X-linked agammaglobulinemia (XLA) is an inherited inborn error of immunity caused by low or absent Bruton tyrosine kinase activity, resulting in impaired B cell development, poor immunoglobulin production, and severe, recurrent infections. Immunoglobulin replacement is the standard of care.
Despite adequate replacement, some patients experience severe infectious complications. In this report, a 19-year-old male with XLA on immunoglobulin replacement with sufficient IgG levels (∼580) presented with fever of unknown origin (FOU). Physical exam notable for echthymic lesions of the anterior thighs near subcutaneous immunoglobulin injection sites.
During workup for FOU, an echocardiogram demonstrated a newly reduced left ventricular ejection fraction (25%) and pericardial effusion. He started cefepime, metronidazole, and vancomycin and was given high-dose intravenous immunoglobulin (IVIG).
He underwent right heart catheterization and endomyocardial biopsy. During cardiac MRI, he experienced cardiac arrest, ultimately requiring venoarterial extracorporeal membrane oxygenation.
Blood cultures and extensive infectious workup, including EBV/CMV PCR, were negative. Lyme screen was negative but results uninterpretable in this patient on IVIG, who cannot make IgM antibodies. A skin biopsy grew Staphylococcus hominis, Corynebacterium striatum group, and Gram-positive bacilli (probable Dermabacter species), consistent with normal skin flora. Given initial concern for non-Helicobacter pylori Helicobacter infection, skin and cardiac biopsies were submitted for Warthin-Starry stain and demonstrated abundant spirochetes. Microbial cell-free DNA sequencing was positive for Borrelia burgdorferi alone, without evidence of non-pylori Helicobacter species. Antibiotics were changed to gentamicin, doxycycline, and meropenem for a 6-week course.
He showed steady improvement, was subsequently extubated, and weaned off hemodynamic support. A repeat echocardiogram demonstrated recovery of his ejection fraction to 65%. Cardiac MRI at the end of therapy showed no residual myocardial enhancement to suggest scar, inflammation, or infiltration.
Patients with XLA are susceptible to fastidious organisms, including members of the Helicobacteraceae family. Increased susceptibility to spirochetes has not been described. Differentiating between spirochete and non-pylori Helicobacter infections can be challenging on Warthin-Starry stain if multiple helical bacteria cluster together, and both groups can have difficulties culturing from peripheral blood. This case is unique in that it describes severe Lyme myocarditis and represents a situation where cell-free DNA sequencing was critical in identifying the causative infectious organism.
