Sarcoid arthritis

INTRODUCTION — 

Sarcoidosis, a multisystem disorder of unknown etiology, is characterized pathologically by the presence of noncaseating granulomas in affected organs (see "Pathology and pathogenesis of sarcoidosis"). It typically affects young adults, and, although any organ may be affected, the disorder commonly presents with one or more of the following three abnormalities:

●Bilateral hilar adenopathy

●Pulmonary infiltrates

●Skin and/or eye lesions

Musculoskeletal disease in patients with sarcoidosis is less common. However, joint manifestations may be clinically significant in patients with acute sarcoidosis [1,2]. Chronic arthritis and other musculoskeletal manifestations may also occur.

The articular manifestations of sarcoidosis and the diagnosis, differential diagnosis, and treatment of sarcoid arthritis will be reviewed here.

General issues related to sarcoidosis and its pathogenesis, as well as the muscular, skeletal, and other rheumatic manifestations of sarcoidosis, including discussions of diagnosis and treatment, are discussed separately. (See "Clinical manifestations and diagnosis of sarcoidosis" and "Pathology and pathogenesis of sarcoidosis" and "Sarcoid myopathy" and "Sarcoidosis of bone".)

PATHOGENESIS — 

The mechanism underlying the development of an acute or chronic arthritis among patients with sarcoidosis is not well understood. Risk factors have been best defined for Löfgren syndrome, which is the most common form of acute arthritis among patients with sarcoidosis. (See 'Patients with an acute arthritis' below.) These include:

●Infectious/environmental – Reports of seasonal clusters of Löfgren syndrome suggest that an infectious or environmental agent, as yet unknown, may be pathogenetically important [3,4].

●Genetic – Löfgren syndrome has an association with the presence (or absence) of several haplotypes:

•DQB1*0201 – In a study of patients with sarcoidosis from the United Kingdom and the Netherlands, DQB1*0201 positivity was associated with a better outcome and greater likelihood of Löfgren syndrome than DQB1*0201 negativity [5]. DQB1*0201-negative patients took longer to recover and were more likely to need treatment at an early stage.

•DRBI*03 – In a series of 301 Swedish patients with Löfgren syndrome, DRB1*03 positivity was associated with a better outcome than DRB1*03 negativity [6]. All of the DRB1*03-positive patients had complete resolution of their disease in two years, whereas almost half of the DRB1*03-negative patients developed chronic disease.

•DRB1*15 – The absence of HLA-DRB1*15 has been associated with the development of a chronic arthritis among patients presenting with Löfgren syndrome. In a study of 153 patients with Löfgren syndrome followed for at least two years, patients who were HLA-DRB1*15 negative were more likely to develop relapsing disease and/or a chronic arthritis [7]. (See "Human leukocyte antigens (HLA): A roadmap", section on 'Class II region'.)

EPIDEMIOLOGY

●Acute sarcoid arthritis – An acute sarcoid arthritis is present in approximately 10 percent of patients with sarcoidosis [1]. It typically presents in patients less than 40 years old and is more common among women than men.

Among patients with sarcoidosis, an acute arthritis most commonly presents as part of Löfgren syndrome. However, Löfgren syndrome is seen in less than 5 to 10 percent of patients with sarcoidosis [1,8,9]. (See 'Patients with an acute arthritis' below.)

The true incidence and prevalence of acute sarcoid arthritis are unclear, since the diagnosis may be difficult when a patient presents with articular complaints alone; in this setting, the presence of sarcoidosis is established only after more commonly involved organs, such as the eye or lung, become affected. For example, in one study of patients who presented with an early inflammatory arthritis (ie, less than two years' duration), the prevalence of sarcoidosis was 4.4 percent [3].

●Chronic sarcoid arthritis – Chronic sarcoid arthritis is present in approximately 0.2 to 2 percent of patients with sarcoidosis. [9-11]

LABORATORY AND RADIOLOGIC FEATURES

Synovial fluid — Synovial fluid in patients with sarcoid arthritis is typically mildly inflammatory, with either neutrophilic or lymphocytic predominance, but may be noninflammatory in some patients with chronic arthritis [12,13]. Occasionally, synovial fluid may be bloody [14].

However, joint effusions are uncommon among patients with sarcoidosis, and large joint effusions are especially rare. Synovial fluid analysis is generally used to evaluate for alternate diagnoses rather than to establish a diagnosis sarcoid arthritis [14]. (See 'Differential diagnosis' below.)

