Case Files Pediatrics, (LANGE Case Files) 4th Ed.

CASE 44

A mother brings her 11-month-old daughter to the clinic because of a persistent facial rash. The child is restless at night and scratches in her sleep. She is otherwise healthy. Physical examination reveals a well-nourished, healthy-appearing white female with dry, red, scaly areas on the cheeks, chin, and around the mouth as well as on the extensor surfaces of her extremities. The areas on the cheeks have a plaque-like, weepy appearance. The diaper area is spared. The remainder of the child’s examination is normal.

Image What is the most likely diagnosis?

Image What is the most appropriate next step in the evaluation?

Image What is the best management for this condition?

ANSWERS TO CASE 44: Atopic Dermatitis

Summary: An 11-month-old female infant has dry, red, scaly areas on the extensor surfaces of her skin and on the cheeks, chin, and around the mouth, with sparing of the diaper area.

• Most likely diagnosis: Atopic dermatitis.

• Next step in evaluation: Further history to determine rash duration and exacerbating factors, and family history for atopic dermatitis, allergic rhinitis, and asthma.

• Best management: Topical corticosteroids, frequent use of emollients, and control pruritus.

ANALYSIS

Objectives

1. Describe incidence, etiology, and risk factors for atopic dermatitis.

2. Discuss diagnostic criteria and differential diagnoses for atopic dermatitis.

3. Describe treatment and follow-up of atopic dermatitis.

4. Be familiar with other conditions associated with atopic dermatitis.

Considerations

A new rash in an infant can reflect a viral infection, as many viruses have skin manifestations. However, the lack of associated symptomatology such as fever makes infection unlikely. This child’s history and examination, however, are consistent with atopic dermatitis. Further history may reveal additional risk factors for allergic disease. Treatment involves avoiding aggravating factors and ensuring intensive skin hydration.

APPROACH TO:

Atopic Dermatitis

DEFINITIONS

ATOPIC DERMATITIS (AD):A patch or plaque of erythematous skin with intense pruritus; the most common eczematous eruption in childhood.

CONTACT DERMATITIS: An adverse reaction of the skin to an outside agent. Includes primary irritant dermatitis (eg, irritant diaper rash) and allergic contact dermatitis (eg, poison ivy, nickel allergy).

ECZEMA: General term for a skin condition consisting of acutely inflamed papules and plaques, frequently associated with serous discharge and pruritus. Eczematous eruptions include atopic dermatitis, seborrheic dermatitis, and contact dermatitis.

EMOLLIENT: Cream or lotion that restores water and lipids to the epidermis; those containing urea or lactic acid are more lubricating and may be more effective; creams lubricate better than lotions.

FLEXURAL AREAS: Areas of repeated flexion and extension, which often perspire on exertion (antecubital fossae, neck, wrists, ankles).

LICHENIFICATION: Epidermal thickening, with normal skin lines resembling a washboard.

SEBORRHEIC DERMATITIS: Self-limited scaly, erythematous, and/or crusty eruption limited to areas of the skin with a high concentration of sebaceous glands (eg, cradle cap).

CLINICAL APPROACH

Atopic dermatitis (eczema) typically is pruritic, recurrent, and flexural in older children and symmetrical in adults. The term atopy was coined to describe a group of patients who had a personal or family history of “hay fever,” asthma, dry skin, and eczema. More than 15 million American adults and children have atopic dermatitis. The highest incidence is seen among children, and the lifetime prevalence of atopic dermatitis is 20% in children aged 3 to 11 years. Sixty-five percent of patients develop symptoms in the first year of life and 90% before the age of 5 years. The etiology is unknown, but is thought to be related to immune factors. Seventy percent of atopic patients have a family history of asthma, “hay fever,” or eczema.

The cause of AD is thought to be multifactorial, involving genetic abnormalities of the epidermal barrier, immune function, environmental exposures, and infection. Recent studies have linked an abnormal epidermal barrier to mutations in the filaggrin (FLG) gene. Initial studies linked loss-of-function mutations of the FLG gene to ichthyosis vulgaris; more recent research, based on the known association of ichthyosis vulgaris with AD, led to evidence suggesting these same mutations are important risk factors for AD. Abnormal epidermal barrier function results in increased transepidermal fluid losses, leading to the ubiquitous finding of dry skin in AD patients. The abnormal epidermis also allows easier entrance of allergens and bacteria, stimulating an immune reaction.

