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Patients with antisynthetase syndrome, ACPA may have overlapping rheumatoid arthritis
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Patients with antisynthetase syndrome who test positive for anti-citrullinated peptide / protein antibodies may also have rheumatoid arthritis and may not respond well to conventional treatments, according to research published in Medicine.
Researchers identified seven patients with anti-citrullinated peptide / protein antibodies (ACPA) among 284 patients with antisynthetase syndrome from nine centers in France, along with 10 patients who met select criteria for antisynthetase syndrome and ACPA positivity identified through direct contact with more than 1,400 rheumatologists in a French registry. Demographics, clinical history, comorbidities, imaging data and other patient details were collected. After onset of symptoms, mean patient follow-up was 96.2 months in ACPA-negative patients and 93.2 months in ACPA-positive patients.
In most patients with ACPA and antisynthetase syndrome (88%), polyarthralgia and / or polyarthritis were the initial symptoms observed, followed by myositis in 41% and interstitial lung disease (ILD) in 35%. Symptoms of ACPA were present for 3 months after the antibodies were detected, whereas antisynthetase antibodies were detected 2 months after the onset of antisynthetase syndrome.
An initial diagnosis of RA was reported in six patients, followed by antisynthetase syndrome in five patients, dermatomyositis in three patients, polymyositis in one patient and RA- antisynthetase syndrome overlapping syndrome in two patients. All 17 patients with ACPA had some form of arthritis, compared with 41% of patients with ACPA-negative antisynthetase syndrome, with an odds ratio of 49.5 for arthritis.
Compared with the ACPA-negative group, swollen joints counts were significantly higher in the ACPA-positive group. Arthritis was always symmetrical and primarily found in the metacarpophalangeal joints in 14 patients with ACPA, in the wrists of 10 patients and in the hands of eight patients, according to the researchers. Knee, ankle and proximal interphalangeal joint involvement occurred less commonly.
ILD was present in 82% of patients in both groups, but patients with ACPA had higher forced volume capacity and higher diffuse lung carbon dioxide than the ACPA-negative group. Additionally, none of the patients had pulmonary rheumatoid nodules. About 80% of patients in both groups were affected by myositis, and 47% of ACPA-positive patients had Raynaud’s phenomenon.
All patients with ACPA received the disease-modifying anti-rheumatic drug (DMARD) prednisone, and 13 received methotrexate, five received hydroxychloroquine, five received leflunomide, four received cyclophosphamide, two received sulfasalazine or mycophenolate mofetil, and one received immunoglobulin. Biologic treatments — including Rituxan (rituximab, Genentech) in eight patients; Remicade (infliximab, Janssen) in four patients; and Enbrel (etanercept, Amgen), Humira (adalimumab, AbbVie), Actemra (tocilizumab, Genentech) and Orencia (abatacept, Bristol-Meyers Squibb) in one patient each — were used in 59% of the ACPA-positive patients
Compared with DMARDs, treatment with biologic agents, particularly anti-tumor necrosis factor and anti-CD20 agents, were more effective at improving refractory arthritis, according to the researchers. – by Shirley Pulawski
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Leonard H. Calabrese, DO
The association of anticitrullinated peptide/protein antibodies (ACPA) and rheumatoid arthritis (RA) is strong with specificity data in the region of 95% to 97%. In terms of predictive tests, this is robust data that affords positive predictive value. It also reveals that a few percent of ACPA-positive patients do have RA – at least at the time of testing. This should not be surprising as there are no perfect tests in medicine.
The most common scenario for ACPA positivity in the absence of RA is a patient who is tested for non-specific musculoskeletal complaints but fails to fulfill ACR/EULAR criteria. We now know that ACPA can antedate clinical RA for many years, thus, this is not surprising again. We also know some first-degree relatives of ACPA-positive RA patients have positive tests and many patients will never develop RA.
The study by the French network led by Alain Meyer, MD has given us a detailed account of ACPA positivity in the setting of antisynthetase syndrome (ASS). Given the limitations of this retrospective study, I found it of interest that several patients were diagnosed initially with RA and then subsequently diagnosed with ASS when they developed the classical findings of dermopathy, myositis, etc. These patients had erosive disease, but it mostly looked like ACPA-negative ASS. As previously reported, the patients did not do well with anti-TNFs with several flaring upon therapy. On the other hand, rituximab was successfully used by the researchers’’ description.
What is the take-home message? First, I will make an effort to screen for ACPA in more overlap conditions with prominent joint involvement. These settings clearly include ASS, systemic lupus erythematosus and primary Sjögren’s syndrome. Second, I am intrigued, even with all the inherent limitations of retrospective reporting, that rituximab may have good clinical activity on both the joints as well as the systemic manifestations.
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