CRPS - Hand (Complex Regional Pain Syndrome)

Definition. Complex regional pain syndrome is a chronic pain condition characterised by spontaneous or evoked pain that is disproportionate in time or degree to the usual course of any known trauma. It typically affects one limb, usually the upper, after an injury, and the mechanism involves peripheral inflammation, sympathetic coupling and central sensitisation (neuroplasticity).

Who. Women outnumber men about 3:1 and the peak is middle age, 50-70 years; the upper limb is affected more than the lower. The event is a fracture or other trauma, and the commonest precipitant in practice is a distal radius fracture. A tight cast and a psychological predisposition, the anxious patient, add to the risk.

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Neurogenic inflammation. Release of CGRP and substance P leads to vasodilation, which is the warm phase, and to plasma extravasation, which is the oedema.

Sympathetic coupling. Alpha-adrenergic receptors are expressed on nociceptors, so circulating catecholamines trigger pain. This is why stress exacerbates the condition.

Central sensitisation. The central changes explain why pain persists even after the tissue heals:

• Wind-up - dorsal horn neurons become hyperexcitable, an NMDA-receptor-mediated process
• Cortical reorganisation - the representation of the hand in the homunculus shrinks and blurs
• Disinhibition - loss of descending inhibitory control

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IASP types. Type I, the old reflex sympathetic dystrophy, develops after an initiating noxious event that is not limited to the distribution of a single peripheral nerve. Type II, the old causalgia, develops after a nerve injury; see nerve injury and regeneration for the classification of the underlying lesion, which is what distinguishes Type II and may itself be treatable. CRPS not otherwise specified (NOS) partially meets the criteria, a catch-all that allows treatment without full diagnostic certainty.

Stages. The three-stage sequence is historical but useful:

• Stage 1 (acute, warm), 0-3 months - warm, swollen, red, sweating; the pain is burning
• Stage 2 (dystrophic, cold), 3-12 months - cold, clammy, cyanotic; osteoporosis begins
• Stage 3 (atrophic), over 12 months - atrophy of skin and muscle, contractures (clawing), intractable pain

Early treatment prevents progression to Stage 3. The sequence has not been validated as a fixed temporal progression and many patients do not follow it, so the warm versus cold phenotype is more clinically useful than rigid staging.

The Budapest criteria. The diagnosis is clinical. To diagnose CRPS the patient must meet all of the following:

1. Continuing pain disproportionate to the inciting event
2. Symptoms - the patient reports at least one symptom in three of the four categories
   • Sensory: hyperalgesia, hyperaesthesia, allodynia
   • Vasomotor: temperature asymmetry, skin colour changes
   • Sudomotor/oedema: sweating changes, oedema
   • Motor/trophic: decreased range of motion, weakness, tremor, hair, nail or skin changes
3. Signs - the patient displays at least one sign in two of the four categories at the time of evaluation
4. Exclusion - no other diagnosis better explains the signs and symptoms

How good they are. The Budapest clinical criteria are sensitive (0.99) with markedly improved specificity (0.68) over the older IASP criteria (0.41); the stricter Budapest research criteria reach a specificity of 0.79 (Harden et al., Pain 2010).

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What the signs look like. Compare the two hands under the same ambient conditions: colour, swelling, sweating and temperature are all judged against the other side.

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Algorithm

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Differential Diagnosis

CRPS is a diagnosis of exclusion (Budapest criterion 4). Actively rule out the following before committing to the label:

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No test makes the diagnosis; the Budapest criteria do, and they are clinical. Investigations support the diagnosis, exclude the mimics or pick out the patient for a particular treatment.

Triple-phase bone scan (technetium-99). Three phases, each with its own finding:

• Phase 1 (flow) - asymmetric, increased blood flow
• Phase 2 (pool) - soft-tissue uptake
• Phase 3 (delayed) - diffuse peri-articular uptake in all joints of the hand and wrist

Sensitivity is not as high as often quoted. Pooled across 21 studies it is 0.80 with specificity 0.85, and when the Budapest criteria are the reference standard sensitivity falls to 0.55 (Wertli 2017 meta-analysis). Because it cannot rule CRPS in, a positive scan does not make the diagnosis; because a negative scan makes CRPS less likely without excluding it, it cannot overturn a patient who meets the Budapest criteria. Its practical value is highest early, positive scans being commoner with disease duration under 52 weeks, and in flagging the high-uptake patient who is the one most likely to respond to a bisphosphonate. The phases and their pitfalls are set out in bone scan interpretation.

