At 7.1%, vitamin C deficiency in the US is rare. Unfortunately, identifying scurvy is complex, frustrating, and time-consuming for both patient and provider.
Severe Vitamin C Deficiency (Scurvy)
HISTORY OF THE PRESENT ILLNESS
A 24-year-old cisgender heterosexual man presented to the Infectious Disease (ID) clinic to be evaluated for HIV preexposure prophylaxis (PrEP). He is sexually active with women and recently had an encounter with a trans woman commercial sex worker. He uses condoms during about half of his encounters and has never had an STI.
Upon review of systems, he complains of several months’ worth of severe fatigue, some non-healing skin ulcers, and difficult bowel movements requiring occasional digital self-disimpaction, but no blood in the stool. PrEP labs are ordered, and a complete blood count (CBC) is added due to his fatigue. He is prescribed PrEP to start if his HIV test is negative and is told to follow up in 3 months.
PAST MEDICAL HISTORY
The patient’s medical history includes T1 paraplegia with neurogenic bowel and bladder due to a motor vehicle accident 7 years prior. Surgical history includes a small bowel resection of the jejunum and ileum, appendectomy, T5-T12 laminectomy and spinal fusion, and orthopedic hardware placement in the left shoulder, right wrist, and pelvis. He uses a wheelchair.
Prior to admission, the patient had been taking ibuprofen and oxycodone/acetaminophen as needed for pain, baclofen, oxybutynin, and pregabalin 200 mg twice daily.
The patient has no family history of anemia, chronic ulcers, or autoimmune diseases. He lives in an apartment complex and generally orders take-out cheesesteaks and fries. He is sexually active, occasionally drinks beer, and denies tobacco or illicit drug use.
The patient appeared well developed and well nourished and was mobile using an electric wheelchair. All his vital signs were within normal limits. His abdomen was soft upon palpation, with multiple well-healed scars from abdominal surgeries and surgical scars on his left shoulder.
The physical exam was remarkable for bilateral approximately 5 cm ulcers on the anterior thighs, which appeared shallow, with minimal erythema and healthy granulation tissue without exudate.
The patient notes that he rests his arms on his legs while in the wheelchair and denies decubitus ulcers. His neurological exam was notable for T1 paraplegia with hyperreflexia of the legs.
Initial labs were significant for microcytic anemia with mean corpuscular volume (MCV) of 69 fL (79-97 femtoliters), low hemoglobin of 8.8g/dL (13.0-17.0 g/dL), and high platelet count of 413 x 109/L (150-379 x 109/L). The remainder of the CBC and basic metabolic panel were unremarkable. He is HIV-negative.
The patient began tenofovir DF/emtricitabine (Truvada) and continued to follow up with ID for PrEP care at regular intervals. ID continued to follow his hematologic abnormalities and ulcers. Follow-up ferritin was 6 ng/mL (30-400 ng/mL) and reticulocyte count was 2% (0.6%-2.6%).
To address the anemia, the patient was placed on IV iron and low-dose oral iron as he could not tolerate the constipating effects of full-dose oral iron. Repeat labs a few months later revealed an increase in hemoglobin to 12g/dL and an MCV of 78 fL. The IV iron was stopped, and the patient noted that his fatigue had resolved but that the skin ulcers remained unchanged.
Given the lack of apparent infectious etiology, the patient was referred to dermatology for a biopsy of the ulcers. Doxycycline was initiated by dermatology for empiric therapy due to suspicion of an infectious agent. A swab of the ulcer had few white blood cells, no organisms, and no growth. Despite continuance of low-dose oral iron, the patient’s hemoglobin and MCV began to drift down. IV iron treatment was resumed, with an observed increase in hemoglobin, yet the ulcers remained.
Experts in hematology and gastroenterology were consulted, and their evaluations deemed the iron deficiency an “insensible loss” due to the patient’s occasional manual disimpaction for his neurogenic bowel. The patient was discharged from their care, and no endoscopy or further workup was performed.
