Differential diagnosis of musculoskeletal involvement in rheumatoid arthritis, sle, and systemic scleroderma

Bone, muscle, and joints involvement in rheumatoid arthritis, systemic lupus, and systemic scleroderma

1. Differential diagnosis of joint, muscle and bone involvement in rheumatoid arthritis , systemic lupus erythematous, and systemic scleroderma

2. Overview Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that affects many organs but more predominantly synovial tissue and joints, manifesting with symmetric , inflammatory, peripheral polyarthritis. It typically leads to deformity and destruction of joints through the erosion of cartilage and bone . Arthritis symptoms typically first develop in the hands and wrists in a symmetric, proximal distribution. Feet and large joints may also be involved. Epidemiology : overall world prevalence is approx. 1%. With a female to male ratio of 3:1, ages 30-50 Pathogenesis : IgM autoantibodies to FC portion of IgG, forming immune complexes which deposit in joints resulting in inflammation. Clinical features : Musculoskeletal pain which decreases with activity, tenderness, swelling, subcutaneous nodules, morning stiffness >30minutes Polyarthritis of MCP and PIP joints, but it commonly does NOT involve DIP joints. Wrists, elbows, ankles, knees also commonly are involved. Persistent symmetric polyarthritis (synovitis) of hands and feet (hallmark feature ) affected joints show inflammation with swelling, tenderness, warmth, and decreased range of motion (ROM).  Joint and tendon destruction may lead to deformities such as ulnar deviation,  boutonniere and swan neck deformities,   hammertoes, and occasionally, joint ankylosis . Other commonly observed manifestations: tenosynovitis, periarticular osteoporosis, carpal tunnel syndrome, generalized osteoporosis

3. The radiographic hallmarks of rheumatoid arthritis are: erosions; important early finding, frequently in the radial side of the metacarpophalangeal (MCP) joints  Soft tissue swelling: fusiform and periarticular; represents a combination of joint effusion, edema, and tenosynovitis. This can be an early/only radiological finding. Osteoporosis; initially juxta-articular and later generalized Symmetrical or concentric joint space narrowing Hands and Wrists Involvement The disease tends to affect the proximal joints in a bilateral, symmetrical distribution. PIP and MCP joints (specially 2 nd and 3 rd MCP) Ulnar styloid Triquetrum DIP joints are spared

4. Late changes include: Subchondral cyst Subluxation causing: a) ulnar deviation of MCP joints, b) boutonniere and swan neck deformities Hitchhiker’s thumb deformity Carpal instability, ulnar translocation Anykylosis Scallop sign; erosion of ulnar aspect of distal radius   Feet similar to the hands, there is a predilection for the PIP and MTP joints (specially 4 th  and 5 th   MTP) Involvement of subtalar joint Hammertoe deformity Hallux valgus

5. Knee Joint effusion Typically involves lateral or non-weight bearing portion of the joint Loss of joint space involving all three compartments Prepatellar bursitis Hip Concentric loss of joint space Acetabular protrusio Shoulder Erosion of distal clavicle, marginal erosions of humeral head, reduction in acromiohumeral distance “high-riding shoulder” due to subacromial-subdeltoid bursitis Spine Cervical spine is more frequently involved in RA, thoracic and lumbar involvement is rare. Findings include: erosions, atlantoaxial subluxation

6. Diagnosis of RA is based on the diagnostic criteria developed by American college of rheumatology 2010. A total score of 6+ is classified as rheumatoid arthritis. Investigations include: CPR and ESR (elevated) Serological markers: RF, anti-CCP, ACPA Radiography: erosions, swelling of soft tissue, joint narrowing, juxtoarticular osteoporosis Ultrasound: assess synovial proliferation and inflammation of superficial joints, tenosynovitis, bursitis MRI: sensitive to early and subtle features of RA

