The Clinical Picture
Scurvy is not a disease of the past: 18% of Americans don't get enough vitamin C.
Fabrizio Galimberti, MD, PhD
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Natasha A. Mesinkovska, MD, PhD
Department of Dermatology and Dermatopathology, University of California Irvine
Address: Natasha Atanaskova Mesinkovska, MD, PhD, Department of Dermatology and Dermatopathology, University of California Irvine, Gottschalk Medical PLaza, 1 Medical PLaza Drive, Irvine, CA 92697; firstname.lastname@example.org
ABSTRACTCertain vitamin and mineral deficiencies may be recognized by their cutaneous signs. This case-based article reviews deficiencies of zinc and vitamins A, B2, B3, B6, and C, discussing their consequences and skin findings.
Although vitamin and mineral deficiencies are relatively uncommon in the United States and other developed countries, physicians must be alert to them, particularly in specific populations such as infants, pregnant women, alcoholics, vegetarians, people of lower socioeconomic status, and patients on dialysis, on certain medications, or with a history of malabsorption or gastrointestinal surgery. The skin is commonly affected by nutritional deficiencies and can provide important diagnostic clues.
This article reviews the consequences of deficiencies of zinc and vitamins A, B2, B3, B6, and C, emphasizing dermatologic findings.
A 65-year-old woman who had been on total parenteral nutrition for 4 months after undergoing surgical debulking for metastatic colon cancer was admitted for evaluation of a rash on her face and extremities and failure to thrive. The rash had started 10 days earlier as small red papules and vesicles on the forehead and progressed to cover the forehead and lips. She had been prescribed prednisone 20 mg daily, but the condition had not improved.
Physical examination revealed numerous violaceous papules, plaques, and vesicles on her face, legs, and feet (Figure 1). The vesicles were tender to touch and some were crusted. Biopsy of a lesion on her leg revealed psoriasiform dermatitis with prominent epidermal pallor and necrosis (Figure 2), suggestive of a nutritional deficiency.
Blood testing revealed low levels of alkaline phosphatase and zinc. She was started on zinc supplementation (3 mg/kg/day), and her cutaneous lesions improved within a month, confirming the diagnosis of zinc deficiency.
Zinc is an essential trace element
Zinc is an essential trace element required for function of many metalloproteases and transcription factors involved in reproduction, immunology, and wound repair. Additionally, its antioxidant properties help prevent ultraviolet radiation damage.1
The recommended dietary allowance (RDA) for zinc is 11 mg/day for men and 8 mg/day for women, with higher amounts for pregnant and lactating women.1 The human body does not store zinc, and meat and eggs are the most important dietary sources.1
The normal plasma zinc level is 70 to 250 µL/dL, and hypozincemia can be diagnosed with a blood test. For the test to be accurate, zinc-free tubes should be used, anticoagulants should be avoided, the blood should not come into contact with rubber stoppers, and blood should be drawn in the morning due to diurnal variation in zinc levels. Additionally, zinc levels may be transiently low secondary to infection. Thus, the clinical picture, along with zinc levels, histopathology, and clinical response to zinc supplementation are necessary for the diagnosis of zinc deficiency.2
Since zinc is required for the activity of alkaline phosphatase (a metalloenzyme), serum levels of alkaline phosphatase correlate with zinc levels and can be used as a serologic marker for zinc levels.3
Zinc deficiency is a worldwide problem, with a higher prevalence in developing countries. It can result from either inadequate diet or impaired absorption, which can be acquired or inherited.
Acrodermatitis enteropathica, an inherited form of zinc deficiency, is due to a mutation in the SLC39A4 gene encoding a zinc uptake protein.4 Patients typically present during infancy a few weeks after being weaned from breast milk. Clinical presentations include diarrhea, periorificial (eg, around the mouth) and acral dermatitis, and alopecia, although only 20% of patients have all these findings at presentation.5 Occasionally, diaper rash, photosensitivity, nail dystrophy, angular stomatitis, conjunctivitis, blepharitis, and growth retardation are observed. Serum levels of zinc and alkaline phosphatase are low.5 Clinical and serologic markers improve within 2 to 3 weeks with oral zinc supplementation (2–3 mg/kg/day).
