Managing Pain in Active or Well-Controlled Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease, characterized by the presence of autoantibodies and multiorgan system involvement. SLE generally strikes women of childbearing age and affects about one in 2,000 individuals. Women of African descent and Hispanic ethnicity are affected more frequently than white women, and the disease tends to be more severe in these two patient populations.
A clinical diagnosis of SLE is made using the medical history, physical examination, and supporting laboratory data to determine whether an individual meets four of 11 classification criteria as defined by the American College of Rheumatology (see box, page 80).1 Although the SLE classification criteria were created to facilitate enrollment of individuals with phenotypically similar disease into clinical trials, they also are used in clinical practice.
Arthritis is one criterion for SLE, and more than 90% of individuals with SLE will have arthritis during the course of their disease. Arthritis in SLE is defined as arthritis of two or more peripheral joints, as evidenced by joint tenderness, swelling, or effusion. SLE classically produces a nonerosive arthritis, in contrast to rheumatoid arthritis (RA), which is characterized by bone erosions at the site where the synovial lining inserts into bone. Despite the lack of erosive change, SLE arthritis can be deforming due to ligament and tendon damage, termed Jaccoud’s arthropathy.
There are many potential causes of pain in SLE (see Table 1, page 81). Many people with SLE have secondary fibromyalgia, and individuals occasionally present with widespread pain as the initial manifestation of SLE. Other organ system involvement can be painful, such as serositis (pleuritis or pericarditis). Neurologic system involvement may create painful peripheral neuropathy or headache syndromes. Raynaud’s phenomenon occurs in many people with SLE and can be painful. Avascular necrosis (AVN) is a frequent complication both of SLE and its treatment, as glucocorticoid therapy raises the risk for AVN. In patients with SLE, AVN most commonly involves hips, shoulders, and knees, though other joints may be involved.
Challenges of Pain Management In SLE
A key challenge is determining the source of the patient’s pain. Sometimes the pain is clearly related to active SLE, and treatment of the active inflammation relieves the pain. However, in many cases, the pain is multifactorial, so the approach to management must be multifaceted as well. Determining whether the pain is due to active disease can be daunting for individuals who are not familiar with SLE and its typical presentations and manifestations; there is a tendency to assume that all complaints in patients with SLE are somehow related to the disease. This assumption often produces delays in other medical diagnoses and iatrogenic complications, especially from overuse of glucocorticoids. In addition, our understanding of the pathophysiology of SLE arthritis is incomplete. Therefore, most treatment approaches are borrowed from the management of other arthritic diseases.
A second major challenge is the lack of treatment guidelines for SLE. There are few studies and no published guidelines that address management of pain and arthritis in SLE. As of 2011, only four drugs were approved by the FDA for the treatment of SLE. These drugs are aspirin (approved in 1948), hydroxychloroquine and corticosteroids (1955), and belimumab (Benlysta, 2011)—the first SLE drug to be approved in more than 50 years. Given the few FDA-approved medications and the severity of disease, nearly all therapies used for management of SLE are employed off-label.
Is This Patient’s SLE Active?
How can a specialist in pain management determine the cause of pain in a patient with SLE? For any provider, determining SLE activity requires a targeted history and physical examination with the use of selected laboratories to support a diagnosis of active lupus (see Table 2). The patient’s pain description can help determine if inflammatory pain is present.
Classically, inflammatory arthritis causes morning stiffness and prolonged inactivity (gel phenomenon). The pain of lupus arthritis often is present in the morning, lasts at least 30 to 60 minutes and improves with activity within a few hours of awakening, and then worsens again in the late afternoon and early evening. A careful joint exam is necessary, as the swelling from SLE arthritis can be subtler than that of RA. Just like RA, SLE arthritis often involves the wrists and metacarpophalangeal and proximal interphalangeal joints, but it also can be periarticular, involving ligaments and tendons. In active SLE arthritis, joints are tender to palpation with mild joint swelling, evidenced by difficulty palpating the joint line. Certain laboratory abnormalities suggest active SLE as well. These include hypocomplementemia (low C3 and C4), cytopenias (lymphopenia, anemia, and thrombocytopenia), and elevated serum inflammatory markers.
General Approach to Pain Management in SLE
Treating Inflammatory Arthritis
Since the vast majority of SLE patients have arthritis, the cornerstone of pain management in SLE should be treatment of the inflammatory arthritis in concert with a rheumatologist. The choice of pharmacotherapy depends on the severity of the inflammation. Mild inflammatory arthritis is managed with hydroxychloroquine and nonsteroidal anti-inflammatory drugs (NSAIDs). Moderate to severe inflammatory arthritis may require treatment with glucocorticoids at low to moderate doses (5-20 mg of prednisone daily) as well as immunosuppressive therapy with methotrexate, azathioprine, mycophenolate, or other agents. Biologic agents also may be considered, specifically belimumab. Data are emerging in support of the use of other biologic agents, such as abatacept (Orencia), for management of SLE, while rituximab (Rituxan) was shown ineffective for treatment of SLE in a randomized controlled trial.2 Investigational agents, such as an anti-CD22 antibody, are in late-stage clinical trials.
Pain in the hips or shoulders or pain without swelling in the knees of a patient with SLE should raise the possibility of AVN. Although not a rare complication of high-dose steroid use in patients with SLE, AVN also can occur in lupus patients without exposure to corticosteroids. Although advanced AVN can be detected on plain radiographs, early changes may require magnetic resonance imaging for visualization. AVN pain tends to be constant, dull, and aching and is worse with movement of the joint.