Imaging

●Plain radiographs – In patients with acute sarcoid arthritis, plain radiographs of the hands and other joints are essentially normal. Although soft tissue swelling may be identified, no erosions or joint space narrowing are seen [1].

In patients with chronic sarcoid arthritis, cystic phalangeal lesions may be present but are not well-correlated with symptoms or with arthritis. An "apple core deformity" of the digit has also been described. (See "Sarcoidosis of bone".)

●Ultrasonography and magnetic resonance imaging (MRI) – Ultrasonography and MRI studies reveal that ankle swelling in most patients with Löfgren syndrome will demonstrate periarticular inflammation (soft tissue and tenosynovitis) rather than true joint swelling [15,16].

MRI can demonstrate tenosynovitis, tendonitis, bursitis, and joint effusion/synovitis but is nonspecific and cannot differentiate sarcoid arthritis from other forms of arthritis [17]. Hypervascular subcutaneous edema is commonly seen in patients presenting with the acute arthritis of Löfgren syndrome [16].

●Gallium-67 scanning – On gallium-67 scanning, the radioisotope is concentrated within the joints with varying intensity in patients with sarcoidosis and arthritis. However, the uptake of this radioisotope is not specific for a diagnosis of sarcoid arthritis and does not appear to correlate with the acuity or chronicity of the joint disease.

Other tests — Patients with sarcoid arthritis often have an elevated serum angiotensin-converting enzyme (ACE) level, although this is not specific for this diagnosis [18].

Other diagnostic tests may be used to establish a diagnosis of sarcoidosis, which is required to diagnose chronic sarcoid arthritis and some forms of acute sarcoid arthritis. These tests are reviewed in detail elsewhere. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Laboratory testing'.)

DIAGNOSIS

Patients with an acute arthritis — An acute sarcoid arthritis should be considered in any patient under 40 years old who presents with an acute symmetric oligo- or polyarthritis (algorithm 1). Acute sarcoid arthritis typically involves both ankles (in addition to other joints).

With Lofgren syndrome — An acute sarcoid arthritis presents most often as part of Löfgren syndrome, which is characterized by the triad of fever, hilar adenopathy, and erythema nodosum [19]. Such patients may be diagnosed with an acute sarcoid arthritis based on clinical features alone [20].

Acute sarcoid arthritis in the setting of Löfgren syndrome most commonly presents as an oligoarthritis (ie, involving two to five joints), although it can also present as a polyarthritis (ie, involving more than five joints). The arthritis typically involves the lower extremities and includes both ankles. [2,21]. In a meta-analysis that included 8574 patients with sarcoidosis, the pooled prevalence estimate (PPE) of ankle arthritis among patients with acute sarcoid arthritis was 87 percent [2]. Other commonly involved joints included the knee (46 percent), wrists (34 percent), and hands (25 percent). Hip, foot, and shoulder involvement were each present in fewer than 4 percent of patients.

Erythema nodosum may be absent; it is more common among female compared with male patients presenting with Löfgren syndrome [4].

Without Lofgren syndrome — Less commonly, acute sarcoid arthritis may present in the absence of Löfgren syndrome.

●Under 40 years, with bilateral ankle arthritis – For patients under 40 years who present with an oligo- or polyarthritis that includes both ankles, we suggest obtaining a chest radiograph to evaluate for the presence of hilar lymphadenopathy. If the chest radiograph does not demonstrate hilar lymphadenopathy, we would perform a high-resolution computed tomography (CT) scan, which is more sensitive for detecting hilar lymphadenopathy. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'HRCT scan'.)

In this scenario, the presence of hilar adenopathy is adequate to confirm the diagnosis of an acute sarcoid arthritis. The acute arthritis is generally oligoarticular (87 percent) and symmetric (76 percent) and most commonly involves ankles (>90 percent), often bilaterally, followed by other large joints in lower extremities [3]. (See 'Differential diagnosis' below.)

●Other presentations – Less commonly, other patterns of involvement may be seen. These include:

•Isolated involvement of the small joints of the hands, mimicking the acute onset of rheumatoid arthritis [22,23]

•Migratory arthritis, mimicking rheumatic fever [23,24].

