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267 International Journal of Research in Pharmacology & Pharmacotherapeutics Available online at www.ijrpp.com Print ISSN: 2278 – 2648 Online ISSN: 2278 - 2656 IJRPP | Volume 2 | Issue 1 | 2013 Review article A Review on Alternative Therapy for Acne * 1Swalin Parija, 2Sunil Kumar Kanungo, 3Sudhansu Ranjan Swain 1,2 Institute of Pharmacy & Technology, Salipur, Dist- Cuttack, Pin-754202, Odisha. 3 MET Group of Institutions, MIT Campus, Ram Ganga Vihar Phase-2, Moradabad-244001 (UP) ABSTRACT Acne is the cutaneous pleomorphic disorder of the pilosebaceous unit involving abnormalities in sebum production, and it is characterized by both inflammatory (papules, pustules and nodules) and noninflammatory (comedons, open and closed) lesions. Propionibacterium acnes and Staphylococcus epidermidis are common pus forming microbes responsible for the development of various forms of acne vulgaris. A number of factors contribute to the development of acne lesions these include internal hormones, bacteria, some medications, certain chemicals/products that come in contact with the skin, local pressure to the skin surface, and stress. Traditionally, attention has focused mostly on over-production of sebum as the main contributing factor of acne. More recently, more attention has been given to narrowing of the follicle channel as the second main contributing factor. Common therapies that are used for the treatment of acne include topical, systemic, hormonal, herbal, and combination therapy. Topically used agents are benzoyl peroxide, antibiotics and retinoids. Systemically used agents are antibiotics and isotretinolin. While acne cannot be cured, it can be controlled. The goal of treating acne is to reduce the symptoms and to prevent permanent scarring. Key words: Acne, Papules, Pustules, Nodules, Propionibacterium acnes, Staphylococcus epidermidis. INTRODUCTION Acne is a condition of the skin that is caused by excessive oil secretion of the sebaceous glands (oil glands) and the excess production of keratin inside the hair follicles (hyperkeratinization).These two conditions cause dead skin cells and excess oil to be trapped inside the pores, these results in pore clogging and the formation of a comedo. Trapped sebum and dead skin cells in the pore are the major food source of the acne-causing bacteria known as Propionibacterium Acnes. The availability of more sebum makes the population of the bacteria grow.1,2 PATHOPHYSIOLOGY3-6 Acne lesions arise from pilosebaceous units, which consist of sebaceous glands and small hair follicles. These units are found everywhere on the body ____________________________________ * Corresponding author: Swalin Parija E-mail address: [email protected] except the palms and soles. Pilosebaceous density is greatest on the face, upper neck and chest, at roughly nine times the concentration found elsewhere on the body. Obstruction of the pilosebaceous canal is the primary cause of acne and occurs because of a variety of factors. The first factor is sebum overproduction stimulated by hypersensitivity to androgenic steroids. Excess sebum production combined with increased epithelial cell turnover leads to formation of microcomedones, which can progress to open comedones, commonly termed "blackheads," or to closed comedones, often called "whiteheads" (figure-I). The combination of sebum and desquamated cells provides an environment that is ripe for the growth of Propionibacterium acnes, the principal organism in inflammatory acne lesions. 268 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273] Proliferation of P. acnes leads to the conversion of sebum to free fatty acids, which are irritating and stimulate the immune response, leading to the development of inflammatory lesions5 (figure II). ACNE VULGARIS; MILD TO MODERATE ACNE VULGARIS CONSISTS OF THE FOLLOWING TYPES OF ACNE SPOTS.6-10 cause of acne conglobata is unknown. Treatment usually includes isotretinoin (Accutane), and although acne conglobata is sometimes resistant to treatment, it can often be controlled through aggressive treatment over time. Whiteheads (Most Common): Whiteheads result when a pore is completely blocked, trapping sebum (oil), bacteria, and dead skin cells, causing a white appearance on the surface. Blackheads: Blackheads result when a pore is only partially blocked, allowing some of the trapped sebum (oil), bacteria, and dead skin cells to slowly drain to the surface. The black color is not caused by dirt. Rather, it is a reaction of the skin’s own pigment, melanin, reacting with the oxygen in the air. Papules: Papules are inflamed, red, tender bumps with no head. Pustules: A pustule is similar to a whitehead, but is inflamed, and appears as a red circle with a white or yellow center. Nodules: (more severe type) As opposed to the lesions mentioned above, nodular acne consists