Algodystrophy (Complex Regional Pain Syndrome)

Definition, Etiology, PathogenesisTop

Complex regional pain syndrome (CRPS) type 1 is also termed algodystrophy, Sudeck atrophy, reflex sympathetic dystrophy, shoulder-hand syndrome, posttraumatic dystrophy, or posttraumatic osteoporosis.

CRPS is characterized by pain, perfusion abnormalities, atrophic changes, and functional impairment, which usually develop in response to a noxious stimulus. It mainly affects the limbs, involving areas that extend beyond those innervated by a single nerve. Unlike in CRPS type 2 (previously labeled causalgia), peripheral nerve injury is not part of the process.

The severity of symptoms is substantially higher than the strength of the stimulus would suggest. CRPS can manifest at any age (including childhood). CRPS tends to occur more frequently in women than in men.

Common triggers include:

1) Trauma (in up to 70% of patients; eg, in a third of patients following a Colles fracture).

2) Invasive procedures (eg, carpal tunnel release, arthroscopy, spine surgery).

3) Internal diseases (eg, myocardial infarction, pulmonary tuberculosis, cancer, pulmonary fibrosis).

4) Stroke or other brain injury with hemiplegia.

It may also be idiopathic (~20% of patients). The pathogenesis of CRPS remains unclear.

Clinical Features and Natural HistoryTop

In most cases CRPS involves the wrists, while the knees, ankles, and feet are less common locations. An entire limb (shoulder-hand or hip-foot syndromes) or the face or trunk can sometimes be affected. The involvement is usually asymmetric; in patients with bilateral disease changes in the contralateral limb develop as the condition progresses.

Common symptoms include:

1) Severe, chronic, burning pain outside the area of trauma (not affecting muscles or joints).

2) Excessive sensitivity to mechanical, thermal, and painful stimuli.

3) Hyperesthesia (excessive physical sensory perception), allodynia (perception of pain with stimuli that do not normally cause pain) and hyperpathia (pain with mild stimuli, particularly repetitive ones).

4) Decreased sensitivity to stimuli with limb elevation, increased sensitivity with active and passive movement, changes in ambient temperature, and during emotional stress.

5) Locomotor symptoms including muscle weakness, impaired motion, tremor, muscle spasms, and contractures.

6) Atrophic dermatologic changes including skin atrophy, hyperkeratosis, changes in skin creases, fingertips, hair (thickening), and nails (thickening, whitening, browning, or furrowing).

7) Vascular and autonomic symptoms including pallor or erythema, warming or cooling of the affected extremity compared with the contralateral limb, edema (in >80% of patients; initially pitting, later indurated), and increased sweating.

Natural history: The Steinbrocker classification includes the following stages of CRPS (all of which may or may not manifest in a given patient):

1) Stage 1 (acute) is usually 1 to 3 months in duration (but may last for up to 12 months) and includes pain, hyperesthesia, warming or cooling, and abnormal sweating. In most cases the disease resolves at this stage.

2) Stage 2 (dystrophic) may last for 1 to 2 years and includes pain, atrophic changes of the skin, hair, and nails, as well as cooling of the skin.

3) Stage 3 (atrophic or chronic) lasts for several years and includes skin atrophy, contractures, bone changes, and impaired limb function, which are usually irreversible.

DiagnosisTop

Diagnostic Tests

1. Imaging studies: Radiographs of the affected limb typically demonstrate patchy osteoporosis that is most pronounced in periarticular areas and either forms a pattern of streaks or is irregular in appearance. Soft tissue edema is also visible. Bone marrow edema can be seen on magnetic resonance imaging (MRI) scanning.

2. Functional studies of the autonomic nervous system: Sympathetic blockade (eg, by administering IV phentolamine) is considered an accessory diagnostic test, with clinical improvement supporting the diagnosis of CRPS.

3. Three-phase bone scintigraphy: This is performed within the first few months of symptom onset and shows a relatively increased unilateral radiotracer uptake in joints distant from the trauma site during the late phase. This supports the diagnosis; however, the absence of this abnormality does not exclude the disease.

Diagnostic Criteria

To make the diagnosis of CRPS, all of the following criteria must be fulfilled:

1) Persistent pain without a clear cause or hyperesthesia extending beyond the area innervated by a single nerve and significantly more extensive than suggested by the triggering trauma.

2) Edema, vasomotor dysfunction, or sweating in the area of pain. These features do not need to occur at the time of establishing diagnosis (ie, a history of their occurrence is sufficient for diagnosis).

3) Exclusion of other known causes of the presenting symptoms.

More complex but likely equally sensitive and probably more specific criteria (Budapest Criteria) for the diagnosis of CRPS are available for use.Evidence 1Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007 May-Jun;8(4):326-31. doi: 10.1111/j.1526-4637.2006.00169.x. PMID: 17610454.

Differential Diagnosis

Differential diagnosis should include:

1) CRPS type 2 (previously known as causalgia, which includes symptoms [mainly pain] caused by nerve injury).

2) Inflammatory: Panniculitis, inflammatory arthritis.

3) Infectious: Cellulitis, osteomyelitis.

4) Vascular: Deep vein thrombosis.

5) Neoplastic.

6) Musculoskeletal: Fractures.

7) Neurogenic: Polyneuropathy.

