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Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus

Arthritis and other musculoskeletal manifestations of systemic lupus erythematosus
Literature review current through: May 2024.
This topic last updated: Jan 18, 2024.

INTRODUCTION — Involvement of the musculoskeletal system is extremely common in patients with systemic lupus erythematosus (SLE). Arthralgia, arthritis, osteonecrosis (avascular necrosis of bone), and myopathy are the principal manifestations. Osteoporosis, often due to glucocorticoid therapy, may increase the risk of fractures.

The musculoskeletal manifestations of SLE in adults are reviewed here. SLE in children and an overview of the clinical manifestations of SLE in adults are presented separately. (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)

JOINT INVOLVEMENT — Joint involvement is the most common feature observed in patients with systemic lupus erythematosus (SLE) and has been noted in up to 95 percent of patients [1,2]. Such symptoms are known to have a negative impact on quality of life [3]. Joint symptoms are often the first symptom of SLE and are present in approximately 75 percent of patients at the time of diagnosis [4].

Clinical characteristics — The manifestations of joint involvement in patients with SLE are heterogeneous and range from mild arthralgias to more severe arthropathy [2]. Other characteristic features of the arthritis associated with SLE are as follows:

Nonerosive arthritis – The arthritis of SLE is typically nonerosive and is generally different from that of rheumatoid arthritis (RA) (table 1) [5-8]. The arthritis and arthralgias of SLE tend to be migratory; symptoms in a particular joint may be gone within 24 hours but can often last longer. Although any joint can be involved, the arthritis is usually symmetric and polyarticular, with a predilection for the knees, carpal joints, and joints of the fingers, especially the proximal interphalangeal (PIP) joint. The ankles, elbows, shoulders, and hips are less frequently involved. Involvement of the sacroiliac joints and cervical spine may occur but is rare. Monoarticular arthritis is unusual and suggests an alternative cause such as infection.

Over 25 percent of patients with SLE and joint symptoms have proven synovitis on magnetic resonance imaging (MRI) or ultrasound [9,10]. Synovial effusions are less frequent. When they occur, they are usually small, and the fluid is clear or slightly cloudy [11]. In contrast to the highly inflammatory exudates of RA, the synovial fluid in SLE is only mildly inflammatory, with low protein levels and white blood cell counts (similar to a transudate) [8].

Although typically considered nonerosive, imaging with ultrasound or MRI has revealed that chronic synovitis and erosions in patients with SLE are more common than previously thought [9,12,13]. The presence of antibodies to citrullinated peptides/proteins in patients with SLE is associated with erosive arthritis, and are present in approximately 5 to 10 percent of patients with SLE [14-17]. This antibody profile can be observed in patients with overlapping features of both SLE and RA, which has been referred to as Rhupus. This form of SLE-related arthritis is rare and is discussed further below. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Differential diagnosis' and 'Rhupus' below.)

Synovial histopathology tends to be nonspecific, with superficial fibrin-like material and local or diffuse synovial cell lining proliferation [8]. Vascular changes have included perivascular mononuclear cells, lumen obliteration, enlarged endothelial cells, and thrombi; blood vessel fibrinoid necrosis (eg, vasculitis) is uncommon [18].

Hand deformity – Although the arthritis of SLE is generally considered to be nondeforming, joint deformities such as ulnar deviation, thumb subluxation, and boutonniere and swan neck deformities, as seen in RA, have been noted in 15 to 50 percent of patients with SLE [5-8,19,20]. These deformities, referred to as Jaccoud arthropathy, are typically easily reducible; they are thought to be due to lax joint capsules, tendons, and ligaments that cause joint instability. Risk factors for joint deformity include treatment with glucocorticoids, presence of anti-Ro/SSA and/or anti-La/SSB antibodies [21], or longstanding disease [19].

Tendinopathy – Tenosynovitis has been noted in 10 to 44 percent of patients, including epicondylitis, rotator cuff tendinitis, Achilles tendinitis, tibialis posterior tendinitis, and plantar fasciitis [8,19,22,23]. Infrapatellar and Achilles tendon ruptures are rare [24].

Pain from arthralgias/arthritis must be distinguished from fibromyalgia, which is common among patients with SLE (see 'Fibromyalgia' below). The arthritis in patients with SLE must also be distinguished from osteoarthritis and RA. (See 'Rhupus' below.)

The approach to diagnostic imaging for polyarticular joint pain and the utility of various imaging modalities for joint pain are presented separately. (See "Evaluation of the adult with polyarticular pain" and "Imaging techniques for evaluation of the painful joint".)

