The Role of Ultrasound in Psoriatic Arthritis Diagnosis

Psoriatic arthritis (PsA) is a form of arthritis that affects some people who have psoriasis. PsA accounts for approximately 20% of referrals to early arthritis clinics and presents a significant diagnostic and management challenge. To learn more about how PsA is diagnosed and the role of ultrasound in diagnosis, Medscape spoke with Philip J. Mease, MD, director at Seattle Rheumatology Associates and director of rheumatology research at Providence Swedish Medical Center, Seattle, Washington. A Q&A with Dr Mease follows.
Philip J. Mease, MD: It was 30% in a study in which I was lead author. The study involved 40 different dermatology clinics with dermatologists specializing in psoriasis in North America and Europe. The dermatologists were requested to take all serial psoriasis patients coming into the clinic and then refer them on to a rheumatologist. The rheumatologists did a history, physical, laboratory tests, and imaging in some centers. In our center in Seattle, we were able to do ultrasound and MRI scanning. The basic question was how many of these individuals had psoriatic arthritis. The answer was out of roughly a thousand patients studied, 30% had evidence of psoriatic arthritis. But what was very important was that 41% of that group were not aware they had psoriatic arthritis before being involved in the study. So, that leaves about 12% of patients who are out there with psoriasis who have psoriatic arthritis and don’t know they have it.
In the study, there was a question of whether the imaging made a real difference in the diagnosis of psoriatic arthritis, and we found it didn’t make a huge difference. It didn’t uncover a whole bunch of patients that were not clinically suspected. But, as we talk, you will see that I am a great proponent of ultrasound and the importance of ultrasound to uncover cases that are not obvious and that are not clear. But, in this study, the totality of the history and physical was almost as good as adding the laboratory and imaging, in terms of diagnosing psoriatic arthritis.
There are some other studies out there regarding prevalence of psoriatic arthritis in psoriasis patients, and they come up with similar numbers; the low end is 20% and the high end is 40%.
Mease: Because we can better prevent damage. There was a famous study done in Dublin where they had an early arthritis clinic and they were able to see patients relatively early in their disease. In the study, they looked at the totality of psoriatic arthritis patients and the observation was made that, if you diagnose psoriatic arthritis more than 6 months after onset of symptoms, there were multiple things that were worse in that patient group. Further down the road, these people had more structural damage, they had worse physical function, they had more of a likelihood of developing a condition called arthritis mutilans, which is a highly destructive condition of joints. So, the outcomes were worse if there was a delay in diagnosis.
We did a study in the CorEvitas registry in the US, where we asked a similar question, but we used a 1-year timepoint. What we were able to show is that patients who had a delayed diagnosis were less able to achieve minimal disease activity (MDA). MDA is a composite measure where there are seven different items in it. We usually start a patient on a therapy, and we use MDA as a target of treatment. Some of the items include getting to a state of having less than or equal to one tender joint, less than or equal to one swollen joint, a skin score of less than 3% body surface area covered with psoriasis, and a state of pain being less than 20 out of a score of 100. There are seven items, and if you achieve at least five of them, then you are in a state of minimal disease activity, which corresponds to not feeling the need to change therapies. It is correlated with less structural damage. It is correlated with better work productivity and better function. We found that if a patient had a delay in diagnosis, they were less able to get in a state of MDA with the treatments. The disease is more treatable if you catch it early.
Mease: There is an overactivity of inflammatory lymphocytes and other cells of the immune system, for example neutrophils. These immune cells are misreading the barcode on the individual’s cells in their joints in the tissues where tendons or ligaments insert into bone in the spine, in the skin, in the nails. There is an inflammatory activation of immune cells inappropriately. The inflammatory cells think they are responding to something foreign or bad like an invading virus or a cancer cell, but instead it is normal healthy tissue. There is an accumulation of these activated lymphocytes and inflammatory molecules that leads to pain, swelling, redness, and loss of physical function in those particular musculoskeletal areas.
Mease: The usual context is that it is musculoskeletal pain arising in a person who already has a diagnosis of psoriasis. On average, psoriasis begins 10 years before the psoriatic arthritis begins, but in some patients, it will be simultaneous. In a handful of patients, the psoriatic arthritis manifests before psoriasis appears. 
