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Therapy of acne.

Today acne vulgaris is a disease which can be well controlled using a combination of topical, systemic, and physical therapeutic modalities. However, successful acne management depends to a large extent on physician interest and the ability of the physician to apply therapy to the evolutionary stage of the disease and to the disturbed pathogenetic mechanisms. It is this author's opinion that grades I and II comedonal and papulopustular acne can be effectively treated solely with topical preparations, particularly the concurrent use of tretinoin with benzoyl peroxide or topical antibiotics. The majority of patients with grades III and IV inflammatory disease require oral antibiotics in addition to aggressive topical treatments. Intralesional steroids can be effective in all grades of acne when lesions develop an inflammatory nodulocystic quality. The physician should consider the use of estrogen (in females) or oral vitamin A in the small group of patients with grades III and IV inflammatory-cystic acne that has been unresponsive to conventional therapy. Combined systemic therapies of high-dose antibiotics, systemic corticosteroids, and sulfones clearly take precedence over topical preparations in conglobate acne and acne fulminans. Finally, oral isotretinoin, alone and perhaps in combination with more conventional modalities, should play an important role in the future management of severe inflammatory-cystic acne.

Acne Vulgaris↗

Uptake of 3H-testosterone in the skin of healthy women and in the skin of patients with acne vulgaris.

Skin samples of interscapular region were taken from healthy women and patients with Acne vulgaris. The material was incubated with 3H-testosterone. The incubation of a part of the material was preceeded by an incubation with the unlabelled testosterone. An autoradiography was employed to detect and localize an uptake of 3H-testosterone in the skin. A significantly greater 3H-testosterone uptake was noted in the stratum basale and stratum spinosum of epidermis, sebaceous glands and hair sheaths and, in patients with Acne vulgaris, also within hair sacs and comedons.

Acne Vulgaris↗

A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris.

BACKGROUND: One approach to suppressing the overgrowth of antibiotic-resistant bacteria is to develop combination products composed of active constituents with complementary but distinct mechanisms of antibacterial action. OBJECTIVE: The purpose of this study was to compare the antimicrobial and clinical efficacy and tolerability of clindamycin phosphate 1%/benzoyl peroxide 5% gel formulation with matching clindamycin 1% gel in the treatment of acne vulgaris. METHODS: This 16-week, single-center, double-blind, randomized, parallel-group study compared the combination gel with clindamycin monotherapy applied BID in patients 13 to 30 years of age with mild to moderate acne and facial Propionibacterium acnes counts > or = 10(4) colony-forming units per square centimeter of skin. RESULTS: Seventy-nine patients were enrolled and randomly assigned to receive the combination gel (n = 40) or clindamycin monotherapy (n = 39). Seventy patients (50 males, 20 females; mean age, 18.2 years) were included in the intent-to-treat group. The combination gel treatment produced significantly greater reductions (P < or = 0.046) from baseline in total lesion counts and in numbers of inflammatory lesions and comedones compared with clindamycin monotherapy. Greater reductions in the severity of acne also were observed in the physician's and patient's Clinical Global Improvement scale scores and in other secondary efficacy measurements. Reductions in clindamycin-resistant P acnes counts were observed relative to baseline in the combination gel group; in contrast, P acnes counts increased by >1,600% in the clindamycin monotherapy group at week 16 (P = 0.018 vs combination gel). Reductions in inflammatory (r2 = 0.31; P = 0.016) and total (r2 = 0.28; P = 0.027) lesions were correlated with decreases in clindamycin-resistant bacteria. Also, significant correlations were observed between the percent change from baseline in total lesion counts (r2 = 0.44; P < 0.001) and comedo counts (r2 = 0.50; P < 0.001) and the log10 change from baseline in total P acnes counts. CONCLUSIONS: The total P acnes count (P = 0.002) and the clindamycin-resistant P acnes count (P = 0.018) were significantly reduced after 16 weeks of treatment with combination gel compared with clindamycin monotherapy. These reductions in total P acnes and clindamycin-resistant P acnes counts correlated with reductions in total acne lesions.

Acne Vulgaris↗

A randomized, parallel, vehicle-controlled comparison of two erythromycin/benzoyl peroxide preparations for acne vulgaris.

