The Utility of IgG4/IgG Ratio in the Diagnosis of Multicentric Castleman Disease: A Case Report of HHV8+ Castleman Disease in a Patient with Classical Hodgkin's Lymphoma.

Background/

Objectives

Multicentric Castleman Disease (MCD) is a rare lymphoproliferative disorder that can mimic IgG4-related disease (IgG4-RD), particularly in patients presenting with elevated serum IgG4. Accurate diagnosis is crucial given differing treatments and prognoses. Case Presentation: We describe a 76-year-old male with fever, lymphadenopathy, and elevated inflammatory markers. Labs revealed an elevated IgG4 of 133 mg/dL and total IgG of 1410 mg/dL, yielding an IgG4/IgG ratio of 9.43%. Lymph node biopsy showed nodular sclerosing classical Hodgkin lymphoma, for which he received five cycles of A + AVD. Persistent symptoms, elevated IL-6, and HHV8 viremia prompted repeat biopsy, which demonstrated HHV8-positive MCD. Rituximab was initiated, which resulted in clinical and radiographic resolution.

Methods

We performed a systematic review of the English-language literature from 2000 to 2025, identifying 23 studies that contained MCD cases with individual-level serum IgG4 and IgG data. A total of 36 unique cases were included.

Results

The mean IgG4/IgG ratio was 14.61%, which is substantially lower than ratios typically seen in IgG4-RD. To our knowledge, our case is the only reported instance of HHV8-associated MCD with elevated IgG4.

Conclusions

A mildly elevated IgG4/IgG ratio may favor the diagnosis of MCD over IgG4-RD. Serum IgG4 and total IgG should be considered when suspecting Castleman Disease.