Most common causes of death in patients with SLE

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What are the four most common causes of death in patients with SLE? The most common morbidities?

The overall 5-year survival rate has improved in the last 20 years to 95% and 10-year survival to 90% likely due to earlier diagnosis and aggressive management of comorbidities. However, mortality is increased three times compared with a healthy, age-matched population. Some have emphasized the bimodal pattern of mortality in SLE. Death early in the disease is generally a reflection of active lupus or its treatment (infection), whereas death late in disease is due to active disease, atherosclerosis, and malignancy. The most common causes of death are:

• Infection: accounts for 20% to 25% of all deaths and increased five times compared with the general population. All infections (bacterial, fungal, tuberculous, nontuberculous mycobacterial, viral) are increased mostly related to the complications of immunosuppressive therapy, especially due to prolonged use of high-dose corticosteroids. For each increase of prednisone by 10 mg/day, the risk of serious infection increases 11-fold.

• Active SLE: accounts for 35% of deaths especially during first 5 years of disease. Lupus nephritis with renal failure, CNS lupus, vasculitis, and pneumonitis are most lethal.

• Cardiovascular disease: accounts for 30% to 40% of deaths particularly after 10 years of disease. The risk of coronary artery disease (2.5 times), stroke (2.5 times), and peripheral artery disease (9 times) is increased in SLE patients compared with age-matched general population. Factors playing a role in the development of premature atherosclerosis in SLE patients include corticosteroid therapy, hyperlipidemia from renal disease, proinflammatory high-density lipoprotein, HTN, smoking, coagulation abnormalities, elevation of inflammatory mediators such as type I IFNs, obesity, and vasculopathy from immune injury.

• Malignancy: accounts for 5%–10% of deaths. Overall, the risk of malignancy does not appear to be greatly increased (standardized incidence ratio [SIR]1.14 [CI 1.05–1.23]).

• HPV-associated cervical cancer risk is increased (SIR 5) compared with the general population and may be exacerbated by exposure to immunosuppressives and ineffective clearance of the virus. Patients aged <26 years should be offered the HPV vaccine and should have annual Pap test including testing for HPV DNA if at risk.

• Risk of hematologic malignancies (SIR 2.75) and non-Hodgkin’s lymphoma (SIR 3.64) is increased and may be related to the use of immunosuppressive medications.

• Lung cancer risk is also mildly increased (SIR 1.4) in smokers.

• Squamous cell skin cancers can arise in discoid lesions.

The most common morbidities (SLE damage index) seen in SLE patients are renal failure, AVN, neuropsychiatric deficits, cardiovascular disease, disfiguring skin lesions, and osteoporosis.

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