From the Guidelines
Yes, complement C3 and C4 levels can be lowered due to medication side effects, as seen with medications such as eculizumab, which acts as a terminal complement inhibitor by binding C5 and inhibiting cleavage of C5 to C5A 1.
Medications Affecting Complement Levels
Several medications are known to cause this effect, including:
- Hydralazine
- Procainamide
- Isoniazid
- Minocycline
- Certain anticonvulsants like phenytoin and carbamazepine These medications can induce a drug-induced lupus-like syndrome that leads to complement consumption.
Mechanism and Reversibility
The mechanism typically involves the formation of immune complexes that activate and deplete complement proteins in circulation. This medication effect is usually reversible upon discontinuation of the offending drug, with complement levels gradually returning to normal over weeks to months.
Diagnostic Considerations
If a patient shows unexplained low C3 and C4 levels, a thorough medication review should be conducted, especially if they're also experiencing symptoms like rash, joint pain, or fever. It's essential to consider other conditions like active lupus, glomerulonephritis, or certain infections in the differential diagnosis.
Measurement of Complement Levels
Measurement of the complement C4 level can provide reliable information regarding the possibility of a C1INH deficiency, as seen in hereditary angioedema (HAE) 1. A normal C4 level during an attack of angioedema strongly suggests an alternative diagnosis rather than C1INH deficiency.
From the Research
Complement C3 and C4 Levels and Medication Side Effects
- The provided studies do not directly address the question of whether Complement C3 and C4 levels can be low due to medication side effects 2, 3, 4, 5, 6.
- However, some studies suggest that certain medications, such as corticosteroids and immunoglobulins, can affect complement levels 3.
- For example, a case report found that a patient with autoimmune hemolytic anemia had low C3 and C4 levels, which returned to normal after treatment with plasmapheresis and intravenous immunoglobulin 3.
- Another study found that COVID-19 patients with low C3 and C4 levels had a higher risk of poor outcomes, but it did not investigate the effect of medications on complement levels 5, 6.
- A study on ANCA-associated renal vasculitis found that low C3 levels were associated with poor outcome, but it did not examine the effect of medications on complement levels 4.
- A study on immune thrombocytopenia found that patients with low C4 levels had more severe disease, but it did not investigate the effect of medications on complement levels 2.