Three Cases Highlight the Challenges Of Treating Rheumatoid Arthritis
Differential diagnosis and comorbidities, such as infectious diseases and malignancy, can hamper the ability to manage the patient with rheumatoid arthritis.
Theumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease that can lead to considerable disability. It is found worldwide and is approximately three times more common in women than men. Although it may occur at any age, the peak incidence of RA is found in the 4th or 5th decade of life, and is present in almost 5% of women by age 70. This is in contrast to a 1% to 2% incidence rate found in the general population.1
The pathogenesis of RA involves inflammation of the synovial lining of the affected joints that can result in injury and damage leading to less function in patients. Much of the joint damage that occurs in RA is seen early in the course of the disease, usually within the first one or two years. It is therefore imperative that clinicians try to secure the diagnosis as soon as possible in order to start appropriate therapy (Table 1).
Frequently the diagnosis may be elusive, and only as we treat the patient do we find that the response to therapy is less than we desire. This may be due to a number of factors including resistant disease and other illnesses that may confound our ability to interpret patient response and even laboratory results.
In this article, we discuss three cases that have presented challenges in our practices, and how we proceeded in evaluation, treatment, and further care.
First Case: 60-year-old Woman with 3-month History of Joint Pain
A 60-year-old white woman presented with a 3-month history of joint pain, primarily involving the small joints of her hands and feet. She noted that she had swelling and stiffness in her joints that was worse in the morning, usually lasting over one hour. The stiffness gradually improved but returned towards the late afternoon. The patient also said that she was very fatigued despite sleeping what she thought was soundly.
Examination and Testing
The patient’s general physical examination was unrevealing. The joint examination was abnormal—there was synovitis noted in the first through third metacarpophalangeal joints (MCPs) in both hands and the patient had tenderness in response to squeezing across the metatarsophalangeal joints (MTPs) (squeeze test) in both feet, with swelling noted. The patient’s left knee was also swollen and her right elbow was held in 20° of flexion.
Laboratory data included an elevated rheumatoid factor and a markedly elevated anti-cyclic citrullinated peptide (anti-CCP) antibody. Both her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated (ESR=42 mm/h; CRP=3.9 mg/L). Plain radiographic (x-ray) imaging of her hands and feet suggested early erosions noted at scattered MTPs.
Diagnosis and Treatment
The patient was diagnosed with RA and started on methotrexate 10 mg weekly, advancing to 15 mg over the next few weeks, and eventually increased to a dose of 20 mg, given weekly in divided doses. In addition, she was given 1 mg folic acid daily and 10 mg of prednisone at bedtime (HS).
The patient experienced modest improvement in symptoms over the next 2 months, but both the patient and physician felt there was an inadequate response to her therapy. A biologic agent was added—adalimumab (Humira) subcutaneous 40 mg injection every other week—and within the next month there was considerable improvement in the patient’s symptoms. On follow-up physical examination, the patient clearly had less joint pain, diminished fatigue, reduced morning stiffness, and less swelling of her affected joints. The patient told the clinician that she had an overall sense of improvement and well being. A repeat of her laboratory tests was performed 2 months later, which showed the improvement in markers of inflammation and no change in other levels.
Increase in Symptoms
This pattern of improvement continued for about 3 months until the patient began complaining again of increasing joint pain, which was worse in the morning. She also noticed increasing fatigue, lower abdominal discomfort, and increased forgetfulness. Her feeling of improved health also was diminished. When she awakened each morning, she felt exhausted, as if she “had slept poorly, if at all.”
On physical examination, the patient had generalized pain with joint motion and increased tenderness including the joints and soft tissue regions between the joints. There was no increase in joint swelling and her repeated laboratory tests were unrevealing—the ESR and CRP were minimally elevated and unchanged from prior determination. Because the patient was on methotrexate, her liver function, complete blood count (CBC), and renal function were being monitored.2 All the tests were within normal limits. Her pain level was described as being “moderate to severe.”
How to Proceed?
Our concern was how to proceed. If, indeed, her RA was flaring—should she be switched to a different biologic? She had successfully tapered off her prednisone—should we add this again? Could there be another consideration not obvious at our earlier visits?
We expanded our laboratory testing, and obtained unremarkable results for basic metabolic profile (BMP), thyroid stimulating hormone (TSH), and 25-hydroxy vitamin D levels. Prednisone (10 mg orally) was added HS, but with a minimal response. The patient had been able to return to her job as a secretary for an insurance firm after she had initially improved, but felt the stress level that greeted her upon her return was increased and difficult to handle.
This presented scenario is not uncommonly seen. The diagnosis of fibromyalgia was reviewed with this patient and she was started on the serotonin–norepinephrine reuptake inhibitor (SNRI) duloxetine (Cymbalta) at 30 mg per day, increased to 60 mg per day, with gradual improvement as the dose was escalated.
Her pain level diminished, as did her fatigue—although it still lingered. Despite this, there was an overall sense of improvement and the patient was able to cope with her work situation and daily routine much better.
Pain is the number one reason a patient seeks help at a rheumatologist’s office—and is also the primary reason for follow-up visits. Although it may appear simple to differentiate the pain of RA—where there are physical and laboratory findings that are commonly abnormal—from the pain of fibromyalgia, this may not be the case. In fibromyalgia there is no joint inflammation, and no objective findings of acute or chronic illness may be evident.
RA is associated with synovitis and potential joint injury, where fibromyalgia is thought to be a result of enhanced pain sensitivity, perhaps due to dysfunctional processing of pain stimuli. The other components of ascending and descending pain pathway abnormalities and other theories as to the origin of fibromyalgia are described in detail in our medical literature.3