DIAGNOSTIC PROCEDURES AND RESULTS
Skin ulcers remained unchanged in appearance after the second round of IV iron therapy was concluded. On considering a unifying diagnosis of iron-deficiency anemia and non-healing wounds, a provisional diagnosis of scurvy was made. A vitamin C (ascorbate) level was ordered, but the patient was advised to begin supplemental ascorbate and dietary modification immediately given the wait times needed to coordinate transportation and medical care.
One month after initiation of ascorbate supplementation, patient’s ascorbate blood levels were 0.2mg/dL (0.2-2.0mg/ dL), confirming the diagnosis of vitamin C deficiency (scurvy).
TREATMENT AND FOLLOW-UP
The patient continued ascorbate and oral iron supplementation and reported that ulcers had healed entirely and had not recurred. A repeat CBC showed that the anemia had resolved. The patient and clinician agreed to retain ascorbate and iron supplementation as part of his daily regimen. Repeat labs drawn 1 year later showed an ascorbate concentration of 1.3mg/dL.
Ascorbate is a vitamin that humans cannot synthesize but must obtain exogenously and absorb through the distal small intestine.1 In the US, ascorbate deficiency prevalence is approximately 7.1%.2 Access to ascorbate-rich foods like citrus, spinach, and potatoes can be limited by various environmental, demographic, socioeconomic, and dietary factors. Additionally, smoking, chronic alcohol use, imbalanced diet, certain surgeries, and chronic illnesses may contribute to ascorbate deficiency.2,3
Our patient’s diet lacked ascorbate, and the surgical removal of much of his distal small intestine meant that his intestinal absorption would have been poor. Ascorbate is essential to the synthesis of protein, catecholamine, L-carnitine, and collagen.1,4 Ascorbate aids in the hydroxylation of peptide-bound proline and lysine for the synthesis of procollagen, a precursor to collagen, which is a significant component of bone, skin, tendons, cartilage, and muscle.5
Ascorbate also reduces dietary ferric iron (Fe3+) to the more absorptive ferrous (Fe2+) state. Reduced iron is absorbed primarily in the duodenum and proximal jejunum (which were intact in our patient), then stored as ferritin or used in such proteins as hemoglobin.6-8 Ascorbate deficiency can present symptoms similar to those observed in our patient, like poor wound healing, fatigue, and anemia.
Treatment includes ascorbate supplementation and dietary modification that usually resolve symptoms rapidly.9,10 The use of doxycycline as an empiric treatment for certain infections is a common practice. However, a doxycycline-induced decrease in collagen cross-linking could exacerbate wound healing in patients with ascorbate deficiency.11
Our case exemplifies how caution and close observation must be exercised with empiric antibiotic treatment to minimize risk to the patient. Wellmeaning empiric therapy, in this case, could have exacerbated the patient’s skin ulcer.
Individuals with disabilities face unequal treatment by physicians. This may be attributed to misconceptions about their quality of life, a lack of confidence in treating these patients and of awareness about disability cultural competence and etiquette.12,13 The oversight or dismissal of these concerns leads to patient mistrust of health care professionals and may contribute to worse health outcomes. Better medical education and training are required to address the needs of the estimated 26% of US adults living with some form of disability.14,15
The diagnosis of scurvy is dependent on clinical observation and patient history. The nonspecific symptoms of scurvy may lead to delayed treatment or costly and unnecessary workups before determining a diagnosis. During our patient’s many physician office visits, his ulcers could have been overlooked or attributed to wheelchair use without considering other etiologies.
When factoring clinical and social risk factors and costs to the patient, it is imperative that health care professionals across all disciplines be cognizant of scurvy’s clinical presentation and risk factors. This case report suggests that the concerns of patients with disabilities must be addressed promptly and collaboratively among all health care professionals involved in their care.
Unfortunately, identifying scurvy is complex, frustrating, and time-consuming for both patient and provider. Still, the process can be ameliorated through increased awareness, education, and implementation of more collective and holistic clinical practices.