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[Biotyping of Propionibacterium acnes strains isolated from patients with acne vulgaris].

Propionibacterium acnes is the main bacterial etiologic agent in acne vulgaris pathogenesis. The rate of antibiotic resistant P. acnes isolates is less than 10% in our country. The aim of this study was to biotype P. acnes strains which were isolated from acne vulgaris patients and to investigate the biotype distribution in our region. P. acnes isolates from 64 patients (18 male, 46 female; mean age 19 +/- 3.1 years) were included in the study and biotyped by sugar-specific pH changes using sorbitol, erythritol and ribose. Results were compared with the global acne grading scores and clinical types of the patients. The frequency rates of P. acnes biotypes were found as follows; 40 strains (62.5%) were biotype I, 3 (4.7%) were biotype II, 20 (31.3%) were biotype III and one (1.6%) was biotype IV, whereas biotype V was not detected. The acne cases who were admitted to dermatology outpatient clinics mostly complained of papulopustuler and nodulocystic lesions. Therefore the detection of antibiotic resistance rates of P. acnes strains by mass screening of the community has a growing importance. Since P. acnes biotype III is the main biotype which causes the most severe acne reactions, the 31.3% rate of frequency found in our study, can not be overlooked. As a result, this data should be considered as a guide while prescribing antibiotics for the treatment of acne patients.

Acne Vulgaris↗

The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women.

Acne is common and often leads to significant psychologic and physical morbidity. From clinical experience, acne appears to run in families; however, very few studies have investigated the genetic basis of this very common skin disease. A large twin study based on 458 pairs of monozygotic and 1099 pairs of dizygotic twins, all women with a mean age of 46 y was performed to investigate the relative contribution of genetic and environmental factors on the liability to acne. In addition, potential risk factors were assessed in twins with and without acne in a nested cross-sectional design. Fourteen percent of the twins reported a history of acne. Genetic modeling using acne scores showed that 81% (95% confidence interval 73-87%) of the variance of the disease was attributable to additive genetic effects. The remaining 19% was attributed to unique (i.e., unshared) environmental factors. Of the potential risk factors tested in 400 acne twins and 2414 unaffected twins, only apolipoprotein A1 serum levels were significantly lower in acne twins even after adjusting for age and weight. Family history of acne was also significantly associated with an increased risk. No significant differences were found between acne twins and nonacne twins for weight, body mass index, height, birth weight, hair thinning, reproductive factors as well as cholesterol, triglycerides, high-density lipoprotein, and glucose levels. The lower serum levels of apolipoprotein A1 in acne twins were also confirmed when analyzing acne discordant twin pairs. The evidence of a major genetic influence on acne should stimulate the search for potential genes that may lead to new therapeutic approaches.

Acne Vulgaris↗

Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses.

Acne vulgaris is a common disorder that affects 40-50 million people in the USA alone. The pathogenesis of acne is multifactorial, including hormonal, microbiological and immunological mechanisms. One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). TLRs are pattern recognition receptors that recognize pathogen-associated molecular patterns conserved among microorganisms and elicit immune responses. We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Using transfectant cells we found that TLR2 was sufficient for NF-kappaB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes.P. acnes induced activation of IL-12 and IL-8 production by primary human monocytes, and this cytokine production was inhibited by anti-TLR2-blocking antibody. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for the treatment of this common skin disease.

Acne Vulgaris↗

Antibody response to crude cell lysate of propionibacterium acnes and induction of pro-inflammatory cytokines in patients with acne and normal healthy subjects.

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.

Acne Vulgaris↗

Antibiotic-resistant Propionibacterium acnes on the skin of patients with moderate to severe acne in Stockholm.

The objective was to study the prevalence and antibiotic susceptibility patterns of Propionibacterium acnes strains isolated from patients with moderate to severe acne in Stockholm, Sweden and to determine the diversity of pulsed-field gel electrophoresis types among resistant P. acnes strains. One hundred antibiotic-treated patients and 30 non-antibiotic-treated patients with moderate to severe acne participated in the investigation. Facial, neck and trunk skin samples were taken with the agar gel technique. The susceptibility of P. acnes strains to tetracycline, erythromycin, clindamycin and trimethoprim-sulfamethoxazole was determined by the agar dilution method. The genomic profiles of the resistant strains were determined by pulsed-field gel electrophoresis. In the group of patients treated with antibiotics, resistant P. acnes strains were recovered in 37%, while in the non-antibiotic group of patients the incidence of resistant strains was 13%. Thus antibiotic-resistant P. acnes strains were significantly more often isolated from antibiotic-treated patients with moderate to severe acne than from non-antibiotic-treated patients (odds ratio, 3.8; P=0.01). There was a genetic diversity among the P. acnes strains. Forty-four different patterns of SpeI DNA digests were detected and two predominant clones were found. P. acnes strains exhibited different antibiotic susceptibility patterns and identical genotypes or vice versa. A person can be colonized with different strains with varying degrees of antibiotic resistance. The risk of increased resistance of P. acnes must be considered when treating acne patients with antibiotics, and especially long-term therapy should be avoided.

