When Vitamin And Nutritional Deficiencies Cause Skin And Nail Changes

If patients are not getting enough micronutrients or macronutrients, dermatologic conditions can arise in the skin and nails. Accordingly, this author offers salient insights on cutaneous manifestations of various vitamin and nutritional deficiencies.

Numerous skin and nail changes result from macronutrient and micronutrient deficiency. Macronutrients include carbohydrates, fats and protein whereas micronutrients include vitamins and minerals. In developed countries, vitamin and nutritional deficiencies most commonly result from poverty, restrictive diets, medication, alcoholism and inadequate dietary intake in the ill and elderly. Recognition of skin and nail changes can be an important tool for diagnosing underlying nutritional deficiencies.  

In developed nations, macronutrient deficiency is very rare. Protein and essential fatty acid deficiency occur more frequently than carbohydrate deficiency due to the high carbohydrate content of many foods. Both protein and essential fatty acid deficiencies result in cutaneous and nail disorders as these nutrients serve as building blocks for these structures.

Protein is a critical nutrient for human growth and maintenance of body tissues. Proteins perform a large array of functions including catalyzing metabolic reactions, replicating DNA, transporting molecules and cell signaling. Amino acids are the primary constituent of protein. The nutritional characteristics of a protein depend on its amino acid composition. There are nine essential amino acids: histidine, lysine, isoleucine, leucine, methionine, tryptophan, threonine, valine and phenylalanine.

Protein-energy malnutrition results from inadequate protein intake. In developed countries, protein deficiency is most commonly associated with disease and advanced age. Severe protein deficiency results in kwashiorkor, which is characterized by edema, irritability, anorexia, ulcerating dermatoses and liver enlargement.^1,2 In addition to ulcerating dermatoses, there are several other dermatologic manifestations of protein deficiency including desquamative rash, hair discoloration and thinning, skin depigmentation, impaired wound healing and dermatitis.^1,2

Essential fatty acids are those that people must ingest as the body cannot synthesize them. The two essential fatty acids are linoleic acid (omega-6 fatty acid) and alpha-linolenic acid (omega-3 fatty acid). Essential fatty acid deficiency is very rare as even small amounts of dietary intake can prevent deficiency. In cases of essential fatty acid deficiency, scaly dermatitis, alopecia and intellectual disability can result.³

Understanding The Dangers Of Vitamin Deficiency
Vitamin deficiencies are frequent causes of several dermatologic disorders. Deficiencies of water-soluble vitamins, such as most B vitamins and vitamin C, may develop after weeks to months of under-nutrition. Deficiencies of fat-soluble vitamins, such as vitamins A, D, E, K and B12, can take up to a year to develop because the body stores them in relatively large amounts.

Biotin is a water-soluble B vitamin that acts as a coenzyme for essential reactions for fat and carbohydrate metabolism. Biotin deficiency is extremely rare due to several factors including a low daily biotin requirement, wide distribution of biotin in readily available foods, biotin synthesis from intestinal bacteria and homeostatic mechanisms for scavenging and recovering biotin from body waste.^4,5 However, biotin deficiency can result from total parental nutrition, protein deficiency, prolonged anticonvulsant therapy, severe malnutrition, prolonged oral antibiotic therapy, consumption of raw egg whites, alcohol abuse and excessive antidiuretic medication use.⁶

Dermatologic signs of biotin deficiency include thinning of hair and hair loss, patchy red rash (most commonly near the mouth), seborrheic dermatitis and fungal skin and nail infections.⁶ Other conditions associated with biotin deficiency include hallucinations, lethargy, anorexia, depression, myalgia and paresthesias.⁶

Folate is required for red blood cell production and DNA synthesis. Folate deficiency is a common disorder and results from under-nutrition, alcoholism, malabsorption, increased folate demand (pregnancy and lactation) and medications such as metformin, triamterene (Dyrenium, WellSpring Pharmaceutical), oral contraceptives, anticonvulsants and methotrexate.⁷ Symptoms of folate deficiency include weakness, loss of appetite and weight loss.⁸ Severe folate deficiency results in megaloblastic anemia, which is characterized by large, abnormally nucleated erythrocytes. Symptoms of megaloblastic anemia include weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations and shortness of breath.^9,10 Dermatologic manifestations of folate deficiency include painful oral mucosa, pallor and changes in skin, hair or fingernail pigmentation.^9,10

A Closer Look At Specific Vitamin Deficiencies
Niacin (vitamin B3). Niacin plays an important role in cell metabolism, namely oxidation-reduction reactions. Pellagra is a disorder that results from a chronic lack of niacin. Pellagra is rare in developed countries. It most commonly arises in areas where maize is a substantial part of the diet. Maize is a poor source of niacin because the gastrointestinal tract does not assimilate bound niacin unless it has been treated with alkali.¹¹ Pellagra is classically described by the four D’s: diarrhea, dermatitis, dementia and death.¹²

