[The presence and pathogenetic significance of human acne virus in hormonal acne diseases (acne vulgaris, indurata and conglobata)].
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The majority of recent publications on the immunology of Propionibacterium acnes relate to the potential use of the bacterium as an adjuvant or its use in rodent models of human inflammatory disease. These studies have increased the understanding of the potential effects of Propionibacterium acnes on cells of the mononuclear phagocyte system. Research into the immunology of acne and the role that Propionibacterium acnes plays in inflammatory acne has been limited, with efforts being focussed on the problems of Propionibacterium acnes resistance to antibiotics. Recent studies have indicated that inflammatory acne is a T cell-mediated disease, but whether Propionibacterium acnes is the initial stimulus for either the specific or non-specific recruitment of T cells in acne lesions is still a matter for conjecture.
In order to determine which structures in Propionibacterium acnes are most antigenic to severe acne patients, we studied the specificity of anti-P. acnes antibodies in serum from 15 nodulocystic acne patients and 5 normals. Complement fixation titers to P. acnes cell wall fractions were determined using guinea pig serum as a complement source. The mean titers of patients and normals to whole cells were 39.6 and 3 (p less than 0.1); to crude cell wall, 138 and 8 (p less than 0.01); and to protein and nucleic acid-free cell wall, 225 and 9.33 (p less than 0.001), respectively. The mean precipitin titer to P. acnes cytosol was 12.7 for patients and 0 for normals. Immunoelectrophoresis of cytosol from 8 P. acnes strains were developed with each of the 15 patient sera. A single broadly migrating anionic antigen was detected. The antigen was also present in P. acnes culture supernatants. Sephadex G-100 chromatography of cytosol revealed a single peak of antigenic reactivity at Mr = 100,000. Three patients' sera revealed a second weakly reacting antigen in the cytosol preparation. Twentyfold concentration of immunoglobulin from patient sera failed to reveal any other antigenic reactivities. The antigen was found to be resistant to nuclease, pronase, and lysozyme treatment; was precipitable with 70% ethanol; and was destroyed by sodium m-periodate--findings that are consistent with a carbohydrate structure.
We studied the susceptibility of antimicrobial agents to Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) isolated from acne patients. We measured the minimum inhibitory concentrations (MICs) of the following five drugs: roxithromycin (RXM), erythromycin (EM), clindamycin (CLDM), minocycline (MINO) and ofloxacin (OFLX), which are frequently used to treat acne and skin infections. We found many resistant strains of S. epidermidis and some resistant strains of P. acnes. There was a correlation between the resistance of S. epidermidis and the former therapy for acne, but no distinct correlation between the resistance of P. acnes and the former therapy for acne.
Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.
Systemic and topical antimicrobial treatment for acne vulgaris remains the mainstay method of therapy in Japan. Strains of Propionibacterium acnes (P. acnes) resistant to erythromycin (EM), clindamycin (CLDM), tetracycline (TC), doxycycline (DOXY) and minocycline (MINO) have been reported. The aim of the present study was to examine the antimicrobial susceptibility to 10 currently used antimicrobial agents of 50 strains of P. acnes isolated from acne lesions and identified using a Rap ID ANA II panel. Minimum inhibitory concentrations (MIC) were determined by the agar dilution method according to the criteria of the Japan Society of Chemotherapy. EM, ampicillin (ABPC), and CLDM were the most potent drugs, followed by MINO, nadifloxacin (NDFX), cephalexin (CEX), DOXY, ofloxacin (OFLX), and TC. In terms of the MIC80, EM and ABPC were the most potent, followed by CLDM, NDFX, MINO, CEX, DOXY, OFLX, TC and gentamycin (GM). Although most of the strains used were susceptible to the antimicrobial agents tested, strains of P. acnes resistant (MIC 12.5 mug/ml) to EM (4%), CLDM (4%), DOXY (2%) and TC (2%) were observed. In this study, no strains of P. acnes resistant to MINO were seen, suggesting that oral MINO is the most useful treatment for acne vulgaris with minimal risk of bacterial resistance.
BACKGROUND: Steroid acne is a folliculitis that can result from systemic or topical administration of steroid, and has been described as showing a similar clinical picture to Pityrosporum folliculitis, but there have been few reports about the incidence of Pityrosporum ovale and the effect of antimycotic drugs in steroid acne and other acneiform eruptions. Our purpose was to describe the association between steroid acne and P. ovale, and to confirm the superior efficacy of oral antifungal drugs over anti-acne drugs in the treatment of steroid acne. METHODS: The history, clinical features direct microscopy, histopathologic analysis, and therapeutic results of 125 cases with steroid acne or other acneiform eruptions were described and compared. RESULTS: Over 80% of patients with acneiform eruption receiving systemic steroid revealed significant numbers of P. ovale in the lesional follicle. Furthermore, oral antifungal drug (itraconazole) showed significantly better clinical and mycologic effects than any other group of medications used in this study. CONCLUSIONS: Steroid acne and other acneiform eruptions showing discrete follicular papules and/or pustules localized to the upper trunk and acneiform facial skin lesions associated with multiple acneiform lesions on the body in the summer period should be suspected as Pityrosporum folliculitis. In addition, oral antifungal drugs recommended for Pityrosporum folliculitis; however, it will require a larger case-control study to confirm the superiority of antifungal therapy over anti-acne treatment.
