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The red face: Atopic dermatitis
The Red Face: Atopic Dermatitis YELENA M. MIRENSKY, MD
A
topic dermatitis is a genetically determined cutaneous affliction characterized by redness, scaling, lichenification, and pruritus, affecting approximately 10% of the population.’ This allergic disorder is conceptually similar to asthma and allergic rhinitis. Other than a nonspecific spongiosis, there is no pathognomonic histopathology, nor are there diagnostic laboratory parameters for this disorder. A patient with atopic dermatitis demonstrates a constellation of clinical features, most prominent being increased irritability of the skin, intense pruritus, and chronic scratching leading to lichenification. Physiologic abnormalities include specific vasomotor alterations, increased susceptibility to viral, bacterial, and fungal infections, and abnormalities in humoral and cell-mediated immunity.
Historical Aspects Atopic dermatitis has carried a plethora of names through the ages. Its prevalence, difficulty encountered in describing characteristic symptoms of the disease, and lack of definable cause for the disorder have led to different theories about its etiology and have contributed to the diversity of nomenclature used to describe it. The term eczema or boiling over was first used by Aetius of Amida in the 6th century CE. In Materia Medica and Therapeutics Henry G. Piffard, the 19th century New York dermatologist, discussed eczema at length, dividing it into four main categories: acute or subacute in form, and acute or chronic in duration. He provided the reader with a whole dictionary of names to subdivide eczema depending on the appearance and location of the lesions. “Eczema is undoubtedly due,“ he writes, “to the blood From the Department of Medicine, Greater Baltimore Medical Center, Baltimore, Maryland. Address correspondence to Yelena M. Mirensky, MD, 7221Brook Falls Terrace, Baltimore, MD 22209.
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1993 by Elseuier
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condition resulting from imperfect assimilation of the food and deficient oxidation of the protein compounds.” Keeping in step with the emphasis on the digestive process in vogue at the time, he assures the reader that a “carnivorous” diet and dry skin with decreased ability to sweat are some of the main causes. Consequently, in addition to a herbivorous diet, he recommends the use of Turkish baths, oral purgatives, diuretics, salicylic acid, tar, and arsenic to alleviate the symptoms. Speaking of eczema on the face in adult men, he urges that “it is necessary first of all to remove, by epilation, all the hairs that proceed from diseased follicles in order that remedial applications may penetrate them.” 2 In the 1880s and 1890s bacteria were proposed as the cause of eczema. During the same era, Louis Brocq and Louis Jaquet named a specific subset of lichen neurodermatitis. They felt this disorder was associated with a nervous personality.3 In 1932 positive wheal reactions to skin tests led Arthur Coca, Fred Wise (1881- 1950), and Marion Sulzberger (1895 - 1983) to use the term atopic dermatitis, now universally accepted for the disease.3 Their concepts of immunologic abnormalities continue to be believed by most investigators today.
Etiology Although the etiology of atopic dermatitis is unknown, defects in humoral and cell-mediated immunity play a major role in this genetically determined disorder. A positive family history of asthma, allergic rhinitis, or atopic dermatitis in over 75% of patients with atopic dermatitis has led to the concept of autosomal dominant mode of inheritance, but no specific HLA locus has been identified to date.* On the humoral level, elevated IgE levels, the most consistent defect, are present in 80% of the patients with
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atopic dermtitis, although the degree of elevation has not been shown always to correlate with the severity of the disease. IgE antibodies specific for housedust, housedust mite, and human dander are also found in some atopic patients, although their significance is unknown.5-7 Elevated IgE levels have been found in the majority of children with atopic dermatitis, and elevated IgG and IgE serum complement-fixing immune complexes are found in some.* In contrast to other allergic disorders, attempts at desensitization therapy have been unsuccessful in most patients with atopic dermatitis. Defects in cell-mediated immune responses are evidenced in elevated susceptibility of atopics to cutaneous bacterial, viral, and fungal infections such as vaccinia, molluscum contagiosum, verruca vulgaris, and Staphylococcus aureus. Incidence, severity, and length of these infections are all greater in atopic individuals than in the rest of the population. In addition, decreased numbers of suppressor T-lymphocyte cells,9 depressed monocyte and neutrophil chemotaxis, decreased hypersensitivity skin test reactivity to dinitrochlorobenzene and Candida albicans,10-12 and decreased CAMP levels have all been documented in atopic patients.13J4 Subsequent development of atopic dermtitis in persons receiving bone marrow transplants from donors with the disorder further confirms the hematopoietic cell dysfunction hypothesis.15 Numerous studies showing premenstrual flaring of atopic dermatitis suggest that sex hormones may also play a role, although the exact mechanism is, once again, unknown.16 Atopic dermatitis is also common in dogs. Affected dogs develop immediate-type hypersensitivity reactions to inhaled antigens, such as pollens, wool, housedust, feathers, molds, and trees. Severe pruritus leads to biting, scratching, and excoriations. In young dogs the pruritic episodes appear to be seasonal; they become continuous as the animal ages. Interestingly, asthma has not been reported in atopic dogs. In addition, in contrast to humans, desensitization therapy is a highly effective form of treatment in canines, suggesting a different etiology.“J8 In Eastern Europe present-day theories as to the etiology of atopic dermatitis are often divergent from those found in Western Europe and the Americas. For example, in Russia, psychiatric factors and defective enzyme production in the liver are considered primary causes, in addition to those accepted in the West, and HLA phenotype D7 is said to be linked to atopic dermatitis.19 Although the etiology of atopic dermatitis remains unknown, a hereditary immune deficiency is undoubtedly at the core.
Table 1. Facial Signs Associated 1. 2. 3. 4. 5. 6. 7. 8. 9.
With Atopic Dermatitis
Blepharitis Dennie-Morgan fold (infraorbital fold) Erythema “Furrowed mouth syndrome” (cheilitis) Lichenification Pallor Postauricular fissures “Raccoon face” (darkening of the periorbital spaces) Scaling
Epidemiology There is no dissension among experts in the field that atopic dermatitis is a common disease. But just how common is it? Reported prevalence rates in children vary from 3% cited in one clinical study’ to 24% in another.*O Differences in diagnostic criteria cited by different investigators partially account for such a wide range. Most workers agree that close to 10% of the population is affected,’ with an increased prevalence in the last 20 year.*l*** The disease has been reported to be more common in whites,23 but in my experience (in the Philadelphia area) both white and black patients are seen equally frequently. Possibly, city dwellers are affected more often,’ or they may be more likely to seek medical care.
