Musculoskeletal Sarcoidosis

Background and Evaluation

• Sarcoidosis is a systemic disease of unknown cause characterized by formation of immune granulomas in any organ, most commonly lungs and intrathoracic lymph nodes.
• Musculoskeletal manifestations of sarcoidosis include arthropathy, myopathy, and bone involvement
  • reported incidence of musculoskeletal sarcoidosis ranges widely from 3% to 39%
  • musculoskeletal symptoms reported to be present at the time of initial diagnosis in only about 7% of patients.
• Up to 12% of patients are reported to have arthropathy.
  • There are 3 distinct clinical presentations of arthropathy in patients with sarcoidosis
    • Lofgren Syndrome, which develops during initial 6 months after diagnosis of sarcoidosis
      • in women, erythema nodosum is specifically observed
      • in men, periarticular inflammation around ankles or true ankle arthritis without erythema nodosum is more commonly observed
      • in children, bilateral uveitis and arthritis is typical (similar to juvenile idiopathic arthritis)
    • Acute arthropathy, which can be the initial and sole manifestation of sarcoidosis, presenting as arthralgia and periarthritis
      • nearly all joints can be affected, particularly medium sized joints of lower extremities
      • most common pattern of sarcoid arthropathy is oligoarthritis with bilateral involvement of ankle joints
    • Chronic arthropathy, which is the least common, and may present as oligo- or polyarticular joint disease, often with other sarcoidosis affecting other organs.

• Up to 50% of patients are reported to have skeletal muscle involvement, but < 3% are reported to be symptomatic
  • Muscle weakness, pain, or nodules are indicative of sarcoid myopathy.
  • There are 3 distinct patterns of muscular involvement
    • Chronic myopathy (most common) characterized by insidious onset of symmetrical proximal muscle weakness (trunk and neck muscles may be involved):
      • normal levels of muscle enzymes typical
      • myopathic changes may be seen on neurophysiology studies, comparable to other muscular disorders.
    • Nodular myopathy characterized by palpable nodes in the muscle(s), most commonly symmetric in the lower extremities, which are often painful:
      • normal levels of muscle enzymes typically present
      • neurophysiology studies typically normal.
    • Acute myopathy (least common) characterized by rapid onset of proximal muscle weakness and myalgia (similar other inflammatory myopathies):
    • elevated levels of creatinine kinase
    • noncaseating granulomas with pronounced lymphocytic infiltration on muscle biopsy.

• Between 1% and 15% of patients are reported to have bone involvement.
  • Often associated with chronic and severe forms of sarcoidosis with concomitant hepatic, lymph node, and/or extrathoracic involvement
  • Commonly asymptomatic (often detected incidentally), but symptoms may include:
    • pain
    • limited exercise capacity
    • numbness
    • swelling or deformity of fingers (most common peripheral involvement).
  • Asymmetric small bone disease of hands and feet is often present, and may be unilateral or bilateral.
  • Axial bones may also be affected.
  • Serum calcium and alkaline phosphatase levels are typically normal.
  • 3 distinct patterns of bone lesion include:
    • permeative ("moth-eaten") lesions involving cortex of phalanges
    • lytic lesions (also called bone cysts) appear as cortical defects in heads of phalanges or round punch-out lesions
    • sclerotic lesions typically found in spine and appear similar to lesions seen in metastatic disease.
  • Bone involvement is commonly associated with overlying skin disease.

• Management considerations based on clinical presentation of arthropathy:

• • in patients with Lofgren syndrome, colchicine and hydroxychloroquine are often used
    
  • most cases of acute polyarthritis will resolve spontaneously, although steroids may be useful if needed
  • in patients with chronic arthropathy, treatment with immunosuppressive drugs is typically required.

• Corticosteroids typically used and treatment regimens are often similar to those used to manage other inflammatory myopathies, although increased rate of relapse reported.
• Consensus is lacking on optimal treatment of symptomatic sarcoid bone disease.