Treatment includes reversing the cause of deficiency and supplementing iron. Calculation of the total iron deficit can help inform iron supplementation. First-line therapy for IDA is oral ferrous sulfate 325 mg (65 mg elemental iron) 3 times daily. Newer studies suggest 40 to 80 mg oral iron should be taken every other day to increase absorption.39 Other iron salts, such as ferrous gluconate (325 mg is equivalent to 38 mg elemental iron), have been used. Iron absorption is enhanced by an acidic environment. Parenteral iron is utilized in patients with uncorrectable blood loss, malabsorption, renal failure, intolerance to oral iron, and nonadherence in those who are unable to receive transfusions. Iron infusions are favored in frail patients, such as the elderly and those with chronic kidney disease or heart failure.35 Multiple parenteral iron formulations exist, and their use should be driven by underlying patient comorbidities and potential risks. Packed red blood cell transfusions should be considered in acute blood loss, hypoxia, or cardiac insufficiency.
Essential Fatty Acid Deficiency
Essential fatty acids (EFAs) including linoleic and α-linolenic acid cannot be synthesized by the human body and must be obtained through diet (mostly plant oils). Essential fatty acids have various functions, including maintaining phospholipid membrane integrity, forming prostaglandins and leukotrienes, and storing energy.40 Essential fatty acids are important in the structure and function of the stratum corneum and are crucial in maintaining epidermal barrier function.41 Increased epidermal permeability and transepidermal water loss may be the first signs of EFA deficiency (EFAD).42
The cutaneous manifestations of EFAD include xerosis, weeping eczematous plaques, and erosions in intertriginous sites. The lesions may progress to widespread desquamation and erythema. With time, the skin can become thick and leathery. Alopecia may occur, and hair may depigment.7 Additional findings include poor wound healing and increased susceptibility to infections.43,44
Essential fatty acid deficiency may occur when dietary fat intake is severely restricted or in malabsorptive states.45,46 It develops in patients on prolonged TPN, typically when receiving fat-restricted nutrition,47,48 as occurs in hypertriglyceridemia.47 Essential fatty acid deficiency has developed in patients on TPN containing EFAs,47 as the introduction of novel intravenous lipid emulsions has resulted in varying proportions of EFA.40 Premature neonates are particularly at risk for EFAD.49
The diagnosis of EFAD involves the measurement of the triene to tetraene ratio. A ratio of more than 0.2 suggests EFAD, but the clinical signs are not seen until the ratio is over 0.4.40 Low plasma levels of linoleic, linolenic, and arachidonic acids also are seen. Elevated liver function tests are supportive of the diagnosis. Biochemical findings typically are seen before cutaneous manifestations.40
Treatment of EFAD includes topical, oral, or intravenous replacement of EFAs. Improvement of EFAD with the application of topical linoleic acid to the skin has been reported.50 Patients receiving TPN should undergo assessment of parenteral lipid emulsion to ensure adequate fatty acid composition.
Vitamin A Deficiency
Vitamin A (retinol) is a fat-soluble vitamin that plays a critical role in keratinization, epithelial proliferation, and cellular differentiation.6 Vitamin A is found in animal products as retinyl esters and in plants as beta-carotene. Vitamin A has 2 clinically important forms: all-trans retinoic acid and 11-cis-retinal. All-trans retinoic acid is involved in cellular differentiation and regulating gene transcription, while 11-cis-retinal is key to rhodopsin generation required for vision. Vitamin A deficiency presents with early ophthalmologic findings, specifically nyctalopia, or delayed adaptation to the dark.51 Xerophthalmia, abnormal conjunctival keratinization, and Bitot spots subsequently develop and may progress to corneal ulceration and blindness.6
Vitamin A deficiency manifests in the skin as follicular hyperkeratosis, or phrynoderma. Notably, numerous other micronutrient deficiencies may result in phrynoderma. Clinically, multiple pigmented keratotic papules of various sizes, many with a central keratinous plug, are distributed symmetrically on the extensor elbows, knees, shoulders, buttocks, and extremities. The skin surrounding these lesions may be scaly and hyperpigmented.52 Generalized xerosis without preceding nyctalopia has been reported.53 Accompanying pityriasis alba may develop.52 Lesions on the face may mimic acne, while lesions on the extremities may simulate a perforating disorder. Histopathology of phrynoderma reveals epidermal hyperkeratosis, follicular hyperkeratosis, and follicular plugging.52