•Uveoparotid fever (Heerfordt's syndrome), ie, acute arthritis associated with fever, enlarged parotid glands, facial nerve palsy, and uveitis [9] (see "Clinical manifestations and diagnosis of sarcoidosis", section on 'Common extrapulmonary findings and pathognomonic syndromes')

For such patients, the diagnosis of an acute sarcoid arthritis requires two components:

•A diagnosis of sarcoidosis

•The presence of an inflammatory arthritis

Establishing the presence of an inflammatory arthritis requires a clinical evaluation, supplemented by serum, synovial, and imaging studies where appropriate.

The approaches to diagnosis of sarcoidosis and inflammatory arthritis are reviewed in detail elsewhere. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Initial evaluation' and "Evaluation of the adult with polyarticular pain".)

●Acute sarcoid arthritis in children – Acute arthritis in children with sarcoid is generally accompanied by uveitis and rash [21]. Hilar adenopathy generally absent.

When this syndrome appears in the first decade of life (usually before age 4), it may represent Blau syndrome, an early-onset form of sarcoidosis associated with granulomatous uveitis, dermatitis, and a symmetric arthritis. (See "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'Blau syndrome'.)

Patients with a chronic arthritis — A diagnosis of chronic sarcoid arthritis can be made in a patient with sarcoidosis and evidence of chronic joint disease (algorithm 2). Chronic sarcoid arthritis generally develops after a diagnosis of sarcoidosis has already been established.

Most patients with chronic sarcoid arthritis are older than 50 years, and did not initially present with Löfgren syndrome. Upper-extremity involvement is more common in chronic arthritis compared with lower-extremity involvement [2].

Patients with sarcoidosis and one of the following presentations may be diagnosed presumptively as having chronic sarcoid arthritis [25-27]:

●Nondeforming, chronic inflammatory arthritis

●Jaccoud's type deformity of the hands

●Joint swelling adjacent to a sarcoid bone lesion

●Dactylitis

For patients with other patterns of joint involvement, chronic sarcoid arthritis is a diagnosis of exclusion. Other conditions with similar musculoskeletal features must be excluded prior to making a diagnosis of chronic sarcoid arthritis. This approach is similar to the approach used to evaluate patients suspected of having rheumatoid arthritis, which is discussed in detail elsewhere. (See "Diagnosis and differential diagnosis of rheumatoid arthritis", section on 'Differential diagnosis'.)

The utility of laboratory testing and of other diagnostic procedures to establish a diagnosis of sarcoidosis is discussed in more detail elsewhere. (See "Clinical manifestations and diagnosis of sarcoidosis".)

Limited role for synovial biopsy — We do not routinely perform synovial biopsy to establish a diagnosis of sarcoid arthritis. The finding of sterile noncaseating granulomatous inflammation on synovial biopsy is supportive but is not pathognomonic of sarcoidosis. However, a paucity of data exists concerning the characteristics of synovial tissue in acute or chronic sarcoid arthritis.

When indicated for diagnostic purposes (eg, in patients with oligo- or polyarthritis in whom the diagnosis remains unclear despite extensive clinical, laboratory, serologic, and imaging evaluations), the biopsy should be performed arthroscopically; closed synovial membrane biopsies are not helpful [28].

Several samples of synovial tissue obtained by arthroscopically directed biopsy may be submitted for the following studies:

●Fresh (unfixed) tissue – For microbiologic studies, including mycobacterial and fungal stains and cultures

●Absolute alcohol fixed tissue – For processing with water-free stains (eg, Wright-Giemsa) and examination under polarizing microscopy to exclude urate or calcium pyrophosphate crystal deposition (CPPD) tophi

●Formalin fixed tissue – For routine light microscopy

These studies are largely directed towards evaluating for diagnoses that may mimic sarcoid arthritis [12,28-30]. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of sarcoid arthritis includes several rheumatic, infectious, and granulomatous diseases. Key diagnoses to consider include the following:

●Rheumatic

•Reactive arthritis – Reactive arthritis is a type of seronegative spondyloarthritis that commonly leads to inflammation of the spine and oligoarthritis involving lower-extremity joints, especially the ankles [3].

The following features favor a diagnosis of reactive arthritis over sarcoid arthritis (see "Reactive arthritis"):

-Involvement of spine and asymmetrical lower-extremity joint involvement

-The absence of hilar lymphadenopathy on chest radiograph

-Presentation following enteritis or urethritis

In a prospective study of 189 patients presenting with symptoms suggestive of reactive arthritis, 17 (9 percent) were eventually diagnosed with acute sarcoid arthritis [31]. Ten had Löfgren syndrome, and all 17 had bilateral ankle involvement.