Atopic dermatitis occurs in three phases: infant (birth to 2 years), childhood (2 to 12 years), and adult (>12 years). Infants are rarely born with atopic dermatitis, but typically develop the first signs of inflammation during the third month of life. A common scenario is a baby who, during winter months, develops dry, red, scaling cheeks without perioral and paranasal involvement. The chin is often involved; the diaper area is usually spared. The infant is uncomfortable because of intense pruritus and is often restless during sleep. Atopic dermatitis resolves in approximately 50% of infants by the age of 18 months. The most common finding in the childhood phase is inflammation in flexural areas. Perspiration stimulates burning and itching, initiating an itch–scratch cycle. Initial papules rapidly coalesce into plaques that ultimately become lichenified when scratched. The exudative lesions typical of the infant phase are not common in the childhood phase. The adult phase begins near the onset of puberty. The reason for the resurgence of inflammation may be related to hormonal changes. Adult phase disease includes flexural inflammation, often accompanied by hand dermatitis, inflammation around the eyes, and lichenification of the anogenital area. White dermographism may be seen, demonstrated by stroking the skin of a patient with AD; after the initial red line develops, a white line replaces it without wheal. Other findings include keratosis pilaris, accentuated palmar creases, small fissures at the base of the earlobe, and Dennie-Morgan creases under the lower eyelid.

Two misconceptions about atopic dermatitis are common. The first is that eczema is an emotional disorder. Patients with skin inflammation lasting for months or years are often irritable, a normal response to a frustrating disorder. The second misconception is that atopic skin disease is precipitated by an allergic reaction. Atopic individuals frequently have respiratory allergies and, when skin tested, are informed that they are “allergic to everything.” Individuals with atopy may react with a wheal when challenged with a needle during skin testing, but this is a characteristic of atopic skin and is not necessarily an allergic response. Evidence to date indicates that most cases of atopic dermatitis are precipitated by environmental stress on genetically compromised skin and not by interaction with allergens.

Patient Evaluation

Evaluation of the child with atopic dermatitis involves ruling out other potential causes of the child’s rash through a complete personal history (Table 44-1), family history, and physical examination to obtain a proper diagnosis and initiate treatment. Skin is evaluated for locations and nature of affected areas (patches, weepiness, lichenification), extent of skin dryness, and warmth or tenderness (possible secondary infection). Eyes, nose, throat, and chest are examined for evidence of allergic rhinitis or asthma (watery eyes, dark circles under eyes, runny nose, wheezing).

Image

Table 44-1 • QUESTIONS TO ASK WHEN INVESTIGATING RASHES

Laboratory studies are not particularly helpful in diagnosing atopic dermatitis. A serum immunoglobulin E (IgE) level is often elevated. Culture of the skin is performed if superinfection is suspected.

The differential diagnosis includes seborrheic dermatitis (cradle cap), which usually begins on the scalp in the first few months of life and may involve the ears, nose, eyebrows, and eyelids. The greasy brown scales of seborrheic dermatitis are in contrast to the erythematous, weeping, crusted lesions of infantile atopic dermatitis. Other considerations include scabies, irritant dermatitis (perioral fruit juice dermatitis), allergic contact dermatitis (poison ivy), and eczematoid dermatitis (infectious lesion near a draining ear). Rare conditions might include ichthyosis, severe combined immune deficiency (SCID), Wiskott-Aldrich, zinc deficiency, drug reactions, and Letterer-Siwe disease.

Treatment

Treatment goals include preserving and restoring the skin barrier by using emollients, eliminating inflammation and infection with medications, reducing scratching through antipruritic use, and controlling exacerbating factors. Some recommend limiting bathing to brief baths or showers of moderate temperature with mild and preferably nonsoap cleansers (Cetaphil). Drying soaps (Ivory) are avoided. Lubricants (Eucerin) are applied immediately after bathing and air- or pat-drying. Some products contain urea (Nutraplus) or lactic acid (Lac-Hydrin); they have special hydrating qualities and may be more effective than other moisturizers. Lotions and creams may sting shortly after application due to bases or specific ingredients, such as lactic acid. If itching and stinging continue with each application, another product should be selected.

Topical corticosteroids used to control inflammation vary in potency; percentage is not an indication of potency. Lower-potency preparations (glucocorticoid groups VI and VII) can be used for longer periods to treat chronic symptoms involving the trunk and extremities. Lower-potency steroids are generally used for infants and can be added to moisturizers to cover large areas of affected skin. The lower-dose steroids have no associated adverse endocrinological side effects. Fluticasone propionate (Cutivate) is the only Food and Drug Administration (FDA)-approved topical corticosteroid cream for infants as young as 3 months. Fluorinated corticosteroids are generally avoided on the face, genitalia, and the intertriginous area because they may depigment and thin the skin. Higher-potency steroids (glucocorticoid groups I and II) are used only for short periods and on lichenified areas; the face and skin folds are avoided. Ointment preparations are generally preferable because they result in better penetration of the corticosteroid, thus reducing the incidence of irritant and hypersensitivity reactions. Application is usually once to twice daily, dependent upon the preparation used. The lowest effective potency steroid preparation should be used. Lubrication often is continued after corticosteroids are discontinued.

