efficacious and preferred by patients relative to desonide ointment.24 In a randomized controlled trial of 44 subjects with atopic dermatitis (ages 12 and older), subjects were treated with either desonide ointment or hydrogel twice daily for 4 weeks. The two formulations provided similar improvements in eczema signs and symptoms, but desonide hydrogel was rated by patients as significantly better than desonide ointment (P less than 0.05) in both absorption (at week 4) and (lack of) greasiness (at week 2). Other studies have demonstrated that desonide hydrogel can provide rapid alleviation of pruritus within 1 week and, importantly, does not suppress the HPA axis in pediatric patients.22, 23 Secondary Bacterial Infections Secondary bacterial infections are common complications of AD. Frequently caused by Staphylococcus aureus and Streptococcus pyogenes, such infections present with weeping, crusted, or pustulated lesions. Up to 80 to 100% of AD patients are colonized by S. aureus, compared to 5-30% of the general population.25, 26 Importantly, the density of S. aureus bacteria on the skin has been correlated with the clinical severity of AD.27 Several factors predispose AD patients to secondary bacterial infections. Due to mutations in filaggrin, patients with AD suffer from an inherent epidermal barrier dysfunction.28 The atopic immune response, including the overexpression of interleukin (IL)-4 and IL-13, may lead to further inhibition of filaggrin gene expression.29 In addition, the altered expression and secretion of antimicrobial peptides, which normally serve as endogenous antibiotics, contributes to innate susceptibility.30, 31 Topical antibiotics are integral to the treatment of bacterial infections in AD. Mupirocin 2% ointment is widely used, although concern exists over rising rates of resistance among S. aureus strains.32, 33 Methicillin-resistant Staphylococcus aureus (MRSA) represents a particularly troubling issue in the AD population, where rates of colonization are substantially higher than in the general population.34 Those with moderate-to-severe AD are especially at risk for MRSA colonization, which has in turn been linked to MRSA skin and soft tissue infections.35, 36 Retapamulin is a semisynthetic member of the pleuromutilin family of antimicrobials. Pleuromutilins were initially discovered in 1950s, with the first compounds—tiamulin and valnemulin—being approved for veterinary use. Pleuromutilin agents block protein synthesis in bacteria by binding to domain V of 23S rRNA and interfering with substrate binding.37 This mechanism of action is distinct from other antimicrobials, thereby reducing the likelihood of cross-resistance.38 The growing rates of anti-microbial resistance in bacteria, most notably MRSA, represent an important clinical consideration in selecting treatments. Retapamulin may provide an alternative not preferred treatment option for MRSA, especially where concern exists over mupirocin-resistance. In a study from six US dermatology centers, the susceptibility of S. aureus strains to different antimicrobials was tested.39 Among 218 isolates of S. aureus, 10.6% were mupirocin-resistant compared to only 0.5% that were retapamulin-resistant. Similar results were seen in a large analysis of 403 MRSA isolates, which found that 9% of strains were mupirocin-resistant versus only 0.25% that were retapamulin-resistant.40
Treatment regimens continue to evolve as clinicians and scientists gain greater insight into the pathophysiology of AD. Early intervention with emollients and topical steroids remain principle components to therapy, and the arrival of topical calcineurin inhibitors and phosphodiesterase-4 inhibitors has now provided an even wider range of options. Continued pediatric research into biologic agents, such as interleukin-4 and -13 inhibitors, as well as Janus kinase inhibitors, are likely to yield safe and effective systemic therapies in the near future. Importantly, the comorbidities of AD, such as infection, allergy, and psychosocial impairment, are increasingly being recognized and addressed in a multidisciplinary approach.In patients with poor control of AD, secondary bacterial infections are common complications, and the appropriate selection of antibiotic therapy can be challenging when faced with bacterial resistance. Although mupirocin remains a preferred first-line agent, growing concerns over MRSA resistance make retapamulin a treatment alternative in such pathogenic environments.
- Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66 Suppl 1:8-16.
- Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a general population. J Am Acad Dermatol. 1994;30(1):35-9.
- Thomsen SF. Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy. 2014;2014:354250.
- Kuster W, Petersen M, Christophers E, Goos M, Sterry W. A family study of atopic dermatitis. Clinical and genetic characteristics of 188 patients and 2,151 family members. Arch Dermatol Res. 1990;282(2):98-102.
- Brown SJ, McLean WH. One remarkable molecule: filaggrin. J Invest Dermatol. 2012;132(3 Pt 2):751-62.
- Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315-27.
- Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-32.
- Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008;4(10):525-33.
- De Bosscher K, Vanden Berghe W, Haegeman G. The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev. 2003;24(4):488-522.
- Sokolova A, Smith SD. Factors contributing to poor treatment outcomes in childhood atopic dermatitis. Australas J Dermatol. 2015;56(4):252-7.
- Wolkerstorfer A, Visser RL, De Waard van der Spek FB, Mulder PG, Oranje AP. Efficacy and safety of wet-wrap dressings in children with severe atopic dermatitis: influence of corticosteroid dilution. Br J Dermatol. 2000;143(5):999-1004.
- Kircik L, Del Rosso J. A novel hydrogel vehicle formulated for the treatment of atopic dermatitis. J Drugs Dermatol. 2007;6(7):718-22.
- Kahanek N, Gelbard C, Hebert A. Desonide: a review of formulations, efficacy and safety. Expert Opin Investig Drugs. 2008;17(7):1097-104.
