Acrodermatitis enteropathica results from a defect in zinc metabolism inherited as an autosomal recessive trait. Zinc is chelated in the gastrointestinal tract by an oligopeptide that is normally destroyed in the bowel. Zinc deficiency results in skin and bowel lesions, as well as alterations in mental status. If the disorder is not treated, death occurs from infection and/or marasmus. Blood zinc levels confirm the diagnosis. Dramatic recovery and normal development occur when dietary zinc is supplemented. Acrodermatitis enteropathica, an inherited disorder resulting from the malabsorption of zinc, is one of the few reversible causes of developmental delay in infants. If untreated, this rare disorder is fatal. However, prompt diagnosis and proper treatment can quickly return an affected infant to normal.
A female infant was delivered by emergency cesarean section because of fetal distress. She was apparently healthy at birth, with high Apgar scores and no detectable abnormalities. The infant was the first living child of four pregnancies; the mother had had two prior miscarriages and one stillbirth. The mother had intended to breastfeed, but she became ill with cholecystitis when the infant was a few days old.
From the time the infant was placed on formula, she had persistent feeding problems, characterized by vomiting, diarrhea and intractable crying. Over the next few months, these problems worsened in spite of several changes of formula. There was a strong family history of milk allergy, and the infant had a high IgE titer, which suggested allergy. She also had recurrent ear infections and severe Candida albicans infections in the diaper area (Figure 1).
By the age of ten months, the infant’s failure to thrive had become a significant illness. She was below the third percentile for both height and weight and was falling farther behind the anticipated growth curves. She began to regress developmentally, and she stopped crawling and smiling. In addition to recurrent monilial skin rashes, she developed generally edematous skin and persistent rashes over the knees, elbows and face (Figure 2).
The diagnosis of acrodermatitis enteropathica was suggested by a dermatologist and was confirmed by both the clinical picture and a low blood zinc level. Treatment involved zinc supplementation and a community effort to provide fresh breast milk for the infant. With treatment, the infant improved dramatically. Within 24 hours of receiving breast milk and zinc supplement, she stopped vomiting and resumed smiling. Within one week, the edema, rash and other symptoms resolved. She began to put on weight and to regain her expected developmental status.
Formula was reintroduced, and the infant continued to do well on formula plus zinc supplement. On a normal diet plus zinc supplement, she became a lively toddler (Figures 3 and 4). Challenges for the family physician included monitoring her progress and counseling the parents about the possibility of future children being affected by the same condition.
Acrodermatitis enteropathica is characterized by bowel and skin lesions. The classic description of the disorder includes bowel dysfunction, pathognomonic skin eruptions and profound mood changes occurring at the time an infant is weaned from breast milk. Characteristically, a previously healthy infant develops profuse, pale diarrhea. If the diarrhea becomes extremely severe, marasmus may occur.
Simultaneously, two characteristic skin lesions develop. These lesions initially resemble moist eczema around orifices and psoriasiform plaques over bony prominences, but they quickly progress to cover large areas. Blood-filled blisters, paranychia and hair loss also occur. Superinfection with C. albicans is a common complication.
Mood and behavior changes include avoidance of eye contact and extreme irritability. Smiling is lost early. The characteristic picture is that of a miserable child who sits with head hung down and views the world surreptitiously and suspiciously through sidelong glances.
If acrodermatitis enteropathica is not diagnosed and treated, death occurs from infection and/or marasmus.
Etiology and Pathogenesis
Acrodermatitis enteropathica results from a defect in zinc metabolism that is inherited as an autosomal recessive trait. The disorder may be more common in populations of Scandinavian descent, although this observation may be the result of the number of case reports from Britain and Scandinavia since the disease was first described in 1942. “Typical” patients are female children and children of both sexes with red hair.
Because zinc is critical to the production and function of a wide range of human enzymes, a variety of clinical symptoms appear in this disorder. The predominance of skin and gastrointestinal problems reflects the high rates of cell division and protein synthesis in these systems.
The fundamental defect in acrodermatitis enteropathica is believed to be an inability to absorb zinc from the gastrointestinal tract due to chelation of the metal by an oligopeptide. In normal infants, this peptide is destroyed by an oligopeptidase secreted by enterocytes in the intestinal lining. Infants with acrodermatitis enteropathica have a genetic defect in the enterocytes, resulting in failure to produce oligopeptidase. Therefore, these infants chelate zinc, which leads to a functional deficiency (Figure 5).
The disorder is not seen before weaning in breast-fed infants, because the oligopeptide is not produced in the digestion of human milk. Thus, zinc absorption is not compromised until other protein sources are introduced into the diet.
Diagnosis and Treatment
The diagnosis of acrodermatitis enteropathica is based on clinical features, particularly the characteristic skin lesions. Biopsies of the skin and the intestinal lining show nonspecific changes. Depleted blood zinc levels confirm the diagnosis in a child who shows severe symptoms in the skin and bowel and exhibits strong changes in mood and behavior at the time of weaning from breast milk.
Until recently, the treatment of choice for acrodermatitis enteropathica was diiodohydroxyquinoline, which was believed to act by chelating the oligopeptide. It now appears that zinc supplementation alone can abate symptoms and permit normal growth and development. The zinc dosage must be individually determined and continually adjusted for each patient, taking into account the changing demands of growth and other stresses, such as intercurrent illness. The minimum zinc supplement for infants is 35 to 50 mg per day.
It is becoming apparent that zinc therapy must be lifelong in patients with acrodermatitis enteropathica. With careful management, however, patients with this previously fatal disorder should enjoy a normal life and have a normal life-span. [Figures 1 to 5 Omitted]
REFERENCES Moynahan EJ, Grupper C. Acrodermatitis enteropathica and other zinc deficiency disorders. In: Fitzpatrick TB, ed. Dermatology in general medicine. 2d ed. New York: McGraw-Hill, 1979:1371-5. Chandra RK. Acrodermatitis enteropathica: zinc levels and cell-mediated immunity. Pediatrics 1980;66:789-91. Danbolt N, Closs K. Acrodermatitis enteropathica. Acta Derm Venereol [Stockh] 1942;23:127-69. Behrman RE, Vaugham VC 3d, eds. Nelson Textbook of pediatrics. 12th ed. Philadelphia: Saunders, 1983:1683. Gonzales JR, Botet MV, Sanchez JL. The histopathology of acrodermatitis enteropathica. Am J Dermatopathol 1982;4:303-11. Janaki VR, Augustine SM, Kamalam A, Thambiah AS. Acrodermatitis enteropathica. J Indian Med Assoc 1981;76:43-4. Moynahan EJ. Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder [Letter]. Lancet 1974;2(7877):399-400.
ANNE WALLING, M.D. is vice-chairman of the Department of Family and Community Medicine at the University of Kansas School of Medicine-Wichita. Dr. Walling received her medical degree from St. Andrew’s University, Scotland, and completed advanced training in Scotland and England. MARTHA HOUSEHOLDER, M.D. is in private practice in dermatology in Wichita. Dr. Householder graduated from the University of Kansas School of Medicine, Kansas City, and completed postgraduate training at the Johns Hopkins University School of Medicine, Baltimore. ADRIAN WALLING, M.D. is medical director of Equicor Health Plan in Wichita and clinical associate professor in the Department of Family and Community Medicine at the University of Kansas School of Medicine-Wichita. Dr. Walling is a graduate of St. Andrew’s University and a member of the Royal College of General Practitioners of the United Kingdom.
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