What is the cause of systemic inflammation?

From the Guidelines

Systemic inflammation is a serious condition that requires immediate attention, and the most effective way to manage it is by addressing the underlying cause and using anti-inflammatory medications, such as NSAIDs or corticosteroids, as needed, while also incorporating lifestyle modifications to reduce inflammation and prevent long-term complications 1.

Causes and Symptoms of Systemic Inflammation

Systemic inflammation is a widespread inflammatory response that affects the entire body, rather than being confined to a specific area. It occurs when the immune system releases inflammatory mediators like cytokines and chemokines into the bloodstream, causing inflammation throughout multiple organ systems. This condition can result from various triggers including infections (bacterial, viral, fungal), autoimmune disorders, chronic diseases, severe injuries, or prolonged stress. Common symptoms include fever, fatigue, joint and muscle pain, skin rashes, and general malaise.

Diagnosis and Treatment

Blood tests typically show elevated inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and certain pro-inflammatory cytokines. Treatment focuses on addressing the underlying cause while managing symptoms. Anti-inflammatory medications like NSAIDs (ibuprofen 400-800mg every 6-8 hours or naproxen 250-500mg twice daily) may help reduce inflammation and relieve symptoms. In more severe cases, corticosteroids such as prednisone (typically 5-60mg daily depending on severity) might be prescribed.

Lifestyle Modifications

Chronic systemic inflammation is particularly concerning as it's associated with increased risk of serious conditions including cardiovascular disease, diabetes, cancer, and neurodegenerative disorders. Lifestyle modifications including anti-inflammatory diets rich in fruits, vegetables, and omega-3 fatty acids, regular exercise, stress management, and adequate sleep can help reduce systemic inflammation naturally. According to the most recent guidelines, incorporating these lifestyle modifications can help mitigate the risks associated with systemic inflammation 1.

Key Considerations

It's essential to note that systemic inflammation can have a significant impact on various aspects of health, including cardiovascular risk, as highlighted in recent guidelines 1. Additionally, the management of systemic inflammation should be tailored to the individual's specific needs and underlying conditions, taking into account the potential benefits and risks of different treatment approaches, as discussed in recent studies 1.

From the FDA Drug Label

The data reflect the percentage of patients whose test results were considered positive for antibodies to etanercept in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Autoantibodies Patients with RA had serum samples tested for autoantibodies at multiple time points In RA Studies I and II, the percentage of patients evaluated for antinuclear antibodies (ANA) who developed new positive ANA (titer ≥ 1:40) was higher in patients treated with Enbrel (11%) than in placebo-treated patients (5%) Adverse reactions have been reported during post approval use of Enbrel in adults and pediatric patients. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Enbrel exposure Immune disorders:macrophage activation syndrome, systemic vasculitis, sarcoidosis Musculoskeletal and connective tissue disorders:lupus-like syndrome Skin and subcutaneous tissue disorders:cutaneous lupus erythematosus, cutaneous vasculitis (including leukocytoclastic vasculitis), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subcutaneous nodule, new or worsening psoriasis (all sub-types including pustular and palmoplantar)

Systemic Inflammation may be associated with the use of etanercept, as evidenced by the development of:

• Autoantibodies in patients with RA, including ANA and anti-double-stranded DNA antibodies
• Immune disorders, such as macrophage activation syndrome, systemic vasculitis, and sarcoidosis
• Musculoskeletal and connective tissue disorders, including lupus-like syndrome
• Skin and subcutaneous tissue disorders, such as cutaneous lupus erythematosus and cutaneous vasculitis 2

From the Research

Systemic Inflammation Overview

• Systemic inflammation is a coordinated set of physiologic actions that serve to fight infection, heal wounds, and promote recovery from external stressors 3
• It can have profound effects on morbidity and manifest an increased risk of mortality, especially in cases of chronic low-grade to acute severe responses 3

Causes and Effects of Systemic Inflammation

• Protein calorie malnutrition can result in immunodeficiency, leaving the individual at risk of infection 3
• Low-grade chronic inflammation, as seen in obesity, diabetes, and the metabolic syndrome, can lead to serious health risks 3
• Systemic inflammation is a common denominator to a variety of cardiovascular and non-cardiovascular diseases, including hypertension, metabolic diseases, and rheumatic disorders 4

Treatment Options for Systemic Inflammation

• Therapies to down-regulate the systemic inflammatory response by targeting the source of inflammation may dramatically improve patient outcome in chronic inflammatory states and some acute inflammatory conditions 3
• Non-pharmacological strategies, such as lifestyle changes and dietary measures, can help modulate inflammation and restore balanced crosstalk between the human genome and the microbiome 4
• Colchicine in combination with non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to be effective in treating adult-onset Still's disease with serositis 5
• Corticosteroids and immunosuppressive agents, such as azathioprine, methotrexate, and mycophenolate mofetyl, can be used as second-line therapy for recurrent pericarditis 6

Specific Treatment Options for Recurrent Pericarditis

• Colchicine monotherapy has been compared to NSAID monotherapy or combination therapy for the prevention of recurrent pericarditis in patients with heart failure with reduced ejection fraction and/or coronary artery disease, with no significant difference in outcomes observed 7
• The use of colchicine, NSAIDs, and corticosteroids in the treatment of recurrent pericarditis is supported by various studies, highlighting the need for personalized treatment approaches 5, 6, 7