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Home , Folate deficiency, Koilonychia, Kwashiorkor, Marasmus, Pellagra, Vitamin B12 deficiency

HOSPITAL CONSULT

IN PARTNERSHIP WITH THE SOCIETY FOR HOSPITALISTS

Nutritional Dermatoses in the Hospitalized Patient

Melissa Hoffman, MS; Robert G. Micheletti, MD; Bridget E. Shields, MD

Nutritional deficiencies may arise from inadequate nutrient intake, abnormal nutrient absorption, or improper nutrient PRACTICE POINTS utilization.4 Unfortunately, no standardized algorithm for • Nutritional deficiencies are common in hospitalized screening and diagnosing patients with exists, patients and often go unrecognized. making early physical examination findings of utmost • Awareness of the risk factors predisposing patients importance. Herein, we present a review of acquired nutri- to nutritional deficiencies and the cutaneous manifes- tional deficiency dermatoses in the inpatient setting. tations associated with undernutrition can promote copy early diagnosis. -Energy Malnutrition • When investigating cutaneous findings, undernutri- tion should be considered in patients with chronic Protein-energy malnutrition (PEM) refers to a set of , malabsorptive states, psychiatric illness, related disorders that include , and strict dietary practices, as well as in those using (KW), and marasmic KW. These conditions frequently are certain medications. seen in developing countries but also have been reported 5 • Prompt nutritional supplementation can prevent patient in developed nations. Marasmus occurs from a chronic morbidity and mortality and reverse skin . deficiencynot of protein and calories. Decreased insulin pro- duction and unopposed catabolism result in sarcopenia and loss of bone and subcutaneous .6 Affected patients include children who are less than 60% ideal body weight Cutaneous disease may be the first manifestation of an underlying nutri- 7 tional deficiency, highlighting the importance of early recognition by der- (IBW) without or . Kwashiorkor matologists. Undernutrition occurs when there is an imbalance between is the edematous form of PEM that develops from iso- nutrient intake and metabolic demand. Many hospitalized patients are lated protein deficiency, resulting in edema, , and Do 6 in catabolic states due to chronic illness, , , or immunosuppression. deficiencies, oxida- medication. These patients are at an increased risk for undernutrition tive stress, slow protein catabolism, and excess antidi- and therefore associated cutaneous disease. This review details the risk uretic hormone have been proposed as potential drivers factors for nutritional deficiency, illustrates the presentations of cutane- 8 ous disease, reviews diagnostic workups, and provides suggestions for of KW. Kwashiorkor affects children between 60% and supplementation in the undernourished patient. 80% IBW. Marasmic KW has features of both , Cutis. 2020;105:296-302, 308. including children who are less than 60% IBW but with associated edema and/or hypoproteinemia.9 Although PEM is uncommon in adults, hospitalized he World Health Organization defines malnutri- patients carry many predisposing risk factors, including tion as deficiencies, excesses, or imbalances in infections, malabsorptive conditions, psychiatric disease, T an individual’s intake of energy and/or nutrients.1 and chronic illness (eTable). Patients with chronic infec- This review will focus on undernutrition, which may tions present with findings consistent with marasmic KW result fromCUTIS macronutrient or micronutrient deficiencies. due to lean body mass loss. Undernutrition in the hospitalized patient is a common The cutaneous findings in PEM are related to dysmatu- yet underrecognized phenomenon, with an estimated ration of epidermal keratinocytes and resultant epidermal prevalence of 20% to 50% worldwide.2 Malnutrition is an atrophy.10 Patients with marasmus exhibit dry, wrinkled, independent risk factor for patient morbidity and mortality loose skin due to subcutaneous fat loss. Emaciated chil- and has been associated with increased health care costs.3 dren often lose their buccal fat pads, and reduced perianal

From the Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia. The authors report no conflict of interest. The eTable is available in the Appendix online at www.mdedge.com/dermatology. Correspondence: Bridget E. Shields, MD, 3400 Civic Center Blvd, Philadelphia, PA 19104 ([email protected]).

