JAMA CLINICAL CHALLENGE

Lower Extremity Purpura

Figure 1. Purpuric Eruption on Lower Extremity

Huan J. Chang, MD, MPH

50-YEAR-OLD WOMAN COMES TO your office for evaluation of a vasculitic-appearing cutaneous eruption of unknown duration on the lower extremities. Her medical history includes heavy smoking with sub-

For editorial comment see p 1910. See www.jama.com for online Clinical Challenge.

sequent chronic obstructive pulmonary disease (COPD). Findings from a general physical examination show her to be a cachectic woman who appears older than her stated age. Cutaneous examination reveals a perifollicular, hyperkeratotic purpuric eruption on her lower extremities (FIGURE 1). Pertinent laboratory values showed megaloblastic anemia, low serum folate levels, and a mild elevation of liver function test results.1

What Would You Do Next? A. Do nothing; the rash will resolve over time B. Obtain a biopsy of the lesion C. Prescribe oral antibiotics D. Prescribe topical steroids
Author Affiliation: Dr Chang (tina.chang @jama-archives.org) is Contributing Editor, JAMA. JAMA Clinical Challenge Section Editor: Huan J. Chang, MD, Contributing Editor. We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr Chang at tina .chang@jama-archives.org. JAMA, May 11, 2011Vol 305, No. 18 1911

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JAMA CLINICAL CHALLENGE

Diagnosis Scurvy What to Do Next Obtain a biopsy of the lesion. The key clinical feature in this case is making the diagnosis of the cause of purpura in this woman who is a heavy smoker. The fact that the patient is cachectic suggests she has not been eating properly. The differential diagnosis of purpura includes vasculitis, drug eruptions, and coagulopathies. Distinguishing among these conditions would require performing a skin biopsy, which is the preferred course of action in this case (answer B). The punch biopsy of the involved area revealed a sparse, focal, perifollicular, and perivascular lymphocytic inflammatory infiltrate (FIGURE 2). Extravasated erythrocytes were present in a perifollicular distribution, and there was overlying follicular hyperkeratosis. Deeper tissue sections showed a corkscrew-shaped hair shaft in 1 follicle (FIGURE 3). Adults with scurvy typically manifest hyperkeratotic perifollicular papules and corkscrew hairs. Treatment for scurvy requires large doses of vitamin C with rapid improvement in findings, so doing nothing will not solve the problem. It would be premature to prescribe topical steroids or antibiotics for this patient without first establishing a diagnosis. In this patient, biopsy results were suspicious for scurvy. Vitamin C levels were undetectable, confirming the diagnosis. Comment Humans, other primates, and guinea pigs must consume ascorbic acid (vitamin C) from external sources, such as fresh fruits and vegetables, because they are unable to synthesize it endogenously. Scurvy is caused by vitamin C deficiency and is rarely encountered in developed countries. Normal adults require 60 to 90 mg vitamin C daily; smokers require more (110-125 mg/ d), secondary to increased oxidative stress.2 Vitamin C is a cofactor for lysyl hydroxylase, an enzyme essential in
1912 JAMA, May 11, 2011Vol 305, No. 18

Figure 2. Punch Biopsy Showing Extravasated Erythrocytes

Figure 3. Punch Biopsy Showing Corkscrew-Shaped Hair Shaft

Hematoxylin-eosin staining, original magnification 40.

Hematoxylin-eosin staining, original magnification 20.

hydroxylation of proline and lysine residues in the cross-link formation of collagen. Risk factors predisposing patients to scurvy include psychiatric illness, alcoholism, drug abuse, inadequate diet, and food allergy.3,4 Manifestations of ascorbic acid deficiency do not typically begin until 8 to 12 weeks after inadequate intake has begun. Patients generally present with phrynoderma (follicular hyperkeratosis), perifollicular petechiae, gingival bleeding, and corkscrew-shaped hairs, although clinical presentation varies. Hematomas, ecchymoses, sacral osteopenia, radiographic bone lesions, weakness, gingival hypertrophy, and anemia are frequently seen.5 The diagnosis of scurvy is made by measuring the level of vitamin C in the blood. This can be done using 1 of 2 available methods: serum ascorbic acid assay or white blood cell ascorbic acid assay. White blood cell ascorbic acid assay is thought to be more accurate because it does not vary with diet.6 If the skin appears hyperkeratotic on physical examination, scurvy should be included in the differential diagnosis and vitamin C level should be determined. Once scurvy is recognized, treatment must be promptly instituted. The recommendedtreatmentscheduleforadults is 1 to 2 g of ascorbic acid for the first 2 to 3 days. Then 500 mg should be administered daily for the next week. Sub-

sequently, 100 mg should be given daily for the following 1 to 3 months.7 Treatment is aimed not just at raising serum levels of vitamin C but also at replenishing residual body stores. Pharmacologic replacement should be accompanied by dietary modification. Providing adequate therapy also involves identifying and resolving the underlying cause of a nutritional deficiency.
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Additional Contributions: This JAMA Clinical Challenge article is based on a previously published article (Chisholm C, Brouha B, Lee P, et al. Lower extremity purpura in a woman with psychosis. Arch Dermatol. 2010;146[10]:1167-1172). REFERENCES 1. Chisholm C, Brouha B, Lee P, Hansen D, Cockerell C. Lower extremity purpura in a woman with psychosis: quiz casescurvy. Arch Dermatol. 2010;146 (10):1167-1172. 2. Hampl JS, Taylor CA, Johnston CS. Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health. 2004;94(5): 870-875. 3. De Luna RH, Colley BJ III, Smith K, Divers SG, Rinehart J, Marques MB. Scurvy: an often forgotten cause of bleeding. Am J Hematol. 2003;74(1): 85-87. 4. Des Roches A, Paradis L, Paradis J, Singer S. Food allergy as a new risk factor for scurvy. Allergy. 2006; 61(12):1487-1488. 5. Velandia B, Centor RM, McConnell V, Shah M. Scurvy is still present in developed countries. J Gen Intern Med. 2008;23(8):1281-1284. 6. Shidfar F, Baghai N, Keshavarz A, Ameri A, Shidfar S. Comparison of plasma and leukocyte vitamin C status between asthmatic and healthy subjects. East Mediterr Health J. 2005;11(1-2):87-95. 7. Le ger D. Scurvy: reemergence of nutritional deficiencies. Can Fam Physician. 2008;54(10): 1403-1406.

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