Vitamin C Deficiency — Scurvy

Scurvy is a severe nutritional deficiency disease resulting from inadequate intake or absorption of ascorbic acid (vitamin C), an essential water-soluble vitamin required for collagen synthesis and multiple enzymatic reactions. Although rare in developed nations, scurvy remains clinically significant in specific populations including homeless individuals, elderly patients with poor nutrition, those with severe malabsorption disorders, and patients on restrictive diets lacking fresh fruits and vegetables. The disease causes characteristic mucocutaneous bleeding, poor wound healing, and bone abnormalities through disruption of collagen cross-linking. Recognition of scurvy is critical for board examinations as it represents a prototypical nutritional deficiency with distinctive clinical findings and a dramatic response to supplementation, making it an ideal testing case for nutritional assessment competency.

Ascorbic acid functions as a mandatory cofactor for prolyl hydroxylase and lysyl hydroxylase, enzymes that catalyze hydroxylation of proline and lysine residues in procollagen. These hydroxylation reactions are absolutely essential for stable cross-linking of collagen triple helices through hydrogen bonding between hydroxylated residues. Without adequate vitamin C, newly synthesized collagen contains unhydroxylated proline and lysine, rendering the triple helix unstable, prone to degradation, and mechanically weak. This explains the pathognomonic bleeding manifestations and impaired wound healing—tissues dependent on structural integrity (gingiva, blood vessel walls, skin) become friable and fail under normal mechanical stress.

Vitamin C is a critical reducing agent necessary for converting dietary ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), the form optimally absorbed in the proximal small intestine. Vitamin C deficiency leads to decreased absorption of non-heme iron, potentially exacerbating anemia in patients with marginal iron stores. Additionally, vitamin C deficiency impairs iron mobilization from storage sites, as it is required for ferroxidase activity in iron metabolism pathways.

Ascorbic acid serves as a major antioxidant protecting cells from reactive oxygen species (ROS) and free radical damage. Deficiency results in accumulated intracellular oxidative stress, impairing neutrophil function, cell-mediated immunity, and antibody production. This contributes to impaired wound healing and increased susceptibility to secondary infections observed in scurvy patients.

Osteoblasts require vitamin C for hydroxylation of procollagen during osteoid (unmineralized bone matrix) formation. In scurvy, osteoid production is severely impaired, leading to defective bone healing and characteristic radiographic findings including subperiosteal hemorrhages, "scorbutic rosary" at the costochondral junctions, and the Wimberger ring sign (sclerotic ring around epiphyseal centers). Additionally, bleeding into subperiosteal spaces damages the periosteum, further compromising bone integrity.

Blood vessel walls require adequate collagen in the basement membrane and supporting connective tissue for structural integrity. Vitamin C deficiency causes progressive weakening of capillary and arteriolar walls, predisposing to spontaneous hemorrhage, particularly in tissues subject to mechanical stress or increased intravascular pressure.

Vitamin C is necessary for hydroxylation of trimethyllysine to γ-butyrobetaine in the pathway of carnitine synthesis. Deficiency may contribute to myalgias and fatigue through impaired fatty acid oxidation in mitochondria, though this is a minor mechanism compared to collagen defects.

The most common cause globally, particularly in populations with limited access to fresh fruits and vegetables. Risk factors include poverty, food insecurity, severe dietary restrictions (strict vegan diets lacking supplementation, elimination diets), prolonged hospitalization with poor dietary provision, alcoholism with malnutrition, and elderly individuals living alone with poor dietary habits. Humans cannot synthesize vitamin C endogenously and have no storage capacity; deficiency develops after approximately 8-12 weeks of near-zero intake.

Inflammatory bowel disease (Crohn's disease, ulcerative colitis) with extensive small bowel involvement impairs vitamin C absorption. Celiac disease causes mucosal damage reducing absorptive surface. Post-gastrectomy or short bowel syndrome from extensive surgical resection limits absorption. Chronic diarrhea from any cause increases fecal losses. Cystic fibrosis may impair fat-soluble nutrient absorption, though vitamin C is water-soluble.

Chronic infection and sepsis increase oxidative stress and consumption of vitamin C as tissues attempt to manage ROS. Chronic wounds or major burns dramatically increase collagen synthesis demands, requiring 200+ mg daily (normal requirement is 75-90 mg). Malignancy is associated with increased oxidative metabolism. Chronic renal disease with dialysis may cause losses or inadequate replacement, though dialysis does not remove significant vitamin C.

Dialysis may remove water-soluble vitamins depending on membrane characteristics. Some sources cite slightly increased urinary losses with certain medications, though clinical significance is minimal in the setting of adequate intake.

