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The retinoic acid derivative Ro 11-1430 in Acne vulgaris. A controlled multicenter trial against retinoic acid.

In a double-blind controlled multicenter trial consisting of 257 patients with acne vulgaris an 8-week topical treatment with the retinoic acid derivative Ro 11-1430 (0.1% lotion) was compared with vitamin A acid (0.05% lotion) and the lotion alone (placebo). In reducing the number of comedones vitamin A acid was superior to Ro 11-1430, which was significantly better than placebo. The reduction in number of papules and pustules was not statistically significant on either treatment. Local side effects, i.e. erythema, desquamation, burning and pruritus occurred more frequently and were more severe on vitamin A acid than on Ro 11-1430 and placebo which did not differ. No correlation was found between incidence and severity of local reactions and therapeutic effect.

Acne Vulgaris↗

Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can be successfully transplanted and studied on the nude mouse; (b) after androgen stimulation, sebaceous gland volume, cell size, and labeling index increase; (c) microcomedones can be produced in the human skin grafts by the application of a comedogenic substance. Thus, this model demonstrates significant potential for the future study of human sebaceous gland physiology and pathology.

Acne Vulgaris↗

Excision of rhinophyma with the carbon dioxide laser: a ten-year experience.

Rhinophyma is a disfiguring disease of the nasal skin, primarily affecting white men in the fifth to seventh decades of life. Hypertrophy of the sebaceous apparatus leads to an enlarged, erythematous nasal tip with comedones. Modalities of treatment include dermabrasion, freehand scalpel shave, cryosurgery, electrocautery, excision and closure with local flaps, and laser resection. A retrospective review of 18 patients treated with carbon dioxide laser excision of rhinophyma from 1983 to 1993 is presented. Discussion includes technique, postoperative care, complications, recurrence, operative blood loss, length of follow-up, time to complete reepithelialization, and pathologic findings. The carbon dioxide laser is a relatively safe, cosmetically efficacious, and curative method of treating rhinophyma.

Aged↗

Dermatotoxicity of agricultural chemicals in the dorsal skin of hairless dogs.

Dermatotoxicity of agricultural chemicals (ACs) with or without ultraviolet (UV) irradiation was histologically examined using hairless descendants of Mexican hairless dogs. ACs examined were pentachlorophenol sodium salt, 2,4-dichlorophenoxyacetic acid (DCPAA), Maneb, and Zineb. One day after cessation of the 7-day AC treatment, the skin treated with DCPPA and Maneb indicated only slight histological changes. The UV + AC-treated sites had as much pigmentation as the control sites. Fourteen days after cessation of treatment, dogs treated with Maneb showed marked reactions such as epidermal degeneration, vasodilation, and intradermal infiltration of inflammatory cells. These histological changes were more severe in the UV + AC-treated sites. Zineb induced comedones with well-developed pilosebaceous glands. These results suggest that hairless dogs may be useful laboratory animals for the investigation of dermatotoxicity of ACs in conjunction with UV irradiation.

2,4-Dichlorophenoxyacetic Acid↗

Rhino-9J (hr(rh9J)): a new allele at the hairless locus.

A spontaneous mutation arose in the MRL/MpJ-Fas(lpr)/Fas(lpr) colony in which mice lost hair after completion of the first hair cycle. Hair loss was progressive from head to tail. As these mice aged, they developed wrinkled skin and long curved nails. Histologically, affected skin developed comedones (pilary cysts), deep dermal cysts, and dermal foreign body granulomas associated with rupture of the follicles. The alopecic epidermis was acanthotic. The mutation was autosomal recessive. Crosses with RHJ/Le +/hr(rhJ) (rhino-J) mutant mice yielded affected offspring with the same phenotype, verifying the presence of a new allele of rhino, a mutation at the hairless (hr) locus on mouse chromosome 14.

Alleles↗

Azithromycin compared with minocycline in the treatment of acne comedonica and papulo-pustulosa.

This open study was conducted in 72 outpatients with acne vulgaris, to compare the clinical efficacy and tolerability of azithromycin and minocycline. Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles every 10 days and minocycline was administered 100 mg daily for 6 weeks. Improvement was assessed 6 weeks after initiation of treatment with a four-graded scale. A satisfactory clinical response was observed in 75.8% of the patients treated with azithromycin and in 70.5% of those treated with minocycline. There were no significant differences between these two acne treatments in terms of reduction of the number of lesions (p> 0.05). Both agents were well tolerated and mild side effects were reported in 10.3% of azithromycin and 11.7% of minocycline treated patients. We conclude that azithromycin is at least as clinically effective and well tolerated as minocycline as treatment of facial comedonic and papulopustular acne.

