22 - ATOPIC DERMATITIS Flashcards
AD is a chronic or chronically relapsing disorder with major features of:
- Pruritus
- Eczematous dermatitis (acute, subacute, or chronic) with typical morphology and agespecific patterns
- Facial and extensor involvement in infancy
- Flexural eczema or lichenification in children and adults
- Commonly associated with the following:
- Personal or family history of atopy (allergic rhinitis, asthma, atopic dermatitis)
- Xerosis or skin barrier dysfunction
- Immunoglobulin E reactivity
chronic inflammatory skin disease primarily beginning in childhood with a variable natural course
Atopic dermatitis (atopic eczema, AD)
Itch is the hallmark symptom of the disease, often unrelenting in severe cases, and leads to sleep disturbance and excoriated, infection-prone skin. Patients with AD often additionally have atopic comorbidities such as allergic asthma and allergic rhinitis and experience a significantly impaired quality of life.
DIAGNOSTIC CRITERIA
Hanifin Rajka criteria
CUTANEOUS FINDINGS
Acute eczematous lesions are characterized by erythematous papulovesicles, often with pinpoint crusting or frank weeping.
More subacute to chronic lesions often display scale, excoriation, and lichenification.
The distribution of eczematous lesions vary according to the patient’s age (Fig. 22-1) and disease activity. During infancy, the AD is generally more acute and primarily involves the face (Fig. 22-2), the scalp, and the extensor surfaces of the extremities (Fig. 22-3). 20 The diaper area is usually spared. In older children and in those who have long-standing skin disease, the patient develops the chronic form of AD with lichenification and localization of the rash to the flexural folds of the extremities (Fig. 22-4).
Features of Atopic Dermatitis
DIFFERENTIAL DIAGNOSIS
Because AD is currently not defined by a unique diagnostic biomarker, a number of inflammatory skin diseases, immunodeficiencies, skin malignancies, genetic disorders, infectious diseases, and infestations may share symptoms and signs with AD (Table 22-3). These should be considered in the initial evaluation of a patient presenting with an eczematous rash but also if a patient with a diagnosis of AD is not responding to appropriate therapy. Infants presenting in the first year of life with failure to thrive, diarrhea, a generalized scaling erythematous rash, and recurrent cutaneous or systemic infections should be evaluated for severe combined immunodeficiency syndrome. Omenn syndrome, caused by mutations in RAG1 and RAG2 as well as several other genes, is an autosomal recessive severe combined immunodeficiency that can present with an erythrodermic rash, as well as elevated IgE, eosinophilia, diarrhea, lymphadenopathy, hepatosplenomegaly, and susceptibility to infections. 65 The dermatitis can be eczematous though with pachydermia. Other immunodeficiency with eczematous rash includes immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome. 66 IPEX results from mutations of Foxp3, a gene located on the X chromosome that encodes a DNA-binding protein required for development of regulatory T cells. Besides dermatitis, patients typically present with a recalcitrant enteropathy, as well as autoimmune features such as type 1 diabetes, thyroiditis, hemolytic anemia, or thrombocytopenia. Wiskott-Aldrich syndrome is an X-linked recessive disorder characterized by an eczematous rash associated with thrombocytopenia along with
variable abnormalities in humoral and cellular immunity and severe bacterial infections.
372
Hyper-IgE syndrome caused by STAT3 mutations is an autosomal dominant multisystem disorder characterized by recurrent deep-seated bacterial infections, including cutaneous cold abscesses and pneumonias with pneumatocele formation due to S. aureus.67 Although S. aureus is an important pathogen in this disorder, infection with other bacteria, including gram-negative species (eg, Pseudomonas aeruginosa) and nontuberculous mycobacteria and fungi (eg, Aspergillus) may occur, including invasive disease. STAT3 is an essential transcription factor for Th17 T-cell development, and because Th17 T cells play an essential role in protecting against Candida spp., patients with mutations in STAT3 are susceptible to chronic mucocutaneus candidiasis. In infancy, patients may present with a papulopustular eruption of the face and scalp. Other features of HIE syndrome include skeletal abnormalities with coarse facial features and prominent frontal bossing, dental anomalies with retained primary teeth, bone fractures, and osteoporosis. Despite elevated serum IgE levels, patients usually are not atopic. Patients with mutations in the gene encoding dedicator of cytokinesis 8 protein (DOCK8) have an immunodeficiency that accounts for most cases of autosomal recessive HIE.68 These patients have an eczematous dermatitis with recurrent viral infections, including some with central nevous system involvement. Patients may present with recalcitrant warts secondary to human papilloma virus, disseminated molluscum or recurrent herpes simplex infections. Malignancies, including squamous cell carcinomas and lymphomas, are an important cause of death in patients starting in the second decade of life. Another unique feature in patients with DOCK8 is that many have associated food allergies. Patients with tyrosine kinase 2 deficiency can also present with an eczematous rash with high serum IgE and recurrent cutaneous staphylococcal infections.