BACKGROUND: Acne vulgaris is an exceedingly common condition in adolescence and may extend into adult life in some individuals. Even though this condition is at times minimized, it has been found to have a profound impact in the quality of life of many affected individuals. Acne scarring can be even more of a source of psychological and social problems than active acne is, and when inadequately treated, the latter can lead to the former. Moderate and severe acne vulgaris usually require a regimen of systemic and/or topical medications, which are given for several months or even years and frequently require multiple visits to the physician office, the laboratory, etc. This results in loss of time at school and considerable expense. Side effects from medications and the frequent need to use alternative drugs when there is no response to medical treatment are possible. OBJECTIVE: To evaluate the role of a novel medical device that uses radiofrequency as a source of energy to produce volumetric tissue heating, while sparing the epidermis, allowing for a procedure with no down time and no postoperative care required. METHODS: Twenty-two patients, 10 women and 12 men, ranging in age from 16 to 28, with moderate to severe, scarring, cystic, active, acne vulgaris participated. Only nine of these patients were on concomitant medical treatment such as oral antibiotics or topical agents. All 22 patients were treated with a new nonablative radiofrequency unit, which delivers a concomitant spray of cryogen for epidermal sparing. One session was done in 20 patients and two sessions in 2 patients. The average fluence per energy delivery was 72 J/cm2. Follow-up ranged from 1 to 8 months. Patient questionnaires and active acne lesion counts were used to evaluate the response to treatment. RESULTS: Excellent response was seen in 82% (n=18). Modest response was seen in 9% (n=2), and no response was seen in 9% (n=2); t-test on active lesion counts before treatment and after treatment was less than 0.009004. No side effects were identified on any of these patients. No down time from the procedure was seen. Only topical anesthesia, ELA-Max 5% (Ferndale Labs, Ferndale, MI) was used; 59% of patients were on no acne medication before, during, or after the procedure. CONCLUSIONS: Nonablative radiofrequency appears to be a new safe and effective treatment alternative for moderate to severe acne vulgaris. Further research is in progress to evaluate this treatment modality in a larger number of patients.
To investigate the inflammatory and immunological aspects of severe acne, we examined the luminol-enhanced chemiluminescence of whole blood, T-cell subsets and natural killer cell functions in 11 patients with severe nodular acne and 4 patients with acne fulminans. In patients with severe nodular acne, the active phase of the disease, compared to the values in remission (means 47 mV, SD 24.8 and 32 mV, SD 8.3, p < 0.05). The patients with acne fulminans also showed high values in the active phase of the disease (mean mV 68.3, SD3.5) compared to remission (mean 30.5 mV, SD 15.3). No marked alterations were seen in the percentages of T-helper cells, T-suppressor cells or DR-positive lymphocytes or in the levels of soluble interleukin 2 receptor. The percentages and activities of natural killer cells did not show any significant changes either. Five patients (4 with severe nodular acne and one with acne fulminans, accounting for 33% of all patients) carried HLA Cw6 antigen, which is a significantly increased frequency compared to health controls (pc = 0.015). The present chemiluminescence results suggest that peripheral blood neutrophils are activated in patients with severe acne.
A questionnaire was presented to 2009 18--19 year old military recruitment candidates which enabled assessment of antipathy towards patients with severe acne vulgaris, the occupational handicap associated with severe acne and subjective inhibitions in acne patients. In addition, these persons were examined clinically with regard to presence of acne vulgaris. Finally, the level of education of the persons questioned was determined. The investigations show that severe acne has an appreciable disease rating. This results from antipathy of other people, the occupational inpediment and the psychological inhibitions of the acne patient. This disease rating appears to be objectively greater the lower the level of education of the acne patient. The disease rating does not appear to be entirely clear to the acne patient with a low level of education.
