Mrs. H, a 55-year-old Caucasian, presented as a new patient transfer with symptoms of uncomplicated acute bronchitis. She described five other similar illnesses over the past several months, noting a chronic cough between episodes. Mrs. H also had persistent fatigue, depressed mood, memory loss, and dry skin, and she reported vague pain, edema, and myalgia in the lower extremities.
Her medical history included hypertension, depression, hypothyroidism, gastroesophageal reflux disease, iron deficiency anemia, asthma, and allergic rhinitis. She had also had benign colon polyps, breast cancer, ovarian cyst, and choriocarcinoma. Surgical history included Roux-en-Y gastric bypass surgery for obesity, breast lumpectomy, and partial hysterectomy.
Current medications were amlodipine/benazepril (Lotrel), fluoxetine (Prozac), metoclopramide (Reglan), omeprazole (Prilosec), Armour thyroid, vitamin B12 injections, cetirizine (Zyrtec), montelukast (Singulair), and etodolac (Lodine).
Her family history was positive for cancer of the colon, lung, ovary, and breast. Mrs. H was a nonsmoker who described her alcohol use as infrequent and denied using illicit drugs.
1. Examination findings
Despite her medical woes, Mrs. H appeared well. Vital signs were BP 128/82 mm Hg, pulse regular at 80 beats per minute, temperature 98.2oF, and respiratory rate 16 breaths per minute. BMI was 27 with central obesity. Her hair was normal, but her skin exhibited mild pallor and xerosis.
ENT findings were consistent with an upper respiratory illness. Lung auscultation revealed scattered, mild wheezes. Her legs exhibited mild edema. Neurologic exam demonstrated a fine resting tremor of the hands and a flat affect. Remote memory was impaired. Gynecologic exam was unremarkable.
2. Diagnostic studies
Laboratory evaluation of Mrs. H’s thyroid function revealed an elevated thyroid-stimulating hormone (TSH)
(6.74 µIU/mL) and low free thyroxine (0.6 ng/dL). Her hemoglobin was also low (11.6 g/dL), but her mean corpuscular volume was normal.
Other results within normal limits included folate, iron, total iron-binding capacity, fecal occult blood, vitamin B12, vitamin B1, 25-hydroxyvitamin D, CA-125, creatine kinase, magnesium, urinalysis, erythrocyte sedimentation rate, and a comprehensive metabolic panel. Chest x-ray revealed nothing out of the ordinary. A screening pelvic ultrasound demonstrated a right ovarian mass that appeared to be a benign cyst.
3. Diagnosis and management
Mrs. H’s symptoms, medical history, and laboratory tests suggested undertreated hypothyroidism, ACE inhibitor-induced cough, edema associated with amlodipine or a nonsteroidal anti-inflammatory drug, and tremor due to metoclopramide. I began by titrating Mrs. H’s thyroid-hormone replacement and switching her antihypertensive to losartan (Hyzaar), changes I expected would resolve her hypothyroid symptoms and relieve her edema. The etodolac was stopped permanently because of the risk of anastomotic ulceration related to her Roux-en-Y surgery. Supportive care led to resolution of her acute bronchitis.
However, evaluation two months later revealed persistent edema, depression, fatigue, and vague lower-limb pain. Mrs. H also had new complaints of moderate low back pain, mild generalized weakness, and spontaneous limb ecchymoses.
A repeat TSH determination was suppressed (0.09 µIU/mL). Spine films to investigate the back pain were unremarkable for the patient’s age. Normal prothrombin time and partial thromboplastin time ruled out coagulopathy. Those findings, along with persistence of her edema, depression, fatigue, and limb pain, plus new complaints of pain, weakness, and ecchymoses, led to suspicion of scurvy. A vitamin C determination was very low at <0.12 mg/dL (normal 0.2-1.9 mg/dL), incriminating scurvy as the cause of her symptoms.
Vitamin C therapy led to rapid improvement in most of Mrs. H’s symptoms. Her thyroid-replacement dose was lowered.
Because humans cannot synthesize vitamin C, they are dependent on exogenous dietary sources. Vitamin C is abundant in citrus fruits and many vegetables. It is absorbed in the small intestine; any excess is renally excreted. Clinical manifestations of deficiency have been observed after about one month on a vitamin C-free diet. Scurvy usually occurs at vitamin C levels <0.1 mg/dL, but symptoms may occur at levels <0.25.
Vitamin C deficiency is not uncommon. The Third National Health and Nutrition Examination Survey found that among a sample of 15,769 Americans aged 12-74 years, 14% of males and 10% of females were vitamin C-deficient.1 De-ficiency is most common in the mentally ill, patients on self-imposed restrictive diets, smokers, and alcoholics. Other risk factors are pregnancy, thyrotoxicosis, anorexia due to any cause, type 1 diabetes, dialysis, small-intestinal disorders, and iron-overload disorders.
Gastric bypass surgery and proton-pump inhibitor (PPI) use have more recently been identified as risk factors. A study of gastric bypass patients one year after surgery revealed that 34.6% were vitamin C-deficient.2 Even short courses of PPIs have been shown to reduce bioavailability of vitamin C.3
Early symptoms of vitamin C deficiency are weakness, anorexia with weight loss, malaise, depression, and lethargy. Later symptoms include myalgia; dyspnea; bone pain; ecchymosis; poor wound healing; edema; hemorrhages in the eyes, muscles, and joints; friable and bleeding gingiva; perifollicular skin hemorrhages; and hair and skin dystrophy. Anemia is often present. Very late symptoms include hypotension, congestive heart failure, jaundice, convulsions, and death. Given the vague early symptoms and common risk factors, increased vigilance for avitaminosis C is prudent.
Mrs. H’s diet was well-balanced. Her disease was most likely a complication of gastric bypass and PPI use.
Mrs. H is currently doing well. Moreover, she has had no further episodes of bronchitis, suggesting that scurvy perhaps had reduced her immune function. I have since diagnosed and cured scurvy in four additional patients, each of whom presented with several early symptoms and had more than one risk factor. One patient was status post gastric bypass surgery, smoked, and drank alcohol daily. All four patients were taking PPIs. Two had poor diets. I was able to diagnose and treat them prior to development of any hemorrhagic complications. I now routinely screen for vitamin C deficiency in any patient with early symptoms. I also routinely prescribe vitamin C supplementation for those on PPI therapy.
Dr. Cave is a family physician in private practice in Navarre, Fla.
- Hampl JS, Taylor CA, Johnston CS. Vitamin C deficiency and depletion in the United States: The Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health. 2004;94:870-875.
- Clements RH, Katasani VG, Palepu R, et al. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72:1196-1202; discussion 1203-1204.
- Henry EB, Carswell A, Wirz A, et al. Proton pump inhibitors reduce the bioavailability of dietary vitamin C. Aliment Pharmacol Ther. 2005;22:539-545.