•Crystal-induced arthritis – Gout and acute calcium pyrophosphate crystal arthritis (previously known as pseudogout) can cause an acute mono- or oligoarthritis of the great toes and/or ankles, including podagra, which may look similar to sarcoid arthritis.

Unlike sarcoid arthritis, gout and pseudogout are typically intensely inflammatory (with severe redness, tenderness, and swelling) and resolve within a few days to a week with conservative treatment.

Confirmation of these diagnoses requires demonstration of characteristic crystals in the synovial fluid using polarizing light microscopy. (See "Gout: Clinical manifestations and diagnosis" and "Calcium pyrophosphate crystal deposition (CPPD) disease: Clinical manifestations and diagnosis".)

•Rheumatoid arthritis – Rheumatoid arthritis can involve joints of the lower extremity, including the ankles, which is also characteristic of sarcoid arthritis.

Rheumatoid arthritis can be distinguished from sarcoid arthritis by characteristic history and examination findings, including the typical hand involvement seen in rheumatoid arthritis and positive testing for rheumatoid factor and anti-citrullinated peptide antibodies. (See "Clinical manifestations of rheumatoid arthritis" and "Diagnosis and differential diagnosis of rheumatoid arthritis".)

•Juvenile idiopathic arthritis – Young children with juvenile idiopathic arthritis may present with an inflammatory arthritis and uveitis, which is a pattern also seen in some young children with sarcoid arthritis [32].

Because children with sarcoidosis typically lack hilar lymphadenopathy, this finding cannot be used to distinguish juvenile idiopathic arthritis from sarcoid arthritis.

Sarcoid arthritis is more likely to be associated with erythema nodosum, hypercalcemia, and elevated serum levels of angiotensin-converting enzyme (ACE). Chronic sarcoid arthritis can be destructive but lacks the severe erosions, joint deformities, and joint fusions that can be found with late-stage juvenile idiopathic arthritis. (See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications", section on 'Sarcoidosis'.)

•Acute rheumatic fever – Acute rheumatic fever can be associated with a migratory arthritis, similar to some patients with sarcoid arthritis.

However, acute rheumatic fever is also associated with Sydenham chorea, erythema marginatum, and subcutaneous nodules, which are not characteristic of sarcoid arthritis.

Acute rheumatic fever is typically diagnosed using the revised Jones Criteria, which are reviewed in detail elsewhere (table 1). (See "Acute rheumatic fever: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

●Infectious

•Tuberculous arthritis and Poncet disease – Mono- or oligoarthritis of lower-extremity joints, especially knees, is seen in patients with tuberculosis (TB).

TB may cause an arthritis either through direct infection of the joint or by inducing a reactive arthritis.

-Direct infection – Tuberculous joint infection is typically monoarticular.

-Reactive arthritis – Poncet disease is an inflammatory arthritis associated with TB, in which the organism typically cannot be identified in the joint. It is commonly an acute, symmetrical polyarthritis of both large and small joints.

Unlike sarcoidosis, pulmonary TB is associated with a productive cough, weight loss, and a high erythrocyte sedimentation rate (ESR). A diagnosis of pulmonary TB may be made through histopathology or culture of the organism. (See "Bone and joint tuberculosis" and "Diagnosis of pulmonary tuberculosis in adults", section on 'General diagnostic approach'.)

•Histoplasmosis – Histoplasmosis can cause arthritis or arthralgias as well as erythema nodosum, both of which are also characteristic of sarcoid arthritis.

Histoplasmosis is usually seen in immunocompromised hosts and regions where histoplasmosis is endemic. It typically presents with pneumonia with mediastinal or hilar lymphadenopathy, pulmonary nodules, and/or cavitary lesions.

A diagnosis of histoplasmosis can be made by detection of Histoplasma antigen by enzyme immunoassay in the urine, blood, or bronchoalveolar lavage fluid. (See "Pathogenesis and clinical features of pulmonary histoplasmosis" and "Diagnosis and treatment of pulmonary histoplasmosis".)

●Other – Other conditions can also be associated with granulomatous histopathologic changes in synovial tissue. These conditions include:

•Heritable disorders, such as Blau syndrome

•Foreign body granulomas (eg, plant thorns, sutures, sea urchin fragments)

•Other idiopathic granulomatous disorders (eg, Crohn disease, lymphomatoid granulomatosis)

A detailed discussion of each of these other conditions is beyond the scope of this topic, but, in general, these diagnoses may be distinguished from sarcoidosis based on the clinical presentation, physical examination, and routine laboratory findings that demonstrate features characteristic of these other conditions (see appropriate topic reviews).