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adipose may lead to rectal prolapse. Increased lanugo hair small amounts and frequent intervals.5 Skin-directed therapy may be present on the face, and alopecia of the scalp may is aimed at restoring epidermal function and hydration, with occur.6 In KW, cutaneous disease progresses from conflu- regular moisturization and application of barrier creams, such ent hyperkeratosis to a dry atrophic epidermis that erodes as zinc oxide ointment or petrolatum.10 easily, leaving underlying pale . The resultant pattern is one of hyperpigmented plaques with slightly raised borders, and hypopigmented patches and erosions Zinc is an essential trace element that provides regulatory, described as flaky paint (Figure 1).5 Lesions structural, and catalytic functions across multiple bio- appear first in areas of friction. The hair often is dry and chemical pathways6 and serves as an enzymatic cofactor brittle; curly hair may straighten and scale.11 Red-yellow and key component for numerous transcription factors.17 to gray-white hypopigmentation may develop, denoting Zinc is derived from sources, and its concentration periods of inadequate nutrition. The flag sign describes correlates with protein content.18 Zinc is found in both alternating horizontal bands of hypopigmentation inter- animal and plant-based proteins, albeit with a lower oral spersed with bands of pigmented hair. The nails usually bioavailability in the latter. Zinc deficiency may be inher- are thin and soft and may exhibit the nail flag sign, char- ited or acquired. Primary acrodermatitis enteropathica is acterized by horizontal bands of white and red.12 Cheilitis, an autosomal-recessive disorder of the solute carrier fam- angular , and vulvovaginitis may be present.6 ily 39 member 4 gene, SLC39A4 (encodes zinc transporter In adults, and body mass index can be ZIP4 on enterocytes); the result is abnormal zinc absorp- used to assess nutritional status, along with a focused tion from the small intestine.18 history and physical examination. Complete blood cell Acquired zinc deficiency copyoccurs from decreased dietary count, electrolyte levels, and blood urea nitrogen should be zinc intake, impaired intestinal zinc absorption, excessive assessed, as and often accompany zinc elimination, or systemic states of high catabolism or PEM.13 In KW, and hypoproteinemia low albumin (eTable). Total parenteral nutrition–associated are invariably present. Although prealbumin may be a deficiency has arisen when nutritional formulations did not valid prognostic indicator of disease outcomes and mor- contain trace elements during national shortages or when tality in patients at risk for malnutrition, checking other prolonged TPN was not anticipated and trace elements were serum biomarkers remains controversial.14 Focused testing removed.19 Zinc levels may already be low in patients with may be warranted in patients with risk factors for chronic chronicnot illness or , so even a short period on infectious processes, such as human immunodeficiency TPN can precipitate deficiency.18,19 Diets high in phytate may virus or tuberculosis.6 Skin biopsy may solidify the diagno- result in zinc deficiency, as phytate impairs intestinal zinc sis of PEM. Hypertrophy of the stratum corneum, atrophy absorption.20 Approximately 15% of patients with inflamma- of the stratum spinosum and stratum granulosum, and tory bowel disease experienced zinc deficiency worldwide.21 increased basal layer melanin have been reported.15 In Crohn disease, zinc deficiency has been associated with Treatment involves initial fluid resuscitation and cor- active intestinal inflammation, increased risk for hospitaliza- Do 22,23 rection of electrolyte imbalances, followed by nutritional tion, surgeries, and disease-related complications. replacement.13 Oral or enteral tube feedings are preferred Medications such as antiepileptics, antimetabolites, over total parenteral nutrition (TPN), as they enhance recov- or penicillamine may induce zinc deficiency, highlight- ery of the .16 Refeeding should occur in ing the importance of medication review for hospitalized patients (eTable). Catabolic states, frequently encoun- tered in hospitalized patients, increase the risk for zinc deficiency.24 Patients with necrolytic migratory erythema (associated with pancreatic glucagonomas) often experi- ence 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 CUTIS Zinc also plays an important role in cutaneous immune function.26 Zinc deficiency presents with sharply demar- cated, 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 sur- faces may be affected. Erosions often become secondarily impetiginized. Other cutaneous findings include , stomatitis, , , onychodys- FIGURE 1. Dermatitis resembling flaky paint in a patient with protein- energy malnutrition (kwashiorkor). trophy, generalized alopecia, and delayed wound heal- ing.26 Histopathology of skin lesions is characterized by

