Philip Rask Lage-Hansen

Can unexplained pain in rheumatoid arthritis be explained?

Chronic widespread pain poses a huge challenge in the management of the patient with rheumatoid arthritis (RA), affecting approximately one third of this patient population. However, pain is not always caused by disease activity (inflammation), but can be associated to central pain mechanisms as seen in fibromyalgia (FM). FM is characterized by widespread pain and tenderness; often accompanied by disturbed sleep, fatigue, cognitive impairment, emotional distress and multiple symptoms from various organ systems. The prevalence of FM varies between 1-3 percent in the general population. However, among patients with RA the prevalence is reported to be 12-17%. In generally the pain, felt by the fibromyalgia patients is considered to be due to lower pain thresholds because of abnormal central pain processing. Pain reported by RA patients with concomitant FM could be explained by this phenomenon.

Little is known about RA patients fulfilling criteria for FM. Several reports exist, however sample sizes in these studies are relatively small, endpoints are few and study designs’ cross sectional. To the authors’ knowledge, no previous reports have investigated whether concomitant FM is present at the time of diagnosis of RA or develops as the disease progresses. In our first study, patients diagnosed with RA from 2010 and later will undergo investigations for coexisting FM. All patients were screened for FM when the RA diagnose was given. This will clarify if FM develops over years or is preexisting of any RA diagnosis. The question is important because FM cannot be treated efficient. If FM develops over years, it is important to identify predictors for this condition because there could be potentially goals for early interventions.

Different measures have been made when RA was diagnosed. Each measurement will now be investigated as potentially predictors for the development of FM. Furthermore, sophisticated measurements of the patients will characterize the pain felt and help establishing knowledge regarding the pain. Is it due to low pain threshold and is it likely that abnormal central pain processing is responsible.

In our second study, we will examine the role of concomitant FM in RA patients regarding the response to the initiation of biological treatment. An earlier study found that a significant number of patients treated with the expensive biologics had concomitant FM. Furthermore, they all reported high grade of pain but no objective measurements suggested that pain was caused by inflammation. However, the study was cross sectional. In our study, patients will be examined longitudinal. Does concomitant FM predict worse or better outcomes for RA when treated with biologics? A newer study has found ultrasound to be unnecessary when assessing RA patients. We aim for investigating the use of ultrasound in predicting treatment response. Patients who are to be treated with biologics will undergo examination for FM and joints will be assessed by ultrasound. The prognostic probabilities of treatment response of ultrasound and coexistence of FM will be investigated. This will answer two important questions: Should Ultrasound be used in the daily clinic or not, and do patients with FM and suspected inflammation on ultrasound benefit from treatment?

Thirdly, we aim for investigating if FM pain in RA patients can be explained by changes in the architecture of the tissue seen in the microscope. Muscles studies of FM patients have not found any histopathological explanation of the pain felt, however an old study of muscle changes in RA patients found changes that could explain muscle pain. Small fiber neuropathy (SFN) is a condition associated with autoimmune diseases, and evidence suggests that SFN is likely to contribute to the pain in FM. To our knowledge, no muscle-biopsy study or skin-biopsy study has been performed on RA patients with FM. The existing knowledge regarding this population of patients is therefore absent. Patients from our first study will undergo muscle and skin biopsies if diagnosed with FM. Matched controls without FM will be examined as well for comparisons. This has never been done before, and if there is any positive results, this will be a target for future treatment.

I see RA patients with and without FM every day in the clinic and is aware of the pitfalls and complications in these patients. I therefore consider myself the best person to investigate this matter.