Other diagnoses that may mimic the presentation of sarcoid are discussed in detail elsewhere. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Differential diagnosis'.)

TREATMENT

Overall approach

Acute sarcoid arthritis — Acute sarcoid arthritis is generally self-limited. Therefore, short courses of antiinflammatory medications (eg, nonsteroidal antiinflammatory drugs [NSAIDs], glucocorticoids) are usually adequate to address symptoms until the disease resolves.

Rarely, patients with acute sarcoid arthritis may require other immunosuppressive agents, similar to the approach to treatment of chronic sarcoid arthritis.

Chronic sarcoid arthritis — For most patients with chronic sarcoid arthritis, pharmacotherapy is dictated by the extraarticular manifestations of sarcoidosis, which may require treatment with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or a tumor necrosis factor (TNF) inhibitor. These therapies are generally adequate to treat the joint disease [33].

For patients who lack such extraarticular manifestations, we use the approach outlined below (algorithm 3), which is based upon case reports, small uncontrolled studies, and our clinical experience [34-38]; there have been no well-designed randomized trials of treatments for the arthritis seen in these patients.

When applying this algorithm, it is important to assess the patient objectively to distinguish arthritis from the effects of fatigue, which patients may interpret as persistent, diffuse joint pain [39,40]. (See "Evaluation of the adult with polyarticular pain", section on 'Joint examination'.)

Pharmacotherapy

Initial therapy with an NSAID — We suggest initial therapy with an NSAID in antiinflammatory doses (eg, ibuprofen 600 to 800 mg three to four times daily or naproxen 375 to 500 mg twice daily) rather than glucocorticoids or other therapies.

Patients with both acute and chronic sarcoid arthritis may respond to treatment with NSAIDs alone. Because acute sarcoid arthritis is often self-limiting, these patients may not need prolonged NSAID therapy. Patients with chronic sarcoid arthritis may require longer courses of NSAID therapy for symptomatic relief.

Glucocorticoids for NSAID resistance — In patients with continued symptoms despite a trial of NSAID therapy for at least two weeks at antiinflammatory doses, we suggest oral glucocorticoid therapy (prednisone 10 to 20 mg orally once daily initially, then gradually tapered as tolerated over two to four weeks) rather than continued trials of different NSAIDs.

Adding sequential therapy for suboptimal response

Hydroxychloroquine — In patients with an inadequate response to glucocorticoids or who are unable to prevent flares of arthritis with tapering of glucocorticoids (flare with prednisone less than 7.5 mg daily), we add hydroxychloroquine (HCQ; up to 400 mg daily, not to exceed 5 mg/kg daily based upon actual body weight) [33,41,42].

In a retrospective case series of patients with sarcoidosis, 52.2 percent were able to taper completely off of glucocorticoids after treatment with HCQ 200 mg twice daily [43].

csDMARD — In patients who have continued symptoms of arthritis despite treatment for at least three months with prednisone plus HCQ, we add a conventional synthetic disease-modifying antirheumatic drug (csDMARD).

We start with low-dose MTX (7.5 to 15 mg once weekly). For those who do not respond, we increase to full-dose MTX (15 to 25 mg once weekly). Alternatively, we add leflunomide (10 to 20 mg once daily) to low-dose MTX in patients who cannot tolerate higher doses of MTX [44].

●Methotrexate – MTX is administered using the same regimen employed for rheumatoid arthritis (ie, maximum dose of 25 mg weekly, which may be given either orally or subcutaneously). The use and adverse effects of MTX are described in detail separately. (See "Use of methotrexate in the treatment of rheumatoid arthritis" and "Major adverse effects of low-dose methotrexate".)

The use of MTX for patients with sarcoid arthritis is supported by limited case series and our clinical experience [34,37,45].

●Leflunomide – We use leflunomide as an adjunctive or alternative DMARD when patients cannot tolerate MTX, using the same regimen employed for rheumatoid arthritis. The use and adverse effects of leflunomide are described in detail separately. (See "Pharmacology, dosing, and adverse effects of leflunomide in the treatment of rheumatoid arthritis".)

The use of leflunomide for patients with sarcoid arthritis is supported by our clinical experience, and case series demonstrating efficacy for other manifestations of sarcoidosis, including pulmonary, cutaneous, ocular, and sinonasal [44].

