A Diagnostic Challenge: A Case of Acrodermatitis Enteropathica without Hypozincemia and with Maternal Milk of Low Zinc Level

Abstract: Acrodermatitis enteropathica is a rare and distinct form of zinc deficiency with a requirement of life‐long zinc supplementation and inherited in a recessive manner. Transient nutritional zinc deficiency is also a well known condition mimicking acrodermatitis enteropathica like skin changes in preterm and term infants who are generally breastfed with a low level of zinc containing milk. Here, a 4‐month‐old male, term and fully breastfed acrodermatitis enteropathica case without hypozincemia and with maternal milk of low zinc level is presented.     

Acrodermatitis enteropathica in full-term breast-fed infant

BACKGROUND: Acrodermatitis enteropathica is a rare autosomal recessive disorder, caused by impaired absorption of zinc from the gastrointestinal tract. Symptoms of acrodermatitis enteropathica occur within the first few months after birth and tend to appear shortly after discontinuation of breast-feeding. We report a breast-fed infant with acrodermatitis enteropathica. CASE REPORT: A full term, 4-month-old girl, consulted in dermatologic department for persistent and refractory anogenital lesions since the age of 1 month, with progressive erythematous, vesiculous and squamous lesions, sometimes erosive in a peri orificial and acral pattern. She was calm and healthy baby. She was breast feeding. The diagnosis of acrodermatitis enteropathica was confirmed by decreased plasma zinc level (14 microg/100 ml). Breast milk zinc levels was low (46 microg/100 ml), as plasma zinc level of the mother (94 microg/100 ml). A genetic study showed that she was homozygous for the mutation, whereas her brother and parents were heterozygous. She was given zinc sulphate, and her condition has improved significantly. DISCUSSION: Acrodermatitis enteropathica is characterized by a characteristic clinical feature and the diagnosis is confirmed by decreased plasma zinc level. Acrodermatitis enteropathica in exclusively breast fed infant is rare, it was essentially reported in premature babies. Our case report is particular because it's concerning a full-term breast-fed infant, with zinc deficiency in breast milk and mother's decreased plasma zinc level.     

Zinc therapy in acrodermatitis enteropathica]

Report of two patients with acrodermatitis enteropathica, one of them 20 years old and with very severe symptoms of the disease. Oral therapy with zinc resulted in complete cure within two months. The theory about chelating of dietary zinc in patients with acrodermatitis enteropathica is discussed.     

Acrodermatitis enteropathica-like skin eruption in a case of short bowel syndrome following jejuno-transverse colon anastomosis

Acrodermatitis enteropathica is a rare autosomal recessive disorder of zinc deficiency. Zinc is an essential trace element in human metabolism and acquired zinc deficiency may manifest with skin eruptions simulating acrodermatitis enteropathica. We report an unusual case of acrodermatitis enteropathica-like skin eruption due to deficiency of zinc and other nutritional factors in a patient who has undergone extensive small bowel resection and jejuno-transverse colon anastomosis for mesenteric ischemia.     

Malignant melanoma and dermatofibrosarcoma in a 60-year-old patient with lifelong acrodermatitis enteropathica

The life course of acrodermatitis enteropathica is recorded in a 62-year-old white man. Initially saved in infancy by breast-feeding and good medical care, later in his twenties he responded well to diiodohydroxyquinoline (Diodoquin) therapy, his only residua being dermatitis, hoarseness, and short stature. Subsequently untreated, this patient years later developed not only a dermatofibrosarcoma but also a large amelanotic malignant melanoma. Both were successfully excised. Subsequently, oral zinc therapy initiated for the first time cleared his acrodermatitis, which had been present for 60 years. It is suggested that this patient's malignancies developed as a result of an immune deficiency state typically found in acrodermatitis enteropathica. On this basis, acrodermatitis enteropathica may be viewed as having a malignant potential over the long term. The zinc-dependent nature of the immune deficit, however, suggests that lifelong daily zinc supplementation is an appropriate prophylactic measure.     

Hereditary zinc deficiency (Adema disease) in cattle, an animal parallel to acrodermatitis enteropathica.

