Persistent scurvy after vitamin C supplementation in a high-risk patient: a case report

Introduction

Background

Scurvy, a multi-organ syndrome resulting from vitamin C deficiency, was first described in 1550 BC (1). Although it is largely perceived as an ancient disease, modern advances in nutrition supplementation and education have not eliminated vitamin C deficiency, and the prevalence of vitamin C deficiency remains higher than expected (2).

Vitamin C deficiency is primarily caused by the inadequate consumption of vitamin-rich fruits and vegetables. In the modern era, however, additional causes include inadequate gastrointestinal absorption and increased serum clearance from oxidative stress or exogenous filtration during dialysis. Risk factors for vitamin C deficiency in the United States (US) reflect these causes and include socioeconomic barriers to fresh fruit and vegetable access, significant alcohol consumption, inflammatory gastrointestinal disease, chronic glucocorticoid or proton pump inhibitor use, smoking, malignancy, and dialysis (1,3). Vitamin C is an essential vitamin and plays a role in collagen and neurotransmitter synthesis as well as antioxidant reactions (3). Scurvy can therefore present with a diversity of signs and symptoms including mood changes, anemia, easy bruising or bleeding, gingivitis, and dermatologic manifestations such as follicular hyperkeratosis and perifollicular hemorrhage (1,4).

Modern cases of scurvy often involve pediatric patients who are at higher risk of self-restricted dieting. Adult cases are less commonly reported, and among published case reports, the majority are attributed to significant alcohol use or limited intake of fruits and vegetables secondary to intellectual disability, psychiatric illness, or preference for processed foods (5-14). On review, one notable case described a middle-aged man with housing insecurity who was also experiencing multiple opportunistic infections from newly-diagnosed acquired immunodeficiency syndrome (AIDS) (15). In most cases, scurvy was suspected after identification of unexplained ecchymoses or gingivitis, with fewer cases reporting characteristic follicular abnormalities on dermatologic examination. Virtually all published cases report resolution of clinical and laboratory evidence of scurvy after vitamin C supplementation.

Rationale and knowledge gap

Scurvy is underdiagnosed in the US, and most published cases do not reflect common medical and social risk factors for vitamin C deficiency, including dialysis and food insecurity. The risk of incomplete treatment of vitamin C deficiency among patients experiencing social barriers to care is not previously reported and also warrants investigation. We present the case of a middle-aged man on hemodialysis with food insecurity who developed characteristic follicular manifestations of scurvy. This case is unique in both the intersection of medical and social risk factors for scurvy represented and the incomplete resolution of vitamin C deficiency after high-dose supplementation.

Objective

The aim of this report is to highlight the diversity of risk factors for vitamin C deficiency in the modern era and the challenges of treating it for patients experiencing barriers to adequate nutrition and healthcare access. We present this case in accordance with the CARE reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-24-69/rc).

Case presentation

We present a case of a 51-year-old man with medical history notable for end-stage renal disease on hemodialysis, untreated hepatitis C, and poly-substance use disorder including an 18-pack-year cigarette smoking history, with social history notable for housing instability, who presented to the emergency department in December 2023 with bleeding around his dialysis catheter site. On interview, he reported 1 day of non-traumatic bleeding around his catheter as well as sub-acute, episodic loss of consciousness, short-term memory loss, and confusion not associated with substance use that had progressively worsened since experiencing physical assault involving head strike 1 month prior to presentation. He additionally endorsed missing his last dialysis session 2 days prior to presentation. His medication history was notable for extended-release buprenorphine, transdermal nicotine patch, sodium zirconium cyclosilicate, lokelma, calcium carbonate-vitamin D, and a renal multivitamin that included vitamin B3, vitamin B7, vitamin C, folic acid, and zinc. He reported inconsistent use of his medications. His mental status at this time was noted to be fully alert and oriented with intact cognition.