TNF inhibitor — In patients with an inadequate response to a csDMARD, we add infliximab (5 mg/kg administered by intravenous infusion every four to eight weeks) to the csDMARD. Infliximab is used in a similar fashion to that employed for the treatment of rheumatoid arthritis. For patients with refractory disease, the dose is titrated up to 10 mg/kg every four to eight weeks.

The administration and adverse effects of TNF inhibitors are described in detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects" and "Treatment of rheumatoid arthritis in adults resistant to initial conventional synthetic (nonbiologic) DMARD therapy".)

●Agent selection – We prefer infliximab because of a randomized clinical trial that suggested a response among patients with extrapulmonary manifestations of sarcoidosis, although this finding did not achieve statistical significance compared with the placebo group at week 24 (8 of 19 versus 0 of 8) [46]. Additionally, infliximab appeared to be effective in the treatment of some patients with resistant sarcoidosis in two randomized trials [47,48].

We avoid etanercept, which has not been useful in the treatment of sarcoid pulmonary [49] or eye disease [50]. However, there are a few case reports of benefit from etanercept in chronic sarcoid arthritis that was not responsive to conventional treatments [51,52]. There are no data supporting the use of other TNF inhibitors for the treatment of sarcoidosis. However, we have used adalimumab, given its similarity to infliximab.

●Caveats – Despite the possible benefit of anti-TNF agents in some patients with pulmonary or extrapulmonary sarcoidosis, the apparently paradoxical development of granulomatous pulmonary disease consistent with sarcoidosis has been reported as a rare complication of treatment with these agents for other conditions [53]. In most patients, there was resolution of both the symptoms and the radiographic findings following withdrawal of the drug. Whether TNF inhibitors can precipitate sarcoid-like reactions in patients with a known diagnosis of sarcoid is less clear. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Pulmonary disease'.)

The use of TNF inhibitors in pulmonary sarcoidosis is reviewed in detail separately. (See "Treatment of pulmonary sarcoidosis refractory to initial therapy", section on 'Tumor necrosis factor antagonists'.)

Synovectomy for refractory disease — In the very infrequent patient resistant to medical therapy, synovectomy is a treatment option. Because the diffuse synovitis observed in sarcoidosis does not appear to cause surface cartilage erosions, arthroscopic synovectomy is usually straightforward, and synovitis is recurrent only in joints where synovectomy is not complete [54]. (See "Synovectomy for inflammatory arthritis of the knee", section on 'Synovectomy'.)

Duration of therapy — We generally continue the effective treatment regimen (including the minimal dose of glucocorticoids required to maintain remission) for approximately one year before initiating a gradual taper of medications over the subsequent 6 to 12 months to the minimum effective dose.

Some patients may require only six to nine months of a stable regimen before beginning to taper, depending upon their clinical response to treatment. Treatment-refractory disease is rare. (See 'Synovectomy for refractory disease' above.)

The strategy we use is similar to the strategy used for tapering immunosuppression in patients with rheumatoid arthritis, which is discussed in detail elsewhere. (See "General principles and overview of management of rheumatoid arthritis in adults".)

PROGNOSIS — 

Acute and chronic sarcoid arthritis both have a good prognosis.

●Acute sarcoid arthritis – In patients who present with an acute sarcoid arthritis without Löfgren syndrome, the arthritis is typically self-limiting.

In patients who present with an acute sarcoid arthritis with Löfgren syndrome, the erythema nodosum typically disappears in a few months, but the joint symptoms may persist up to two years. Approximately one-third of patients have a more persistent arthritis [22]; rarely, the arthritic symptoms are recurrent [22]. Joint damage is generally not seen in acute sarcoid arthritis [21,31,55].

●Chronic sarcoid arthritis – Chronic sarcoid arthritis generally responds well to immunosuppression. Often, the choice of immunosuppression is dictated by the presence of extraarticular features of sarcoidosis, which is generally adequate to treat chronic sarcoid arthritis. The use of systemic immunosuppression for the management of sarcoidosis is discussed elsewhere. (See "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Other patients'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Approximately 10 percent of patients with sarcoidosis will have an acute arthritis, which most commonly presents in association with Löfgren syndrome. Chronic sarcoid arthritis is present in 0.2 to 2 percent of patients with sarcoidosis. (See 'Epidemiology' above.)

