|Year : 2017 | Volume
| Issue : 4 | Page : 274-280
Treatment guidelines for atopic dermatitis by Indian Society for Pediatric Dermatology task force 2016 - Part-2: Topical therapies in atopic dermatitis
Deepak Parikh1, Sandipan Dhar2, Sahana Srinivas3, Ramkumar Rammoorthy4, Rashmi Sarkar5, Arun Inamadar6, Manish Shah1, Raghubir Banerjee7, Amrinder Jit Kanwar8, Vibhu Mendiratta9, Renu George10, Ram Gulati11
1 Department of Pediatric Dermatology, Wadia Children Hospital, Mumbai, Maharashtra, India
2 Department of Pediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India
3 Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru, India
4 Department of Pediatric Dermatology, Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu, India
5 Department of Dermatology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
6 Department of Dermatology, Sri B. M. Patil Medical College, BLDE University, Bijapur, Karnataka, India
7 Department of Dermatology, Vivekananda Institute of Medical Science, Kolkata, West Bengal, India
8 Department of Dermatology, Sharda Hospital, Greater Noida, Uttar Pradesh, India
9 Department of Dermatology, Lady Hardinge Medical College, New Delhi, India
10 Department of Dermatology, Christian Medical College, Vellore, Tamil Nadu, India
11 Department of Dermatology, Santokba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India
|Date of Web Publication||29-Sep-2017|
Department of Pediatric Dermatology, Institute of Child Health, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Parikh D, Dhar S, Srinivas S, Rammoorthy R, Sarkar R, Inamadar A, Shah M, Banerjee R, Kanwar AJ, Mendiratta V, George R, Gulati R. Treatment guidelines for atopic dermatitis by Indian Society for Pediatric Dermatology task force 2016 - Part-2: Topical therapies in atopic dermatitis. Indian J Paediatr Dermatol 2017;18:274-80
|How to cite this URL:|
Parikh D, Dhar S, Srinivas S, Rammoorthy R, Sarkar R, Inamadar A, Shah M, Banerjee R, Kanwar AJ, Mendiratta V, George R, Gulati R. Treatment guidelines for atopic dermatitis by Indian Society for Pediatric Dermatology task force 2016 - Part-2: Topical therapies in atopic dermatitis. Indian J Paediatr Dermatol [serial online] 2017 [cited 2018 Jan 20];18:274-80. Available from: http://www.ijpd.in/text.asp?2017/18/4/274/215801
These guidelines are prepared by ISPD task force. It reflects the groups' experience, opinion and recommendation on the current treatment of atopic dermatitis in the Indian scenario.
| Disclaimer|| |
Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be interpreted as setting a standard of care or be considered inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific therapy should be made by the physician and the patient in the light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the disease. This guideline reflects the best available data at the time the guideline was prepared. The results of future studies may require revisions to the recommendations in this guideline to reflect new data.
This guideline outlines various treatment options. The available evidence was evaluated using a unified system called “The strength of Recommendation Taxonomy.” Grades are assigned on the basis of quality and consistency of available evidence [Table 1] and [Table 2].
| Topical Steroids in Atopic Dermatitis|| |
The goals of topical corticosteroid (TCS) therapy in atopic dermatitis (AD) are measured in terms of progressive reduction to change of the therapy to a topical nonsteroidal agent at the same time ensuring the absence of relapse after reduction in the frequency of application and/or stepping down to a lower potency steroid.
TCS has been ranked in terms of potency into four groups (Mild to super- or ultra-potent) including seven classes (Class I–VII). [Table 3] depicts the classification of TCSs. Super- or ultra-potent TCSs are not recommended for AD therapy as they are more likely to cause hypothalamic-pituitary-adrenal (HPA) suppression in children. Both mometasone furoate and fluticasone propionate are characterized by high selectivity and affinity to receptors with a lower risk of inducing side effects.
