Therapeutic Guideline Overview

Introduction

Treatments for atopic dermatitis (AD) have evolved over the years. As our understanding of the underlying pathophysiology grows, treatment options broaden and treatment strategies are refined. This chapter provides a bird’s-eye view on the general therapeutic guideline, taking into account the recently published consensus. Following this chapter, the section Clinician’s Corner will then be divided into discussions of therapeutics from the perspectives of encountering the external factors (see Chapter 20, Chapter 21, Chapter 22 ), the internal factors (see Chapter 23 ), and the combined approaches (see Chapter 24, Chapter 25, Chapter 26, Chapter 27 ).

Overview of recently published guidelines

This chapter serves to provide a unified, consolidated overview of recently published therapeutic guidelines for the management of AD. Guidelines and similar documents, including consensus statements and expert management recommendations, are pursued and published to assist in the clinical care and management of AD patients. Many of these are produced through professional organizations that relate to specialty societies, including dermatology and allergy organizations, as well as pediatric and other primary care health care professional groups. Guidelines may vary by region, country, and continent; others are international initiatives. This chapter aims to review and emphasize the most essential current guidelines related to caring for patients with AD across the age groups, conscious that it can only relate a selection of them with cursory sampling of the actual recommendations.

This chapter will draw most of its focus from the American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Joint Task Force 2012 AD Practice Parameter (JTF) and the 2014 American Academy of Dermatology (AAD) guidelines. The JTF Practice Parameter is an update of the 2004 parameter on AD; it is a single document with an executive summary, followed by evidence-based summary statements and an annotated flowchart of the diagnosis and management of AD. The AAD guidelines are organized into four separate publications. The AAD work group and JTF ranked their recommendations in similar manners, AAD from “A” to “C” and JTF from “A” to “D.” Both of these are based on the grade of evidence available for these clinical practices.

Diagnostic and severity grading criteria for atopic dermatitis

The diagnosis of AD is clinically based. In making this diagnosis, physicians should consider patient history, lesion morphology and distribution, and associated clinical signs. Various groups have created formal guidelines to aid in making a correct and reliable diagnosis of AD, though guideline criteria vary in sensitivity, specificity, and applicability to epidemiologic or clinical studies versus utility in clinical practice.

The 1980 Hanifin and Rajka criteria is one of the earliest and most recognized sets of diagnostic criteria for AD. The diagnosis of AD requires that one must meet 3 of 4 major criteria and 3 of 23 minor criteria ( Table 19.1 ). Though comprehensive and commonly used in clinical trials, the criteria can be difficult to incorporate into clinical practice—additionally, several of the minor criteria are nonspecific or uncommon ( ). Several international groups have proposed modifications to address these limitations (e.g., Kang and Tian criteria, International Study of Asthma and Allergies in Childhood [ISAAC] criteria) ( ). A systematically distilled version of the Hanifin and Rajka criteria created by the UK Working Party is often utilized for epidemiologic studies. The core set consists of one mandatory and five major criteria, all of which do not require laboratory testing. Both the Hanifin and Rajka and the UK Working Party diagnostic schemes have been validated in studies and tested in several different populations. The original UK criteria cannot be applied to very young children, although revisions to include infants have since been proposed ( ).

A 2003 consensus conference directed by the American Academy of Dermatology suggested diagnostic schemes based on revised Hanifin and Rajka criteria that are simplified and applicable to the wide age range that can be affected by this disease ( Table 19.2 ) ( ). This version has been formally validated in children, but not adults ( ); however, it has been accepted by many for use in clinical trials, as well as considered a pragmatic approach for the clinical setting. The JTF and AAD guidelines both define AD as a chronic pruritic inflammatory disease that more commonly affects the pediatric population and is a diagnosis that is clinically based on patient’s history, characteristic clinical findings, and exclusion of other dermatoses. Both of these guidelines agree that the disease can be familial; however, the AAD guidelines associate AD with history of type 1 allergies, allergic rhinitis, and asthma ( ). The JTF guidelines assert the necessity of an atopic history, whereas the AAD guidelines only distinguish atopy as an important feature. The JTF guidelines outline the typical appearance according to the chronicity of AD lesions as pruritic, erythematous papulovesicular lesions associated with excoriation and serous exudate in the acute setting, whereas findings of lichenification, papules, and excoriations can be seen in patients with chronic AD. In contrast, AAD guidelines focus more on the standardized criteria based on the revised Hanifin and Rajka diagnostic schemes discussed earlier (see Table 19.1 ) ( ).

Multiple guideline’s criteria discuss the differential diagnosis and suggest judicial use of skin biopsy specimens or other tests (such as serum immunoglobulin E [IgE], potassium hydroxide preparation, contact allergy patch testing, and/or genetic testing), which may be helpful to rule out other or associated skin conditions. The AAD guidelines mandate the exclusion of other common cutaneous disorders before the diagnosis of AD; however, the JTF guidelines suggest this through thorough reevaluation. Other considerations discussed by the AAD work group include the lack of a requirement for specific biomarkers for a diagnosis or severity assessment and recommend against routine IgE levels ( ).

Severity grading criteria

There are a myriad of disease severity scales, the most common being the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Investigator’s Global Assessment (IGA), and the Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score.

As there are currently more than 20 different named instruments to measure the severity of AD, all of which assess different aspects of AD in different ways, a major obstacle exists in advancing evidence-based treatment. Because of this, the global Harmonising Outcome Measures for Eczema (HOME) initiative was created with the aim to standardize and validate a core set of outcome measurements for AD. As outlined on the HOME for eczema group webpage, the HOME outcome domains are divided into four categories: clinical signs measured by using a physician-assessed instrument, symptoms measured by using a patient-assessed instrument, health-related quality of life, and long-term control of flares ( ).

