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Scurvy Due to Selective Diet in a Seemingly Healthy 4-Year-Old Boy Andrew Nastro, MD,a,g,h Natalie Rosenwasser, MD,a,b Steven P. Daniels, MD,c Jessie Magnani, MD,a,d Yoshimi Endo, MD,e Elisa Hampton, MD,a Nancy Pan, MD,a,b Arzu Kovanlikaya, MDf

Scurvy is a rare disease in developed nations. In the field of pediatrics, it abstract primarily is seen in children with developmental and behavioral issues, fDivision of Pediatric Radiology and aDepartments of malabsorptive processes, or diseases involving dysphagia. We present the Pediatrics and cRadiology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, New York; bDivision of case of an otherwise developmentally appropriate 4-year-old boy who Pediatric Rheumatology and eDepartment of Radiology, developed scurvy after gradual self-restriction of his diet. He initially Hospital for Special Surgery, New York, New York; and d presented with a limp and a rash and was subsequently found to have Division of Neonatal-Perinatal Medicine, University of Michigan, Ann Arbor, Michigan gDepartment of Pediatrics, and hematuria. A serum C level was undetectable, and after review of NYU School of Medicine, New York, New York hDepartment of the MRI of his lower extremities, the clinical findings supported a diagnosis of Pediatrics, Bellevue Hospital Center, New York, New York scurvy. Although scurvy is rare in developed nations, this diagnosis should be Dr Nastro helped conceptualize the case report, considered in a patient with the clinical constellation of lower-extremity pain contributed to writing the introduction, initial presentation, hospital course, and discussion, and or arthralgias, a nonblanching rash, easy bleeding or bruising, fatigue, and developed the laboratory tables while he was anemia. This case highlights the importance of carefully assessing a child’s a pediatric resident at NewYork-Presbyterian/Weill dietary and developmental status at well-child visits, which can help avoid Cornell Medical Center, and he is now a fellow in a more invasive workup. Academic General Pediatrics at the NYU School of Medicine/Bellevue Hospital Center; Dr Rosenwasser contributed to writing the introduction, initial presentation, and discussion, helped develop the laboratory tables, and provided editing for the case Scurvy is caused by a lack of dietary developmentally appropriate children. report; Drs Daniels and Kovanlikaya contributed to intake, with early symptoms We present a case of a 4-year-old boy writing the discussion, annotated the images, and contributed editing to the case report; Drs Pan and including fatigue, weakness, and a lack with a restricted diet diagnosed with Hampton helped conceptualize the case report and of appetite. Later symptoms include scurvy and highlight many of the contributed editing to the case report; Dr Magnani follicular hyperkeratosis, gingival unique features of this case. contributed to writing the hospital course and bleeding, corkscrew hairs, petechiae, discussion and editing the case report while she , arthralgias, , was a pediatric resident at NewYork-Presbyterian/ INITIAL PRESENTATION Weill Cornell Medical Center, and she is now hemarthrosis, microfractures, bone a neonatal-perinatal medicine fellow at the 1 pain, bone loss, and osteoporosis. The A seemingly healthy 4-year-old boy University of Michigan; Dr Endo provided the symptoms of scurvy are due to presented to our orthopedic clinic with radiologic images and performed their initial reads defective production because right-leg pain and had been limping for and contributed to writing the initial presentation and discussion and editing the case report; and all vitamin C is essential for proper 3 weeks after a recent fall at school. He authors approved the final manuscript as submitted 1 collagen formation. had been diagnosed with streptococcal and agree to be accountable for all aspects of pharyngitis 2 weeks before his the work. In the pediatric population, scurvy symptoms and was treated with a full DOI: https://doi.org/10.1542/peds.2018-2824 occurs almost exclusively in children course of antibiotics. Plain radiographs Accepted for publication May 17, 2019 with autism, developmental and of the tibia, fibula, and knees bilaterally behavioral issues, malabsorptive Address correspondence to Andrew Nastro, MD, were unremarkable (Fig 1). On physical Department of Pediatrics, Bellevue Hospital Center, processes, or iron overload, and in examination, he had a marked limp Administration Building, 3rd Floor, Room A314, disorders causing dysphagia or favoring the right side and limited 462 1st Avenue, New York, NY 10016. E-mail: – impaired swallowing.1 5 Scurvy in an abduction and internal and external [email protected] otherwise healthy child is a rare rotation of the right hip. He did not occurrence and is not commonly cited have tenderness, erythema, or warmth To cite: Nastro A, Rosenwasser N, Daniels SP, in pediatric literature. Self-restrictive of either lower extremity. His et al. Scurvy Due to Selective Diet in a Seemingly diets due to “picky eating” could lead to neurologic examination result was Healthy 4-Year-Old Boy. Pediatrics. 2019;144(3): e20182824 nutritional deficiencies in otherwise normal. He was referred to

Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 144, number 3, September 2019:e20182824 CASE REPORT laboratory workup was notable for an Nephrology was consulted for his elevated erythrocyte sedimentation microscopic hematuria. Complement rate (ESR) of 17 mm per hour component 3 and 4 levels were found (Table 1). Antistreptolysin O antibody to be within normal limits. Hepatic and anti-DNase B antibody levels transaminases, thyroid function, and were found to be within normal serum calcium were also noted to be limits. Naproxen was prescribed within normal limits (Table 1). for pain. Additional laboratories showed iron- deficiency anemia and vitamin D On follow-up in the rheumatology deficiency (Tables 1 and 2). His fi FIGURE 1 of ce, he was noted to have serum vitamin C level result was Anteroposterior radiographs of both knees worsening limp with refusal to bear returned 48 hours after it was sent demonstrate no fracture or periosteal reaction. weight and a new rash on his lower in our rheumatology office as ,5 Subtle growth-arrest lines are noted in the extremities, which was follicular with m fi mol/L, which led to a diagnosis of distal femurs bilaterally, which are nonspeci c. nonblanching pinpoint lesions. L, left; R, right. scurvy. The reference range for Further history revealed some easy vitamin C is 24 to 114; levels .24 bleeding with brushing of his teeth, are considered normal, levels 11 rheumatology clinic because of and he was found to have mild to 23 are mild to moderate concern for poststreptococcal gingivitis on examination. deficiency, and levels ,11 are severe reactive arthritis or transient Considering his evolving physical deficiency.2 A detailed dietary fi synovitis. At the rheumatology clinic, examination ndings, including history revealed that the patient a review of systems was notable for a petechial rash and not being able to had a limited diet consisting of an intermittent rash (Fig 2) over the bear weight, our differential was primarily of waffles, yogurt, pasta arms and legs for the past 2 years, broadened to include malignancy, with butter, goldfish crackers, peanut with little improvement seen with the vasculitidies, and vitamin C butter, chicken nuggets, and water. fi use of topical emollients. His de ciency. Further laboratory work The parents reported that the developmental history was notable was sent, which showed an ESR of 39, patient’s diet had always been picky for speech delay, which had resolved hemoglobin of 7.9, and microscopic and had gradually narrowed from without intervention. He was doing hematuria (Table 1). Given his age 18 months through 4 years. well in prekindergarten and meeting progression of symptoms to the point Celiac disease was considered as all developmental milestones at the of acutely not bearing weight, a possible malabsorptive cause of time of presentation. He was found to additional imaging was done. An scurvy; however, his tissue fl be at the 10th percentile for weight ultrasound showed trace joint uid in transglutaminase immunoglobulin and 18th percentile for height, and the right hip, which was symmetric A (IgA) and total IgA levels were there was no history of or when compared with the left hip. An within normal limits. reduced height velocity. On MRI of the pelvis and femurs was examination, he did not have any ordered because of the persistent The patient was started on vitamin C rashes other than mild atopic clinical suspicion for an infectious or supplementation at 100 mg every fl dermatitis and petechiae around his in ammatory process (Fig 3), which 8 hours for 1 week followed by venipuncture site. His initial did not show any abnormality of the 100 mg daily along with iron, vitamin hips but did show bilateral symmetric D, and a multivitamin. His bone marrow in the distal femoral culture results were negative, and his metaphyses with periostitis and bone biopsy showed evidence of prominent surrounding soft-tissue chronic inflammation and no edema that were concerning for evidence of malignancy. His pain and multifocal or ambulation quickly improved. On malignancy. A surgical bone biopsy hospital day 8, he was discharged with culture and pathology was with follow-up appointments, performed. including and feeding therapy. At his 3-month follow-up, his pain had resolved, and he was HOSPITAL ADMISSION AND COURSE ambulating normally. Additionally, his FIGURE 2 The patient was admitted vitamin C and vitamin D levels Petechial rash noted on presentation to the postoperatively for empirical normalized, and his anemia and rheumatology clinic. antibiotics and further workup. hematuria had resolved.