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granular layer loss, epidermal , confluent parakera- tosis, spongiosis, dyskeratosis, and psoriasiform hyper- plasia.27 Acquired bullous acrodermatitis enteropathica has been reported as a histologic mimicker of 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 and anti- coagulants 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 phospha- tase, can be a quick way to assess zinc status. Serum FIGURE 2. Koilonychia in a patient with iron-deficiency anemia. albumin also should be measured; because zinc is carried by albumin in the blood, hypoalbuminemia may result in saturation are key to early identification of IDA.35 Ferritin secondary zinc deficiency.18 levels lower than 30 µg/L confirm the diagnosis. Decreased Zinc replacement therapy is largely through oral sup- transferrin saturation and increased total iron binding plementation and should start at 0.5 to 2.0 mg/kg/d in capacity aid in the diagnosis of IDA. Serum ferritin is an adults with acquired disease.29,30 Zinc sulfate is the most acute-phase reactant, and levelscopy may be falsely elevated affordable and is the supplement of choice, with 50 mg of in the setting of inflammation or infection. elemental zinc per 220 mg of zinc sulfate (~23% elemen- Treatment includes reversing the cause of deficiency and tal zinc).31 Alternative zinc salts, such as zinc gluconate supplementing iron. Calculation of the total iron deficit can (13% elemental zinc), may be used. Patients with malab- help inform iron supplementation. First-line therapy for IDA sorptive disorders often require parenteral supplementa- is oral ferrous sulfate 325 mg (65 mg elemental iron) 3 times tion.32 Clinical symptoms often will resolve within 1 to daily. Newer studies suggest 40 to 80 mg oral iron should 2 weeks of supplementation.29 In patients with primary be taken every other day to increase absorption.39 Other acrodermatitis enteropathica, lifelong supplementation iron salts,not such as ferrous gluconate (325 mg is equivalent with 3 mg/kg/d elemental zinc should occur.6 Calcium and to 38 mg elemental iron), have been used. Iron absorption is may reduce zinc absorption, while zinc supplemen- enhanced by an acidic environment. Parenteral iron is utilized tation can interfere with and iron absorption.33 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 Iron is an essential component of the hemoglobin mol- are favored in frail patients, such as the elderly and those with Do 35 ecule. Iron homeostasis and are tightly chronic disease or heart failure. Multiple parenteral regulated processes that drive erythropoiesis. Only 5% to iron formulations exist, and their use should be driven by 10% of dietary iron is absorbed through nutrition, while underlying patient comorbidities and potential risks. Packed the remainder is recycled from red cell breakdown. Both transfusions should be considered in acute normal iron levels and iron deficiency (ID) are defined by blood loss, hypoxia, or cardiac insufficiency. age and gender.34 Iron-deficiency anemia (IDA) is one of the most common cause-specific worldwide.35 Essential Fatty Acid Deficiency is the most common and earliest symp- Essential fatty acids (EFAs) including linoleic and tom of ID. In a single study, pallor was predictive of α-linolenic acid cannot be synthesized by the human anemia in hospitalized patients; however, absence of body and must be obtained through diet (mostly plant pallor did not rule out anemia.34 Dyspnea on exertion, oils). Essential fatty acids have various functions, includ- tachycardia, dysphagia, and pica also may be reported. ing maintaining membrane integrity, form- Cutaneous CUTISmanifestations include koilonychia (Figure 2), ing prostaglandins and leukotrienes, and storing energy.40 glossitis, pruritus, angular cheilitis, and . Essential fatty acids are important in the structure and Plummer-Vinson syndrome is characterized by microcytic function of the stratum corneum and are crucial in main- anemia, glossitis, and dysphagia. taining epidermal barrier function.41 Increased epidermal Risk factors for ID include insufficient dietary consump- permeability and transepidermal water loss may be the tion,36 blood loss, malabsorptive states,37,38 and increased iron first signs of EFA deficiency (EFAD).42 requirements (eTable). Patient fragility (eg, elderly, chronic The cutaneous manifestations of EFAD include xero- disease) is a newly described risk factor where correction of sis, weeping eczematous plaques, and erosions in inter- ID may impact morbidity, mortality, and quality of life.35 triginous sites. The lesions may progress to widespread Iron deficiency can be present despite a normal hemo- and erythema. With time, the skin can globin level. Serum ferritin and percentage transferrin become thick and leathery. Alopecia may occur, and hair

