Scurvy is a constellation of clinical manifestations caused by vitamin C deficiency. Although scurvy is rare, especially in developed countries, there have been sporadic case reports of scurvy in children and adults in recent years. Patients with scurvy can present with an array of clinical features that mimic primary rheumatologic, infectious, or hematologic conditions. Given the present-day rarity of this disease, the consideration of scurvy as a diagnosis is often overlooked by physicians, leading to extensive laboratory and radiographic testing and unnecessary delays in diagnosis and treatment.1
Three cases of children presenting to pediatric specialty clinics with complaints of difficulty walking and refusal to bear weight are presented. All had been evaluated by several specialists and had undergone extensive investigation before the diagnosis of scurvy was entertained. We emphasize the importance of taking a dietary history in pediatric patients, summarize the clinical manifestations of scurvy, and stress the importance of having a high index of suspicion for vitamin C deficiency in at-risk patients with compatible symptoms.
A 5-year-old white girl presented to the pediatric rheumatology clinic with refusal to bear weight. Three months prior, she began to limp, favoring her right leg. There was no morning stiffness or joint swelling. She was evaluated at her pediatrician’s office, where hip radiographs were normal. One month prior, she began to have trouble walking up stairs, which progressed to complete refusal to walk because of leg pain. She was referred to a sports medicine physician, who obtained repeat radiographs and magnetic resonance imaging (MRI) of the right hip, which showed no abnormalities. Laboratory studies showed a normal complete blood count and erythrocyte sedimentation rate of 30 mm/h (reference range, 0–20 mm/h). She was referred to an oral surgeon 1 month prior for loose teeth, pain on chewing, and spontaneous bleeding from blister-like lesions on her gums. A punch biopsy of her gingiva performed by the oral surgeon was nondiagnostic. She had also lost 5 lb over the last 3 months. She had a history of mild eczema and was not on any medications. There was no relevant family history. She had met her developmental milestones on time; however, she had difficulty accepting foods with certain textures. She also had sensitivity to certain sounds and frequently had “meltdowns” with changes in her daily routine.
On examination, weight was 19 kg (50th percentile), and height was 82 cm (less than third percentile); vital signs were normal. The examination was remarkable for gingival hyperplasia with areas of necrosis and hemorrhage (Fig. 1) and pain on passive range of motion of the knees and hips bilaterally, without effusion. Her skin demonstrated diffuse hyperkeratotic papules on the extremities. She had generalized weakness in the lower extremities, and she was able to lift her hips and knees against gravity but not to resistance. She refused to bear any weight. Her deep tendon reflexes were intact.
She was admitted to the hospital, where laboratory studies including complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, coagulogram, uric acid, urine vanillylmandelic acid, and homovanillic acid were essentially unremarkable. Her muscle enzymes including creating kinase and aldolase were normal. Bone marrow biopsy was normal. A computed tomography scan of the chest, abdomen, and pelvis did not reveal any abnormalities; magnetic resonance imaging of the thoracolumbar spine was also unremarkable. Radiographs of the lower extremities revealed diffuse osteopenia, with metaphyseal sclerotic lines most prominent in the distal femur (Fig. 2). Although her parents endorsed a good diet, it became apparent during her hospitalization that there were deficits. Her diet consisted solely of fast-food hamburgers, sweet tea, and soda. The diet was devoid of all fruits, vegetables, juices, or milk. A vitamin C level was less than 0.1 mg/dL (reference range, 0.6–2.0 mg/dL), and 25-hydroxyvitamin D level was 8 ng/mL (reference range, 30–100 ng/mL). She was started on vitamin C, 300 mg/d plus vitamin D, 4000 U/d. She was discharged 1 week later with improvement of her gum lesions. At 3 weeks after discharge, her leg pain had improved, and she began walking again. Six months after diagnosis, she continues to follow up with speech therapy and child psychology. She has made slow progress, now chewing carrots and green beans. Given the long distance to our hospital, the parents transitioned her care to a nearby hospital.
