• Anqi Zhang

Polymyalgia Rheumatica Study in UMCG

To destroy one of the risk factors for your happy old life



Have you ever heard of polymyalgia rheumatica? I guess not. In this article, I will explain this type of disease and how badly it affects life. And how fortunately, there is a silver lining behind this.


Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder characterized by severe pain and stiffness affecting the neck, shoulders, and hips[i]. The lifetime risk of developing PMR has been estimated at 2.43% for women and 1.66% for men[ii], ranking it as the most common rheumatic inflammatory disease in the elderly worldwide. The highest incidence of PMR is seen in people of European descent, although PMR can occur worldwide in any ethnic group[iii]. That means, one in a hundred people might encounter it. But do not be too nervous about it yet. PMR normally occurs in people older than 50 years, and the mean age of onset is 73 years. However, due to aging of the population, a marked increase in the incidence of PMR is expected.


Like many other common elderly diseases, PMR is closely associated with aging and thus a risk factor for a happy life at a later stage. Everyone has thought about the unstoppable aging, and their life when they get older. Well, at least I have. I image myself as an elderly person in a peaceful garden where golden sunlight paves the lawn:


I fell asleep for the third time in the same day after reading a Greek mythology book for two seconds. Hours later, I finally decided to get up and enjoy a delicious brunch, just like the good old times.


Oh, wait! What if I have polymyalgia rheumatica?


I feel my shoulder are so stiff and painful that I cannot make a fancy brunch anymore. The book just lies there, laughing at me suffering from the pain. I feel a bit sad, for even painkillers will not save me this time. The pain has ruined the morning beauty completely. I ask to the sky: “Medicine, the mighty medicine, where are you when I am needing you?”


So far, the first choice for the management of this type of disease is glucocorticoid treatment. Glucocorticoids (GCs) are steroid hormones that are widely used for the treatment of inflammation, autoimmune diseases, and cancer. However, the long-term use of glucocorticoids has severe side effects, such as osteoporosis, fractures, diabetes mellitus, hypertension, and mental problems[iv]. Sounds like just many other sufferings for the elderly. Targeted therapies in urgent need are currently lacking for polymyalgia rheumatica. Unfortunately, very little is known about the immunopathogenesis of it, which hinders the selection and introduction of a novel therapy for polymyalgia rheumatica patients.


Now enough with the sad stories, the article is bringing good news. Currently, an excellent team at the University Medical Centre of Groningen is working on the immunopathology of polymyalgia rheumatica to find a novel therapy with less use of steroid hormones or even no steroid hormones at all for these patients. And how is that possible? Well, polymyalgia rheumatica is an autoimmune disease. That means, our immune system, which is supposed to fight against external stress (such as viruses and bacteria), has overkilled and turned to damage our own cells. To deal with this problem, we have to study which part went wrong in this immune war and the reason behind the disease, which scientists named “pathogenesis”. Once we get clear with the mechanism behind the disease, we can target the culprit and win this war.


Talking about the culprit, so far, we have suspected macrophages the most. Macrophages are a type of immune cells that kill microorganisms, remove dead cells, and stimulate the action of other immune system cells. Some researchers already found that abundant macrophages had infiltrated the synovium in the shoulder of patients. Is not it just suspicious? Mr. Macrophage definitely does not have an alibi for this crime, and accumulating evidence has proved that it is not a coincidence. The team research on polymyalgia rheumatica at UMCG is currently investigating whether the macrophage is the key player in the pathogenesis and if so, by what pathway it leads to the catastrophe in the inflamed tissues. With fingers crossed, we are hoping to illustrate soon the mystery of how macrophage damages the tissue. Based on those understandings of the mechanism, biomedical scientists can later develop a novel treatment that targets specifically the pivotal pathway by which the culprit causes the inflammation.


Will the small but versatile macrophage really be the key to solving the mystery of polymyalgia rheumatica and opening an entirely new world for its treatment development? Will the elderly at the risk of getting polymyalgia rheumatica finally be free from the extreme pain in the shoulder and hips and have the liberty to read any book and enjoy any brunch in the morning just as in the old days? With great curiosity and in pursuit of benefiting the big masses, I joined this team as a fresh PhD student to solve this puzzle with the other researchers in December 2021. Feeling very excited to throw myself into this research, I even wrote a poem for my research goal:


Sometimes I wonder,

where to stay when we get older.

In sunny California?

Or wonderful Cuba.

But no matter where we are,

We are not with PMR.

Shouldn’t it be beautiful?


 

[i] Gonza-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ, et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum 2009; 61: 1454–61. [ii] Crowson, C. S., Matteson, E. L., Myasoedova, E., Michet, C. J., Ernste, F. C., Warrington, K. J., ... & Gabriel, S. E. (2011). The lifetime risk of adult‐onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis & Rheumatism, 63(3), 633-639. [iii] Michet, C. J., & Matteson, E. L. (2008). Polymyalgia rheumatica. BMJ (Clinical research ed.), 336(7647), 765–769. https://doi.org/10.1136/bmj.39514.653588.80 [iv] Buttgereit, F., Dejaco, C., Matteson, E. L., & Dasgupta, B. (2016). Polymyalgia rheumatica and giant cell arteritis: a systematic review. Jama, 315(22), 2442-2458.

 

Anqi Zhang is a first-year PhD student in the department of Clinical Immunology and Rheumatology. She obtained her master’s degree in Biomedical Sciences at the University of Groningen, where she found herself interested in scientific research on immunology and passionate in healthcare. Her PhD project is to explore the pathogenesis behind polymyalgia rheumatica and the opportunities of developing a novel therapy in order to manage this disease in a safer and efficient way.