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may depigment.7 Additional findings include poor wound deficiencies, including A deficiency.54 In chronic alco- healing and increased susceptibility to infections.43,44 hol use, even mild cutaneous changes may be the first clue to Essential fatty acid deficiency may occur when dietary low serum retinol.55 fat intake is severely restricted or in malabsorptive can be diagnosed by measur- states.45,46 It develops in patients on prolonged TPN, typi- ing serum retinol levels, with levels lower than 20 µg/dL cally when receiving fat-restricted nutrition,47,48 as occurs being diagnostic of deficiency.56 Decreased serum retinol in hypertriglyceridemia.47 Essential fatty acid deficiency in patients hospitalized with flaring irritable bowel dis- has developed in patients on TPN containing EFAs,47 as order has been repeatedly reported.57-59 Notably, serum the introduction of novel intravenous emulsions has retinol concentration does not decline until reserves of resulted in varying proportions of EFA.40 Premature neo- vitamin A are nearing exhaustion.33 nates are particularly at risk for EFAD.49 The US Food and Drug Administration requires manu- The diagnosis of EFAD involves the measurement of facturers to list retinol activity equivalents on labels. One the triene to tetraene ratio. A ratio of more than 0.2 sug- international unit of retinol is equivalent to 0.3 µg of gests EFAD, but the clinical signs are not seen until the retinol activity equivalents.60 The treatment of vitamin A ratio is over 0.4.40 Low plasma levels of linoleic, linolenic, deficiency involves high-dose oral supplementation when and arachidonic acids also are seen. Elevated liver function possible.61 Although dependent on age, the treatment tests are supportive of the diagnosis. Biochemical findings dose for most adults with vitamin A deficiency is 3000 µg typically are seen before cutaneous manifestations.40 (10,000 IU) once daily. Treatment of EFAD includes topical, oral, or intrave- Phrynoderma has been specifically treated with salicylic nous replacement of EFAs. Improvement of EFAD with acid ointment 3% and intramuscular vitamin A.62 Topical urea copy63 the application of topical linoleic acid to the skin has been cream also may treat phrynoderma. reported.50 Patients receiving TPN should undergo assess- ment of parenteral lipid emulsion to ensure adequate fatty Vitamin B2 acid composition. Vitamin B2 () is absorbed in the small intestine and converted into 2 biologically active forms—flavin adenine Vitamin A Deficiency dinucleotide and flavin mononucleotide—which serve as Vitamin A (retinol) is a fat-soluble vitamin that plays a criti- cofactors in metabolic and oxidation-reduction reactions. cal role in keratinization, epithelial proliferation, and cellular Malabsorptivenot disorders and bowel resection can lead to differentiation.6 Vitamin A is found in animal products as riboflavin deficiency.64 Other at-risk populations include retinyl esters and in plants as beta-carotene. Vitamin A has those with restrictive diets,65 psychiatric illness, or systemic 2 clinically important forms: all-trans retinoic acid and 11-cis- illness (eTable). Riboflavin can be degraded by light (defi- retinal. All-trans retinoic acid is involved in cellular differen- ciency has been reported after phototherapy for neonatal tiation and regulating gene transcription, while 11-cis-retinal jaundice66) and following boric acid ingestion.67 Medications, is key to rhodopsin generation required for vision. Vitamin A including long-term treatment with antiepileptics, may lead Do 68 deficiency presents with early ophthalmologic findings, spe- to riboflavin deficiency. cifically nyctalopia, or delayed adaptation to the dark.51 Riboflavin is critical to maintaining collagen production. Xerophthalmia, abnormal conjunctival keratinization, and Riboflavin deficiency may manifest clinically with extensive Bitot spots subsequently develop and may progress to corneal seborrheiclike dermatitis,44 intertrigolike dermatitis,69 or oral- ulceration and blindness.6 ocular-genital syndrome.70 Angular cheilitis may accompany Vitamin A deficiency manifests in the skin as follicu- an atrophic tongue that is deep red in color. The scrotum is lar hyperkeratosis, or phrynoderma. Notably, numerous characteristically involved in men, with confluent dermatitis other micronutrient deficiencies may result in phrynoderma. extending onto the thighs and sparing the midline. Red pap- Clinically, multiple pigmented keratotic papules of various ules and painful fissures may develop. Balanitis and phimosis sizes, many with a central keratinous plug, are distrib- have been reported. Testing for riboflavin deficiency should be uted symmetrically on the extensor elbows, knees, shoul- considered in patients with refractory seborrheic dermatitis. ders, buttocks, and extremities. The skin surrounding these Riboflavin stores are assessed by the erythrocyte glutathi- lesions mayCUTIS be scaly and hyperpigmented.52 Generalized one reductase activity coefficient.44 A level of 1.4 or higher is xerosis without preceding nyctalopia has been reported.53 consistent with deficiency. Serum riboflavin levels, performed Accompanying pityriasis alba may develop.52 Lesions on the after a 12-hour fast, may support the diagnosis but are less face may mimic , while lesions on the extremities may sensitive. Patients with -6-phosphate deficiency can- simulate a perforating disorder. Histopathology of phryno- not be assessed via the erythrocyte glutathione reductase derma reveals epidermal hyperkeratosis, follicular hyperkera- activity coefficient and may instead require evaluation of tosis, and follicular plugging.52 24-hour urine riboflavin level.44 Patients at risk for vitamin A deficiency include those with conditions that affect intestinal fat absorption, underlying psychiatric illness, or chronic disease (eTable). Chronic alco- Vitamin B3 (, , nicotinic acid) is found hol use predisposes patients to a multitude of micronutrient in plant and animal products or can be derived from its