7. Advanced RA

8. Typical changes in RA, MCP osteopenia, marked erosions

9. Degenerative changes with marked erosions

10. Scallop sign

11. SLE Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune inflammatory disease that can affect any part of the body. SLE is a disease of unknown aetiology with a variety of presenting features and manifestations . Characterized by microvascular inflammation with the generation of numerous autoantibodies, particularly antinuclear antibodies (ANA) The majority of the pathology in SLE is related to deposits of immune complexes in various organs, which triggers complement and other mediators of inflammation Diagnosis can be difficult because lupus mimics many other diseases; it requires clinical and serologic criteria . Epidemiology Female:Male 10:1 Peak in 20s-30s More common in black patients

12. Musculoskeletal manifestations: joint pain, with small joints of the hand and wrist usually affected. Arthralgia, arthritis, osteonecrosis (avascular necrosis of bone), and myopathy are the principal manifestations. Arthralgia, myalgia, and frank arthritis may involve the small joints of the hands, wrists, and knees  In contrast to rheumatoid arthritis, SLE arthritis or arthralgia may be asymmetrical, with pain that is disproportionate to swelling . Also the arthritis and arthralgia of SLE tend to be migratory, morning stiffness is usually measured in minutes. The arthritis of SLE is generally considered to be non-deforming . Involves joint space loss, subchondral sclerosis, osteophyte, and ulnar deviation of the phalanges without erosions such as in RA Diagnosis is based on SLICC Classification Criteria 2012 . Requirements: >4 of the following criteria (at least 1 clinical and 1 laboratory)  OR  biopsy proven lupus nephritis with positive ANA or Anti-dsDNA

13. Clinical criteria Malar  rash bullous lupus, photosensitivity Discoid rash, hypertrophic lupus Oral ulcers or nasal ulcers Non-scarring alopecia Synovitis Serositis Nephritis Cerebritis , myelitis, neuropathy Hemolytic anemia leukopenia  or lymphopenia Thrombocytopenia Immunological criteria ANA Anti-dsDNA Anti-Sm Antiphospholipid antibody Low complement C3, low C4 Direct Coombs' test in the absence of haemolytic anaemia

14. Musculoskeletal manifestations Symmetric polyarthritis: represents the most common presenting complaint clinically. Usully worse in the morning. Areas of involvement most commonly are the small joints of hands, wrists (PIP, MCP), knees, and shoulders Tenderness, edema, and effusions accompany a polyarthritis that is symmetric, nonerosive , and usually nondeforming . Characteristic hand deformities are swan neck deformities that result from recurrent synovitis and inflammation of the joint capsule, tendons, and ligaments. These deformities are usually reducible and nonerosive . Deforming non-erosive arthropathy : due to ligamentous laxity and muscle contracture, not articular destruction. More common in long-standing disease. Non-erosive arthritis involving two or more joints can be diagnostic. The presence of deformities without erosions differentiates it from rheumatoid arthritis. It develops approx. in 5-40% of patients when articular abnormalities are present. Myositis: clinically observed in 30-50% of patients. Jaccoud arthropathy is the term used to describe the nonerosive hand deformities due to chronic arthritis and tendonitis that develop in 10% of patients with SLE. The most common radiographic anomalies in SLE are periarticular osteopenia and soft-tissue swelling without erosions. Radiographic features Demonstrates soft tissue swelling of the involved joints(interphalangeal joints is most common), periarticular osteoporosis, and normal joint spaces. Carpal instability may be seen in 15% of patients  Osteonecrosis – most common location is femoral head – manifests as focal pain Calcifications linear or nodular calcification in the subcutaneous and deep soft tissues may be seen, specially around small joints of extremities. Stress fractures Osteomyelitis and septic arthritis

15. Tendinopathies: include tenosynovitis, bursitis, spontaneous tendon weakening and eventually rupture, more affecting weight-bearing joints as a complication of steroid therapy. Imaging features also include capsular swelling, edematous and proliferative tenosynovitis and synovial hypertrophy Subcutaneous nodules: particularly over flexor tendons of the hands Diagnosis is based on clinical presentation, ANA screening, imaging findings, ACR diagnostic criteria, and lab tests including: CBC, antiphospholipid antibodies, anti-dsDNA, and anti-Sm antibodies, ESR(elevated), CPR (normal in flare ups). Treatment Hydroxychloroquine is recommended in all patients NSAIDS to manage arthralgia Corticosteroids, dose depends on severity, but they are given for short time to minimize side effects Methotrexate and azathioprine should be considered in case of poor symptom control after a trial of corticosteroids and hydroxychloroquine.

