A 69-year-old man from Wisconsin passed away unexpectedly at home in August. Three weeks prior, he presented with symptoms including hot flashes, sweating, shortness of breath, cough, blurry vision, right eye pain, epigastric pain, right shoulder pain, ankle swelling, redness, a swollen neck lymph node, and loss of balance. He also reported multiple bug bites. His medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus. Autopsy findings are shown in the following photos.
The correct answer is ...
This decedent’s gross autopsy showed spotty areas of fibrosis in the heart. Histology showed carditis characterized by interstitial and perivascular lymphoplasmacytic infiltrates with background fibrosis that formed an intersecting curvilinear pattern (“road-map” distribution). The inflammatory infiltrates spanned across the left ventricle, ventricular septum, right ventricle, and the conduction system. Notably, his Lyme antibody modified two-tier test (both IgG and IgM) returned positive. These findings, along with clinical symptoms and geographic location, were consistent with Lyme carditis.
Lyme disease is the most common tick-borne infection in the United States, with an annual report of about 30,000 cases. The spirochetes of Borrelia burgdorferi sensu lato complex are transmitted by ticks (Ixodes ricinus complex), with the peak infection in late spring and summer. Clinical histories can be nonspecific, including viral-like symptoms, malaise, muscle and joint pains, lymphadenopathy, and shortness of breath. Erythema migrans (EM) rash occurs in 70%–80% of patients during the early stage. In the early disseminated phase, cardiovascular symptoms, including atrioventricular block, can occur in about 1.1% of Lyme infection, while fatal myocarditis is rare.
The diagnosis of Lyme carditis is based on clinical history, histology, and serology. Typical autopsy findings include pancarditis with interstitial and perivascular infiltrates, with limited myocyte necrosis. A key differential to hypersensitivity myocarditis is the lack of prominent eosinophilic infiltrates. Warthin-Starry stain (WS), a silver nitrate-based method, is helpful to identify spirochetes, but may have limited sensitivity and specificity due to the low load of the spirochetes and high background staining. Other methods include Borrelia burgdorferi immunohistochemistry (IHC) and nuclear acid detection using polymerase chain reaction (PCR).
Serology testing for Lyme disease includes standard two-tier testing algorism (STTT) and modified two-tier testing algorism (MTTT). For MTTT, enzyme immunoassay (EIA) for total antibody testing against VlsE1 and pepC10 antigens is performed first. If positive, whole cell sonicate (WCS) IgG and IgM testing is performed to confirm the infection. In patients without past Lyme disease, MTTT has been reported to have comparable specificity (≥99%) to STTT, and close to 100% sensitivity for patients with carditis, neuroborreliosis, or arthritis.
It is reasonable to consider arrhythmogenic cardiomyopathy as a potential differential diagnosis for sudden cardiac death. However, the typically gross findings would include fatty or fibrofatty infiltration of the right ventricle with chamber dilation, and histology would show transmural fibrofatty replacement of the myocytes. Given the medical history of hypertension, hyperlipidemia, and diabetes, acute myocardial infarction can be suspected. Autopsy for early infarct may be negative, or demonstrate pale discoloration, hemorrhage, and myocardium softening. Neither of the two scenarios would have pancarditis with extensive lymphoplasmacytic infiltrates.
Yi Zhu, M.D., Ph.D.
Resident, Anatomic Neuropathology
Ross Zumwalt, M.D.
Senior Associate Consultant, Anatomic Pathology