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precursor . Niacin deficiency results Conditions that increase risk for deficiency in , characterized by dermatitis, , and are highlighted in the eTable and include malabsorp- diarrhea.71 The most prominent feature is a symmetrically tive disorders; psychiatric illness82; and chronic disease, 83 distributed photosensitive dermatitis of the face, neck especially end-stage renal disease. Vitamin B6 deficiency (called Casal necklace)(Figure 3), chest, dorsal hands, and associated with chronic alcohol use is due to both inad- extensor arms. The eruption may begin with erythema, equate vitamin B6 intake as well as reduced hepatic stor- vesicles, or bullae (wet pellagra) and evolve into thick, age.78 Medications such as , hydralazine, and oral 71 82 hyperpigmented, scaling plaques. The skin may take on contraceptives may decrease vitamin B6 levels (eTable). 72 a copper tone and become atrophic. Dull erythema with Vitamin B6 can be measured in the plasma as pyri- overlying yellow powdery scale (called sulfur flakes) at doxal 5′-phosphate. Plasma concentrations of less than follicular orifices has been described on the nasal bridge.73 20 nmol/L are suggestive of deficiency.82 Indirect tests Causes of niacin deficiency include malabsorptive include tryptophan and loading.6 The treat- conditions, malignancy (including tumors), ment of vitamin B6 deficiency is determined by symp- parenteral nutrition, psychiatric disease,74,75 and restric- tom severity. Recommendations for oral supplementation tive diets (eTable).76 Carcinoid tumors divert tryptophan range from 25 to 600 mg daily.82 Symptoms typically to resulting in niacin deficiency.77 improve on 100 mg daily.6 The diagnosis of niacin deficiency is based on 75 clinical findings and response to supplementation. Low B9 and B12 niacin urinary metabolites (N-methylnicotinamide and Deficiencies of vitamins B9 (folic acid, folate) and B12 2-pyridone) may aid in diagnosis.6 Treatment generally (cobalamin) have similar clinicalcopy presentations. Folate is includes oral nicotinamide 100 mg every 6 hours; the dose essential in the metabolism of amino acids, , and can then be tapered to 50 mg every 8 to 12 hours until .6 Cobalamin, found in animal products, is a symptoms resolve. Severe deficiency may require parenteral cofactor for and methylmalonyl- nicotinamide 1 g 3 to 4 times daily.75 CoA mutase.84 is the main finding in folate or cobalamin deficiency. Neurologic findings only Vitamin B6 accompany cobalamin deficiency. Risk factors for folate 6 Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal) is deficiency include malabsorptive conditions, chronic found in whole grains and plant and animal products. alcoholnot use,85 and medication use (eTable).6 Vitamin B6 functions as a coenzyme in many metabolic Cobalamin absorption requires gastric acid and intrin- pathways and is involved in the conversion of tryptophan to sic factor binding in the duodenum. Deficiency may occur niacin.44 Absorption requires hydrolysis by intestinal phos- from strict diets, psychiatric illness, ,86 decreased phates and transport to the liver for rephosphorylation prior gastric acid secretion,87 abnormal function, to release in active form.6 or intestinal infections.6

Cutaneous findings associated with vitamin B6 deficiency Generalized cutaneous hyperpigmentation may be Do78 88 include periorificial and perineal seborrheic dermatitis, the first manifestation of vitamins B9 and B12 deficiency. angular stomatitis, and cheilitis, with associated burning, Typically accentuated in acral creases and the oral cavity, 6 redness, and tongue edema. Vitamin B6 deficiency is a rarely pigmentation may mimic Addison disease. Hair depig- reported cause of burning mouth syndrome.79 Because mentation and linear streaking of the nails are reported.84 vitamin B6 is involved in the conversion of tryptophan to nia- The tongue becomes painful and red with atrophy of the cin, deficiency also may present with pellagralike findings.70 filiform papillae (Hunter glossitis).78 Linear lesions on Other clinical symptoms are outlined in the eTable.80,81 the tongue and hard palate may serve as an early sign of cobalamin deficiency.89 is diagnosed by measuring the plasma folate level; coincidental cobalamin deficiency should be excluded. Deficiency is managed with oral supplementation (when possible) with 1 to 5 mg of CUTIS folate daily.6 Cobalamin deficiency is based on low serum levels (<150 pg/mL is diagnostic).86 Cobalamin defi-

ciency may take years to develop, as exists in large body stores.6 Serum methylmalonic acid may be elevated in patients with clinical features but normal- 86 low serum vitamin B12 level. Treatment of is with oral (2 mg once daily) or parenteral (1 mg every 4 weeks then maintained at once monthly) . For patients with neurologic symptoms, FIGURE 3. Photosensitive dermatitis of the neck and upper chest intramuscular injection should be given.86 The underlying (Casal necklace) seen in vitamin B3 deficiency (pellagra). cause of deficiency must be elucidated and treated.