Clinical Manifestations Extreme pruritus, a chronic waxing and waning course, and a typical age-dependent distribution are the hallmarks of atopic dermatitis. 24Unable to control the urge to scratch, atopics excoriate the skin, irritating it, and thereby causing more itching. They scratch most forcefully at night, when conscious control is diminished. The presence of a primary lesion in atopic dermatitis remains a topic of debate. Is pruritus the primary event, with the lesions resulting from the irritation caused by scratching?25,26 Do erythematous lesions on the skin appear first and pruritus follows? *’ Whether it is the itch that rashes or the rash that itches, extreme pruritus causes much suffering for patients with atopic dermatitis. Lack of sleep can aggravate constant discomfort. Unceasing scratching and chronic lesions on socially important body areas, especially the face, contribute to social ostracism. Not covered by clothing, the “red face” of a patient with atopic dermatitis is perhaps the most readily observed clinical feature (Table 1). Manifestations of the disease vary with age as well with the individual patient. Although classic patterns exist, many patients present with atypical features. Generally, in the infant phase (3 4 months to 2 years), x the face is involved in addition to
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the extensor surfaces of the limbs, the trunk, and the diaper area.8 Pruritic erythema on the cheeks evolves into papules, vesicles, and erosions. These progress to weeping crusty lesions that can cover the forehead, chin, periauricular area, and the scalp.27,28 Hyperkeratosis of the scalp in atopic dermatitis can look similar to the “cradle cap” of seborrheic dermatitis. The nose is frequently spared.?’ In the childhood (3 - 12 years) phase, the lesions migrate to involve the popliteal fossae and the antecubital areas, the feet, and the hands.28 Perifollicular accentuation is common in dark-skinned patients.26 Facial involvement can be extensive. Pruritic, dry, scaly, erythematous lesions can appear on the eyelids, on the lateral posterior neck, and around the mouth.27,28 Constant rubbing and licking of the perioral area leads to lip cheilitis, severe enough to be called the “furrowed mouth syndrome.” Rubbing the eyelids causes swelling and constant tearing. Blepharitis, vernal conjunctivitis, and, in severe cases, cornea1 irritation and abrasion can result.27 Periorbital darkening, the “raccoon face,” is typical. Horizontal anterior neck folds are common, and the Dennie Morgan infraorbital fold is present in 70% of the cases.8 Dry skin and lichenification often represent atopic dermatitis in adults. The face is once again the primary target (Fig 1). Flexural areas, hands, feet, and nipples can also be involved. Manifestations are similar to those seen in the juvenile phase. In some, erythema and scaling are not limited to the face, but can include the neck and the shoulders.29 Others show marked facial pallor.27 Although always present in atopics, white dermographism is not specific for this disorder.*O The skin of patients with psoriasis or mycosis fungoides also turns white on stroking. In 70% of patients, iontophoresis causes a delayed blanch response, whereas the application of nicotinic acid produces no response or blanching in contrast to the normal erythema.27
Diagnosis There are no pathognomonic histologic or laboratory findings in atopic dermatitis. This clinical diagnosis is based on a characteristic constellation of clinical features. Nearly all patients present with at least three of the major manifestations and some of the minor nonspecific manifestations listed in Table 2. Distribution, morphology, and severity vary greatly from patient to patient. Moreover, on the same individual, the disease may look very differently over time. The nonspecific histopathologic findings include spongiosis and lichenification. In acute dermatitis intercellular and intracellular edema may be present. A mononuclear infiltrate is seen in the spongiotic
epidermis. More chronic lesions show epidermal hyperplasia and parakeratosis. Helper T lymphocytes predominate in the dermal infiltrate. Increased numbers of Langerhans cells can be seen in the chronic lichenified lesions, but not in the unaffected skin.30 Similar findings are seen in contact, nummular, and dishydrotic dermatitides. Although there are no pathognomonic laboratory tests, eosinophilia in the peripheral smear and elevated IgE levels support the diagnosis of atopic dermatitis (AD).
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1993;21:235-242 Table 2. Diagnostic Criteria for Atopic Dermatitis Major -1. 2. 3. 4.
Minor 1. 2. 3. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Criteria Chronically relapsing course History of atopy (asthma, allergic rhinitis, or atopic dermatitis) PlUlituS
Typical distribution Facial and extensor involvement in infancy and early childhood Flexural lichenification in older children and adults Criteria Cheilitis Cradle cap (dermatitis of the scalp in infancy) Delayed blanch response Hand/foot dermatitis Ichthyosis vulgaris Immediate skin test reactivity Itching when sweating Perifollicular accentuation Keratosis pilaris Seasonal variation Susceptibility to cutaneous infections (particularly Staphylococcus aureus and herpes simplex) White dermographism Wool intolerance Xerosis
Adapted, with permission,from Hanifin.’
Experimentally, decreased CAMP levels and decreased numbers of killer T cells have been found in patients with AD.9,13J4 Increased norepinephrine and acetyl choline levels in the skin and blood vessels have also been documented. In the future, these findings may prove useful in routine diagnosis and provide clues as to the etiology of the disease. Differential
Diagnosis
Other causes of the red face may be similar in appearance to that seen in atopic dermatitis (Table 3). In infancy, atopic dermatitis mimics seborrheic dermatitis. The latter, however, is usually more greasy and less pruritic. Typically appearing before 2 months of age, seborrheic dermatitis may be confined to the head.‘,lO Early or partially treated psoriasis can look like atopic dermatitis. Silvery scales come off on scratching the psoriatic lesions. Even exposure to cold, windy air can result in red, scaly skin on the face.26 Primary irritant contact dermatitis is also a possibility, especially in women who use many commercial preparations on their face.‘O In teenagers and adults, nummular dermatitis needs to be considered. The coinshaped papulovesicular lesions of this idiopathic disorder, however, more commonly affect the lower limbs.8 Rare diseases similar in appearance to atopic dermatitis include Wiskott -Aldrich syndrome, Leiner’s disease, X-linked agammaglobulinemia,lo and hyper-IgE syndrome.’ Wiskott - Aldrich syndrome is an X-linked reces-
sive disorder. When the family history is unknown, the presence of thrombocytopenic purpura and recurrent infections differentiate this disease. Leiner’s disease, a generalized inflammatory dermatitis, associated with abnormal complement activity and lowered neutrophilic chemotaxis, often begins on the face. It is rarely seen in infants past 3 months of age. This disorder progresses to a generalized erythroderma that resolves within 2 weeks.32 Patients with X-linked agammaglobulinemia are easily differentiated by the absence of IgE. The papular, mildly erythematous eruption seen on the face of patients suffering from the hyper-IgE syndrome resembles atopic dermatitis. Deep staphylococcal infections and extremely elevated IgE levels easily distinguish this disorder. Associated
Disorders
Disorders associated with atopic dermatitis include pityriasis alba, keratosis pilaris, and ichthyosis vulgaris. There is an increased incidence of fungal, bacterial, and viral infections, anterior subcapsular cataracts, atopic rhinitis, and asthma. In addition, vitiligo and alopecia areata may be more common in atopic patients.** Pityriasis alba is especially prevalent in dark-skinned children with atopic dermatitis.27J8 In addition to the face, asymptomatic patches of erythema, fine scaling, and subsequent hypopigmentation with indistinct borders can appear on the upper arms. Fortunately, this loss of pigment is not permanent.26 Keratosis pilaris, often extensive in atopics, should not be confused with pustular acne or miliaria rubra. In addition to being found on the face, the uniformly small (l2 mm) follicular papules and pustules also commonly affect the upper arms and the thighs. Fifty percent of patients with ichthyosis vulgaris also have features of atopic dermatitis. Most believe this to be a genetic association. Because their skin is so dermatitic, atopics show greater incidence and severity of microbacterial infections. Staphylococcus aureus is a common colonizer of atopic skin, frequently leading to impetigo.28 Flares of atopic dermatiTable 3. Differential Diagnosis of Atopic Dermatitis (Limited to the Face) 1. 2. 3. 4. 5. 6. 7. 8. 9.
