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Title: Infantile: A Review

Running Title: Acne Infantile

Authors: Armaghan Kazeminejad1, Lotfollah Davoodi2, Zohreh Hajheydari1,*, Mohammad Jafar Ghahari3

1. Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Science, Sari, Iran. 2. Antimicrobial Resistance Research Center, Department of Infectious Diseases, Mazandaran University of Medical Science, Sari, Iran. 3. Department of Health, Faculty of Health Sciences, Mazandaran University of Medical Science, Sari, Iran.

*Corresponding Author: Email: [email protected]

To appear in: Journal of Pediatrics Review

Received date: 2020/09/29 Revised date: 2021/06/21 Accepted date: 2021/08/24

This is a “Just Accepted” manuscript, which has been examined by the peer-review process and has been accepted for publication. A “Just Accepted” manuscript is published online shortly after its acceptance, which is prior to technical editing and formatting and author proofing. Journal of Pediatrics Review provides “Just Accepted” as an optional and free service which allows authors to make their results available to the research community as soon as possible after acceptance. After a manuscript has been technically edited and formatted, it will be removed from the “Just Accepted” web site and published as a published article. Please note that technical editing may introduce minor changes to the manuscript text and/or graphics which may affect the content, and all legal disclaimers that apply to the journal pertain.

Please cite this article as: Kazeminejad A, Davoodi L, Hajheydari Z, Ghahari MJ. Acne Infantile: A Review. Journal of Pediatrics Review. Forthcoming 2021.


Abstract Context: Acne vulgaris is a in children. Its presentation and differential diagnosis differs. Evidence acquisition: In this narrative review we conducted a review of articles published in English on by searching in databases including Google Scholar, PubMed and Scopus during 1981-2019. Results: A total of 35 articles were selected for review. The treatment of acne often involves use of various medications that target several types of acne lesions. Different factors involved in the pathogenesis of acne and different degree of acne severity. The same principle and treatment strategy apply to all age groups diagnosed with acne. Conclusions: The treatment strategy for infantile acne is similar to treatment of acne at any age .Treatment is based on severity of the acne and risk of future scar. Keywords: Infantile acne

1. Context Pediatric acne is divided into five subgroups: neonatal, infantile, midchildhood, preadolescent and adolescent. Its prevalence in children is less than 2% (1, 2). Infantile acne presents between approximately 6 weeks and 12 months of age (3-10). Infantile acne presents non inflammatory and inflammatory acne such as papules, comedones, inflammatory papules, pustules, comedons, nodules and . Lesions are usually distributed in cheeks but can involve the chest and back (6). Most children diagnosed with infantile acne have a mild to moderate period and no treatment was need, resolving within 6 to 12 months of initial onset (11). This disease may be remain for one to two years and has been increased incidence and severity of adult acne (12, 13). In clinical presentation most cases resolve by 4 or 5 years of age, but some persist into puberty (7, 9). Sometimes infantile acne is severe and remain (14-17), and when additional signs of virilization are revealed, underlying endocrinopathies must be evaluated (4, 12, 14, 18-20), in this situation physical examination is need with attention to the assessment of developmental parameters such as height, weight, growth curve, testicles, mammary glands, presence of pubic hair, , clitoral hypertrophy or increased muscle mass. In the case of any abnormalities bone age evaluation and initial hormonal tests (FSH, LH, testosterone, dehydroepiandrosterone sulphate) should be done then referred to a pediatric endocrinologist (21). This disease can affect either sex but has a higher prevalence in males (5, 22). Higher prevalence of infantile acne in boys can also be explained by the increased secretion of LH which stimulates testicular androgen synthesis (5, 12). The etiology of infantile acne include genetic predisposition and heightened activity in response to normal levels of circulating androgens (14, 16, 23) and propionibacterium acnes also plays a role in the etiopathogenesis of acne. Case reports of Malassezia as a cause of infantile acne are available (24, 25). Infant skin is dominated by Firmicutes phylum and their number is significantly higher than Actinobacteria, which include Propionibacterium genus (26). Studies shown that these bacteria contribute to the development of acne by stimulating keratinocyte proliferation and the synthesis of proinflammatory substances such as interleukin 8 (27). Infantile acne can form scarring (3, 9, 28-30) and risk of scarring is difficult to estimate (19), therefore in sever case treatment is need. Differential diagnoses include: periorificial dermatitis, keratosis pilaris, exogenous agents (steroid acne, acne pomade, ) and infections (e.g., molluscum contagiosum), acne


venenata, angiofibroma, milia, syringoma, bilaterasl nevus commdonicus and Chloracne (3, 6).

