Differential Diagnosis of Complex Regional Pain Syndrome
The differential diagnosis of CRPS requires systematic exclusion of alternative conditions through comprehensive history, physical examination, and targeted diagnostic testing, as CRPS remains a diagnosis of exclusion. 1, 2
Key Diagnostic Approach
Begin by documenting the chronology and symptomatology of pain onset, specifically noting whether pain is disproportionate to the initial trauma and whether it has persisted beyond expected tissue healing timeframes. 1 The pain history must include onset, quality, intensity, distribution, duration, and course, with particular attention to exacerbating and relieving factors. 1
Critical Historical Features to Document
- History of preceding trauma or surgery occurring 4-6 weeks prior to symptom onset, as CRPS typically develops within this timeframe following direct injury. 3
- Progressive pain that gradually increases in intensity and spreads within the affected limb, sometimes extending to the contralateral limb. 2, 4
- Pain characteristics described as excruciating, burning, and worsened by touch or stimulation, distinguishing CRPS from other pain syndromes. 2, 4
- Duration of symptoms for at least 12 months to classify as chronic CRPS, as this temporal distinction affects diagnostic criteria and treatment approach. 2, 5
Physical Examination Findings Specific to CRPS
The physical examination must include appropriately directed neurologic and musculoskeletal evaluation with attention to asymmetric limb findings. 1, 5
- Sensory abnormalities including allodynia (pain from non-painful stimuli) and hyperalgesia (exaggerated pain response) are hallmark features that distinguish CRPS from other conditions. 2, 6
- Autonomic dysfunction manifesting as temperature dysregulation, skin color changes, and abnormal sweating patterns in the affected limb. 2, 6
- Motor impairment including functional limb weakness and decreased active range of motion that is disproportionate to the initial injury. 2, 6
- Trophic changes such as hair loss, tissue changes, and skin discoloration particularly in chronic cases. 2, 4
Conditions to Exclude in the Differential
Musculoskeletal Disorders
- Facet joint pain, intervertebral disc pathology, or muscle/fascial pain represent the majority of nontraumatic cervical or neck pain and must be distinguished from CRPS. 1
- Inflammatory arthritis, ankylosing spondylitis, or diffuse idiopathic skeletal hyperostosis should be considered, particularly with systemic symptoms. 1
Neurologic Conditions
- Peripheral neuropathy from diabetes or multiple sclerosis, which can present with neuropathic pain but typically follows a different distribution pattern. 1
- Cervical radiculopathy or myelopathy, which may present with upper extremity pain but follows dermatomal patterns. 1
- Post-traumatic nerve injury (distinguishes CRPS Type II from Type I), requiring documentation through clinical examination or diagnostic testing. 2
Vascular and Infectious Etiologies
- Vascular insufficiency or thrombosis, which can cause limb pain and color changes but with different temporal patterns. 1
- Infection including osteomyelitis or soft tissue infection, particularly in patients with history of intravenous drug use or recent surgery. 1
- Malignancy or tumor involvement, especially with intractable pain or constitutional symptoms. 1
Psychiatric and Functional Disorders
- Generalized nociplastic pain syndromes including fibromyalgia, which must be differentiated as CRPS is a regional, not generalized, condition. 5
- Somatoform disorders or conversion disorder, though psychological factors may coexist with CRPS. 7
Diagnostic Testing Strategy
Primary Diagnostic Modality
Three-phase bone scintigraphy is the most useful imaging modality for CRPS, with pooled sensitivity of 78% and specificity of 88%. 2 This test demonstrates increased periarticular uptake in affected limbs and can help confirm the diagnosis when clinical presentation is equivocal.
Supplementary Imaging
- MRI has higher specificity (91%) but lower sensitivity (35%) for CRPS-I, making it unsuitable as a screening test but useful for excluding alternative diagnoses such as occult fracture, osteomyelitis, or tumor. 2
- High-resolution ultrasound and MRI may be particularly useful in suspected CRPS Type II to directly visualize nerve pathology and detect signs of muscle denervation. 2
Emerging Objective Tools
- Quantitative sensory testing (QST), skin biopsy for intraepidermal nerve fiber density (IENFD), functional MRI, and serum biomarkers of neuroinflammation may support diagnosis in complex or uncertain cases. 5
Critical Diagnostic Pitfalls to Avoid
CRPS does not demonstrate a placebo response except at very early time points (15-30 minutes), distinguishing it from other pain syndromes. 2, 4 This characteristic can help differentiate CRPS from functional or somatoform disorders during diagnostic nerve blocks.
- Failing to recognize that CRPS is a diagnosis of exclusion leads to premature diagnosis without adequate evaluation for alternative conditions. 5
- Not documenting the temporal relationship between trauma and symptom onset obscures the typical 4-6 week latency period characteristic of CRPS. 3
- Overlooking the requirement for symptoms in at least three of four categories (sensory, vasomotor, sudomotor/edema, motor/trophic) according to Budapest Criteria. 5
- Misinterpreting normal imaging as excluding CRPS, since diagnosis is primarily clinical and imaging serves to exclude alternative diagnoses. 2
Psychosocial Evaluation Component
The psychosocial evaluation should include assessment of anxiety, depression, anger, psychiatric disorders, and coping mechanisms, as these factors influence treatment success and may coexist with CRPS. 1 Document the impact on activities of daily living, sleep, interpersonal relationships, and vocational function. 1 Note any history of depression or post-traumatic stress disorder, as some association with CRPS diagnosis has been demonstrated. 7