Downloaded from www.aappublications.org/news by guest on September 28, 2021 2 NASTRO et al TABLE 1 Results of Laboratory Tests: Preadmission Through Day of Admission 12 Test and Units Reference Range 11 Days Before 2 Days Before 1 Day Before Day of Admission Day of Day of Admission Admission Admission Admission 11 Admission 12 Electrolytes, mg/dL Calcium 8.9–10.3 9.5 — 9.2 7.3 (L) —— Phosphorus 2.4–4.7 ———— —45 Complete blood count White blood cell count per mL 6.0–14.5 3 103 7.5 — 5.2 (L) 4.0 (L) —— Red blood cell count per mL 3.70–5.30 3 106 4.21 — 3.25 (L) 3.83 —— Hemoglobin, g/mL 10.5–13.5 10.1 (L) — 7.9 (L) 9.2 (L) —— Hematocrit, % 33.0–39.0 30.8 (L) — 24.2 (L) 27.6 (L) —— Mean corpuscular volume, fL 70.0–86.0 73.2 — 74.5 (L) 71.9 —— Platelets per mL 150–450 3 103 344 — 241 192 —— Differential, % Neutrophil 45.0–75.0 ——40.5 55.8 —— Lymphocyte 20.0–50.0 ——50.3 36 —— Inflammatory markers C-reactive protein, mg/dL 0–0.99 1 —— 0.75 —— ESR, mm/h 0–15 17 (H) 39 (H) — 8 —— Urine studies White blood cells per HPF 0–5 — 0 7 (H) 0 0 — Red blood cells per HPF 0–4 — 39 (H) 37 (H) 0 13 (H) — Protein, mg/dL ——00 8 ,673 Sodium, mmol/L ——————— Calcium/creatinine ratio ,0.36 ——0.86 0.66 0.88 — Complement studies, mg/dL Compliment component 3 79–152 ———— 142 — Compliment component 4 18–55 ———— 35 — Vitamin studies Vitamin D,1,25-OH, pg/mL 19.9–73 ———— ,5 — Vitamin C, mmol/L 23–114 ——,5 ——— Coagulation studies Prothrombin time, s 10.2–12.9 ——14.4 (H) ——— International normalized ratio 0.9–1.1 ——1.2 (H) ——— Activated prothrombin time, s 27.2–36.2 ——34.8 ——— H, laboratories that are above the reference range; HPF, high-power field; L, laboratories that are below the reference range. —, not applicable.

DISCUSSION workup involving invasive MRI is sensitive although not procedures and a delay in the specificforfindings related to Our case is unique in that a 4-year-old 1,4–6 child with no known gastrointestinal diagnosis of scurvy. scurvy. Although metaphyseal disorder, normal swallowing, signal abnormalities are Classically described radiographic nonspecific and can be seen with and no diagnosis of autism or findings of scurvy that were not hematologic malignancies, a neurodevelopmental disorder present in our case include a Pelkan metastatic disease, and developed scurvy by gradually spur, which represents a healing osteomyelitis, the presence of restricting his diet. Imaging studies metaphyseal pathologic fracture, and bilateral symmetric lower- are often obtained in children who a Wimberger ring sign, which extremity metaphyseal signal present with diffuse musculoskeletal denotes a thin sclerotic cortex changes, periosteal reaction, and pain, and osteomyelitis is commonly 3,6–8 surrounding a lucent epiphysis. adjacent soft-tissue edema should a differential consideration in cases Periosteal new bone formation 7,8 4,5 raise the possibility of scurvy. In of scurvy. If one is not familiar secondary to subperiosteal children with extremity pain and with the imaging features of scurvy, hemorrhage, a dense provisional MRI findings suggestive of scurvy, it is easy to misinterpret the calcification immediately adjacent to obtaining a dietary history and abnormalities on MRI as something the physis (Frankel line), and an a serum vitamin C level can confirm more ominous yet more common, adjacent lucent band more a diagnosis of scurvy and avoid such as osteomyelitis or a malignancy, diaphyseal in location (Trummerfeld more invasive diagnostic tests. – as occurred in this case. In many of line) are also classically described.6 8 the recently described cases in the In our case, these findings were not Identification of scurvy or any other literature, there is often an extensive present. nutritional deficiency in the pediatric

Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 144, number 3, September 2019 3 population should prompt a search for a secondary cause. Malabsorptive processes, such as celiac disease and Crohn disease, can present insidiously in children and should be considered, especially in the setting of poor growth. It should also be notedthatelevatedESRandanemia are commonly seen in scurvy.9–11 The relationship between scurvy and elevated ESR is not well understood.9 Elevated C-reactive protein and fibrinogen are also seen in scurvy.11 Anemia is often due to concurrent iron or folate deficiency and is also possibly due to chronic microhemorrhages, gastrointestinal FIGURE 3 losses, or intravascular hemolysis.10 Coronal inversion recovery (A) demonstrates symmetric abnormal hyperintense signal within the Ourpatienthadirondeficiency, bilateral distal femoral metaphyses (arrows) in A with corresponding T1 hypointensity (arrows in B) normal folate levels, and normocytic and adjacent periostitis (arrowheads). Also note the abnormal signal within the soft tissues adja- cent to the distal femurs. anemia.

