Lessons of the month 2: Meningococcal epiglottitis and connective tissue disease associated with C2 deficiency

A 68-year-old woman was referred for immunological investigation following an episode of meningococcal epiglottitis with associated septicaemia. Several years previously, she had been diagnosed with undifferentiated connective tissue disease. On investigation, alternative pathway complement function was normal; however, classical pathway complement activation was reduced. C1q, C3 and C4 levels were all measured and found to be within their respective normal ranges, but C2 levels were low. Sequencing of the C2 gene was subsequently performed, confirming a diagnosis of type 1 C2 deficiency (C2D).

C2D is usually hereditary and inherited in an autosomal recessive manner. C2D is often asymptomatic, however, some patients suffer from infections with encapsulated bacteria and/or autoimmune diseases, particularly systemic lupus erythematosus. Recognition of complement pathway deficiency is important due to the predisposition to severe and/or recurrent infections by encapsulated bacteria. Immunisations have the potential to reduce both mortality and morbidity not only for the patient but also for any affected relatives.