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. 14-13).51,52 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 anti-inflammatory and immunomodulatory agents may be necessary.53
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, which serve as portals of entry for skin pathogens, irritants, and allergens. FLG gene mutations have also been shown to result in decreased epidermal levels of natural moisturizing factor.54 This problem can become aggravated during the dry winter months and in certain work environments. Warm soaking baths for approximately 10 minutes followed by the application of an occlusive emollient or topical medication to retain moisture can give such patients excellent symptomatic relief. Bathing without emollient use may result in drier skin.55 Use of an effective emollient combined with hydration therapy helps to restore and preserve the stratum corneum barrier, and may decrease the need for topical glucocorticoids. Moisturizers are available in the form of lotions, creams, or ointments. Some lotions and creams may be irritating due to added preservatives, solubilizers, and fragrances. Lotions containing water may be drying due to an evaporative effect.
Hydrophilic ointments can be obtained in varying degrees of viscosity according to the patient's preference. Occlusive ointments are sometimes not well tolerated because of interference with the function of the eccrine sweat ducts and the induction of folliculitis. In these patients, less occlusive agents should be used.
Topical therapy to replace abnormal epidermal lipids, improve skin hydration, and decrease skin barrier dysfunction may be useful therapeutically. Studies have shown benefits of topical preparations with distinct compositions of lipids and ceramides, as well as a nonsteroidal cream containing palmitamide MEA, an essential fatty acid, and a hydrolipidic cream with glycyrrhetinic acid (MAS063ADP).56,57 Further clinical studies to define the benefits relative to traditional moisturizers and topical anti-inflammatory agents will be helpful.
Hydration, by baths or wet dressings, promotes transepidermal penetration of topical glucocorticoids. Dressings may also serve as an effective barrier against persistent scratching, allowing more rapid healing of excoriated lesions.58 Wet dressings, or “wet wraps” are recommended for use on severely affected or chronically involved areas of dermatitis refractory to therapy.59 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.
Topical Anti-Inflammatory Therapy
A recent study looked at TEWL, as well as several other parameters of epidermal barrier including stratum corneum hydration and dye penetration.60 The authors found improvement in all parameters when AD patients were treated with both a topical steroid (betamethasone valerate 0.1% cream) and a topical calcineurin inhibitor (pimecrolimus 1% cream) applied to paired lesions of the upper extremities. Electron microscopic evaluation of barrier structure showed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in the calcineurin inhibitor-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies in the steroid-treated skin. Both treatments normalized epidermal differentiation and reduced epidermal hyperproliferation. Both anti-inflammatory therapies increased expression of filaggrin and involucrin in the skin. Betamethasone valerate was superior in reducing clinical symptoms and epidermal proliferation, but twice daily use over the 3-week period of the study led to epidermal thinning. The authors concluded that since pimecrolimus improved the epidermal barrier and did not cause cutaneous atrophy, it might be more suitable for long-term treatment of AD. However, the finding that the topical steroid was more effective in reducing clinical symptoms and inflammation supports the use of topical steroids for acute intervention of AD flares.
Topical Glucocorticoid Therapy
Topical glucocorticoids are the cornerstone of treatment for anti-inflammatory eczematous skin lesions. Because of potential side effects, most physicians use topical glucocorticoids only to control acute exacerbations of AD. However, recent studies suggest that once control of AD is achieved with a daily regimen of topical glucocorticoid, long-term control can be maintained in a subset of patients with twice weekly applications of topical fluticasone to areas that have healed but are prone to developing eczema.61
Patients should be carefully instructed in the use of topical glucocorticoids to avoid potential side effects. The potent fluorinated glucocorticoids should be avoided on the face, the genitalia, and the intertriginous areas. A low-potency glucocorticoid preparation is generally recommended for these areas. Patients should be instructed to apply topical glucocorticoids to their skin lesions and to use emollients over uninvolved skin. Failure of a patient to respond to topical glucocorticoids is sometimes due in part to an inadequate supply. It is important to remember that it takes approximately 30 g of cream or ointment to cover the entire skin surface of an adult once. To treat the entire body twice daily for 2 weeks requires approximately 840 g (2 lb) of topical glucocorticoids.