Treatment of arthritis — Arthralgias and arthritis associated with SLE typically respond to the use of hydroxychloroquine alone. Short courses of nonsteroidal antiinflammatory drugs (NSAIDs) may occasionally be needed to control symptoms but should be used cautiously especially if the patient also has kidney involvement.

Some patients may demonstrate features of a more severe or persistent arthritis, and additional immunosuppressive therapy may be needed. Our approach to managing such patients is described further below. (See 'Mild to moderate symptoms' below and 'Persistent or severe symptoms' below.)

Mild to moderate symptoms

Hydroxychloroquine – All patients with SLE should be initiated on hydroxychloroquine at the time of their diagnosis with SLE, unless otherwise contraindicated. Hydroxychloroquine has been shown to be effective for the amelioration of joint symptoms, as well as for the prevention of disease flares, of damage accrual, and for delaying mortality [25-32]. We use hydroxychloroquine, typically dosed at 200 to 400 mg/day with adjustments based on body weight (the dose should not exceed 5 mg/kg of real [actual] body weight/day) or blood level (within the therapeutic range) to avoid retinal toxicity. We typically counsel patients that the effect on joint symptoms is not observed until two to three months after initiation of hydroxychloroquine. The role of hydroxychloroquine in the management of SLE is discussed in detail separately. (See "Systemic lupus erythematosus in adults: Overview of the management and prognosis", section on 'Approach to drug therapy' and "Antimalarial drugs in the treatment of rheumatic disease".)

There are limited data regarding the efficacy of hydroxychloroquine for the treatment of arthritis associated with SLE. In a trial including 71 patients with SLE and arthritis and arthralgias, patients randomly assigned to receive hydroxychloroquine experienced a greater improvement in subjective joint pain at 48 weeks of follow-up compared with placebo [25].

NSAIDs – For patients with persistent joint pain while on antimalarials, we suggest oral nonsteroidal antiinflammatory drugs (NSAIDs) for symptomatic relief of arthritic pain rather than glucocorticoids, preferably at the lowest dose and shortest duration possible [33]. Topical diclofenac may be used for patients with hand and knee pain who want to limit the systemic side effects of oral NSAIDs. Our approach to using NSAIDs for symptomatic relief of RA symptoms is presented separately (see "Initial treatment of rheumatoid arthritis in adults", section on 'NSAIDs'). Alternatively, acetaminophen (up to 3 g/day in the absence of liver disease or alcohol abuse) may be used if NSAIDs are contraindicated, not tolerated, or ineffective.

Nonpharmacologic therapies – Patients with arthritis related to SLE may benefit from the addition of nonpharmacologic therapies similar to those used to treat other forms of inflammatory arthritis, including use of assistive devices and referral to physical or occupational therapy. Nonpharmacologic therapy for arthralgia and arthritis are discussed in detail elsewhere. (See "Nonpharmacologic therapies for patients with rheumatoid arthritis", section on 'Physical and occupational therapy' and "Overview of joint protection".)

Persistent or severe symptoms — Patients with more persistent or severe arthritic and/or inflammatory symptoms may require additional immunosuppressive therapy. This may include some patients with Rhupus, which is a term that describes patients with overlapping features of SLE and RA and is discussed further below. (See 'Rhupus' below.)

Glucocorticoids – For patients with persistent joint pain secondary to arthritis that has not resolved while on antimalarials and NSAIDs, or for whom NSAIDs are contraindicated, we suggest a short course of glucocorticoids rather than continuing NSAIDs. Based upon our clinical experience, we usually initiate therapy with prednisone 5 to 20 mg/day, depending upon the severity of joint inflammation and upon the minimal dose required to obtain initial control. However, patients with concomitant systemic flares may require higher doses of glucocorticoids to control other disease manifestations. If courses of glucocorticoids longer than two to four weeks are required to control isolated arthritis symptoms, an alternative immunosuppressive therapy or disease-modifying antirheumatic drug (DMARD) should be added so that the glucocorticoid can be tapered. NSAIDs and glucocorticoids should not be used at the same time due to the increased risk of adverse gastrointestinal events. (See "Initial treatment of rheumatoid arthritis in adults", section on 'Glucocorticoids'.)