When the dermatologist or primary care doctor visits with a patient who has brought their musculoskeletal pain to the attention of the doctor, that is when psoriatic arthritis can be first diagnosed, and then it can be confirmed when the dermatologist or primary care physician refers the patient to a rheumatologist. The rheumatologist will take a history, do a physical exam, and do laboratory tests. Imaging is done in some centers. Then we put all that together. Sometimes a patient has features of inflammatory arthritis, and they might say, ‘I get up in the morning and I feel like the tin man in the Wizard of Oz, and I feel really stiff for an hour or two and then I loosen up.’ Perhaps a patient may present with a visible swelling at the joint. Sometimes a patient will have an elevation of inflammatory markers in their blood, but this is only the case in about 40% of patients. We have plenty people who have active inflammation, but normal inflammation markers in the blood. X-rays at an early stage of psoriatic arthritis are often normal, so this is where ultrasound — in the case of peripheral joints like fingers, toes, knees, etc. — is really important. And the MRI scans are important for diagnosing the spine aspect of it. Ultrasound is a very sensitive way to detect inflammation in joints.
Mease: Practically speaking that is correct, but there are more than that.
Mease: The most common is plain x-ray. As the disease persists and advances, one can detect structural damage changes to the peripheral joints or the spine, but this is often a later finding. This is why it is so important to use these more sensitive advanced imaging modalities. X-ray is the most common and then ultrasound and then MRI. Ultrasound requires that a physician be trained to do an ultrasound. So, that is either a rheumatologist who has learned to operate ultrasound and interpret it, or it is an imaging specialist like a radiologist. MRI scans are obviously done in the imaging department of a medical center. In the United States, MRI scans are fairly ubiquitously used, but, if you go into the developing world, there are fewer MRI machines, and that is where x-rays are more commonly used. Then there is ultrasound, which is an intermediate. With some training, you can learn how to use ultrasound, and you can use it in the clinic. You can wheel it right in and use it at the bedside. You can use ultrasound as an extension of your examining fingers.
Mease: While arthritis, meaning inflammation of the lining tissue of joints, is a key important point of psoriatic arthritis, another really important clinical aspect is something we call enthesitis. Ultrasound is useful in diagnosing enthesitis. The [enthesis] anatomically is anywhere where a tendon or ligament inserts into the bone anywhere in the body. Classic places where enthesitis occurs in psoriatic arthritis are places like the Achilles tendon insertion into the heel, the plantar fasci insertion into the heel, the tendons and ligaments around the knee and the kneecap, and even the tendons and ligaments that constitute the rib cage. Enthesitis does not occur in rheumatoid arthritis or osteoarthritis. So, this is a key tissue area that gets inflamed in psoriatic arthritis and sometimes even proceeds the arthritis. 
Sometimes I will see a patient in the clinic who will come in with a swollen finger joint that their dermatologist has easily identified as psoriatic arthritis but then when I start quizzing them, they will say, ‘Oh yeah, I had a really pesky Achilles tendon problem last year that lasted several months that eventually went away.’ Perhaps they will say, ‘I had a persistent chest pain, and I ended up getting worked up for a coronary artery problem or a lung problem and nothing was found … So, you are telling me this could have been psoriatic arthritis manifestation a year ago?’ Enthesitis is an important part of the psoriatic arthritis. I can sometimes treat people really effectively for their arthritis and skin disease with drugs, but they will still have a really painful Achilles tendon and need to wear an orthopedic boot. So, we have to ask about each of these clinical domains, skin, joints, enthesitis, when we are quizzing patients about how they are doing and piecing together the puzzle. There are characteristic findings on ultrasound for the arthritis aspect and characteristic findings for the enthesitis aspect. 
On ultrasound for the arthritis aspect, we may see a thickening of the lining tissue of the joints, which represents an increase in the lymphocyte cell number. Another example is increased blood flow. On the ultrasound machine, the doppler signal allows us to look for increased vascularization of the lining tissue of the joint and that is consistent with inflammation being present. Inflammation is not only an increased number of cells in the lining tissue, but an increased number of these tiny feeder blood vessels, we call it neovascularization, and that is really easily visible on ultrasound. Neither of these findings are something that you would see on x-ray, and only the thickening part could you see on an MRI scan. This is the way we can positively diagnose the condition.
But there is another way ultrasound can be helpful. It can help detect people with concomitant fibromyalgia. Somewhere between 15% and 20% of patients with psoriatic arthritis may have concomitant fibromyalgia. Fibromyalgia is a fascinating condition in which the tissue is normal, but in the brain is experiencing pain and fatigue. Ultrasound can detect these patients. 
So, ultrasound is helpful to rule in but also rule out active inflammation as a cause of pain.
Mease: Because ultrasound can be used all over the world, it helps overcome some of the equity issues between resource rich and resource challenged countries and societies. There are improvements in machines. They are now hand-held ultrasound machines that you wear on your belt, and you can walk from room to room with them. What I love about ultrasound is it can overcome some of the equity barriers.
Philip J. Mease, MD, has disclosed no relevant financial relationships.