Adema disease and acrodermatitis enteropathica, two parallel syndromes in calves of Friesian descent and in man, are described. Both are congenital zinc deficiency disorders with a lethal course if left untreated. Complete recovery follows oral zinc therapy. Symptoms and findings are set out in Table I. Diseased calves may serve as animal models for further studies on acrodermatitis enteropathica and the biological role of zinc.     

Acrodermatitis enteropathica with anorexia nervosa

Acrodermatitis enteropathica is a rare hereditary or acquired disorder of hypozincemia. It is characterized by acral and periorificial dermatitis, alopecia, diarrhea and growth retardation. Anorexia nervosa is characterized by low body weight, body image distortion with an obsessive fear and is also associated with various cutaneous findings including acrodermatitis enteropathica. We report a 37‐year‐old female with acrodermatitis enteropathica showing acquired zinc deficiency with anorexia nervosa.     

Novel SLC39A4 mutations in acrodermatitis enteropathica

Acrodermatitis enteropathica is an autosomal recessive disease characterized by skin involvement due to defective intestinal zinc absorption. Usually, the skin lesions include erythema, erosions, and small blisters in perioral, perianal regions, and hands and feet, which develop soon after weaning from the breast. The acrodermatitis enteropathica gene has been localized to chromosomal region 8q24.3 and subsequently the SLC39A4 gene has been disclosed as the acrodermatitis enteropathica gene. SLC39A4 mutations have been demonstrated in several acrodermatitis enteropathica families, and in this study we have examined two Japanese acrodermatitis enteropathica families for SLC39A4 mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all 12 exons and flanking intronic sequences, followed by direct nucleotide sequencing. It revealed three novel mutations, 1017ins53, which creates a premature termination codon, and two mis-sense mutations, R95C and Q303H.     

Self-Limiting Acrodermatitis Enteropathica

A variant of acrodermatitis enteropathica is described that has its onset before weaning and clears when the child starts its normal solid diet. A pedigree with three interrelated families is reported where 10 children were afflicted with this variant. They had symptoms of hypozincemia for a brief period during infancy. At the time of this study, they were symptom-free and their serum zinc levels were found to be within normal limits. The term "self-limiting acrodermatitis enteropathica" is proposed for the variant. In one lactating mother, the mammary zinc secretion was determined and was found to be deficient and unresponsive to oral zinc supplements. The possible mode of inheritance is also discussed.     

Acrodermatitis enteropathica treated by zinc

A case of acrodermatitis enteropathica has, after 14 years essential treatment with Diodoquin, been able to abandon this therapy on exhibition of zinc.     

Acquired acrodermatitis enteropathica secondary to alcoholism

Acrodermatitis enteropathica is a zinc deficiency disorder characterized by well-demarcated, erythematous, eczematous plaques in a periorificial and acral distribution. Hereditary and acquired forms have been described. We report a case of acquired acrodermatitis enteropathica secondary to alcoholism. Treatment of the underlying disorder and zinc replacement therapy resulted in rapid resolution of the condition.     

ACRODERMATITIS ENTEROPATHICA*

A case of acrodermatitis enteropathica is reported in which there was a clinical response to zinc therapy despite a normal pretreatment plasma zinc level. Unusual features are the absence of diarrhoea and the large doses of zinc required for control of the disorder.     

Zinc therapy of acrodermatitis enteropathica

An 8-year-old girl had excellent treatment results for acrodermatitis enteropathica with an initial dose of 100 mg zinc sulphate given daily and followed by 50 mg daily maintenance.     

Acrodermatitis enteropathica in total parenteral nutrition caused by Crohn disease

A 26 years old patient was suffering from Morbus Crohn and showed the signs and symptoms of an acrodermatitis enteropathica. The beginning of the parenteral nutrition preceded the signs of acrodermatitis for 30 days. The serum zinc level was normal. After therapy with zinc aspartate the dermatitis healed within one week.     