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Plain radiographs. Patchy osteopenia, Sudeck's atrophy, appears late, after 3-4 weeks. It is specific but not sensitive in the early warm phase.

Ultrasound. An emerging modality for soft-tissue and vascular change: increased blood flow on Doppler, soft-tissue oedema and synovial thickening. It is non-invasive, radiation-free and dynamic, but operator-dependent and may miss subtle change; its use is in monitoring the response to treatment and ruling out other pathology.

MRI and thermography. Both can document the phenotype; neither replaces the Budapest criteria.

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Stellate ganglion block. Local anaesthetic is injected around the sympathetic chain at C6 (Chassaignac's tubercle). If the pain is relieved and there are signs of sympathetic block, Horner's syndrome (ptosis, miosis, anhidrosis) and warmth, the block confirms sympathetically maintained pain (SMP); a successful block that does not relieve the pain implies sympathetically independent pain (SIP). A diagnostic block can separate the two, but high-quality evidence for durable therapeutic benefit is limited and inconsistent, and the response does not reliably predict long-term outcome.

Algorithm

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Prevention. Vitamin C 500mg daily for 50 days after a wrist fracture is the regimen from Zollinger's two RCTs, in which CRPS fell from 10.1 to 2.4 percent in the 2007 dose-response trial. Ekrol's 2014 JBJS Am RCT randomised 336 patients to the identical regimen and found no difference in CRPS rate or function at one year, with scattered signals the other way, including a higher 6-week CRPS rate in nondisplaced fractures. Two level-1 trials of the same protocol disagree, which is why UK guidance treats it as optional.

Many units still give every wrist-fracture patient verbal and written instruction for vitamin C. It is cheap and low-risk, so prescribing it is reasonable; present it as a unit policy on contested evidence, not as established prevention. The other preventive measures are aggressive acute pain management, which reduces central sensitisation, and avoiding the constriction of a tight cast.

Physical therapy is the mainstay. Desensitisation is massage with different textures. Stress loading (Watson) is active loading without joint motion: in "scrubbing" the patient moves a scrub brush back and forth on a table with weight bearing, and in "carrying" the patient carries a weighted bag in the hand throughout the day, providing proprioceptive input without painful joint motion.

Mirror therapy (Ramachandran). The unaffected hand is placed in front of a mirror and the affected hand hidden behind it; the patient moves the unaffected hand and watches the reflection, which tricks the brain into thinking the bad hand is moving pain-free. Graded motor imagery (GMI) runs laterality recognition, then imagined movement, then the mirror, and re-trains the brain without triggering peripheral pain signals.

Start it early. In McCabe's controlled study mirror visual feedback produced analgesia in CRPS of less than 8 weeks' duration and no benefit once the disease was chronic, so it is an intervention with a window, not a rescue for long-standing disease. Moseley's graded motor imagery RCT, which finishes with mirror therapy after laterality recognition and imagined movement, reduced pain by 23mm on VAS versus 10mm for control and held the gain at 6 months; if the limb is already chronic, the structured GMI sequence is the better bet than the mirror alone.

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Algorithm

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Pharmacotherapy. Drugs are chosen for the problem stopping therapy:

• Simple analgesia - paracetamol, NSAIDs
• Neuropathic agents - gabapentin, pregabalin, amitriptyline (a tricyclic)
• Bisphosphonates - reduce bone turnover and pain; the evidence supports their use, and they are particularly useful when the bone scan shows high uptake
• Steroids - a short course of oral prednisolone in the acute inflammatory phase
• Topical - DMSO cream, a free-radical scavenger, and capsaicin

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Interventional pain. Stellate ganglion blocks are given as a series of 3-5; a spinal cord stimulator (SCS) is for refractory cases. Be precise about what SCS delivers, because the only randomised trial followed its own patients long enough to answer it. At 6 months Kemler's RCT showed real pain relief (2.4cm VAS reduction versus a 0.2cm increase in controls) but no improvement in functional status, and complications in 6 of 24 implanted patients.

