Diagnostic Radiology/Musculoskeletal Imaging/Joint Disorders/Sarcoidosis

Sarcoidosis is an inflammatory disorder characterized by the formation of noncaseating granulomas in tissues without other known cause for granulomatous disease. The disease has a diversity of clinical manifestations, most commonly affecting the lungs, skin, lymph nodes, and eyes, but can involve any organ system, including the musculoskeletal system.

History
The first case of sarcoid was described by Jonathan Hutchinson over one hundred years ago at King's College Hospital in London. The first person to recognize bone involvement in sarcoidosis was Karl Kreibich in 1904. He found multiple radiolucencies, particularly in the distal end of the second phalanges, on the radiograph of a patient with sarcoid. After examining 60 histologic samples and not identifying any tubercule bacilli, he concluded that lupus pernio, the hallmark of chronic sarcoidosis and associated bone lesions, was a distinct granulomatous process unrelated to tuberculosis.

Epidemiology
The prevalence of sarcoid is estimated to be 10 to 20 per 100,000 people. Incidence varies among geographic regions as well as with ethnicity, with blacks having a three to four time increased risk compared to other ethnicities. In the United States, African Americans have a tenfold increased risk for sarcoid compared to Caucasians while Asians are rarely affected.

Clinical manifestations depend on ethnicity, chronicity of illness, site and extent of tissue involvement, and activity of the granulomatous process. African Americans are more likely to present acutely and to have more severe disease than Caucasians, who tend to present with asymptomatic and chronic disease.

Clinical Presentation
The disease presents between 20 and 40 years of age in 70 to 90 percent of patients. About one half of cases are diagnosed incidentally in asymptomatic patients by an abnormality on a routine chest radiograph. The most common organ system affected by sarcoid is the lung, with the most common presenting symptoms being cough, dyspnea, and chest pain. Patients may also suffer from fatigue, weight loss, weakness, malaise, fever, and ocular disease.

Musculoskeletal involvement usually occurs in patients with generalized disease. Affected patients may present with an acute polyarthritis (especially of the ankle joints), usually occurring in association with erythema nodosum and occasionally with acute uveitis. Involvement of muscle and bone is less common and usually indicates a chronic and prolonged clinical course.

Pathophysiology
The diagnosis of sarcoid is based on compatible clinical and radiographic findings, supportive laboratory data (elevated ACE levels, anergy, elevated serum gamma globulins, positive Kveim test), and evidence of noncaseating granulomas in the absence of other causes for such lesions.

The exact etiology and pathogenesis of sarcoid remains unknown. Several hypotheses exist regarding the involvement of bone in this disease, including:
 * high levels of 1,25(OH)2D3 causing stimulation of osteoclastic activity and bone resorption
 * granuloma induction of a local osteoclastic reaction
 * granuloma production of an osteoclastic activating factor inducing bone resorption

Joints
Joint symptoms and signs occur in 10 to 35 percent of patients with sarcoidosis and occur more frequently in women than in men. Articular disease in sarcoid can be divided into two types: acute and chronic polyarthritis.

The acute pattern is seen in the first six months of symptoms and has a self-limiting course, typically resolving in 4 to 6 weeks. The knees, ankles, elbows, PIP joints, and wrists are the most commonly affected joints. The arthralgia is thought to be due to the effect of inflammatory cytokines on the joints rather than direct granulomatous changes. Monoarthritis and effusion are uncommon. Conventional radiographs of symptomatic joints are usually unremarkable or show only osteoporosis and soft-tissue swelling. Sonographic findings include joint effusions, tenosynovitis, and subcutaneous inflammation. Patients may have elevated ESR and C reactive protein.

When the acute polyarthritis manifests as periarticular ankle inflammation in combination with erythema nodosum and mediastinal lymphadenopathy, the term Lofgren syndrome is given.

Six months or more after the diagnosis of sarcoid, up to 40% of patients may develop joint symptoms due to granulomatous arthritis. The granulomatous synovitis usually follows a chronic transient or relapsing course which may eventually lead to irreversible joint damage. Chronic polyarthritis is more common in women. Involved joints include the knees, ankles, PIP joints, and occasionally the wrists or shoulders. Dactylitis of the fingers may also be seen.

Unlike the acute form of polyarthritis, which is often seen with erythema nodosum, this arthritis is commonly associated with cutaneous sarcoid. Radiographic findings related to joint disease are unusual unless there is extension of osseous disease to subchondral bone. Mild joint space narrowing and erosions can be seen but are nonspecific findings.

Acute or chronic sarcoid arthropathy is a clinical diagnosis and MR imaging is usually not sought. However, MR imaging may be helpful for lesions that are not detected by conventional radiography. Tenosynovitis, tendonitis, bursitis, and synovitis can be seen on MR but are nonspecific findings and may require biopsy for diagnosis of granulomatous involvement.

Muscles
Sarcoid myopathy may demonstrate either myopathic or nodular type involvement. Discrete sarcoidal muscle lesions are reported in 1.4% of known sarcoidosis cases although muscle biopsies demonstrate skeletal muscle granulomas in 50-80% of sarcoidosis patients, usually in asymptomatic patients.

Nodular sarcoid myopathy has a characteristic MR appearance that allows accurate diagnosis. The sarcoid nodules appear as focal intramuscular masses, usually at the musculotendinous junction, are often multiple and bilateral in distribution, and have a lower extremity predominance. Their appearance is described as a "dark star" with central areas of fibrosis that have low signal intensity on all sequences and peripheral areas of bright signal intensity on T2WI and enhancement on post-contrast images (Moore, et al.).

