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12 Articles in Volume 12, Issue #1
Ask the Expert: Escalating Opioids
Can Yoga and Stretching Exercises Relieve Chronic Low Back Pain?
Cortisol Screening in Chronic Pain Patients
Editor's Memo: FDA Removes Homeopathic HCG; Helps Legitimate Use In Pain Treatment
Formulation: The Four Perspectives of a Patient in Chronic Pain
Guide to Chronic Pain Assessment Tools
How to Select an In-Office Electromagnetic Field Device
Letters to the Editor: Hormone Therapies
Managing Pain in Active or Well-Controlled Systemic Lupus Erythematosus
PPM Editorial Board Examines Steps to Prevent Accidental Overdoses
Saliva Drug Screening in the Office Setting: Detection of Drug Use and Abuse
Understanding the Toxicology of Diazepam

Managing Pain in Active or Well-Controlled Systemic Lupus Erythematosus

Patients with this disease often experience pain related to arthritis and secondary fibromyalgia syndrome.

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).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). 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.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.

Treating Non-arthritic Causes of Pain
The approach to pain management in SLE is similar to that for other painful conditions, namely, a stepwise approach that employs both pharmacologic and adjunctive therapies (see Figure). Initial treatment can be acetaminophen and/or NSAIDs at therapeutic dosages. NSAIDs should be avoided in patients with lupus nephritis. Although aspirin is approved to treat SLE, it is rarely used in high doses. Low-dose aspirin is commonly used for primary prevention of cardiovascular disease, which is markedly increased in individuals with SLE, and to prevent thromboembolic disease in patients with antiphospholipid antibodies. If acetaminophen and NSAIDs are ineffective and the lupus disease activity is being addressed, one can add tramadol and consider adjunctive therapies for pain (see Table 3). The selection and dosing of opioid analgesics is not addressed in this article, as usage mirrors that in other chronic inflammatory arthritic conditions.

A recent study identified sleep disturbance in 62% of a population of patients with SLE.3 Chronic sleep deprivation may have detrimental effects on the immune system, although this interaction has not been fully explored in SLE.Adequate sleep is important for pain management, so attempts to restore a normal sleep cycle should be employed. Medications that address sleep as well as pain, such as tricyclic antidepressants, muscle relaxants, and atypical antiepileptics or pregabalin (Lyrica), often are helpful in this regard. When any of these medications are used with corticosteroids, though, patients should be counseled about the potential for weight gain, which can be substantial and can eventually worsen pain through increased load on joints.

If a patient’s difficulty is only with sleep initiation, then agents such as zolpidem (Ambien, others) or zaleplon (Sonata) may be useful, although these agents are intended for short-term use and do not address the pain that may be the root cause of SLE patients’ sleep disturbance. Likewise, temazepam (Restoril, others) may be useful for patients with SLE who have difficulty initiating and maintaining sleep, but do not cite pain as a reason for difficulty sleeping.

Pain is worse when it is associated with depression. Also, pain and other manifestations of SLE may lead to depression and anxiety, which should be addressed.I generally consider using antidepressants after addressing sleep disturbance. The serotonin norepinepherine reuptake inhibitors (SNRIs) are a group of antidepressants that have been shown to be effective for chronic pain. These include venlafaxine; duloxetine (Cymbalta), which is approved for treatment of osteoarthritis, fibromyalgia, and diabetic neuropathy; and milnacipran (Savella), which is approved for treatment of fibromyalgia syndrome. In patients with SLE and chronic pain, adding one of these agents can be especially helpful for addressing both mood and pain complaints. If a patient with SLE does not respond as expected to one of these agents, I recommend psychiatry consultation since depression is a common manifestation of neuropsychiatric lupus, which may require a multi-faceted approach to both diagnosis and management.