- Freeman S, Howard A, Foley P, Rosen R, Wood G, See JA, et al. Efficacy, cutaneous tolerance and cosmetic acceptability of desonide 0.05% lotion (Desowen) versus vehicle in the short-term treatment of facial atopic or seborrhoeic dermatitis. Australas J Dermatol. 2002;43(3):186-9.
- Hebert AA, Cook-Bolden FE, Basu S, Calvarese B, Trancik RJ, Desonide Hydrogel Study G. safety and efficacy of desonide hydrogel 0.05% in pediatric subjects with atopic dermatitis. J Drugs Dermatol. 2007;6(2):175-81.
- Jorizzo J, Levy M, Lucky A, Shavin J, Goldberg G, Dunlap F, et al. Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol. 1995;33(1):74-7.
- Wong VK, Fuchs B, Lebwohl M. Overview on desonide 0.05%: a clinical safety profile. J Drugs Dermatol. 2004;3(4):393-7.
- Verdeso (desonide) Foam [package insert]. Research Triangle Park NSL, Inc; 2013. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2013/021978s010lbl.pdf (accessed April 30, 2018).
- Abram AZ, inventor; Stiefel West Coast LLC, assignee. Mousse composition. US patent 7,029,659 B2. April 18, 2006.
- U.S. Food and Drug Administration CfDEaRMRMRDF. Available at: https:// www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021978s000_MedR. pdf (accessed April 30, 2018).
- Hebert AA, Desonide Foam Phase IIICSG. Desonide foam 0.05%: safety in children as young as 3 months. J Am Acad Dermatol. 2008;59(2):334-40.
- Eichenfield LF, Basu S, Calvarese B, Trancik RJ. Effect of desonide hydrogel 0.05% on the hypothalamic-pituitary-adrenal axis in pediatric subjects with moderate to severe atopic dermatitis. Pediatr Dermatol. 2007;24(3):289-95.
- Kircik L. The effect of desonide hydrogel on pruritis associated with atopic dermatitis. J Drugs Dermatol. 2014;13(6):725-8.
- Trookman NS, Rizer RL. Randomized controlled trial of Desonlde Hydrogel 0.05% versus Desonide Ointment 0.05% in the treatment of mild-to-moderate atopic dermatitis. J Clin Aesthet Dermatol. 2011;4(11):34-8.
- Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol. 1974;90(5):525-30.
- Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K. Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica. 1985;170(1):35-9.
- Williams RE, Gibson AG, Aitchison TC, Lever R, Mackie RM. Assessment of a contact-plate sampling technique and subsequent quantitative bacterial studies in atopic dermatitis. Br J Dermatol. 1990;123(4):493-501.
- Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441-6.
- Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DeBenedetto A, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124(3 Suppl 2):R7-R12.
- Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C, et al. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006;117(4):836-41.
- Mallbris L, Carlen L, Wei T, Heilborn J, Nilsson MF, Granath F, et al. Injury downregulates the expression of the human cathelicidin protein hCAP18/ LL-37 in atopic dermatitis. Exp Dermatol. 2010;19(5):442-9.
- Upton A, Lang S, Heffernan H. Mupirocin and Staphylococcus aureus: a recent paradigm of emerging antibiotic resistance. J Antimicrob Chemother. 2003;51(3):613-7.
- Jones JC, Rogers TJ, Brookmeyer P, Dunne WM, Jr., Storch GA, Coopersmith CM, et al. Mupirocin resistance in patients colonized with methicillin-resistant Staphylococcus aureus in a surgical intensive care unit. Clin Infect Dis. 2007;45(5):541-7.
- Warner JA, McGirt LY, Beck LA. Biomarkers of Th2 polarity are predictive of staphylococcal colonization in subjects with atopic dermatitis. Br J Dermatol. 2009;160(1):183-5.
- Jagadeesan S, Kurien G, Divakaran MV, Sadanandan SM, Sobhanakumari K, Sarin A. Methicillin-resistant Staphylococcus aureus colonization and disease severity in atopic dermatitis: a cross-sectional study from South India. Indian J Dermatol Venereol Leprol. 2014;80(3):229-34.
- Lo WT, Wang SR, Tseng MH, Huang CF, Chen SJ, Wang CC. Comparative molecular analysis of meticillin-resistant Staphylococcus aureus isolates from children with atopic dermatitis and healthy subjects in Taiwan. Br J Dermatol. 2010;162(5):1110-6.
- Schlunzen F, Pyetan E, Fucini P, Yonath A, Harms JM. Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin. Mol Microbiol. 2004;54(5):1287-94.
- Brooks G, Burgess W, Colthurst D, Hinks JD, Hunt E, Pearson MJ, et al. Pleuromutilins. Part 1. The identification of novel mutilin 14-carbamates. Bioorg Med Chem. 2001;9(5):1221-31.
- Biedenbach DJ, Bouchillon SK, Johnson SA, Hoban DJ, Hackel M. Susceptibility of Staphylococcus aureus to topical agents in the United States: a sentinel study. Clin Ther. 2014;36(6):953-60.
- Harrington AT, Black JA, Clarridge JE, 3rd. In vitro activity of retapamulin and antimicrobial susceptibility patterns in a longitudinal collection of methicillin-resistant Staphylococcus aureus isolates from a veterans affairs medical center. Antimicrob Agents Chemother. 2015;60(3):1298-303.
Leon H. Kircik MD firstname.lastname@example.org