In advanced CRPS it may be also important to exclude chronic vascular insufficiency and thoracic outlet syndrome.

TreatmentTop

No reliable data confirm the effectiveness of any treatment for CRPS type 1. Patient education is universally important. Psychotherapy has been shown to have some utility.

1. Pharmacotherapy:

1) Anti-inflammatory treatment: Oral or IV glucocorticoid regimens, dimethylsulfoxide cream, and IV free radical scavengers such as mannitol have been studied with small sample sizes, with most evidence not showing significant change in pain or composite CRPS scores.

2) Bisphosphonate therapy: Although the evidence is limited, benefits of bisphosphonates are best documented among all CRPS interventions.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (small sample sizes). Duong S, Bravo D, Todd KJ, Finlayson RJ, Tran Q. Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis. Can J Anaesth. 2018 Jun;65(6):658-684. doi: 10.1007/s12630-018-1091-5. Epub 2018 Feb 28. PubMed PMID: 29492826. O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009416. doi:
10.1002/14651858.CD009416.pub2. Review. PubMed PMID: 23633371; PubMed Central PMCID: PMC6469537. It is possible that these effects may be more likely in CRPS with accompanying bone mineral density loss (osteopenia or osteoporosis). Inhibition of bone resorption may lead to decrease in bone demineralization and associated benefits in pain and function.

3) Calcitonin: Effects are likely due to inhibition of bone resorption and possible beta-endorphin–mediated analgesic action. Calcitonin has been shown to be potentially more effective than placebo and as effective as beta-blockers, griseofulvin, oral acetaminophen (INN paracetamol), and IV bisphosphonates.

4) N-methyl-D-aspartate (NMDA)-receptor antagonists: Effects are possibly due to neuropathic pain modulatory action. Limited evidence suggests IV ketamine may provide short-term pain relief, although no sustained effect was found beyond 4 to 11 weeks after treatment.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (small sample size) and inconsistency. O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009416. doi: 10.1002/14651858.CD009416.pub2. Review. PubMed PMID: 23633371; PubMed Central PMCID: PMC6469537.

5) Tadalafil: Effects are possibly due to its vasodilatory action. Limited evidence suggests tadalafil may provide small but significant short-term CRPS-related pain relief, although with no significant change in function.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (small number of studies, small sample size) and risk of bias (baseline imbalances). O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009416. doi: 10.1002/14651858.CD009416.pub2. Review. PubMed PMID: 23633371; PubMed Central PMCID: PMC6469537.

6) Systemic local anesthetic agents: High-dose IV lidocaine may have a slightly larger analgesic effect compared with other agents such as diphenhydramine, at least in the short term.

2. Epidural and IV regional blocks: Epidural clonidine may provide immediate pain relief when CRPS-related pain is refractory to sympathetic blockade. IV regional blocks with atropine have generally not been found to be effective for sympathetically-maintained pain. IV regional blocks with bretylium or with lidocaine may provide longer duration of analgesia than lidocaine alone, and very limited evidence suggests ketanserin may be effective in reducing CRPS-related pain. IV regional blocks with droperidol and guanethidine have not been found to be effective, and the former has been associated with frequent adverse events.

3. Botulinum toxin A sympathetic blockade: This may effectively increase analgesic duration alongside local anesthesia compared with local anesthesia alone, although it is unclear what degree of pain relief can be attributed to this intervention.

4. Neurostimulation: No evidence is available supporting the effectiveness of repetitive transcranial magnetic stimulation. There is low-quality evidence supporting spinal cord stimulation in conjunction with physiotherapy for CRPS-related pain control and health-related quality of life but not for function.

5. Physiotherapy: Low-quality evidence suggests multimodal physiotherapy in conjunction with medical management may be more effective at reducing short-term (3 months) pain and long-term (12 months) impairment but not long-term pain, compared with social work plus medical management control arm.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (small sample size) and inconsistency. Smart KM, Wand BM, O'Connell NE. Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II. Cochrane Database Syst Rev. 2016 Feb 24;2:CD010853. doi: 10.1002/14651858.CD010853.pub2. Review. PubMed PMID: 26905470. Physiotherapy may involve the use of heat or cold, depending on the phase of the disease and general condition of the patient. Limb elevation is used in patients with edema. Prevention of contractures is necessary.

6. Other modalities (for which evidence is very limited): Graded motor imagery and mirror therapy (physiotherapies), acupuncture (in conjunction with rehabilitation therapy), gabapentin,Evidence 6Weak recommendation (downsides likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision (small sample size) and inconsistency. O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009416. doi: 10.1002/14651858.CD009416.pub2. Review. PubMed PMID: 23633371; PubMed Central PMCID: PMC6469537. sarpogrelate hydrochloride, local anesthetic sympathetic blockade, sympathectomy, pulsed electromagnetic field therapy, relaxation training, tactile discrimination training, stellate ganglion block under ultrasonography, manual lymphatic drainage with or without anti-inflammatory agents, physical therapy or exercise, and laser therapy.

PreventionTop

The following preventative strategies are generally recommended:

1) Avoidance of nerve damage during surgical procedures.

2) Early mobilization after surgery.

3) Physiotherapy.

4) Administration of vitamin C (500 mg/d for ~2 months) in patients after wrist fracture or before surgical treatment of foot fractures.