The clinical picture of Castleman disease-a systematic review and meta-analysis

• Publications on CD clinical presentation are limited; we describe lab abnormalities and symptomatology of CD subtypes from 1998 patients.

• Constitutional symptoms and splenomegaly are more common in HHV8+MCD vs iMCD; renal dysfunction is more common in iMCD vs HHV8+MCD.

Castleman disease (CD) encompasses a spectrum of rare disorders, including unicentric (UCD), idiopathic multicentric (iMCD), and human herpesvirus 8-associated MCD (HHV8+MCD). We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following PRISMA guidelines, to describe and compare subtypes. We extracted data on clinical symptoms and laboratory parameters as stated in international consensus diagnostic criteria for iMCD, and estimated the frequency of each criterion using meta-analyses. We analyzed 32 studies describing 559 UCD, 1023 iMCD, and 416 HHV8+MCD cases. Though many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+MCD, patients with HHV8+MCD had significantly higher rates of constitutional symptoms (46.6% vs 98.6%, p=0.038) and splenomegaly (48.2% vs 89.2%, p=0.031). Renal dysfunction was significantly more common in patients with iMCD than patients with HHV8+MCD before adjustment (36.9% vs 17.4%, p=0.04, adjusted p=0.1). Patients with UCD had lower rates of symptoms and laboratory abnormalities, though these were present in 20% of patients and were particularly pronounced in pediatric UCD. There are many similarities in the symptomatology of iMCD and HHV8+MCD; many patients experience constitutional symptoms and organ dysfunction. Differences between these subtypes likely reflect differences in pathophysiology and/or comorbidity burdens.