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

Abstract

Castleman disease (CD) encompasses a spectrum of rare disorders, including unicentric CD (UCD), idiopathic multicentric CD (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 preferred reporting items for systematic reviews and meta-analyses 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. Although 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 = .038) and splenomegaly (48.2% vs 89.2%; P = .031). Renal dysfunction was significantly more common in patients with iMCD than in patients with HHV8+ MCD before adjustment (36.9% vs 17.4%; P = .04; adjusted P = .1). Patients with UCD had lower rates of symptoms and laboratory abnormalities, although 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.

Graphical abstract

Figure 1.

Current classification of CD. NOS, not otherwise specified; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TAFRO, thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly; TB, tuberculosis.

Figure 2.

Study flow diagram. RCT, randomized controlled trial.

Figure 3.

Average percentage of laboratory findings. Aggregate cohort-level data showing average percentage of laboratory findings in patients with UCD, iMCD, or HHV8⁺ MCD (95% CIs) identified using a random effect meta-analysis model. ns, not significant.

Figure 4.

Average percentage of symptoms. Aggregate cohort-level data showing average percentage of symptoms in patients with UCD, iMCD, or HHV8⁺ MCD (95% CIs) identified using a random effects meta-analysis model. ns, not significant.