BACKGROUND: Topical erythromycin/benzoyl peroxide (EBP), marketed for acne treatment, must be compounded by a pharmacist and requires subsequent refrigeration, warranting the development of alternate formulations. OBJECTIVE: This trial compared the efficacy and tolerability of a single-use EBP combination package (EBP Pak) with those of its matching vehicle control (VC Pak) and the original, reconstituted formulation packaged in a jar (EBP Jar). The matching VC for the original formulation (VC Jar) was used to achieve study blinding. METHODS: In this double-blind, parallel-group, multicenter study, patients were randomly assigned to the 4 treatment arms. The primary efficacy evaluations were lesion reductions from baseline and treatment success (as defined by a Physician's Global Acne Severity score of 0 [clear] or 0.5 [sparse comedones with few or no inflammatory lesions]). Secondary evaluations were Physician's Global Acne Severity scores, facial-oiliness scores, and end-point patient evaluations of global improvement and treatment acceptability. Tolerability was based on the incidence and severity of adverse events. RESULTS: Three hundred twenty-seven patients (age range, 12-46 years) were randomly assigned to the 4 treatment groups (EBP Pak, 124; VC Pak, 42; EBP Jar. 121; VC Jar, 40). Mean percent reductions in total acne lesions, inflammatory acne lesions, and come-dones from baseline were significantly greater with EBP Pak than with VC Pak (P < or = 0.001 for the intent-to-treat patient population after 8 weeks). Statistical significance for all lesion parameters was demonstrated at week 2 (P < 0.05) and maintained throughout the study. At 8 weeks, a significantly greater proportion of patients demonstrated treatment success with the EBP Pak compared with VC Pak (28% vs 2%, respectively; P < 0.001). The EBP Pak was comparable to the EBP Jar in terms of reduction in acne lesions, Physician's Global Acne Severity scores, and end-of-treatment patient evaluations of global improvement. No serious drug-related adverse events were reported. CONCLUSIONS: Results of this 8-week trial demonstrate that the single-use combination package of EBP is well tolerated, effective, and comparable to the original formulation for the treatment of acne vulgaris in this selected patient population.

Acne Vulgaris↗

Defensins and acne.

Acne a disease of the pilosebaceous unit is characterised by hypercornification and hyperkeratosis of outer root sheath (ORS) and sebaceous duct and perilesional infiltrate. Lesions may be characterised as "non"-inflammatory versus inflammatory. Hypercornification of the distal ORS and the pilosebaceous duct in concert with increased sebum production and abnormalities of the microbial flora are considered to be major factors in the pathogenesis of acne vulgaris. However, the basic mechanisms involved in the development of inflammation during acne vulgaris remain unclear. We have investigated the expression patterns of two antimicrobial peptides, human beta-defensin 1 (hBD1) and human beta-defensin 2 (hBD2) in healthy human hair follicles as well as in peri- and intralesional skin of acne vulgaris lesions such as comedones, papules and pustules. Strong hBD1 and hBD2 immunoreactivity was found in all suprabasal layers of the epidermis, and all permanent compartments of the hair follicle including the distal ORS of the hair follicle and the pilosebaceous duct. Moreover, marked hBD1 and hBD2 expression was also detected in the hair follicle stem cell compartment. In contrast, the proximal follicle bulb which undergoes apoptotic regression and is also able to regenerate following injury did not express hBD1 or hBD2. The majority of acne biopsies displayed a marked upregulation of hBD2 IR in the lesional and perilesional epithelium; in particular in pustules, and a less marked upregulation of hBD1 IR. The upregulation of beta-defensins expression in acne vulgaris lesions when compared to controls suggests that beta-defensins may be involved in the pathogenesis of acne vulgaris.

Acne Vulgaris↗

Pyoderma faciale: a clinical study of twenty-nine patients.

Pyoderma faciale is a distinctive entity. Twenty-nine patients with this process were seen in the Mayo Clinic from 1969 to 1980. Twenty-seven patients had follow-up that ranged from 1 month to 11 years, and twenty-two had follow-up of 3 years or more. Clinical features that characterize the patients were (1) female predominance, (2) onset later than teenage acne vulgaris, generally at 19 to 40 years of age, (3) rapid onset and progression, (4) facial involvement with sparing of the back and chest, (5) cysts, swelling, and purulent drainage with a lack of comedones, and (6) paucity of systemic complaints. Patients were treated with multiple forms of therapy simultaneously, often including Vleminckx packs, oral antibiotics, incision and drainage, ultraviolet B, and intralesional steroids. Of twenty-five patients available for follow-up at 1 year, twenty-three had achieved remission, though fifteen patients required ongoing treatment to maintain optimal control. Twenty-three patients had scarring as a sequela. Patients with pyoderma faciale represent a subset of patients with acne in whom the outlook is favorable with appropriate therapy.

Acne Vulgaris↗

Essential fatty acids and acne.

Acne is characterized by hyperkeratosis of the follicular epithelium, leading to horny impactions that may lie dormant as open or closed comedones or may cause inflammation of the follicle. Although persons with acne have consistently been observed to have elevated levels of sebum secretion, no mechanism relating sebum secretion rates to comedogenesis is known. Acne patients have also been shown to have low levels of linoleic acid in their skin surface lipids. To explain this observation, the hypothesis is advanced that the linoleate concentration in human sebum depends on the quantity of linoleic acid present in each sebaceous cell at the commencement of its differentiation and on the extent to which this initial charge is diluted by subsequent endogenous lipid synthesis in each sebaceous cell. A corollary hypothesis holds that low concentrations of linoleate in sebum impose a state of essential fatty acid deficiency on the cells of the follicular epithelium and induce the characteristic response of hyperkeratosis. Both hypotheses could hold, without there being a systemic deficiency of linoleic acid, simply as the result of elevated lipogenesis in individual sebaceous cells.