A 5-year-old African American boy presented with leg pain and refusal to walk for 6 weeks. Four weeks before presentation, he was evaluated by his pediatrician who noted no fever, weight loss, night sweats, joint swelling, or rashes. There was no family history of rheumatologic or hematologic diseases. Laboratory studies included hemoglobin 10.2 g/dL and platelets of 495,000/µL. Lactate dehydrogenase and uric acid were normal.
He was referred to the pediatric hematology clinic, where he was diagnosed with iron-deficiency anemia, and iron supplementation was prescribed. He returned 1 week later for follow-up and continued to refuse to walk. Radiographs of the legs demonstrated metaphyseal lucent bands in the distal femur and proximal tibia (Fig. 3). Bone marrow aspiration and biopsy demonstrated no abnormalities. Magnetic resonance imaging of the legs showed extensive marrow edema with enhancement of the bilateral distal femoral and proximal tibial metaphyses with edema of the periosteum and nearby musculature. Bone biopsy of the left tibia showed focal areas of loose fibrous tissue with admixed lymphocytes and plasma cells with fragment of bone undergoing resorption, consistent with chronic osteomyelitis. Gram stain and aerobic and aerobic cultures were all negative.
He was referred to our pediatric diagnostic center, where his weight was 21 kg (70th percentile) and height was 108 cm (30th percentile), and vital signs were normal. There was gingival hypertrophy. The distal femur and proximal tibia were mildly enlarged bilaterally, without erythema or warmth. He would stand but refused to walk. His speech was delayed, but he understood and answered questions appropriately. A diet history was obtained. Since infancy, he had never transitioned to solid foods. His mother pureed his food for each meal; these meals consisted only of pureed, canned, cheese-filled ravioli. He drank only apple juice. Vitamin C level was less than 0.1 mg/dL, and 25-hydroxyvitamin D was 28 ng/mL. Urine vanillylmandelic acid and homovanillic acid were normal. He was started on 300 mg/d of vitamin C plus vitamin D and iron supplementation. Because of his speech delay and aversion to solid foods, he was referred to speech therapy. Two weeks later, the leg pain had resolved, and he could walk well. Two months after diagnosis, he had undergone speech therapy once and continued to refuse taking other foods.
A 5-year-old boy with autism, developmental delay, and bilateral optic nerve dysplasia presented to his pediatrician with right hip pain and difficulty walking. Lower-extremity radiographs showed osteopenia and growth arrest lines in the distal femurs and proximal tibias. His 25-hydroxyvitamin D level was 16 ng/mL, and he was started on vitamin D 1000 units every other day. Vitamin C level was less than 0.1 mg/dL, but the patient was lost to follow-up, and no treatment was initiated. The mother returned him to the pediatrician’s office 5 months later because he continued to refuse to walk and had weight loss. Weight for age had fallen from the 50th to less than the third percentile in that interval. His diet consisted of taquitos, frozen pizza rolls, the crust of fish sticks, nacho cheese snacks, and water. He had a healthy, well-nourished 12-year-old sister and a 9-year-old brother with mental retardation and seizures. At baseline, he could walk and run. He had limited receptive and expressive language.
On admission, his weight was 13.6 kg (less than the third percentile), and height was 101 cm (less than the third percentile); vital signs were normal. Eye examination showed nystagmus. Dentition and gingiva were normal. There was no joint swelling or overt muscular weakness. His muscle bulk was reduced, and reflexes were normal. Vitamin D level had normalized, and vitamin B12, vitamin B1, and folic acid levels were all normal. Thyroid studies, calcium, phosphorus, magnesium, and parathyroid hormone were normal. Vitamin C level remained less than 0.1 mg/dL. Lower-extremity radiographs showed marked osteopenia and sclerosis about the provisional zones of calcification of each distal femur (Fig. 4). Bone density scan showed osteoporosis. Vitamin C replacement was initiated. After 2 weeks of treatment, he was able to walk with hand holding, and repeat vitamin C level was 1.1 mg/dL. He continues to follow with speech therapy, nutrition, physical therapy, and occupational therapy as an outpatient. Six months after diagnosis, he continued to refuse fruits and vegetables despite speech therapy, nutrition, and physical therapy.