Severe depression, dementia, and other conditions impairing self-care or appetite. Homelessness represents one of the highest-risk populations in developed countries due to inability to procure or store fresh foods and associated comorbidities.

Often the first symptom, developing insidiously after weeks of deficiency. Patients describe progressive lethargy and decreased exercise tolerance. Mechanism relates to both impaired carnitine synthesis limiting fatty acid oxidation and systemic metabolic dysfunction from collagen defects throughout tissues.

Muscle and joint pain are prominent complaints, particularly in the legs and lower extremities. The pain is often severe enough to limit mobility. Arthralgias may mimic inflammatory arthritis but lack the persistent swelling and warmth of true arthritis. Mechanism involves both collagen defects in musculotendinous structures and possibly direct myopathy.

Perifollicular hemorrhages and bleeding gums are classic presentations. Bleeding begins at the gum line, particularly around teeth, and is accompanied by halitosis and loosening of teeth from inflammatory destruction of the periodontal ligament (which is rich in collagen). Gingival bleeding may lead to secondary bacterial infection and severe gingivitis. This finding is essentially pathognomonic when combined with appropriate dietary history.

Spontaneous bleeding into skin manifests as petechiae (small, non-blanching red/purple spots) and larger purpura, typically distributed over lower extremities, buttocks, and areas subject to pressure or trauma. Lesions have a characteristic perifollicular distribution with hemorrhage surrounding hair follicles (perifollicular hemorrhages), sometimes with a "corkscrew" appearance of distorted hairs due to fragmented hair shafts. These occur due to capillary wall fragility and are typically painless and non-pruritic.

Previous healed wounds may spontaneously reopen and bleed. New wounds heal poorly with friable tissue and delayed epithelialization. Hemorrhage into wound spaces impairs healing further. This can be catastrophic in surgical patients—a classic board scenario involves an elderly patient presenting with reopened surgical sites weeks to months after surgery, ultimately traced to scurvy.

Loose teeth develop as the periodontal ligament (Sharpey's fibers in cementum) degrades due to collagen deficiency. Anemia may develop or worsen due to impaired iron absorption and chronic blood loss from multiple bleeding sites. Some patients present with oral mucosal bleeding or sore throat.

Edema may develop from impaired collagen in blood vessel walls and tissues, predisposing to fluid accumulation. Hyperkeratotic follicles with surrounding erythema appear on the skin, particularly on the lower extremities and buttocks. Follicles may contain coiled hairs ("corkscrew hairs") visible on careful inspection.

Severe bone pain, particularly along the long bones, develops from subperiosteal hemorrhages and defective osteoid formation. Infants may assume the "pithed frog" position (legs drawn up and externally rotated) due to severe leg pain from subperiosteal hemorrhages. Growth may be stunted in children with chronic deficiency.

Fever is generally absent unless secondary infection supervenes. Weight loss occurs from poor intake and malabsorption. Irritability, depression, and mood disturbances are common.

Infantile scurvy (ages 6-24 months) presents with extreme irritability, refusal to move or bear weight ("pithed frog" position), severe bone pain, subperiosteal hemorrhages on imaging, and gingival bleeding if teeth have erupted. Chronic/subclinical scurvy may present predominantly with impaired wound healing or recurrent infections rather than classic bleeding manifestations.

The diagnosis begins with a careful nutritional history specifically addressing intake of citrus fruits, berries, tomatoes, and other vitamin C-rich foods. Inquiry should include socioeconomic status, access to fresh foods, dietary restrictions, gastrointestinal symptoms suggesting malabsorption, and previous gastrointestinal surgery. A dietary intake of essentially zero vitamin C-containing foods for 8+ weeks strongly raises suspicion. History of recent or reopened wounds adds diagnostic weight.

Gingival bleeding and perifollicular hemorrhages are the classic findings. Careful examination of the lower extremities for petechiae with perifollicular distribution is essential. Assessment of wound status (delayed healing, spontaneous reopening) and tooth mobility should be performed. Checking for corkscrew hairs is valuable though not always present.

Fasting plasma vitamin C concentration <11 μmol/L (or <0.2 mg/dL) confirms deficiency. Levels <25 μmol/L (0.45 mg/dL) indicate depleted body stores and risk for scurvy. The normal reference range is approximately 23-85 μmol/L (0.4-1.5 mg/dL). This test is definitive but requires proper specimen handling (kept on ice, analyzed promptly) as vitamin C oxidizes rapidly. Plasma levels can decrease rapidly with intercurrent illness and do not perfectly reflect total body stores, but they are the standard diagnostic test.