Tacrolimus (Protopic) and pimecrolimus (Elidel) are nonsteroidal, immunomodulator topicals for treatment of atopic dermatitis. Tacrolimus 0.03% and pimecrolimus 1% are approved for use in children 2 years and older. These agents are recommended for short-term and long-term intermittent therapy, on a twice-daily basis, in patients not adequately responsive to, or intolerant of, conventional therapy. Neither is FDA approved for children less than 2 years of age, and both carry FDA “Black Box” warnings concerning their possible association with malignancies when used for extended periods of time. Their exact role for use in children is under investigation; consultation with a pediatric dermatologist may be indicated.

Oral antihistamines are used to reduce itching. Because symptoms of atopic dermatitis are often worse at night, sedating oral antihistamines (hydroxyzine, diphenhydramine) may offer an advantage over nonsedating agents. Less-sedating agents include loratadine (Claritin) and cetirizine (Zyrtec). Doxepin (Sinequan) has tricyclic antidepressant and antihistamine effects and may be useful in some cases. Topical antihistamines (Caladryl) are avoided because of the potential for skin irritation or toxicity due to absorption. Fingernails should be cut short to prevent further skin damage through scratching.

Patients with secondary bacterial infections (Staphylococcusor Streptococcus sp) often require antibiotic therapy. Topical antibiotic therapy with mupirocin (Bactroban) may be used for limited areas of infection or in the nose to reduce chronic Staphylococcus aureus carriage. Oral antibiotics are indicated for more extensive areas of infection. First-generation cephalosporins, erythromycin, penicillinase-resistant penicillins, or clindamycin are chosen based on local susceptibility patterns. Patients with evidence of superinfection with herpes simplex virus require oral or intravenous acyclovir.

The role of food allergies in the management of atopic dermatitis is controversial. Dietary manipulation in a child (usually less than about 3 years of age) with a strong history of exacerbation of symptoms upon exposure to a particular food may be helpful. A 4- to 6-week trial excluding eggs and milk in children, followed by a rechallenge, may be justified, especially in a child who does not respond to first-line treatment.

Consultation with a pediatric dermatologist may be warranted for patients with an unclear diagnosis, who fail to respond to treatment, or who have extensive skin involvement. Consultation also may be appropriate for patients with ocular or serious infectious complications and for patients requiring oral steroid therapy.

Other skin eruptions can be confused with atopic dermatitis. Contact dermatitis is the reaction of skin to an outside agent. This category of eczematous eruptions includes both primary irritant contact dermatitis and allergic contact dermatitis. Primary irritant dermatitis can be caused by harsh detergents and soaps, bubble baths, saliva, urine, and feces. Examples of primary irritant contact dermatitis in the pediatric population include diaper dermatitis, lip-licker’s dermatitis, and shin guard dermatitis seen in soccer and hockey players. Allergic contact dermatitis is a delayed T-cell hypersensitivity reaction (type IV) that occurs 7 to 14 days after initial exposure, and 1 to 4 days after subsequent exposures. The most common cause is exposure to plants of the genus Toxicodendron (formerly called Rhus) that includes poison oak, ivy, and sumac. Also common in the pediatric population is nickel allergy, causing irritation below the umbilicus where the inside of nickel-containing pant snaps rub and irritation of the earlobes in patients wearing nickel-containing earrings. Allergic contact dermatitis can also trigger an “id” reaction of widespread pruritic papules in nonexposed areas.

COMPREHENSION QUESTIONS

44.1 A mother brings her 2-week-old son to the clinic for a well-baby visit. Her only concern is a rash on his face and scalp that began a week earlier. Examination reveals a healthy white male with normal vital signs and a normal examination except for yellowish, waxy-appearing, adherent plaques on the scalp, forehead, cheeks, and nasolabial folds. Which of the following therapies is appropriate for this condition?

A. High-potency topical steroid

B. Topical mupirocin

C. Phototherapy

D. Topical ketoconazole or low-dose steroids

E. Topical antifungal

44.2 An 8-year-old girl arrives at your clinic complaining about a minimally itchy rash on her chest, abdomen, and arms. It started with one small, scaly, red area on her chest and then spread. She is taking no medications. Physical examination reveals salmon-colored, flat, finely scaly, oval eruptions on her chest, abdomen, back, and upper arms. Which of the following is appropriate advice or therapy?