TABLE 2 Results of Laboratory Tests: Day of Admission 13 and After Test and Units Reference Range Day of Day of Day of Day of Follow-up Admission 13 Admission 15 Admission 16 Admission 17 13mo Electrolytes, mg/dL Calcium 8.9–10.3 9 8.6 (L) — 9 9.9 Ionized calcium 4.9–5.4 ————5.2 Phosphorus 2.4–4.7 5.0 (H) 3.3 — 4.2 4.9 Complete blood count White blood cell count per mL 6.0–14.5 3 103 8.5 5.4 (L) ——8.6 Red blood cell count per mL 3.70–5.30 3 106 3.91 3.18 (L) ——5.1 Hemoglobin, g/dL 10.5–13.5 9.1 (L) 7.6 (L) ——12.8 Hematocrit, % 33.0–39.0 28.4 (L) 23.7 (L) ——38.8 Mean corpuscular volume, fL 70.0–86.0 72.8 74.5 ——76.8 Platelets per mL 150–450 3 103 401 372 ——322 Inflammatory markers ESR, mm/h 0–15 45 (H) ———— Urine studies White blood cells per HPF 0–5 —— 1 — 0 Red blood cells per HPF 0–4 —— 5 — 3 Calcium/creatinine ratio ,0.36 ———0.18 0.18 Vitamin studies Vitamin D,1,25-OH, pg/mL 19.9–73 ———34 — Vitamin D,25-OH, ng/mL 30.0–80.0 20.7 (L) ———— Zinc, mg/dL 60–120 53 (L) ———80

Vitamin B12, pg/mL 180–914 514 ———— Vitamin C, mmol/L 23–114 ————65 Iron studies Iron, mg/dL 45–182 21 (L) ———53 (L) Total iron binding capacity, mg/dL 240–405 202 (L) ———18 Iron saturation, % 13–53 10 (L) ———295 , ng/mL 23.9–336 43.1 ———— Celiac studies tTG IgA, U/mL 0–3 — 1 ——— Total IgA, mg/dL 25–154 ———303 (H) 186 (H) Toxin studies Lead, mg/dL 0.0–4.9 — ,2.0 ——— H, laboratories that are above the reference range; HPF, high-power field; L, laboratories that are below the reference range; tTG, tissue transglutaminase. —, not applicable.

Downloaded from www.aappublications.org/news by guest on September 28, 2021 4 NASTRO et al cannot synthesize vitamin C, should be considered in a clinical biopsy, and extensive laboratory so we depend strictly on exogenous constellation of lower-extremity tests. A nutritional survey should be contribution. Vitamin C, unlike many pain, nonblanching rash, easy considered before the initiation of other , is not stored in the bleeding or bruising, fatigue, anemia, any invasive testing, and a daily body and can deplete quickly if the or arthralgias. It is important to multivitamin should be considered diet becomes deficient. A minimal frequently reassess a child’s dietary for children with a restricted diet. daily intake of vitamin C is history and developmental status Children with a restricted diet can be required.12,13 For children ages 4 to 8, because developmental and referred to a nutritionist or feeding the minimum daily recommended behavioral issues can evolve subtly therapist to ensure that they receive 14 amount is 25 mg. Symptoms usually over the first few years of a child’s adequate nutrition from their diet to begin ∼1 to 3 months after life. Nutritional etiologies should be avoid easily correctable nutritional 15 inadequate vitamin C intake. included on the differential diagnosis deficiencies and diseases such Vitamin C is an essential cofactor for for children who develop a serious as scurvy. collagen synthesis, and defective illness, and it is critical to keep in collagen synthesis in scurvy leads to mind the physical examination characteristic dermatologic and findings of vitamin deficiencies. fi 1 ABBREVIATIONS skeletal ndings. These are generally Identifying nutritional deficiencies seen once serum levels become through a thorough dietary ESR: erythrocyte fi , m 11,15 de cient ( 11.4 mol/L). evaluation can help avoid sedimentation rate Although scurvy is rare in hospitalization and expensive IgA: immunoglobulin A developed nations, this diagnosis diagnostic studies, such as MRI, bone