Physical examination was notable for non-icteric sclera, normal oral mucosa, a soft and non-distended abdomen, oozing around the dialysis catheter, warm extremities with mild pitting edema, and patchy lower extremity alopecia with corkscrew hairs (Figures 1,2, red arrow), swan-neck hairs (Figure 1, blue arrow), and perifollicular petechiae (Figure 2, green arrow) without ecchymoses. Laboratory testing showed undetectable serum vitamin C levels (<0.1 mg/dL; reference range, 0.4–2.0 mg/dL), confirming a diagnosis of scurvy. Additional laboratory panels prior to hemodialysis initiation were notable for blood urea nitrogen (BUN) 94 mg/dL (reference range, 6–23 mg/dL), ammonia 232 µmol/L (reference range, 11–60 µmol/L), hemoglobin 9.1 g/dL (reference range, 13.5–18.0 g/dL), selenium 84 mcg/L (reference range, 110–165 mcg/L), and zinc 47 mcg/dL (reference range, 60–106 mcg/dL). The patient’s dry weight after hemodialysis was noted to be 11% lower than 3 months prior, concerning for severe malnutrition.

Figure 1 Patchy alopecia on the patient’s right thigh with corkscrew hairs (red arrow) and swan-neck hairs (blue arrow).

Figure 2 Another region of alopecia on the patient’s left thigh with corkscrew hairs (red arrow) and perifollicular petechiae (green arrows).

Treatment for vitamin C deficiency was initiated with 14-day supplementation of enteral vitamin C 500 mg twice daily. The cause of the patient’s sub-acute changes in mental status was suspected to be multifactorial, and treatment included hemodialysis for uremic encephalopathy, lactulose and rifaximin therapy for hepatic encephalopathy, and additional supplementation of selenium and zinc for a possible background of malnutrition-associated cognitive dysfunction.

The patient’s dietary history was notable for meals containing primarily salad and fruits such as grapes; however, the patient reported experiencing up to 3 days of unintentional fasting at times due to food insecurity and housing instability. Nutrition counseling and supplemental nutrition assistance resources were provided. The patient had a self-directed discharge on hospital day 20 in a stable condition with resolution of his uremia. Examination prior to discharge showed reduced peripheral edema and resolution of dialysis catheter site bleeding. However, despite completing 14 days of nutrition supplementation, his dermatologic symptoms persisted. He was re-admitted 120 days later in April 2024 for altered mental status, at which time a follow-up micronutrient panel revealed improved but persistently low serum vitamin C (0.1 mg/dL; reference range, 0.4–2.0 mg/dL), selenium (107 mcg/L; reference range, 110–165 mcg/L), and zinc (57 mcg/dL; reference range, 60–106 mcg/dL). He reported taking his medications irregularly at this time and was advised to continue his prescribed nutritional supplements, which included a multivitamin with vitamin C 60 mg daily. A detailed follow-up dermatologic exam was not able to be completed prior to repeat self-directed discharge.

Ethical statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). There were no adverse or unanticipated events. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

This case represents clear clinical and laboratory evidence of scurvy diagnosed in a middle-aged male with a history of chronic kidney disease on hemodialysis, untreated hepatitis C, tobacco use disorder, and housing instability who presented with sub-acute mental status changes and unexplained bleeding from his dialysis catheter. He was found to have lower extremity alopecia, perifollicular petechiae, corkscrew hairs, and swan-neck hairs. Scurvy was confirmed by an undetectable serum vitamin C, and he completed a full course of vitamin C supplementation in addition to multiple hemodialysis sessions during his admission with resolution of his unexplained bleeding. He was prescribed a multivitamin on discharge; however, follow-up 120 days later revealed improved but persistently low serum vitamin C levels.

Strengths and limitations

This is a report of a single patient, so while it adds to the literature on modern presentations of scurvy, it may not be generalizable to a larger population. Our patient had a self-directed discharge at both presentation and follow-up, which limited both our ability to establish longitudinal care and our understanding of his adherence to the recommended micronutrient supplementation in the outpatient setting. The lack of follow-up examination also limited our assessment of the persistence of the patient’s dermatologic findings. However, strengths of this report include a detailed description and visualization of several dermatologic manifestations of scurvy and emphasis on several modern but less frequently published risk factors for scurvy.

Comparison to similar research

Previous case reports have documented scurvy in a variety of populations, including pediatric patients and adults with limited dietary intake, such as those with alcohol use disorder, certain psychiatric illnesses, or sole consumption of processed foods (5-14). This case is consistent with findings that scurvy can present with a range of non-specific symptoms and that dermatologic signs can be pivotal for diagnosis. In contrast to many published cases, however, this report also highlights the importance of recognizing chronic illness, the need for dialysis, and barriers to food access as important risk factors for scurvy in the modern era.