Journal Article↗

Acne and Propionibacterium acnes.

The involvement of microorganisms in the development of acne has a long and checkered history. Just over 100 years ago, Propionibacterium acnes (then known as Bacillus acnes) was isolated from acne lesions, and it was suggested that P. acnes was involved in the pathology of the disease. The 1960s saw the use of antibiotics to treat acne, and the consequent clinical success combined with reductions in P. acnes gave new impetus to the debate. Over the past two decades, the inevitable emergence of antibiotic-resistant strains of P. acnes as a consequence of acne therapy not only has reopened the debate as to the role of P. acnes in acne, but also has created some serious health care implications.

Acne Vulgaris↗

Intergeneric and intrageneric inhibition between strains of Propionibacterium acnes and micrococcaceae, particularly Staphylococcus epidermidis, isolated from normal skin and acne lesions.

Two hundred and forty-one strains or resident skin bacteria comprising 93 isolates of Propionob acterium acnes and 148 of Micrococcaceae derived from 36 acne patients and 8 control subjects were screened for their ability to inhibit 32 indicator strains, including 20 strains of P. acnes and 12 strains of Staphylococcus epidermidis derived from patients with all grades of acne and from normal skin. Fifty-three strains (22%) showed some activity against at least one indicator strain. Both broad- and narrow-spectrum inhibition was detected. Inhibitory isolates of P. acnes outnumbered inhibitory Micrococcaceae by four to one. There was a low frequency of inhibition of S. epidermidis by Micrococcaceae (2.7%) and by P. acnes (1.1%) and a higher frequency of inhibition of P. acnes by Micrococcaceae (9.5%) and by P. acnes (40.8%). Furthermore, 81.8% of the subjects sampled possessed strains inhibitory to P. acnes. The significance of this finding is, as yet, unknown. No difference in the prevalence of active strains in normal (20%) and acne (22.5%) skin was detected. These findings suggest that the possession of inhibitory strains and conversely the possession of sensitive strains does not predispose to acne.

Acne Vulgaris↗

Acne prevalence in secondary school students and their perceived difficulty in accessing acne treatment.

AIMS: To describe the epidemiology of acne in New Zealand adolescents and their access to acne treatment. METHODS: Secondary analysis of data collected in the 'Youth2000' survey. A random sample of 12,934 Year 9-13 students, from 133 secondary schools across New Zealand, was invited to participate. The survey included items asking about self-perceived acne and access to acne treatment. RESULTS: The 'Youth2000' school response rate was 85.7%, the student response rate 75.0%, and the overall response rate 64.3%. Of the 9570 students who completed the questions on acne, 67.3% reported having acne. 'Problem acne' was reported by 14.1% of students and was more frequently reported by female, Pacific, and older students. Students with 'problem acne' (as well as female, Maori, and Pacific students) were significantly more likely to report difficulty accessing medical treatment for acne (46.0% vs 13.3%; OR 5.29). These differences persisted after controlling for socioeconomic factors. CONCLUSIONS: Acne is perceived as a significant health problem by nearly 1 in 7 adolescents. For those with 'problem acne,' effective treatment is available but not necessarily accessible. There are also disparities in access to treatment, particularly for females, Maori, and Pacific ethnic groups. This important youth health issue needs to be addressed.

Acne Vulgaris↗

Make-up improves the quality of life of acne patients without aggravating acne eruptions during treatments.

Boehncke et al. suggested that decorative cosmetics can improve the quality of life (QOL) of skin diseases. But dermatologists sometimes discourage female acne patients from applying make-up since decorative cosmetics are considered one of the aggravating factors for acne eruptions. The purpose of this study is to assess whether make-up application interferes with acne treatments and how QOL changes when the make-up items are designed for acne patients and used in order to disguise acne eruptions. Eighteen female acne patients were trained by a make-up artist and advised to apply acne-designed basic and decorative cosmetics for 2 to 4 weeks while their acne was appropriately treated. The acne-severity and QOL of patients were assessed before and after the study. The results revealed that the number of acne eruptions decreased even though patients were applying make-up. The QOL scores of Skindex-16, GHQ30 and anxiety state index greatly improved. Our results suggest that dermatologists should encourage acne patients to utilize appropriate make-up to improve their QOL.