Methotrexate – For patients with SLE and persistent arthritis while on antimalarials, or an arthritis that is requiring courses of glucocorticoids longer than two to four weeks, we suggest adding methotrexate to avoid the need for glucocorticoids while controlling joint disease. Patients unable to tolerate or take methotrexate can try leflunomide as an alternative unless otherwise contraindicated [34,35]. However, both methotrexate and leflunomide are teratogenic and contraindicated in women who are pregnant or contemplating becoming pregnant. There are limited data regarding the use of methotrexate or leflunomide for arthritis associated with SLE, and this approach is largely based on indirect evidence from the treatment of RA. A systematic review of nine studies (three of which were randomized controlled trials) including patients with SLE with predominantly mucocutaneous or arthritis features found that methotrexate use was associated with a statistically significant reduction in disease activity as well as the average dose of glucocorticoids used by patients [36]. Methotrexate and leflunomide are dosed in the same manner as that used for RA. (See "Initial treatment of rheumatoid arthritis in adults", section on 'Initial therapy with methotrexate' and "Initial treatment of rheumatoid arthritis in adults", section on 'Alternatives to methotrexate'.)

For patients with persistent arthritis unresponsive to methotrexate or leflunomide after three to six months of therapy, the choice of subsequent agent depends on several factors including considerations regarding other disease manifestations, comorbidities, cost of treatments, and availability of specific agents. Belimumab and anifrolumab may be preferable for patients with SLE with predominantly both skin and joint manifestations. Other options include azathioprine, rituximab, as well as other agents typically used to treat RA (eg, abatacept, janus kinase inhibitors, and tumor necrosis factor [TNF] inhibitors). Available data regarding the use of these agents for patients with SLE and arthritis are limited:

Belimumab – Belimumab, a human monoclonal antibody that inhibits the soluble form of a B-cell survival factor (known as B lymphocyte stimulator [BLyS] or B-cell activating factor [BAFF]), appears to be useful for patients with joint and skin manifestations of SLE. The pivotal trials for belimumab demonstrated improvements in musculoskeletal outcomes in patients with SLE [37,38]. Post hoc analyses have further examined the results of these trials, and reported benefits include decreased musculoskeletal and mucocutaneous involvement and decreased requirements for glucocorticoids [39-43]. A Cochrane review including six randomized trials found that belimumab alone or in combination with other immunosuppressive drugs in patients with SLE (but not active nephritis or central nervous system involvement) resulted in reduced disease activity as measured by a validated disease activity score, with an absolute risk difference of 13 percent improvement (95% CI 8-17 percent) [44].

Anifrolumab – Anifrolumab, a type I interferon receptor antagonist (immunoglobulin [Ig] G1 kappa monoclonal antibody), may be used as an alternative to belimumab for patients with persistent joint symptoms, although more data are needed to determine its role in therapy. The use of anifrolumab for patients with SLE is based on data from three randomized trials in which patients with SLE demonstrated improvement in composite indices of disease activity and/or a reduction in glucocorticoid dose [45-47]. The trials included patients classified as having moderate to severe SLE despite standard therapies, but patients with manifestations of severe lupus nephritis or neuropsychiatric disease were excluded. These trials are discussed in more detail separately. (See "Systemic lupus erythematosus in adults: Overview of the management and prognosis".)

A post hoc analysis of pooled data from one of the pivotal randomized trials suggests that anifrolumab may be most effective for patients specifically with joint and skin involvement of SLE [48]. At 52 weeks, a greater percentage of patients receiving anifrolumab (56.7 percent) demonstrated a near complete resolution of arthritis as defined by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) when compared with placebo (42.6 percent; odds ratio [OR] 1.88 [90% CI 1.16-3.04]). Findings related to arthritis were also more favorable for the anifrolumab group when compared with placebo as measured by the British Isles Lupus Assessment Group (BILAG; 69.1 versus 49.5 percent; OR 2.47 [90% CI 1.48-4.12]), as well as for the swollen and tender joint counts.

Azathioprine – The efficacy of azathioprine in controlling SLE-associated arthritis is extrapolated from results of RA trials. Also, azathioprine has been shown to decrease activity of nonrenal manifestations, which include patients with SLE and musculoskeletal manifestations such as arthritis [49-51]. Information regarding dosing, monitoring, and adverse effects of azathioprine can be found separately. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases".)

Rituximab – The use of rituximab is largely based on observational studies showing a reduction in disease activity with rituximab [52-54]. Additional information regarding dosing and adverse effects of rituximab can be found elsewhere. (See "Systemic lupus erythematosus in adults: Overview of the management and prognosis", section on 'Approach to drug therapy' and "Rituximab: Principles of use and adverse effects in rheumatoid arthritis".)