The finger-tip unit (0.5 g = 2 adult palm size) should be used as a guide of external dose application technique. [Table 4] shows practical guide to topical steroid therapy in children. Formulations used differ depending on the clinical stage of AD. A cream base should be used if lesions of AD are weepy and inflamed (acute lesions), an ointment base is appropriate for dry or lichenified lesions (chronic lesions), and a lotion base is recommended for hairy areas. Dose tapering should be done in a calculated manner to avoid withdrawal bounce back, tapering which should consist of using a less potent corticosteroid daily, or continuing the initial more potent one in reduced frequency.
|Table 4: Finger.tip unit topical steroid dose in different age group children|
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TCSs in AD can be administered in the form of:
- Intermittent therapy
- Weekend therapy
- Intermittent hot-spot therapy (hot spots imply the body areas known to relapse commonly, for example, antecubital fossa).
Optimally, a TCS should be used for only a few weeks (2–3 weeks) in a continuous therapy and then used twice weekly in intermittent therapy., To increase the patient compliance and reduce side effects in children with AD and in lichenified lesions of AD, it is suggested that a moderately potent topical steroid should be initially applied twice daily and then changed to once daily application, once an acute or intractable lesion remits. This method also reduces the chance of tachyphylaxis observed with strong/potent TCSs. Subsequently, switching to a lower potency TCS is practical. TCSs also reduce the skin colonization by Staphylococcus aureus which is an added advantage  (Strength of recommendation 1, Level of evidence 1).
Probable side effects of TCS therapy include skin atrophy, telangiectasias, striae, steroid-induced acne and/or rosacea, hypertrichosis, and systemic absorption leading to HPA suppression. Usually, they are seen with high potency TCS use and more so when applied to the skin around the eyes and face. Skin atrophy, telangiectasias, and hypo-pigmentations are more common in prepubertal children. Strategies for withdrawal of TCSs should be in place for all children who require prolonged treatment. These can be either gradual substitution by emollients, weekend-only use, or sequential therapy with nonsteroidal agents. “Steroid phobia” is a barrier to TCS use and it needs to be addressed by meticulous counseling. Overstated fear of TCS by patients (e.g., net savvy parents), misinformed professional colleagues, and the general community are the major barriers to effective management of AD using TCSs.
In recent years, the wet-wrap treatment (WWT) has been advocated as a relatively safe and efficacious intervention in children with severe or refractory AD. WWT using diluted steroids is a relatively safe addition to the therapeutic treatment options for children with severe and/or refractory AD. Explanation and education about WWT are extremely important in the treatment of AD.
Recommendations for Topical Corticosteroids in Atopic Dermatitis
- TCSs are used as first-line therapy along with appropriate use of moisturizing agents
- TCSs are best used until acute skin flares are under control
- During maintenance treatment, TCS can be applied weekly twice (weekend therapy) to “hot spots” for up to 6–8 weeks. Avoid face, flexural surfaces, and diaper area
- Adequate and suitable quantities of TCS to be used should be discussed with the patient attendant/care giver. They should be counseled regarding finger-tip unit
- TCS can be applied to areas of broken down skin including severely inflamed skin after suitable cleansing of the part to reduce oozing
- The choice of potency, frequency, and duration of use of TCS should be based on clinical judgment depending on the location, severity, and chronicity of eczema, and the age of the patient
- Initial use of moderately potent TCS for short period (5–7 days) followed by mild TCS to avoid tachyphylaxis and other side effects of potent TCS is recommended
- Avoid combination of topical steroid with antibacterial.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
- Katayama I, Kohno Y, Akiyama K, Aihara M, Kondo N, Saeki H, et al. Japanese guideline for atopic dermatitis 2014. Allergol Int 2014;63:377-98.
- WHO Model Prescribing Information: Drugs Used in Skin Diseases. Available from: http://www.apps.who.int/medicinedocs/en/d/Jh2918e/32.html#Jh2918e. 32.1. [Last accessed on 2016 May 25].
- Long CC, Finlay AY. The finger-tip unit – A new practical measure. Clin Exp Dermatol 1991;16:444-7.
- Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol 2012;26:1045-60.
- Rubel D, Thirumoorthy T, Soebaryo RW, Weng SC, Gabriel TM, Villafuerte LL, et al. Consensus guidelines for the management of atopic dermatitis: An Asia-Pacific perspective. J Dermatol 2013;40:160-71.
- Hanifin JM, Cooper KD, Ho VC, Kang S, Krafchik BR, Margolis DJ, et al. Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association “Administrative Regulations for Evidence-Based Clinical Practice Guidelines”. J Am Acad Dermatol 2004;50:391-404.