●Laboratory and imaging features – Synovial fluid in patients with arthritis is typically mildly inflammatory, with either neutrophilic or lymphocytic predominance. Plain radiographs may demonstrate cystic lesions or an "apple core deformity" associated with chronic, but not acute, sarcoid arthritis. Patients with acute sarcoid arthritis may have radiologic evidence of periarticular inflammation, but this is not specific. (See 'Laboratory and radiologic features' above.)

●Diagnosis

•Acute sarcoid arthritis – A diagnosis of acute sarcoid arthritis can be made clinically in patients presenting with Löfgren syndrome or a patient under 40 years who presents with an acute arthritis, including the ankles, in combination with hilar adenopathy. For other patients, the diagnosis of an acute sarcoid arthritis requires establishing a diagnosis of sarcoidosis and an inflammatory arthritis. Children with acute sarcoid arthritis generally have uveitis and rash but not hilar lymphadenopathy.

•Chronic sarcoid arthritis – A diagnosis of chronic sarcoid arthritis can be made in a patient with sarcoidosis and one of the characteristic manifestations of chronic sarcoid arthritis (eg, nondeforming arthritis with granulomatous synovitis, Jaccoud's type deformity of the hands, joint swelling adjacent to a sarcoid bone lesion, or dactylitis). For other presentations, this is a diagnosis of exclusion.

We do not use synovial biopsy to diagnose either acute or chronic sarcoid arthritis. (See 'Diagnosis' above.)

●Differential diagnosis – The differential diagnosis of sarcoid arthritis includes several rheumatic diseases, including reactive arthritis, crystalline arthritis, rheumatoid arthritis, and infectious mimics of pulmonary sarcoidosis that sometimes have associated joint manifestations (eg, Mycobacterium tuberculosis and Histoplasma capsulatum). (See 'Differential diagnosis' above.)

●Treatment – Treatment may be dictated by the presence of extraarticular manifestations of sarcoid, such as pulmonary disease, that may also require therapy (see 'Treatment' above). In patients who lack extraarticular disease that requires treatment, our approach is as follows (algorithm 3):

•In most patients with acute sarcoid arthritis, we suggest initial therapy with a nonsteroidal antiinflammatory drug (NSAID) in antiinflammatory doses rather than glucocorticoids or other therapies (Grade 2C). An NSAID (eg, ibuprofen 600 to 800 mg three to four times daily or naproxen 375 to 500 mg twice daily) is often sufficient to control symptoms. Additionally, acute sarcoid arthritis is usually self-limiting, precluding the need for prolonged therapy with NSAIDs in the majority of patients. (See 'Initial therapy with an NSAID' above.)

•In patients with an inadequate response to a trial of NSAID therapy for at least two weeks at antiinflammatory doses, we suggest oral glucocorticoid therapy rather than continued trials of different NSAIDs (Grade 2C). For example, prednisone could be initiated at 10 to 20 mg orally once daily, then gradually tapered as tolerated over two to four weeks. (See 'Glucocorticoids for NSAID resistance' above.)

•In patients with an inadequate response to glucocorticoids or who are unable to prevent flares of arthritis with tapering of glucocorticoids (eg, flare with prednisone less than 7.5 mg daily), we suggest adding hydroxychloroquine (HCQ) (Grade 2C). HCQ may be dosed up to 400 mg daily, not to exceed 5 mg/kg daily based upon real body weight. (See 'Hydroxychloroquine' above.)

•In patients with continued symptoms after another three months, we suggest adding low-dose methotrexate (MTX) 7.5 to 15 mg weekly (Grade 2C). If the patient is unable to taper prednisone to less than 5 to 7.5 mg daily, we increase MTX to 25 mg weekly. Alternatively, in patients who cannot tolerate higher doses of MTX, we suggest adding leflunomide 20 mg daily to low-dose MTX. (See 'csDMARD' above.)

•In patients with an inadequate response to a three-month trial of either MTX 25 mg weekly or MTX plus leflunomide, we suggest adding infliximab (Grade 2C). We use infliximab 5 mg/kg, administered by intravenous infusion every four to eight weeks. (See 'TNF inhibitor' above.)

●Prognosis – For patients presenting with acute sarcoid arthritis without Löfgren syndrome, the arthritis is typically self-limiting. Approximately one-third of patients presenting with an acute sarcoid arthritis with Löfgren syndrome will have a persistent arthritis. Chronic sarcoid arthritis generally responds well to immunosuppression.