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Vitamin C Deficiency common yet underrecognized in the hospitalized patient Vitamin C (ascorbic acid) is an essential cofactor for the and serve as an independent risk factor for patient morbidity hydroxylation of proline and lysine residues in collagen and mortality.3 Awareness of the cutaneous manifestations of synthesis. Plant-based are the main dietary source undernutrition as well as the risk factors for nutritional defi- of vitamin C, and deficiency presents clinically as . ciency may expedite diagnosis and supplementation, thereby Cutaneous findings include follicular hyperkeratosis, improving outcomes for hospitalized patients. perifollicular petechiae, and curled hair shafts (corkscrew hairs)(Figure 4). Ecchymoses of the lower extremities, REFERENCES forearms, and abdomen may be seen. Nodules represent- 1. Mehta NM, Corkins MR, Lyman B, et al. 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The physiologic response and associated clinical benefits from provision of early enteral nutrition. Nutr Clin Pract. 2009;24:305-315. 17. Ogawa Y, Kinoshita M, Shimada S, et al. Zinc and skin disorders. Nutrients. 2018;10:199. 18. Maverakis E, Fung MA, Lynch PJ, et al. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol. 2007;56:116-124. 19. Wiznia LE, Bhansali S, Brinster N, et al. Acquired acrodermatitis entero- pathica due to zinc-depleted parenteral nutrition. Pediatr Dermatol. CUTIS 2019;36:520-523. 20. Sandstead HH, Freeland-Graves JH. Dietary phytate, zinc and hidden zinc deficiency. J Trace Elem Med Biol. 2014;28:414-417. 21. Vagianos K, Bector S, McConnell J, et al. Nutrition assessment of patients with inflammatory bowel disease. JPEN J Parenter Enteral Nutr. 2007;31:311-319. 22. Schoelmerich J, Becher MS, Hoppe-Seyler P, et al. 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CONTINUED FROM PAGE 302 94. Lux-Battistelli C, Battistelli D. Latent scurvy with tiredness and leg pain

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the first manifestation of dietary vitamin B12 deficiency. Indian J Dermatol C in Alzheimer patients despite an adequate diet. Int J Geriatr Psychiatry. Venereol Leprol.CUTIS 2006;72:389-390. 1998;13:749-754. 89. Graells J, Ojeda RM, Muniesa C, et al. Glossitis with linear lesions: an early 101. Bhattacharyya P, Giannoutsos J, Eslick GD, et al. Scurvy: an unrecognized

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308 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2020. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. HOSPITAL CONSULT 74 17 continued 65 18 increased increased 16 19 impaired growth, growth, impaired 83 dizziness, dysphagia, xeropthalmia, xeropthalmia, 66 18 18 shrunken wasted dyspnea on exertion, 18 66 Poor wound healing, increased Poor wound healing, increased fatty restriction, infections, growth anemia, liver, appearance keratomalacia, Bitot spots, corneal ulceration, blindness, tachycardia, , , pica altered bony development altered infections (severe measles if infections (severe unvaccinated), Kwashiorkor: symmetric edema, secondary infections anasarca, Diarrhea, photosensitivity, anorexia, anorexia, Diarrhea, photosensitivity, , , , infections, increased failure, growth pica pubertal delay, Fatigue, Nyctalopia, Marasmus: ; chronic to thrive; chronic Marasmus: failure diarrhea, Systemic Manifestations

; 49

82

65 75 ; alopecia 48 ; stomatitis; 19 pale erythema, flag sign 17 copy ; angular cheilitis scaling scalp dermatitis, 16 74 pruritus, angular cheilitis, hyperpigmentation, scaling hyperpigmentation, scaling weeping eczematous plaques, 52 77 74 desquamation and erythema, 82 50 cheilitis, angular stomatitis, vulvovaginitis 74 8 66 16 not Marasmus: dry, wrinkled, loose skin; loss of buccal fat pads;  Marasmus: dry, lanugo hair; alopecia; petechiae and purpura; impaired increased nail growth  Kwashiorkor: flaky paint dermatitis, confluent hyperkeratosis, hyperpigmented plaques, hypopigmented patches, cutaneous at frictional sites, and erosions atrophy of the hair and nails, glossitis; paronychia; onychodystrophy; Beau lines onychodystrophy; glossitis; paronychia; delayed wound healing telogen effluvium alopecia, hair depigmentation, petechiae, purpura intertriginous erosions, Cutaneous Manifestations • • Periorificial, perianal, and acral dermatitis; sharply demarcated, pink, eczematous and flaccid pustules and bullae; scaly, psoriasiform plaques; erosions plaques, pityriasis alba Symmetric phrynoderma, pigmented keratotic papules, Pallor, koilonychia, glossitis, Pallor, cutaneous xerosis,  Diffuse diffuse cutaneous xerosis, diffuse

