Comorbidities in rheumatology – a two-way street

Vijaya Prasanna Parimi MD, DM
Senior Superspecialist, Department of Clinical Immunology and Rheumatology, ESIC Medical College and Superspeciality Hospital, Hyderabad, Telangana, Hyderabad

Autoimmune rheumatic diseases (AIRDs) and comorbidities have a complex bidirectional relationship due to shared risk factors and systemic inflammation. Comorbidities may accentuate AIRDs, and AIRDs can make it difficult to treat associated comorbidities, which has a substantial impact on these patients’ outcomes and presents a challenge to medical professionals in managing them.

Atherosclerosis: Inside the blockade

The hallmark of rheumatic diseases is chronic inflammation. Inflammatory arthritis (rheumatoid arthritis, spondyloarthritis) and connective tissue diseases are both characterized by the perpetuation of inflammation through antibodies, immune complex deposition, and generation of inflammatory cytokines. It directly results in endothelial inflammation and dysfunction, with an imbalance between nitric oxide synthesis and reactive oxygen species production and an influx of inflammatory cells. These actions set off a chain reaction that prolongs inflammation promotes plaque formation in arteries, and raises the risk of hypertension and cardiovascular disease risk events in those with AIRDs. The pain and fatigue associated with AIRDs promote inactivity and obesity. This results in an increased risk for hypertension, dyslipidemia, diabetes mellitus, and cardiovascular events.

Certain drug therapies also pose an increased risk for the development of these comorbidities. The obvious are glucocorticoids for diabetes mellitus, NSAIDs for renal injury and hypertension, and leflunomide for hypertension to name a few. Hypertension can increase the rate of progression to ESRD in SLE and vasculitis due to glomerular hyperfiltration and renal arteriosclerosis. Diabetes increases the risk of infections and in turn disease flares. Central obesity is a pro-inflammatory state in itself and through adiponectin drives various inflammatory diseases like Psoriasis, Psoriatic arthritis and gout.

Invisible battles: Mental health in chronic diseases

Beyond its impact on cardiovascular health, AIRDs have a bearing on other comorbidities as well. Depression, anxiety, and insomnia are common in patients with AIRDs due to the direct effects of antibodies or indirectly through chronic pain and stress. These conditions can in turn intensify pain and reduce treatment adherence which further interferes with the effective management of these patients.

Two giants: Cancer risk in rheumatic diseases

There is also an increased risk of developing malignancies in AIRDs due to chronic inflammation, infections, and immunosuppressive therapy (IST). Chronic inflammation disrupts the body’s ability to regulate cell growth and division, increasing the risk of abnormal growth and cancer development. Immune dysregulation and oxidative stress disrupt the balance between pro-inflammatory and anti-inflammatory responses, allowing carcinogenic viruses, such as Human papillomavirus and Epstein-Barr virus to reactivate and establish infections and the development of cancer. IST weakens the immune system and impairs its ability to combat cancerous cells resulting in an increased risk of cancers in individuals with AIRDs.

Various other comorbidities, like osteoporosis, fibromyalgia, and others, may have a unique effect on a patient’s disease course and limit the available treatment options for both conditions. Early diagnosis, proper treatment, and monitoring can reduce their negative impact on AIRDs, and improve prognosis.

In conclusion, healthcare providers must recognize the “two-way street relationship” between comorbidities and AIRDs. Implementation of holistic healthcare strategies to improve outcomes and quality of life with an emphasis on prevention, screening, and management is crucial for effective patient care.

Suggested reading:

  1. Nikiphorou E, Nash P. Comorbidities in RA: bringing them to the limelight. Rheumatology. 2023;62(SI3):SI235–6.
  2. Cappelli LC, Shah AA. The relationships between cancer and autoimmune rheumatic diseases. Best Practice & Research Clinical Rheumatology. 2020;34(1):101472.
  3. Sloan M, Wincup C, Harwood R, Pollak TA, Efhalia Massou, Bosley M, et al. Prevalence and identification of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases: an international mixed methods study. Rheumatology. 2024;63(5):1259-1272.