- Paller AS. The 2004 Process of Care: Treatment Options for the Management of Atopic Dermatitis. New York: Millennium CME Institute; 2004.
- Williams HC. Established corticosteroid creams should be applied only once daily in patients with atopic eczema. BMJ 2007;334:1272.
- Darsow U, Wollenberg A, Simon D, Taïeb A, Werfel T, Oranje A, et al. ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol 2010;24:317-28.
- Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006;54:1-5.
- Saraswat A. Topical corticosteroid use in children: Adverse effects and how to minimize them. Indian J Dermatol Venereol Leprol 2010;76:225-8.
- Oranje AP, Devillers AC, Kunz B, Jones SL, DeRaeve L, Van Gysel D, et al. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel's opinion and review of the literature. J Eur Acad Dermatol Venereol 2006;20:1277-86.
| Topical calcineurin inhibitors in atopic dermatitis|| |
Tacrolimus and pimecrolimus are immunosuppressive macrolactones produced by Streptomyces bacteria. Their role in atopic dermatitis (AD) is mainly a steroid sparing agent. Treatment with topical calcineurin inhibitors (TCIs) significantly reduces flares and the need for topical corticosteroids. 
| Therapeutic Efficacy And Safety|| |
TCIs have been found to be effective and safe in the management of AD in children in short- and long-term studies from the West and India. ,,,,, TCIs are usually recommended in children >2 years of age. Although studies have shown that tacrolimus ointment 0.1% is safe in children,  currently, as per the Food and drug administration guidelines only tacrolimus ointment 0.03% is recommended for use in children aged 2-15 years. Similarly, pimecrolimus cream 1% has been reported to be safe in infants (Strength of recommendation A, Level of evidence 1).
The most common side effects are stinging and burning at the site of application which usually diminishes with use. TCIs have not been found to increase the risk of bacterial, fungal or viral infections in immunocompetent individuals (with the exception of folliculitis in adults). , (Strength of recommendation A, Level of evidence 1). The use of these agents in the presence of overt infection is not recommended. It should also be used with caution in those having diseases with a severely damaged skin barrier. Tachyphylaxis and rebound are not observed with TCIs. 
Risk of Malignancy
Rare cases of lymphoma and nonmelanoma skin cancers have been reported with the use of these agents. The observed incidence of nonmelanoma skin cancers in patients with AD treated with tacrolimus ointment is similar to the reported incidence of nonmelanoma cancer in a comparable population.  A recent cochrane review reported that both tacrolimus formulations were safe and there was no evidence to support the possible increased the risk of malignancies. The authors, however, cautioned that the reliability and strength of evidence was limited by the lack of data  (Strength of recommendation B, Level of evidence 1). Sun protection is recommended while on treatment with topical calcineurin inhibitors. ,
Dosing and Frequency of Application
Most studies report twice daily application of TCIs. Proactive treatment includes intensive topical anti-inflammatory therapy until visible skin lesions have cleared followed by continuous low-level use of topical-anti-inflammatory agents to previously affected skin areas to maintain remission. Tacrolimus ointment applied twice/thrice weekly has been found to be effective in proactive therapy. (Strength of recommendation A, Level of evidence 1) Tacrolimus ointment 0.03% was found to be safe when used up to 1 year , (Strength of recommendation A, Level of evidence 1). Pimecrolimus cream has also been found to be effective for maintenance therapy. 
Topical Calcineurin Inhibitors and Immunization
The fact sheet put out by National Eczema Society, United Kingdom, December, 2015 (www.eczema.org) has said that it is wise to avoid treatment with topical tacrolimus for 3 weeks after vaccination.  In the case of live vaccines, treatment with topical tacrolimus is best avoided for 28 days before and after vaccination, to avoid the additional theoretical possibility of an infection. Due to the potential risk of vaccination failure, the manufacturers of tacrolimus advice that vaccination should be administered either before commencement of treatment with tacrolimus or after a tacrolimus-free interval of 2 weeks. The same applies for pimecrolimus. 
