Vitamin C Deficiency in a Developed Country Simulating Systemic Vasculitis, The Importance of not Anchoring Diagnoses

Summary: Kevin Cai Zhen1, MD; Anayesha Singh1, MS; Payton Kotlarz1, MS; Jesse Boodoo,1,2 MD. Internal Medicine Residency Program, Florida State University College of Medicine, Sarasota Memorial Hospital, Sarasota, USA1; Sarasota Arthritis Center, Sarasota, USA2. Background: Scurvy is the clinical manifestation of vitamin C deficiency. Scurvy is very uncommon in the United States. The prevalence in the US is currently around 7.1%, markedly decreased from the 13% prevalence from the 90s1-2. Scurvy presents with hair follicle abnormalities, fatigue, poor wound healing, and bleeding, typically gingival or hemarthrosis. It can mimic rheumatologic disorders with elevated ESR and CRP, arthralgias, petechiae, and anemia3. It is diagnosed clinically supported by plasma levels. Supplementation for 1-3 months is recommended4. Our patient initially presented with findings that suggested a systemic vasculitis was present. This case will highlight a unique display of scurvy and emphasize exploring discordant symptoms and clinical findings. Case description: A 42-year-old Caucasian male presented to the rheumatology clinic for evaluation of a petechial rash. He was initially admitted to a local hospital with spontaneous hemorrhage in his right lower extremity, along with fatigue, joint pain, and a petechial rash. He was found to be severely anemic. Initial hematological investigations, including a bone marrow biopsy, were inconclusive. Inflammatory markers were elevated, with an erythrocyte sedimentation rate (ESR) of 44 and C-reactive protein (CRP) of 7.8 mg/dL. A skin biopsy was performed, and the pathologist interpreted the results as possibly indicative of urticarial vasculitis. Subsequently, he was referred to rheumatology for further evaluation after stabilization and discharge. At his initial visit, he was noted to have significant bruising in the right lower extremity (image 1), along with warmth and prominent swelling around the right knee and ankle. A petechial rash was also present involving the left lower extremity. He reported that the petechial rash had started two months before hospitalization, initially being mild and intermittent before worsening and becoming more persistent. He was sent for further laboratory testing and a repeat skin biopsy with dermatology with direct immunofluorescence. Two weeks later, follow-up laboratory testing revealed unremarkable results, with a low positive antinuclear antibody (ANA) titer of 1:40 and negative findings for double-stranded DNA (dsDNA), ribonucleoprotein (RNP), Smith, SSA, SSB, myeloperoxidase (MPO), proteinase 3 (PR-3), rheumatoid factor, cyclic citrullinated peptide (CCP), and antiphospholipid antibodies. The repeat skin biopsy with direct immunofluorescence was negative. His rash showed improvement, now appearing more perifollicular, with coiled hairs noted (image 2). A vitamin C level test was performed, revealing an undetectable level. He was initiated on a daily regimen of 1000 mg of Vitamin C. Symptoms significantly improved within one week, and he returned to baseline after six weeks. Discussion: The presence of corkscrew hair and hemarthrosis in this patient is characteristic of scurvy, although initially, his symptoms mimicked those of a vasculitis rash5. There have been several reported cases of scurvy presenting with a vasculitis-like rash. Some cases exhibit a more typical presentation, characterized by a diffuse nonpruritic perifollicular rash, while others, like ours, present with severe anemia necessitating blood transfusion6. It's noteworthy that, similar to vasculitis, scurvy can lead to elevated ESR and CRP levels; however, these markers are nonspecific7. In some instances, patients undergo a workup suggestive of vasculitis, demonstrating perivascular lymphohistiocytic inflammation with focal perifollicular erythrocyte extravasation, as observed in our case8. Conversely, another case presented with painful, palpable purpura mimicking scurvy9. Across all these cases, recovery was not observed until vitamin C deficiency was confirmed, and supplementation initiated, as seen in our patient 6-10. Although the initial biopsy suggested urticarial vasculitis in our patient, the absence of urticaria in both the physical exam and medical history, coupled with inconclusive workup for vasculitis, warranted further exploration. Conclusion: This case underscores the importance of obtaining a comprehensive social history, maintaining a broad differential diagnosis, and investigating alternative explanations when clinical presentations are discordant. A high level of suspicion for determining the etiology of persistent symptoms was crucial to achieving the correct diagnosis. Acknowledgements: The authors thanks Dr. Robert Smith, PhD who was instrumental in guiding the process of completion of this case report. No third-party financial support was received. References: 1. Ravindran, Ravilla D et al. “Prevalence and risk factors for vitamin C deficiency in north and south India: a two centre population based study in people aged 60 years and over.” PloS one vol. 6,12 (2011): e28588. doi:10.1371/journal.pone.0028588 2. Schleicher, Rosemary L et al. “Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES).” The American journal of clinical nutrition vol. 90,5 (2009): 1252-63. doi:10.3945/ajcn.2008.27016 Abdullah, Muhammad, et al. “Vitamin C (Ascorbic Acid).” StatPearls, StatPearls Publishing, 1 May 2023. 3. Maxfield L, Daley SF, Crane JS. 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