Cutaneous manifestations of niacin deficiency include sunlight sensitivity, dermatitis, hair loss and red skin lesions.¹² Skin lesions in pellagra tend to be symmetric and occur in sun-exposed areas and on pressure points. The appearance of skin lesions in pellagra can be variable but the symmetric distribution at pressure points and sun-exposed skin is more pathognomonic.¹² Lesions can develop in a glove-like distribution on the hands (pellagrous glove) or in a boot-shaped distribution on the feet and legs (pellagrous boot).12 Additionally, sunlight can cause casal necklace, an erythematous rash in the distribution of a broad collar and butterfly-shaped lesions on the face.¹²

Vitamin B6. Vitamin B6 is an important cofactor in many enzymatic reactions of amino acid, lipid and glucose metabolism. It plays an important role in hemoglobin synthesis and function. While rare, dietary deficiency of vitamin B6 can result from excessive food processing, under-nutrition, malabsorption, renal disease and alcoholism. Other causes include the use of pyridoxine-inactivating drugs such as anticonvulsants, isoniazid (Laniazid), cycloserine (Seromycin), hydralazine (Apresoline, Novartis), corticosteroids or penicillamine (Cuprimine, Valeant Pharmaceuticals).^13,14 Isolated vitamin B6 deficiency is uncommon and usually associated with low levels of other B vitamins.

The classic clinical syndrome for vitamin B6 deficiency is a seborrheic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis (scaling on the lips and cracks at the corners of the mouth), conjunctivitis, intertrigo, sideroblastic anemia (due to impaired heme synthesis) and neurologic symptoms of somnolence, confusion, depression and neuropathy.^13,14

Vitamin B12. Vitamin B12 plays a key role in metabolism, nervous system function and red blood cell formation. Specifically, it has important functions in DNA synthesis and regulation, fatty acid metabolism and amino acid metabolism.¹⁶ Causes of vitamin B12 deficiency include inadequate diet (vegan diet), impaired absorption (lack of intrinsic factor, decreased GI acid secretion, small bowel disease) and drugs (antacids, metformin, nitrous oxide).¹⁶ The main clinical syndrome resulting from vitamin B12 deficiency is pernicious anemia, which is characterized by megaloblastic anemia.

Gastrointestinal symptoms of vitamin B12 deficiency include abdominal pain and weight loss as well as neurologic symptoms including sensory and motor neuropathy, seizure, depression and dementia.¹⁷ Cutaneous manifestations of vitamin B12 deficiency include pallor and brown-gray fingernail and toenail discoloration.¹⁸

Vitamin A. Vitamin A is important in the maintenance of epithelial tissues. Vitamin A is present in fish oils, liver, egg yolks, butter and vitamin A-fortified diary products. Additionally, vitamin A is a product of beta-carotene and other provitamin carotenoids that are part of green leafy and yellow vegetables, and deep and bright colored fruit. Vitamin A deficiency can result from inadequate intake, fat malabsorption and liver disorders, and can lead to numerous ophthalmologic, systemic and dermatologic conditions.

Ocular manifestations of vitamin A deficiency include xerophthalmia (dry eyes), keratomalacia (corneal necrosis/ulceration), nyctalopia (night blindness), Bitot’s spots (conjunctival lesions) and photophobia.²⁰ Dermatologic manifestations of vitamin A deficiency include generalized xerosis and follicular hyperkeratosis.¹⁹ Xeroses resulting from vitamin A deficiency are characterized by fine wrinkles and scales.¹⁹ Follicular hyperkeratosis is characterized by red-brown follicular papules with a central keratotic spinous plug.¹⁹ These lesions are usually clustered around the bony prominences of the elbows and the knees, but may extend further up and down the extremities.¹⁹

Vitamin C. Vitamin C is a cofactor in numerous collagen synthesis reactions and plays an essential role in collagen and amino acid formation. Vitamin C is an antioxidant that supports immune function and is also essential to wound healing. Severe vitamin C deficiency results in scurvy, which is characterized by general weakness, anemia, gum disease and skin hemorrhages.^21,22 In developed nations, scurvy is very rare and milder vitamin C deficiency resulting from under- or malnutrition is more common.

Systemic symptoms of vitamin C deficiency include fatigue, weakness, weight loss, myalgia and arthralgias.^20,21 Dermatologic manifestations of vitamin C deficiency result from defects in connective tissue development and include rough skin, follicular hyperkeratosis, coiled hair, perifollicular hemorrhages, easy bruising, petechiae and skin tears.^20,21 Deficiency also results in poor wound healing and secondary infections.^20,21

When Patients Are Not Getting Enough Minerals, Iron Or Zinc
Six micronutrients (sodium, potassium, calcium, magnesium, chloride and phosphorus) and nine trace minerals (zinc, selenium, molybdenum, chromium, copper, iodine, iron, manganese and fluorine) are required in the human diet. Mineral deficiency can result from inadequate consumption, inadequate digestion or absorption, and increased demand for minerals. Mineral deficiencies are more common in children due to their increased requirements secondary to growth.