16. Scleroderma systemic Scleroderma is an autoimmune connective tissue disorder characterized by multisystem fibrosis and soft tissue calcification. There are two primary types of scleroderma: localized and systemic (also called systemic sclerosis ). The disease is characterized by widespread deposition of collagen and other extracellular matrix proteins. O ccurs as a result of an abnormal immune response. Small vessels are involved early in the disease, accounting for the involvement of organs with a dense capillary network. This results in perivascular fibrosis and gradual luminal stenosis. Raynaud phenomenon occurs in almost all patients with systemic sclerosis Musculoskeletal Manifestations Scleroderma may affect joints (arthritis, arthralgia), tendons (rubs, tenosynovitis) and muscles (myalgia, weakness, more rarely myositis). Friction tendon rubs, seen on the hands, knees, and ankles, indicate a poor prognosis. Digital retractions in flexion due to skin sclerosis and calcinosis, lead to major functional disorders. Limitation of movement, and joint swelling may be present. Systemic sclerosis begins as joint pain in 15% of patients. It begins as inflammatory myopathy in 10% of patients. Weakness is present in 80% of patients

17. ACR diagnostic criteria for systemic sclerosis

18. Musculoskeletal features Phalangeal changes consisting of bone absorption, skin atrophy, and soft tissue calcification. These features are classic, and their presence alone should suggest the correct diagnosis. In some cases however the joint changes predominate. The wrist is frequently involved. The interphalangeal joints are also affected but to a lesser degree and in an asymmetric manner . The presence of soft tissue calcification is extremely important. It’s rarely seen in rheumatoid arthritis or SLE. When identified, soft tissue calcification is therefore considered diagnostic for scleroderma and in some patients is the only differential feature.

19. Musculoskeletal manifestations Radiographic features Bone changes Acro- osteolysis (resorption of the distal phalanges) Periarticular osteopenia Joint space narrowing Erosions Severe resorption of the first CMC joint with radial subluxation is a characteristic feature on hands radiographs Soft tissue changes Subcutaneous and periarticular calcification Atrophy, specially at tips of fingers Flexion contractures

20. Other less common documented musculoskeletal findings: rib resorption (bilateral superior rib notching, predominantly along posterior surface), mandibular angle resorption (+/- loss of lamina dura), radius and ulnar resorption Terminal phalangeal sclerosis Serological markers Elevated ESR RF – positive in 30-40% of patients Antinuclear antibodies – 35-95% of patients Anti SCL-70: positive in 30-70% of patients, particularly in limited disease Anti-centromere antibodies (20-40% of patients, in limited disease particularly)

21. Musculoskeletal symptoms treatment Carpal tunnel syndrome symptoms may require local corticosteroid injections although frequently these symptoms resolve spontaneously. Myositis may be treated cautiously with steroids (first choice), or with methotrexate or azathioprine in corticosteroid-resistant cases or when there are contraindications to corticosteroid use. Doses of prednisone greater than 40 mg/d are associated with a higher incidence of scleroderma-associated renal crisis. Arthralgia’s can be treated with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).

22. Acro- osteolysis and soft tissue calcifications

23. Multiple soft tissue calcifications, joints destruction, ankyloses of 2 nd finger DIP.

24. Calcifications of subcutaneous tissue

25. Extensive soft tissue calcifications and osteoporosis

26. Bibliographies www.medscape.com www.ncbi.nlm.nih.gov radiopaedia.org www.aafp.org wikem.org www.uptodate.com sclerodermanews.com