A. Topical mupirocin

B. High-dose topical steroid

C. Reassurance or “supportive” therapy

D. Three sequential weekly penicillin injections

E. Topical antifungal

44.3 A father brings his 8-month-old daughter to an emergency room for worsening skin rash and fever. He reports that his daughter usually has weepy, red lesions on her face that are relatively well controlled with bathing her with gentle soaps, using topical emollients and steroids, and giving oral antihista-mines. Over the previous few days, however, the rash has gotten progressively worse and the child has become “sicker.” Your physical examination reveals a lethargic child with an oral temperature of 103°F (39.4°C). The child’s cheeks are red and contain numerous red, punched-out, and umbilicated vesicles; some lesions are pustular. Which of the following would you prescribe?

A. Intravenous acyclovir

B. Prednisolone

C. Topical bacitracin

D. Intravenous methylprednisolone

E. Topical acyclovir

44.4 An 8-month-old child has refractory eczema that was first noticed at 2 months of age. His past medical history reveals multiple episodes of otitis media and pneumonia, and he has now developed severe nose-bleeds. You suspect a primary immunodeficiency. Which of the following is the next best test in your evaluation?

A. Chromosomal analysis

B. Chest computed tomography (CT)

C. Complete blood count

D. CD4 cell count

E. Referral to ear, nose, and throat (ENT) for nasal endoscopy

ANSWERS

44.1 D. Seborrheic dermatitis presents in infancy and adolescence. The chronic, symmetrical eruption, characterized by overproduction of sebum, affects the scalp, forehead, retroauricular region, auditory meatus, eyebrows, cheeks, and nasolabial folds. More commonly known as “cradle cap” in infants, this self-limited eruption typically develops between 2 to 3 months of age primarily on the scalp. The scale is yellow and waxy, and typically comes off with frequent shampooing. The scale may be loosened with a small amount of oil. In infants who do not respond to shampooing with baby shampoo, an antidandruff shampoo containing antifungal medication (Nizoral) or selenium may help, as will low-to medium-potency topical corticosteroids.

44.2 C. Pityriasis rosea is preceded by a “herald patch,” an annular, scaly, erythematous lesion. The lesions are salmon-colored and in a Christmas-tree formation, following the lines of the skin. The cause is unknown. Treatment may include antihistamines, topical antipruritic lotions and creams, low-dose topical corticosteroids, and phototherapy. The rash usually lasts up to 6 weeks and then resolves. It can be confused with nummular eczema and tinea versicolor. In the sexually active adolescent, syphilis should also be considered.

44.3 A. Atopic infants may develop rapid onset of diffuse cutaneous herpes simplex. The disease is most common in areas of active or recently healed atopic dermatitis, particularly the face. High fever and adenopathy occur 2 to 3 days after the onset of vesiculation. Viral septicemia can be fatal. Eczema herpeticum of the young infant is a medical emergency. The child should be admitted immediately for intravenous acyclovir.

44.4 C. This patient most likely has Wiskott-Aldrich syndrome, an X-linked condition with recurrent infections, thrombocytopenia, and eczema. Infections and bleeding usually are noted in the first 6 months of life. Potential infections include otitis media and pneumonia caused by poor antibody response to capsular polysaccharides, and fungal and viral septicemias caused by T-cell dysfunction. A complete blood count could aid diagnosis; thrombocytopenia usually is in the 15,000 to 30,000/mm3 range, and platelets are typically small. In addition to eczema, these children have autoimmune disorders and a high incidence of lymphoma and other malignancies.


CLINICAL PEARLS

Image Atopic dermatitis is a chronic, itchy disease that often begins in childhood. In infancy, the itchy eruption is found on the face and cheeks; by childhood, the rash is noted in flexural areas.

Image Baseline therapy for atopic dermatitis is avoidance of drying soaps and replenishment of skin hydration with emollients; topical steroids may be required.


REFERENCES

Buckley RH. Immunodeficiency with thrombocytopenia (Wiskott-Aldrich syndrome). In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:2467-2468.

Chatila TA. Wiskott-Aldrich syndrome. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gerson AA, eds.Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:761-762.

Holland KE. Atopic dermatitis. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gerson AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:1257-1259.

Leung DYM. Atopic dermatitis (atopic eczema). In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: WB Saunders; 2011: 801-807.

Sampson HA. Atopic dermatitis. In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006: 2423-2427.