This report describes the case of a patient with a 14-month course of severe oligoarthritis associated with acne. Pure cultures of Propionibacterium acnes were isolated from synovial tissue and synovial fluid specimens collected from the same joint after a 4-month interval. After 2 months of treatment with roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal antiinflammatory drug (NSAID), followed by 4 months of treatment with azithromycin 1 gm/week and an NSAID, the synovitis persisted. Cultures of skin lesions and synovial fluid at this time were negative. Although P acnes has previously been isolated from bone specimens obtained from patients with osteitis associated with acne, this is the first report of the isolation of this microorganism from the synovial tissue of a patient with arthritis associated with acne. Our findings raise the question of the role of P acnes in the pathogenesis of arthritis associated with acne.
The minimal inhibitory concentration (MIC) of Propionibacterium acnes in seventy-five acne patients receiving long-term antibiotic therapy demonstrated the emergence of resistant strains. The mean MIC in thirty-three patients receiving long-term tetracycline was four to five times higher than that found in control groups of acne patients not receiving antibiotic therapy and controls free of acne. The average MIC for erythromycin was more than 100 times higher in those receiving long-term antibiotic therapy. In a second group of sixty-two patients, the clinical course and number of P. acnes were correlated with the presence of "resistant strains" defined as P. acnes with a tenfold increase in MIC to tetracycline or erythromycin. Patients with resistant strains had higher counts of P. acnes and clinically were not doing as well as those with sensitive strains.
BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K. OBJECTIVES: To determine whether similar or different resistance mechanisms occur in resistant P. acnes isolates from outside the U.K. METHODS: The phenotypes and genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared. Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA. RESULTS: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)). As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains. This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics. Two further point mutations (at E. coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K. However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical. Consistent with previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia. All the P. acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive to trimethoprim. CONCLUSIONS: This study shows that 23S and 16S mutations identified in the U.K. conferring antibiotic resistance in P. acnes are distributed widely. However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved. This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A. Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.
Propionibacterium acnes is a member of the resident cutaneous flora. Sebaceous follicles involved in acne are characterized by the accumulation of abnormally desquamated corneocytes and excess sebum-the microcomedo. This environment provides ideal growth conditions for P acnes. Several orders of magnitude level of P acnes are found in microcomedos. P acnes produces a variety of chemotactic factors and proinflammatory molecules that are responsible for the inflammatory phase of acne. Antibiotic therapy works by reducing the viable number of P acnes as well as by reducing the production of inflammatory stimuli. Antibiotic therapy has been a mainstay of treatment for more than 30 years. In the last decade, decreased sensitivity to antibiotics has developed and clinical resistance has been described. This development threatens the usefulness of antibiotic therapy in the future.
Acne is a common disease that in cases of extreme disfiguration can have severe consequences for the personality development of young people and is associated with a relatively high prevalence of depression and suicide. Spontaneous regression is common, but acne can extend into the fourth and fifth decades of life. The pathogenesis is still not fully understood. Factors promoting the development of acne are: increased sebum production, ductal cornification, bacterial colonization of the pilosebaceus ducts and inflammation. However, there is evidence that inflammation is not a factor but rather a consequence of the interaction of the other three factors. Propionibacterium acnes releases pro-inflammatory cytokines as well as antigens and mitogen(s), with cellular and non-cellular responses to these products triggering inflammation. Treatment is often frustran. Therapeutical strategies are needed based on new understandings of the pathomechanisms involved in acne. The aim of this review is to summarize the data on aetiopathological factors in acne and their contribution to acne pathology and therapy.
The intradermal injection of 140 micrograms of Propionibacterium acnes (CN 6134) into the ears of female Sprague-Dawley rats produced a chronic inflammation with formation of acneiform lesions. Inflammation was characterized by more than a doubling of ear thickness at 24 h and a peak of 3-4 times control levels at day 21. At 42 days post injection ears were still 3 times normal thickness. Histologically there was early polymorph accumulation giving way to macrophages and lymphocytes by day 7. Pilosebaceous follicles overlying the inflamed area lost their sebaceous glands and became hyperplastic cords of cells that grew down and encapsulated inflammatory loci. By day 9 many of these follicles had become secondary comedones. Three isolates of P. acnes from inflammatory acne lesions and 4 of 5 isolates from non-acne patients produced results similar to that of the strain CN 6134. In these cases the number of histologically evident secondary comedones was correlated with ear thickness. In contrast, samples of Streptococcus lactis, Escherichia coli B, and Staphylococcus epidermidis failed to produce this combination of chronic inflammation and high lesion count. Benzoyl peroxide, tetracycline, erythromycin, phenidone, naproxen, and cis and trans retinoic acid were inactive as inhibitors of P. acnes CN 6134-induced ear thickening. The corticosteroid fluocinolone acetonide produced dramatic suppression of inflammation, but upon cessation of treatment the ears returned to inflamed levels. The specificity for P. acnes, the formation of acneiform lesions, and the recalcitrance of the inflammation suggest our model is indeed relevant to acne.