A case of progressive joint pain and rash in a 5-year-old

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A 5-year-old nonverbal boy with autism spectrum disorder and global developmental delay presented to the emergency department with bilateral lower-extremity bruising and progressive difficulty ambulating. What's the diagnosis?

The case

A 5-year-old nonverbal boy with autism spectrum disorder and global developmental delay presented to the emergency department with bilateral lower-extremity bruising and progressive difficulty ambulating.

One month prior, he began limping, and his mother noticed a new bruise on his right heel. Two weeks later, he presented to orthopedics after developing bilateral ankle swelling and a new bruise on his left ankle. A radiograph of his left leg did not show any osseous abnormalities. Over the next several days, his symptoms progressively worsened, and he was no longer able to walk. His mother reported that he appeared in pain, except when lying in a froglike position. During this time, his mother also noticed swelling in his knees, fine bumps overlying his hair follicles, and bruising on his left calf.


A review of his symptoms included profound fatigue and “not acting like himself.” His mother denied trauma, recent travel, or other illnesses in the past month and said he did not take any medications or supplements. She reported that his aversion to certain textures and tastes led to a very poor diet, consisting of cheese crackers, corn chips, toaster pastries, pepperoni, chocolate bars, and sandwich cookies. He was no longer eating chicken nuggets, which were a staple of his diet until the past couple of months. His mother also reported that he unintentionally lost approximately 10 pounds over the past month. She denied that he had fever, mouth sores, gum bleeding, shortness of breath, rhinorrhea, emesis, blood or mucus in his stool, and abdominal pain.

Hospital course

At time of admission, the patient was noted to have petechiae, ecchymosis, and a perifollicular rash, as well as joint pain with passive range of motion—specifically, internal rotation of his hips and extension of his knees. He had tenderness to palpation of his paraspinal muscles, most significant in his lumbar region. He did not have any appreciable joint swelling. Pain prevented him from walking. Initial laboratory findings included microcytic anemia (hemoglobin, 10.7 g/dL; mean corpuscular volume, 72.6 fL), elevated erythrocyte sedimentation rate (45 mm/h), elevated C-reactive protein (3.26 mg/ dL), and elevated uric acid (7.6 mg/ dL). Results were in the normal range for platelet count (421 K/mm3), white blood cell (WBC) count (8.94 K/ mm3), liver function (aspartate aminotransferase, 24 U/L; alanine aminotransferase, 9 U/L; total bilirubin, 0.2 mg/dL), lactate dehydrogenase (LDH; 269 U/L), and prothrombin time (15 s)/activated partial thromboplastin time (28.3 s).

Rheumatology, dermatology, and hematology/oncology were consult- ed for further evaluation of the boy’s anemia and petechial rash. An MRI of his abdomen, pelvis, and lumbar spine was obtained to evaluate for abdominal mass, subclinical joint effusions, and another osseous source of pain and inflammation. The MRI showed abnormal enhancement of the costochondral junctions, left ischium adjacent to the triradiate cartilage, lumbar spinal processes, lumbar paraspinal musculature, and synovitis in the hips, with small hip effusions concerning for autoimmune process, vitamin deficiency, or postinfectious phenomenon. There was no infiltrative marrow disease or appreciable intra-abdominal mass.

Blood cell counts, including WBC, hemoglobin, and platelets, were normal. Pathology evaluated his peripheral smear and did not find any abnormal cell lines. The patient was noted to initially have an elevated uric acid that normalized with hydration. His LDH and total bilirubin level were normal, making hemolysis unlikely. He was noted to have a low iron level and decreased percentage of total iron-binding capacity saturation, consistent with iron deficiency anemia. Ferritin was normal and not depressed, as would be expected in iron deficiency anemia, likely due to its role as an acute phase reactant.

Given the patient’s limited dietary intake and MRI findings concerning for a vitamin deficiency, his laboratory evaluation was expanded. Serum levels of zinc (65.4 μg/dL) and lead (< 2 mcg/dL) were normal. Vitamin A (0.12 mg/L; reference range [ref], 0.2-0.5 mg/L), vitamin C (< 0.09 mg/ dL; ref, 0.4-2 mg/dL), and vitamin D (25-hydroxy, 11.5 ng/mL) were low.