There are seven classes of topical glucocorticoids, ranked according to their potency based on vasoconstrictor assays. Because of their potential side effects, the ultrahigh-potency glucocorticoids should be used only for very short periods of time and in areas that are lichenified but not on the face or intertriginous areas. The goal is to use emollients to enhance skin hydration and low-potency glucocorticoids for maintenance therapy. Midpotency glucocorticoids can be used for longer periods of time to treat chronic AD involving the trunk and extremities. Newer formulations of topical steroids include gel formulations without alcohol bases that moisturize skin, and solutions, oils, foams, and shampoos that may be useful on hair-bearing surfaces.
Factors which influence topical glucocorticoid potency and side effects include the molecular structure of the compound, the vehicle, the amount of medication applied, the duration of application, occlusion, as well as host factors, including age, body surface area and weight, skin inflammation, anatomic location of treated skin, and individual differences in cutaneous or systemic metabolism. Side effects from topical glucocorticoids are directly related to the potency ranking of the compound and the length of use, so it is incumbent on the clinician to balance the need for a more potent steroid with the potential for side effects. In addition, ointments have a greater potential to occlude the epidermis, resulting in enhanced systemic absorption when compared to creams. Side effects from topical glucocorticoids can be divided into local side effects and systemic side effects resulting from suppression of the hypothalamic–pituitary–adrenal axis. Local side effects include the development of striae, skin atrophy, perioral dermatitis, and acne rosacea. The potential for potent topical glucocorticoid to cause adrenal suppression is greatest in infants and young children. Several topical steroid formulations have been specifically tested for safety and received specific US Federal Drug Administration (FDA) approval for use in younger children such as desonide hydrogel and nonethanolic foam, fluocinolone acetonide oil, and fluticasone 0.05% cream.62–65 Mometasone cream and ointment are approved for children aged 2 years and older.
Because normal-appearing skin in AD shows evidence of immunologic dysregulation, the use of topical corticosteroids as maintenance therapy has been reported in several controlled studies.66 Once control of AD with a once daily regimen was achieved, long-term control could be maintained with twice weekly application of fluticasone to previously involved areas. Given recent insights into skin barrier and immunologic abnormalities and colonization of normal-appearing skin in AD by S. aureus, it is important to appreciate that proactive therapy is an attempt to control residual disease, not just application of an active drug to nonaffected skin.67
Topical Calcineurin Inhibitors
Topical tacrolimus and pimecrolimus have been developed as nonsteroidal immunomodulators.68 Tacrolimus ointment 0.03% has been approved for intermittent treatment of moderate to severe AD in children aged 2 years and older, with tacrolimus ointment 0.1% approved for use in adults; pimecrolimus cream 1% is approved for treatment of patients aged 2 years and older with mild–moderate AD. Both drugs have proven to be effective with a good safety profile for treatment up to 4 years with tacrolimus ointment69 and up to 2 years with pimecrolimus cream.70 A frequently observed side effect with TCIs is a transient burning sensation of the skin. Importantly, treatment with TCIs is not associated with skin atrophy,71 thus they are particularly useful for the treatment of areas such as the face and intertriginous regions. Ongoing surveillance and recent reports have not shown a trend for increased frequency of viral superinfections, especially eczema herpeticum.72 The long-term safety of TCIs has not been established. Rare cases of skin malignancy and lymphoma have been reported with topical tacrolimus, though the level of data quality and applicability of these reports was judged low in the report of a scientific consensus conference.73 Importantly, a case-control study of a large database that identified a cohort of 293,253 patients with AD found no increased risk of lymphoma with the use of TCIs.74 Twice to three times weekly maintenance therapy using tacrolimus ointment has also been reported in both adults and children with AD.75,76
Identification and Elimination of Triggering Factors
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. 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 facilitates 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, but chlorine should be rinsed off immediately after swimming and the skin lubricated. Although ultraviolet (UV) light may be beneficial to some patients with AD, sunscreens should be used to avoid sunburn. However, because sunscreens can be irritants, care should be used to identify a nonirritating product.