of acne spots which are much larger, can be quite painful and can sometimes last for months. Cysts: (more severe type) An acne cyst can appear similar to a nodule, but is pusfilled, and has been described as having a diameter of 5mm or more across. The stages of acne are illustrated in figure IV. This is an abrupt onset of acne conglobata which normally afflicts young men. Symptoms of severe nodulocystic, often ulcerating acne are apparent. As with acne conglobata, extreme, disfiguring scarring is common. Acne fulminans is unique in that it also includes a fever and aching of the joints. Acne fulminans does not respond well to antibiotics. Isotretinoin (Accutane) and oral steroids are normally prescribed. Acne Conglobata Severe cystic acne characterized by cystic lesions, abscesses, communicating sinuses, and thickened, nodular scars. Conglobata acne is the most severe form of acne and is more common in males. It is characterized by numerous large lesions, which are sometimes interconnected, along with widespread blackheads. It can cause severe, irrevocable damage to the skin, and disfiguring scarring. It is found on the face, chest, back, buttocks, upper arms, and thighs. The age of onset for acne conglobata is usually between 18 and 30 years, and the condition can stay active for many years. As with all forms of acne, the Gram-Negative Folliculitis This condition is a bacterial infection characterized by pustules and cysts, possibly occurring as a complication resulting from a long term antibiotic treatment of acne vulgaris. It is a rare condition, and we do not know if it is more common in males or females at this time. Fortunately, isotretinoin (Accutane) is often effective in combating gram-negative folliculitis. Pyoderma short time This type of severe facial acne affects only females, usually between the ages of 20 to 40 years old, and is characterized by painful large nodules, pustules and sores which may leave scarring. It begins abruptly, and may occur on the skin of a woman who has never had acne before. It is confined to the face, and usually does not last longer than one year, but can wreak havoc in a very short time. THE MOST SEVERE TYPES OF ACNE INCLUDE6-10: Acne Fulminans THE DIAGNOSIS OF ACNE Acne is classified into four grades according to the comedones present, amount of inflammation present, breakout severity, how widespread the acne is and the areas affected in the body. Grade I: The mildest form of acne with symptoms of blackhead, whitehead and minor pimples. Grade II: There are more blackheads and whitehead on the skin; papules and pustules are frequently found. Grade III: Grade III acne displays the characteristic redness and inflammation. Grade IV: Also known as cystic acne, grade IV is the most severe category of acne. The skin will www.ijrpp.com 269 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273] exhibit numerous pustules, blackheads and whiteheads. nodules, cysts, TREATMENT BASIC OF ACNE TREATMENT17-23 o o o o Antibacterial Examples: Benzoyl Peroxide (Topical), Azelaic Acid (Topical), Topical and Oral Antibiotics Keratolytic/Comedolytic Examples: Alpha-Hydroxy Acid Family (Glycolic Acid, Lactic Acid), Beta-Hydroxy Acid Family (Salicylic Acid), Retinoids (Retinoic Acid) Anti-Androgens Examples: Spironolactone (Aldactone, Spiritone), Cyproterone acetate (Androcur, Climen, Diane 35, Ginette 35), Flutamide (Eulexin), nilutamide (Anandron, Nilandron), Finasteride (Proscar, Propecia) Sebosuppresive agents Example of oral sebosuppresive agent: Oral Isotretinoin (Accutane), Example of topical sebosuppresive agents: (Zinc Oxide, Copper Peptide, Isolutrol, Topical Niacinamide) SYSTEMIC THERAPY FOR ACNE Recommendations: 5 TREATMENT VEHICLE2 In the treatment of acne, the vehicle (cream, gel, lotion or solution) may be as important as the active agent. Consequently, it is important to assess the patient's skin type. Creams are appropriate for patients with sensitive or dry skin which require a nonirritating, nondrying formulation. Patients with oily skin may complain of an "oily" feel with creams. Patients who have oily skin may be more comfortable with gels, which have a drying effect. However, gels may cause a burning-type irritation in some patients and may prevent certain kinds of cosmetics from adhering to the skin. Lotions can be used with any skin type, and they spread well over hair-bearing skin. Yet lotions contain propylene glycol and thus may have burning or drying effects. Solutions are mainly used with topical antibiotics, which are often dissolved in alcohol. Like gels, solutions work best in patients with oily skin. TOPICAL THERAPY FOR ACNE Recommendations5 Topical therapy is a standard of care in acne treatment. Topical retinoids are important in acne treatment. Benzoyl peroxide and combinations with erythromycin or clindamycin are effective acne treatments. Topical antibiotics (eg, erythromycin and clindamycin) are effective acne treatments. However, the use of these agents alone can be associated with the development of bacterial resistance. Salicylic acid is moderately effective in the treatment of acne. Azelaic acid has been shown to be effective in clinical trials, but its clinical use, compared to other agents, has limited efficacy according to experts. Data from peer-reviewed literature regarding the efficacy of sulfur, resorcinol, sodium sulfacetamide, aluminum chloride, and zinc are limited. Employing multiple topical agents that affect different aspects of acne pathogenesis can be useful. However, it is the opinion of the work group that such agents not be applied simultaneously unless they are known to be compatible. Systemic antibiotics are a standard of care in the management of moderate and severe acne and treatment-resistant forms of inflammatory acne. Doxycycline and minocycline are more effective than tetracycline, and there is evidence that minocycline is superior to doxycycline in reducing P acnes. Although erythromycin is effective, use should be limited to those who cannot use the tetracyclines (ie, pregnant women or children under 8 years of age because of the potential for damage to the skeleton or teeth). The development of bacterial resistance is also common during erythromycin therapy. Trimethoprim-sulfamethoxazole and trimethoprim alone are also effective in instances where other antibiotics cannot be used. Bacterial resistance to antibiotics is an increasing problem. The incidence of significant adverse effects with antibiotic use is low. However, adverse effect profiles may be helpful for each systemic antibiotic used in the treatment of acne. HORMONAL THERAPY FOR ACNE Recommendations5 www.ijrpp.com Estrogen-containing oral contraceptives can be useful in the treatment of acne in some women. 270 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273] Oral antiandrogens, such as spironolactone and cyproterone acetate, can be useful in the treatment of acne. While flutamide can be effective, hepatic toxicity limits its use. There is no evidence to support the use of finasteride. There are limited data to support the effectiveness of oral corticosteroids in the treatment of acne. There is a consensus of expert opinion that oral corticosteroid therapy is of temporary benefit in patients who have severe inflammatory acne. In patients who have well-documented adrenal hyper androgenism, low-dose oral cortico steroids may be useful in treatment of acne. Table 1. Treatment and Adverse Effects of Different Acne Types Acne type Treatment Drugs used Adverse effects Comedonal Topical retinoid and other agent Isotretinoin Tretinoin Adapalene Azelaic acid Skin irritation Skin irritation and low tolerability Skin irritation Local irritation Papulopostular Topical retinoid and/or benzoyl peroxide Benzoyl peroxide Cutaneous irritation, dryness, bleaching of hair and clothes Mild acne Moderate acne Papulopostular Oral antibiotics and topical retinoids/ benzoyl peroxide or oral isotretinoin Oxytetracycline Minocycline Doxycycline Erythromycin Azithromycin Nodular Oral antibiotic and a topical retinoids/ benzoyl peroxide or oral isotretinoin Oral isotretinoin Severe acne Oral isotretinoin or hormonal Spironolactone or high-dose oral antibiotics Oral contraceptive and topical retinoids and Corticosteroids benzoyl peroxide Gastrointestinal upset and vaginal candidiasis Vertigo and hyperpigmentation of skin Gastrointestinal upset and photosensitive Gastrointestinal upset and vaginal candidiasis Gastrointestinal upset Teratogenicity Menstrual irregularities Vascular thrombosis, melasma and weight gain Adrenal suppression Table 2. Cutaneous Side-effects From Topical Acne Treatments and Potential Novel Systems for Agent Delivery115 Common Topical Acne Treatments Cutaneous Side-effects Potential Novel Systems for Agent Delivery Retinoids (e.g., adapalene, tazarotene, tretinoin) Burning, peeling, erythema, dryness, photosensitivity Microsponges, liposomes, nanoemulsions, aerosol foams Benzoyl peroxide Dryness, erythema, peeling, hair and clothing Polymers, fullerenes discoloration Clindamycin phosphate Erythema, dryness, allergic contact dermatitis Aerosol foams, polymers, nanomemulsions Erythromycin Dryness, erythema, peeling, allergic contact dermatitis Aerosol foams, polymers, nanomemulsions Salicylic acid Dryness, erythema, peeling Polymers, microsponges www.ijrpp.com 271 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273 273] MISCELLANEOUS THERAPY FOR ACNE5 Recommendations Intralesional corticosteroid injections are effective in the treatment of individual acne nodules. There is limited evidence regarding the benefit of physical modalities including glycolic acid peels and salicylic acid peels. Chemical peels Both glycolic acid-based based and salicylic acid based peeling preparations have been used in the treatment of acne. There is very little evidence from clinical trials published in the peer peer-reviewed literature supporting the efficacy of peeling Figure I. Comedonal regimens.170-172. 