Acne Vulgaris↗

Efficacy and tolerability of a topical erythromycin/tretinoin combination preparation in acne treatment: post-marketing surveillance study involving over 6500 patients.

The good efficacy and tolerability of an alcoholic erythromycin/tretinoin solution was confirmed in a multicentre data investigation of over 6500 patients. The mean score for comedones declined clearly from 1.9 to 0.9 during treatment (average duration 70 days). The score for papules and pustules was reduced from 1.6 to 0.5. Overall medical assessment indicated 'very good' to 'good' efficacy in 86.1% of documented cases. Adverse drug reactions during treatment were mostly only very mild and were nearly always the known symptoms of redness, scaling, dryness and itching. Overall assessment of tolerability was 'very good' or 'good' in 88.1% of cases.

Acne Vulgaris↗

Attenuation of mild hyperandrogenic activity in postpubertal acne by a triphasic oral contraceptive containing low doses of ethynyl estradiol and d,l-norgestrel.

The effect of a low dose triphasic oral contraceptive (OC) was evaluated during a 6-month treatment period in 41 patients (mean age, 25.4 +/- 0.7 yr) who had grade I-IV postpubertal acne and normal menses. The OC contained three dose levels of ethynyl estradiol and dl-norgestrel. Acne lesions were assessed, and serum androgen levels were measured during a control cycle and between days 17-21 of treatment cycles 1, 2, 3, and 6. Four patients dropped out after 3 months of treatment. Acne was significantly improved after the first OC cycle. After six cycles, the number of comedones had decreased by 79.6 +/- 3.2% (range, 50-100%) in 69.4% of the patients. Mean baseline levels of testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were in the upper third of the normal range, with elevated individual values in 18.9%, 36.5%, and 26.8% of the women, respectively. Mean baseline levels of androstenedione, free testosterone (T), and 3 alpha-androstanediol glucuronide (3 alpha-diol-G) were above the normal range, with elevated individual values in 51.2%, 75.0%, and 85.4% of the patients, respectively. Sex hormone-binding globulin (SHBG) levels were below the normal range in 26.8% of the cases. At the end of the first OC cycle, there was a significant (P less than 0.01) decrease in all androgen precursors and a 2-fold increase in SHBG. Androstenedione and free T decreased into the normal range during OC intake. Serum 3 alpha-diol-G levels remained elevated, but had decreased by 34.5% at cycle 6 (P less than 0.05). These results show that the triphasic OC has significantly improved acne in postpubertal women for whom acne was the main manifestation of mild hyperandrogenic activity. The improvement in acne corresponded to a decrease in adrenal/ovarian androgens and free T, which led to a decreased metabolism to 3 alpha-diol-G, presumably by the sebaceous glands. The increase in SHBG is considered an estrogenic effect, and the triphasic formulation containing low dose dl-norgestrel is not androgenic but, rather, an estrogen-dominant formulation; as such, this product is recommended in women requiring contraception who also have idiopathic acne.

Acne Vulgaris↗

Atrichia with papular lesions resulting from mutations in the rhesus macaque (Macaca mulatta) hairless gene.

Atrichia with papular lesions (APL) is a rare form of hair loss with an autosomal recessive mode of inheritance that is characterized by the absence of normal hair follicles, and formation of intradermal cystic structures. Mutations in the hairless (hr) gene in mice and humans have been implicated in the development of this phenotype. Hairless is a putative transcription factor containing a single zinc-finger DNA binding domain, with restricted expression in brain and skin. Here, we describe the complete hr cDNA sequence from the rhesus macaque (Macaca mulatta) and report the identification of a compound heterozygous mutation in a hairless rhesus macaque born from unrelated parents. Cutaneous biopsy samples from the affected macaque revealed abnormalities, including the replacement of normal hair follicles with dermal cysts and comedones, reminiscent of the skin phenotype observed in hairless mice and humans with APL.

Alopecia↗

Vitamin A acid: a review of its pharmacological properties and therapeutic use in the topical treatment of acne vulgaris.

Vitamin A acid (retinoic acid: tretinoin) is a vitamin A derivative used in the topical treatment of acne. It acts by 'unseating' comedones, improvement developing slowly over a period of 2 to 3 or more months, and is also said to prevent the formation of new lesions. About three-quarters of patients with acne vulgaris benefit from treatment. In controlled studies, results achieved after a 3 to 4 months course of treatment were superior to those with sulphur-resorcinol-salicylic acid. When compared with benzoyl peroxide, results were variable and appear to depend on the length of treatment, the types of formulations used, and the concentrations compared. Application of vitamin A acid should be continued until the patient has been free of new lesions for several months. Further continued application at a less frequent interval or using a less active dosage form may help to prevent exacerbations of acne. A systemic antibacterial agent such as tetracycline can be given as well as in patients with moderate to severe lesions. Vitamin A acid is used in conjunction with gentle washing (to remove surface oil) but should be applied to a dry skin to avoid unnecessary irritation. Patient education and encouragement are crucial during the initial phase of treatment when microcomedones may be converted to pustules prior to desquamation.