Acquired forms of zinc deficiency are linked to poor socioeconomic status, diet, infections, renal failure, pancreatic insufficiency, cystic fibrosis, and malabsorption syndromes.1,6,7 Cutaneous findings in acquired cases of zinc deficiency are similar to those seen in acrodermatitis enteropathica. Periorificial lesions are a hallmark of this condition, and angular cheilitis is an early manifestation. Eczematous annular plaques typically develop in areas subjected to repeated friction and pressure and may evolve into vesicles, pustules, and bullae.2 On biopsy study, lesions are characterized by cytoplasmic pallor, vacuolization, and necrosis of keratinocytes, which are common findings in nutritional deficiencies.8 Dystrophic nails, structural hair changes, and diminished growth of both hair and nails have been reported.2
Cutaneous lesions due to hypozincemia respond quickly to zinc supplementation (1–3 mg/kg/day), usually without permanent damage.2 However, areas of hypo- and hyperpigmentation may persist.
VITAMIN C DEFICIENCY
A 59-year-old bilateral lung transplant patient with a history of chronic kidney disease on peritoneal dialysis for the past 2 years was admitted for peritonitis. He had developed tender violaceous papules and nodules coalescing into large plaques on his arms and perifollicular purpuric macules on both legs 3 days before admission (Figure 3). The lesions were painful to the touch, and some bled at times. Tender gums, bilateral edema, and corkscrew hair were also noted (corkscrew hair is shown in another patient in Figure 4).
Biopsy of a lesion on the forearm was consistent with lymphangiectasia secondary to edema. Staining for bacteria and fungi was negative.
Serologic investigation revealed low vitamin C serum levels (7 µmol/L, reference range 23–114 µmol/L). Supplementation with 1 g/day of vitamin C was started and resulted in gradual improvement of the purpura. The patient died 4 months later of complications of comorbidities.
An important antioxidant
Vitamin C, or ascorbic acid, is an important antioxidant involved in the synthesis of tyrosine, tryptophan, and folic acid and in the hydroxylation of glycine and proline, a required step in the formation of collagen.9 Humans cannot synthesize vitamin C and must acquire it in the diet.9 Plants are the most important dietary sources.9 Although vitamin C is generally not toxic and its metabolites are renally cleared, diarrhea and other gastrointestinal disturbances can occur if large amounts are ingested.10
Vitamin C deficiency is rare in developed countries and is linked to malnutrition. Risk factors include alcoholism, severe psychiatric illness, anorexia, and low socioeconomic status. Moreover, multiple conditions including stress, viral illness, smoking, fever, and use of antibiotics lead to diminished vitamin C bioavailability.9 Patients on dialysis are at increased risk of vitamin C deficiency since it is lost during the process.11
The RDA for vitamin C is 90 mg for men and 75 mg for women, with higher requirements during pregnancy and lactation.12 This is much higher than the amount needed to prevent scurvy, 10 mg/day.13
The classic manifestations of vitamin C deficiency are scurvy and Barlow disease, also known as infantile scurvy.
Early manifestations of vitamin C deficiency such as fatigue, mood changes, and depression appear after 1 to 3 months of inadequate intake.13 Other manifestations are anemia, bone pain, hemorrhage into joints, abnormal vision, and possibly osteoporosis.
Cutaneous findings are a hallmark of scurvy. Follicular hyperkeratosis with fragmented corkscrew hair and perifollicular hemorrhages on posterior thighs, forearms, and abdomen are pathognomonic findings that occur early in the disease.13 The cutaneous hemorrhages can become palpable, particularly in the lower limbs. Diffuse petechiae are a later finding along with ecchymosis, particularly in pressure sites such as the buttocks.13 “Woody edema” of the legs with ecchymosis, pain, and limited motion can also arise.14 Nail findings including koilonychia and splinter hemorrhages are common.13,14
Vitamin C deficiency results in poor wound healing with consequent ulcer formation due to impaired collagen synthesis. Hair abnormalities including corkscrew and swan-neck hairs are common in scurvy due to vitamin C’s role in disulfide bond formation, which is necessary for hair synthesis.13
Scurvy also affects the oral cavity: gums typically appear red, swollen, and shiny earlier in the disease and can become black and necrotic later.13 Loosening and loss of teeth is also common.13
Scurvy responds quickly to vitamin C supplementation. Patients with scurvy should receive 1 to 2 g of vitamin C daily for 2 to 3 days, 500 mg daily for the next week, and 100 mg daily for the next 1 to 3 months.15 Fatigue, pain, and confusion usually improve in the first 24 hours of treatment, cutaneous manifestations respond in 2 weeks, and hair within 1 month. Complete recovery is expected within 3 months on vitamin C supplementation.15
Scurvy is not a disease of the past: 18% of Americans don't get enough vitamin C.
When managing a patient with chronic alcohol abuse who is beginning to withdraw, expect the unexpected.