OVERVIEW: What every practitioner needs to know
Are you sure your patient has severe eczema? What are the typical findings for this disease?
The hallmark of atopic dermatitis, in any age group, is pruritus. Many pediatricians and dermatologists know atopic dermatitis as “the itch that rashes,” highlighting the persistent and significant pruritus that affects most patients.
Patients also demonstrate marked xerosis – or dryness – of the skin.
The cutaneous lesions are characterized by erythematous, ill-defined dry papules and plaques with associated crusting and excoriation. The common term “eczema” means “to boil over,” describing the classic infantile plaques and crust. Long-standing, chronically rubbed lesions demonstrate lichenification, characterized by skin thickening and accentuation of skin markings.
There is a characteristic distribution of the cutaneous eruption by age (face, trunk and extensors in infants; flexural areas in childhood; face, neck and body in adolescence).
Clinical findings by age
The presentation and anatomic distribution of atopic dermatitis vary by age group.
In infants, the eruption favors the face and scalp, lateral extensor extremities, and trunk. The diaper area is usually spared, reflecting the fact that this area is persistently moist. Skin lesions are red, scaly, ill-defined dry papules and plaques, often with crust and excoriation, in a background of diffuse xerosis and dermatographism (Figure 1, Figure 2, Figure 3).
In childhood, skin lesions favor the flexural surfaces, including the antecubital fossae, popliteal fossae, wrists, ankles, and neck. Patients often have secondary lichenification, characterized by thickening and accentuation of skin markings in an area of skin which has been persistently rubbed (Figure 4, Figure 5).
In adolescents, the face and body often become more diffusely involved as in the infantile pattern, with characteristic central facial pallor. Post-inflammatory hyper- or hypopigmentation is common. Patients frequently exhibit signs commonly associated with atopic dermatitis, including keratosis pilaris, Dennie-Morgan folds (creases under the lower eyelids), hyperlinear palms, “dirty neck” appearance, and keratoconjunctivitis (Figure 6).
What other disease/condition shares some of these symptoms?
The clinical differential diagnosis includes:
Allergic or irritant contact dermatitis
Langerhans cell histiocytosis
What caused this disease to develop at this time?
For reasons not completely elucidated, the skin of patients with atopic dermatitis is dry, inflamed, and prone to irritation and infection, at both a macro- and microscopic level.
Intercellular edema (spongiosis) is present within the epidermis.
Cutaneous inflammation with lymphocytes is prominent. Lesional skin demonstrates T-cell infiltration with a markedly increased CD4:CD8 ratio. There are also increased numbers of Langerhans cells in the skin, and increased levels of IgE and Th2-producing cytokines in the serum of affected patients.
There are numerous hypotheses about how this xerosis and inflammation begin. The cAMP hypothesis postulates that a defect in phosphodiesterase isoforms leads to low cellular cAMP levels and subsequent abnormal modulation of inflammation in the skin and hyperreactivity to infection and irritants. The allergy hypothesis suggests that genetically susceptible individuals develop disease after exposure to antigens, with subsequent proliferation of Th2 lymphocytes and stimulated interleukins.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Laboratory studies are not indicated.
Serum IgE is elevated in 43%-82% of patients, but is not routinely obtained or important for management.
Skin biopsy is not specific, and shows epidermal spongiosis, lymphocytic inflammation and edema within the papillary dermis, with overlying parakeratosis and crust. Skin biopsy is generally not necessary, except to exclude other dermatoses.
Would imaging studies be helpful? If so, which ones?
Imaging studies are not indicated.
Confirming the diagnosis
In 1980, Hanifin and Rajka established standardized criteria for the diagnosis of atopic dermatitis (AD). Patients with AD must have three or more of the following: pruritus, typical morphology and distribution of lesions, chronic or chronically relapsing dermatitis, and/or personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis). They must also have three or more of multiple minor criteria, including xerosis, ichthyosis/keratosis pilaris, elevated serum IgE, nipple eczema, cheilitis, Dennie-Morgan infraorbital folds, pityriasis alba, itch with sweating, and dermatographism, among others.
These diagnostic criteria have been criticized because they do not occur in all children, may occur in normal children, vary by ethnicity, or may be very rare. However, these criteria have been useful in epidemiologic studies, and have been modified by numerous different groups for use in epidemiologic and pharmaceutical studies.