Explanations of findings

Risk factors for vitamin C deficiency can be broadly categorized into those related to inadequate nutritional intake, those related to endogenous catabolism through antioxidant pathways, and those related to increased serum clearance. Our patient presented with risk factors in each category. His exam demonstrated significant 3-month weight loss consistent with malnutrition and a dietary history of infrequent meals related to food insecurity. Interestingly, our patient reported consumption of fruits and vegetables when he did access nutrition. Additional risk factors included chronic inflammation from untreated hepatitis C infection, chronic kidney disease, and smoking. Finally, our patient was dialysis dependent––this represents an independent risk factor for vitamin C deficiency as water soluble vitamins are typically filtered during dialysis and serum reductions of vitamin C can be as high as 40% per session (16). Supplementation of water-soluble vitamins is often recommended for patients on dialysis, including our patient, who was likely not able to access or consistently take his supplement in the outpatient setting (17).

In addition to the above dietary history, our patient had several clinical findings consistent with scurvy, including anemia, unexplained bleeding, altered mental status, and specific dermatologic findings. Although anemia is associated with vitamin C deficiency due to a combination of impaired dietary iron absorption and mucosal blood loss from defective collagen synthesis, our patient’s anemia may have also been explained by chronic kidney disease, chronic illness, and malnutrition (18). Scurvy can also present with unexplained bleeding due to disordered connective tissue formation in blood vessels, although for our patient, uremic platelet dysfunction could not be excluded from the possible causes of catheter site bleeding. Neuropsychiatric manifestations of vitamin C deficiency range from depressed mood to impaired cognition and psychosis and are typically sub-acute to chronic in onset; in this case, additional contributions from toxic-metabolic encephalopathy and traumatic brain injury were likely (4). Dermatologic manifestations, however, are among the most specific findings associated with scurvy. The etiology of the characteristic corkscrew hairs, swan-neck hairs, and perifollicular petechiae reported here is thought to be related to impaired collagen synthesis, which can predispose hair to coil or bend and cause fragile perifollicular blood vessels to hemorrhage (1,19).

The diagnosis of scurvy is made clinically with a careful symptom and dietary history as well as physical exam. It is supported by low serum vitamin C, although recent vitamin C intake can normalize serum levels even if tissue levels are deficient (20). Additional micronutrient deficiencies, such as selenium and zinc, commonly co-occur and suggest global malnutrition (21). The treatment of scurvy involves prompt vitamin C supplementation, and the appropriate dosing varies based on the severity of the condition and the individual’s requirements (20,22). Constitutional symptoms may improve within 24 hours of treatment while dermatologic and mucosal manifestations resolve within several weeks. Although our patient received 14 days of appropriate high-dose supplementation, he subsequently underwent a self-directed discharge and continued dialysis without regular access to nutrition which may explain his improved but persistently low serum vitamin C level at follow-up.

Implications and actions needed

Previously published reports of scurvy have not often reflected its multifactorial medical and social risk factors, its dermatologic manifestations, or the potential for persistent vitamin C deficiency despite supplementation. This case highlights the contributions of dialysis and food insecurity to vitamin C deficiency, additionally reflecting the specific dermatologic manifestations of scurvy and the importance of continuing vitamin C supplementation after initial treatment. Healthcare providers should maintain a high index of suspicion for nutrient deficiencies and consider a detailed dietary history, clinical nutritionist engagement, and selective laboratory testing when treating high-risk populations presenting with unexplained bleeding, new neuropsychiatric symptoms, or skin and body hair changes. Adequate supplementation with vitamin C should be initiated promptly in suspected cases of scurvy, and nutrition education should be provided to prevent recurrence. Interdisciplinary support, including social work and case management services, may be necessary to ensure adequate treatment of patients experiencing barriers to care.