Acne Vulgaris↗

Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders.

Azelaic acid is a naturally occurring saturated dicarboxylic acid which, on topical application (usually as a 20% cream), has been shown to be effective in the treatment of comedonal acne and inflammatory (papulopustular, nodular and nodulocystic) acne, as well as various cutaneous hyperpigmentary disorders characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna. In addition, azelaic acid has an antiproliferative and cytotoxic effect on the human malignant melanocyte, and preliminary findings indicate that it may arrest the progression of cutaneous malignant melanoma. The mechanism of this selective cytotoxic action of azelaic acid is unclear, but may possibly be related to its inhibition of mitochondrial oxidoreductase activity and DNA synthesis. In controlled studies, topical azelaic acid demonstrated comparable anti-acne efficacy to topical tretinoin, benzoyl peroxide, erythromycin and oral tetracycline, while in patients with melasma azelaic acid proved at least as effective as topical hydroquinone. On topical application azelaic acid is well tolerated, with adverse effects apparently limited to a generally mild and transient local cutaneous irritation. Thus, topical azelaic acid, employed either as monotherapy or in combination with other treatments, is likely to prove of value in the management of acne and several hyperpigmentary disorders, most notably melasma.

Acne Vulgaris↗

Current concepts of the pathogenesis of acne: implications for drug treatment.

The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinisation, bacterial hypercolonisation, as well as immune reactions and inflammation. High sebum concentrations and follicular hyperkeratinisation lead to a change of the follicular milieu with consecutive proliferation of bacteria, chiefly Propionibacterium acnes. This leads to further increased production of the pro-inflammatory cytokines interleukin-1alpha and tumour necrosis factor alpha by T cells and keratinocytes, leading to proliferation of both cell types. Follicular keratinocytes fail to differentiate by apoptosis and produce hypergranulosis similar to the impermeable skin outer layer, resulting in the formation of microcomedones. Further inflammatory responses lead to the development of increasing degrees of severity in inflammatory forms of acne. Retinoids aid the differentiation and reduce the hyperproliferation of keratinocytes, and can inhibit the migration of leucocytes. Combination therapy using retinoids plus benzoyl peroxide or antibacterials can treat existing acne lesions faster than the individual agents alone and can also prevent the development of new lesions. The new retinoids (e.g. adapalene) have not only the typical potent comedolytic activity but also anti-inflammatory effects. When added to antibacterial therapy, topical retinoids demonstrate faster and significantly greater reduction of inflammatory acne lesions and comedones than antibacterials alone.

Acne Vulgaris↗

Optimal management of acne to prevent scarring and psychological sequelae.

Acne vulgaris is one of the most common inflammatory dermatoses and is seen in both the hospital setting and in general practice. Multiple factors are involved in the pathophysiology of acne, including: an alteration in the pattern of keratinization within the pilosebaceous follicles resulting in comedone formation; an increase in sebum production which is influenced by androgens; the proliferation of Propionibacterium acnes; and the production of perifollicular inflammation. Genetic and hormonal factors may also contribute to acne. Better understanding of the pathophysiology of the disease has led to the development of novel therapies which are directed at one or more of the implicated etiologic factors. Systemic antibiotics for acne have been the mainstay of treatment for many years. The main cause for concern following the use of systemic antibiotics is the emergence of antibiotic-resistant strains of P. acnes. Concomitant use of non-antibiotic therapies such as benzoyl peroxide helps to decrease the occurrence of resistance and can be effective in the treatment of resistant and nonresistant propionibacterial strains. However, no one agent is able to eradicate resistant strains completely and as resistant strains correlate to poor clinical response to therapy, prescribing strategies are required to minimize the occurrence of resistance to P. acnes. When assessing acne it is important to take an all embracing approach and to examine carefully for both the clinical and psychologic effects of the disease process. There are numerous forms of acne scarring and it is important to be aware of these as patients who are developing scarring merit early effective therapy. Some patients with acne will develop psychologic problems as a consequence of their condition. Even mild to moderate disease can be associated with significant depression and suicidal ideation and psychologic change does not necessarily correlate with disease severity. Acne scars themselves have been shown to produce significant psychopathology. When initiating treatment it is important to consider the aims of therapy. Treatment should be aimed at achieving clearance of acne, prevention of scarring and, where necessary, relief from any psychologic stress resulting from the acne. Therapy should be commenced early in the disease process in order to prevent scarring and it is important to select appropriate therapies according to the clinical signs and psychologic disability. It is also important to ensure that the patient is able to comply with therapy and clear guidelines regarding treatment, possible adverse effects and realistic expectations should be provided.