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2019 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

REFERENCES 1. Fain O. Musculoskeletal manifestations gingival hypertrophy. N Engl J Med. three recent cases in a major urban of scurvy. Joint Bone Spine. 2005;72(2): 2007;357(4):392–400 center and a review. Semin Arthritis 124–128 Rheum. 2011;41(2):286–290 6. Gulko E, Collins LK, Murphy RC, Thornhill 2. Golriz F, Donnelly LF, Devaraj S, BA, Taragin BH. MRI findings in pediatric 11. Fain O, Pariés J, Jacquart B, et al. Krishnamurthy R. Modern American patients with scurvy. Skeletal Radiol. Hypovitaminosis C in hospitalized patients. scurvy - experience with vitamin C 2015;44(2):291–297 Eur J Intern Med. 2003;14(7):419–425 fi ’ de ciency at a large childrens hospital. 7. Polat AV, Bekci T, Say F, Bolukbas E, 12. Baker EM, Hodges RE, Hood J, Sauberlich – Pediatr Radiol. 2017;47(2):214 220 Selcuk MB. Osteoskeletal HE, March SC. Metabolism of ascorbic-1- 3. Ma NS, Thompson C, Weston S. Brief manifestations of scurvy: MRI and 14C acid in experimental scurvy. report: scurvy as a manifestation of ultrasound findings. Skeletal Radiol. Am J Clin Nutr. 1969;22(5):549–558 2015;44(8):1161–1164 selectivity in children with autism. 13. Levine M. New concepts in the biology J Autism Dev Disord. 2016;46(4): 8. Weinstein M, Babyn P, Zlotkin S. An and biochemistry of ascorbic acid. 1464–1470 a day keeps the doctor away: N Engl J Med. 1986;314(14):892–902 scurvy in the year 2000. Pediatrics. 2001; 4. Harknett KM, Hussain SK, Rogers MK, 14. National Institute of Health, Office of 108(3). Available at: www.pediatrics.org/ Patel NC. Scurvy mimicking Dietary Supplements. Vitamin C. cgi/content/full/108/3/E55 osteomyelitis: case report and review Available at: https://ods.od.nih.gov/ of the literature. Clin Pediatr (Phila). 9. Ferrari C, Possemato N, Pipitone N, factsheets/VitaminC-Consumer/. 2014;53(10):995–999 Manger B, Salvarani C. Rheumatic Accessed August 1, 2017 manifestations of scurvy. Curr 5. Duggan CP, Westra SJ, Rosenberg AE. 15. Hodges RE, Baker EM, Hood J, Rheumatol Rep. 2015;17(4):26 Case records of the Massachusetts Sauberlich HE, March SC. Experimental General Hospital. Case 23-2007. A 9- 10. Mertens MT, Gertner E. Rheumatic scurvy in man. Am J Clin Nutr. 1969; year-old boy with bone pain, rash, and manifestations of scurvy: a report of 22(5):535–548

Downloaded from www.aappublications.org/news by guest on September 28, 2021 PEDIATRICS Volume 144, number 3, September 2019 5 Scurvy Due to Selective Diet in a Seemingly Healthy 4-Year-Old Boy Andrew Nastro, Natalie Rosenwasser, Steven P. Daniels, Jessie Magnani, Yoshimi Endo, Elisa Hampton, Nancy Pan and Arzu Kovanlikaya Pediatrics 2019;144; DOI: 10.1542/peds.2018-2824 originally published online August 14, 2019;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/144/3/e20182824 References This article cites 13 articles, 2 of which you can access for free at: http://pediatrics.aappublications.org/content/144/3/e20182824#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Nutrition http://www.aappublications.org/cgi/collection/nutrition_sub Rheumatology/Musculoskeletal Disorders http://www.aappublications.org/cgi/collection/rheumatology:muscul oskeletal_disorders_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 28, 2021 Scurvy Due to Selective Diet in a Seemingly Healthy 4-Year-Old Boy Andrew Nastro, Natalie Rosenwasser, Steven P. Daniels, Jessie Magnani, Yoshimi Endo, Elisa Hampton, Nancy Pan and Arzu Kovanlikaya Pediatrics 2019;144; DOI: 10.1542/peds.2018-2824 originally published online August 14, 2019;

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