Introduction
Clinical features and differential diagnosis of AD
AD | Infant | Childhood | Adolescent or Adult |
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Lesions | Exudative erythematous weepy papules and plaques | Weepy erythematous papules and plaques intermixed with lichenified plaques, particularly in flexural areas | Erythematous papules and plaques with xerotic scale and crust Lichenified plaques in flexural areas |
Distribution | Scalp, face (without perioral and periorbital involvement) trunk, extensor surfaces | Flexural surfaces, including antecubital and popliteal fossa, wrist, and neck | Hands, flexural surfaces, upper trunk |
Pityriasis alba: Hypopigmented patches on face, upper trunk, upper extremities | |
Keratosis pilaris: Follicular hyperkeratosis of outer arms, lateral cheeks, buttocks, thighs | |
Dennie-Morgan fold (atopic pleat): Extra line on lower eyelid | |
Allergic shiners: Violaceous to gray color of infraorbital area | |
Hyperlinear palms: Increased and exaggerated skin markings on palms | |
Ichthyosis vulgaris: Scaling of extensor extremities, fish-scale appearance of extensor leg | |
Hertoghe sign: Loss of lateral eyebrows | |
White dermatographism: Blanching of skin after stroking | |
Circumoral pallor: Pallor of perioral area | |
Nummular dermatitis: Sharply circumscribed thick coin-shaped scaly plaques |
Disease | Age | Morphology | Distribution | Symptoms |
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AD | Childhood | Erythematous eczematous weepy plaque with fine dry scale | Face, scalp, Extensor surfaces in infants, flexural surfaces in children, trunk, nails | Severe pruritus |
Seborrheic dermatitis | Any age | Salmon-pink fine papules coalescing into poorly defined plaques with variable greasy scaling. | Face, scalp, Retroauricular folds, neck, axillae, inguinal folds | Absent to mild-moderate pruritus |
Psoriasis | Any age | Well-demarcated, pink plaques with adherent silvery scale, confluent bright red plaque with sharply defined borders and relative lack of scale. | Extensor surface of joints (elbows, knees) and extremities, Retroauricular folds, axillae, umbilicus, diaper area, inguinal folds, genitalia, gluteal cleft, nails | Mild-moderate pruritus |
Allergic contact dermatitis | Any age, incidence increases with age | Geometric erythematous eczematous weepy plaques | Based on exposure | Severe pruritus |
Scabies | Any age | Poorly defined erythematous papules, nodules, burrows, pustules, and vesicles | Wrists, interdigital spaces, axillae, umbilicus, nipples, diaper area, | Severe nocturnal pruritus |
Mycosis fungoides | Adulthood, Hypopigmented MF More common in children | erythematous patches, papules, or plaques with subtle scale; polycyclic or annular, hypopigmented patches, often with fine scaling | Buttock, lower trunk, thighs, breasts, and groin | Pruritus |
Dermatomyositis | Childhood and middle age | Violaceous scaly papules, Periorbital violaceous edema | Small joints of hands and elbows, face | Myositis |
Immunodeficiency and metabolic disorders | Infancy | Eczema or eczema-like eruption, erythroderma | Spread, resistant to treatment | Other cutaneous and extracutaenous manifestations Blood testing and genetic investigations upon diagnostic hypothesis |
The etiopathogenesis of itching in AD
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Skin barrier disruption. AD is characterized by systematic epidermal barrier dysfunction; due to, at first, tight junction aberration with reduced expression of some claudins and zonulins. In addition, several mutations in the filaggrin gene have been identified. This filament is essential for controlling transepidermal water loss (TEWL) and maintaining stratum corneum organization and hydration [3‐5]. Itch intensity in AD is associated with increased TEWL. Filaggrin deficiency also leads to an increase in cutaneous pH, which enhances the function of kallikreins, or serine proteases known as pruritogens that are upregulated in AD [3, 6]. Moreover, epidermal barrier dysfunction allows for entry of irritants and pruritogens [6, 7].