2. Further research on the use of peeling in the treatment of acne needs to be conducted in order to establish best practices for this modality. Comedo removal There is limited evidence published in peer reviewed medical literature that addresses the efficacy acy of comedo removal in the treatment of acne, despite its long-standing standing clinical use. It is, however, the opinion of the work group that comedo removal may be helpful in the management of comedones resistant to other therapies. Also, while it cannot affe affect the clinical course of the disease, it can improve the patient’s appearance, which may positively impact compliance with the treatment program. F Figure II. Inflammatory papule and pustule in acne. Figure IV. Nodular odular cystic acne. Figure igure IV. IV STAGES OF ACNE. (a) normal follicle; (b) open comedo (blackhead); (c) closed comedo (whitehead); (d) papule; (e) pustule. www.ijrpp.com 272 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273] MANAGEMENT OF ACNE Lesion type(s) Comedonal lesions Mixed comedonal lesions and papulopustules papules and pustules Prescribe one of the Prescribe any one Prescribe Benzoyl peroxide following: Retinoid+topical antibody Topical retinoid Retinoid+benzoyl peroxide Azelaic acid Retinoid+ benzoyl peroxide Salicylic acid peroxide+topicalantibiotic Azelaic acid+ benzoyl peroxide If results are Unsatisfactory, Increase strength or Change medication Cystic lesions Prescribe course of oral antibiotic + mixed topical therapy If results are Unsatisfactory, add course of oral antibiotic. If results are Unsatisfactory,prescribe retinoid+course of oral antibiotic If results are Unsati -sfactory, consider whether patient is a candidate for oral Isotretinoin therapy. If results are Unsatisfactory, Consider possibility of endocrinopathy If endocrinopathy is identified, treat. If no sign of endocrinopathy is found, consider repeat course of oral Isotretinoin. 273 Swalin Parija et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(1) 2013 [267-273] CONCLUSION Much progress has been made to improve the performance of topical anti-acne care products in recent years.. Future research will be aimed at obtaining a greater understanding of the pathogenesis of acne vulgaris. The pillosebaceous follicle is the target organ of most of the modern drug for the treatment of acne. Currently, several topical and systemic agents are employed for treating acne that affect at least one of the main pathologic factors responsible for development of acne and are associated with several side effects. New excipients, refined processing techniques, and a better knowledge of the physicochemical properties of vehicles and drugs have led to the development of new delivery systems that may result in more advanced anti-acne therapies. Novel drug-delivery systems, such as liposomes, niosoms, micro emulsion, microsponge, hydrogels and solid lipid nano particals of these agents, can play a pivotal role in improving the topical and systemic delivery of the drug treating acne with a concomitant reduction in their side effects. Well controlled clinical trials will be required to confirm the clinical benefits of these new formulations in terms of efficacy, tolerability, compliance, and cosmetic acceptability. REFERENCE [1] White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol 1998; 39(2 pt 3):S34-7. [2] Krowchuk DP, Stancin T, Keskinen R, Walker R, Bass J, Anglin TM. The psychosocial effects of acne on adolescents. Pediatr Dermatol 1991; 8:332-8. [3] Ebling FJ, Cunliffe WJ. Disorders of sebaceous glands. In: Rook A, Wilkinson DS, Ebling FJ, Champion RH, Burton JL, eds. Textbook of dermatology. Vol III. Boston: Blackwell Scientific 1992:1699-744. [4] Zouboulis CC, Eady A, Philpott M.What is the pathogenesis of acne? Exp. Dermatol 2005;14: 143-152 [5] Gollnick H. Current concept of the pathogenesis of acne: implication for drug treatment. Drugs 2003; 63:1579-1596. [6] http://www.e2121.com/acne_images.html [7] http://www.e2121.com/facts_on_acne.html [8] http://www.medicinenet.com/acne/article.html [9] http://www.pharmpedia.com/Acne" [10] www.acne-site.com [11] James WD. Acne. In The New England Journal of Medicine 2005 April 7; 352; 1463 – 1472. [12] Webster GF. Acne vulgaris.BMJ 2002 August, 31: 475-479. [13] http://dermnetnz.org/acne/acne-causes.html "Causes of acne" (Last updated 08 Aug 2007) [14] http://www.acneguide.ca/basics/acne/what_causes_acne.html "What Causes Acne?"(Last modified: Friday, 16-Feb-2007") [15] http://www.nlm.nih.gov/medlineplus/acne.html "Acne" (Topic last reviewed: 13 September 2007) [16] http://www.Rxlist.com ******************************* www.ijrpp.com