Scurvy has been recognized as a potentially fatal disease occurring in individuals who consume inadequate amounts of fresh fruit or vegetables.2 The true prevalence of scurvy in small children is unknown; however, it appears that scurvy is less common in the pediatric population. Based on the 2003 to 2006 cross-sectional study by the National Health and Nutritional Examination Survey, the prevalence of vitamin C deficiency in civilians 6 years or older in the United States is about 6%, but a smaller percentage of 6- to 11-year-old participants (∼0.8%) and adolescents (∼2.8%) were vitamin C deficient.3
Vitamin C is a water-soluble essential micronutrient involved in many biologic and biochemical functions.4 Humans and other primates have lost the ability to synthesize vitamin C as a result of mutation in the gene coding for l-gulonolactone oxidase, the enzyme required for the biosynthesis of vitamin C.5 Vitamin C is a potent antioxidant and a cofactor for several enzymes involved in the biosynthesis of collagen, carnitine, and neurotransmitters.6 The symptoms of scurvy result largely from decreased synthesis of collagen and resultant weakening of collagenous structures in the skeleton and vasculature.
Clinical manifestations of scurvy that have been reported in the literature are summarized in Table 1. In a retrospective study of 28 children with scurvy in Thailand, inability to walk was the most common presentation (96%).7 In the developed world, scurvy remains a rare condition, whereas the differential diagnosis of limp or refusal to walk in children is quite broad and includes many more common conditions.8 It is therefore essential for physicians to have a high index of suspicion for scurvy in at-risk patients who present with these symptoms.
Limited intake of fresh fruits and vegetables is the chief cause of scurvy; the recommended daily intake of vitamin C in children varies with age (Table 2).9 Risk factors for scurvy that have been described in adults include alcoholism, social isolation, elderly age, smoking, and mental or chronic illness.2 In children, groups reported to be at risk include those with oral aversions or inadequate nutritional intake due to various causes including developmental delay,10 cerebral palsy,10 and pervasive developmental disorders.11 Infants who are fed evaporated or boiled milk are also at risk of developing scurvy.7 Of note, our patients all had behavioral abnormalities and oral aversion. In cases 1 and 2, the histories of excessive adherence to routine and unusual sensory behaviors raise suspicion for autism spectrum disorder, whereas case 3 had been formally diagnosed with autism before his presentation with scurvy.
The diagnosis of scurvy is usually based on characteristic clinical findings and a history of poor intake of vitamin C–containing foods. The practical and best confirmatory method for diagnosis of scurvy is the resolution of the manifestations with vitamin C supplementation.12 Plasma ascorbic acid level can be used as an indicator for scurvy,13 although it does not always reflect tissue levels of vitamin C.14 The diagnosis of vitamin C deficiency is usually considered when the plasma concentration is less than 0.19 mg/dL.15 Other laboratory studies in scurvy are nonspecific.
The radiographic changes in scurvy include a ground-glass appearance of the long bones due to trabecular atrophy, periosteal elevations due to subperiosteal hemorrhages, osteoporosis, a zone of provisional calcification at the margins of the growth plate (white line or Fränkel sign; Fig. 2), and around the epiphysis (Wimberger sign; Fig. 4), and a metaphyseal lucent line (scurvy line; Fig. 3) adjacent to the metaphyseal sclerotic line.14 Metaphyseal lucent lines can be seen in children presenting with leukemia or metastatic neuroblastoma. However, the presence of associated sclerotic bands/lines secondary to thickened zone of provisional calcification, as seen in these cases, is a distinguishing feature of scurvy on radiographic evaluation. In addition, lateral extension of the provisional zone of calcification in the metaphysis can result in metaphyseal excrescences or beaks (Corner sign; Fig. 3).16 There are no specific histopathologic alterations in bone described in the scurvy literature, and the findings of chronic nonbacterial osteomyelitis on the biopsy of case 2 are perplexing. There have also been no prior reports of the link between scurvy and osteomyelitis. This patient’s symptoms resolved with vitamin C replacement, without adjunctive antibiotics or anti-inflammatory agents.
