A Case of Scurvy in an Elderly Patient
Pages 29 - 32
A 70-year-old man was brought to the emergency room by his neighbor, who reported a 10-day history of progressive fatigue, leg pain, and generalized weakness. The patient had suffered an ischemic stroke 7 months before and was dependent on his neighbor for his daily care. His past medical history was significant for hypertension. His caretaker also commented on the patient’s decline in function during the last month, noting some “bloody stools,” shortness of breath, “easy bruising,” leg swelling, and a recent “red rash” on his arms and legs. The patient had no known allergies, and his daily medications were aspirin 81 mg orally, lansoprazole 30 mg orally before meals, and hydrochlorothiazide 25 mg orally. He denied use of tobacco or illicit drugs. He drank 1-2 cans of beer per day. The patient was admitted to the Medicine service.
The patient’s initial vital signs were: heart rate 100 beats/min, blood pressure 110/65 mm Hg, respiratory rate 18 breaths/min, and temperature 36.8 degrees C. His height was 1.88 m, and he weighed 67 kg (body mass index = 19). Physical examination revealed lethargy, cachexia, left hemiparesis, poor dentition, gingival erythema, and pitting edema (2+). The skin examination showed small petechiae in the upper and lower extremities and large ecchymoses below the knees bilaterally. He was found to be anemic (hemoglobin 9.1 g/dL, mean corpuscular volume 88) with normal differential, platelet count, prothrombin time (PT), and partial thromboplastin time (PTT). His electrolytes (sodium, potassium, calcium, magnesium, phosphate) were all within normal limits. His chest x-ray was normal, and a computed tomography scan of the brain failed to identify recent lesions. Stool specimen was positive for blood. Urinalysis revealed a urinary tract infection, and appropriate antibiotic therapy was started. Iron and ferritin levels were low normal. B12 and folate levels were also normal. Albumin count was 3.0 g/dL. Work-up for hepatitis, hemolysis, and vasculitis were negative. Idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura were ruled out since the PT and PTT were normal. Doppler ultrasonography of the lower extremities was negative for deep vein thrombosis.
The patient was referred to a gastroenterologist for endoscopy. Esophagogastroduodenoscopy (EGD) revealed mild esophagitis at the gastro-esophageal junction (Los Angeles class A) and normal stomach and duodenum. Colonoscopy revealed diverticulosis of the sigmoid colon and internal hemorrhoids. A source of bleeding was not identified.
Considering the patient’s poor nutritional status, a serum ascorbic acid (vitamin C) level was ordered. It was found to be less than 0.02 mg/dL (normal = 0.2-2.0 mg/dL). The diagnosis of scurvy and malnutrition was made. We re-examined the patient and identified corkscrew-like hairs. A dietary history showed that the patient’s diet consisted entirely of bread, cheese, pasta, canned meatballs, and beer. The patient was started on a high-protein diet with vitamin C supplementation (1 g daily). His improvement was dramatic. After the 10th day of his hospitalization, the patient was back at his baseline with total resolution of his fatigue, extremity pain, generalized weakness, and skin lesions. He was discharged home under the care of a visiting nurse. His hemoglobin was 12.8 g/dL at his 1-month follow-up visit.
Hypovitaminosis C or scurvy (called “the despicable disease”)1 has been described for centuries, first in 1541 by a Dutch physician named Echthius in Cologne, Germany, who thought it was an infectious disease. In 1540, the French explorer Jacques Cartier was told of a remedy for scurvy made of pine tree needles from Native Americans in Canada. The first English reference to the disease appeared in the Oxford English Dictionary in 1565. Scurvy was recognized as an important problem beginning in the 15th century, when it ravaged crews during lengthy seafaring voyages. The Portuguese sailor Vasco da Gama described 100 of his 160 crew members as having developed severe lassitude and swelling of legs, hands, and gums, resulting in fatality.
Scurvy was not, however, limited to sailors. Cases were described during the Peloponnesian war, the Crusades, the Napoleonic wars, the American Civil War, the exploration of the Poles, the Irish famine, the Mormon trail (“Black-Leg disease”), and even among soldiers in World War I.2-7
Two physicians who played a significant role in decreasing mortality from scurvy were John Woodall and James Lind. In 1617, Woodall wrote The Surgeon’s Mate, which described the disease and listed lemon juice as the cure. Woodall was responsible for persuading the East India Company to give lemon juice to its sailors.4 In 1753, Lind published The Treatise on the Scurvy.8 He was a naval surgeon in the British Royal Navy and described his clinical trial on board the HMS Salisbury. On May 20, 1747, he divided 12 sailors suffering from scurvy into six groups of two, and he treated each group with a different remedy. Only the two sailors given two oranges and one lemon daily improved. Unfortunately, it took 41 years before his recommendations were adopted. The British used lime juice instead of lemon or orange juice to prevent the disease; thus, the term “limeys” originated.