Contact dermatitis Nummular dermatitis Hyper-IgE syndrome Liener’s disease Psoriasis Seborrheic dermatitis Windburn Wiskott-Aldrich syndrome X-linked agammaglobulinemia
Clinics in Dermatology 2993;12:235-242 tis are often associated with bacterial infections,33 and improvement has been noted with decreased S. aureus colonization.Z Whether S. aureus has a direct inflammatory effect on the skin is still unclear.25,34 Viral infections common and more severe in atopics include herpes simplex, vaccinia, molluscum contagiosum, and varicella.34,35 These have also been shown to elicit exacerbations of atopic dermatitis. Atopics also show increased antibody titers to Epstein-Barr virus and an increased incidence of upper respiratory infections3’ Interestingly, they often improve following a measles infection. The reason for this phenomenon is unclear.25 Pityrosporon male is also more common in young adults with head-neck-shoulder dermatitis. Possibly, it elicits an allergic reaction, thereby intensifying symptoms of atopic dermatitis. 29 Trichophyton rubrum infections are seen more frequently in atopics than in the general populations.29 Tinea corporis superinfection should be considered when patches of atopic dermatitis are particularly resistant to treatment. Chronic application of topical steroids promotes growth of fungal spores. This “tinea incognito” syndrome needs to be treated with antifungal agents. Alopecia areata and vitiligo are also thought to occur more often in patients with AD,*’ perhaps because this group of patients is likely to seek medical attention. Anterior subcapsular cataracts are present in 16% of atopics.*’ Posterior cataracts are also more common, but these are possibly due to long-term steroid therapy.26*38 Short stature has been noted in over 20% of children with severe atopic dermatitis. Possible etiologic factors include the disease itself, chronic steroid therapy, loss of sleep, and malnutrition brought on by avoidance of many foods.36 Although seborrheic dermatitis is well known to be a common feature of the acquired immune deficiency syndrome (AIDS), the incidence of atopic dermatitis in adult AIDS patients has not yet been determined. Fifty percent of children with AIDS have atopic dermatitis.37 Children with atopic dermatitis are at an increased risk for other atopic disorders. Over half of the children with severe atopic dermatitis developed asthma in one study.38 Present in over 70% of the patients, a family history of atopic disorders, including asthma and allergic rhinitis, is one of the main criteria for diagnosing the disease.
Treatment In treating atopic dermatitis, the most important and perhaps most difficult task is interrupting the itch/scratch cycle. The aim is to treat the damaged skin and control infection, if present, as soon as possible. The ideal regimen for treatment includes an extensive list of instruc-
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tions aimed at treating the inflammation and the infection, alleviating aggravating factors, and hydrating the skin. It involves all aspects of the patient’s life. When compliance is in question, however, the best approach is to make the patient aware of the few most important steps to alleviation of the symptoms.
Steroids Fluorinated and chlorinated topical steroids decrease inflammation, moisturize, and alleviate the itch39; however, steroids with atrophogenic properties should be used judiciously on the face. Highly potent preparations are best reserved for short-term treatment of acute exacerbations. In severe flares oral steroids may be indicated. Oral beclamethasone dipropionate may become a useful oral agent in the future. Metabolized more rapidly than prednisone, it has very few systemic side effects.‘O
Moisturizing Because xerosis is so significant in atopic dermatitis, conflicting concepts of moisturizing have developed. As washing dries the skin, the Scholtz regimen prohibits bathing altogether, with a lipid cleanser being used in its place. 41 In a culture that calls for daily showers, however, compliance with such a regimen is unlikely. A viable alternative is taking cool, short showers, no longer than 3 minutes. In an attempt to alleviate the incessant itching, atopics often take very hot showers. The hot water further dries the skin.26 Cold water has an antipruritic effect without overdrying. Soap should be used only in the pubic and axillary areas, the hands and the face. A lipidfree cleansing lotion can be used everywhere else. Simple emollients should be applied daily. Moisturizing immediately following a shower (within 3 minutes) maintains the stratum corneum hydration before evaporation takes place.30 Choice of moisturizer depends on severity of the xerosis and patient preference. Treatment is particularly important in the winter, when dry air further aggravates the xerosis. Using a humidifier in the bedroom helps by increasing humidity.
Antimicrobials Antimicrobials are routinely used to control staphylococcal infection. Interestingly, they are sometimes helpful even when no overt infection can be seen. Choice of the antimicrobial is best determined using a sensitivity profile of the pathogen. Erythromycin and cephalosporins are often appropriate.
Antihistamines Because of their sedating properties, conventional antihistamines cannot be used extensively in treating atopic
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dermatitis as high doses are needed to achieve an antipruritic effect. Because the mechanism of their antipruritic qualities remains unknown, a wide variety of antihistamines have been used. Hydroxacine is effective when administered at bedtime, allowing for uninterrupted sleep. Recently, the nonsedating third-generation Hl antagonists promise to be helpfu1.42-4 In addition to inhibiting histamine release, these agents inhibit mediator release and interfere with eosinophil migration.43
Other Treatments Adjunct therapy can include colloidal and coal tar baths. Topical preparations containing menthol and phenol possess antipruritic qualities, as do topical anesthetics and antihistamines.24,31 Unfortunately, the risk of sensitization precludes widespread use. Papaverine, aspirin, and ibuprofen were also shown to be effective on oral administration in some cases.25 Sunlight and ultraviolet light treatments have worked.45 Both UVA and UVB treatment were found to reduce the extent of dermatitis.46 In severe cases PUVA therapy is effective, but its use is limited because of the risk of cancer.44*45 In a recent double-blind study, cyclosporine was also found to be effective in treating severe AD in adults.47 Deficiencies of o-6-fatty acid levels found in the epidermal phospholipids of some patients provoked attempts to treat atopics with borage oil and evening primrose seed oil. Unfortunately, there is no conclusive evidence that these modalities are effective.48*49
Aggravating Factors Emotions The extent to which emotional factors play a role in atopic dermatitis is unknown. Studies have shown increased incidences of hyperkinesis in children and of anxiety in adults with atopic dermatitis.50 Some believe these to be primary events. Others feel they are secondary to the discomfort and loss of sleep caused by atopic dermatitis. Situational stress aggravates and possibly elicits flares.27,so Relaxation techniques, such as biofeedback, help some patients. ZWitUntS
Mechanical irritants aggravate dry, itchy skin of atopic patients. Avoiding wool clothing, strong detergents, and household and industrial chemicals prevents itching.26,28 Cotton, linen, and suede are soft and nonirritating.
Sweating Sweating induces itching in patients with atopic dermatitis even more than in normal individuals. Wearing layered clothing helps keep sweating to a minimum. Unfortunately, the patient may need to limit physical exertion during flares. Suggesting swimming as a form of exercise provides a viable alternative.
Seasonal Variation Some patients have seasonal flares. In temperate climates, atopics do better in the summer and worse in the winter, when the air is dry. Hot, humid climates also provoke exacerbations as a result of the itching elicited by sweating. Some patients get worse in spring and summer; maybe inhalant allergens play a role.10*23 Marked improvement has been noted in some patients when they move to a different climate. It is obviously impossible to conclude that the climate change alone was responsible for the improvement.