Given that scurvy arises in the context of suboptimal diet, physicians should seek evidence of other nutritional deficiencies in these patients. All 3 cases had low or borderline low vitamin D levels. Vitamin D deficiency or rickets have also been described as comorbidities in other scurvy reports and should be included in the differential diagnosis of difficulty walking in children.
The treatment of scurvy is vitamin C supplementation and remediation of the condition that led to the deficiency. There is no established regimen for vitamin C supplementation in scurvy. Regimens of 1 g/d for 2 weeks or 100 to 200 mg/d for a longer period have achieved complete recovery.15
In summary, scurvy is a rare disease in developed countries, but it continues to exist. Lower-extremity pain, limp, and refusal to walk are common presenting complaints. Comorbidities such as oral aversion, autism spectrum disorder, nutritional neglect, and other vitamin deficiencies must be considered and addressed. Treatment includes not only vitamin C supplementation but also correction of underlying conditions in order to prevent recurrence.
1. Estienne M, Bugiani M, Bizzi A, et al. Scurvy hidden behind neuropsychiatric symptoms. Neurol Sci
. 2011; 32: 1091–1093.
2. Fain O. Musculoskeletal manifestations of scurvy. Joint Bone Spine
. 2005; 72: 124–128.
3. US Centers for Disease Control and Prevention. Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population 2012
. Atlanta, GA: National Center for Environmental Health; 2012 [cited October 1, 2013 ]. Available at: http://www.cdc.gov/nutrition-report
4. Levine M, Rumsey SC, Daruwala R, et al. Criteria and Recommendations for vitamin C intake. JAMA
. 1999; 281: 1415–1423.
5. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr
. 1999; 69: 1086–1107.
6. Mandl J, Szarka A, Bánhegyi G. Vitamin C: update on physiology and pharmacology. Br J Pharmacol
. 2009; 157: 1097–1110.
7. Ratanachu-Ek S, Sukswai P, Jeerathanyasakun Y, et al. Scurvy in pediatric patients: a review of 28 cases. J Med Assoc Thai
. 2003; 86: S734–S740.
8. Sawyer JR, Kapoor M. The limping child: a systemic approach to diagnosis. Am Fam Physician
. 2009; 79: 215–224.
9. Food and Nutrition Board, Institute of Medicine. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids
. Washington DC: National Academy Press; 2000: 95–185.
10. Choi SW, Park SW, Kwon YS, et al. MR imagining in a child with scurvy: a case report. Korean J Radiol
. 2007; 8: 443–447.
11. Niwa T, Aida N, Tanaka Y, et al. Scurvy in a child with autism: magnetic resonance imaging and pathological findings. J Pediatr Hematol Oncol
. 2012; 34: 484–487.
12. Popovich D, McAlhany A, Adewumi AO, et al. Scurvy: forgotten but definitely not gone. J Pediatr Health Care
. 2009; 23: 405–415.
13. Smith A, Di Primio G, Humphrey-Murto S. Scurvy in the developed world. CMAJ
. 2011; 183: e752–e755.
14. Shah D, Sachdev HPS. Vitamin C (ascorbic acid). In: Kliegman RM, Stanton BF, St Geme JW III, et al. Nelson Textbook of Pediatrics
. Philadelphia, PA: Saunders Elsevier; 2011: 198–199.
15. Heymann WR. Scurvy in children. J Am Acad Dermatol
. 2007; 57: 358–359.
16. Duggan PC, Westra SJ, Roseberg AE. Case records of the Massachusetts General Hospital. Case 23-2007: a 9-year-old boy with bone pain, rash, and gingival hypertrophy. N Engl J Med
. 2007; 357: 392–400.
© 2014 by Lippincott Williams & Wilkins, Inc.