Medications such as antiepileptics, antimetabolites, or penicillamine may induce zinc deficiency, highlighting the importance of medication review for hospitalized patients (eTable). Catabolic states, frequently encountered in hospitalized patients, increase the risk for zinc deficiency.24 Patients with necrolytic migratory erythema (associated with pancreatic glucagonomas) often experience low serum zinc levels.25
The skin is the third most zinc-abundant tissue in the human body. Within keratinocytes, zinc is critical to normal proliferation and suppression of inflammation.17 Zinc also plays an important role in cutaneous immune function.26 Zinc deficiency presents with sharply demarcated, flaccid pustules and bullae that erode into scaly, pink, eczematous or psoriasiform plaques. Lesions are found preferentially in acral and periorificial sites, often with crusting and exudate. The groin and flexural surfaces may be affected. Erosions often become secondarily impetiginized. Other cutaneous findings include angular cheilitis, stomatitis, glossitis, paronychia, onychodystrophy, generalized alopecia, and delayed wound healing.26 Histopathology of skin lesions is characterized by granular layer loss, epidermal pallor, confluent parakeratosis, spongiosis, dyskeratosis, and psoriasiform hyperplasia.27 Acquired bullous acrodermatitis enteropathica has been reported as a histologic mimicker of pemphigus foliaceous in patients on TPN.28
Diagnosis of zinc deficiency is made by measuring plasma zinc levels. Fasting levels should be drawn in the morning, as they can fluctuate based on the time of day, stress levels, or inflammation.6 Sample hemolysis and anticoagulants high in zinc may falsely elevate plasma zinc. A normal zinc level is greater than 70 µg/dL; however, normal levels do not rule out deficiency.18 Measurement of zinc-dependent enzymes, such as alkaline phosphatase, can be a quick way to assess zinc status. Serum albumin also should be measured; because zinc is carried by albumin in the blood, hypoalbuminemia may result in secondary zinc deficiency.18
Zinc replacement therapy is largely through oral supplementation and should start at 0.5 to 2.0 mg/kg/d in adults with acquired disease.29,30 Zinc sulfate is the most affordable and is the supplement of choice, with 50 mg of elemental zinc per 220 mg of zinc sulfate (~23% elemental zinc).31 Alternative zinc salts, such as zinc gluconate (13% elemental zinc), may be used. Patients with malabsorptive disorders often require parenteral supplementation.32 Clinical symptoms often will resolve within 1 to 2 weeks of supplementation.29 In patients with primary acrodermatitis enteropathica, lifelong supplementation with 3 mg/kg/d elemental zinc should occur.6 Calcium and folate may reduce zinc absorption, while zinc supplementation can interfere with copper and iron absorption.33
Iron Deficiency
Iron is an essential component of the hemoglobin molecule. Iron homeostasis and metabolism are tightly regulated processes that drive erythropoiesis. Only 5% to 10% of dietary iron is absorbed through nutrition, while the remainder is recycled from red cell breakdown. Both normal iron levels and iron deficiency (ID) are defined by age and gender.34 Iron-deficiency anemia (IDA) is one of the most common cause-specific anemias worldwide.35
Fatigue is the most common and earliest symptom of ID. In a single study, pallor was predictive of anemia in hospitalized patients; however, absence of pallor did not rule out anemia.34 Dyspnea on exertion, tachycardia, dysphagia, and pica also may be reported. Cutaneous manifestations include koilonychia (Figure 2), glossitis, pruritus, angular cheilitis, and telogen effluvium. Plummer-Vinson syndrome is characterized by microcytic anemia, glossitis, and dysphagia.
Figure 2. Koilonychia in a patient with iron-deficiency anemia.
Risk factors for ID include insufficient dietary consumption,36 blood loss, malabsorptive states,37,38 and increased iron requirements (eTable). Patient fragility (eg, elderly, chronic disease) is a newly described risk factor where correction of ID may impact morbidity, mortality, and quality of life.35
Iron deficiency can be present despite a normal hemoglobin level. Serum ferritin and percentage transferrin saturation are key to early identification of IDA.35 Ferritin levels lower than 30 µg/L confirm the diagnosis. Decreased transferrin saturation and increased total iron binding capacity aid in the diagnosis of IDA. Serum ferritin is an acute-phase reactant, and levels may be falsely elevated in the setting of inflammation or infection.