Acne Vulgaris↗

Topical therapy for acne vulgaris. How do you choose the best drug for each patient?

Although management of acne is sometimes difficult, primary care physicians can offer a number of treatment plans to patients with this skin condition. Comedonal acne usually responds to topical keratolytics, such as salicylic acid, benzoyl peroxide, adapalene, and tretinoin. Inflammatory acne is usually treated with topical therapy plus a systemic antibiotic. Nodulocystic acne generally requires an 8-week course of systemic antibiotics. If the nodulocystic acne does not improve, minocycline or isotretinoin may be needed. Topical therapy is often helpful in the long-term management of nodulocystic acne. New products are available that deliver topical agents in novel ways that decrease skin irritation. With the proper tools and instructions in use, most patients have significant improvement in their acne.

Acne Vulgaris↗

Chloracne, "the hallmark of dioxin intoxication".

Clinical experiences and laboratory studies are described involving a population of workers who were exposed in a plant making 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), including a trichlorophenol runaway reaction. Workers were followed for a period of four years, and 30 years later a mortality analysis was done on those exposed to runaway reaction material to determine possible increased risks for causes of death. Subsequently, a morbidity study on 436 employees involving three cohorts was carried out to determine the long-term health effects associated with the production of 2,4,5-T including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mortality and morbidity studies demonstrated that the standardized mortality ratio for all causes of death was 69, and for cancer at all sites and cardiovascular disease it was 100 and 68, respectively. The most significant observations emerging from the morbidity study were that 86% of the exposed persons developed chloracne at some time and that 52.7% still had chloracne on examination 20 to 30 years after the initial exposure. There appeared to be no evidence, on a long-term basis, of increased risks for cardiovascular disease, hepatic disease, renal disease, central and peripheral nerve problems, reproductive problems, or birth defects among the exposed and those who had chloracne among the exposed. Studies on the cell kinetics and pathogenesis of chloracne indicate that TCDD induces the modulation of undifferentiated sebaceous gland cells to keratinocytes. This action results in a disappearance of sebaceous glands and substitution of closed comedones and keratin cysts. Production workers have the highest frequency and severity of chloracne and systemic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne.

Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions. We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower. Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.

Acne Vulgaris↗

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

Follicular mycosis fungoides is a rare variant of mycosis fungoides (MF). Structural-wise there are several acneiform lesions made up of comedones, cysts and hyperkeratosis. The main histological finding is atypical lymphocytic infiltration around follicular structures, without epidermotropism. The association with follicular mucinosis is widely discussed in the literature. We report a case of follicular (MF) and review the cases published to date.

Humans↗

[Effective and safe pharmacotherapy of acne vulgaris and treatment of sun-damaged skin].

An inevitable condition for the pharmacist is a basic knowledge of dermatological changes which are prominent in acne and solar impairment of the skin to be able to recommend in a qualified manner an effective and safe treatment to the patient. However, sufferers of the more serious forms of acne should always be referred to their general practitioner, or preferentially a dermatologist. Acne vulgaris is an androgen-induced disorder, but three major mechanisms for the development of the disease have been identified: hypertrophy of the sebaceous gland, hyperkatosis of the follicular epithelium, and proliferation of microbial flora, particularly Propionibacterium acnes. The basis of all lesions is the microcomedone which is developed into the ripe comedone. Inflammatory lesions are thought to be due to proliferation of P. acnes. In the selfmedication of common acne, benzoyl peroxide, which in a 5-10% lotion exerts antimicrobial and keratolytic properties, proved to be useful. Patients appreciate a lot its instant effect which is visible after just one day of treatment. Salicylic acid is another effective drug, which, when used on the long-term basis, has comedolytic properties; it reduces the number of microcomedones and counteracts plugging of the follicles. In addition, in healthy young women who take oral contraception, a triphasic combined oral preparations of contraceptives with newer progestins, notably with norgestimmate, which is practically free of androgenic effects, are recommended with advantage for the treatment of moderate acne vulgaris without any adverse effects. Solar impairment of the skin, the so-called solar ageing, is clinically indistinguishable from biological ageing. Changes connected with solar impairment appear mostly in the dermis, where solar elastosis develops, the skin gets drier and wrinkle formation appears. For the treatment, hydroxy acids are recommended, namely salicylic acid, which is very effective, because in combination with a suitable vehicle it produces desquamation or exfoliation. Desquamation is beneficial as it gives a youthful appearance to the skin.

Acne Vulgaris↗