Atopic dermatitis and diathesis – symptoms and treatment

Definition of the disease. Causes of the condition

Atopic dermatitis (endogenous eczema) is a chronic recurrent inflammatory skin condition accompanied by intense itching and the appearance of eczematous and lichenoid eruptions.
This form of dermatosis often coexists with other allergic diseases such as bronchial asthma, allergic rhinitis and conjunctivitis, food allergies, as well as ichthyosis. This combination exacerbates the course of atopic dermatitis.

Prevalence of atopic dermatitis
The incidence among children is 10-12% of cases, and among adults, it is 0.9%, of which 30% concurrently suffer from bronchial asthma, and 35% from allergic rhinitis.

Causes and risk factors of atopic dermatitis
Atopic dermatitis is an immune-dependent disease. A powerful factor in its development is mutations in the genes encoding filaggrin – a structural protein of the skin that participates in the formation of the skin barrier, prevents water loss, and the entry of large amounts of allergens and microorganisms. Therefore, atopic dermatitis is mainly inherited from parents, more often from the mother than from the father.
Such a genetic mutation itself does not lead to atopic dermatitis but predisposes to its development. This “programmed” tendency is now commonly referred to as diathesis. It is not an independent disease and can lead to the development of atopic dermatitis only under the influence of triggering factors. These include:

• Atopogens – environmental allergens that induce the formation of allergic antibodies, increasing the sensitivity of mast cells and basophils:
  1. Food atogens (cow’s milk, wheat, shellfish, soy, chocolate, citrus fruits);
  2. Pollen atogens (ragweed, mugwort, birch, alder);
  3. House dust atogens (animal hair, dust mites, mold fungi, paper dust, varnishes, paints);
• Food products (sweets, smoked foods, spicy dishes, alcoholic beverages);
• Medications (antibiotics, vitamins, sulfonamides, pyrazolone derivatives);
• Overcooling;
• Emotional stress.
  External factors play a significant role in exacerbating atopic dermatitis:

1. Climatic conditions (the disease often occurs in Scandinavian countries in the spring-autumn period);
2. Pollutants in the domestic environment (smoke, perfumes);
3. Solvent vapors (acetone, turpentine);
4. Harmful working conditions (skin contamination with solid oil particles, frequent friction and pressure, aggressive solvents, and detergents).
   Internal factors include:
5. Viral infections (EBV mononucleosis, AIDS, infectious hepatitis);
6. GI diseases (pancreatitis, infectious gastritis);
7. Endocrine system diseases (thyrotoxicosis, dysmenorrhea, menopause).

Symptoms of atopic dermatitis

The clinical presentation of the disease depends on the age at which the symptoms first appeared. The disease typically begins in early childhood, subsides by school years, but can reappear during puberty and later.

There are three phases of the disease:

• Infantile phase: from 7-8 weeks to 1.5-2 years;
• Childhood phase: from 2 to 12-13 years;
• Adult phase: from the onset of puberty and older.

As these phases transition, the localization of atopic dermatitis gradually changes.

In the infantile phase, atopic dermatitis manifests acutely as infantile eczema. This is characterized by the appearance of red swollen papules (nodules) and patches that ooze and crust over. These eruptions mainly affect the skin of the cheeks and forehead, the lateral surface of the neck, the upper chest, the flexural surfaces of the limbs, and the palms of the hands. The hairy part of the head may develop accumulations of scaly crusts called “cradle cap.”

During the childhood phase, the disease presents as childhood eczema. It starts with itching and mild swelling, smoothing out fine folds of the skin. However, the fold under the lower eyelid becomes more pronounced (Dennie’s sign).

The primary element of the skin rash becomes vesicular (blister-like) eruptions. These then develop into eczematous patches the size of a coin, covered with small bloody scabs. This type of rash is also called flexural eczema because it mainly occurs on the flexural surfaces of the hands and feet.

The only constant symptom of the disease, regardless of age, is intense, sometimes agonizing itching. In various skin injuries, inflammatory mediators accumulate, lowering the skin’s sensitivity threshold to various irritants. As a result, scratching leads to eczematous inflammation.

The course of atopic dermatitis depends on the season: exacerbations occur in winter, leading to relapses, while partial or complete remission is observed in summer.

During exacerbations, scaling, papules resembling red flat lichen, and areas of lichenification – thickening of the skin with increased folds – appear at the sites of regressing eruptions. The process becomes widespread, affecting mainly the skin folds of the elbow and knee joints, face, neck, and backs of the hands. It often persistently affects the dorsal surface of the hands, acquiring the pattern of “chronic eczema of the hands in atopic individuals.”

During prolonged exacerbations, the general condition deteriorates. Some individuals develop signs of asthenic-depressive syndrome – increased fatigue, irritability, and anxiety.

During remission, the skin becomes dry (atopic xerosis), pale, and irritable.

In addition to the main manifestations of the disease, i.e., eczema and itching, symptoms of accompanying diseases become more pronounced, such as:

• Follicular keratosis (“goose skin”);
• Vulgar ichthyosis (scaling of the skin, folding of the palms) – occurs in 1.6-6% of cases. People with congenital ichthyosis often develop subcapsular cataracts.