Iron deficiency is the most common nutritional deficiency in the world. Iron has numerous functions in the body including carrying oxygen to tissues, serving as cytochromes to carry electrons within cells, facilitating oxygen storage in muscle and facilitating numerous enzymatic reactions in tissues.²³ Iron deficiency can range from depleted iron stores without functional impairment to iron deficiency anemia, which affects several organ systems. Iron deficiency has several dermatologic manifestations including pallor, hair loss, brittle nails, nails with a central groove and koilonychia (spoon shaped nails).¹⁸ Additional symptoms of iron deficiency anemia include anxiety, irritability, sleepiness, heart palpitations, syncope and shortness of breath.²³

Zinc is a mineral that is an important component of numerous enzymes and plays an essential role in several biochemical pathways. Zinc deficiency most commonly results from inadequate dietary intake but can also result from inadequate absorption (small bowel disease) and increased loss (diuretics, hepatic insufficiency).²⁴ Symptoms of zinc deficiency include hypogonadism, alopecia, impaired immunity, anorexia, dermatitis, night blindness, anemia, lethargy and impaired wound healing.¹⁶ Specific dermatologic manifestations of zinc deficiency include dermatitis, xerosis, seborrheic dermatitis, thin hair and impaired wound healing.¹⁶

Pertinent Insights On Specific Lower Extremity Skin And Nail Manifestations
Several skin and nail changes can be signs of an underlying nutritional deficiency. Recognition of these symptoms caused by nutritional deficiency can help aid in the diagnosis and subsequent treatment.

Pallor. Pallor results from decreased oxyhemoglobin in the skin. Severe anemia can lead to skin pallor. Anemia is associated with numerous nutritional deficiencies including iron deficiency, zinc deficiency, vitamin B12 deficiency, vitamin B6 deficiency and folate deficiency.

Impaired wound healing. Impaired wound healing can result from nutritional deficiencies, including protein, vitamin C and zinc deficiency. Protein-energy malnutrition can affect wound healing. Serum albumin and total lymphocyte count are valid tests of a patient’s protein nutrition status.²⁵ Serum albumin levels less than 3.5 mg/dL and total lymphocyte counts less than 1,500/mm³ are associated with delayed wound healing.²⁵ Researchers have shown that nutritional supplementation with protein dense oral supplements improves wound healing.²⁶ Malnutrition with resulting zinc and vitamin C deficiency can also result in impaired wound healing. Zinc and vitamin C supplementation may aid in the wound healing process.^27,28

Dermatitis. Dermatitis is characterized by itchy, erythematous, edematous, vesicular, weeping, flaking and crusting patches of skin. Protein, essential fatty acid, niacin (vitamin B3) and zinc deficiency can result in dermatitis.

Seborrheic dermatitis. Seborrheic dermatitis is an inflammatory skin condition that causes erythema and flaky, white to yellowish scales to form on oily sebaceous gland rich areas, such as the scalp and nasolabial fold. Seborrheic dermatitis can be a symptom of vitamin B6, biotin and zinc deficiency.

Petechiae. Petechiae are small 1-2 mm red or purple spots on the skin that result from minor hemorrhage due to broken capillary blood vessels. Petechiae can result from both niacin (vitamin B3) and vitamin C deficiency.

Follicular hyperkeratosis. Follicular hyperkeratosis is a skin condition characterized by excessive development of keratin in hair follicles, resulting in red-brown follicular papules with a central keratotic plug. The follicle openings are often closed with a white plug of sebum. Several vitamin deficiencies can result in follicular hyperkeratosis including vitamin A, B and C deficiency.^19,29 Several studies have shown that supplementation with vitamins and essential fatty acids can lead to improvement and resolution of this condition.²⁹

Xerosis. Xerosis is abnormal dryness of the skin and mucous membrane. This condition is characterized by dry, scaling, itching, and cracking skin. Both vitamin A and zinc deficiency can result in xerosis.

Nail color changes. Nail plate discoloration can result from several nutritional deficiencies. Research has shown vitamin B12 deficiency to cause brown-gray nail discoloration.¹⁸ White nails can be the result of anemia and pink or red nails may suggest malnutrition with several nutrient and vitamin deficiencies.³⁰ Additionally, biotin deficiency can increase the risk of fungal nail infections and subsequent nail plate discoloration.³¹

Changes in nail shape and surface. Nutritional deficiencies can cause several changes in the shape and surface of nail plates. A central nail plate ridge can arise from iron deficiency, folic acid deficiency or protein deficiency.³⁰ A central nail groove can result from iron deficiency.³⁰ Beads that appear to drip down the nail like wax are associated with vitamin B deficiencies.¹⁸ Koilonychia is associated with iron deficiency and protein deficiency, especially deficiency of sulfur-containing amino acids.³² Beau’s lines are transverse depressions in the nail plate caused by temporary cessation of nail growth. Researchers have proposed severe zinc deficiency as a cause of Beau’s lines.^31,33  

In Conclusion
Numerous skin and nail changes result from macronutrient and micronutrient deficiency. Recognizing these dermatologic symptoms associated with nutritional deficiencies can be an important diagnostic tool and lead to appropriate treatment.

Dr. Hoffman is in private practice in Boulder, Colo.

References

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