Foods and aeroallergens such as dust mites, animal danders, molds, and pollens have been demonstrated to exacerbate AD. Potential allergens can be identified by taking a careful history and carrying out selective skin-prick tests or specific serum IgE levels. Negative skin tests or serum tests for allergen-specific IgE have a high predictive value for ruling out suspected allergens. However, a normal total serum IgE level does not rule out the possibility of allergen-specific IgE being present. Positive skin or in vitro tests, particularly to foods, often do not correlate with clinical symptoms and should be confirmed with controlled food challenges and elimination diets. Avoidance of foods implicated in controlled challenges results in clinical improvement. Extensive elimination diets, which in some cases can be nutritionally deficient, are rarely, if ever, required, because even with multiple positive skin tests, the majority of patients react to three or fewer foods on controlled challenge. In dust mite-allergic patients with AD, prolonged avoidance of dust mites has been found to result in improvement of their skin disease. Avoidance measures include use of dust mite-proof encasings on pillows, mattresses, and box springs; washing bedding in hot water weekly; removal of bedroom carpeting; and decreasing indoor humidity levels with air conditioning. Because there are many triggers contributing to the flares of AD, attention should be focused on identifying and controlling the flare factors that are important to the individual patient. Infants and young children are more likely to have food allergies, whereas older children and adults are more likely to be sensitive to environmental aeroallergens. Contact allergens have been increasingly recognized in AD. A recent study found that of children with relevant positive reactions, 34% had a diagnosis of AD.77
Although emotional stress does not cause AD, it often exacerbates the illness. AD patients often respond to frustration, embarrassment, or other stressful events with increased pruritus and scratching. In some instances, scratching is simply habitual and less commonly associated with significant secondary gain. Psychological evaluation or counseling should be considered in patients who have difficulty with emotional triggers or psychological problems, contributing to difficulty in managing their disease. It may be especially useful in adolescents and young adults who consider their skin disease disfiguring. Relaxation, behavioral modification, or biofeedback may be helpful in patients with habitual scratching.58
Antistaphylococcal antibiotics are very helpful in the treatment of patients who are heavily colonized or infected with S. aureus.78 Cephalosporins or penicillinase-resistant penicillins (dicloxacillin, oxacillin, or cloxacillin) are usually beneficial for patients who are not colonized with resistant S. aureus strains. Because erythromycin-resistant Staphylococci are common, erythromycin and newer macrolide antibiotics are usually of limited utility. Topical antimicrobials such as mupirocin, fusidic acid, or more recently retapamulin offers some utility in the treatment of impetiginized lesions. A Cochrane Database analysis of interventions for impetigo found that topical mupirocin and topical fusidic acid are equal to or more effective than oral treatment for patients with limited disease and that fusidic acid and mupirocin are of similar efficacy.79 Patients should be cautioned against using topical antibiotics in an “as-needed” manner that can lead to resistant organisms.80
Use of neomycin topically can result in development of allergic contact dermatitis as neomycin is among the more common allergens causing contact dermatitis. However, in patients with extensive superinfection, a course of systemic antibiotics is most practical. Methicillin-resistant Staphylococci may require culture and sensitivity testing to assist in appropriate antibiotic selection. Baths with dilute sodium hypochlorite (bleach) may also benefit AD patients with superinfected eczema, especially those with recurrent MRSA, although they can occasionally be irritating. Of note, a controlled study of twice weekly bleach baths for 3 months showed clinical benefit, although skin colonization by S. aureus did not disappear, even when combined with intranasal mupirocin 5 days each month.81
Herpes simplex can provoke recurrent dermatitis and may be misdiagnosed as S. aureus infection. The presence of punched-out erosions, vesicles, and/or infected skin lesions that do not respond to oral antibiotics should initiate a search for herpes simplex. This can be diagnosed by a Giemsa-stained Tzanck smear of cells scraped from the vesicle base, direct immunofluorescence assay, polymerase chain reaction identification of herpes genetic material, or by viral culture. For infection suspected to be caused by herpes simplex, topical anti-inflammatory agents might be discontinued, at least temporarily. Antiviral treatment for cutaneous herpes simplex infections is of critical importance in the patient with widespread AD because life-threatening dissemination has been reported. Acyclovir, 400 mg three times daily for 10 days or 200 mg four times daily for 10 days by oral administration (or an equivalent dosage of one of the newer antiherpetic medications), is useful in adults with herpes simplex confined to the skin. Intravenous treatment may be necessary for severe disseminated eczema herpeticum. The dosage should be adjusted according to weight in children.
