A comparison of the flora of the comedones of acne vulgaris and comedones in elderly people.
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The factors that initiate the inflammatory response in acne are not known. The presence of pro-inflammatory cytokines in acne comedones was therefore investigated. One hundred eight open comedones were collected from 18 untreated acne patients (10 male, 8 female). Each comedone was homogenized and centrifuged, and the supernatant was analyzed for bioactive and immunochemically detectable IL-1 alpha, IL-1 beta, and TNF alpha. Viable counts of propionibacteria, staphylococci, and Malassezia spp. were determined in the comedone pellet. Bioactive IL-1 alpha-like material was demonstrated in 76% of open comedones (range of 23-4765 pg IL-1 alpha-like bioactivity/mg of comedone material). In 58% of comedones, levels exceeded 100 pg/mg. There was no correlation between IL-1 alpha-like bioactivity and IL-1 alpha determined immunochemically. Bioactive IL-1 beta was not detected in any comedones. Twenty-four percent contained low levels of immunochemical IL-1 beta (range 12-103 pg IL-1 beta/mg comedone material). Bioactive TNF alpha was detected in three comedones with a further five comedones containing immunochemical TNF alpha (range of 61-820 pg TNF alpha/mg comedone material). The majority of open comedones (97%) contained microorganisms. There was, however, no significant correlation (Spearman's rank) between levels of any cytokine, in particular IL-1 alpha-like bioactivity, and numbers of microorganisms. Thus, bioactive IL-1 alpha-like material in the majority of open comedones may be concerned in the initiation of inflammation in acne following spongiosis or rupture of the pilosebaceous follicle wall.
Previous studies using paraffin-embedded sections showed the presence of varying degrees of lipidic calculus (sebolith) formation in the pilosebaceous duct in acne comedonal lesions. The objective of this study was to examine the content of fresh acne comedonal extracts and pustules in polarizable crystalline material. Furthermore, to investigate if the amount of crystalline material correlates with the morphology, evolutionary stage, age and location of the comedone we performed polariscopic examination of 20 fresh acne comedonal extracts and 6 acne pustules. As controls, we used extracts from solar comedones, milia and epidermal inclusion cysts, follicular extracts from acne rosacea lesions, pustules of bacterial folliculitis and extracts from normal follicles from acne-prone individuals. The vast majority of acne comedones contained considerable amounts of polarizable crystalline material. Crystallization was more prominent in closed comedones, long-standing macrocomedones and conglobate comedones. Crystal formation was seen less commonly (p < 0.01) in solar comedones, milia and epidermal inclusion cysts. As shown in this study, crystallization of sebum is a common element of comedogenesis and may possibly contribute to comedo preservation.
Extracts of comedonal material obtained from patients with acne vulgaris were analyzed for albumin, IgG, IgM, IgA, and anti-Propionibacterium acnes antibodies using immunodiffusion and anti-immunoglobulin hemagglutination tests. Extracts were obtained from comedones of patients with (1) comedonal, (2) papulopustular, (3) nodular-cystic, (4) "burned out" acne, (5) patients under oral tetracycline treatment, and (6) with pustules. In all comedonal extracts analyzed, albumin and IgG (ratio approximately 1:2.5) could be detected. IgM, IgA, and C3 could not be found in noninflamed comedones by the techniques used; pustules, however, contained all immunoglobulin classes and albumin in ratios found in serum as well as C3. The anti-P. acnes antibody activity in the comedonal extracts was associated with the IgG class. Immunofluorescence microscopical examination of material from single comedones obtained by the cyano-acrylate technique showed IgG antibody on rod-shaped bacteria. The amount of IgG and albumin in comedonal extracts from the various patient groups was not different. It is concluded that IgG (and antibody of the IgG class) in comedones is derived from the serum and selectively accumulated in the follicle by an unknown mechanism.
