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Atopic Dermatitis : Diagnosis & Pathogenesis

Posted Dec 27 2011 10:10pm
Cases in Atopic DermatitisMedscape Pediatrics CME Lawrence F. Eichenfield, MDProfessor of Clinical Pediatrics and Medicine (Dermatology), University of California Pathogenesis and Diagnosis of Atopic DermatitisAtopic dermatitis (AD) is a common inflammatory skin disorder affecting 10%-20% of children during their first decade of life. It is characterized by a pruritic, scaling rash that follows a fluctuating course. In approximately 60% of patients, AD starts in the first year of life. Newborns and infants usually have involvement on the cheeks, chin, and extremities. As the child ages, the rash typically transitions to classic involvement of the flexural antecubital and popliteal fossae. Fortunately, AD frequently resolves when the patient grows older.The pathogenesis of AD is complex and multifactorial. Acute AD is characterized by strong type 2 T-helper (TH2) cell responses with production of interleukin (IL)-4, IL-5, and IgE antibodies, whereas chronic AD has immunologic features more consistent with TH1-mediated responses. Recent evidence also suggests a possible role for TH17 cells.There is a significant barrier defect in people with AD. Many have mutations in the epidermal proteins that result in epidermal barrier dysfunction. The epidermis of skin affected with AD often has decreased levels of filaggrin, a protein responsible for aggregation and adhesion of the cornified envelope; ceramides, the predominant lipids of the cornified envelope; and antimicrobial peptides, such as beta-defensins and cathelicidins, proteins of the innate immune system that resist cutaneous colonization and infection. Further exacerbating the epidermal barrier of people with AD is increased transepidermal water loss. As a result of these barrier defects, allergen absorption and bacterial colonization and infection are enhanced, which further potentiates the immunologic dysfunction present in skin affected by AD.The diagnosis of AD is usually not challenging. However, other diagnoses should be considered if the presentation is atypical. Differential diagnoses include scabies, psoriasis, allergic contact dermatitis, immunodeficiency diseases, metabolic conditions, nutritional disorders, Langerhans cell histiocytosis, and various other disorders as suggested by the patient's presentation.Because AD is part of an atopic triad that includes asthma and allergic rhinitis, it is important to ask patients and parents whether there is a history of any of these in the patient or family. If there is such a history, AD is more likely. A child has a 20% risk for AD if one parent is affected and a 50% risk if both parents are affected. Furthermore, the concordance rate between monozygotic twins is 80%, and the concordance rate between dizygotic twins is 20%.Findings on physical examination that support a diagnosis of AD include typical pruritic eczematous dermatitis, hyperlinear palmar dermatoglyphics (increased fine skin lines), Dennie-Morgan fold (infraorbital line caused by edema), allergic shiners (dark periorbital skin due to sinus congestion and venous congestion), allergic salute (horizontal crease on the dorsal nose secondary to chronic allergies and rubbing), keratosis pilaris (spiny papules on the anterolateral upper arms), and ichthyosis vulgaris (fish-like scales on the skin). The diaper area of infants and toddlers with AD is characteristically spared, partially due to the occlusive hydration effect of diapers. The presence of significant rash in this area should prompt the consideration of other etiologies.There are many proposed diagnostic criteria for AD. Perhaps the most practical, sensitive, and validated for use in epidemiologic studies are the UK Working Party's Diagnostic Criteria for Atopic Dermatitis (Table 1). To meet these criteria, the patient must have pruritus and 3 or more minor criteria.Table 1. UK Working Party's Diagnostic Criteria for Atopic DermatitisA. Required Criterion1. PruritusB. Minor Criteria (≥ 3 of the following must be present)1. Onset < 2 years of age2. History of flexural involvement3. History of asthma or hay fever (or history of these conditions in parent or sibling if patient is < 4 years of age)4. History of general dry skin in the last year5. Visible flexural eczema (or eczema involving the cheeks/forehead and outer limbs in children < 4 years of age)Similarly, the American Academy of Dermatology Consensus Conference stated that AD is best thought of as a syndrome with features classified as "essential," "important," and "associated" (Table 2).Table 2. American Academy of Dermatology Consensus Conference Definition of Atopic DermatitisA. Essential Features (must be present)1. Pruritus2. Eczema (acute, subacute, chronic)a. Typical morphology and age-specific patterns*b. Chronic or relapsing historyB. Important Features (seen in most cases, adding support to the diagnosis)1. Early age at onset2. Atopya. Personal and/or family historyb. IgE reactivity3. XerosisC. Associated Features (helpful in suggesting the diagnosis but too nonspecific for defining or detecting AD for research or epidemiologic studies)1. Atypical vascular responses (eg, facial pallor, white dermographism, delayed blanch response)2. Keratosis pilaris/hyperlinear palms/ichthyosis3. Ocular/periorbital changes4. Other regional findings (eg, perioral changes/periauricular lesions)5. Perifollicular accentuation/lichenification/prurigo lesionsExclusionary ConditionsDiagnosis of AD depends on excluding such conditions as scabies, seborrheic dermatitis, allergic contact dermatitis, ichthyosis, cutaneous lymphoma, psoriasis, and immune deficiency diseases* Patterns include (1) facial, neck, and extensor involvement in infants and children; (2) current or prior flexural lesions in any age group; and (3) sparing of groin and axillary regions.
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