Dermatophyte infections can complicate AD and may contribute to exacerbation of disease activity. Patients with dermatophyte infection or IgE antibodies to Malassezia may benefit from a trial of topical or systemic antifungal therapy.
The treatment of pruritus in AD should be directed primarily at the underlying causes. Reduction of skin inflammation and dryness with topical glucocorticoids and skin hydration, respectively, often symptomatically reduce pruritus. Inhaled and ingested allergens should be eliminated if documented to cause skin rash in controlled challenges. Systemic antihistamines act primarily by blocking the H1 receptors in the dermis, thereby ameliorating histamine-induced pruritus. However, histamine is only one of many mediators that can induce pruritus of the skin. Therefore, certain patients may derive minimal benefit from antihistaminic therapy. Some antihistamines are also mild anxiolytics and may offer symptomatic relief through tranquilizing and sedative effects. Studies of newer, nonsedating antihistamines show variable results in the effectiveness of controlling pruritus in AD, although they may be useful in the subset of AD patients with concomitant urticaria or concurrent allergic rhinitis.
Because pruritus is usually worse at night, the sedating antihistamines, for example, hydroxyzine or diphenhydramine, may offer an advantage with their soporific side effects when used at bedtime. Doxepin hydrochloride has both tricyclic antidepressant and H1- and H2-histamine receptor-blocking effects. It can be used in doses of 10–75 mg orally at night or up to 75 mg bid in adult patients. If nocturnal pruritus remains severe, short-term use of a sedative to allow adequate rest may be appropriate. Treatment of AD with topical antihistamines is generally not recommended because of potential cutaneous sensitization. However, short-term (1 week) application of topical 5% doxepin cream has been reported to reduce pruritus without sensitization. Of note, sedation is a side effect of widespread application of doxepin cream, and allergic contact dermatitis has been reported.
Coal tar preparations may have antipruritic and anti-inflammatory effects on the skin, although usually not as pronounced as those of topical glucocorticoids.82 Tar preparations may be useful in reducing the potency of topical glucocorticoids required in chronic maintenance therapy of AD. Newer coal tar products have been developed that are more acceptable with respect to odor and staining of clothes than some older products. Tar shampoos can be beneficial for scalp dermatitis and are often helpful in reducing the concentration and frequency of topical glucocorticoid applications. Tar preparations should not be used on acutely inflamed skin, because this often results in skin irritation. Side effects associated with tars include folliculitis and photosensitivity. There is a theoretic risk of tar being a carcinogen based on observational studies of workers using tar components in their occupations; however, epidemiologic studies do not confirm similar outcomes when used topically.83
Natural sunlight is frequently beneficial to patients with AD. However, if the sunlight occurs in the setting of high heat or humidity, thereby triggering sweating and pruritus, it may be deleterious to patients. Broadband UVB, broadband UVA, narrowband UVB (311 nm), UVA-1 (340 to 400 nm), and combined UVAB phototherapy can be useful adjuncts in the treatment of AD. Investigation of the photoimmunologic mechanisms responsible for therapeutic effectiveness indicates that epidermal LCs and eosinophils may be targets of UVA phototherapy, with and without psoralen, whereas UVB exerts immunosuppressive effects via blocking of function of antigen-presenting LCs and altered keratinocyte cytokine production. Photochemotherapy with psoralen and UVA light may be indicated in patients with severe, widespread AD, although studies comparing it with other modes of phototherapy are limited. Short-term adverse effects with phototherapy may include erythema, skin pain, pruritus, and pigmentation. Long-term adverse effects include premature skin aging and cutaneous malignancies (see Chapters 237 and 238 for detailed discussion of phototherapy and photochemotherapy, respectively).
AD patients who appear erythrodermic or who have widespread severe skin disease resistant to outpatient therapy should be hospitalized before considering systemic alternative therapies (see section “Systemic Therapy”). In many cases, removing the patient from environmental allergens or emotional stresses, intense patient education, and assurance of compliance with therapy results in a sustained improvement in their AD. Clearing of the patient's skin during hospitalization also allows the patient to undergo allergen skin testing and appropriately controlled provocative challenges to correctly identify or rule out potential allergens.