47

13

34 53

70 60 zinc- 38 chronic chronic short 62 21-23 30

, 77 46 intestinal 8

79 Do menstruation 53 cystic fibrosis eating disorders

73 4 intestinal bypass 69 12 , 44 41

64 gastric antral der, attention deficit der, 61 72 58 52 54,55 41 surgery, diverticulitis, pancreatic insufficiency, pancreatic 7

52 IBD, zinc-deficient TPN, 33 53 20

connective tissue disease 51,52 59 52 intestinal bypass surgery, esophagitis, antimetabolites, antiepileptics

, 1 57 26 76 52 ; chronic diarrhea ; chronic substance abuse, 28,29 36,37 40 chronic alcohol use chronic 80 hookworm infection 10,11 chronic alcohol use chronic 63

celiac disease, eatic insufficiency, IBD, biliary disease, eatic insufficiency, IBD, 81

chronic intestinal giardiasis chronic 42,43 71 6 celiac disease, 19 malignancy, 27 38 78 renal disease, sickle cell renal 32 54

45 35 , , , atrophic 15 IBD, peptic ulcer disease, 5 53 extracorporeal photopheresis, extracorporeal 53,52

premature infants premature 52,56 67,68 dialysis Mycobacterium tuberculosis infection 14 24,25 2,3 ; chronic alcohol use ; chronic cystic fibrosis, 39 31 long-term use of proton pump inhibitors long-term use of proton Whipple disease, , 9 52 33 54

CUTIS Helicobacter pylori infection, 56 chronic granulomatous disease chronic vascular ectasia, Cameron ulcer, epistaxis ulcer, vascular ectasia, Cameron procedures, deficient breast , deficient breast malignancy, chronic infection, burns, trauma, surgery chronic malignancy, bowel syndrome, bypass surgery  Malabsorption: cystic fibrosis, intake: strict diets (vegan, vegetarian),  Decreased  Malabsorption: high-phytate diets, penicillamine,  Medication induced: EDTA, ACE inhibitors, and angiotensin  Excessive elimination: thiazides, loop , blockers receptor illness: hepatic disease,  Chronic celiac disease,  Malabsorption: celiac disease anti-  Medication-induced: long-term use of aspirin or nonsteroidal inflammatories, autism spectrum disor  Psychiatric illness: mood disorders, developmental disorders hyperactivity disorder,  Blood loss: blood donation,  Other: pancr  Malabsorption: cystic fibrosis, hepatic disease, intestinal bypass surgery, intravascular or traumatic hemolysis,  Psychiatric illness: chronic alcohol use, Psychiatric illness: chronic  Chronic illness: CKD, heart failure, Chronic IBD, celiac disease, Malabsorption: intestinal bypass surgery, • Medication induced: antiepileptics • Risk Factors • Infection: HIV/AIDS, • illness: CKD, • Chronic • • • • • Psychiatric illness: eating disorders, • • • • • • • elderly, •  kidney disease chronic syndrome, illness: nephrotic • Chronic • syndrome illness: nephrotic • Chronic • Psychiatric illness: chronic alcohol use • Psychiatric illness: chronic • Psychiatric illness: eating disorders, • Decreased intake: severe dietary restriction intake: severe • Decreased • Inherited: SLC39A4 gene mutation • Decreased intake: strict diets (vegan/vegetarian) • Decreased intake: TPN • Decreased Risk Factors and Manifestations of Nutritional Deficiency e TABLE. Condition Protein-energy malnutrition Zinc deficiency Iron deficiency Iron Essential fatty acid deficiency Vitamin A deficiency APPENDIX

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108 109

110 102 76 108 Megaloblastic anemia, pallor, Megaloblastic anemia, pallor, fatigue irritability, Fatigue, epistaxis, loose teeth, mood changes, bony depression Psychiatric symptoms, dementia, diarrhea increased irritability, depression, infections Sideroblastic microcytic anemia, microcytic Sideroblastic , Megaloblastic anemia, fatigue, pallor irritability, sequelae neurologic neurologic symptoms, neurologic Rare, predominantly predominantly Rare, mucocutaneous symptoms seen Systemic Manifestations red papules red 18,76 oral-ocular-genital oral-ocular-genital copper tone to 102 91 18 104 linear lesions on the linear lesions on the 113 113 glossitis, angular cheilitis, glossitis, angular cheilitis, 16 16 copy intertrigolike dermatitis,

75 , solute carrier family 39 member 4; TPN, total parenteral nutrition; , solute carrier family 39 member 4; TPN, total parenteral

114 114 seborrheiclike dermatitis 139 18 cheilitis, glossitis, perineal eruption SLC39A4 101 dull erythema with yellow powdery scale over follicular orifices

