The Risk of Pulmonary Embolism in Patients With Pemphigus: A Population-Based Large-Scale Longitudinal Study

Abstract

Growing evidence suggests that inflammation may pose an atypical risk factor for pulmonary embolism (PE), as it drives venous thrombosis via several pathways. The increased risk of PE in several autoimmune diseases has lent weight to this concept. However, the relative risk of PE among patients with pemphigus has not yet been established. We aimed to examine the risk of PE in patients with pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the relative risk (RR) of PE among 1,985 patients with pemphigus relative to 9,874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of PE was 3.0 (95% CI, 2.2–4.0) and 1.2 (95% CI, 1.0–1.5) per 1,000 person-years among patients with pemphigus and controls, respectively. The period prevalence of PE corresponding to the study period was 2.2% (95% CI, 1.6–2.9%) among cases and 0.9% (95% CI, 0.7–1.1%) among controls. Patients with pemphigus were twice as likely to develop PE as compared to control subjects (adjusted RR, 1.98; 95% confidence interval [CI], 1.29–3.04). The highest PE risk was observed during the 1st year following the diagnosis of pemphigus (adjusted RR, 3.55; 95% CI, 1.78–7.09) and decreased over time. The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted RR, 1.82; 95% CI, 1.11–2.98). In conclusion, pemphigus is associated with an increased risk of PE, particularly during the 1st year of the disease. An awareness of this risk should be increased, additional precipitating factors for PE should be avoided, and thromboprophylaxis may be evaluated in high-risk patients. Further research is required to establish this risk.

Successful Thrombolysis for High-Risk Pulmonary Embolism in a Patient With Extensive Pemphigus Vulgaris

“…4 In a population-based large-scale study, the overall risk of pulmonary embolism was 2-fold higher in pemphigus vulgaris patients, reaching a 3.55-fold increase during the first year, then decreasing over time. 11 In the same cohort, presence of peripheral arterial disease, systemic corticosteroid therapy, and smoking were independent factors associated with pulmonary embolism risk. 11 Considering other potential risk factors such as immobilization, or comorbidities, these patients may warrant assessment of the risk benefit ratio of thromboprophylaxis.…”

Considerations on Immunization and Immunosuppression of Patients With Autoimmune Blistering Diseases During COVID-19 Pandemic in Brazil: Case Report

“…Previous studies revealed that patients with active pemphigus and bullous pemphigoid have higher risk of venous thromboembolism, possibly related to increased expression of tissue factor and pro-inflammatory cytokines leading to a prothrombotic state ( 21 , 22 ). An Italian multicenter cohort study demonstrated a 15-fold risk of venous thromboembolism in patients with active BP ( 21 ), whereas a Israeli population-based study showed a 2-fold risk of pulmonary embolism in pemphigus patients, mainly during the first year of the disease ( 22 ).…”

“…Previous studies revealed that patients with active pemphigus and bullous pemphigoid have higher risk of venous thromboembolism, possibly related to increased expression of tissue factor and pro-inflammatory cytokines leading to a prothrombotic state ( 21 , 22 ). An Italian multicenter cohort study demonstrated a 15-fold risk of venous thromboembolism in patients with active BP ( 21 ), whereas a Israeli population-based study showed a 2-fold risk of pulmonary embolism in pemphigus patients, mainly during the first year of the disease ( 22 ). Additional studies are necessary to determine the benefits of thromboprophylaxis in such patients, especially in the context of COVID-19 pandemic, as the SARS-CoV-2 infection may further activate the coagulation cascade and increase the risk of life-threatening thromboembolic events ( 14 , 23 ).…”

Immunobullous diseases, prothrombotic state, and COVID ‐19: Role of prophylactic anticoagulation in bullous pemphigoid and pemphigus

“…At the same time, pemphigus has about 2-fold risk of pulmonary thromboembolism. 10 The risk is proportional to the intensity of the underlying disease, with treatment with corticosteroids contributing to a reduction in risk. The dermatology guidelines (before as well as after COVID-19 pandemic) have not, however, recommended routine prophylactic anticoagulation in AIBDs.…”

“…Bullous pemphigoid is known to be a prothrombotic state with approximately 15‐fold increased risk of venous thromboembolism in the acute phase, 9 which decreases to 1.5‐fold during the remission phase. At the same time, pemphigus has about 2‐fold risk of pulmonary thromboembolism 10 . The risk is proportional to the intensity of the underlying disease, with treatment with corticosteroids contributing to a reduction in risk.…”