With irrational treatment and repeated exposure to irritating agents, paradoxical vegetative skin reactions occur in addition to fresh eruptions:

• Increased sweating on dry and apparently healthy skin areas (occurs as exacerbation subsides);
• In response to mechanical irritation, the skin becomes sharply white.

Furthermore, symptoms such as:

• Periorbital changes (folds under the lower eyelids, shadows);
• Polyadenitis (inflammation of multiple lymph nodes) – occurs with severe disease progression.

Classification and stages of development of atopic dermatitis

The classification of atopic dermatitis is based on the assessment of the extent of the process, the nature of the lesions, and the severity of itching. Therefore, two variants of the disease are distinguished:

1. Mild: Characterized by individuals with high levels of IgE antibodies to food and dust mites. This course is marked by eruptions resembling eczema and areas of lichenification located on the skin of the neck, face, and folds of large joints. In response to irritants, the skin may become pale or acquire a mixed hue. Exacerbations mainly occur in spring and autumn, up to 4 times a year. It responds to treatment with topical corticosteroids and calcineurin inhibitors. Sanatorium-resort treatment is conducted to prevent recurrence.
2. Severe: Typical for patients with concomitant diseases and a tendency to contact sensitivity to metals with a normal level of IgE antibodies. The course is characterized by lichenoid and eczematous eruptions affecting all limbs, torso, face, and neck. Axillary and inguinal lymph nodes enlarge to the size of a walnut and become dense and slightly painful. Eyebrow hairs break off. Examination reveals contact sensitivity to nickel and chromium. Women are more often affected. Regression occurs only under the influence of systemic therapy with immunosuppressants, corticosteroids, and selective UV-A. Patients with this course are hospitalized more than 4 times a year.

Depending on the degree of involvement of the skin, three forms of the disease are distinguished:

• Limited;
• Disseminated;
• Universal (erythroderma).

In the limited form, eruptions appear on the skin of the neck, elbow and popliteal folds, palms and soles, in the area of the radiocarpal and tibiotalar joints. The skin beyond these lesions appears healthy. Itching is paroxysmal.

In the disseminated form, the rash appears on the skin of the forearms, shoulders, shins, thighs, and torso. Extensive areas of lichenoid papules with excoriations and crusts develop on a reddish-edematous background. The borders of the lesions are indistinct. The skin is dry with flaky desquamation. Itching leads to insomnia.

In the universal form, the rash covers more than 50% of the body surface except for the palms and nasolabial triangle. The skin is bright red, tense, hardened, covered with numerous cracks, especially in the folds. Patients are bothered by unbearable itching, leading to scratching that deeply injures the skin. Eyebrow hairs are broken in the brow and mustache area. Fever up to 38.2 °C and chills occur.

Based on the predominant eruptions, three types of atopic dermatitis are distinguished:

• Erythematous-squamous with lichenification (more common in childhood);
• Exudative;
• Lichenoid (more common in adults).

Complications of atopic dermatitis

During the course of the disease, various infectious complications associated with exacerbation stages often occur. During stabilization, impetigo may appear in the affected areas.

Complications of the infantile phase:

• Candidiasis: begins with the appearance of a whitish strip of softened horny layer in the depths of the folds. Then, small blisters and extensive erosions develop, with flaps of epidermis at the edges.
• Herpetiform eczema Kapoši: blisters and pustules appear on the skin with a navel-like depression in the center and the size of a pinhead or pea. The serous content of the blisters quickly becomes hemorrhagic (fills with blood). The rash often appears on the skin of the face, neck, and hairy part of the head, less commonly in places of scratching on the trunk and limbs.

Complications of the childhood phase:

• Staphylococcal impetigo: manifests as a rash of sluggish blisters the size of a pea or a walnut. If opened, the skin remains damaged, surrounded by scraps of epidermis.
• Contagious molluscum: semi-spherical body-colored or pink papules the size of a pinhead or larger with a navel-like indentation in the center. The elements can be single or multiple. When pressed with forceps, a whitish granular mass – “mollusc bodies” – is released.

Complications of the adult phase:

• Dermatophytoses: fungal lesions appear on any parts of the body. They often affect the inguinal folds, buttocks, thighs, and shins. The foci of the fungus are pale in color, covered with flaky scales. Their borders are pink-red and clearly delineate the lesion from healthy epidermis. Around them, there is a convex discontinuous roller, consisting of papules, small blisters, and crusts.
• Keratomycoses: a scaly lichen that appears as light brown eruptions, irregularly shaped spots with uneven “openwork” edges. In people with dark skin, these spots are dark brown, covered with barely noticeable scaly scales, which become well visible when scratched. As the disease progresses, the spots remain depigmented and do not tan.
• Chronic Papillomavirus Infection: Flat nodules appear on the back of the hands and face. They typically measure 3-5 mm in diameter, are slightly raised above the skin surface, and may have a round or polygonal shape. They can appear yellow or blend in with the surrounding healthy skin.

