaris. Material was extracted from pustular lesions and directly plated to aerobic and anaerobic media by sterile swab. Anaerobic bacteria were identified using a commercial kit (API 20A). Aerobic bacteria were defined by standard procedures. RESULTS: 58 BS patients and 37 acne patients were studied. Pustules were cultured from the following sites: BS patients (70 pustules): face (17), back (30), chest (2), arm (4), leg (17); acne patients (37 pustules): face (27), back (6), chest (1), arm (2), leg (1). At least one type of microorganism was grown from each pustule. Staphylococcus aureus (41/70, 58.6%, p = 0.008) and Prevotella spp (17/70, 24.3%, p = 0.002) were significantly more common in pustules from BS patients, and coagulase negative staphylococci (17/37, 45.9%, p = 0.007) in pustules from acne patients. CONCLUSIONS: The pustular lesions of BS are not usually sterile. The microbiology of these lesions is different from ordinary acne. It remains to be determined whether the infection is secondary or has any pathogenic implications. (+info)
Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain.
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Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized by accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue resulting in joint disease. Certain medications have been reported to cause cutaneous hyperpigmentation resembling that of alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible diagnosis of alkaptonuria were examined at the National Institutes of Health Clinical Center between June 2000 and March 2004. The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine. Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels. All 5 patients were women who had taken minocycline for dermatologic or rheumatologic disorders for extended periods. Minocycline-induced hyperpigmentation should be considered in the differential diagnosis of ochronosis. This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria. (+info)
Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.
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OBJECTIVES: To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains. DESIGN: This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks. SETTING: Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England. PARTICIPANTS: Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face. INTERVENTIONS: Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group). MAIN OUTCOME MEASURES: The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots). RESULTS: The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study. CONCLUSIONS: The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability). (+info)
Prevalence of facial acne vulgaris in late adolescence and in adults.
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A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution. (+info)
A systematic review of the evidence for 'myths and misconceptions' in acne management: diet, face-washing and sunlight.
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BACKGROUND: Lay perceptions that diet, hygiene and sunlight exposure are strongly associated with acne causation and exacerbation are common but at variance with the consensus of current dermatological opinion. OBJECTIVES: The objective of this study was to carry out a review of the literature to assess the evidence for diet, face-washing and sunlight exposure in acne management. METHODS: Original studies were identified by searches of the Medline, EMBASE, AMED (Allied and Complementary Medicine), CINAHL, Cochrane, and DARE databases. Methodological information was extracted from identified articles but, given the paucity of high quality studies found, no studies were excluded from the review on methodological grounds. RESULTS: Given the prevalence of lay perceptions, and the confidence of dermatological opinion in rebutting these perceptions as myths and misconceptions, surprisingly little evidence exists for the efficacy or lack of efficacy of dietary factors, face-washing and sunlight exposure in the management of acne. Much of the available evidence has methodological limitations. CONCLUSIONS: Based on the present state of evidence, clinicians cannot be didactic in their recommendations regarding diet, hygiene and face-washing, and sunlight to patients with acne. Advice should be individualized, and both clinician and patient cognizant of its limitations. (+info)