The EASI score evaluates the AD involvement based on the extent of dermatitis and the degree of erythema, papulation, excoriation, and lichenification by body regions. The SCORAD takes into consideration both the physician’s objectives on extent and severity as well as the subjective patient assessment of itch and sleeplessness. The Patient-Oriented Eczema Measure (POEM) is a short questionnaire solely based on the patient’s perspective in relation to symptoms and frequency. The Three Item Severity Scale (TISS) is another simplified scale that shows promise for future use in clinical practice, although it needs further testing.

The available literature suggests that the SCORAD index, the EASI score, and POEM severity scale have been adequately tested and validated, and therefore their use can be considered when practical ( ). For clinical studies, the HOME group states that all trials should measure the core domains (as referenced earlier) as this will enable trials to be compared and combined in meta-analyses. Worldwide consensus was reached that these core outcome domains should be used in all future AD trials. However, the inclusion of core outcomes does not preclude the use of any additional domains, scales, or instruments. The HOME group recommends the use of EASI score for the clinical signs core outcome, and POEM for patient reported symptoms core outcome. For the quality of life core outcome, they recommend the Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children, and the Infants’ Dermatitis Quality of Life Index (IDQoL) for infants. The RECAP (Recap of Eczema Control for Atopic Eczema) and the ADCT (Atopic Dermatitis Control Tool) are recommended as the long-term control outcome measures ( ).

These scales are primarily used in clinical trials and only rarely in clinical practice. IGA, as its name reflects, uses investigational global assessments (IGAs) in its studies. Many different IGAs have been utilized, and recently a validated IGA has been developed and recommended for use by the .

Body surface area (BSA) is a standard assessment in clinical studies and may be a useful measure in clinical practice.

The AAD guidelines state that for the general management of patients with AD, available disease severity measurement scales are not recommended for routine clinical practice because they were not designed for this purpose. Additionally, they recommend that clinicians ask general questions about itch, sleep, impact on daily activity, and persistence of disease, and currently available scales should be used mainly when practical ( ).

Nonpharmaceutic agents: moisturization, wet wrap therapy, and bleach baths

Topical therapies are the mainstay of AD treatment and are commonly used with other interventions to combat different components of this complex disease. In this section we focus on the current guidelines with reference to the JTF and AAD recommendations on these common nonpharmaceutic therapies: moisturizers, wet wrap therapy, and bleach baths.

Moisturization

Xerosis is one of the cardinal clinical features of AD. Dryness, essentially ubiquitous in AD patients, is secondary to a dysfunctional epidermal barrier and transepidermal water loss—factors that moisturizers help alleviate to some degree. Moisturizers may include emollients (i.e., glycol, soy sterols), occlusive agents (i.e., petrolatum, dimethicone, mineral oil), and humectants (i.e., glycerol, lactic acid, urea).

Moisturizers help to hydrate the skin—this has been supported both subjectively by patients and objectively by means of microscopy to assess changes in the skin’s capacitance/conductance. A number of clinical trials have shown that moisturizers lessen the symptoms and signs of AD, including pruritus, erythema, fissuring, and lichenification. Additionally, multiple randomized clinical trials have demonstrated that moisturizer use decreases the amount of prescription antiinflammatory treatments needed for disease control.

Most all guideline documents state that regardless of severity, moisturizers should be incorporated in all AD patient regimens and continued as part of a maintenance plan for prevention of flares due to strong evidence that it can reduce disease severity and the need for pharmacologic intervention. The JTF and AAD guidelines concur that moisturizers increase skin hydration by improving skin barrier function and reducing transepidermal water loss. Both agree that moisturizers are a main primary treatment for mild disease and an important adjunctive therapy in moderate and severe disease ( ).

It is expert consensus that moisturizers should be applied soon after bathing to improve skin hydration, though there is not an optimal amount or frequency of application defined by systematic studies. In the JTF and AAD guidelines, liberal and frequent application is suggested. The AAD and JTF guidelines acknowledge that most ointments carry the advantage of being preservative and fragrance free; however, no specific recommendations regarding vehicle systems and types of moisturizers have been made ( ).

Prescription emollient devices (PEDs) are generally agents with distinct ratios of lipids that mimic normal skin. They are designed and proposed to target defects in skin barrier function seen in AD patients. They have not been shown to be superior to other moisturizing products, and therefore AAD guidelines do not recommend their use ( ).

Among the few trials that have been conducted to compare and contrast specific moisturizing products, a specific moisturizer has not been deemed superior—this includes the PEDs. Choice of moisturizer is largely based on patient and provider preference, though ideally the chosen agent is effective and free of additives, fragrances, and other sensitizing agents. Despite the lack of specifics, both the JTF and AAD guidelines recommend incorporating moisturizers as part of the AD patient regimen in times of active disease, maintenance, and flare prevention.

Wet wrap therapy

AAD guidelines recommend that the use of wet wrap therapy with or without a topical corticosteroid (TCS) can be advised for patients with moderate to severe AD to decrease disease severity and water loss during flares ( ).

Both the JTF and AAD guidelines recommend wet wrap therapy with use of TCS in the setting of significant flares/refractory disease. This method tends to involve applying TCS followed by wet gauze and a second layer of dry gauze to seal in the medication. Some experts utilize two layers of clothing over TCS as an alternative. Wet wraps help to occlude and increase penetration of the therapeutic agent; additionally, it decreases water loss and provides a barrier against scratching. It should be mentioned that caution should be taken when using mid- to high-potency steroids as there is an increased chance of systemic side effects particularly if used widely on skin, though only the JTF guidelines recommend against overuse of wet wrap therapy ( ).