Complex Regional Pain Syndromes Workup

Updated: Jun 20, 2018
  • Author: Gaurav Gupta, MD, FAANS, FACS; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Laboratory Studies

No specific diagnostic tests confirm the presence of CRPS. However, the differential diagnosis includes other neuropathic conditions, as well as a host of metabolic, systemic, vascular, and rheumatological disorders. Excluding other treatable but serious causes is indicated even in cases that present with the classic signs and symptoms.

  • Blood work for inflammatory arthropathy and vasculitis is indicated, which, in its basic form, includes complete blood count (CBC), erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, rheumatoid factor, complement fixation panel, serum immunoelectrophoresis, and a bone scan. Workup for diabetes should also include a test for hemoglobin A1c.

  • Electromyography (EMG) and nerve conduction studies are helpful in determining the neuroanatomy behind the symptoms and therefore in identifying the etiological process. For example, they confirm the presence of nerve injury, CRPS type II, nerve root avulsion, or a painful neuropathy due to diabetes, which may present with autonomic dysfunction.

  • Vascular studies of the affected limb(s) should also be considered.


Imaging Studies

Osseous changes are common in CRPS; therefore, most standard diagnostic test results used to support or refute clinical evidence for this diagnosis demonstrate changes, or a lack thereof, in the bones and joints.


In the chronic stages of CRPS, plain radiographs may reveal endosteal and intracortical excavation, resorption of subperiosteal and trabecular bone, localized bone demineralization, and/or osteoporosis. [59]

Bone scintigraphy

See the list below:

  • Compared with radiography, 3-phase bone scintigraphy has higher sensitivity (97% vs 73%) and specificity (86% vs 57%) in early postfracture CRPS. [60]

  • 3-phase bone scintigraphy can provide valuable information during the first year and is useful in differentiating CRPS from other pain syndromes. [61] Homogeneous unilateral hypoperfusion in the perfusion and blood-pool phases is considered characteristic of CRPS and repudiates osteoporosis due to inactivity. These 2 initial phases are seen at 30 seconds and 2 minutes postinjection, respectively. At 3 hours postinjection, the mineralization phase shows increased unilateral periarticular uptake. This pathological uptake is thought to be highly sensitive and specific to CRPS. [60, 62] On the other hand, scintigraphy only shows significant changes during the first year. Additionally, this test is less valuable in children than in adults due to its higher variability. [63]

Magnetic resonance imaging (MRI)

MRI scans have demonstrated changes in joints (joint effusion) and soft tissues with CRPS with high sensitivity but less specificity. [64]


Other Tests

Quantitative sensory testing

Bedside testing for allodynia and hyperalgesia is important to remove subjectivity from the sensory portion of the examination when confirming the diagnosis of CRPS. Detailed sensory testing can document impairment of warm and cold sensations; heat pain; static, dynamic, and pinprick allodynia; heat and mechanical hyperalgesia; and temporal summation. [65, 66]

Autonomic function testing (AFT)

AFT includes infrared thermometry, infrared thermography, quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), and laser Doppler flowmetry. Skin temperature differences can be easily assessed by infrared thermometry or thermography. [67] Currently, a characteristic sensory pattern has not been identified. Such a pattern would allow clinicians to determine the presence of CRPS and quantify the individual signs of each patient so that responses to successful treatments can be measured and documented. Caution is necessary with AFT since autonomic differences are dependent on environmental conditions that can alter pertinent test dynamics within minutes. Therefore, measurements should be repeated at the beginning, middle, and end of a patient visit.

In a study of 21 patients with CRPS, enhanced sudomotor output was demonstrated with QSART and TST in the affected limb compared with the contralateral limb within the mean disease duration of 5 weeks. [68] At a mean duration of 94 weeks, TST findings remained abnormal, whereas QSART showed no differences from healthy subjects.

In a study using laser Doppler flowmetry to assess vascular reflex responses, 3 different vascular regulation patterns were demonstrated in CRPS type I. With short-term CRPS (ie, with a mean duration of 4 mo), the affected limb showed higher perfusion than the contralateral limb. In patients with a mean CRPS duration of 15 months, the affected limb showed either higher or lower skin perfusion than the contralateral limb. Finally, in patients with a mean CRPS duration of greater than 20 months, the affected limb showed lower perfusion of the skin. Skin temperature changed correspondingly for each pattern. [27]

Neurogenic inflammation

In the fluid of artificially produced blisters, significantly higher levels of proinflammatory mediators and vasoactive substances, such as interleukin-6, tumor necrosis factor-alpha, tryptase, and endothelin-1, were observed in the affected extremities of patients with CRPS type I compared to the uninvolved extremities. Also, nitrate/nitrite levels have been shown to be reduced. [69, 70, 71] Findings such as these may lead to diagnostic tools in the future. However, a direct relationship between the signs and symptoms of CRPS type I and these proinflammatory mediators cannot be assumed because these findings are still in evidence after the CRPS improves. [72]

Skin biopsies

One hypothesis is that CRPS type I is caused by persistent minimal nerve injury, particularly distal degeneration of the small-diameter axons. [73] This theory was investigated in studies where quantitative mechanical and thermal sensory testing was performed, followed by quantification analysis of epidermal neuritic densities and skin biopsies. Axonal densities were diminished at CRPS-affected sites in 17 of 18 patients by an average of 29%. Control subjects had no painful-site neurite reductions; however, the relationship of these findings to distinct pathophysiological mechanisms remains unclear. [74]

Muscle biopsies

Skeletal muscles in the affected extremities demonstrate (1) a decrease in type 1 fibers, (2) an increase in lipofuscin pigment, (3) atrophic fibers with a slight angular appearance, and (4) severely thickened basal membrane layers in the capillaries.

Peripheral nerve biopsies

In the affected extremities, efferent nerve fibers are unchanged histologically; with afferent fibers, only C fibers have demonstrated histopathological abnormalities, which consist of denervation of the Schwann cell stacks, miniature axon sprouts, and an obvious increase in collagen pockets. C-fiber loss may be noted as well. Sometimes, multiple basal membranes surround the small endoneural vessels.