Treatment of adult patients with atopic dermatitis

Introduction

Atopic dermatitis (AD), also known as neurodermatitis or atopic eczema, is a chronic, relapsing skin condition characterized by itching. This skin condition is considered one of the biggest health problems worldwide, with its prevalence constantly increasing. Statistically, about 10-20% of children and 1-3% of adults suffer from AD.

Etiology

The exact etiology of the disease is not known, although a genetic predisposition is observed and the disease is associated with atopy in the family. People with AD are linked to increased production of immunoglobulin E (IgE), abnormal lipid metabolism, disrupted formation of epidermal proteins, and a tendency towards pathological skin microflora. These features are genetically inherited. The disease is greatly influenced by psychosomatics and the individual's ability to cope with stress. Stress mechanisms are important due to the release of different mediators. It is these mediators that determine the exacerbation or new manifestation of AD. There are cases where AD appears not from childhood but in adulthood, triggered by anxiety-inducing events (1).

Clinic and Diagnosis

In many countries, the diagnosis of AD is based on subjectively assessed clinical signs and symptoms, which are divided into major and minor categories. The severity of AD is assessed using the SCORAD (Scoring Atopic Dermatitis) scale, which also evaluates itching and sleep disturbances caused by changes in skin condition. SCORAD helps assess skin erythema (redness), edema, oozing and crusting, excoriations, lichenification, and dryness in different areas of the skin (Figure 1) (2).

AD can be allergic, triggered by certain factors and associated or not associated with IgE. Another type of AD is non-allergic dermatitis. Both types can be intermittent, persistent, or go into remission. Although blood immunoglobulins are considered to modify the clinical course, there are no specific laboratory diagnostic criteria for diagnosing AD. Exacerbations of the disease are often linked to seasonal changes, stress, changes in patient activity, staphylococcal infection, or contact irritant reactions.

When examining a patient, it is important to have 3 or more major diagnostic criteria, i.e., itching, personal or family history of atopy, chronic or chronically relapsing course, localization and rash typical for the age. The most common localization for adult patients is hands and eczema around the eyes. AD is most commonly localized on the hands and feet, but in adults, it occurs less frequently. At the same time, 3 or more minor criteria must be detected, including skin dryness, accentuation of palm lines, ichthyosis, keratosis pilaris, positive skin prick tests, increased IgE levels, early onset of the disease, increased sensitivity to infections, cheilitis, Dennie-Morgan fold, nipple eczema, anterior subcapsular cataract, darkening of the skin around the eyes, pityriasis alba, itching after sweating, wool or food intolerance, white dermographism, and the influence of stress on the course of the disease.

Treatment

Patients with AD usually do not require emergency treatment, but it is important to consider the impact of the disease on their quality of life. It is worth noting that the skin of AD patients is much more sensitive to additional bacterial, viral, or fungal infections, which not only worsen the skin condition but also affect overall well-being. AD is treated in stages, which must be followed to optimize skin condition.

Figure 1. Visual assessment of AD severity scale (14)

Stage I

Skin dehydration develops in every patient with eczema. Depending on the time of year, the conditions causing this state change. Moisturizing the skin is one of the key and primary treatment and support methods. The most suitable method is a 5-minute lukewarm water bath, during which emollients are generously applied in the first 3 minutes. Since city water is often hard and acidic, it is worth recommending alkalizing it with sodium hypochlorite. Baths can be supplemented with skin-friendly oils that help retain moisture in the deeper layers of the skin and protect against evaporation into the environment. For adult patients, this should be done at least 1-2 times a day. Due to endogenous moisture deficiency, it is recommended to leave the body damp after baths, applying heavy emollients to better absorb water through the horny layer. To reduce possible erosion and excoriations, wet wraps soaked in corticosteroid solution can be recommended. It is important to wash the skin gently, choosing cleansers that do not damage the skin, to prevent additional damage to the skin barrier.

Another equally important point of the first stage of treatment is to identify allergens that worsen the disease, suspecting allergic origin AD. Skin prick tests can be used to identify allergens. If an allergy to a particular component is identified, it is necessary to avoid it.

Topical steroids are currently one of the most popular treatment methods for skin conditions, often improving the skin's condition without causing strong systemic effects compared to oral medications. Combining steroid preparations with regular moisturizing of the skin leads to very good results. This treatment is also divided into several stages: therapy starts with 1% hydrocortisone powder, mixed with a hypoallergenic ointment base, and applied 2 times a day to skin lesions. The second (medium-strength) stage uses triamcinolone or betamethasone valerate 2 times a day, especially suitable for treating eczematous lesions on the trunk. Steroids should be tapered according to a schedule. The dose is reduced when the rash elements begin to decrease. In a study conducted in the Netherlands involving patients with AD, it was found that when corticosteroids are used around the eyes, eyelids, or periorbital area, potential provocation of glaucoma or cataracts should be taken into account. It is recommended to monitor patients for these conditions, considering their family history. Supportive remission therapy may involve the use of 1.25% hydrocortisone powder. This ointment is used as a long-term measure to prevent exacerbations of the skin condition.