Acne Vulgaris↗

Effect of zinc gluconate on propionibacterium acnes resistance to erythromycin in patients with inflammatory acne: in vitro and in vivo study.

Tetracyclines and macrolide antibiotics have been in use for acne treatment for more than 20 years. Since 1992 increasing resistance to these antibiotics, and especially to erythromycin, is reported with Propionibacterium acnes. Zinc salts have demonstrated their efficacy in inflammatory acne treatment as well as their bacteriostatic activity against Propionibacterium acnes. The objective of our work was firstly to determine whether the clinical anti-inflammatory efficacy of zinc salts was altered in the presence of erythromycin resistant strains in vivo, and secondly to study the in vitro and in vivo effect of zinc on the sensitivity of Propionibacterium acnes strains to erythromycin. Thirty patients with inflammatory acne were treated by zinc gluconate with a daily dose of 30 mg for two months and bacteriologic samples were taken at D0, D30 and D60. In vivo, this study displayed a reduction in the number of inflammatory lesions after a 2-month treatment whether or not Propionibacterium acnes carriage was present. Concurrently, in vitro addition of zinc salts in the culture media of Propionibacterium acnes reduced resistance of Propionibacterium acnes strains to erythromycin. Thus, association of zinc salts via a systemic route and topical erythromycin treatment seems an interesting option in the light of an increasing number of patients carrying erythromycin resistant Propionibacterium acnes strains.

Acne Vulgaris↗

Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL.

BACKGROUND: Keratinocytes form the first line of defence in the skin and alert the host to danger by the production of a number of cytokines and chemokines. However, the interaction of commensal microorganisms with keratinocytes has not been well studied. OBJECTIVES: To investigate the effect of viable and nonviable cells of Propionibacterium acnes in both exponential and stationary growth phases, and of P. acnes GroEL on cytokine production by human primary keratinocytes. METHODS: Actively proliferating or contact-inhibited keratinocytes were cocultured with viable or formaldehyde-killed P. acnes cells in either the exponential or stationary phase of growth. Culture supernatants were assayed by enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor (GM-CSF). Keratinocytes were also stimulated with different concentrations of P. acnes GroEL and supernatants assayed for cytokines. RESULTS: Viable P. acnes in the stationary phase of growth stimulated keratinocyte monolayers to produce significantly higher amounts of IL-1alpha, TNF-alpha and GM-CSF than unstimulated keratinocytes. Viable exponential-phase bacteria stimulated production of significantly higher amounts of TNF-alpha and GM-CSF but these levels were significantly lower than those for stimulation with stationary-phase bacteria. Nonviable P. acnes from either growth phase was not able to stimulate cytokine production. P. acnes GroEL at concentrations in the range 0.05-1.0 micro g mL(-1) was able to induce increased production of cytokines by keratinocytes in a dose-dependent manner. This was analogous to stimulation with Escherichia coli GroEL. CONCLUSIONS: Stimulation of cytokine production by P. acnes and P. acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms.

Cell Division↗

The Acne Quality of Life Index (Acne-QOLI): development and validation of a brief instrument.

BACKGROUND: Acne affects many people and can be detrimental to affected patients' quality of life. Assessing the impact of acne on quality of life requires well-validated and reliable measures of acne-specific quality of life that are brief and easy to administer and interpret. OBJECTIVES: This paper reports on the development and validation of the Acne Quality of Life Index (Acne-QOLI) for use in clinical care, research, and product development. METHODS: Focus groups consisting of people from demographically different populations were conducted to identify the most relevant domains of functioning affected by acne; on the basis of these findings, candidate items were developed. An initial item pool of 58 items was included in a survey of 480 persons with mild to severe acne ranging in age from 12 to 62 years. Factor analysis and qualitative analysis were used to reduce the item pool to 21 items. The construct validity, concurrent validity, internal consistency, and test-retest reliability of the items were evaluated. RESULTS: The 21-item Acne-QOLI showed excellent face validity, content validity, concurrent validity, and construct validity. High internal consistency and test-retest reliability were also found. CONCLUSIONS: Quality of life is now recognized as an important outcome in medical care. The Acne-QOLI is a brief and easily administered and interpreted measure of acne-related quality of life that can be used in clinical care, research, and product development.

Acne Vulgaris↗

Polymorphonuclear leukocyte lysosomal release in response to Propionibacterium acnes in vitro and its enhancement by sera from inflammatory acne patients.