Other agents – Other agents including abatacept and janus kinase inhibitors (eg, baricitinib) also used for the treatment of RA can also improve the arthritis associated with SLE and have been found to be safe [55-58]. Although TNF inhibitors are known to induce antinuclear antibodies and, less commonly, lead to drug-induced SLE, they are not contraindicated in patients with SLE. However, in our experience, TNF inhibitors are of little benefit in patients with SLE, with the exception of those whose arthritis is more consistent with Rhupus. (See 'Rhupus' below and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'JAK inhibitors' and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'TNF inhibitors'.)

Total joint arthroplasty is sometimes required in patients with SLE. In one cohort of 500 patients with SLE followed at a single center in Great Britain, arthritis was present in 94 percent, but only 4 percent (19 patients) underwent at least one total joint replacement between 1978 and 2008 [59]. The findings most often associated with undergoing joint replacement were osteonecrosis and overlapping features of RA (in 10 and 11 patients, respectively). An analysis of data from a large hospitalization database in the United States suggested that patients with SLE are at increased risk for postoperative mortality after joint arthroplasty [60]. However, pain and functional outcomes of arthroplasty appear to be comparable with those of the general population undergoing arthroplasty for osteoarthritis [61].

BONE INVOLVEMENT

Osteonecrosis — Asymptomatic osteonecrosis (also called avascular, aseptic, or ischemic necrosis) has been reported in up to one-third of patients with systemic lupus erythematosus (SLE) [62,63]. Estimates of the prevalence of symptomatic osteonecrosis are lower and closer to approximately 10 percent [64]. Although the femoral head is the most common site for osteonecrosis, the humeral head, tibial plateau, and scaphoid (navicular) can also be affected [5,65-67]. Osteonecrosis is usually bilateral and is often asymptomatic. When symptoms occur, femoral head involvement usually manifests as pain in the groin, especially with weightbearing. The clinical manifestations and diagnosis are discussed in detail separately. (See "Clinical manifestations and diagnosis of osteonecrosis (avascular necrosis of bone)".)

Risk factors for osteonecrosis among patients with SLE include treatment with glucocorticoids and disease activity [67-69]. The risk of glucocorticoids and other factors leading to the development of osteonecrosis are discussed in detail separately. (See "Clinical manifestations and diagnosis of osteonecrosis (avascular necrosis of bone)", section on 'Glucocorticoids' and "Clinical manifestations and diagnosis of osteonecrosis (avascular necrosis of bone)", section on 'Risk factors'.)

The management of osteonecrosis is the same as for those without SLE. Patients with SLE who require total hip or knee arthroplasties typically do as well as those without SLE [61,70,71]. The approach to therapy of osteonecrosis is discussed separately. (See "Treatment of nontraumatic hip osteonecrosis (avascular necrosis of the femoral head) in adults".)

Osteoporosis — Several population-based studies have reported a higher prevalence of osteoporosis among patients with SLE compared with the general population [72,73]. The risk of hip and vertebral fracture are almost two- and threefold higher, respectively, when compared with the general population [74,75]. In addition to conventional risk factors for osteoporosis (eg, age, postmenopausal status), other risks factors in patients with SLE include use of glucocorticoids, high disease activity, and renal failure [76-79]. Decreased serum 25-hydroxyvitamin D levels are more common among patients with SLE compared with healthy subjects [80]. In addition, low 25-hydroxyvitamin D levels appear to be associated with increased disease activity in patients with SLE [81]. Thus, vitamin D monitoring with supplementation when needed should be part of routine management. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

Certain general principles should be followed in all patients to minimize bone loss, particularly in patients receiving therapy with glucocorticoids. The treatment of osteoporosis and prevention of glucocorticoid-induced osteoporosis are presented in detail separately. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Briefly, important elements in management include:

Modification of lifestyle factors (ie, elimination of cigarette smoking, limitation of alcohol consumption, and maintenance of a weightbearing exercise regimen). (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'General measures'.)

Limitation of glucocorticoid therapy to the lowest possible dose and duration required. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'General measures'.)

Administration of calcium and vitamin D. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Calcium and vitamin D'.)

Measurement of bone mineral density and administration of pharmacologic therapy when needed. Other aspects of osteoporosis are discussed elsewhere:

(See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

(See "Evaluation and treatment of premenopausal osteoporosis".)

(See "Use of biochemical markers of bone turnover in osteoporosis".)

