Ankylosing spondylitis and RA: Possible comorbidities?

A February 2023 case report published in Cureus examined the development of ankylosing spondylitis (AS) in a patient with a long history of rheumatoid arthritis (RA).^[] This underscores the fact that, while uncommon, the two diseases can exist simultaneously.^[]

This isn’t the first time researchers have found this to be true, though. Reports dating back to 1976 say the two diseases can co-occur, as noted by a report in StatPearls.^[]

A history of misdiagnosis

The 2023 case report sheds light on the issue that physicians still find it challenging to differentiate between the two diseases. This isn’t surprising, as both AS and RA are two of the most common chronic, inflammatory, rheumatic diseases, according to the StatPearls report. More so, AS has been historically misdiagnosed as RA. 

Physicians should know that the two conditions’ etiologies are different, as are the symptoms they cause.

A brief look at AS and RA

According to Norman B. Gaylis, MD, FACP, MACR, a rheumatologist at the Arthritis and Rheumatic Disease Specialties Clinic in Aventura, Florida, the diseases share some similarities at first glance. For example, patients with both AS and RA report stiffness and pain in the joints, Dr. Gaylis told MDLinx. 

The diseases differ when you look more closely, however.

The pain is also generally asymmetrical. Morning stiffness is a key symptom of AS, as it is in RA. 

“There are also genetic predispositions for AS which can be found in HLA-B27 antibody testing,” Dr. Gaylis adds. It is worth noting that testing negative for HLA-B27 doesn’t rule out AS, while testing positive doesn’t necessarily lead to AS, either.^[]

RA, however, typically affects the joints of the hands, wrists, and knees.^[] “RA presents with bilateral and symmetrical pain, creating a mirror image of pain in the body—seen in the same places on both sides of the body,” Dr. Gaylis says. Some people with RA may test positive for the HLA-DR4 gene.^[]

A closer look at the case report

The case report shared the account of a 52-year-old female with previously diagnosed RA and osteoarthritis. The study specified that she was treated with methotrexate and tacrolimus, both of which are immunosuppressive drugs used to treat RA.

“Initially, we considered that she might have had an exacerbation of osteoarthritis or rheumatoid arthritis because she visited the outpatient department frequently due to joint pain,” the report’s authors write. Diclofenac, a nonsteroidal anti-inflammatory drug, was then prescribed—but her pain persisted. 

After 2 weeks, the patient returned for imaging, when “pelvic radiography revealed bilateral sacroiliac joint deformation. Other pelvic MRI … showed a high-intensity lesion on the joints, indicating the presence of sacroiliac joint inflammation,” according to the report. The patient also experienced limited movement in her spinal joints. 

At this point, the patient was diagnosed with AS, and was treated with weekly injections of etanercept. 

How was AS eventually diagnosed in this case? 

The report’s authors theorize that the patient’s AS was caused by chronic inflammation (from her RA) triggering inflammation in the SI joints. More specifically, the authors postulate that cytokine interactions—including tumor necrosis factor (TNF) and interleukins (IL) 1 and 6—could have led to the patient’s diagnosis of AS. This is because AS can be triggered by immune cells and cytokines (including TNF, IL-1, and others). TNF is also at play in RA. 

“Although there are differences in aberrant immune cells,” the authors write, “increasing TNF can stimulate various immune cells systematically, resulting in both diseases.”

The authors also state, “This case suggests that patients with long-term rheumatoid arthritis can develop AS during follow-up and that the seropositivity of rheumatoid factors and anti-cyclic citrullinated peptide (anti-CCP) antibodies cannot rule out AS.”

But what does this mean, exactly? Blood tests to confirm the seropositivity of rheumatoid factor (RF) as well as anti-CCP antibodies are some of the diagnostic criteria for RA.^[] On the other hand, AS is considered a seronegative spondyloarthropathy.^[]

Dr. Gaylis also theorized that it’s possible, regarding this case report, that the patient’s positive RF could have led to a misdiagnosis—and that the patient had AS all along. This may be possible due to the fact that RF isn’t specific to RA, while research has shown anti-CCP may be more accurate.^[] 

How to distinguish RA from AS

According to Stella Bard, MD, a rheumatologist at NY Arthritis, physicians need to consider AS as a differential diagnosis for RA in specific cases. 

Essentially, physicians need to do some diagnostic digging. They will want to run bloodwork and send patients for imaging.

“There might be a knee-jerk reaction to labeling rheumatoid arthritis with any presentation of inflamed joints, [but] as long as there is spine stiffness involved—other than the neck—such as the mid back, low back, or pelvis, AS should be at the top of your list of differential diagnoses,” Dr. Bard says.

Dr. Bard adds another differentiating variable between RA and AS: “RA is erosive to bone while AS grows extra bone as spurs.”

The importance of correct and early diagnosis cannot be understated, Dr. Bard stresses. “It's possible that a patient … presents with inflamed joints and inflamed neck or mid back—as women with AS often present with. [However], they are mistaken for having RA due to RF+ and treated for RA—only to have the AS develop and progress,” she says. It’s important to know that some treatments for RA are not effective in AS, according to Dr. Bard. This is also noted by the authors of the Cureus case report. 

“As a rheumatologist,” he says, “I look for all manifestations of these diseases. I review the symptoms, how they present, and look for all options for my patients. I suggest that others do the same.”