In myopathic sarcoid myopathy, there are nonspecific findings of symmetric proximal muscle atrophy with fatty replacement and increased signal intensity of involved muscle on T2WI. Corticosteroid therapy may be a confounding factor in evaluating potential sarcoid muscle atrophy with the differentation based on clinical findings. MRI may be helpful in delineating the extent of fatty replacement and indicating an optimal location for muscle biopsy.

Bone
Reports of bone involvement in sarcoid have ranged between 1 and 13 percent, with an average of 5 percent. An accurate percentage is difficult to obtain as many skeletal lesions are asymptomatic, screening skeletal surveys are not routinely performed, and minor cystic bone changes can be seen in normal individuals.

The general pattern of osseous lesions is summarized below:
 * Distribution: often bilateral
 * Site of origin: cortical with preservation of periosteum
 * Location: most commonly the hands and feet, although the long bones, skull, vertebrae, pelvis, ribs, sternum, and calcaneus can rarely be affected
 * Position: usually at the ends of affected bones
 * Shape: cystic or lacelike with minimal involvement of adjacent soft tissues or extensive bone erosion with pathologic fracture
 * Calcification: absent

Radiologic Findings
Nuclear scintigraphic findings are usually positive before lesions can be seen on radiography. The radiographic manifestations of sarcoidosis vary with the region of the skeleton affected.

Small bone sarcoidosis
Lesions affecting the small bones of the hands and feet typically have a lytic or lacy reticular appearance on conventional radiographs. Lytic lesions are either minute cortical defects in the phalangeal heads or larger rounded punched-out lesions involving the cortex and medulla. The middle and distal phalanges are the most frequently involved. The lytic lesions likely represent an osteoporotic process producing local and destructive tunneling. The lacy reticular pattern is seen when the tunneling of the cortex is followed by remodeling of the cortical and trabecular architecture. The concave shape of the phalangeal shafts then becomes more tubular. There is often accompanied soft tissue swelling. More localized lytic lesions are also seen, forming cystic defects that may become surrounded by a thin rim of sclerosis as they heal.



Fig. 1 The lacy reticular pattern of bone loss is seen in the right hand of this patient afflicted with osseous sarcoid, particularly in the middle phalanx of the third digit and the proximal phalanx of the fifth digit. Note the preservation of joint spaces.



Fig. 2 The same lacy pattern is demonstrated in the left hand of the same patient. Note the subcortical tunneling in the middle phalanx of the fifth digit.



Fig. 3 A similar pattern of bone loss is seen in this radiograph of the wrist.

In an advanced sclerotic phase, a sequestrum may be seen. Fractures are rare but may occur with extensive lytic disease. Alignment deformities may result due to pathologic fractures with bone collapse rather than secondary to actual joint abnormalities.



Fig. 3 Extensive lytic lesions and subcortical tunneling. There is also acro-osteolysis of the distal phalanges of the third and fourth digits.

Lesions occult to plain radiography may be seen with MR imaging which may demonstrate bone marrow lesions, extension of granulomas beyond the cortex, periosseous soft tissue involvement, or fine perpendicular lines extending from the ghost cortex. Although MR imaging is not necessary for the diagnosis of small bone sarcoidosis, it may be helpful in certain clinical situations, such as differentiating the cause for dactylitis in a patient with sarcoid and gout.

Large Bone sarcoidosis
Detection of sarcoid lesions involving the long bones and axial skeleton is considered uncommon. Lesions may be painful or asymptomatic. Neither bone scintigraphy nor skeletal surveys have been found to be good screening studies for sarcoid lesions.


 * Radiographic images of sarcoid involving the long bones: Wilcox et al.: Bone sarcoidosis. Current Opinion in Rheumatology 2000, 12:321-330.

Large bone sarcoid lesions may be radiographically occult or seen as focal lytic lesions or sclerosis. On MR, the lesions may be indistinct or well-marginated and of varying sizes. The signal intensity characteristics are variable but the lesions typically have low intensity on T1WI, increased intensity on inversion-recovery, T2WI, and fat-saturated proton-density weighted images, and may enhance after contrast administration. Signal intensity is likely related to the activity of the disease process. There have been cases of resolution on follow-up studies with ghosts of the prior lesions having signal intensities consistent with fat or fibrosis.

Skull and Face
Calvarial lesions may be expansile and can be evaluated best with CT. MR may be used to assess for associated soft tissue involvement. Facial bone involvement usually reflects the presence of granulomatous disease in adjacent structures.


 * Radiographic images of sarcoid involving the petrous temporal bone: Ng, Matthew and John K. Niparko: Osseous sarcoidosis presenting as a destructive petrous apex lesion. American Journal of Otolaryngology 2002, 23:241-245.

Spine
Vertebral sarcoidosis is rare and may have a lytic, mixed lytic and sclerotic, or rarely, a predominantly sclerotic appearance. Lesions tend to affect the lower thoracic and upper lumbar spine with preservation of intervertebral disc spaces. Radiographic appearance may simulate osteomyelitis or tumor. Biopsy is often needed to establish a diagnosis.


 * Radiographic images of vertebral sarcoidosis: Rua-Figueroa et al.: Vertebral sarcoidosis: Clinical and Imaging Findings. Seminars in Arthritis and Rheumatism 2002, 31:436-352.

Treatment
Osseous sarcoid responds poorly to corticosteroids and other drugs used in treating sarcoid. Corticosteroids decrease pain and soft tissue swelling but do not completely normalize bone abnormalities and increase the risk of osteoporosis, fractures, and avascular necrosis. Colchicine, indomethacin, and other NSAIDs may be used for symptomatic relief.