Fractures — The risk of fracture in patients with SLE is five times that of the general population [82,83]. Osteopenia and osteoporosis may account for much of the increased risk (see 'Osteoporosis' above). The magnitude of the fracture risk is illustrated by a cohort study of approximately 700 women with SLE and an equivalent number of age-matched controls; a fivefold increase in fracture among those with SLE was noted [82]. Variables that were significantly associated with the time from diagnosis to that of fracture included older age at the time of diagnosis of SLE, longer disease duration, longer duration of glucocorticoid use, less use of oral contraceptives, and menopause status. Vertebral fractures, found in up to 20 percent of patients with SLE, have been associated with intravenous use of methylprednisolone at any time and with male sex [84].

The presence of antiphospholipid antibodies (aPL) may be associated with an increased risk of nontraumatic fractures. This was illustrated in one study that linked aPL to an increased risk of metatarsal (stress) fractures in patients with SLE [85].

MUSCLE INVOLVEMENT — Myalgias, muscle tenderness, or muscle weakness occurs in up to 70 percent of patients with systemic lupus erythematosus (SLE) and may be the reason that the patient initially seeks medical attention [5,86-88]. However, severe muscle weakness, atrophy, or myositis is relatively uncommon (7 to 15 percent) [5,89,90]. Pathologic examination reveals perivascular and perifascicular mononuclear cell infiltrates in 25 percent of patients [22]. Other histologic findings include muscle atrophy, microtubular inclusions, mononuclear infiltrate, fiber necrosis, and, occasionally, vacuolated muscle fibers [91]. Significant elevations in creatinine kinase (CK) (eg, ≥500 units/L) are rare, occurring in less than 5 percent of patients with SLE, and may suggest an overlap syndrome [92]. (See "Undifferentiated systemic rheumatic (connective tissue) disease and overlap syndromes" and "Mixed connective tissue disease", section on 'Musculoskeletal'.)

In addition to SLE itself, rarely, glucocorticoids and antimalarial drugs can cause muscle weakness [86,87]. Medication-induced myopathy is generally easily differentiated from SLE-induced myopathy or myositis:

Serum levels of CK and/or aldolase are usually normal in patients with glucocorticoid-induced myopathy, although lactate dehydrogenase (LDH) values may be elevated in some cases [93]. Muscle biopsy reveals an increase in the number of sarcolemmal nuclei, rowing and centralization of the nuclei, vacuolization and loss of fiber cross-striations, and phagocytosis, but does not reveal the inflammation characteristic of SLE [94].

Muscle enzymes are also typically normal in patients with antimalarial-induced myopathy. Muscle biopsy may reveal vacuolar changes but not inflammation.

Establishing the correct diagnosis has important implications for therapy. Lupus myositis responds to treatment with glucocorticoids (using a regimen similar to that in polymyositis), while glucocorticoid-induced myopathy responds to a reduction in or withdrawal of glucocorticoid therapy. Antimalarial myopathy responds to stopping the drug, but it may take months for the myopathy to improve, partly due to the months-long half-life of hydroxychloroquine. (See "Initial treatment of dermatomyositis and polymyositis in adults" and "Glucocorticoid-induced myopathy" and "Drug-induced myopathies".)

Other medications that may also cause myopathy, most often resulting in myalgias but also more severe muscle disease, include statins being used for treatment of hyperlipidemia. (See "Statin muscle-related adverse events".)

COMORBID AND OVERLAP CONDITIONS

Fibromyalgia — Reported prevalence rates of fibromyalgia in patients with systemic lupus erythematosus (SLE) vary widely (from 20 to 40 percent) but in general, are much higher than in the general population [95,96]. The symptoms are detrimental to the patient's quality of life and may increase disability [97]. The diagnosis of fibromyalgia may be challenging in the setting of SLE, particularly among patients with fatigue and pain. (See "Clinical manifestations and diagnosis of fibromyalgia in adults" and "Treatment of fibromyalgia in adults" and "Overview of chronic widespread (centralized) pain in the rheumatic diseases", section on 'Systemic lupus erythematosus and Sjögren's disease'.)

Rhupus — The term "Rhupus" has traditionally been used to describe patients with overlapping features of both SLE and rheumatoid arthritis (RA) [98,99]. Whether Rhupus is clinically and immunologically a distinct entity, a true overlap of SLE and RA, or a subset of patients with SLE remains a matter of debate. The main feature of Rhupus is an RA-like arthritis that must be differentiated from the more common nonerosive and nondeforming arthritis observed in SLE. Also, when compared with patients with SLE, patients with Rhupus tend to have lower disease activity scores and are less likely to have severe organ involvement (eg, kidney involvement and hematologic abnormalities) [100,101]. Subcutaneous nodules that occur characteristically in patients with RA have been noted in patients with Rhupus [5,102]. Among patients with Rhupus, the prevalence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies is higher compared with patients with SLE [99]. (See "Undifferentiated systemic rheumatic (connective tissue) disease and overlap syndromes".)