Vitamin C is a water-soluble vitamin that was first isolated in 1928 by Hungarian chemist Albert von Szent-Györgyi.3 He named it ascorbic acid (for its “anti-scorbutic” effects) in 1932 and received the Nobel Prize in 1937.5 Humans, other primates, and guinea pigs cannot synthesize ascorbic acid like other living organisms, and so are dependent on ascorbic acid from dietary sources. The enzyme L-gluconolactone oxidase, which usually would catalyze the conversion of L-gluconogammalactone to L-ascorbic acid, is defective due to a mutation or inborn error in carbohydrate metabolism. Ascorbic acid is a necessary cofactor in the synthesis of collagen.9 During the pro-alpha chain processing in the rough endoplasmic reticulum of the cell, lysine and proline residues are hydroxylated to hydroxylysine and hydroxyproline. This is an important step for the collagen fiber cross-linking. The hydroxylases need vitamin C as a reducing agent and molecular oxygen. In scurvy, collagen fibers cannot be cross-linked, greatly decreasing the tensile strength of the fiber. This results in the breakdown of connective tissue in and around the walls of blood vessels.
Scurvy is characterized by bleeding due to capillary fragility, poor healing of wounds, and, in children (Cheadle-Möller-Barlow syndrome), bone abnormalities (scurvy rosary).10 The most characteristic physical finding is the perifollicular hemorrhage, a hyperkeratotic follicle surrounded by a pink halo. Hairs may acquire a corkscrew appearance. Other manifestations include purpura, intramuscular hemorrhage, gingival involvement in dentulous patients, edema, exertional dyspnea,11 and emotional disturbances that can include apathy, depression, bipolar disorder, and anxiety.12,13 Anemia is common and multifactorial, with causes including hemorrhage into tissues, altered metabolism, deficiencies of folate and iron, gastrointestinal (GI) blood loss, and intravascular hemolysis.14 Late signs include icterus and fever, and sudden death can occur. Other, less common manifestations of scurvy include ocular hemorrhages,15 Sjögren’s syndrome,16 femoral neuropathy (resulting from hemorrhage into the femoral sheaths),17 impaired vascular reactivity,18 and arthritis.11 Rare cases of cardiac involvement in patients with scurvy have been reported.19,20
Lind8 reported the onset of scurvy in sailors after a 1.5-month period at sea and described lassitude as its early and consistent symptom. Depletion-repletion studies in volunteers using a vitamin C–free diet have shown that plasma vitamin C level falls below 0.2 mg/dL in less than 1 month. At these concentrations, fatigue is usually noted, with physical signs soon appearing.21,22 The recommended daily allowance for vitamin C varies. The Food and Nutrition Board of the United States National Academy of Sciences recommended allowances for vitamin C are 75 mg per day for women and 90 mg per day for men. Higher doses are recommended for smokers, alcoholics, persons with diabetes, and those who are severely ill. More recent recommendations suggest 120 mg daily.23 Some experts feel that the level should be as high as 200 mg daily to match the level present in five servings of fruits and vegetables daily, a diet shown to decrease cancer risk.
Vitamin C intake has been reported to be less than 60 mg per day in 20-30% of U.S. adults,24 and even lower among many population subgroups. Since the first symptom is fatigue, a common, nonspecific complaint, subclinical vitamin C deficiency is much more common than is generally noted.25,26 Population subgroups at risk are the elderly (who sometimes have “tea-and-toast” diets), the socially isolated, alcoholics, food faddists,27,28 patients with psychiatric illness,29 and young children (eating exclusively cow’s milk formula).30 Cigarette smokers require increased intake of vitamin C due to lower vitamin C absorption. Pregnant and lactating women and patients with thyrotoxicosis require increased intake of vitamin C because of increased utilization. Vitamin C deficiency has recently been noted in refugees who are dependent on external suppliers for their food and have limited access to fresh fruits and vegetables.31 Large doses of vitamin C (eg, more than 1 g/day) may increase the risk of kidney stones, particularly oxalate stones.23
The correct diagnosis of scurvy can be delayed because the disease can mimic disorders such as vasculitis, systemic bleeding disorders, and deep vein thrombosis; patients with scurvy are often evaluated for other disorders. Knowledge of the manifestations of scurvy and higher levels of suspicion of the high-risk groups is important for clinicians to help in prevention. Taking a patient’s extensive dietary history can be very helpful; a plasma or leukocyte vitamin C level finding can confirm the clinical diagnosis. Capillary fragility can be checked by inflating a blood pressure cuff and observing a patient’s forearm for petechiae.
Treatment of scurvy is simple and effective. The usual dose in adults is 100 mg orally 3-4 times daily until 4 g have been administered, then 100 mg per day. Orally-administered vitamin C is well absorbed from the GI tract. It can also be given intravenously or intramuscularly in special circumstances. A diet rich in vitamin C should be initiated simultaneously.32 Foods rich in vitamin C are citrus fruits (especially grapefruit and lemons) and vegetables (eg, broccoli, green peppers, tomatoes, cabbage).
Patients respond quickly to oral therapy, and the prognosis is excellent: spontaneous bleeding ceases within 1 day, muscle and bone pain stop quickly, bleeding and sore gums heal in 2-3 days, and ecchymoses heal within 12 days. In advanced scurvy, serum bilirubin normalizes in less than 1 week, and anemia is corrected in 2-4 weeks.32
Scurvy is a relatively uncommon diagnosis, but the consequences of a missed diagnosis can be dire. Clinicians should consider hypovitaminosis C or other nutritional deficiencies in such high-risk groups as the elderly, those who are socially isolated, alcoholics, food faddists, patients with psychiatric illness, and young children. With a high level of suspicion, knowledge of the symptomatology, and a thorough dietary history, the diagnosis can be easily made. The treatment of scurvy is simple and effective.
The authors report no relevant financial relationships.