Systemic therapies discussed below were reviewed in a consensus conference.53
The use of systemic glucocorticoids, such as oral prednisone, is rarely indicated in the treatment of chronic AD. Some patients and physicians prefer the use of systemic glucocorticoids to avoid the time-consuming skin care involving hydration and topical therapy. However, the dramatic clinical improvement that may occur with systemic glucocorticoids is frequently associated with a severe rebound flare of AD after the discontinuation of systemic glucocorticoids. Short courses of oral glucocorticoids may be appropriate for an acute exacerbation of AD whereas other treatment measures are being instituted. If a short course of oral glucocorticoids is given, it is important to taper the dosage and to begin intensified skin care, particularly with topical glucocorticoids and frequent bathing followed by application of emollients to prevent rebound flaring of AD.
Cyclosporine is a potent immunosuppressive drug that acts primarily on T cells by suppressing cytokine transcription. The drug binds to cyclophilin, an intracellular protein, and this complex, in turn, inhibits calcineurin, a molecule required for initiation of cytokine gene transcription. Multiple studies demonstrate that both children and adults with severe AD, refractory to conventional treatment, can benefit from short-term cyclosporine treatment. Various oral-dosing regimens have been recommended: 5 mg/kg has generally been used with success in short-term and long-term (1 year) use, whereas some authorities advocate body-weight-independent daily dosing of adults with 150 mg (low dose) or 300 mg (high dose) daily of cyclosporine microemulsion. Treatment with cyclosporine is associated with reduced skin disease and an improved quality of life (see Chapter 233 for further discussion). Discontinuation of treatment may result in rapid relapse of skin disease, although some patients may have sustained remission. Elevated serum creatinine or more significant renal impairment and hypertension are specific side effects of concern with cyclosporine use.
Mycophenolate mofetil is a purine biosynthesis inhibitor used as an immunosuppressant in organ transplantation, which has been used for treatment of refractory inflammatory skin disorders (see Chapter 233). Open-label studies report that short-term oral mycophenolate mofetil, 2 g daily, as monotherapy results in clearing of skin lesions in adults with AD resistant to other treatment, including topical and oral steroids and psoralen and UVA light. The drug has generally been well tolerated with the exception of one patient developing herpes retinitis that may have been secondary to this immunosuppressive agent. Dose-related bone marrow suppression has also been observed. Similar results were previously reported in another open study of ten patients with a mean reduction in the SCORAD (SCORing Atopic Dermatitis) index of 68% in all ten patients. Of note, not all patients benefit from treatment. Therefore, the medication should be discontinued if patients do not respond within 4 to 8 weeks. Dose finding and well-controlled studies are needed for this drug.
Methotrexate is an antimetabolite with potent inhibitory effects on inflammatory cytokine synthesis and cell chemotaxis. Methotrexate has been used for adult AD patients with recalcitrant disease, although controlled trials are lacking. Dosing more frequently than the typical weekly dosing for psoriasis has been advocated.84 In open-label studies, initial improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 weeks +/– 3.17).
Azathioprine is a purine analog with anti-inflammatory and antiproliferative effects. It has been used for severe AD, and several controlled trials have been reported in adults and children.85,86 Myelosuppression is a significant adverse effect. Thiopurine methyl transferase levels may predict individuals at risk.87
IFN-γ is known to suppress IgE responses and downregulate Th2 cell proliferation and function. Several studies of patients with AD, including a multicenter, double-blind, placebo-controlled trial88 and two long-term open trials,89,90 have demonstrated that treatment with recombinant human IFN-γ results in clinical improvement. Reduction in clinical severity of AD correlated with the ability of IFN-γ to decrease total circulating eosinophil counts. Influenza-like symptoms are commonly observed side effects early in the treatment course.
Treatment of patients with severe AD and elevated serum IgE levels with monoclonal anti-IgE has shown lack of efficacy in three adult patients91 and significant improvement in three adolescent patients.92 In an open study of 11 adult patients with high IgE levels treated with anti-IgE, some patients had very good clinical improvement, others had none and several had worsening of their AD based on change in SCORAD.93 To date, specific markers have not been found to identify potential responders.