If you are able to confirm that the patient has severe eczema, what treatment should be initiated?
– Skin hydration: The cornerstone of atopic dermatitis treatment and maintenance is skin hydration, and all patients should be treated with twice daily with a thick emollient. Ointments or creams are preferred, as they are thicker, penetrate better, and are better tolerated on skin sensitive to stinging or burning. Parents should be advised to use products with minimal ingredients, no fragrance, and those that come from a “pot” or “jar” rather than a pump (i.e., thicker ointment or cream based products).
– Bathing: Frequency of bathing in atopic dermatitis treatment has long been controversial. Many authors recommend infrequent bathing, in an effort to minimize a constant “wet-dry cycle” that can ultimately dehydrate the skin. However, many patients with atopic dermatitis find bathing soothing, and bathing can soften the skin and aid in application of topical products. It is very important to educate parents about post-bath skin care. A thick emollient should be applied to the skin immediately after the skin is dry from the bath (within 5-10 minutes) to avoid water loss from the stratum corneum. This technique is termed “soak and smear” by many dermatologists.
– Wet dressings: Occlusive wet dressings at bedtime can soothe itchy skin, help topical ointments penetrate more efficiently, and control acute flares. Patients apply the prescribed topical steroid (or thick bland emollient such as petrolatum) to the affected skin, cover with a damp cotton dressing and a final layer of a dry cotton dressing. For hands and feet, white cotton “tube” socks work well. For younger children or more diffuse cutaneous involvement, cotton pajamas are preferred. The dressings can be left in place overnight, or can be used during the day for shorter treatments. Using wet dressing in 3-6 day treatment “bursts” can significantly improve acute flares of atopic dermatitis.
– Irritants: The impaired skin barrier makes patients with atopic dermatitis extremely prone to irritation from topical products, including soap, shampoo, topical medications, certain fabrics, and grass. These irritants should be avoided. Patients should be bathed in clear water, and should use a synthetic detergent or soap substitute only if necessary.
– Allergy: Food and environmental allergy may be a trigger for flares in some patients, but most authors do not believe that food allergy is “causative.” Food elimination diets are not recommended unless allergy testing indicates a specific allergen.
– Pruritus: Use of oral antihistamines is helpful in treating the pruritus associated with atopic dermatitis. However, most studies have shown no specific effect on the pruritus itself, but rather indicate that control of itch comes primarily from sedation. Many children with atopic dermatitis have abnormal sleep cycles because of intense pruritus. A sedating antihistamine at bedtime can be helpful for these patients. Hydroxyzine (1 mg/kg orally at bedtime) is preferred. A morning non-sedating antihistamine can also be helpful, particularly in patients who have other atopic symptoms (allergic rhinitis).
– Topical steroids: Medium-potency topical steroids should be used on areas of affected skin twice daily until the areas are clear. Once clear skin is achieved, the area should be treated with twice daily emollient as maintenance therapy. If and when the skin flares, the topical steroid should be re-instituted as needed. Parents should be reassured that topical steroids, when used in appropriate strength on areas of actively inflamed skin, have an excellent safety profile and very minimal risk of systemic side effects. Poor response to topical steroids almost always stems from inappropriate or under-use of the product. Parents often have anxiety about the safety of topical steroids, and will discontinue use before the skin is adequately treated. They should be reassured and encouraged to treat the skin until clearance or near-clearance of plaques is achieved.
– Systemic steroids: Systemic steroids should be avoided in patients with atopic dermatitis. While they can be helpful for acute flares, rebound flares are often severe once systemic steroids are discontinued. Long-term side effects of chronic systemic steroids make their use in atopic dermatitis inappropriate.
– Phototherapy: Patients with severe or diffuse disease, intense pruritus, or failure to respond to appropriate topical treatment may benefit from ultraviolet light therapy. The preferred treatment is narrow-band UVB (311 nm), which maximizes the therapeutic effects of ultraviolet radiation (reduction in pruritus and inflammation) while minimizing side effects of more broad-band light (photoaging and malignancy).