A miniaturized sensitive bioassay was used to detect tetracycline in open comedones following topical twice daily application of 0.22% tetracycline hydrochloride for a minimum of 4 weeks to the facial skin of patients with mild to moderate acne. The lower limit of detection was 4.8 +/- 0.8 ng per comedone or per 10 microliters. Using this method, 111 of 155 open comedones from 15 patients were found to contain a detectable amount of tetracycline, ranging from 1.8 to 156.9 ng per comedone, and between 4.5 and 1140.1 ng per mg comedonal material. There was a significant effect of comedone weight on tetracycline content, with smaller comedones containing proportionately more tetracycline. The Spearman rank correlation coefficient was -0.5619 (P < 0.001). All 111 comedones in which tetracycline was detected contained sufficient drug to inhibit fully antibiotic-sensitive propionibacteria. However, conditions favourable to the selection and overgrowth of highly tetracycline-resistant strains (MIC > or = 32 micrograms/ml) prevailed in at least 18.7% (29 of 155) of the comedones tested.
BACKGROUND: Comedones, often in a periorbital distribution, have been claimed to be associated with pitch tar. OBJECTIVE: This cross-sectional study compares the incidence of periorbital comedones between a group of individuals exposed to pitch tar and a control group. METHODS: The incidence of periorbital comedones was determined in workers (n = 55) at a tar distillation plant. A comparison group (n = 55) not exposed to pitch tar was also examined for the presence of facial comedones. The respective incidence rates were compared by using the Fisher exact test. RESULTS: Eighteen percent (10/55) of the study group and 4% (2/55) of the control group had periorbital comedones. The study group had a significantly greater incidence of periorbital comedones (P =.01). CONCLUSION: The incidence of periorbital comedones is significantly greater in individuals exposed to pitch tar. Further studies are needed to elucidate the potential relationship between pitch tar and periorbital comedones.
To understand the basis for the anti-inflammatory activity of tetracyclines in acne, we compared the cytokine profiles [interleukin 1 (IL-1) alpha and beta, tumor necrosis factor (TNF) alpha, and IL-6] and bacterial flora of 66 open comedones removed from eleven patients before and after at least 8 weeks treatment with either tetracycline or minocycline. Pre-treatment, the only cytokine regularly recovered from comedones was bioactive IL-1 alpha-like material. The mean concentration of IL-1 alpha-like bioactivity/mg comedonal material rose from 272.0 +/- 88.6 pg to 844.3 +/- 196.7 pg following treatment (p < 0.05, Wilcoxon matched pairs). All six minocycline-treated patients showed an increase in bioactive IL-1 alpha-like material compared with three of five tetracycline-treated patients. The incidence (p < 0.001, chi 2) and concentration (p < 0.05, Wilcoxon) of immunochemical IL-beta were also raised post-treatment, although significantly more patients assigned to minocycline therapy had detectable levels of this cytokine before therapy was initiated. However, the mean concentration of IL-1 beta/mg comedonal material post-treatment was similar in both groups (72.5 +/- 23.3 pg for tetracycline-treated compared with 78.6 +/- 41.9 pg for minocycline-treated patients). The other cytokines were either absent (IL-6) or present in < 10% of comedones (TNF alpha) before and after therapy. Following treatment, only three of 11 patients showed a decrease of > or = 1 log10 in propionibacterial numbers/mg comedonal material, whereas six patients showed an increase of > 0.5 log10 in numbers of staphylococci. In eight patients, the increase or decrease in staphylococcal numbers correlated with the change in concentration of IL-1 alpha-like bioactivity. This is the first study to show an effect of antibiotic therapy on cytokine levels in vivo. Increased levels of IL-1 in comedones destined to become inflamed may enhance resolution and promote repair of the damaged follicular epithelium. Hence, these results provide further evidence of the augmentation of immune responses by tetracyclines and support the hypothesis that epidermal IL-1 plays a physiologic role in wound healing.
The effect of isotretinoin on experimentally induced comedones was studied by means of histoplanimetry and scanning electron microscopy (SEM). To induce comedone formation, insoluble cutting oil was applied to the ventral surface of the ears of rabbits for 2 weeks. After comedones formed, isotretinoin was fed to the rabbits by a feeding tube, daily, for 4 weeks. A low dose (2.0 mg/kg) and a high dose (20.0 mg/kg body weight) were selected for two different groups. Soybean oil served as the vehicle. Histoplanimetrically, the high-dose group showed a significant decrease in size of comedones when compared to the control group and the low-dose group [P less than 0.005], and in the high-dose group, the follicular lumen contained a small number of loose, non-adherent, horny cells. Upon SEM examination, the comedones were seen to have a 'chrysanthemum' appearance before treatment. After treatment, the high- and low-dose groups both showed evidence of the elimination of comedones on three-dimensional analysis.