Immunomodulatory ointment therapy is also important for the skin. One of the most popular is tacrolimus, which acts as a calcineurin inhibitor. Its goal is to reduce T-lymphocyte differentiation by blocking calcineurin inhibitors. This results in a weaker response to skin irritants. Researchers conducted a study comparing the effect of immunomodulators on improving skin condition with 1% hydrocortisone ointment and a placebo. Treatment with immunomodulators can cause unpleasant side effects, including skin burning. To reduce this sensation, it is important to apply the medication to dry skin. The skin usually adapts to the effects of the medication within 2-3 days. For adult patients, a 0.1% concentration tacrolimus preparation is recommended for treating severe and moderate stages of the disease. Accurate prescription of this preparation is important, as a study on the malignant processes and formations caused by calcineurin inhibitors in the body has been ongoing in the United States since 2006. These statements are not yet substantiated. In this case, it is important to accurately determine the stage of AD and follow a stepwise algorithm, prescribing topical immunomodulators only when external treatment with steroids is ineffective.

There are many theories about the influence of IgE on the course of the disease and that immunomodulatory therapy should be effective for this type of disease. Studies have been conducted with omalizumab, which blocks the mentioned Ig, but randomized, placebo-controlled studies did not reveal a significant impact on the clinical course of the disease. Patients with AD suffer from itching, and scratches often serve as additional gateways for infection to spread. Hydroxyzine and diphenhydramine preparations are used to reduce itching, along with antibiotic ointments. If there is no therapeutic effect, antihistamine and antibacterial treatment should be administered orally.

Stage II

In Lithuania, radiation therapy with UV-A, UV-B, their combination, or their combination with psoralen (UV-A (PUVA)) or UV-B1 (narrowband UV-B) therapy is often used. PUVA is commonly used. When using it, psoralens increase skin sensitivity to UV rays, thus achieving greater effectiveness. Phototherapy causes erythema and is often associated with the development of malignant skin lesions, although it has been proven to effectively reduce inflammatory skin reactions in various skin diseases.

Stage III

Systemic treatment of the disease usually involves oral glucocorticoids, combined with external treatment and phototherapy. Methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil are usually chosen for this purpose as they have been the most effective in studies. For biologic subcutaneous injection therapy in patients with AD, an anti-IL-4Ra preparation (dupilumab) is used. This drug mainly targets interleukin-4, interleukin-13, and their blocking has been proven in phase 2 clinical trials. Since 2017, the drug has been prescribed to adult patients with moderate to severe AD who have not responded to all external skin treatment stages or for whom these measures cannot be prescribed for other health reasons. Evaluating clinical outcomes, the indications for this therapy were expanded at the beginning of 2019 - the drug is allowed to be prescribed to children from 12 years of age. Dupilumab continues to be studied. According to scientists, it will be one of the main medications for treating moderate and severe AD. Topical phosphodiesterase-4 inhibitors have also been included in the treatment algorithms for moderate to severe AD. This decision was made after two placebo-controlled trials where patients with severe forms of the disease almost eliminated their skin rashes after 28 days of applying the drug.

Other Treatment Methods

Patients with AD experience significant psychological difficulties, so they are often offered psychological help. Caring for atopic skin requires specific knowledge, so taking the time to educate patients is also very important. Recently, probiotics are increasingly being used to treat AD. Scientists find a lot of evidence for this: bacterial products can induce an immune response mediated by T1 cells, not T2 cells, which allows suppressing the production of allergic IgE antibodies. Some studies have revealed that pregnant and breastfeeding women with AD should take probiotics to reduce the development of AD in children (11, 12, 13).

It is important to consider non-medical factors such as gentle and non-irritating clothing, cool room temperature, especially at night, to reduce itching, improve sleep quality, use of air humidifiers at home, especially in conditioned environments with evaporated moisture. It is important to pay attention to the everyday use of detergents and cleaners. It is important to carefully monitor patients' diet. If necessary, a balanced and skin-friendly diet should be ensured.

Summary

AD is a skin disease that significantly affects the quality of human life. Proper and continuous patient treatment and education, assistance in integration into society, continuous monitoring, and evaluation of the condition are important. It is necessary to prevent factors that trigger the disease. In order to effectively combat exacerbations of this skin condition, it is necessary to monitor treatment algorithms and stages, and search for new treatment methods or combinations that are most suitable for the patient.

Publication "Internistas" No. 8, 2019.

Aistė Ramanauskaitė Vilnius University Faculty of Medicine

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