– Topical immunosuppressants: Tacrolimus and pimecrolimus are topical calcineurin inhibitors that can be a safe and effective alternative to topical steroids in patients with recalcitrant atopic dermatitis. They act by binding immunophilin, and the complex competitively inhibits calcineurin. Calcineurin activation of multiple interleukins, interferons, and mast cell mediators is thus inhibited, and the inflammatory cascade is blocked.
Tacrolimus ointment is available in 0.1% (FDA approved for patients over age 12) and 0.03% (approved for patients under age 12). Neither is approved for use under age 2. Pimecrolimus is available in a cream. Both appear to be well tolerated and approximately as efficacious as low to mid-potency topical steroids (although comparative studies are lacking). Most common reported side effects are local irritation or stinging. These products offer the benefit of no potential for steroid atrophy of the skin, but long-term safety and potential risk for cutaneous malignancy is not known.
– Systemic immunosuppressants: Cyclosporine, azathioprine, and mycophenolate mofetil have been used successfully in patients with severe disease or those recalcitrant to standard topical therapies. Because of the potential significant side effects associated with these therapies, and the need for monitoring of blood levels and laboratory values, these medications should be administered in consultation with a dermatologist.
– Education: Education of family members and other caregivers is absolutely critical in successful treatment of atopic dermatitis. Parents should be familiar with the chronic, relapsing and remitting course of the disease, the importance of consistent topical therapy and avoidance of triggers, and the crucial role skin care maintenance plays in reducing the number and severity of skin flares.
What are the adverse effects associated with each treatment option?
Side effects of topical emollients include skin irritation (particularly if fragranced or urea-containing products are used) or unacceptable cosmetic appearance (i.e., thick, white creams).
The most common side effect of oral antihistamines is sedation and, in some children, irritability, headaches, or dry mouth.
Topical glucocorticoids can cause skin atrophy and striae, particularly if superpotent or fluorinated steroids are used on areas of thin skin. Perioral dermatitis (“steroid rosacea”), telangiectasia, and folliculitis can also be induced. There is a risk of systemic absorption and subsequent hypothalamic-pituitary axis suppression if potent topical steroids are used on a large body surface area or under occlusion. This effect is transient and rare. Studies evaluating growth suppression in patients subjected to long-term topical glucocorticoids are inconclusive.
What are the possible outcomes of severe eczema?
It is difficult to predict long-term prognosis. Most patients with atopic dermatitis will improve as they become older. The severity and persistence of flares in early childhood can herald more persistent disease into adulthood. Those with other signs of atopy (asthma, allergic rhinitis) may also have more persistent disease.
What causes this disease and how frequent is it?
Atopy (the tendency toward atopic dermatitis, asthma, and allergic rhinitis) is common, with an estimated prevalence of approximately 20%.
There is a slight female predominance, and it is more common in more industrialized countries, higher socioeconomic populations, and smaller family sizes. These findings suggest that decreased exposure to infectious and environmental antigens predisposes to the development of atopic symptoms.
Atopy appears to be, at least in part, inherited in a polygenic fashion. Monozygotic twin concordance has been estimated at 75% (dizygotic 15%).
Multiple studies implicate filaggrin gene defects in the development of atopic dermatitis, and several specific gene loci are being investigated.
How do these pathogens/genes/exposures cause the disease?
Defects in skin barrier function and lymphocytic inflammation of the skin lead to the characteristic cutaneous findings.
Other clinical manifestations that might help with diagnosis and management
What complications might you expect from the disease or treatment of the disease?
While atopic dermatitis plaques do not heal with scarring, patients who scratch frequently and excoriate the skin may induce scars. Patients with significant pruritus also suffer from disrupted sleep cycles, poor concentration, and abnormal sensory integration.
Topical steroids carry low risks of skin atrophy, systemic absorption, and suppression of the HPA axis. These side effects are very rare in patients who are treated appropriately. Super high potency steroids should be avoided on the face and genitals, as risk of atrophy and striae are increased in these anatomic areas.
