Acquired zinc deficiency in an adult female.

Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. Acquired cases are reported occasionally in patients with eating disorders or Crohn's disease. We report a 24-year-old housewife with acquired isolated severe zinc deficiency with no other comorbidities to highlight the rare occurrence of isolated nutritional zinc deficiency in an otherwise normal patient.

What was known?

Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. The clinical syndrome of zinc deficiency is characterized by a triad of acral dermatitis, alopecia and diarrhea. Acquired cases are reported occasionally in patients with eating disorders or Crohn's disease.

Introduction

Zinc deficiency can be inherited, in the form of acrodermatitis enteropathica (ADE), a disorder of zinc absorption or acquired, usually described in alcoholics.[1] Zinc is an essential element playing important catalytic, structural and regulatory functions in the human body.[1] Deficiency of zinc results in multi-systemic manifestations, sometimes having fatal outcomes if not picked up early and corrected. The clinical syndrome of zinc deficiency is characterized by a triad of acral dermatitis, alopecia and diarrhea.[1] We present a case of acquired zinc deficiency showing the typical triad in a 24-year-old female patient, diagnosed and treated wrongly earlier, and highlight the dramatic response that occurred with zinc supplementation.

Case Report

A 24-year-old housewife presented with erosions on the body and recurrent diarrhea of 6 months duration. Six months ago, she initially developed a blister and erosion on her left leg; later she developed similar erosions on hands, perioral area, perineum, and over bony prominences. She had a history of weight loss of around 5 kg in 6 months, along with hair loss, fatiguability, soreness of mouth and poor wound healing. She had no other comorbidities; there was no family history of similar illness. There was no history of bowel disturbances. She was recently married and was a housewife. Her food intake was poor for the last one year or so. She was treated with systemic steroids by a private practitioner, who suspected pemphigus vulgaris, but she did not have any improvement. On physical examination, the pale looking well built lady had multiple well defined, moist, erythematous erosions with irregular margins over bilateral dorsa of hands and feet, perioral area [Figure 1a], cubital fossae, perigenital [Figure 1b], perineal area, gluteal region and thighs. Scalp showed diffuse hair loss. Nails had Beau's lines and oral mucosa revealed glossitis. Her hemoglobin was 12 g/dl. Otherwise, all her routine investigations including sugar profile, serology for human immunodeficiency virus (HIV), and hepatitis B surface antigen (HBsAg) were normal. Serum alkaline phosphatase was 32 IU/l; serum zinc was 9.49 μg/ dl. Ultrasonogram of abdomen and upper gastrointestinal endoscopy was normal. Skin biopsy showed epidermal spongiosis and pallor, broad parakeratosis, thinning of granular layer and superficial dermal infiltrate, consistent with nutritional deficiency. Serum B12 and ferritin were normal. She was treated with oral cloxacillin and elemental zinc 50 mg three times daily. The erosions started drying up in 3 days and healed in a week. She was discharged on daily zinc and iron supplements, after total clearance of skin lesions in two weeks [Figures 2a and b]. On follow up at 6 months, she did not relapse.

Figure 1

(a-b) Perioral and perigenital involvement by erythema, oozing and crusted lesions

Figure 2

(a and b) Clearance of lesions following zinc therapy after 2 weeks

Discussion

Zinc is an important constituent of the catalytic site of many vital metalloenzymes in the body like carbonic anhydrase and alkaline phosphatase.[1] Zinc finger proteins, like those seen in retinoic acid and vitamin D receptors play an important role in structural differentiation of many organs including the skin. Zinc also plays a role as an ionic signal regulating gene expression. Zinc transporting proteins are expressed by two gene families, ZnT and ZiP that play opposite roles in zinc trafficking. Zinc is absorbed primarily in the jejunum by the transporting protein ZiP4. Zinc levels progressively decrease in human breast milk; however bioavailability is higher in breast milk than cow's milk.[1] It is found in good amounts in protein rich food especially animal protein. Its bioavailability is decreased by phytates and iron.