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Immunological disorder. Skin barrier dysfunction and inflammation lead to an aberrant type 2 immune response, with increased IgE production, eosinophilia, mast cell activation, and overexpression of Th2 cytokines (IL-4, IL-5, IL-13). This cascade promotes production of epithelial-derived cytokines, namely, thymic stromal lymphopoietin (TSLP). TSLP influences innate lymphoid cells (ILCs) and increases the production of Th2 chemokines [4, 5, 8].
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Hyperinnervation of skin and central sensitization of itch. An increase in nerve fiber density in the epidermis reported in AD, which is partly explained by the increase in nerve growth factor observed in the plasma of AD patients. Moreover, some studies have implicated involvement of central nervous system structures and astrocytes in sensitization of itch. Other studies have revealed a central neural circuit that is critical for signal processing of itch [9, 10].
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Itch mediators/pruritogens. The sensation of itching is mediated by cytokines, neuropeptides, and endogenous secreted factors. These itch-inducing factors act on sensory neurons to drive itch sensation. Histamine is one of the earliest identified pruritogens; among four receptors, H1R and H4R are potential mediators of pruritus. Others endogenous and exogenous factors produced from inflammation and xerosis result in the induction of non-histaminergic itch (i.e. protease astryptase, dust mites, Staphylococcus aureus, or substance P, TSLP, Notch proteins) [5‐7, 11]. Recently, a role of IL-31 produced by Th2 cells has been recognized in inducing itch [12, 13].
Symptoms and complications
Symptoms
Complications
Therapeutic patient education
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AD is a multidisciplinary disease with discordant opinions between specialists
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clinical features are polymorphic in the same day in the same patient
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early age of disease onset
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lack of specific treatment against pruritus
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sleep disturbance involving the family
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scarce compliance due to chronicity, time and costs for dressing
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esthetic damage
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psychosocial impact
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a theoretical aspect explaining the disease, its evolution and stressing its benign prognosis
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providing specific educational leaflets to the parents and children with adequate language
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a practical demonstration of dressing, patient massage, bandaging etc.
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strategies and tools for coping with itching and sleep disturbance (such as distraction techniques and their illustration)
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continuous evaluation of the patient and family perception
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psycho-diagnostic testing and psychotherapeutic intervention, when required.
Medical treatment
Topical therapy
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Hydration. Emollients and moisturizers are a mainstay of pruritus management. As undressing could deteriorate itching, emollients should be applied on xerotic/lichenified skin not covered by clothes twice daily, and at least once daily to the entire surface of the skin, and more when undressing children for other reasons. They should be regularly applied, even during remission to prevent itching, flares, and complications [22, 23, 26, 27]. Emollients “plus” are non-medicated products containing active ingredients [28, 29].
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Calcineurin inhibitors: tacrolimus ointment (0.03 and 0.1%) and pimecrolimus cream (1%) are immunomodulators used for moderate/severe and mild forms, respectively. It is important to take into account the age limit and possible contraindications (immunosuppression, exudative and infected lesions) [18‐20, 32, 33].
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The application of a topical medication followed by bandaging or wet dressing (a double layer of gauze or tubular dressings, the first layer moistened and the second layer dry) is indicated in exudative, infected or lichenified lesions, and protects against scratching and environmental irritants. It is also useful to promote absorption of topical products. Thus, it is important to take into account possible side effects, especially with concomitant corticosteroids [38, 39].
Phototherapy
Systemic therapy
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Target therapy. Biologic agents against pathogenic cytokines and their receptors are a relatively new group of therapeutics [45]. Dupilumab (anti IL-4 and 13) is recommended as a disease-modifying drug for moderate-to-severe AD in Europe [52]. Treatments with ustekinumab (anti IL-12 and IL-23), tralokinumab (anti IL-13), or nemolizumab (anti-IL-31) are still experimental [53‐56]. Oral drugs such as TSLP antagonists and JAK inhibitors are under development [57, 58]. Their use should be restricted to very selected cases and used in specialized centers.