Diet Certain foods elicit/exacerbate skin lesions in some patients with atopic dermatitis. In conflicting studies, the frequency of such a reaction has been shown to be 0 to 96%.32*51 Appearing early in life, in approximately 10 to 15% of atopics, these reactions are severe enough to be addressed in treatment. Patients who report a worsening of their symptoms following ingestion of a particular food and patients with severe disease that does not respond well to treatment are likely candidates.*l On the face the manifestations of food allergy can include pruritus, edema, and erythema of the perioral area, the lips, and the oral mucosa.51,52 In addition to skin symptoms, gastrointestinal and respiratory symptoms of vomiting, abdominal discomfort, diarrhea, and wheezing can also 0ccur.l Two types of mechanisms have been postulated: true allergic sensitization and “pseudoallergic” or idiosyncratic reactions. The allergic reactions are likely IgEmediated type 1 reactions51; however, immune complex and delayed-type reactions may also play a role.*l Nonimmunologic mechanisms may include enzymatic or metabolic release of histamine and other mediators. Eggs, milk, peanuts, and seafood can elicit reactions, as can spicy and sour foods. *l~~*Patients are usually allergic to one or two foods only.*l Positive skin and RAST tests are not pathognomonic for clinical sensitivity. As food plays a major role in the disease process of only a few patients, oligoantigenic diets should not be instituted routinely. In addition to hampering a normal lifestyle, they can lead to inadequate nutrition. Oral provocation tests are the only
Clinics in Dermatology 1993;12:235-242 effective way to determine if a food aggravates atopic dermatitis.*r They can be used if there is strong evidence against a certain food by history. Food sensitivity may decrease in time - an oral challenge test 1 year later may yield different results. 53 Pediatricians and allergists tend to use elimination diets in treatment of AD more often than dermatologists, perhaps because they see a different patient population. It is not clear if exclusive breastfeeding early in life and delayed introduction of certain foods reduce the severity or delay the onset of AD in infants with a heavy family Avoidance of cow’s milk, history of the disease. 2*,52*54~55 peanuts, fish, soy, wheat, chocolate, citrus fruits, peas, strawberries, and tomatoes has been suggested. If the mother is agreeable, exclusive breastfeeding for the first 6 months and avoidance of eggs, cow’s milk, and fish by the infant until 1 year of age and by the mother while she breastfeeds can be tried.2*,27*52,56
Prognosis Usually appearing in early childhood, atopic dermatitis waxes and wanes throughout the patient’s life. Severity, duration, and pattern of the disease are highly variable. Predicting the course of atopic dermatitis in an individual patient remains virtually impossible. The lesions typically appear around 3 to 4 months of age,24 get better and worse during childhood, and improve with age. Some patients remit by the late teens, but almost half continue to have symptoms throughout their adult lives. Conflicting longitudinal studies cite cure rates from 40 to 90%.* Variations in patient populations, diagnostic criteria, and degree of aggravating factors contribute to the confusion. Factors found to be associated with a worse prognosis include positive family history of atopic dermatitis, presence of asthma or hayfever, female sex, severe disease, onset before the age of two, and a “reversed pattern,” that is, involvement of the elbows, dorsal hands, and knees.17*22 Recently Guillet and Guillet also found that a child exhibiting definite food allergy was likely to have severe disease.38 In all cases, although atopic dermatitis is not necessarily limited to the face, facial lesions are significant and are sometimes the primary manifestation of the disease.
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3. Sulzberger MB. Historical notes on atopic dermatitis: Its names and nature. Semin Dermatol 1983;2:1-4. 4. Cookson W, Hopkin JM. Dominant Inheritance of atopic immunoglobulin-E responsiveness. Lancet 1988;1:86-8. 5. De Groot AC, Young E. The role of contact allergy to aeroallergens in atopic dermatitis. Contact Dermatitis 1989; 21:209-14. 6. Ewan PW, Champion RH, Parish WE. Atopic dermatitis and the house dust mite. Recent advances in dermatology. New York: Churchill Livingstone, 1992;9:95 - 118. 7. Beck HI, Korsgaard J. Atopic dermatitis and the house dust mite. Br J Dermatol 1989;120:245-251. 8. Ruiz-Maldonado R, Parish LC, Beare JM. Textbook of pediatric dermatology. Philadelphia: Gnme & Stratton, 1989: 587-600. 9. Kang K, Cooper KD, Vanderbark A. Immunoregulation in atopic dermatitis: T-lymphocyte subsets defined by monoclonal antibodies. Semin Dermatol. 1983;2:20-5. 10. Satayaviboon S, Ray MC. Applied immunodermatology. New York: Igaku Shoin, 1992:54-66. 11. Hanifin JM, Lobitz WC Jr. Newer concepts of atopic dermatitis. Arch Dermatol 1977;113:663. 12. Elliot ST, Hanifin JM. Delayed cutaneous hypersensitivity and lymphocyte transformation: dissociation in atopic dermatitis. Arch Dermatol 1979;115:36-9. 13. Hanifin JM. Phosphodiesterase and immune dysfunction in atopic dermatitis. J Dermatol Sci 1990;1:1- 6. 14. Hanifin JM. Pharmacological abnormalities in atopic dermatitis. Allergy 1989:44(suppl 9):41-6. 15. Brown MA, Hanifin JM. Atopic dermatitis. Curr Opin Immunol 1989-1990;2:531-4. 16. Kemmett D, Tidman MJ. The influence of the menstrual cycle and pregnancy on atopic dermatitis. Br J Dermatol 1991;125:59-61. 17. Muller GH, Kirk RW, Scott DW. Small animal dermatology, Philadelphia: WB Saunders, 1989;450 - 64. 18. Bevier DE. Long-term management of atopic disease in the dog. Vet Clin North Am Small Anim Pratt 1990; 20:1487- 1507. 19. Glukhensky BT, Grand0 SA. Immunodependent toses. Kiev: Sdorovja, 1990: 54- 118.
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31. Blaylock WK. Atopic dermatitis. Dermatol Immunol Allergy 1985;24:315-22. 32. Ruiz-Maldonado R, Parish LC, Beare JM. Textbook of peclatric dermatology. Philadelphia: Grune & Stratton, 1989: 164. 33. Svejgaard E. The role of microorganisms in atopic dermatitis. Semin Dermatol 1990;9:255-61. 34. Rystedt I, Strannegard IL, Strannegard 0. Infections as contributing factors to atopic dermatitis. J Allergy 1989; 44(suppl9):79-83. 35. Fivenson DE’, Breneman DL, Wander AH. Kaposi’s varicellifom eruption. Absence of ocular involvement. Arch Dermatol 1990;126:1037-9. 36. David TJ. Short stature in children with atopic eczema. Acta Derm Venereol (Stockh) 1989;144:41-4. 37. Froschl MJ, Land HG, Landthaler M. Seborrheic dermatitis and atopic eczema in human immunodeficienty virus infection. Semin Dermatol 1990;9:230-2. 38. Guillet G, Guillet MH. Natural history on sensitizations in atopic dermatitis. A 3-year follow-up in 250 children: Food allergy and high risk of respiratory symptoms. Arch Dermatol 1992;128:187-92. 39. Thiers BH. Topical steroids therapy of atopic skin diseases. Allergy Proc 1989;10:413-6. 40. Heddle RJ, Soothill JF, Bulpitt CJ. Combined oral and nasal beclomethasone dipropionate in children with atopic ec-
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42. Behrendt H, Ring J. Histamine, antihistamines and atopic eczema. Clin Exp Allergy, 1990:2O(suppl4):25-30. 43. Hanifin JM. Immunologic aspects of atopic dermatitis. Immunodermatology 1990;8:747-50. 44. Hanifin JM. The role of antihistamines in atopic dermatitis. J Allergy Clin Immunol 1990;86:666-9. 45. Hanifin JM. Recognizing and managing clinical problems in atopic dermatitis. Allergy Proc 1989;10:397-402. 46. Jekler J, Larko 0. UVA solarium vs. UVB phototherapy of atopic dermatitis: A paired-comparison study. Br J Dermato1 1991;125:569-72. 47. Sowden JM, Berth-Jones J, Ross JS, et al. Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis. Lancet 1991;338:13740. 48. Wright S, Burton J. Oral evening primrose oil improves atopic eczema. Lancet 1982;1:1120. 49. Bamford JT, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and gamma-linoleic acids). J Am Acad Dermatol 1985;13:959. 50. Cotteril JA. Psychophysiological Dermatol 1990;9:216-9.