Unlike allergic rhinitis and extrinsic asthma, immunotherapy with aeroallergens has not proven to be efficacious in the treatment of AD. There are anecdotal reports of both disease exacerbation and improvement. A recent study of specific immunotherapy over 12 months in adults with AD sensitized to dust mite allergen showed improvement in SCORAD as well as reduction in topical steroid use.94 However, well-controlled studies are still required to determine the role for immunotherapy with this disease. More recently, a controlled study with sublingual immunotherapy showed benefit in a subset of children with AD sensitized to dust mite allergen.95 This data need to be reproduced in a larger pediatric population, given the natural history of AD.
Extracorporeal photopheresis consists of the passage of psoralen-treated leukocytes through an extracorporeal UVA light system. Clinical improvement in skin lesions associated with reduced IgE levels has been reported in a few patients with severe, resistant AD who were treated with extracorporeal photopheresis and topical glucocorticoids.96
Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG was shown to reduce the incidence of AD in at-risk children during the first 2 years of life.97 Mothers were given either placebo or Lactobacillus GG daily for 4 weeks before delivery and then either the mother (if breast-feeding) or the infant continued with daily therapy for 6 months. In a follow-up study, the same group assessed the persistence of potential to prevent AD at 4 years.98 The results suggest that the preventive effect of Lactobacillus GG on AD could extend beyond infancy.
In a second study, children with AD treated with two Lactobacillus strains for 6 weeks experienced improvement of their eczema compared to placebo-treated patients, although their SCORAD index did not change significantly.99 The treatment response was found to be more pronounced in patients with positive skin-prick tests and elevated IgE levels. Another study of children with moderate to severe AD treated for 8 weeks with L. fermentum in a placebo-controlled study showed persistent improvement in SCORAD at 16 weeks.100 These studies suggest that probiotics, or at least some Lactobacillus strains, may have preventative, lasting effects on the incidence of AD in a subset of patients. More research into subgroups of responders, optimal therapy [route (i.e., directly to infant or via mother's milk); length of treatment; strain of Lactobacillus], as well as mechanisms involved is clearly needed.101
A recent meta-analysis found a modest role for probiotics in children with moderately severe disease in reducing SCORAD (mean change from baseline, –3.01; 95% confidence interval, –5.36 to –0.66; P = .01).102 Duration of probiotic administration, age, and type of probiotic used did not affect outcomes. Another meta-analysis found that current evidence is more convincing for probiotics’ efficacy in prevention, rather than treatment of AD in children.103 In contrast to earlier studies, supplementation with Lactobacillus GG during pregnancy and early infancy neither reduced the incidence of AD nor altered the severity of AD in affected children, but was associated with increased rate of recurrent episodes of wheezy bronchitis.104 A Cochrane review concluded that probiotics are not an effective treatment for eczema in children and that probiotic treatment carries a small risk of adverse events.105
Chinese Herbal Medications
Several placebo-controlled clinical trials have suggested that patients with severe AD may benefit from treatment with traditional Chinese herbal therapy (see Chapter 241). They had significantly reduced skin disease and decreased pruritus. However, the beneficial response of Chinese herbal therapy is often temporary, and effectiveness may wear off despite continued treatment. The possibility of hepatic toxicity, cardiac side effects, or idiosyncratic reactions remains a concern. The specific ingredients of the herbs also remain to be elucidated and some preparations have been found to be contaminated with corticosteroids. At present, Chinese herbal therapy for AD is considered investigational.
A pilot randomized, double-blind placebo-controlled study looked at the benefit of oral vitamin D supplementation in children with AD from February to March in Boston.106 Eleven pediatric patients primarily with mild AD were treated with either vitamin D (1,000 IU ergocalciferol) or placebo once daily for a month. IGA score improved in four of six subjects in the vitamin D group (80%), as compared to one of five subjects in the placebo group (p = 0.04). In addition, there was a greater reduction in EASI score in the vitamin D, as compared to the placebo group, although the difference was not statistically significant. In addition, in a controlled study, 14 healthy subjects and 14 subjects with AD were supplemented with 4,000 IU per day of oral vitamin D3 (cholecalciferol) for 3 weeks.107 Expression of the AMP cathelicidin was significantly increased in the skin biopsies of AD lesions, as compared to those in healthy skin or uninvolved AD skin, suggesting a role for oral vitamin D in improving innate immune responses in AD patients.108