Acne Vulgaris↗

Historical perspectives of tretinoin.

The vitamin A acid story began when topical application of vitamin A (retinol) produced no therapeutic results in dyskeratotic conditions. It was logical to try metabolites of retinol topically. I published results of studies in 1962 that showed that topical tretinoin was beneficial in ichthyosis, actinic keratoses, and other hyperkeratotic conditions. It was reported in 1969 that topical tretinoin was effective in acne vulgaris, principally by preventing and dislodging comedones. It was subsequently demonstrated that tretinoin produced a distinctive kind of hyperplasia of human epidermis that was associated with early shedding of horny cells. Knowledge that the keratinization process was being profoundly altered stimulated interest in synthesizing retinol derivatives (retinoids) that could be administered orally. The development of 13-cis-retinoic acid was an outcome of this interest, a compound that astonished dermatologists by often producing permanent clearing of acne conglobata. The antitumor effects of tretinoin were already demonstrated by 1974, when it was shown to cause regression in many basal cell cancers. Today the cancer chemopreventive capability of retinoids is being intensively investigated in various organs. An international symposium held in Flims, Switzerland in 1975 demonstrated keen awareness of the therapeutic potential of tretinoin and the rapid growth of basic knowledge of the pharmacology of retinoids. From extensive clinical experience new applications for topical tretinoin came to light, ranging from the treatment of flat warts, lichen planus, and Darier's disease, and most recently in retarding photoaging. Perhaps for the first time in history, dermatologists can take credit for pioneering a drug development program that has had a profound influence on medical practice.

Germany, West↗

Erythromycin 2% gel in comparison with clindamycin phosphate 1% solution in acne vulgaris.

One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution. Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment. Both medications significantly reduced the numbers of papules and open and closed comedones. No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment. By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment. No patient was terminated from the study for side effects. Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.

Acne Vulgaris↗

Treatment of nevus comedonicus with ammonium lactate lotion.

A patient with an extensive nevus comedonicus, which is associated frequently with the development of large inflammatory cysts and abscesses within the nevus, responded dramatically within 1 month to a once-daily application of 12% ammonium lactate lotion. A marked beneficial effect on the comedonal component of the nevus was noted. One inflammatory cyst has developed in an area left untreated by the patient, but none have occurred in treated areas since therapy with ammonium lactate lotion was begun. Previous treatments, which were either ineffective or of minimal effectiveness, included oral isotretinoin, topical tretinoin, salicylic acid, lactic acid, and d-tartaric acid creams.

Administration, Topical↗

Nevus comedonicus associated with epidermal nevus.

A 21-year-old man had a zosteriform nevus comedonicus associated with a surrounding hyperpigmented maculopapular eruption, which had the histologic appearance of epidermal nevus. Scanning electron microscopic examinations of the comedones and the surrounding epidermal nevus showed a common feature, that is, chrysanthemum-like keratotic plugs. The association of a nevus comedonicus with an epidermal nevus and the common scanning electron microscopic findings of both suggest that a nevus comedonicus probably is an uncommon form of epidermal nevus.

Adult↗

The prevalence of hidradenitis suppurativa and its potential precursor lesions.

BACKGROUND: The morbidity of hidradenitis suppurativa can be considerable, but little is known about its epidemiology. OBJECTIVE: Our purpose was to describe the 1-year and point prevalences of hidradenitis suppurativa and its potential precursor lesions. METHODS: We obtained the histories and examined an unselected sample (599 persons) of the general population (1-year prevalence), and we performed physical examinations for a consecutive sample of 507 persons undergoing screening for sexually transmitted diseases (point prevalence). RESULTS: The point prevalence was 4.1% (95% confidence interval [CI] = 3.0-6.0) on the basis of objective findings. The 1-year prevalence of hidradenitis was 1.0% (CI = 0.4-2.2) on the basis of subject recollection only. The patients in the sample on which point prevalence is based were younger than those in the unselected sample of the general population (p < 0.001). Hidradenitis was significantly more common in women (p = 0.037), which may result from a female preponderance of genitofemoral lesions (odds ratio [OR] = 5.4; CI = 1.5 - 19.3). No sex difference was found in the prevalence of axillary lesions. CONCLUSION: Hidradenitis suppurativa is significantly more common than hitherto estimated. The female preponderance of patients is confirmed, except for patients with axillary lesions. Additional longitudinal studies are necessary to assess the importance of potential precursor lesions such as noninflamed nodules or comedones.