aspects of eczema. Semin
51. Binkley KE. Role of food allergy in atopic dermatitis. Int J Dermatol 1992;31:611-4. 52. Rajka G. Dietary associations in atopic dermatitis. Semin Dermatol 1983;2:30-3. 53. Sampson HL, Scanlon SM. Natural history of food hypersensitivity in children with atopic dermatitis. J Pediatr 1989;115:23-7. 54. Broadbent JB, Sampson HA. Food hypersensitivity and atopic dermatitis. J Pediatr Clin North Am 1988;35: 115-30. 55. Businco L, Cantani A. Food allergy in children: Diagnosis and treatment with sodium chromoglycate. Allergol Immunopathol 1990;18:339-48. 56. Chandra RK, Puri S, Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants. Br Med J 1989;299:228-30.
A
topic dermatitis is a genetically determined cutaneous affliction characterized by redness, scaling, lichenification, and pruritus, affecting approximately 10% of the population.’ This allergic disorder is conceptually similar to asthma and allergic rhinitis. Other than a nonspecific spongiosis, there is no pathognomonic histopathology, nor are there diagnostic laboratory parameters for this disorder. A patient with atopic dermatitis demonstrates a constellation of clinical features, most prominent being increased irritability of the skin, intense pruritus, and chronic scratching leading to lichenification. Physiologic abnormalities include specific vasomotor alterations, increased susceptibility to viral, bacterial, and fungal infections, and abnormalities in humoral and cell-mediated immunity.
Historical Aspects Atopic dermatitis has carried a plethora of names through the ages. Its prevalence, difficulty encountered in describing characteristic symptoms of the disease, and lack of definable cause for the disorder have led to different theories about its etiology and have contributed to the diversity of nomenclature used to describe it. The term eczema or boiling over was first used by Aetius of Amida in the 6th century CE. In Materia Medica and Therapeutics Henry G. Piffard, the 19th century New York dermatologist, discussed eczema at length, dividing it into four main categories: acute or subacute in form, and acute or chronic in duration. He provided the reader with a whole dictionary of names to subdivide eczema depending on the appearance and location of the lesions. “Eczema is undoubtedly due,“ he writes, “to the blood From the Department of Medicine, Greater Baltimore Medical Center, Baltimore, Maryland. Address correspondence to Yelena M. Mirensky, MD, 7221Brook Falls Terrace, Baltimore, MD 22209.
0
1993 by Elseuier
Science Publishing Co., Inc.
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condition resulting from imperfect assimilation of the food and deficient oxidation of the protein compounds.” Keeping in step with the emphasis on the digestive process in vogue at the time, he assures the reader that a “carnivorous” diet and dry skin with decreased ability to sweat are some of the main causes. Consequently, in addition to a herbivorous diet, he recommends the use of Turkish baths, oral purgatives, diuretics, salicylic acid, tar, and arsenic to alleviate the symptoms. Speaking of eczema on the face in adult men, he urges that “it is necessary first of all to remove, by epilation, all the hairs that proceed from diseased follicles in order that remedial applications may penetrate them.” 2 In the 1880s and 1890s bacteria were proposed as the cause of eczema. During the same era, Louis Brocq and Louis Jaquet named a specific subset of lichen neurodermatitis. They felt this disorder was associated with a nervous personality.3 In 1932 positive wheal reactions to skin tests led Arthur Coca, Fred Wise (1881- 1950), and Marion Sulzberger (1895 - 1983) to use the term atopic dermatitis, now universally accepted for the disease.3 Their concepts of immunologic abnormalities continue to be believed by most investigators today.
Etiology Although the etiology of atopic dermatitis is unknown, defects in humoral and cell-mediated immunity play a major role in this genetically determined disorder. A positive family history of asthma, allergic rhinitis, or atopic dermatitis in over 75% of patients with atopic dermatitis has led to the concept of autosomal dominant mode of inheritance, but no specific HLA locus has been identified to date.* On the humoral level, elevated IgE levels, the most consistent defect, are present in 80% of the patients with
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atopic dermtitis, although the degree of elevation has not been shown always to correlate with the severity of the disease. IgE antibodies specific for housedust, housedust mite, and human dander are also found in some atopic patients, although their significance is unknown.5-7 Elevated IgE levels have been found in the majority of children with atopic dermatitis, and elevated IgG and IgE serum complement-fixing immune complexes are found in some.* In contrast to other allergic disorders, attempts at desensitization therapy have been unsuccessful in most patients with atopic dermatitis. Defects in cell-mediated immune responses are evidenced in elevated susceptibility of atopics to cutaneous bacterial, viral, and fungal infections such as vaccinia, molluscum contagiosum, verruca vulgaris, and Staphylococcus aureus. Incidence, severity, and length of these infections are all greater in atopic individuals than in the rest of the population. In addition, decreased numbers of suppressor T-lymphocyte cells,9 depressed monocyte and neutrophil chemotaxis, decreased hypersensitivity skin test reactivity to dinitrochlorobenzene and Candida albicans,10-12 and decreased CAMP levels have all been documented in atopic patients.13J4 Subsequent development of atopic dermtitis in persons receiving bone marrow transplants from donors with the disorder further confirms the hematopoietic cell dysfunction hypothesis.15 Numerous studies showing premenstrual flaring of atopic dermatitis suggest that sex hormones may also play a role, although the exact mechanism is, once again, unknown.16 Atopic dermatitis is also common in dogs. Affected dogs develop immediate-type hypersensitivity reactions to inhaled antigens, such as pollens, wool, housedust, feathers, molds, and trees. Severe pruritus leads to biting, scratching, and excoriations. In young dogs the pruritic episodes appear to be seasonal; they become continuous as the animal ages. Interestingly, asthma has not been reported in atopic dogs. In addition, in contrast to humans, desensitization therapy is a highly effective form of treatment in canines, suggesting a different etiology.“J8 In Eastern Europe present-day theories as to the etiology of atopic dermatitis are often divergent from those found in Western Europe and the Americas. For example, in Russia, psychiatric factors and defective enzyme production in the liver are considered primary causes, in addition to those accepted in the West, and HLA phenotype D7 is said to be linked to atopic dermatitis.19 Although the etiology of atopic dermatitis remains unknown, a hereditary immune deficiency is undoubtedly at the core.
Table 1. Facial Signs Associated 1. 2. 3. 4. 5. 6. 7. 8. 9.