Open comedones from thirty-eight patients with acne vulgaris on the face or back were compared for microbial flora. A total of eighty-three comedones from the face and sixty-three from the upper back were individually processed for quantitative bacterial analysis. The greatest difference between the flora of comedones at these two sites was that 44.6% of comedones from the back (compared to 9.6% from the face) harboured no aerobic cocci. The decreased prevalence of staphylococci in the lesions from the back reflects the relative absence of these organisms in isolated follicles from normal uninvolved skin of the back. The geometric mean count of anaerobes in comedones from the back was in the same range as the count found in isolated follicles in normal uninvolved skin in a previous study. This work supports the concept that the bacterial flora of comedones is an extension of the follicular flora and may be unrelated to the event of comedogenesis.
In the first experiment, the skin sebum and humidity, perspiration ability of sweat glands, and histology of spontaneous comedones were examined in hairless descendants of Mexican hairless dogs. The skin of females showed lower humidity than that of males. Some animals with a large number of comedones exhibited remarkably high skin sebum scores. The comedones were distributed throughout the dorsal skin, and a cluster of lesions was found mainly in the limbs and prepuces. The sweat glands showed no perspiration in the sudorific test. Histologically, both infant and adult animals had lesions of micro- and/or "blackhead" comedones. Plugged follicles containing abundant keratic substances associated well-developed sebaceous glands. Spontaneous comedones in the skin of hairless dogs were grossly and histologically similar to the acne vulgaris observed in human beings. The skin of some adult animals showed a large number of protrusive comedones which were solid cystic structures containing organized substances. In the second experiment, three kinds of antiacne agents (sulfur and camphor, sulfur and resorcinol, and ibuprofen piconol) were applied daily to the test sites for one month. These antiacne agents caused prominent extrusion of keratin plugs from follicular sites. The results suggest that the hairless dogs are a predictive model for evaluating the efficacy of antiacne agents proposed for acne treatment.
To assess the variability of surface and comedone pH in one and the same individual and between individuals, pH measurements were made on extracted single comedone material and on the adjacent skin surface, at face and back sites on 56 acne patients. The pH values were normally distributed. The mean values were: comedone pH 5.52 and surface pH, 5.26. The pH ranges were similar: comedones 4.01 to 6.85 and surface, 4.10 to 6.81. There was no correlation between comedone pH and adjacent skin surface pH. On each person and at one site there was variability of surface pH and comedone pH. Variability of pH from person to person was greater than within an individual at the same site.
OBJECTIVE: To determine the distinction between a comedo and an infundibular cyst of Favre-Racouchot disease. SETTING: A university hospital. PATIENTS: From the 8 patients included in the study, 19 cysts and comedones were evaluated. MAIN OUTCOME MEASURE: The distinguishing features between the cysts and comedones of Favre-Racouchot disease. RESULTS: All lesions were histologically indistinguishable from the primary comedones of acne vulgaris, except for the presence of a marked actinic elastosis in the surrounding dermis. The presence of a variable number of hair shafts and an abundant amount of bacteria, which was positive in the results of Gram staining and periodic acid-Schiff reaction and intermingled with sebum and eosinophilic laminated horny material within the dilated infundibulum, characterizes a comedo and differentiates it from an infundibular cyst. CONCLUSIONS: The cysts and comedones of Favre-Racouchot disease are closed and open comedones. They can be easily differentiated from an infundibular cyst by the histopathologic features rather than by the connection to the surface.