100 not Angular stomatitis, cheilitis, glossitis, burning tongue, pellagralike dermatitis, intertrigo, syndrome (cheilitis; angular stomatitis; glossitis; deep red, atrophic atrophic (cheilitis; angular stomatitis; glossitis; deep red, syndrome dermatitis extending onto the thighs), tongue; scrotal  Pellagra (photosensitive dermatitis of the face, neck [Casal necklace], chest, dorsal hands, and extensor arms; vesicles or bullae (wet pellagra); thick, hyperpigmented, scaling plaques), Generalized cutaneous hyperpigmentation (accentuated in acral intertriginous sites, oral cavity), creases, Generalized cutaneous hyperpigmentation (accentuated in acral intertriginous sites, oral cavity), creases, depigmented hair, linear streaking of nails, linear streaking depigmented hair, Follicular hyperkeratosis, perifollicular petechiae, curled hair shafts hairs), ecchymoses, nodules (intramuscular and (corkscrew subcutaneous hemorrhage), woody edema, gingival hyperplasia, linear splinter hemorrhages depigmented hair, linear streaking of nails, linear streaking depigmented hair, and fissures, balanitis, phimosis and fissures, Seborrheiclike dermatitis, (sulfur flakes), skin, tongue and hard palate tongue and hard tongue and hard palate tongue and hard Cutaneous Manifestations

134

119

106 IBD, 16 138

89 hospitalization Do dialysis intestinal

127 117 elderly 105 85 133 103 124 99 137 76 intestinal 95

84 115 phototherapy, dementia, 88 130 110 136 etion (proton pump inhibitors, etion (proton chronic GVHD, chronic celiac disease, eating disorders obsessive-compulsive disorder anorexia nervosa, anorexia

132 123 104 118 126 112

chronic alcohol use chronic

93 nilotinib 98

IBD, 110 , 129 103 94 122

dialysis,

TPN 120 86 92 103 131 121 16

38

intestinal bypass surgery, celiac disease, intestinal bypass surgery, 97 decreased intrinsic factor (pernicious anemia), intestinal decreased

128 111 90 116

IBD low socioeconomic status, 16 inborn errors of metabolism inborn errors 96

pregnant or lactating women, pregnant 125 135 87 110 CUTIS 107 boric acid ingestion psychiatric disorders bypass surgery, bypass surgery Malabsorption: intestinal surgery, intestinal bypass surgery  Malabsorption: intestinal surgery,  Other: elderly, tumors,  Malabsorption: carcinoid  Malabsorption: IBD, oral contraceptives,  Medications: , ,  Medication induced: isoniazid, hydralazine, theophylline, cycloserine, penicillamine, oral contraceptives gastric acid secr  Malabsorption: decreased  Malabsorption: Whipple disease, Psychiatric illness: chronic alcohol use,  Psychiatric illness: chronic celiac disease, Whipple disease, Zollinger-Ellison syndrome celiac disease, Whipple Zollinger-Ellison chronic diarrhea chronic infection (bacterial overgrowth, giardiasis, Diphyllobothrium latum ), giardiasis, infection (bacterial overgrowth, antiepileptics, H2 ), • Psychiatric illness: eating disorders, • Other: elderly • Psychiatric illness: chronic alcohol use • Psychiatric illness: chronic • Psychiatric illness: chronic alcohol use, eating disorders • Psychiatric illness: chronic • • Medications: antiepileptics • • • • • intake: strict diets (vegan/vegetarian) • Decreased • alcohol use, • Psychiatric illness: chronic • Medication induced: • Other: elderly, • • overload, illness: iron • Chronic • Decreased intake: strict diets • Decreased • Chronic illness: hypothyroidism • Chronic • Psychiatric illness: chronic alcohol use, • Psychiatric illness: chronic • Medication induced: vemurafenib, • Other: autism, • Chronic illness: hepatic disease, hepatocellular carcinoma, • Chronic Risk Factors • Decreased intake: strict diets (vegan/vegetarian), • Decreased intake: strict diets, • Decreased • Malabsorption: celiac disease intake: strict vegan diet • Decreased

2 3 6 9 12 continued deficiency Vitamin B Condition Vitamin B Vitamin B Vitamin B Vitamin C deficiency Abbreviations: HIV, human immunodeficiency virus; IBD, irritable bowel disease; CKD, chronic kidney disease; human immunodeficiency virus; IBD, irritable bowel disease; CKD, chronic HIV, Abbreviations: ethylenediaminetetraacetic acid; ACE, angiotensin-converting enzyme; GVHD, graft-vs-host disease. EDTA, deficiency deficiency deficiency deficiency Vitamin B

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