With Atopic Dermatitis
Blepharitis Dennie-Morgan fold (infraorbital fold) Erythema “Furrowed mouth syndrome” (cheilitis) Lichenification Pallor Postauricular fissures “Raccoon face” (darkening of the periorbital spaces) Scaling
Epidemiology There is no dissension among experts in the field that atopic dermatitis is a common disease. But just how common is it? Reported prevalence rates in children vary from 3% cited in one clinical study’ to 24% in another.*O Differences in diagnostic criteria cited by different investigators partially account for such a wide range. Most workers agree that close to 10% of the population is affected,’ with an increased prevalence in the last 20 year.*l*** The disease has been reported to be more common in whites,23 but in my experience (in the Philadelphia area) both white and black patients are seen equally frequently. Possibly, city dwellers are affected more often,’ or they may be more likely to seek medical care.
Clinical Manifestations Extreme pruritus, a chronic waxing and waning course, and a typical age-dependent distribution are the hallmarks of atopic dermatitis. 24Unable to control the urge to scratch, atopics excoriate the skin, irritating it, and thereby causing more itching. They scratch most forcefully at night, when conscious control is diminished. The presence of a primary lesion in atopic dermatitis remains a topic of debate. Is pruritus the primary event, with the lesions resulting from the irritation caused by scratching?25,26 Do erythematous lesions on the skin appear first and pruritus follows? *’ Whether it is the itch that rashes or the rash that itches, extreme pruritus causes much suffering for patients with atopic dermatitis. Lack of sleep can aggravate constant discomfort. Unceasing scratching and chronic lesions on socially important body areas, especially the face, contribute to social ostracism. Not covered by clothing, the “red face” of a patient with atopic dermatitis is perhaps the most readily observed clinical feature (Table 1). Manifestations of the disease vary with age as well with the individual patient. Although classic patterns exist, many patients present with atypical features. Generally, in the infant phase (3 4 months to 2 years), x the face is involved in addition to
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the extensor surfaces of the limbs, the trunk, and the diaper area.8 Pruritic erythema on the cheeks evolves into papules, vesicles, and erosions. These progress to weeping crusty lesions that can cover the forehead, chin, periauricular area, and the scalp.27,28 Hyperkeratosis of the scalp in atopic dermatitis can look similar to the “cradle cap” of seborrheic dermatitis. The nose is frequently spared.?’ In the childhood (3 - 12 years) phase, the lesions migrate to involve the popliteal fossae and the antecubital areas, the feet, and the hands.28 Perifollicular accentuation is common in dark-skinned patients.26 Facial involvement can be extensive. Pruritic, dry, scaly, erythematous lesions can appear on the eyelids, on the lateral posterior neck, and around the mouth.27,28 Constant rubbing and licking of the perioral area leads to lip cheilitis, severe enough to be called the “furrowed mouth syndrome.” Rubbing the eyelids causes swelling and constant tearing. Blepharitis, vernal conjunctivitis, and, in severe cases, cornea1 irritation and abrasion can result.27 Periorbital darkening, the “raccoon face,” is typical. Horizontal anterior neck folds are common, and the Dennie Morgan infraorbital fold is present in 70% of the cases.8 Dry skin and lichenification often represent atopic dermatitis in adults. The face is once again the primary target (Fig 1). Flexural areas, hands, feet, and nipples can also be involved. Manifestations are similar to those seen in the juvenile phase. In some, erythema and scaling are not limited to the face, but can include the neck and the shoulders.29 Others show marked facial pallor.27 Although always present in atopics, white dermographism is not specific for this disorder.*O The skin of patients with psoriasis or mycosis fungoides also turns white on stroking. In 70% of patients, iontophoresis causes a delayed blanch response, whereas the application of nicotinic acid produces no response or blanching in contrast to the normal erythema.27
Diagnosis There are no pathognomonic histologic or laboratory findings in atopic dermatitis. This clinical diagnosis is based on a characteristic constellation of clinical features. Nearly all patients present with at least three of the major manifestations and some of the minor nonspecific manifestations listed in Table 2. Distribution, morphology, and severity vary greatly from patient to patient. Moreover, on the same individual, the disease may look very differently over time. The nonspecific histopathologic findings include spongiosis and lichenification. In acute dermatitis intercellular and intracellular edema may be present. A mononuclear infiltrate is seen in the spongiotic
epidermis. More chronic lesions show epidermal hyperplasia and parakeratosis. Helper T lymphocytes predominate in the dermal infiltrate. Increased numbers of Langerhans cells can be seen in the chronic lichenified lesions, but not in the unaffected skin.30 Similar findings are seen in contact, nummular, and dishydrotic dermatitides. Although there are no pathognomonic laboratory tests, eosinophilia in the peripheral smear and elevated IgE levels support the diagnosis of atopic dermatitis (AD).
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1993;21:235-242 Table 2. Diagnostic Criteria for Atopic Dermatitis Major -1. 2. 3. 4.
Minor 1. 2. 3. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Criteria Chronically relapsing course History of atopy (asthma, allergic rhinitis, or atopic dermatitis) PlUlituS
Typical distribution Facial and extensor involvement in infancy and early childhood Flexural lichenification in older children and adults Criteria Cheilitis Cradle cap (dermatitis of the scalp in infancy) Delayed blanch response Hand/foot dermatitis Ichthyosis vulgaris Immediate skin test reactivity Itching when sweating Perifollicular accentuation Keratosis pilaris Seasonal variation Susceptibility to cutaneous infections (particularly Staphylococcus aureus and herpes simplex) White dermographism Wool intolerance Xerosis
Adapted, with permission,from Hanifin.’
Experimentally, decreased CAMP levels and decreased numbers of killer T cells have been found in patients with AD.9,13J4 Increased norepinephrine and acetyl choline levels in the skin and blood vessels have also been documented. In the future, these findings may prove useful in routine diagnosis and provide clues as to the etiology of the disease. Differential
Diagnosis
Other causes of the red face may be similar in appearance to that seen in atopic dermatitis (Table 3). In infancy, atopic dermatitis mimics seborrheic dermatitis. The latter, however, is usually more greasy and less pruritic. Typically appearing before 2 months of age, seborrheic dermatitis may be confined to the head.‘,lO Early or partially treated psoriasis can look like atopic dermatitis. Silvery scales come off on scratching the psoriatic lesions. Even exposure to cold, windy air can result in red, scaly skin on the face.26 Primary irritant contact dermatitis is also a possibility, especially in women who use many commercial preparations on their face.‘O In teenagers and adults, nummular dermatitis needs to be considered. The coinshaped papulovesicular lesions of this idiopathic disorder, however, more commonly affect the lower limbs.8 Rare diseases similar in appearance to atopic dermatitis include Wiskott -Aldrich syndrome, Leiner’s disease, X-linked agammaglobulinemia,lo and hyper-IgE syndrome.’ Wiskott - Aldrich syndrome is an X-linked reces-
sive disorder. When the family history is unknown, the presence of thrombocytopenic purpura and recurrent infections differentiate this disease. Leiner’s disease, a generalized inflammatory dermatitis, associated with abnormal complement activity and lowered neutrophilic chemotaxis, often begins on the face. It is rarely seen in infants past 3 months of age. This disorder progresses to a generalized erythroderma that resolves within 2 weeks.32 Patients with X-linked agammaglobulinemia are easily differentiated by the absence of IgE. The papular, mildly erythematous eruption seen on the face of patients suffering from the hyper-IgE syndrome resembles atopic dermatitis. Deep staphylococcal infections and extremely elevated IgE levels easily distinguish this disorder. Associated
Disorders
Disorders associated with atopic dermatitis include pityriasis alba, keratosis pilaris, and ichthyosis vulgaris. There is an increased incidence of fungal, bacterial, and viral infections, anterior subcapsular cataracts, atopic rhinitis, and asthma. In addition, vitiligo and alopecia areata may be more common in atopic patients.** Pityriasis alba is especially prevalent in dark-skinned children with atopic dermatitis.27J8 In addition to the face, asymptomatic patches of erythema, fine scaling, and subsequent hypopigmentation with indistinct borders can appear on the upper arms. Fortunately, this loss of pigment is not permanent.26 Keratosis pilaris, often extensive in atopics, should not be confused with pustular acne or miliaria rubra. In addition to being found on the face, the uniformly small (l2 mm) follicular papules and pustules also commonly affect the upper arms and the thighs. Fifty percent of patients with ichthyosis vulgaris also have features of atopic dermatitis. Most believe this to be a genetic association. Because their skin is so dermatitic, atopics show greater incidence and severity of microbacterial infections. Staphylococcus aureus is a common colonizer of atopic skin, frequently leading to impetigo.28 Flares of atopic dermatiTable 3. Differential Diagnosis of Atopic Dermatitis (Limited to the Face) 1. 2. 3. 4. 5. 6. 7. 8. 9.
