Rheumatoid Arthritis and Asthma: Where They Overlap

Rheumatoid arthritis (RA) and asthma are both chronic inflammatory diseases that primarily affect different systems—joints in RA and airways in asthma. Despite their distinct manifestations, research suggests they share underlying immune mechanisms that may increase the likelihood of co-occurrence in some individuals.

Understanding how these conditions intersect can provide insights into potential risk factors, overlapping symptoms, and challenges in diagnosis and treatment.

Shared Immune Pathways

Both RA and asthma stem from dysregulated immune responses, with overlapping inflammatory mechanisms driving their progression. A key factor in both diseases is the role of T-helper (Th) cells—Th1 and Th17 in RA, and Th2 in asthma. While traditionally considered distinct, research suggests Th17 cells, associated with RA, may also contribute to severe asthma. Elevated interleukin-17 (IL-17) levels have been detected in asthma patients with neutrophilic inflammation, a pattern more commonly linked to autoimmune diseases like RA. This suggests a subset of asthma patients may experience immune dysregulation similar to RA, leading to overlapping inflammatory profiles.

Cytokine activity further highlights these shared mechanisms. Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine central to RA, also plays a role in airway inflammation and hyperresponsiveness in asthma. Some studies indicate TNF-α inhibitors, used in RA treatment, can improve asthma symptoms in patients with both conditions. Likewise, interleukin-6 (IL-6), elevated in RA, has been linked to airway remodeling and steroid resistance in asthma, underscoring its role in chronic inflammation across different organ systems.

Autoantibodies provide another point of convergence. While RA is classically associated with rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), these autoantibodies have also been detected in some individuals with severe asthma, particularly those with systemic inflammation. This suggests an autoimmune component in certain asthma cases. Additionally, shared genetic predispositions, such as variations in the HLA-DRB1 gene, indicate some individuals may be more prone to developing multiple inflammatory diseases rather than a single disorder.

Pulmonary Involvement In Rheumatoid Arthritis

Lung complications are a significant yet often underrecognized aspect of RA, affecting both respiratory function and overall prognosis. While joint inflammation is the hallmark of RA, pulmonary manifestations can develop in a substantial subset of patients, sometimes preceding joint symptoms. Interstitial lung disease (ILD) is one of the most serious respiratory complications, with prevalence estimates ranging from 10% to 30%, depending on diagnostic criteria. RA-associated ILD (RA-ILD) typically presents with a usual interstitial pneumonia (UIP) pattern, characterized by progressive fibrosis and restrictive lung dysfunction. High-resolution computed tomography (HRCT) is the gold standard for detecting early fibrotic changes, as pulmonary involvement is often asymptomatic until advanced stages.

Beyond ILD, airway abnormalities are another common pulmonary manifestation of RA. Bronchiolitis obliterans and follicular bronchiolitis contribute to airflow obstruction and respiratory symptoms. Bronchiolitis obliterans results from chronic inflammation and fibrosis of the small airways, leading to airflow limitation that can resemble chronic obstructive pulmonary disease (COPD). Follicular bronchiolitis, associated with lymphoid hyperplasia, may cause persistent cough and exertional dyspnea. Pulmonary function tests (PFTs) help detect these abnormalities, often revealing obstructive or mixed ventilatory defects even in asymptomatic patients.

Pleural disease is another well-documented pulmonary complication, manifesting as pleuritis, pleural effusions, or pleural thickening. While RA-related pleural effusions are typically small and asymptomatic, larger effusions can cause pleuritic chest pain and dyspnea. These effusions are often exudative with low glucose levels, elevated lactate dehydrogenase (LDH), and a predominance of mononuclear cells, distinguishing them from other causes like infection or malignancy. Thoracentesis can aid diagnosis, but recurrent or symptomatic effusions may require corticosteroids or pleurodesis in refractory cases.

Overlapping Clinical Features

RA and asthma, despite affecting different organ systems, share notable symptom overlap that can complicate diagnosis and management. Both conditions involve periods of exacerbation and remission, with symptom severity fluctuating over time. Environmental triggers such as air pollution, respiratory infections, or stress can exacerbate both diseases, making it difficult to determine whether respiratory symptoms stem from asthma alone or RA-associated lung involvement. Patients with both conditions may experience breathlessness, wheezing, or chest tightness, which can sometimes be misattributed to asthma when RA-related pulmonary complications are also contributing factors.

Systemic fatigue further connects these conditions. In RA, fatigue is linked to persistent inflammation and metabolic dysregulation, while in asthma, nocturnal airway obstruction and poor sleep quality contribute to daytime exhaustion. When both diseases coexist, the cumulative burden of inflammation and respiratory impairment can significantly reduce daily functioning.

Musculoskeletal discomfort is another overlapping feature. While joint pain and stiffness are hallmarks of RA, some asthma patients report musculoskeletal pain, particularly in the chest wall and upper back. Chronic coughing and labored breathing can strain intercostal muscles, leading to soreness that may be mistaken for RA-related musculoskeletal pain. Additionally, prolonged corticosteroid use, common in both conditions, increases the risk of osteoporosis and myopathy, further complicating symptom attribution.

Genetic And Environmental Links

Genetic predisposition and environmental factors contribute to the development of both RA and asthma. Studies have identified shared genetic markers that increase susceptibility to chronic inflammatory diseases. Variants in the HLA-DRB1 gene, a well-established risk factor for RA, have also been associated with asthma in certain populations. While the mechanisms remain under investigation, researchers suggest these alleles may influence immune regulation in a way that predisposes individuals to multiple inflammatory disorders.

Environmental exposures also play a role, particularly in genetically predisposed individuals. Cigarette smoke is a well-documented trigger for RA, increasing the risk of seropositive RA by up to 50%, particularly in individuals carrying HLA-DRB1 risk alleles. Tobacco smoke is also a well-known irritant in asthma, exacerbating airway inflammation and reducing treatment efficacy. Occupational exposures to silica, pesticides, and other airborne pollutants have been linked to higher incidences of both diseases, reinforcing the role of environmental triggers in disease development.

Distinct Diagnostic Perspectives

Distinguishing between RA and asthma in patients with overlapping symptoms requires a thorough diagnostic approach. Pulmonary function tests (PFTs) are central to this assessment. In asthma, spirometry typically reveals reversible airway obstruction, whereas RA-related lung disease, such as ILD or bronchiolitis obliterans, may present with restrictive or fixed obstructive patterns. Diffusing capacity for carbon monoxide (DLCO) measurements can further differentiate these conditions, as reduced DLCO is commonly observed in RA-ILD but not in uncomplicated asthma.

Imaging provides additional clarity when clinical presentations are ambiguous. High-resolution computed tomography (HRCT) is particularly useful in detecting RA-related lung involvement, often revealing reticular opacities, honeycombing, or ground-glass changes indicative of ILD. In contrast, asthma generally lacks persistent structural abnormalities on HRCT, though airway wall thickening and air trapping may be observed in severe cases. Bronchoscopy with bronchoalveolar lavage (BAL) can further delineate inflammatory profiles, with RA-ILD often exhibiting lymphocytic or neutrophilic inflammation, while asthma is typically associated with eosinophilic or mixed cellular profiles.

Given these complexities, a multidisciplinary approach involving rheumatologists, pulmonologists, and allergists is often necessary to establish an accurate diagnosis and optimize treatment strategies.