Differential Diagnosis for Recurrent Bacterial Infections
- Single most likely diagnosis:
- Classical pathway (C1-C3) deficiency: This is the most common complement deficiency associated with recurrent bacterial infections, particularly those caused by encapsulated organisms like Streptococcus pneumoniae. The classical pathway plays a crucial role in the opsonization and clearance of these pathogens.
- Other Likely diagnoses:
- Lectin pathway (MBL) deficiency: As you mentioned, defects in the lectin pathway, particularly mannose-binding lectin (MBL) deficiency, can predispose individuals to recurrent infections, including bacterial infections. MBL is important for the recognition and binding to carbohydrate patterns on the surface of pathogens, initiating the complement cascade.
- Alternative pathway (factor D, properdin) deficiency: Deficiencies in the alternative pathway can also lead to increased susceptibility to bacterial infections, as this pathway is crucial for the direct activation of the complement system on microbial surfaces.
- Do Not Miss diagnoses:
- Terminal pathway (C5-C9) deficiency: While less common, deficiencies in the terminal components of the complement system (C5-C9) can lead to severe and recurrent infections, particularly with Neisseria species. This is because the terminal pathway is essential for the formation of the membrane attack complex (MAC), which is necessary for the lysis of these bacteria.
- Combined immune deficiency: Conditions like combined immunodeficiency can present with recurrent infections due to a broader impairment of the immune system, including both cellular and humoral immunity.
- Rare diagnoses:
- Properdin deficiency: This is a rare X-linked condition that affects the alternative pathway of the complement system, leading to increased susceptibility to bacterial infections.
- Factor H or factor I deficiency: These deficiencies affect the regulation of the alternative pathway and can lead to uncontrolled activation of the complement system, resulting in increased susceptibility to certain infections.