Contact dermatitis Nummular dermatitis Hyper-IgE syndrome Liener’s disease Psoriasis Seborrheic dermatitis Windburn Wiskott-Aldrich syndrome X-linked agammaglobulinemia
Clinics in Dermatology 2993;12:235-242 tis are often associated with bacterial infections,33 and improvement has been noted with decreased S. aureus colonization.Z Whether S. aureus has a direct inflammatory effect on the skin is still unclear.25,34 Viral infections common and more severe in atopics include herpes simplex, vaccinia, molluscum contagiosum, and varicella.34,35 These have also been shown to elicit exacerbations of atopic dermatitis. Atopics also show increased antibody titers to Epstein-Barr virus and an increased incidence of upper respiratory infections3’ Interestingly, they often improve following a measles infection. The reason for this phenomenon is unclear.25 Pityrosporon male is also more common in young adults with head-neck-shoulder dermatitis. Possibly, it elicits an allergic reaction, thereby intensifying symptoms of atopic dermatitis. 29 Trichophyton rubrum infections are seen more frequently in atopics than in the general populations.29 Tinea corporis superinfection should be considered when patches of atopic dermatitis are particularly resistant to treatment. Chronic application of topical steroids promotes growth of fungal spores. This “tinea incognito” syndrome needs to be treated with antifungal agents. Alopecia areata and vitiligo are also thought to occur more often in patients with AD,*’ perhaps because this group of patients is likely to seek medical attention. Anterior subcapsular cataracts are present in 16% of atopics.*’ Posterior cataracts are also more common, but these are possibly due to long-term steroid therapy.26*38 Short stature has been noted in over 20% of children with severe atopic dermatitis. Possible etiologic factors include the disease itself, chronic steroid therapy, loss of sleep, and malnutrition brought on by avoidance of many foods.36 Although seborrheic dermatitis is well known to be a common feature of the acquired immune deficiency syndrome (AIDS), the incidence of atopic dermatitis in adult AIDS patients has not yet been determined. Fifty percent of children with AIDS have atopic dermatitis.37 Children with atopic dermatitis are at an increased risk for other atopic disorders. Over half of the children with severe atopic dermatitis developed asthma in one study.38 Present in over 70% of the patients, a family history of atopic disorders, including asthma and allergic rhinitis, is one of the main criteria for diagnosing the disease.
Treatment In treating atopic dermatitis, the most important and perhaps most difficult task is interrupting the itch/scratch cycle. The aim is to treat the damaged skin and control infection, if present, as soon as possible. The ideal regimen for treatment includes an extensive list of instruc-
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tions aimed at treating the inflammation and the infection, alleviating aggravating factors, and hydrating the skin. It involves all aspects of the patient’s life. When compliance is in question, however, the best approach is to make the patient aware of the few most important steps to alleviation of the symptoms.
Steroids Fluorinated and chlorinated topical steroids decrease inflammation, moisturize, and alleviate the itch39; however, steroids with atrophogenic properties should be used judiciously on the face. Highly potent preparations are best reserved for short-term treatment of acute exacerbations. In severe flares oral steroids may be indicated. Oral beclamethasone dipropionate may become a useful oral agent in the future. Metabolized more rapidly than prednisone, it has very few systemic side effects.‘O
Moisturizing Because xerosis is so significant in atopic dermatitis, conflicting concepts of moisturizing have developed. As washing dries the skin, the Scholtz regimen prohibits bathing altogether, with a lipid cleanser being used in its place. 41 In a culture that calls for daily showers, however, compliance with such a regimen is unlikely. A viable alternative is taking cool, short showers, no longer than 3 minutes. In an attempt to alleviate the incessant itching, atopics often take very hot showers. The hot water further dries the skin.26 Cold water has an antipruritic effect without overdrying. Soap should be used only in the pubic and axillary areas, the hands and the face. A lipidfree cleansing lotion can be used everywhere else. Simple emollients should be applied daily. Moisturizing immediately following a shower (within 3 minutes) maintains the stratum corneum hydration before evaporation takes place.30 Choice of moisturizer depends on severity of the xerosis and patient preference. Treatment is particularly important in the winter, when dry air further aggravates the xerosis. Using a humidifier in the bedroom helps by increasing humidity.
Antimicrobials Antimicrobials are routinely used to control staphylococcal infection. Interestingly, they are sometimes helpful even when no overt infection can be seen. Choice of the antimicrobial is best determined using a sensitivity profile of the pathogen. Erythromycin and cephalosporins are often appropriate.
Antihistamines Because of their sedating properties, conventional antihistamines cannot be used extensively in treating atopic
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dermatitis as high doses are needed to achieve an antipruritic effect. Because the mechanism of their antipruritic qualities remains unknown, a wide variety of antihistamines have been used. Hydroxacine is effective when administered at bedtime, allowing for uninterrupted sleep. Recently, the nonsedating third-generation Hl antagonists promise to be helpfu1.42-4 In addition to inhibiting histamine release, these agents inhibit mediator release and interfere with eosinophil migration.43
Other Treatments Adjunct therapy can include colloidal and coal tar baths. Topical preparations containing menthol and phenol possess antipruritic qualities, as do topical anesthetics and antihistamines.24,31 Unfortunately, the risk of sensitization precludes widespread use. Papaverine, aspirin, and ibuprofen were also shown to be effective on oral administration in some cases.25 Sunlight and ultraviolet light treatments have worked.45 Both UVA and UVB treatment were found to reduce the extent of dermatitis.46 In severe cases PUVA therapy is effective, but its use is limited because of the risk of cancer.44*45 In a recent double-blind study, cyclosporine was also found to be effective in treating severe AD in adults.47 Deficiencies of o-6-fatty acid levels found in the epidermal phospholipids of some patients provoked attempts to treat atopics with borage oil and evening primrose seed oil. Unfortunately, there is no conclusive evidence that these modalities are effective.48*49
Aggravating Factors Emotions The extent to which emotional factors play a role in atopic dermatitis is unknown. Studies have shown increased incidences of hyperkinesis in children and of anxiety in adults with atopic dermatitis.50 Some believe these to be primary events. Others feel they are secondary to the discomfort and loss of sleep caused by atopic dermatitis. Situational stress aggravates and possibly elicits flares.27,so Relaxation techniques, such as biofeedback, help some patients. ZWitUntS
Mechanical irritants aggravate dry, itchy skin of atopic patients. Avoiding wool clothing, strong detergents, and household and industrial chemicals prevents itching.26,28 Cotton, linen, and suede are soft and nonirritating.
