What are the typical presentation and pathogenesis of scurvy in pediatric patients?

Presentation and Pathogenesis of Scurvy in Children

Pathogenesis

Scurvy results from insufficient intake of vitamin C (ascorbic acid), which is essential for collagen synthesis, leading to defective connective tissue formation throughout the body. 1

• Vitamin C is critical for hydroxylation of proline and lysine residues in collagen synthesis, and its deficiency causes impaired collagen formation affecting blood vessels, bone matrix, and connective tissues throughout the body 1
• The condition develops in older infants and children given exclusively cow's milk without vitamin supplementation, as cow's milk contains insufficient vitamin C, particularly when subjected to ultra-heat temperature (UHT) processing 1, 2
• Well-cooked foods destroy vitamin C, and children fed exclusively cooked foods with minimal or no fresh fruits and vegetables are at high risk 2
• Children with restrictive or selective dietary habits are particularly vulnerable, including those with developmental delay, autism spectrum disorder, physical disabilities, or neuropsychiatric disorders 3, 4, 5

Clinical Presentation

Musculoskeletal Manifestations (Most Common)

The hallmark presentation in children is limping or refusal to walk (96% of cases) with tenderness of the lower limbs (86%), often mimicking more serious conditions like malignancy or autoimmune disease. 2, 5

• Pain and pseudoparalysis of the lower extremities occur due to subperiosteal hemorrhages, particularly affecting the metaphyseal regions of long bones 1
• Joint swelling and severe arthritis can develop, sometimes mistaken for inflammatory arthropathies like IgA vasculitis 3
• Children typically present between 1-4 years of age (93% of cases), with a median age of 29 months 2

Mucocutaneous Manifestations

• Bleeding gums and gingival swelling (36% of cases), with friable gingival tissue and loose teeth on examination 2, 3
• Perifollicular hemorrhages, petechiae, and ecchymoses, particularly on the lower extremities 3, 5
• Follicular hyperkeratosis with corkscrew hairs visible on skin examination 3
• Poor wound healing and easy bruising 3, 6

Constitutional Symptoms

• Irritability, asthenia, and refusal to eat are common early manifestations 3, 6
• Fever occurs in approximately 18% of cases 2
• Severe weight loss and failure to thrive may develop 3

Hematologic Findings

• Anemia is common, often severe, and may be accompanied by hematochezia or other bleeding manifestations 6, 3
• Elevated inflammatory markers frequently mislead clinicians toward infectious or inflammatory diagnoses 3, 5

Radiographic Findings

Characteristic radiographic changes include osteopenia, increased sclerosis of the zones of provisional calcification, dense epiphyseal rings (Wimberger sign), metaphyseal white lines, rarefaction zones, and extensive calcification of subperiosteal hemorrhages. 1

• Subperiosteal hematomas appear as elevated periosteum with calcification 4
• Ring epiphysis and metaphyseal changes are pathognomonic when present 4
• Epiphyseal separation can occur in severe cases (reported in 7% of one series) 2
• Bilateral limb radiographs are essential as findings are typically symmetric 4

Critical Diagnostic Pitfalls

Scurvy is misdiagnosed in 86% of cases initially, most commonly confused with malignancy, osteomyelitis, child abuse, autoimmune diseases (particularly IgA vasculitis), or other metabolic bone diseases. 2, 3, 5

• Normal nutritional status does not exclude scurvy - children may appear well-nourished despite severe vitamin C deficiency 5
• The presence of anemia and elevated inflammatory markers often misleads toward infectious or malignant diagnoses 3, 5
• Metaphyseal changes can resemble classic metaphyseal lesions (CMLs) seen in child abuse, but scurvy shows additional characteristic findings including osteopenia, dense epiphyseal rings, and extensive calcification of subperiosteal hemorrhages that distinguish it 1
• A detailed dietary history is mandatory - specifically asking about intake of fresh fruits, vegetables, and use of UHT milk (average 5.8 boxes/day in affected children) 2

Diagnostic Approach

• Serum vitamin C level is the diagnostic gold standard when scurvy is suspected 5
• Focused dietary history revealing lack of fresh fruits and vegetables, exclusive consumption of well-cooked foods, and/or excessive UHT milk intake should raise immediate suspicion 2, 3
• Skin biopsy showing follicular hyperkeratosis with extravasated perifollicular red blood cells can confirm the diagnosis when clinical suspicion is high 3
• Bilateral skeletal radiographs interpreted by an experienced radiologist can reveal pathognomonic features 4, 5

Treatment and Response

Vitamin C supplementation produces dramatic clinical improvement within the first week of treatment, with resolution of pain, irritability, and ability to walk typically restored rapidly. 2, 3, 6

• The rapid therapeutic response to vitamin C has both diagnostic and therapeutic value 3
• Follow U.S. Recommended Dietary Allowances (RDA) for age when treating scurvy in pediatric patients age 5 months and older 7
• Pediatric patients less than 2 years may be at higher risk of oxalate nephropathy following ascorbic acid administration due to decreased glomerular filtration rate 7