Eczematous skin is at increased risk of superinfection with both bacteria and viruses. Lesional skin of many patients with atopic dermatitis shows a decreased ability to induce human beta-defensins and cathelicidin, products important for natural cellular immunity and bacterial resistance. This translates into increased risk of bacterial infection in some patients with eczema. Yellow crusted, tender, or slow-healing plaques should raise suspicion for secondary bacterial infection. The most common offending pathogens are Streptococcus and Staphylococcus species, which can generally be treated with penicillin- or cephalosporin- antibiotics. Patients with chronic infection should be screened for methicillin-resistant Staphylococcus aureus (MRSA). It should be noted that many eczematous plaques can be quite inflammatory, with oozing of serous fluid that does not indicate infection.
The disrupted skin barrier in patients with atopic dermatitis also predisposes to the development of eczema herpeticum, or infection of lesional skin with herpes simplex virus (HSV) (also called “Kaposi’s varicelliform eruption”). Patients may or may not have a known personal history of HSV infection. The patients present with characteristic red, “punched-out,” well-demarcated ulcers and erosions in eczematous skin. Intact blisters are rare. These patients respond to systemic acyclovir or other antiviral medications. Oral therapy is appropriate for localized infection, but intravenous antivirals may be required for young patients, those with very diffuse cutaneous involvement, or associated systemic illness.
Are additional laboratory studies available; even some that are not widely available?
How can severe eczema be prevented?
There is no vaccine or currently available genetic counseling for prevention of atopic dermatitis.
Good skin care and hydration can minimize frequency and severity of flares in affected patients.
What is the evidence?
Goodyear, HM, Spowart, K, Harper, JI. “'Wet-wrap' dressings for the treatment of atopic eczema in children”. Br J Dermatol. vol. 125. 1991. pp. 604
Hong, E, Smith, S, Fischer, G. “Evaluation of the atrophogenic potential of topical corticosteroids in pediatric dermatology patients”. Pediatr Dermatol. vol. 28. 2011. pp. 393-6.
Jekler, J, Larkö, O. “Combined UVA-UVB versus UVB phototherapy for atopic dermatitis: a paired comparison study”. J Am Acad Dermatol. vol. 22. 1990. pp. 49-53.
Klein, PA, Clark, RA. “An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis”. Arch Dermatol. vol. 135. 1999. pp. 1522-5.
Paller, A, Eichenfield, LF, Leung, DY. “A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients”. J Am Acad Dermatol. vol. 44. 2001. pp. S47-S57.
Sidbury, R, Hanifin, JM. “Old, new, and emerging therapies for atopic dermatitis”. Dermatol Clin. vol. 18. 2000. pp. 1-11.
Hanifin, JM, Rajka, G. “Diagnostic features of atopic dermatitis”. Acta Derm Venereol (Stockh). vol. Suppl 92. 1980. pp. 44-7.
Hata, TR, Kotol, P, Boguniewicz, M. “History of eczema herpeticum is associated with the inability to induce human B-defensin (HBD)-2, HBD-3, and cathelicidin in the skin of patients with atopic dermatitis”. Br J Dermatol. vol. 163. 2010. pp. 659-61.
Kay, J, Gawkrodger, DJ, Mortimer, MJ, Jaron, AG. “The prevalence of childhood atopic eczema in a general population”. J Am Acad Dermatol. vol. 30. 1994. pp. 35-9.
Lapidus, CS. “Role of social factors in atopic dermatitis: the US perspective”. J Am Acad Dermatol. vol. 45. 2001. pp. S41-3.
Leung, DYM, Soter, NA. “Cellular and immunologic mechanisms in atopic dermatitis”. J Am Acad Dermatol. vol. 44. 2001. pp. S1-12.
Morar, N, Cookson, WO, Harper, JI, Moffatt, MF. “Filaggrin mutations in children with severe atopic dermatitis”. J Invest Dermatol. vol. 127. 2007. pp. 1667-72.
Williams, HC. “Is the prevalence of atopic dermatitis increasing?”. Clin Exp Dermatol. vol. 17. 1992. pp. 385-91.
Wüthrich, B. “Clinical aspects, epidemiology, and prognosis of atopic dermatitis”. Ann Allergy Asthma Immunol. vol. 83. 1999. pp. 464-70.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has severe eczema? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has severe eczema, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of severe eczema?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- Other clinical manifestations that might help with diagnosis and management
- What complications might you expect from the disease or treatment of the disease?
- Are additional laboratory studies available; even some that are not widely available?
- How can severe eczema be prevented?
- What is the evidence?