Generalized cutaneous hyperpigmentation may be the first manifestation of vitamins B9 and B12 deficiency.88 Typically accentuated in acral creases and the oral cavity, pigmentation may mimic Addison disease. Hair depigmentation and linear streaking of the nails are reported.84 The tongue becomes painful and red with atrophy of the filiform papillae (Hunter glossitis).78 Linear lesions on the tongue and hard palate may serve as an early sign of cobalamin deficiency.89
Folate deficiency 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 folate daily.6 Cobalamin deficiency is based on low serum levels (<150 pg/mL is diagnostic).86 Cobalamin deficiency may take years to develop, as vitamin B12 exists in large body stores.6 Serum methylmalonic acid may be elevated in patients with clinical features but normal-low serum vitamin B12 level.86 Treatment of vitamin B12 deficiency is with oral (2 mg once daily) or parenteral (1 mg every 4 weeks then maintained at once monthly) cyanocobalamin. For patients with neurologic symptoms, intramuscular injection should be given.86 The underlying cause of deficiency must be elucidated and treated.
Vitamin C Deficiency
Vitamin C (ascorbic acid) is an essential cofactor for the hydroxylation of proline and lysine residues in collagen synthesis. Plant-based foods are the main dietary source of vitamin C, and deficiency presents clinically as scurvy. Cutaneous findings include follicular hyperkeratosis, perifollicular petechiae, and curled hair shafts (corkscrew hairs)(Figure 4). Ecchymoses of the lower extremities, forearms, and abdomen may be seen. Nodules representing intramuscular and subcutaneous hemorrhage can be present.90 Woody edema may mimic cellulitis, while lower extremity hemorrhage may mimic vasculitis. Gingival hyperplasia, hemorrhage, and edema may occur,90 along with linear splinter hemorrhages.91
Figure 4. Perifollicular hemorrhage and corkscrew hairs in a patient with vitamin C deficiency (scurvy).
Hypovitaminosis C has been routinely demonstrated in hospitalized patients.92 Scurvy may occur in patients on strict diets,93 chronic alcohol use,94 psychiatric illness,95 or gastrointestinal tract disease (eTable).96-99 Those with low socioeconomic status70 or dementia100 as well as the elderly also are at risk.101 Scurvy has developed in patients with iron overload and those who are on hemodialysis44 as well as in association with nilotinib use.102 Patients with chronic mucous membrane graft-vs-host disease may exhibit vitamin C deficiency.103
Scurvy is a clinical diagnosis. Vitamin C levels normalize quickly with supplementation. Cutaneous biopsy will exhibit follicular hyperkeratosis, perifollicular hemorrhage, and fibrosis.91
Oral ascorbic acid supplementation should be initiated at 500 to 1000 mg daily in adults.104 The cause of deficiency should be identified, and further supplementation should be decided based on patient risk factors. Lifestyle modifications, such as cessation of smoking and chronic alcohol use, is recommended. The diagnosis of scurvy should prompt workup for additional nutrient deficiencies.
Final Thoughts
Dermatologists play an important role in the early recognition of nutritional deficiencies, as cutaneous manifestations often are the first clue to diagnosis. Nutritional deficiencies are common yet underrecognized in the hospitalized patient and serve as an independent risk factor for patient morbidity and mortality.3 Awareness of the cutaneous manifestations of undernutrition as well as the risk factors for nutritional deficiency may expedite diagnosis and supplementation, thereby improving outcomes for hospitalized patients.