Propionibacterium acnes cells were tested for the ability to trigger lysosomal hydrolase release from human polymorphonuclear leukocytes. Representative strains of P. acnes serotype I and II failed to stimulate lysosomal release in the absence of serum. P. acnes growth culture supernatants failed to trigger release under any test condition. Addition of fresh or heat-inactivated human serum resulted in lysosomal hydrolase release directly proportional to the number of P. acnes/PMN. Pooled sera from acne patients, with a high anti-P. acnes titer stimulated release to P. acnes. Preabsorption of this reagent with P. acnes cells reduced the anti-P. acnes titer and produced 93.37 +/- 11.49% inhibition of lysosomal enzyme release compared to unabsorbed anti-serum. Electron microscopy indicated that P. acnes was readily phagocytosed by PMNs when fresh or heated serum was present.

Acne Vulgaris↗

Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.

Acne Vulgaris↗

Health-related quality of life among patients with facial acne -- assessment of a new acne-specific questionnaire.

The psychosocial effects of facial acne are well accepted but until recently few validated instruments existed which were suitable for use in clinical trials. The aim of this study was to assess measurement characteristics (reproducibility, correlation with acne severity, and sensitivity to detect change after acne therapy) of a new acne-specific quality of life instrument, the Acne-QoL. We found that the Acne-QoL is reliable, valid and able to distinguish differences across severity groups and improvement over 16 weeks of standard therapy. The use of the Acne-QoL should aid physicians in understanding the impact of facial acne on young adults, and may be useful in assessing therapeutic effects in acne clinical trials.

Acne Vulgaris↗

Quality of life and acne in Scottish adolescent schoolchildren: use of the Children's Dermatology Life Quality Index (CDLQI) and the Cardiff Acne Disability Index (CADI).

BACKGROUND: Acne vulgaris is known to adversely affect all aspects of quality of life. However, although acne is thought to occur in the majority of adolescents, there are few data currently available on the impact of acne in this age group. OBJECTIVES: Measurement of the impairment of health-related quality of life (HRQoL) in teenage Scottish schoolchildren in a comparative study using two HRQoL questionnaires. A secondary objective was to collect data on the use and perceived efficacy of medical and over-the-counter (OTC) preparations. STUDY DESIGN: An anonymous cross-sectional survey of 200 adolescent (15-18 years) Dundee schoolchildren was conducted by means of two self-reported questionnaires: the Children's Dermatology Life Quality Index (CDLQI) and the Cardiff Acne Disability Index (CADI). Data on demographics and therapeutic modalities and their perceived efficacy were also collected. ANALYSIS: Statistical analysis was performed using the package Stata 7.0. RESULTS: Self-reported acne was present in 83% of teenagers (147/178), with similar sex distribution (54% male, 46% female). The overall mean CDLQI score (max. 30) was low 1.7 {6% impairment} (CI -1 to 0), range 0-19. Nine pupils scored between 5 and 9 {17-30% impairment} suggesting moderate HRQoL impairment and three scored > 10 {> 33% impairment} indicating severe impairment. The overall mean CADI score (max. 15) of 1.9 {13% impairment}, CI 0 to 1 (range 0-15) was also low, but 12 pupils scored between 5 and 9 {33-60% impairment}, one scoring 10 + {> 67% impairment} and one scoring the maximum, 15 {100% impairment}. There was no significant difference in mean scores between the sexes in either questionnaire (P = 0.5). There was good correlation between the results from the two questionnaires (Spearman's rho = 0.62). Three-quarters (75%) had used OTC products, of which only a third (33%) felt they helped 'a lot'. Fifteen per cent were receiving prescribed treatment from their doctors of which 66% found it helpful. CONCLUSIONS: Self-reported acne occurred in 83% (147/178) of the Scottish teenagers involved in this study, which confirms previous reports of a high prevalence of acne in teenagers. Cross-validation of the CLDQI and CADI demonstrated good correlation and both scales were easy to administer and identified 11% (16/147) of teenagers who perceive their lives to be significantly affected by their acne (8% moderately to severely, 3% severely). It is important to identify and treat such teenagers early to reduce the future socio-economic burden of their acne.

Acne Vulgaris↗

Acne in infancy and acne genetics.

Acne is a disease that can be seen in the first year of age, early childhood, prepubertal age and puberty. Neonatal acne is due mainly to considerable sebum excretion rate, and infantile acne because of high androgens of adrenal origin in girls and of adrenal and testes in boys. These pathogenic mechanisms are characteristic in these ages. Important factors like early onset of comedones and high serum levels of dehydroepiandrosterone sulfate are predictors of severe or long-standing acne in prepubertal age. Hereditary factors play an important role in acne. Neonatal, nodulocystic acne and conglobate acne has proven genetic influences. Postadolescent acne is related with a first-degree relative with the condition in 50% of the cases. Chromosomal abnormalities, HLA phenotypes, polymorphism of human cytochrome P-450 1A1 and MUC1 gene are involved in the pathogenesis of acne. Several other genes are being studied.

Acne Vulgaris↗