Dermatology was also consulted for further evaluation of perifollicular rash. On close observation using a dermatoscope, the team noted perifollicular hemorrhages with corkscrew hairs.

Differential diagnosis

The differential diagnosis was initially broad and can be seen in Table 1. The differential included leukemia, an abdominal mass such as neuroblastoma, transient synovitis, septic arthritis, juvenile idiopathic arthritis (JIA), myositis, Henoch-Schönlein purpura, and nutritional deficiencies. His WBC, platelet counts, and peripheral smear were reassuring and did not support leukemia as a likely diagnosis. Imaging demonstrated synovitis, which could be consistent with JIA, transient synovitis, and nutritional deficiencies, but his dermatologic findings were not consistent with JIA or transient synovitis.

The patient’s clinical findings of arthralgia, hip synovitis, and rash showing perifollicular hemorrhages with corkscrew hairs was most consistent with vitamin C deficiency, also known as scurvy.

Scurvy/vitamin C deficiency

Vitamin C deficiency results from a lack of dietary intake of ascorbic acid, the bioavailable form of the nutrient. Foods high in vitamin C include many fruits and vegetables, including citrus fruits, mango, papaya, kiwifruit, tomatoes, spinach, broccoli, potatoes, and brussels sprouts. The highest vitamin C concentration occurs in the raw food source.1 The nutrient plays an integral role in collagen synthesis. Ascorbic acid assists in the triple-helix formation of collagen, which provides structure for blood vessels, ligaments, cartilage, bone, and skin, and aids wound repair.1 The body can be depleted of vitamin C stores in approximately 1 to 3 months with limited intake or poor absorption from the gut. Due to vitamin C’s effects on collagen formation, as the body becomes depleted, vessel structure weakens and risk of bleeding increases.2

Historically, vitamin C deficiency was associated with situations in which people had limited or no access to a steady dietary intake of fresh fruits and vegetables. The primary example has been sailors on extended voyages, but widespread deficiency has also been associated with major famines and wars that disrupted food supplies.3 More recently, vitamin C deficiency has been associated with children and adults who have limited dietary intake or poor absorption.1

Presenting symptoms

Signs of vitamin C deficiency are often multisystem, including musculoskeletal, dermatologic, and hematologic symptoms, which are initially nonspecific and gradually worsen. Increased fatigue and changes in mood are usually among the first symptoms to arise. Additional symptoms include anorexia, joint pain, joint swelling, perifollicular rash, softening of previous scars, poor wound healing, gingival swelling, and gingival bleeding.3 Because of the joint pain and/or swelling, some patients are thought to have a rheumatologic process, such as JIA, at presentation. Vasculitis may be on the differential because the perifollicular hemorrhages are misinterpreted as a purpuric rash. Malignancy is also typically on the differential due to presentation of anemia, joint complaints, and petechiae.

Laboratory findings

Because laboratory findings are not necessarily reliable, diagnosis is typically based on clinical suspicion. The most available test, the serum ascorbic acid level, is diagnostic if the result is less than 0.2 mg/ dL. However, recent dietary consumption of vitamin C would alter the serum level to falsely normal level. Leukocyte ascorbic acid assay offers an alternative measurement but is not routinely available. The leukocyte assay involves a mixed cell population and provides a more consistent evaluation for total body stores of vitamin C.4

Approximately 75% of patients who are vitamin C deficient are noted to have a normocytic anemia, but they also can have a microcytic or macrocytic anemia, depending on associated deficiencies.2 Additional nutritional deficiencies are common and should be evaluated for, including thiamine (B1), pyridoxine (B6), folic acid, cobalamin (B12), and vitamin D.5

Lastly, due to concern for a potential autoimmune or infectious cause of symptoms, inflammatory markers are often obtained. In vitamin C deficiency, these markers are often elevated; however, the exact mechanism for the elevation remains unclear.2

Musculoskeletal findings

Approximately 80% of patients with vitamin C deficiency present with musculoskeletal complaints, which tend to be more prominent in pediatric patients, who can present with severe myalgias. Children may experience significant thigh pain, leading them to sit in a froglike position, legs flexed and externally rotated.6 Typically, patients will endorse arthralgia in the wrists, knees, and/or ankles and can develop hemarthrosis, often involving either the hips, knees, or ankles. The hemarthrosis is thought to be multifactorial and caused by damage to the synovial vessels and microfractures. Lastly, at the distal ends of the diaphysis, subperiosteal hematomas may be palpable.

