Acrodermatitis enteropathica E83.2

Rare, autosomal recessive disorder in which vesiculopustular, sometimes eczematous, pluriorificial (perioral, genitoanal) and acral skin lesions, as well as diarrhea and alopecia, occur due to inadequate absorption of zinc contained in the normal diet. Similar manifestations occur in acquired zinc deficiency dermatoses.

The congenital, autosomal recessively inherited, primary zinc absorption disorder (gene locus 8q24.3) is discussed. SLC39A4, which encodes the ZIP4 protein, has been identified as the defective gene. The absence of this zinc binding factor (soluble carrier SLC39A4) in the small intestine, which is present in breast milk but not in cow's milk, causes zinc absorption to drop to 2-3% of normal.

Secondary zinc deficiency has been described in chronic inflammatory diseases of the gastrointestinal tract (Crohn's disease, ulcerative colitis), zoeliac disease, secondary to small bowel resections, small bowel fistulas, as well as in parenteral or unilateral nutrition and alcoholic liver cirrhosis. It is thought to be due to defective formation of the specific zinc-binding ligand normally present in the intestine; only small amounts of zinc enter the bloodstream.

Acquired form: Among others, in alcoholism due to inadequate zinc intake/supply with food.

Apparently, zinc deficiency leads to a complete or partial loss of Langerhans cells of the skin. This deficiency in turn seems to lead (at least in animal experiments) to an intensification and chronification of eczema.

Zinc deficiency leads to complex metabolic disturbances with regard to >200 zinc-dependent metalloproteases.

In the hereditary form, the initial manifestation of the disease occurs in infancy, usually after weaning; in the secondary forms, it occurs weeks, months or years after the onset of the underlying disease causing the zinc deficiency.

Symmetrical at the acra and body orifices (mouth, nose, anogenital region).

Triad of acral and pluriorificial dermatitis, alopecia and recurrent diarrhea.

Integument: Clinically, very heterogeneous pictures are found with confluent erythema as well as vesicles, pustules, crusts or scabs. With a more chronic course, recurrent eczematous or ichthyosiform skin lesions, sometimes craquelé-like, acneiform folliculitis, and periorificial and acral persistent psoriasiform erythema are found. Diffuse alopecia of the scalp, eyebrows, and eyelashes; chronic paronychia with nail dystrophies, furthermore Beau-Reil furrows.

Extracutaneous manifestations: recurrent diarrhea, reduced general condition with growth disturbances, recurrent superinfections ( Candida albicans), delayed wound healing; furthermore psychic abnormalities. Also: glossitis, stomatitis, hoarseness, blepharitis, otitis, neurological disorders, growth retardation.

Nonspecific: changing focal ortho- and parakeratosis with diminishing str. granulosum, variable acanthosis, also psoriasiform, partly ballooning keratinocytes, also focal acantholysis; partly subcorneal vesicles. Dermis with unspecific infiltrate, also neutrophil granulocytes.

Acquired zinc deficiency states due to chronic malabsortpion, e.g. in cystic fibrosis, complete parenteral nutrition, vegetarian diet (poor zinc availability!).

Clinically important clinical pictures that are not due to zinc deficiency but have similar clinical symptoms: Atypical psoriasis vulgaris; Acrodermatitis continua suppurativa Hallopeau; Epidermolysis bullosa group; Erythema necroticum migrans; Epidermolysis bullosa simplex, Köbner; Candidosis.

• Substitution with zinc compounds (5 mg/kg bw/day), under regular control of serum zinc levels (normal 80-120 μg/dl) and zinc excretion in 24-hour urine (normal 200-500 μg/24 hrs). Zinc should not be taken with meals.

1. Brandt T (1936) Dermatitis in children with disturbances of the general condition and the absorption of food elements Acta Dermatol Venereol (Stockh) 17: 513-546
2. Brar BK et al (2003) Acrodermatitis enteropathica-like rash in an exclusively breast fed infant with zinc deficiency. J Dermatol 30: 259-260
3. Danbolt N, Closs K (1942) Acrodermatitis enteropathica. Acta Dermatol Venereol 23: 127-169
4. Fölster-Holst R, Höger P (2010) Pustular skin diseases of the newborn. JDDG 7: 569-579
5. Kawamura Tet al. (2012) Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency. J Clin Invest. 122:722-732.
6. Katayama I, Koizumi S, Kodama T, Nakao A, Shimada S.
7. Kury S, Dreno B et al (2002) Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31: 239-240
8. Löffler H, Effendy I (1999) Acrodermatitis-enteropathica-like skin changes due to parenteral nutrition. dermatologist 50: 499-502
9. Maverakis et al (2007) Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol 56: 116-124
10. Nakano A et al (2003) Novel SLC39A4 mutations in acrodermatitis enteropathica. J Invest Dermatol 120: 963-966
11. Neldner KH (1987) Acrodermatitis enteropathica and other zinc-deficiency disorders. In: Fitzpatrick TB et al. Dermatology in general medicine. 3rd ed. 1613-1619
12. Patrizi A et al (2003) Acrodermatitis enteropathica-like eruption: a sign of malabsorption in cystic fibrosis. Pediatric Dermatol 20: 187-188
13. Perafan-Riveros C (2002) Acrodermatitis enteropathica: case report and review of the literature. Pediatric Dermatol 19: 426-431
14. Quirk CM et al (2002) Acrodermatitis enteropathica associated with anorexia nervosa. JAMA 288: 2655-2666
15. Sandstrom B et al (1994) Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function. Arch Ped 148: 980-985
16. Von Velber V et al (2010) Acrodermatitis-enteropathica-like skin changes in Crohn's disease zinc deficiency. Dermatologist 61: 927-929