2. Evidence acquisition In this review, electronic databases, including Google Scholar, PubMed and Scopus were searched. We conducted a review of articles published on infantile acne during 1981-2019. The keywords included infantile acne. In this study we included 35 studies then we selected all studies about infantile acne including 35 articles.

3. Results Acne can be classified as predominantly commedonal, inflammatory or mixed. For treatment presence of scarring, PIH and erythema should be evaluate and severity may be categorized as mild, moderate or severe. The treatment agent in acne are to treat as pathogenic factor such as reducing sebum production preventing the formation of microcomedones ,suppressing p.acne and reducing inflammatory. Several medications are available acne treatment. The treatment program for this disease is similar to treatment of acne at adult age. Generally most patients diagnosed with infantile acne have a mild to moderate period and requiring no treatment, improving within 6 to 12 months of initial onset. There are no FDA-approved medications for the treatment of acne in children, the treatment of infantile acne is essentially the same therapeutic program for acne of adult age (14, 17, 18). Principally treatment is divided two section. Topical treatments are effective in mild cases consisting of comedones and pustules that include benzoyl peroxide, retinoids, azelaic acid and (18, 19). Systemic treatment include oral antibiotics (erythromycin or trimethoprim) or oral isotretinoin were used for severe disease (18, 19). For mild disease, topical agent such as a topical retinoid or benzoyl peroxide is useful. They can be used as monotherapy or in combination with other drugs. In mild inflammatory acne, the addition of a topical (e.g., erythromycin or clindamycin) to the treatment would be appropriate. Studies revealed that use of benzoyl peroxide, because of its inherent nonspecific antimicrobial activity, has shown to be effective in preventing (19, 31). In moderate to severe inflammatory acne, first-line should be erythromycin. Tetracyclines are contraindicated in treatment of infantile acne. in some patients with colonization of Propionibacterium acnes alternative drug is sulfamethoxazole-trimethoprim. Other antibiotics


can be used in infants with severe inflammatory acne are amoxicillin, cephalexin and azithromycin (17). Other drugs include intralesional triamcinolone (2.5 mg/mL) injections for isolated nodules and cysts. Cryotherapy or topical corticosteroids for a short course can be used to treat deep nodules and cysts (3). For cases that are severe and intractable to medications, administration of oral isotretinoin is reasonable to prevent permanent physical and psychosocial sequelae. Fasting blood sugar and lipid profile and liver function test need to be obtained at baseline and on a routine basis throughout its administration (3, 15, 19, 32). Isotretinoin begin with a dose of 0.5 mg/kg per day to prevent an exacerbation at the beginning of therapy. Then the dose can be increased up to 1 mg/kg/day (19). Typical dosage used in the treatment of acne showed no increased risk of bone demineralization or fractures (33, 34), but in few cases the premature closure of lower extremity growth plates were reported in the literature (35). Most often side effects of topical agents are local skin irritations that nees to be managed by decreasing the frequency of application and by moistening the skin with non-comedogenic preparations (5).

4. Conclusion In infantile acne should always involve effective engagement of the parent or and extensive education. The physician should evaluate of potential side-effects, indications and contraindications associated with the treatment of choice (11). Time should also be taken to discuss the importance of expectation management. Infantile acne is usually mild to moderate in its period, and improved within 6 to 12 months from diagnosis. These poinits were important: Establish an accurate diagnosis by actively considering other possible differential diagnoses, evaluate for possible signs of an underlying endocrinopathy, initiate treatment to the appropriate level depending on the severity of lesions, conduct close clinical monitor the ongoing effectiveness of the current treatment regimen and to assess for any potential side- effects, actively engage and educate the parent or caregiver regarding treatment side-effects and expectation management.


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