D3.363 - Systemic Lupus Erythematosus in a Patient with Hyper IgM Syndrome

Background: Hyper IgM Syndrome (HIGM) is a group of rare primary immunodeficiency disorders, characterised by recurrent infections due to impaired class switch recombination, resulting in normal or elevated levels of serum IgM with reduced IgG and IgA levels. Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease, conventionally diagnosed based on clinical features associated with the presence of autoantibodies, particularly antinuclear antibodies (ANA). ANA-negative SLE has a low prevalence and poses a diagnostic challenge, especially in the context of individuals with underlying immunodeficiency. 

Clinical Case: We report the case of a 36-year-old woman with a history of recurrent infections. Laboratory findings revealed elevated levels of serum IgM (16.05g/L), with reduced IgG (1.99g/L) and absent IgA (<0.05g/L), consistent with HIGM. Complement levels (C3 and C4) were low. She also had clinical features consistent with SLE, including photosensitive malar rash, Raynaud’s phenomenon, arthralgia, myalgia and alopecia. Serological tests, including ANA by HEp-2, connective tissue disease screening, anti-double stranded DNA antibodies, extractable nuclear antigen antibodies, and tissue autoantibodies, were negative. She had failed test vaccinations to Pneumovax and Menitorix and was commenced on immunoglobulin replacement therapy for HIGM. Genetic testing for known primary immunodeficiencies (including causes of HIGM) did not identify any pathogenic mutations. Based on clinical features, she was diagnosed with ANA-negative SLE and was commenced on hydroxychloroquine.

Conclusion: HIGM co-existing with SLE is rare. Autoimmunity in primary immunodeficiencies is an uncommon but recognised phenomenon and has been proposed to arise not only from impaired immune tolerance, but also from chronic immune activation due to persistent microbial antigens that the defective immune system fails to clear (Arkwright et al). This case underscores the diagnostic challenge of SLE in the context of antibody deficiency. The concurrence of complex connective tissue diseases and primary antibody deficiency is rare but relevant in clinical practice.

References

Arkwright, P.D., Abinun, M. and Cant, A.J. (2002) ‘Autoimmunity in human primary immunodeficiency diseases’, Blood, 99(8), pp. 2694–2702. doi:10.1182/blood.v99.8.2694.