Recommendations for the Use of Topical Calcineurin Inhibitors in Pediatric Atopic Dermatitis
- TCIs are generally recommended as second - line of treatment for treatment of moderate/severe eczema in immunocompetent children > 2 years of age during the maintenance phase of therapy. It is used on the face and flexures as it does not cause atrophy of the skin. Their use should be avoided during acute flares and if the eczema is infected. Tacrolimus ointment 0.03% or pimecrolimus 1% twice daily may be applied till lesions resolve. Short term therapy for 2-3 weeks is preferable to prolonged continuous therapy. Burning and stinging associated with the use of TCIs are transient
- Pimecrolimus 1% or tacrolimus 0.03% may be used as first-line treatment in cases of mild eczema of the face and flexures. TCIs are also indicated in cases where prolonged use of topical steroids has resulted in significant local adverse effects
- Pimecrolimus 1% may be used in children <2 years of age if the eczema does not respond to topical steroids
- TCIs may also be used sequentially or concomitantly with topical steroids
- Proactive treatment with TCIs applied twice/thrice weekly to areas that flare frequently will help prevent relapses
- The possible risk of developing nonmelanoma skin cancers and lymphomas with long term use of TCIs should be discussed with the guardian/parent. Patients should be advised to use broad spectrum sunscreens 30 min before going outdoors while on treatment with TCIs.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
- Breuer K, Werfel T, Kapp A. Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. Am J Clin Dermatol 2005;6:65-77.
- Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 2001;44:S47-57.
- Ho VC, Gupta A, Kaufmann R, Todd G, Vanaclocha F, Takaoka R, et al. Safety and efficacy of nonsteroid pimecrolimus cream 1% in the treatment of atopic dermatitis in infants. J Pediatr 2003;142:155-62.
- El-Batawy MM, Bosseila MA, Mashaly HM, Hafez VS. Topical calcineurin inhibitors in atopic dermatitis: A systematic review and meta-analysis. J Dermatol Sci 2009;54:76-87.
- Kang S, Lucky AW, Pariser D, Lawrence I, Hanifin JM. Long-term safety and efficacy of Tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001;44:S58-64.
- Saple DG, Torsekar RG, Pawanarkar V, Wali V, Ravichandran G, Dhanalakshmi UR, et al. Evaluation of the efficacy, safety and tolerability of Tacrolimus ointment in Indian patients of moderate to severe atopic dermatitis: A multicentric, open label, phase III study. Indian J Dermatol Venereol Leprol 2003;69:396-400.
- Dhar S, Banerjee R. Topical tacrolimus in atopic dermatitis: A placebo controlled study with 15 children. Indian J Dermatol 2004;49:22-4.
- Fleischer AB Jr. Ling M, Eichenfield L, Satoi Y, Jaracz E, Rico MJ, et al. Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol 2002;47:562-70.
- Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM, et al. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev 2015;2:CD009864.
- Rico MJ, Naylor M, Elmets CA, Su J, Alfanso T, Ducker F, et al. Treatment with tacrolimus ointment is not associated with an increase in non-melanoma cancers (abstract). J Eur Acad Dermatol Venereol 2003;17 Suppl 1:53.
- Paller AS, Eichenfield LF, Kirsner RS, Shull T, Jaracz E, Simpson EL, et al. Three times weekly Tacrolimus ointment reduces relapse in stabilized atopic dermatitis: A new paradigm for use. Pediatrics 2008;122:e1210-8.
- Thaηi D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, et al. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: Results of a randomized, multicentre, comparative study. Br J Dermatol 2008;159:1348-56.
- Luger T, De Raeve L, Gelmetti C, Kakourou T, Katsarou A, Lambert J, et al. Recommendations for pimecrolimus 1% cream in the treatment of mild-to-moderate atopic dermatitis: From medical needs to a new treatment algorithm. Eur J Dermatol 2013;23:758-66.
- Grabenstein JD. What the world's religions teach, applied to vaccines and immune globins. Vaccine 2013;31:2011-23.
| Phototherapy|| |
Phototherapy is the second-line therapy in AD that has failed to respond adequately to emollients, topical corticosteroid (TCS), topical calcineurin inhibitors (TCIs), and environmental modifications.  Various sources of light have been utilized for phototherapy; however, narrowband ultraviolet B (UVB) (NB-UVB) is the safest and most studied therapy in children.