Conclusions

Vitamin C deficiency, or scurvy, can manifest with specific dermatologic signs and less specific systemic symptoms, including changes in cognition and bleeding. This case highlights the importance of considering vitamin C deficiency in patients with complex social and medical histories whose presentation may be explained, in part, by vitamin C deficiency. Vitamin C deficiency is easily reversed with adequate supplementation but can have severe consequences if left untreated. Healthcare providers should therefore maintain suspicion for its signs and symptoms in high-risk patients, consider testing and treatment in suspected cases, and provide patient education and interdisciplinary support to prevent recurrence.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-24-69/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-24-69/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-24-69/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). There were no adverse or unanticipated events. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Gandhi M, Elfeky O, Ertugrul H, et al. Scurvy: Rediscovering a Forgotten Disease. Diseases 2023;11:78. [Crossref] [PubMed]
2. Narayanan S, Kumar SS, Manguvo A, et al. Current estimates of serum vitamin C and vitamin C deficiency in the United States. Curr Dev Nutr 2021;5:1067. [Crossref]
3. Doseděl M, Jirkovský E, Macáková K, et al. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients 2021;13:615. [Crossref] [PubMed]
4. Jaini PA, Alexander J, Elchehabi S, et al. Psychiatric Manifestations of Modern Scurvy: A Case Series and Literature Review. Psychiatric Annals 2023;53:282-8. [Crossref]
5. Wang AH, Still C. Old world meets modern: a case report of scurvy. Nutr Clin Pract 2007;22:445-8. [Crossref] [PubMed]
6. Halligan TJ, Russell NG, Dunn WJ, et al. Identification and treatment of scurvy: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:688-92. [Crossref] [PubMed]
7. Lu RL, Guo JW, Sun BD, et al. Scurvy in a young man: a rare case report. Front Nutr 2023;10:1265334. [Crossref] [PubMed]
8. Joshi R, Gustas-French CN, Fanburg-Smith JC, et al. Scurvy: a rare case in an adult. Skeletal Radiol 2019;48:977-84. [Crossref] [PubMed]
9. Regehr J, Kriwiel M, Roth E, et al. A Case Report of a Modern-Day Scurvy. Kans J Med 2021;14:51-2. [Crossref] [PubMed]
10. Stephen R, Utecht T. Scurvy identified in the emergency department: a case report. J Emerg Med 2001;21:235-7. [Crossref] [PubMed]
11. Montalto M, Porceddu E, Pero E, et al. Scurvy: A Disease not to be Forgotten. Nutr Clin Pract 2021;36:1063-7. [Crossref] [PubMed]
12. Chaudhry SI, Newell EL, Lewis RR, et al. Scurvy: a forgotten disease. Clin Exp Dermatol 2005;30:735-6. [Crossref] [PubMed]
13. Levavasseur M, Becquart C, Pape E, et al. Severe scurvy: an underestimated disease. Eur J Clin Nutr 2015;69:1076-7. [Crossref] [PubMed]
14. 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;41:286-90. [Crossref] [PubMed]
15. Maltos AL, Silva LL, Bernardes AG Junior, et al. Scurvy in a patient with AIDS: case report. Rev Soc Bras Med Trop 2011;44:122-3. [Crossref] [PubMed]
16. Kosmadakis G, Da Costa Correia E, Carceles O, et al. Vitamins in dialysis: who, when and how much? Ren Fail 2014;36:638-50. [Crossref] [PubMed]
17. Wang AY, Elsurer Afsar R, Sussman-Dabach EJ, et al. Vitamin Supplement Use in Patients With CKD: Worth the Pill Burden? Am J Kidney Dis 2024;83:370-85. [Crossref] [PubMed]
18. Fain O. Musculoskeletal manifestations of scurvy. Joint Bone Spine 2005;72:124-8. [Crossref] [PubMed]
19. Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad Dermatol 1999;41:895-906. [Crossref] [PubMed]
20. Pazirandeh S, Burns DL. Overview of water-soluble vitamins: Vitamin C (Ascorbic Acid). UpToDate. Available online: https://www.uptodate.com/contents/overview-of-water-soluble-vitamins
21. Olmedo JM, Yiannias JA, Windgassen EB, et al. Scurvy: a disease almost forgotten. Int J Dermatol 2006;45:909-13. [Crossref] [PubMed]
22. Maxfield L, Daley SF, Crane JS. Vitamin C Deficiency. In: StatPearls. Treasure Island: StatPearls Publishing; 2023.