What is the differential diagnosis for a 40-year-old female with Systemic Lupus Erythematosus (SLE) presenting with moderate left upper limb and shoulder pain without recent trauma?

Differential Diagnosis for Left Upper Limb and Shoulder Pain in a 40-Year-Old Female with SLE

In a 40-year-old woman with SLE presenting with moderate left shoulder and upper limb pain without trauma, the differential diagnosis must prioritize SLE-related musculoskeletal manifestations (inflammatory arthritis, avascular necrosis), followed by age-appropriate rotator cuff pathology, and critically exclude infection given her immunocompromised state.

SLE-Specific Musculoskeletal Manifestations (Primary Considerations)

Lupus Arthritis/Arthropathy

• Joint involvement is one of the most common manifestations of SLE, occurring in the majority of patients 1
• Lupus arthritis typically presents with pain and swelling without joint warmth, distinguishing it from septic arthritis 1
• The arthritis is usually non-erosive but can cause significant pain and functional limitation 2
• Check for polyarticular involvement, as lupus arthritis rarely affects isolated joints 3

Avascular Necrosis (AVN)

• AVN is a recognized complication of SLE and represents a major cause of morbidity, particularly in patients on corticosteroid therapy 4
• The shoulder (humeral head) is a common site for AVN after the hip 4
• Consider this diagnosis especially if the patient has been on long-term glucocorticoid therapy 4
• Pain is typically insidious and progressive, worsening with activity 4

Lupus Myositis

• Muscle inflammation can cause proximal upper limb pain and weakness 2
• Assess for muscle tenderness and weakness on examination 3
• Check creatine kinase levels to evaluate for active myositis 3

Age-Appropriate Degenerative/Mechanical Causes

Rotator Cuff Pathology

• In patients over 35-40 years, rotator cuff disease and degenerative changes are predominant causes of shoulder pain 5, 6
• Even without acute trauma, chronic rotator cuff tears can develop from repetitive microtrauma 7
• Clinical features include pain with overhead activities, weakness on empty can test, and positive impingement signs 7
• SLE patients may have increased susceptibility to tendon pathology due to chronic inflammation 2

Adhesive Capsulitis (Frozen Shoulder)

• More common in patients with autoimmune conditions 7
• Presents with diffuse shoulder pain and restricted passive range of motion on examination 7
• Progressive loss of motion in all planes distinguishes this from rotator cuff disease 7

Critical Exclusions (High Morbidity/Mortality Risk)

Septic Arthritis

• SLE patients have an almost 5-fold increased risk of death compared to the general population, with infections being a common cause of mortality 4
• Immunosuppressive therapy increases infection risk substantially 2
• Requires immediate specialist referral if suspected 6
• Look for fever, acute onset of severe pain, joint warmth, and systemic symptoms 5, 6
• Low threshold for joint aspiration is essential given the catastrophic consequences of missed diagnosis 6

Neuropsychiatric Lupus (Peripheral Neuropathy)

• Neurological manifestations occur frequently in SLE patients and may involve peripheral/cranial neuropathy 4
• Assess for numbness, tingling, weakness, or radiation of pain down the arm 5
• Peripheral neuropathy can present as limb pain with or without sensory deficits 4

Additional Considerations Based on SLE Comorbidities

Osteoporotic Fracture

• SLE patients are at increased risk for osteoporosis, particularly those on long-term glucocorticoid therapy 4
• Do not assume absence of trauma means absence of fracture, as osteoporotic fractures can occur with minimal or unrecognized trauma 5, 6
• Proximal humerus fractures can present with shoulder pain and limited motion 6

Cardiovascular-Related Pain

• SLE patients have increased risk for coronary heart disease and atherosclerosis 4
• Consider referred cardiac pain, especially if pain radiates to left arm 4
• Assess for cardiovascular risk factors and associated symptoms 4

Diagnostic Approach Algorithm

Initial Clinical Assessment

• Document pain characteristics precisely: anterior shoulder suggests rotator cuff; superior shoulder indicates acromioclavicular joint; scapular region may indicate referred pain 5
• Assess for systemic symptoms (fever, constitutional symptoms) that suggest infection or active lupus flare 5, 6
• Evaluate passive and active range of motion to distinguish adhesive capsulitis from rotator cuff disease 7
• Screen for neurological symptoms including numbness, tingling, weakness 5

Laboratory Evaluation

• ESR and CRP should be performed at baseline for diagnosis and prognosis 4
• Check lupus disease activity markers (anti-dsDNA, complement levels) to assess for active disease 4, 2
• Obtain complete blood count to evaluate for cytopenia associated with active SLE 2
• Consider creatine kinase if myositis is suspected 3

Imaging Strategy

• Standard radiography is the mandatory first step, including AP views in internal and external rotation, and axillary or scapular Y view 5, 6
• Plain radiographs can identify fractures, AVN (in advanced stages), and arthritis 6, 7
• MRI without contrast is the preferred advanced imaging for evaluating rotator cuff pathology, occult fractures, AVN, and soft tissue structures 6, 7
• MRI is superior to CT for diagnosing AVN in early stages and all soft-tissue shoulder injuries 6

Critical Pitfalls to Avoid

• Never dismiss the possibility of septic arthritis in an immunosuppressed SLE patient, even with moderate symptoms 4, 6
• Do not overlook AVN, particularly in patients with any history of corticosteroid use 4
• Recognize that lupus arthritis typically lacks joint warmth despite significant pain and swelling 1
• Consider that persistent disease activity is a major contributor to organ damage in SLE 8
• Remember that no single test can differentiate neuropsychiatric lupus from other causes; combination testing is required 4