Complications of the adult phase:

• Dermatophytosis: Fungal infections appear on any part of the body, most commonly affecting the groin, buttocks, thighs, and shins. The affected areas exhibit pale-colored patches covered with flaky scales. The borders of the affected areas are pink to red in color, sharply delineating the lesion from the healthy skin. A raised, discontinuous ridge composed of papules, small blisters, and crusts is present along the edges.
• Keratomycosis: This presents as eruptions of light brown patches with irregular borders and “lace-like” edges. In individuals with dark skin, these patches appear dark brown and are covered with barely noticeable flaky scales that become more prominent upon scraping. Once the condition resolves, the patches remain depigmented and do not tan.

Atopic dermatitis is often mistaken for other conditions. To avoid misdiagnosis, a differential diagnosis is conducted with conditions such as simple and allergic contact dermatitis, nummular eczema, simple ringworm (tinea corporis), psoriasis, scabies, seborrheic dermatitis, mycosis of smooth skin, AIDS, enteropathic dermatitis, and histiocytosis.

Laboratory investigations may include:

• Platelet pathology assessment to exclude Wiskott-Aldrich syndrome.
• Immune status evaluation to exclude Job syndrome.
• Microscopic examination of scales in cases of suspected dermatomycosis.

Sometimes, simply observing the localization of the rash can help distinguish the disease from other conditions. For example, vulgar psoriasis affects extensor surfaces, while atopic dermatitis affects flexural surfaces.

Treatment of atopic dermatitis depends on the severity and duration of the disease:

• Mild Cases: Outpatient treatment is possible for mild cases without sensitivity to allergens or complications.
• Severe Cases: Hospitalization is required for severe cases and when the body reacts to allergens.

Basic therapy involves the use of anti-inflammatory, antipruritic, and antihistaminic drugs to suppress the allergic reaction. It’s essential to alleviate itching, often associated with inflammation, using antihistamines, sedatives, topical corticosteroids, or calcineurin inhibitors (Tacrolimus and Pimecrolimus).

For moderate to severe forms of the disease where topical treatments are ineffective, Dupilumab may be administered (contraindicated for patients under 18 years old).

The second goal of treatment is to correct skin dryness (xerosis), vascular, and metabolic disorders. This involves eliminating triggering factors, avoiding constipation and diarrhea, taking antihistamines, sedatives, and immunomodulatory agents. Reflexotherapy, UV skin irradiation, selective phototherapy, and photochemotherapy are also recommended. Antiseptic moist-drying dressings, hot packs, and paraffin applications are applied to the skin, along with corticosteroid creams.

Diet therapy consists of three stages:

• Diagnostic diet: Excludes suspected allergenic foods from the diet. Improvement during this diet confirms the allergy to the food.
• Therapeutic diet: Excludes not only all food allergens but also triggering factors.
• Expansion of the diet during remission.

In cases of infantile onset, particular attention should be paid to complementary feeding, which should be hypoallergenic. This involves excluding allergenic products and substances such as milk, gluten, sugar, salt, broth, preservatives, artificial colors, and flavors. If the child has gastrointestinal disorders, the first complementary foods should be industrially produced milk-free cereals without sugar and gluten (e.g., buckwheat, rice, and corn). In cases of constipation or excessive body weight in infants, complementary feeding begins with purees made from zucchini, squash, cabbage, and other vegetables. The protein component of the diet includes purees made from rabbit meat, turkey, horse meat, and lamb. Fruit puree consists of green and white apples. Juices are only recommended towards the end of the first year of life.

For general treatment, Desloratadine is recommended, available in syrup form for children over one year old and in tablet form for those aged 12-13 years and older. A short course of glucocorticoids in tablet form is indicated only in cases of severe exacerbation. Corticosteroid creams, gels, and ointments are also recommended for exacerbations and severe forms of the disease. These include hydrocortisone, fluticasone, and others. Zinc pyrithione activated in the form of a 0.2% aerosol, cream, and 1% shampoo is used, taking into account its ability to provoke exacerbations of viral diseases and enhance the effects of the sun.

During hospitalization, infusion therapy is carried out, with intravenous administration of Cyclosporine at an initial dose of 2.5 mg/kg per day. In severe cases, the dose may be increased to 5 mg/kg per day. Once a positive result is achieved, the dosage is gradually reduced until complete cessation. It is recommended to use moisturizing and softening creams such as Locobase Ripa, Liquoid Lipocream, Lipikar, and Dardia lotion.

Living in a warm climate territory (Mediterranean region, desert climate, highlands) for 2-3 years promotes stable remission.

Sources:

1. “Atopic Dermatitis: Treatment and Management” – American Academy of Dermatology Association. Available at: https://www.aad//org/public/diseases/eczema/atopic-dermatitis#treatment
2. “Atopic Dermatitis (Eczema) – Treatment” – Mayo Clinic. Available at: https://www.mayoclinic/org/diseases-conditions/atopic-dermatitis-eczema/diagnosis-treatment/drc-20353279
3. “Treatment of Atopic Dermatitis (Eczema)” – National Eczema Association. Available at: https://nationaleczema//org/eczema/treatment/