Radiographic findings are typically found in the distal end of the long bones. General findings will include osteopenia and loss of trabecular bone matrix. More specific findings, which typically arise later and are not present at disease onset, include the white line of Frankel, Trümmerfeld zone “beaks,” and Wimberger ring zone.6 The white line of Frankel is an irregular and thickened white line at the metaphysis. The Trümmerfeld zone (trümmerfeld is German for “field of rubble”) is superior to the white line of Frankel and is a zone of rarefaction in the metaphysis; healing fractures called beaks may be seen along its periphery. The Wimberger ring sign is a white line around the epiphysis. MRI findings are consistent with radiographic findings, but para-epiphyseal subperiosteal hemorrhages may be more apparent. In addition, MRI imaging may show multifocal symmetrical signal abnormalities within the metaphysis.6

Dermatologic findings

Dermatologic findings associated with vitamin C deficiency aid clinical diagnosis. Clinical findings include gingival bleeding, corkscrew hairs, hyperkeratosis, perifollicular hemorrhages, and ecchymosis.7 Vitamin C is important in the formation of disulfide bonds during formation of hair. Without vitamin C, there is increased disulfide cross-linking of the keratin, leading to abnormal coiling of hair and appearance of corkscrew hairs. In addition, the skin is noted to have a rough texture due to hyperkeratosis. If obtained, a skin biopsy will demonstrate follicular plugging with soft keratin. Because of increased hydrostatic pressure stress at the follicle site, there can also be a petechial rash in a perifollicular distribution, which tends to be more pronounced on the lower extremities.3 Occasionally, the perifollicular rash coalesces and develops a raised appearance concerning for purpura. Besides a perifollicular rash, there can be ecchymosis due to the fragile capillaries leading to bleeds.1 Lastly, because of defective collagen production, previous wounds may soften and new wounds may heal poorly.3


Treatment of vitamin C deficiency includes vitamin C supplementation. For children, the recommended dose is 100 to 300 mg/day for a month. Within a few days, there is typically symptomatic improvement in fatigue, pain, and appetite. Within a couple of weeks, the perifollicular hemorrhages and hyperkeratosis resolve. In about 4 weeks, changes in the hair can be appreciated, with resolution of the corkscrew appearance.

In addition, making sure the child consumes a diet rich in vitamin C through the intake of fresh fruits and vegetables is important. If the child has a restrictive diet, considering supplemental vitamin C may be prudent.

Patient course

The patient was started on supple- mental vitamins C, D, E, K, and A and thiamine, as well as a multivitamin. Within a few days of supplementation, he was noted to have significant improvement in arthralgia. To provide the necessary supplemental nutrition, a gastronomy tube was placed prior to discharge. After discharge, the boy’s speech therapy was increased to 3 times a week with significant improvement in his oral intake.


1. Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK. Scurvy: a disease almost forgotten. Int J Dermatol. 2006;45(8):909-913. doi:10.1111/j.1365-4632.2006.02844.x

2. Mertens MT, Gertner E. Rheumatic manifestations of scurvy: a report of three recent cases in a major urban center and a review. Semin Arthritis Rheum. 2011;41(2):286-290. doi:10.1016/j. semarthrit.2010.10.005

3. Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad Dermatol. 1999;41(6):895-910. doi:10.1016/ s0190-9622(99)70244-6

4. Jacob RA. Assessment of human vitamin C status. J Nutr. 11 1990;120(suppl 11):1480-1485. doi:10.1093/ jn/120.suppl_11.1480

5. Callus CA, Vella S, Ferry P. Scurvy is back. Nutr Metab Insights. 2018;11:1178638818809097. doi:10.1177/1178638818809097

6. Fain O. Musculoskeletal manifestations of scurvy. Joint Bone Spine. 2005;72(2):124-128. doi:10.1016/j. jbspin.2004.01.007

7. Fossitt DD, Kowalski TJ. Classic skin findings of scurvy. Mayo Clin Proc. 2014;89(7):e61. doi:10.1016/j. mayocp.2013.06.030