Adolescent↗

A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial.

BACKGROUND: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. OBJECTIVE: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris. METHODS: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. RESULTS: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. CONCLUSION: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Acne Vulgaris↗

The treatment of acne with topical retinoids: one man's opinions.

Acne is a family of disorders that vary greatly in pathogenesis and clinical manifestation. Accordingly, no simple recipe for treatment can be given, and treatment options vary with the stage and intensity of the disease. Topical retinoids are the mainstay for treating common varieties of acne vulgaris. They also prevent development of comedones, halting progression to inflammatory lesions. Tretinoin was the first retinoid used in the topical treatment of acne more than 25 years ago. Isotretinoin, which has recently become available, is less irritating, but is probably somewhat less effective. Adapalene is a recently introduced topical retinoid used to treat acne. It enjoys therapeutic equivalence to tretinoin but is less irritating. Except for very mild acne cases, topical retinoids should be used concommitantly with other drugs. The operating principle is to choose drugs whose modes of action are different from topical retinoids, that is, antibiotics or benzoyl peroxide. Topical retinoids, however, constitute the core of nearly all therapeutic programs for acne.

Acne Vulgaris↗

[Normal and pathologic sebaceous function. Research in a shallow milieu?].

Modern therapeutic approaches allow to control sebaceous secretion but knowledge about the sebaceous gland and its precise function within the pilosebaceous unit is still insufficient. Steroid hormones are the principal albeit not exclusive regulators of the sebaceous glands. Three phases may be distinguished in sebaceous physiology: secretion-production, stocking in the follicular reservoir, and excretion. Human "native" intracellular sebum, before secretion, is composed of squalene, waxes, and triglycerides. Once secreted, the sebum is colonised by various xenobiots whose development is controlled by several defensive humoral mechanisms and by the contact with ambient oxygen. Oxygen and micro-organisms transform "native" sebum, lysis of triglycerides to fatty acids being the most pronounced activity. Certain components of this complex mixture of molecules present in the sebum are clearly cytotoxic or irritant, provoking reactive follicular hyperkeratosis and comedone formation--the first step to acne. Some lipophilic organisms like Malassezia yeast may be highly antigenic and induce chronic inflammatory reactions like in seborrhoeic dermatitis. Demodex is an inrafollicular parasite feeding on sebum that frequently causes blepharitis. Sebum is also a vehicle transporting and transmitting several endogenous and exogenous molecules, including potential regulatory factors of hair follicles. Recent development of in vitro cultures of functional sebocytes should help to better understand several aspects of the sebaceous gland's biology.

Acne Vulgaris↗

Photocontact dermatitis and chloracne: two major occupational and environmental skin diseases induced by different actions of halogenated chemicals.

Among occupational and environmental disorders, contact or photocontact dermatitis and an acneiform eruption are two major skin disorders. Photocontact dermatitis was historically caused by various halogenated salicylanilides, while the acne is induced by halogenated aromatic hydrocarbons and thus called chloracne. Therefore, it should be noted that halogenated chemical compounds are important causative agents in the occupational and environmental medicine. In photocontact dermatitis, photoconjugation of epidermal cells with a photohaptenic halogenated chemical is the initial step. Langerhans cells serve as antigen-presenting cells and T cells sensitized by photoantigen-bearing Langerhans cells induce this photosensitivity. On the other hand, in chloracne, halogeneted hydrocarbons render keratinocytes of the outer root sheath and sebaceous duct hyperplastic. The dilated infundibulum of most hair follicles is then filled with comedone that consist of many accumulated layers of keratinized cells and sebum. Therefore, halogenated chemicals exhibit different actions, i.e. the induction of an immunologic consequence and the modulation of keratinocyte biology. These two conditions also provide good experimental models for investigating dermatology.

Acne Vulgaris↗

Follicular mycosis fungoides: a case report and review of the literature.

BACKGROUND: Follicular mycosis fungoides is an unusual variant of mycosis fungoides (MF). Unlike classic MF where atypical lymphocytes show a predilection for the epidermis (epidermotropism), follicular MF displays a malignant lymphocytic infiltrate tropic for hair follicles (folliculotropism). This malignant lymphocytic infiltrate results in follicular disruption typically manifesting clinically as plaques, comedones and follicular papules. METHODS: This report describes a 40-year-old patient with follicular MF presenting as nodules on the face and chest. Histologic examination of the patient's biopsy revealed a folliculocentric infiltrate of atypical lymphocytes with sparing of the epidermis. RESULTS AND CONCLUSIONS: Our case is discussed in the context of previously reported cases of follicular MF; we also include a review of all cases of follicular MF published to date that meet the strict criterion for this diagnosis.

Administration, Topical↗

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

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.

Acne Vulgaris↗