Cutaneous manifestations observed during prolonged intravenous feeding: 3 cases. Review of the literature (author's transl)]

3 patients (one infant and two adults) in prolonged intravenous feeding for digestive diseases developed cutaneous symptoms resembling acrodermatitis enteropathica. Essential fatty acid and hypozincemia (in 2 of 3 cases) are found. The dermatitis disappeared slowly with oral alimentation in 2 cases, and in a few days in the third one, with oral zinc sulfate. Review of literature shows that dermatitis occurring during prolonged intravenous feeding is attributed to essential fatty acid, zinc, or less often amino acid, deficiency. But resemblance of dermatitis with acrodermatitis enteropathica in most cases, high frequency of hypozincemia, and dramatic effects of treatment with zinc salts allow to think, that zinc is a key factor. Nevertheless, it is necessary to study simultaneously those different parameters and also vitamins A, E and B to conclude whether it exists or not many deficiencies (related or not) as an etiologic factor for cutaneous symptoms.     

Acrodermatitis enteropathica with Pseudomonas aeruginosa sepsis

Acrodermatitis enteropathica is characterized by eczematous and scaly plaques on the face, scalp, acral, and anogenital regions. In addition to typical lesions, unusual prominent vesiculobullous lesions are also described. We report a full-term, 9-month-old boy who has acrodermatitis enteropathica and Pseudomonas sepsis. In this patient there were clinical findings of sepsis and eczematous vesiculobullous lesions on the periorificial and acral areas. Serum zinc level was extremely low. Pseudomonas aeruginosa was identified in cultures of blood and fluid which was aspirated from the bullous lesions. After oral zinc sulfate and intravenous antibiotic treatment his condition improved within 2 weeks.     

Zinc deficiency with transitory acrodermatitis enteropathica in a boy of low birth weight

A premature male baby fed on his mother's milk developed zinc deficiency and a skin disorder inseparable from acrodermatitis enteropathica. Following zinc therapy the skin lesions healed. Later the treatment was withheld and no recurrence was seen during 30 months’ observation. The boy's zinc deficiency was thought to be due to a high requirement secondary to rapid growth, to poor zinc supply in food and, possibly, to inefficient zinc absorbtion.     

Acrodermatitis enteropathica-like eruption in an infant with nonketotic hyperglycinemia

Acrodermatitis enteropathica is a rare inherited disorder characterized by zinc deficiency and a triad of dermatitis, diarrhea, and alopecia. It is an autosomal recessive condition thought to be due to the inability to absorb zinc from the gastrointestinal tract. Acquired zinc deficiency due to a variety of etiologies may produce a similar clinical picture. These causes include inadequate supply, malabsorption, and low zinc stores. In addition to zinc, deficiencies of other nutrients such as branched chain amino acids have induced an acrodermatitis enteropathica-like eruption. We describe a case of a 26-month-old boy with a rare inborn error of metabolism known as nonketotic hyperglycinemia who developed an acrodermatitis enteropathica-like eruption. In addition to zinc deficiency, the patient was deficient in branched chain amino acids due to a low protein diet instituted to reduce his elevated glycine levels. The rash did not respond to zinc replacement alone, and therefore is most likely a combination of amino acid and zinc deficiency. Acrodermatitis enteropathica-like eruptions have been described in other conditions that cause decreased serum amino acids, such as maple syrup urine disease and organic acidurias. This is the first case describing an association between acrodermatitis enteropathica and nonketotic hyperglycinemia.     

ACUTE ZINC DEPLETION SYNDROME DURING PARENTERAL HYPERALIMENTATION

ABSTRACT: Zinc is an essential trace element whose malabsorption in early childhood may result in a skin disorder known as acrodermatitis enteropathica. Cutaneous lesions typical of acrodermatitis enteropathica have been described during total parenteral nutrition on zinc-deficient intravenous solutions in both adults and children. This condition has been named the “acute zinc depletion syndrome.” A case is described in which a patient, despite a zinc intake of double the daily requirement, manifested the acute zinc depletion syndrome during therapy with combined liquid diet plus parenteral hyperalimentation. Predisposing factors in this individual included a short bowel syndrome and a large oral load of calcium lactate. Zinc metabolism is reviewed with attention to alterations in disease and during hyperalimentation. The clinical manifestations, predisposing factors, therapy and prevention of the acute zinc depletion syndrome are discussed.     

Acrodermatitis enteropathica

A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36 mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was established and the patient responded well to zinc replacement therapy. Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.