Chronic pulmonary aspergillosis and pulmonary embolism/venous thromboembolism: a case series and systematic review of the literature.

Chronic pulmonary aspergillosis (CPA) often arises in the setting of structural lung damage and is associated with chronic inflammation, which increases the risk of venous thromboembolic disease (VTE), including pulmonary embolism (PE). However, the clinical context and pathophysiological mechanisms underlying CPA/VTE remain poorly defined. This study aims to highlight the clinical challenges through a case series and systematic review of existing literature regarding this rare co-occurrence. We present three complex cases from Kiruddu National Referral Hospital in Uganda: two males, one female, aged 44-80 years, with post-tuberculosis lung disease. All three were diagnosed with Aspergillus IgG-positive CPA and confirmed PE (two acute, one with chronic thromboembolic pulmonary hypertension (CTEPH)). One presented with concurrent active tuberculosis (TB) relapse and severe immunosuppression (CD4 T-cells < 200 cells/mm3), and two had HIV. All patients received itraconazole and anticoagulation with rivaroxaban. Two patients survived and are stable on therapy, while one patient died due to septic shock. A systematic search of PubMed, Embase, Scopus, and Web of Science yielded seven studies reporting nine patients with coexisting CPA and VTE/PE. Underlying conditions most frequently included prior TB (n = 3) and chronic obstructive pulmonary disease (n = 3). PE was chronic in three patients (including one with CTEPH), with CPA subtypes ranging from simple aspergilloma to subacute invasive aspergillosis and angioinvasive aspergillosis. Proposed mechanisms included endothelial damage due to Aspergillus angioinvasion and creation of post-PE lung cavities/infarcts suitable for Aspergillus colonization. Anticoagulation was used in six cases, but was complicated by hemoptysis in three. Two-thirds of patients improved with antifungal therapy, while three deaths were reported. CPA may coexist with PE/DVT due to fungal angioinvasion, chronic inflammation, or immobilization from advanced lung disease. Management requires individualized balancing of antifungal and anticoagulation therapy, with heightened vigilance for bleeding.