ADE was first described in 1936 by Brandt and later identified as a definitive disease in 1942 by Danbolt and Closs[2] as an acral rash associated with diarrhea. In 1973, Moynahan and Barnes[3] associated the clinical finding with low plasma zinc level by demonstrating improvement of the patient with zinc supplements. It is inherited as an autosomal recessive with an estimated incidence of 1 per 500,000 children.[1] The onset usually, is shortly after the introduction of cow's milk or low-zinc formulas. It can occur before weaning, due to low mammary secretion of zinc.[4] Classical ADE is believed to be a result of a defect in a zinc transporting protein encoded on chromosome 8q24.3.5 by the gene SLC39A4. It is a histidine-rich transmembrane protein known as hZIP4, involved in zinc uptake.[56]

Acquired zinc deficiency has been reported in numerous conditions like anorexia nervosa, alcoholism, inflammatory bowel disease, blind loop syndromes, total parenteral nutrition, defect of mammary zinc secretion (lactogenic ADE), sprue and other intestinal malabsorption syndromes, pancreatic disorders, burns, malignancies and renal disorders.[7] Our patient had acquired zinc deficiency, due to deficient dietary intake.

The typical dermatologic findings of zinc deficiency are dry, scaly, sharply demarcated, red, eczematous patches on the face (periorificial) and anogenital area, which can become vesicular, pustular or desquamative. On the extensor surfaces of the arms and legs, psoriasiform plaques are typical. Nails show paronychia and transverse ridging. Scalp can show generalized alopecia in profound deficiency or dry, brittle lusterless hair and banding of hair in milder cases.[8] Angular cheilitis and paronychia are early findings.[1] Many of these features were present in our patient.

The systemic features of zinc deficiency are diarrhea, anorexia, growth retardation, photophobia, comeal opacities, hypogeusia, hyposmia, hypogonadism, amenorrhea, anemia, impaired wound healing, hoarseness, neuropsychiatric problems, and perinatal morbidity, due to increased zinc requirement in pregnancy.[8] Immunologic abnormalities like decreased T cell, neutrophils, natural killer (NK) cell and macrophage function result in secondary colonization of erosions and infections. Our patient had anemia, diarrhea and poor wound healing.

In the histopathology, necrolysis, a term describing cytoplasmic pallor, vacuolization,ballooning degeneration, and subsequent confluent necrosis of keratinocytes within the superficial stratum spinosum and stratum granulosum of the epidermis is said to be almost pathognomonic.[1] Other features are confluent parakeratosis, hypogranulosis and psoriasiform hyperplasia.[19] Histopathological differential diagnoses would be necrolytic migratory erythema, seen in glucagonoma and pellagra.

Important clinical differential diagnoses would be epidermolysis bullosa, cystic fibrosis, glucagonoma syndrome, widespread candidiasis, pellagra, seborrheic dermatitis, hypovitaminoses, atopic dermatitis, celiac disease, and congenital periorificial and palmoplantar keratoderma.[1]

The most serious complication of ADE is the high morbidity and mortality caused by secondary infections. The most common pathogens are Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa.[8] In the past, inherited forms were fatal before zinc supplementation was introduced. Accepted treatment nowadays is with supplementation of elemental zinc at a dose of 2 mg/kg/ day, at least two or three times the recommended dietary allowance of 15 mg / day. The most accurate way of establishing diagnosis is by measuring plasma or serum zinc levels, though ADE with normal zinc levels has been reported.[9] When patient is on zinc therapy, monitoring should be done periodically to measure zinc levels, complete hemogram with erythrocyte indices, differential count, serum copper level and occult blood in stool. Side effects are gastric irritation, gastric hemorrhage and hypocupremia.[1]

This case is being reported to highlight that isolated zinc deficiency can occur in adults and should be considered to prevent mismanagement of this otherwise easily treatable condition.

What is new?

Acquired zinc deficiency has been reported in numerous conditions like anorexia nervosa, alcoholism, inflammatory bowel disease, blind loop syndromes, total parenteral nutrition, defect of mammary zinc secretion (lactogenic ADE), sprue and other intestinal malabsorption syndromes, pancreatic disorders, burns, malignancies and renal disorders. Our patient had acquired zinc deficiency, due to deficient dietary intake.