Other diseases to consider in the differential diagnosis of AD include cutaneous T-cell lymphoma, especially in adults without a history of childhood eczema and without other atopic features. 70 Mycosis fungoides (discussed in Chap. 119) is the most common form of CTCL, Sézary syndrome is characterized by generalized erythroderma with lymphadenopathy and circulating malignant T cells (Sézary cells). Although contact dermatitis should be considered in the differential diagnosis of AD (see Chap. 24), contact allergy can also complicate AD, especially in patients whose AD appears to worsen with therapy, typically with TCs. 71 Allergic contact dermatitis complicating AD may appear as an acute flare of the underlying disease. Eczematous dermatitis has been also reported with human immunodeficiency virus infection as well as with a variety of infestations such as scabies. Other diseases that can be confused with AD include psoriasis, ichthyoses, and seborrheic dermatitis. Although psoriasis can typically be distinguished from AD based on characteristic clinical features (see Chap. 28), inverse (flexural) psoriasis or erythrodermic psoriasis may at times present more of a diagnostic challenge. Zinc deficiency can result from dietary deficiency; excessive losses with diarrhea; or chronic disease, including renal or hepatic as well as inadequate absorption associated with an inherited deficiency of the zinc carrier protein ZIP4 and can present with an eczematous rash with a perioral, acral, or perineal distribution.
CLINICAL COURSE AND PROGNOSIS
Most AD starting in childhood is mild in severity, and a review of birth cohort studies found that 80% of cases remitted, at least temporarily, by 10 years of age.73 Symptoms of AD, however, may persist or reemerge in adulthood. One primarily pediatric AD cohort found that more than 80% of patients prescribed calcineurin inhibitors reported persistent symptoms into adulthood. 74 Risk factors reported to be predictive of a persistent disease course include disease severity, later onset disease, genetic mutations in FLG or FLG-2 genes, and early allergic sensitization. 75,76 It is not known whether early or aggressive treatment of AD alters the natural course. For occupational counseling, adults whose childhood AD has been in remission for a number of years may present with hand dermatitis, especially if daily activities require repeated hand wetting.
MANAGEMENT
Successful treatment of AD requires a systematic, multipronged approach that incorporates education about the disease state, skin hydration, pharmacologic therapy, and the identification and elimination of flare factors such as irritants, allergens, infectious agents, and emotional stressors (Fig. 22-7). Many factors lead to the symptom complex characterizing AD. Thus, treatment plans should be individualized to address each patient’s skin disease reaction pattern, including the acuity of the rash, and the trigger factors that are unique to the particular patient. In patients refractory to conventional forms of therapy, alternative antiinflammatory and immunomodulatory agents may be necessary.
IDENTIFICATION AND ELIMINATION OF TRIGGERS
Patients with AD are more susceptible to irritants than are unaffected individuals. Thus, it is important to identify and eliminate aggravating factors that trigger the itch–scratch cycle. These include soaps or detergents, contact with chemicals, smoke, abrasive clothing, and exposure to extremes of temperature and humidity. Alcohol and astringents found in toiletries are drying. When soaps are used, they should have minimal defatting activity and a neutral pH or slightly acidic pH. New clothing may be laundered before wearing to decrease levels of formaldehyde and other added chemicals. Residual laundry detergent in clothing may be irritating. Using a liquid rather than powder detergent and adding a second rinse cycle facilitate removal of the detergent.
Recommendations regarding environmental living conditions should include temperature and humidity control to avoid problems related to heat, humidity, and perspiration. Every attempt should be made to allow children to be as normally active as possible. Certain sports, such as swimming, may be better tolerated than other sports involving intense perspiration, physical contact, or heavy clothing and equipment. Although UV light may be beneficial to some patients with AD, sunscreens should be used to avoid sunburn. However, because sunscreens can be irritants or allergens, care should be used to identify a nonirritating product.
represent the cornerstone of treatment for mild AD and serve as an important flare preventive therapy for all levels of disease severity
EMOLLIENTS
Patients with AD have abnormal skin barrier function with increased transepidermal water loss and decreased water content and dry skin (xerosis) contributing to disease morbidity by the development of microfissures and cracks in the skin. These microfissures may serve as portals of entry for skin pathogens, irritants, and allergens. FLG gene mutations or acquired filaggrin protein deficiencies caused by inflammation have also been shown to result in decreased epidermal levels of natural moisturizing factor. 83 AD xerosis can become aggravated during the dry winter months and in certain work environments.