One of the primary events in the pathogenesis of acne vulgaris is abnormal follicular keratinization. Since oral isotretinoin therapy reduces follicular hyperkeratinization in acne, our study has been designed to determine whether epidermal lipid composition of the epithelium of sebaceous follicles is affected by isotretinoin treatment. Noninflamed early comedones obtained from ten patients with nodulocystic acne before and after the 6th week of isotretinoin therapy (mean daily dose 0.7 mg/kg b. wt.) were used as probes of the hyperkeratinizing follicular epithelium. Comedonal lipids were analyzed by high-performance thin-layer chromatography. Oral isotretinoin caused a decrease of the comedonal glyceride fraction by 36% (P less than 0.01), whereas free sterols and total ceramides increased by 34% (P less than 0.10) and 19%, respectively. The changes of comedonal lipids were associated with a significant elevation of the free sterols/cholesterol sulfate ratio of 86% from pretreatment levels (P less than 0.05). The isotretinoin-induced changes of the comedonal lipid composition in direction to a pattern of epidermal lipids of normal desquamating stratum corneum are discussed as a possible comedolytic mechanism of oral isotretinoin treatment.
INTRODUCTION: Familial dyskeratotic comedones is a rare affection of autosomal transmission and characterized by pseudo-comedone papules predominantly on the limbs. We report a new familial case characterized by its clinical and histological profile. CASE REPORT: A 6 year-old boy presented with a papular, pseudo-comedone eruption that had appeared shortly after birth and had progressively extended symmetrically to both legs. The child's father complained of a similar eruption since childhood. Histological examination of the papules revealed a pseudo-follicular invagination, obstructed by keratin and associated with areas of focal dyskeratosis. Treatment with local retinoids was ineffective. DISCUSSION: Since it is often asymptomatic, the prevalence of dyskeratosis comedones is probably underestimated. A review of the literature on the preceding observations is presented. The dermatites that would represent differential diagnoses because of the presence of comedone-like lesions and/or histological dyskeratosis are discussed.
Comedones were removed from patients on topical clindamycin and assayed for that antibiotic by of two methods. Prominent levels were found in eight of ten patients by one bioassay method. Once whole comedones from a patient were found to be positive, other comedones were microdissected to separate the external and internal portions. Prominent levels of clindamycin were found in the inner portion as early as 2 weeks. Further, the antibiotic could always be found in the internal portion when it was present in the external layers. Using the more sensitive of two bioassay methods, the whole comedonal level of clindamycin ranged from 0 to 5 microgram/mg of comedonal material, with an average level of 0.824 microgram/mg. The significance of this is discussed.
A microbiological survey has been undertaken of comedones isolated by micro-dissection from skin biopsies. Of closed comedones 10.7% and of open comedones 7.1% did not contain Pityrosporum spp., Propionibacterium spp. or Staphylococcus spp., the organisms most frequently associated with the pathogenesis of acne. Mature comedones were more frequently colonised than were young comedones. These results support the argument that the presence of microorganisms is not a prerequisite for comedo formation. Other pathological and ecological implications of these results are discussed.
Comedonal lipids and skin surface lipids were collected from six acne patients and surface lipids were collected from sex- and age-matched controls without acne. Six series of ceramides were found in each sample, the relative amounts of which were determined by thin-layer chromatography/photodensitometry. Acylceramides (ceramide 1) were isolated by preparative thin-layer chromatography and their ester-linked fatty acids were analyzed by gas-liquid chromatography. The comedonal acylceramides contained higher proportions of 16:0, 16:1 delta 6, and 18:1 delta 6 + delta 8 and much less linoleate (18:2 delta 9,12) than the acylceramides from the skin surface. In the surface lipids from legs, acylceramides from the acne patients contained less linoleate than the acylceramides from control subjects. Free fatty acids from the comedones were also isolated and analyzed, and had a composition very similar to the esterified fatty acids of comedonal acylceramides. The results confirm that fatty acids derived from sebum become incorporated into comedonal acylceramides, displacing linoleate, and show that this process even affects the acylceramides of surface epidermis, more so in acne patients than in normal subjects.
The chemoattraction of comedonal material for leukocytes was evaluated. Material from open comedones attracted mononculear leukocytes but did not attract polymorphonuclear leukocytes. At higher concentrations, comedonal material was cytotoxic for leukocytes of both types. Of the comedonal components tested, free fatty acids produced the greatest cytotoxicity. The attraction and killing of leukocytes by comedonal components may be the mechanisms for the initiation or the enhancement (or both) of inflammation in acne vulgaris.