Various sources of light have been utilized for phototherapy, including natural sunlight, NB-UVB, broad band UVB, ultraviolet A (UVA), UVA1, cold light UVA1, full spectrum light (including UVA, infrared, and visible light) and psoralen plus UVA. Artificial light source has been0 shown to achieve better results than natural sunlight.  NB-UVB and UVA1 phototherapy have been best studied for moderate to severe AD. UVA that penetrates to deep dermis works better for acute AD, whereas NB-UVB is more effective for chronic AD.  Due to high expense, long exposure time and heat production, UVA-1 has not found widespread acceptability.
Various studies confirm that NB-UVB has been used safely and effectively in children. ,,, It is often started at a dose of 100-280 mj/cm 2 . If possible, it is worthwhile calculating the minimal erythema dose (MED) and starting at 70% of the MED. NB-UVB is ideally administered 2-3 times a week. Dose is increased by 10%-20% if there is no erythema or erythema lasting <24 h. If erythema stays for >24 h but <48 h, the dose should be kept same. If erythema stays for longer than 48 h, the dose should be decreased by 20%. It takes approximately 25-30 sessions for peak improvement of AD. NB-UVB can be used as maintenance therapy 1-2 times a week for up to a year in children. After a year, usually 3 months holiday is advised; following which NB-UVB can be re-administered, if required (Strength of recommendation 1, Level of evidence 2).
NB-UVB therapy can be combined with topical therapies such as emollients and corticosteroids. At present, combination of NB-UVB with calcineurin inhibitors is not recommended. NB-UVB can be safely administered with methotrexate, but co-administration with cyclosporine should be avoided. The main adverse effects of NB-UVB therapy are erythema, xerosis, tenderness, and sunburn. Side effects are self-limiting and can be treated symptomatically. Phototherapy is usually administered over the entire body, covering the genitals. Protecting the eyes with UV goggles during phototherapy is mandatory.
Recommendations for Phototherapy
- Phototherapy when available is first choice of therapy for AD that fails to respond adequately to emollients, TCS, TCIs, and environmental modifications
- NB-UVB therapy is the most commonly employed phototherapy currently
- NB-UVB is safe and effective for childhood AD
- NB-UVB needs to be administered 2-3 times a week for optimal efficacy
- Approximately 25-30 sessions are required for observing substantial improvement
- NB-UVB has been safely administered for up to a year's duration in children
- NB-UVB therapy can be combined with emollients, TCS and methotrexate. TCIs and oral cyclosporine should not be combined with phototherapy
- Side effects of NB-UVB therapy are mild and include erythema, xerosis, tenderness, and sunburn.
Financial Support and Sponsorship
Activity of ISPD Task Force for Treatment Guidelines for Atopic Dermatitis 2017 is supported by an Unlimited Educational Grant of Curatio Healthcare India Pvt. Ltd.
Conflicts of Interest
There are no conflicts of interest.
- Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 2014;71:327-49.
- Meduri NB, Vandergriff T, Rasmussen H, Jacobe H. Phototherapy in the management of atopic dermatitis: A systematic review. Photodermatol Photoimmunol Photomed 2007;23:106-12.
- Pιrez-Ferriols A, Aranegui B, Pujol-Montcusν JA, Martνn-Gorgojo A, Campos-Domνnguez M, Feltes RA, et al. Phototherapy in atopic dermatitis: A systematic review of the literature. Actas Dermosifiliogr 2015;106:387-401.
- Clayton TH, Clark SM, Turner D, Goulden V. The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapy. Clin Exp Dermatol 2007;32:28-33.
- Jury CS, McHenry P, Burden AD, Lever R, Bisland D. Narrowband ultraviolet B (UVB) phototherapy in children. Clin Exp Dermatol 2006;86:34-8.
- Tan E, Lim D, Rademaker M. Narrowband UVB phototherapy in children: A New Zealand experience. Australas J Dermatol 2010;51:268-73.
- Darnι S, Leech SN, Taylor AE. Narrowband ultraviolet B phototherapy in children with moderate-to-severe eczema: A comparative cohort study. Br J Dermatol 2014;170:150-6.
[Table 1], [Table 2], [Table 3], [Table 4]