What causes elevated serum protein in pediatric patients?

Causes of Elevated Serum Protein in Pediatric Patients

The most common causes of elevated serum protein in pediatric patients are bacterial infections, chronic inflammation, dehydration, and certain chronic diseases affecting protein metabolism. 1

Infectious Causes

• Bacterial infections are the most prevalent cause of significantly elevated serum proteins, particularly through increased acute phase reactants like C-reactive protein (CRP) 1, 2
• Sepsis shows markedly elevated serum proteins, with CRP levels often exceeding 120 mg/L in bacterial infections compared to only 32 mg/L in non-bacterial infections 3, 4
• Bacterial meningitis and bacterial pneumonia are associated with significantly increased serum protein levels, with pneumonia being the most common diagnosis (47-52%) in children with extremely elevated CRP 5, 6
• Cellulitis and other serious bacterial infections can cause protein elevations, with extremely elevated CRP (>30 mg/dL) being strongly associated with bacterial etiology (94.1% of cases) 6

Inflammatory Conditions

• Chronic inflammatory disorders can elevate serum proteins through increased production of acute phase reactants 1, 3
• Kawasaki disease causes significant inflammation with elevated CRP, ESR, and other acute phase proteins 1
• Systemic inflammatory responses in autoimmune conditions like pediatric autoimmune neuropsychiatric disorders can increase serum protein levels 7
• Inflammatory bowel disease, systemic lupus erythematosus, and thyrotoxicosis may increase protein levels, especially in conjunction with dehydration 1

Hematologic and Oncologic Causes

• Chronic hemolytic anemia, β-thalassemia major, and sickle cell disease can lead to elevated serum proteins 1
• Solid tumors can cause significant CRP elevation (median ~46 mg/L) and increased serum proteins 3
• Oncology patients with extremely elevated CRP have high rates of bacteremia (38%) and increased mortality (17.6%) 2

Cardiovascular Causes

• Cerebral venous sinus thrombosis (CVST) in children is associated with elevated serum proteins, especially in the context of prothrombotic disorders 1
• Cardiovascular disease processes can elevate CRP and other inflammatory markers, though typically to lower levels (median ~6 mg/L) than infections 3
• Elevated inflammatory markers including CRP are associated with early atherosclerotic changes and raised lesions in blood vessels 1

Metabolic and Nutritional Causes

• Dehydration can cause relative elevation of serum proteins due to hemoconcentration 1
• Iron deficiency anemia has been associated with elevated serum proteins in children with CVST 1
• Obesity and adiposity are associated with chronic low-grade inflammation and elevated inflammatory proteins 3
• Dietary factors may influence protein levels, with lower intake of grains and vegetables associated with higher CRP levels 1

Clinical Implications

• Extremely elevated serum proteins, particularly CRP >30 mg/dL, are associated with unfavorable outcomes including longer hospital stays and higher mortality rates 2, 6
• Children with extremely elevated CRP appear more ill, require more fluid resuscitation (14.9% vs. 5.3%), and have higher rates of ICU admission (5.0% vs. 1.7%) compared to those with moderately elevated CRP 6
• Serial measurements of serum proteins like CRP are more valuable than single measurements, with normal levels 24-48 hours apart indicating bacterial infection is unlikely 4
• Hypoalbuminemia often accompanies elevated acute phase proteins and is associated with more severe and prolonged acute disease 1

Diagnostic Approach

• Evaluate for infectious causes first, particularly bacterial infections, as they represent the most common etiology of significantly elevated serum proteins in children 5, 6
• Consider inflammatory conditions if infection is ruled out, particularly in children with persistent elevation of inflammatory markers 1, 7
• Assess for dehydration, which can cause relative elevation of all serum proteins 1
• Investigate for hematologic disorders, especially in children with microcytosis or evidence of hemolysis 1
• Consider prothrombotic disorders in children with elevated serum proteins and neurological symptoms 1