An alternative and possibly more accurate reflection of tissue stores, as it represents intracellular vitamin C levels. Levels <11 μmol/L per 10⁷ cells indicate deficiency. However, this test is less commonly available and standardized than plasma levels.

Normocytic or microcytic anemia may be present from chronic blood loss and/or iron malabsorption. Anemia correlates with disease severity. If iron studies reveal iron deficiency concurrent with vitamin C deficiency, both should be treated.

Subperiosteal hemorrhages appear as lucent lines adjacent to long bone metaphyses on X-rays of the legs. The characteristic Wimberger ring sign (sclerotic ring around epiphyseal centers) and Frankel's lines (sclerotic bands along metaphyses) are pathognomonic findings primarily in infantile scurvy. A "ground glass" appearance of bones from osteopenia may be present. These findings, while characteristic, are not necessary for diagnosis if clinical features and low plasma vitamin C are present.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are typically normal, distinguishing scurvy from vitamin K deficiency or coagulopathy. This is an important diagnostic distinction, as patients with bleeding may initially be evaluated for coagulation disorders.

Scurvy diagnosis requires: (1) clinical features consistent with vitamin C deficiency (perifollicular hemorrhages, gingival bleeding, poor wound healing), (2) dietary history of inadequate vitamin C intake or malabsorption, and (3) confirmation with plasma ascorbic acid <11 μmol/L. Not all three criteria must be present simultaneously if clinical suspicion is high, as treatment response can be diagnostic.

Vitamin K deficiency presents with bleeding but has prolonged PT/INR. Scurvy vs. bleeding disorder: Scurvy has normal coagulation studies. Henoch-Schönlein purpura (HSP) has palpable purpura with systemic manifestations but lacks the perifollicular distribution and gingival findings of scurvy. Thrombocytopenia causes petechiae but lacks the perifollicular distribution. Copper deficiency can cause similar bleeding and anemia but is rare; it typically occurs in patients on long-term parenteral nutrition without copper supplementation. Ehlers-Danlos syndrome presents with bleeding and poor wound healing but has genetic basis and lifelong manifestations rather than acute nutritional presentation.

Dosing: 500-1000 mg twice daily orally is the standard initial dose. For severe manifestations, some authorities recommend up to 2000-4000 mg daily divided into multiple doses. Duration: Acute symptoms typically improve within days to 2 weeks; complete resolution usually occurs within 4-8 weeks of supplementation. Continuation for a minimum of 2-3 months ensures complete tissue repletion.

Mechanism: Oral supplements rapidly restore plasma and tissue vitamin C levels, allowing resumption of normal collagen hydroxylation, stabilization of existing collagen, reactivation of immune function, and restoration of vascular integrity. The dramatic clinical response (cessation of bleeding within days, improved wound healing within 1-2 weeks) is often diagnostic when plain diagnosis has been uncertain.

Oral supplementation is preferred and effective for all patients without severe malabsorption or inability to take oral medications. Standard formulations include tablets, chewables, or powders. Tablets should be swallowed whole or dissolved in water; chewable forms may be preferable in elderly or dysphasic patients. For patients with severe malabsorption or inability to take oral medications, intravenous or intramuscular ascorbic acid may be used (250-500 mg daily), though this is rarely necessary.

Non-pharmacological measure of critical importance: Once deficiency is recognized, patients must receive comprehensive dietary counseling to ensure sustained adequate vitamin C intake (75-90 mg daily for adults; 15-45 mg for children depending on age). Education should target incorporation of vitamin C-rich foods: citrus fruits (oranges, lemons, grapefruits), berries (strawberries, blackberries, raspberries), tomatoes, bell peppers, cruciferous vegetables (broccoli, Brussels sprouts), potatoes, and kiwifruit. Emphasis on affordable, accessible sources is crucial for populations with food insecurity. Cooking decreases vitamin C content significantly, so raw or minimally cooked preparations are preferred.

If iron deficiency anemia is present, iron supplementation (ferrous sulfate 325 mg daily or ferrous gluconate 325 mg daily) should be initiated concurrently with vitamin C, as vitamin C enhances non-heme iron absorption. Dosing follows standard iron supplementation protocols with assessment of tolerance (gastrointestinal side effects).

If malabsorption is the underlying cause, addressing the primary disorder is essential. For inflammatory bowel disease, optimize IBD-specific therapy; for celiac disease, strict gluten-free diet; for short bowel syndrome, consider specialized formulas or parenteral supplementation if necessary.