Stress management can be helpful for pain in patients with lupus. One study addressed this by randomizing patients to a biofeedback-assisted cognitive-behavioral therapy (CBT) intervention, symptom-monitoring support, or usual care. The CBT intervention had the most beneficial effect on pain, though improvement was not maintained 9 months after the intervention.6 In the Duke Lupus Registry, we found that abnormal scores on two forms of pain appraisal, pain catastrophizing and self-efficacy for pain, correlate better with troubling SLE symptoms than disease activity does.7 These findings suggest that interventions to improve pain coping skills in individuals with SLE may improve pain overall.

One small study enrolled 15 sedentary women with SLE in a Wii Fit program attempting to improve fatigue, with pain as a secondary outcome. Pain improved significantly with the intervention as measured on the short-form McGill Pain Questionnaire.8 In patients who are able, I encourage including exercise as part of the pain management regimen, and especially encourage patients with SLE to enter arthritis rehabilitation programs. In my experience, low-impact exercise such as walking, swimming/water aerobics, and yoga, as a few examples, are enjoyed by patients with SLE and pain. Individuals with SLE may be limited in their exercise if pain is due to AVN or advanced joint deformities. Additionally, it is important to remind patients with SLE that if they exercise outside, they must be vigilant about sunscreen usage and general photoprotection, as most individuals with SLE are photosensitive, meaning UV light can precipitate a flare of disease.

In a pilot study of 24 patients with SLE, acupuncture was determined to be safe. Of interest, 40% of patients who underwent either acupuncture or minimal needling (sham treatment) had at least 30% improvement on standard measures of pain compared with patients who received usual care. Thus, the role of acupuncture in SLE pain management is not known.9

Special Considerations in SLE Pain Management
Vitamin D status should always be addressed in patients with SLE. Photosensitivity is a criterion for the diagnosis of SLE; photosensitive individuals develop rashes upon ultraviolet light exposure. Patients with SLE are advised to practice sun avoidance and use sunscreen with a high SPF. As a result, across studies, approximately 65% of patients have insufficient levels of vitamin D,10,11 which may contribute to widespread pain in some patients.

As previously described, AVN is not unusual in patients with SLE. AVN pain is chronic and is only relieved by surgery, usually total joint arthroplasty. These procedures often are delayed in SLE because of young patient age. The pain of AVN often requires inclusion of chronic long-acting opioid analgesics as part of a multimodal pain management approach.

In a recent study, fibromyalgia syndrome was no more common in SLE than in other inflammatory arthritides.12 In a patient with SLE, secondary fibromyalgia should be treated the same as primary fibromyalgia, aside from consideration of potential drug interactions. The approach should be multidisciplinary, using medications to help manage sleep disturbance, pain, and depression if present. Patients should be educated in self-management techniques, including aerobic exercise. In addition, improving pain coping skills can be an important adjunctive therapy in fibromyalgia.

Of interest, several studies have shown that the use of complementary and alternative medicine (CAM) is high among patients with SLE, generally more than 40%. A recent study found that among patients with SLE, CAM use in the form of dietary supplements was associated with higher bodily pain scores.13 Therefore, a careful history of the use of complementary and alternative medications should be taken in patients with SLE and pain to identify potential drug interactions and side effects.

More than 90% of individuals with SLE experience pain related to arthritis as part of the disease. Secondary fibromyalgia syndrome is common in SLE. The first challenge in patients with SLE is to ascertain whether their pain is due to active disease. If the pain is due to active disease, then treatment aimed at reducing disease activity should initially be employed. These treatments can include hydroxychloroquine, NSAIDs, glucocorticoids, and immunosuppressive therapies—such as belimumab. If the disease is well controlled and pain persists, then multimodal treatments should be recommended. These treatments can include, in stepwise fashion, analgesics such as acetaminophen, NSAIDs, tramadol, and opioid analgesics. In addition, adjunctive pharmacotherapies to address sleep, mood, and pain perception can be considered. Finally, the use of CAM is frequent in this population, and providers should inquire about potential drug interactions. Acupuncture is not contraindicated in patients with SLE. In addition, patient self-management techniques, as taught by a pain psychologist, can help patients learn ways to cope with pain.

Last updated on: July 26, 2017
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