The daily use of an effective emollient helps to restore and preserve the stratum corneum barrier, decreases the need for topical glucocorticoids and NSAIDs and improves outcomes. Moisturizers are available in the form of lotions, creams, or ointments. Some lotions and creams may be irritating because of added preservatives, solubilizers, and fragrances. Lotions with high water content may be drying because of an evaporative effect and provide few lipids to the skin. Thicker, bland emollients with high lipid content are preferred but are
sometimes not well tolerated because of interference with the function of the eccrine sweat ducts and the induction of folliculitis or itching. In these patients, less occlusive agents should be used. Plain petrolatum is a common lipid base for effective emollients. Petrolatum intercalates into the stratum corneum and appears to upregulate skin barrier and antimicrobial peptide gene expression thought to be beneficial in AD. 84 The benefit of emollients with special additives, such as ceramides, is not clear, although one study found the use of a urea-containing moisturizer provided better clinical results than a standard emollient.85
Hydration, by baths or wet dressings, promotes transepidermal penetration of topical glucocorticoids. The optimal bathing regimen for patients with AD is not known, however, and recommendations vary by specialty. Kohn and colleagues found no differences in outcomes in patients applying TCs to wet skin compared with dry skin, 86 but the “soak and smear” method is often used in recalcitrant disease. 87 Wet dressings or “wet wraps” are recommended for use on severely affected or chronically involved areas of dermatitis refractory to therapy. However, overuse of wet dressings may result in maceration of the skin complicated by secondary infection. Wet dressings or baths also have the potential to promote drying and fissuring of the skin if not followed by topical emollient use. Thus, wet dressing therapy is reserved for poorly controlled AD and should be closely monitored by a physician.
presentation of AD in infancy
Generally more acute and primarily involves the face (Fig. 22-2), the scalp, and the extensor surfaces of the extremities.
The diaper area is usually SPARED.
Presentation of AD in older children and in those who have long-standing skin disease.
Patient develops the chronic form of AD with lichenification and localization of the rash to the flexural folds of the extremities
may be the primary manifestation of AD in many adults
Chronic hand eczema
At least one third of patients will have clinical features of filaggrin deficiency such as ______
ichthyosis vulgaris, keratosis pilaris, and hyperlinear palms
Other specific skin conditions associated with AD
Vitiligo and Alopecia Areata
In atopic march, what disease is often the first atopic disease to develop?
AD
by far the most common infection found in AD
Superficial Staphylococcus aureus infections
indicators of clinically relevant secondary bacterial skin infection in which antibiotic use would be indicated
Erosive plaques, honey-colored crusting, folliculitis, and persistent or multiple tender pustules
most serious virally mediated complication of AD
eczema herpeticum (EH)
incubation period of eczema herpeticum
5 to 12 days
Clinical presentation of eczema herpeticum
Multiple itchy, vesiculopustular lesions erupt in a disseminated pattern; vesicular lesions are umbilicated, tend to cluster, and often become hemorrhagic and crusted (Fig. 22-6).
Punched-out and extremely painful erosions result. These lesions may coalesce to large, denuded, and bleeding areas that can extend over the entire body and be fatal in some cases.
In AD patients, smallpox vaccination (or even exposure to vaccinated individuals) (see Chap. 166) may cause a severe widespread eruption called _____
Eczema Vaccinatum
Exaggerated responses to coxsackie virus have also been reported in patients with AD that may resemble EH and has been termed ________
eczema coxsackium
Children present with hand and foot vesicles or papules that resemble typical hand, foot, and mouth disease, but lesions tend to be more severe and hemorrhagic and involve additional areas involved with eczema. Despite the sometimes dramatic presentation, the skin rash resolves with no negative sequelae.
Malassezia species associated with AD
Malassezia sympodialis (Pityrosporum ovale or Pityrosporum orbiculare)
M. sympodialis is a lipophilic yeast commonly present in the seborrheic areas of the skin.
Histopathology Comparison for Nonlesional Atopic Dermatitis, Acute Atopic Dermatitis, and Chronic Atopic Dermatitis
Histopath finding in NONLESIONAL ATOPIC DERMATITIS
Histopath findings in ACUTE ATOPIC DERMATITIS (<3 DAYS)
Histopath findings in CHRONIC SKIN LESIONS (>3 DAYS)