The treatment of the joint disease associated with Rhupus is largely extrapolated from the management of RA. Management may include use of disease-modifying antirheumatic drugs (DMARDs) as described above. (See 'Treatment of arthritis' above.)

SUMMARY AND RECOMMENDATIONS

Musculoskeletal system involvement in SLE – Different aspects of the musculoskeletal system are often affected by systemic lupus erythematosus (SLE), with arthralgias and arthritis being among the most common. (See 'Introduction' above.)

Joint involvement – Arthritis and arthralgias have been noted in up to 95 percent of patients of patients with SLE and are often present in most patients at the time of diagnosis. The arthritis tends to be migratory, and in contrast to rheumatoid arthritis (RA), plain radiographic evidence of erosions is rare. (See 'Clinical characteristics' above.)

Treatment of arthritis

Mild to moderate symptoms

-All patients with SLE should be initiated on hydroxychloroquine at the time of their diagnosis with SLE, unless otherwise contraindicated. Hydroxychloroquine has been shown to be effective for the amelioration of joint symptoms as well as for the prevention of disease flares. Arthralgias and arthritis associated with SLE typically respond to the use of hydroxychloroquine alone. (See "Systemic lupus erythematosus in adults: Overview of the management and prognosis", section on 'Approach to drug therapy' and 'Mild to moderate symptoms' above.)

-For patients with persistent joint pain while on antimalarials, we suggest oral nonsteroidal antiinflammatory drugs (NSAIDs) for symptomatic relief of arthritic pain rather than glucocorticoids, preferably at the lowest dose and shortest duration possible (Grade 2C). (See 'Mild to moderate symptoms' above.)

Persistent or severe symptoms

-For patients with persistent joint pain secondary to arthritis that has not resolved while on antimalarials and NSAIDs, or for whom NSAIDs are contraindicated, we suggest a short course of glucocorticoids rather than continuing NSAIDs (Grade 2C).

-For patients with SLE and persistent arthritis while on antimalarials, or an arthritis that is requiring courses of glucocorticoids longer than two to four weeks, we suggest adding methotrexate (Grade 2C).

-For patients with persistent arthritis unresponsive to methotrexate or leflunomide after three to six months of therapy, the choice of subsequent agent depends on several factors including considerations regarding other disease manifestations, comorbidities, cost of treatments, and availability of specific agents. Belimumab and anifrolumab may be preferable for patients with predominantly both skin and joint manifestations. Other options include azathioprine and rituximab, as well as other agents typically used to treat RA (eg, abatacept, janus kinase inhibitors, and tumor necrosis factor [TNF] inhibitors). (See 'Treatment of arthritis' above.)

Osteonecrosis – Asymptomatic osteonecrosis (also called avascular, aseptic, or ischemic necrosis) has been reported in up to one-third of patients with SLE, whereas estimates of symptomatic osteonecrosis are lower and closer to 10 percent. Risk factors include treatment with glucocorticoids and disease activity. The management of osteonecrosis is the same as for those without SLE. (See 'Osteonecrosis' above.)

Osteoporosis – Rates of osteoporosis among patients with SLE are higher compared with the general population. In addition to conventional risk factors for osteoporosis (eg, age, postmenopausal status), other risk factors in patients with SLE include use of glucocorticoids, high disease activity, and renal failure. Thus, attention to bone health is important in the management of patients with SLE. (See 'Osteoporosis' above.)

Muscle involvement – Myalgias, muscle tenderness, or muscle weakness occur in up to 70 percent of patients with SLE and may be the reason that the patient initially seeks medical attention. However, severe muscle weakness, atrophy, or myositis is relatively uncommon. (See 'Muscle involvement' above.)

Comorbid and overlap conditions – The reported prevalence rates of fibromyalgia in patients with SLE are much higher than in the general population. "Rhupus," a term traditionally used to describe patients with overlapping features of both SLE and RA, must be differentiated from the more common nonerosive and nondeforming arthritis observed in SLE. (See 'Comorbid and overlap conditions' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Peter H Schur, MD, who contributed to earlier versions of this topic review.

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Topic 4673 Version 32.0

References

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