Sweating Sweating induces itching in patients with atopic dermatitis even more than in normal individuals. Wearing layered clothing helps keep sweating to a minimum. Unfortunately, the patient may need to limit physical exertion during flares. Suggesting swimming as a form of exercise provides a viable alternative.
Seasonal Variation Some patients have seasonal flares. In temperate climates, atopics do better in the summer and worse in the winter, when the air is dry. Hot, humid climates also provoke exacerbations as a result of the itching elicited by sweating. Some patients get worse in spring and summer; maybe inhalant allergens play a role.10*23 Marked improvement has been noted in some patients when they move to a different climate. It is obviously impossible to conclude that the climate change alone was responsible for the improvement.
Diet Certain foods elicit/exacerbate skin lesions in some patients with atopic dermatitis. In conflicting studies, the frequency of such a reaction has been shown to be 0 to 96%.32*51 Appearing early in life, in approximately 10 to 15% of atopics, these reactions are severe enough to be addressed in treatment. Patients who report a worsening of their symptoms following ingestion of a particular food and patients with severe disease that does not respond well to treatment are likely candidates.*l On the face the manifestations of food allergy can include pruritus, edema, and erythema of the perioral area, the lips, and the oral mucosa.51,52 In addition to skin symptoms, gastrointestinal and respiratory symptoms of vomiting, abdominal discomfort, diarrhea, and wheezing can also 0ccur.l Two types of mechanisms have been postulated: true allergic sensitization and “pseudoallergic” or idiosyncratic reactions. The allergic reactions are likely IgEmediated type 1 reactions51; however, immune complex and delayed-type reactions may also play a role.*l Nonimmunologic mechanisms may include enzymatic or metabolic release of histamine and other mediators. Eggs, milk, peanuts, and seafood can elicit reactions, as can spicy and sour foods. *l~~*Patients are usually allergic to one or two foods only.*l Positive skin and RAST tests are not pathognomonic for clinical sensitivity. As food plays a major role in the disease process of only a few patients, oligoantigenic diets should not be instituted routinely. In addition to hampering a normal lifestyle, they can lead to inadequate nutrition. Oral provocation tests are the only
Clinics in Dermatology 1993;12:235-242 effective way to determine if a food aggravates atopic dermatitis.*r They can be used if there is strong evidence against a certain food by history. Food sensitivity may decrease in time - an oral challenge test 1 year later may yield different results. 53 Pediatricians and allergists tend to use elimination diets in treatment of AD more often than dermatologists, perhaps because they see a different patient population. It is not clear if exclusive breastfeeding early in life and delayed introduction of certain foods reduce the severity or delay the onset of AD in infants with a heavy family Avoidance of cow’s milk, history of the disease. 2*,52*54~55 peanuts, fish, soy, wheat, chocolate, citrus fruits, peas, strawberries, and tomatoes has been suggested. If the mother is agreeable, exclusive breastfeeding for the first 6 months and avoidance of eggs, cow’s milk, and fish by the infant until 1 year of age and by the mother while she breastfeeds can be tried.2*,27*52,56
Prognosis Usually appearing in early childhood, atopic dermatitis waxes and wanes throughout the patient’s life. Severity, duration, and pattern of the disease are highly variable. Predicting the course of atopic dermatitis in an individual patient remains virtually impossible. The lesions typically appear around 3 to 4 months of age,24 get better and worse during childhood, and improve with age. Some patients remit by the late teens, but almost half continue to have symptoms throughout their adult lives. Conflicting longitudinal studies cite cure rates from 40 to 90%.* Variations in patient populations, diagnostic criteria, and degree of aggravating factors contribute to the confusion. Factors found to be associated with a worse prognosis include positive family history of atopic dermatitis, presence of asthma or hayfever, female sex, severe disease, onset before the age of two, and a “reversed pattern,” that is, involvement of the elbows, dorsal hands, and knees.17*22 Recently Guillet and Guillet also found that a child exhibiting definite food allergy was likely to have severe disease.38 In all cases, although atopic dermatitis is not necessarily limited to the face, facial lesions are significant and are sometimes the primary manifestation of the disease.
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3. Sulzberger MB. Historical notes on atopic dermatitis: Its names and nature. Semin Dermatol 1983;2:1-4. 4. Cookson W, Hopkin JM. Dominant Inheritance of atopic immunoglobulin-E responsiveness. Lancet 1988;1:86-8. 5. De Groot AC, Young E. The role of contact allergy to aeroallergens in atopic dermatitis. Contact Dermatitis 1989; 21:209-14. 6. Ewan PW, Champion RH, Parish WE. Atopic dermatitis and the house dust mite. Recent advances in dermatology. New York: Churchill Livingstone, 1992;9:95 - 118. 7. Beck HI, Korsgaard J. Atopic dermatitis and the house dust mite. Br J Dermatol 1989;120:245-251. 8. Ruiz-Maldonado R, Parish LC, Beare JM. Textbook of pediatric dermatology. Philadelphia: Gnme & Stratton, 1989: 587-600. 9. Kang K, Cooper KD, Vanderbark A. Immunoregulation in atopic dermatitis: T-lymphocyte subsets defined by monoclonal antibodies. Semin Dermatol. 1983;2:20-5. 10. Satayaviboon S, Ray MC. Applied immunodermatology. New York: Igaku Shoin, 1992:54-66. 11. Hanifin JM, Lobitz WC Jr. Newer concepts of atopic dermatitis. Arch Dermatol 1977;113:663. 12. Elliot ST, Hanifin JM. Delayed cutaneous hypersensitivity and lymphocyte transformation: dissociation in atopic dermatitis. Arch Dermatol 1979;115:36-9. 13. Hanifin JM. Phosphodiesterase and immune dysfunction in atopic dermatitis. J Dermatol Sci 1990;1:1- 6. 14. Hanifin JM. Pharmacological abnormalities in atopic dermatitis. Allergy 1989:44(suppl 9):41-6. 15. Brown MA, Hanifin JM. Atopic dermatitis. Curr Opin Immunol 1989-1990;2:531-4. 16. Kemmett D, Tidman MJ. The influence of the menstrual cycle and pregnancy on atopic dermatitis. Br J Dermatol 1991;125:59-61. 17. Muller GH, Kirk RW, Scott DW. Small animal dermatology, Philadelphia: WB Saunders, 1989;450 - 64. 18. Bevier DE. Long-term management of atopic disease in the dog. Vet Clin North Am Small Anim Pratt 1990; 20:1487- 1507. 19. Glukhensky BT, Grand0 SA. Immunodependent toses. Kiev: Sdorovja, 1990: 54- 118.
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