Increased Pulmonary Flares and IgG Antibody Levels Elevate Risk of Joint Disease in CF, Study Says

Joint disease, or arthropathy, is common among people with cystic fibrosis (CF), and more likely to occur in older and female patients, and those who have more pulmonary flares or elevated blood levels of IgG antibodies, a study suggests.

The higher number of flares and increased antibody concentration may reflect a state of chronic inflammation at the root of this clinically distinct type of joint disease, termed CF arthropathy (CFA).

Chronic lung infections with Aspergillus spp. fungi also correlate with a higher risk of joint problems, the study says.

The study “Clinical manifestations and risk factors of arthropathy in cystic fibrosis” was published in the journal Respiratory Medicine, and was conducted by a team at the Charité – Universitätsmedizin Berlin, in Germany.

Joint pain is a common and disabling symptom among people with CF, reducing their activities and quality of life. However, the clinical symptoms of CFA are variable, and its treatment can be challenging.

So far, a general definition and “systematic data on predisposing risk factors and treatment for CFA are not established,” researchers wrote.

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That is why, in this observational study, researchers wanted to assess the clinical manifestations, frequency, and risk factors of CFA, and to better understand whether CFA is a clinically different disease from reactive arthritis — a painful and inflammatory form of joint disease (arthritis) caused by bacterial infections.

The team analyzed past clinical data and medical records of 186 CF patients (mean age of 27 years) from a single center in Berlin, Germany. Patients were asked about their disease onset, duration, location, and treatment of joint problems.

Of note, CFA was defined in the study as having at least one symptom of joint pain, swelling, reddening, or limitation of movement.

From the 186 patients analyzed, 54 (29%) had experienced joint symptoms at their hands, elbows, shoulder, knees, or ankles. The joints of the hands (fingers and wrists) were the most affected, followed by those of the feet. The most frequent symptoms were joint pain (51%), followed by joint swelling (20%), loss of function (19%), and reddening (10%).

Results showed that a number of risk factors were associated with a higher probability of developing CFA, namely: older age, female gender, high blood concentrations of IgG antibodies, increased number of pulmonary exacerbations, and chronic lung infections with Aspergillus spp. fungi.

The analysis indicated a 2.7-fold higher risk for CFA in females compared to males; a 17% increase in the CFA risk for each pulmonary exacerbation, and a 7% risk increase per year of age. 

In addition, CFA risk increases 7% per each raise of 6.7 micromol per liter in the blood of IgG antibodies. Also, chronic lung infection with Aspergillus fumigatus made it four times more likely for a CF patient to develop CFA.

No specific profile of autoantibodies, which are typically associated with autoimmune forms of arthritis, was discovered in these CF patients.

Many of the CF patients with joint symptoms, however, were positive for antinuclear antibodies (ANA) (54%), some also were positive for anti-cyclic citrullinated peptide (ACPA) (33%), and less for rheumatoid factor (10%). Researchers interpreted these results as evidence of a minor role of autoimmunity in the development of CFA.

Although the underlying cause of CFA remains unclear, the study supports a link between CFA and lung inflammation. “Pulmonary exacerbations and elevated levels of total serum IgG may reflect chronic inflammation in patients with CF and may lead to a specific arthropathy associated with this condition,” the researchers wrote.

Based on the clinical manifestations observed, researchers believe that “CFA is a separate entity” from reactive arthritis. Yet, much remains to be understood about the immunological mechanisms driving CFA.

Overall, “joint symptoms in CF are a frequent and clinically relevant phenomenon with a distinct clinical pattern,” the researchers concluded.

According to the team, CFA is a relevant comorbidity among people with CF, and with the growing number of elderly patients, comorbidities like CFA will play a major role in the future.