Worsening pain in someone with rheumatoid arthritis? Don't assume it's always active disease.
A 65-year-old female presents with a polyarthritis. She has multiple swollen joints in the upper and lower limbs, morning stiffness and pain.
Rheumatoid factor and cyclic citrullinated peptide (CCP) antibody tests are positive, and it is clear she has seropositive rheumatoid arthritis.
She has an initial response to methotrexate, leflunomide and low dose prednisone, but has persistent high disease activity and progresses to biologic therapy.
She starts subcutaneous adalimumab fortnightly injections and responds well to this. Her disease activity score reduces to low levels. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) readings normalise. Examination shows her synovitis has reduced. Prednisone and leflunomide are ceased and she continues combination methotrexate and adalimumab therapy.
A year into therapy she starts to have increasing pain. This coincides with a very stressful period in her life, with retirement and her mother passing away. Her blood tests continue to show normal CRP and ESR readings, and there is joint tenderness but no synovitis on examination.
The pain does not have a clear diurnal variation as might be expected with inflammatory arthritis. She reports her pain to be constant and worse as the day progresses and with activity. In addition, the pain is not specific to her joints and is more widespread.
A power Doppler ultrasound of her hands and feet is performed to assess if there is any underlying subclinical synovitis. This scan confirms the clinical impression that her rheumatoid arthritis is inactive. What could be going on?
My suspicion is that she has developed secondary fibromyalgia, triggered by the recent life stressors.
This is essentially a diagnosis of exclusion and will need investigations to ensure that no other disease process is causing her symptoms. Most patients with fibromyalgia will have a significant sleep disturbance. This includes both initiation of sleep, waking multiple times and waking unrefreshed. There may be associated fatigue, “brain fog” and difficulties with cognition and memory.
In addition, there are frequently multisystem problems including recurrent headaches, irritable bowel syndrome, sensitivity to heat, cold, light or sound, muscle spasms, numbness and tingling, dizziness, dry eyes and mouth, sinus symptoms and mood disorder. Not all of these symptoms need to be present for the diagnosis, but they should be asked about.
Physical examination generally shows multiple areas of tenderness throughout the body. There may be certain areas of sensitive trigger points.
Fibromyalgia can occur either as a secondary problem (often associated with chronic rheumatology conditions) or as a primary diagnosis without underlying disease.
A basic set of investigations should be performed to exclude underlying disease, but extensive imaging is usually not required, unless there is a high index of suspicion. I generally order basic blood tests such as full blood count, kidney function, comprehensive metabolic panel and liver function, as well as a screen for hormonal issues such as thyroid or parathyroid disease.
In the right clinical situation, it may be necessary to check creatine kinase levels or for a paraprotein. Nerve conduction studies could be performed if there is suspicion of a peripheral neuropathy.
It is important to note that investigations are typically normal or only show minor abnormalities that do not explain the wide variety of symptoms. In fact, my suspicion of fibromyalgia is very high in the patient who presents with a wide variety of symptoms but a large number of negative investigations.
Treatment for fibromyalgia is challenging.
A clear diagnosis, validation of the patient’s symptoms and spending time to explain the condition is the most helpful aspect of management. This is time-consuming and needs patience and empathy. If you are feeling overwhelmed, imagine how the patient is feeling!
If done well, this results in less distress, a higher degree of function, and a reduction in the number of investigations, as the wide range of symptoms are not investigated individually.
Multiple studies have shown that graded exercise therapy is effective. This can be quite challenging given the significant pain and reduced function. It usually needs to be of low intensity to gain confidence and can be slowly increased as symptoms allow. This may be something simple such as water-based activity, yoga, tai chi or even walking. For some patients this may be only for a few minutes at the beginning. Exercise can reduce tissue sensitivity to movement, improve sleep and wellbeing.
Involvement of an exercise physiologist or physiotherapist with skills and experience in treating fibromyalgia is crucial. A good exercise physiologist or physiotherapist will help identify pain triggers, teach pacing strategies and assist with a graded exercise routine. A focus on self-management strategies and active treatment is preferred.
In addition to physical therapy, it is important to address any underlying mental health disturbance, including addressing life stressors, grief or bereavement. Psychological consultation may also be of great use for certain individuals.
Sleep is the other area to address. Consider a sleep study if there is suspicion of obstructive sleep apnoea or other sleep disorder. Sleep hygiene should be assessed, then determine if improvements can be made.
Medical therapy has a smaller role to play. Medications to improve sleep may be helpful, including melatonin. I often use low dose amitriptyline (10 to 20 mg nocte). It is preferable to avoid benzodiazepines and opioids given the issues with dependence. In any case, opioids usually only result in a small improvement of pain.
Medications with some proven benefit in treating fibromyalgia include pregabalin, duloxetine and milnacipran (the latter is not approved on the PBS). These medications have a small role to play and as a rough rule of thumb, they help about one third of patients for about one third of the symptoms.
There is an increasing amount of research indicating that fibromyalgia occurs due to alterations in the pain sensing pathways in the central nervous system. Functional MRI and sleep studies show a specific pattern of changes that seem specific for fibromyalgia; however, these are not available for routine clinical use.
There is also interesting early research that suggests there may be an autoimmune basis to fibromyalgia, although more studies are certainly required. It should be noted that corticosteroids rarely help fibromyalgia and should be avoided given their long-term toxicity.
There is currently no test to diagnose fibromyalgia. Thus, it is a diagnosis of exclusion. Assessing the whole patient and appreciating the multisystem nature of the symptoms is paramount in detecting fibromyalgia. While treatment modalities are somewhat limited at the moment, I am hopeful that there will be further diagnostic and therapeutic advances in the future.
Dr Andrew Jordan is a rheumatologist based in Parramatta, Sydney, with a special interest in inflammatory arthritis, gout and PRP injections.