At the 5-year final follow-up of the same 54 patients, SCS plus physiotherapy performed similarly to physiotherapy alone on pain and on every other measured variable, what the authors call the "diminishing effectiveness of SCS over time". Yet 95 percent of implanted patients said they would do it again. So the accurate sentence is that SCS offers early pain relief that erodes, never bought function, and is still valued by the patients who had it, not that it has transformed the disease.

Algorithm

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Surgery is rarely indicated and often harmful.

Indications. There are two:

• An identifiable nerve lesion, a neuroma or a compression, that is driving the CRPS (Type II). A "painful nerve" is different from "CRPS", and fixing the nerve may fix the CRPS
• Contracture release, only in the cold, burned-out phase (Stage 3)

Sympathectomy. Endoscopic transthoracic sympathectomy at T2-T3 is a last resort: the outcome is unpredictable, the pain often recurs, and the risk of compensatory hyperhidrosis elsewhere is significant.

Amputation. Controversial, and only for a useless, dead-weight limb that is interfering with life. The risk of phantom pain and of recurrence of CRPS in the stump is very high; amputation is an admission of defeat, not a cure.

Musculoskeletal Complications

Trophic Changes

Psychological. Depression affects 40-50% of CRPS patients; screen and treat early. Anxiety is very common with chronic pain and CBT is beneficial, pain disrupts sleep and worsens the symptoms, and catastrophising worsens outcomes and is addressed with psychological therapy. CRPS has been called "the suicide disease": actively assess suicide risk and refer.

Functional disability. 30-50% are unable to return to their previous work. Dressing, eating and grooming may be affected, pain and dysfunction lead to social withdrawal, and quality of life is significantly reduced without treatment.

The acute phase after any procedure. Multimodal analgesia, avoiding opioid dependence; oedema control with elevation, compression and contrast baths; protected motion, early active range of movement within pain tolerance; and vitamin C 500mg daily for 50 days.

Rehabilitation Phases

Red flags requiring reassessment. Each points to a different problem:

• Increasing pain despite treatment - consider an alternative diagnosis
• New neurological symptoms - may indicate central sensitisation
• Psychiatric deterioration - urgent mental health referral
• Spread of symptoms - may indicate generalised CRPS

Prognostic Factors

Expected outcomes.

• Full recovery - 10-30% (more in children)
• Significant improvement - 40-60%
• Chronic symptoms - 30-40%
• Severe disability - 10-15%

What decides the outcome. Early diagnosis and treatment is the single most important prognostic factor: treatment started within 3 months has significantly better outcomes, and delayed treatment carries a poor prognosis. Warm CRPS responds better to sympatholytics and early intervention, children do better than adults with higher recovery rates, and a multidisciplinary approach improves outcomes across all patient groups. CRPS can recur, in the same or the opposite limb.

Global Epidemiology

• Incidence: Population-based estimates range from approximately 5 to 26 per 100,000 person-years, with the upper end from a Dutch cohort and the lower end from a US (Olmsted County) cohort.
• Demographics: Female predominance (roughly 3 to 4:1); peak onset in the post-menopausal range (around 50 to 70 years). Upper limb is affected more often than lower limb.
• Commonest trigger: Distal radius fracture is the single most frequent inciting event; CRPS may also follow crush, sprain, surgery or immobilisation.

Side-by-Side Guidance

Areas of Genuine Difference

• Vitamin C prophylaxis: Endorsed by several orthopaedic/trauma groups after distal radius fracture on the Zollinger RCTs, but UK guidance treats it as optional - the largest replication attempt (Ekrol 2014, 336 patients, same 500mg/50-day regimen) found no difference in CRPS rate or function at one year.
• Bisphosphonates: Increasingly recommended in early CRPS-I in European rheumatology practice (neridronate RCTs); used more selectively elsewhere.
• Spinal cord stimulation: Reserved for refractory disease; the Kemler RCT showed pain relief without functional gain, tempering enthusiasm.

High- vs Limited-Resource Practice

• Well-resourced settings: Access to specialist multidisciplinary pain teams, triple-phase bone scan, MRI, sympathetic blocks, neuromodulation and ketamine infusion.
• Limited-resource settings: Diagnosis remains clinical (Budapest criteria need no imaging), and the highest-yield, lowest-cost interventions - early mobilisation, desensitisation, mirror therapy, graded motor imagery, simple analgesia and vitamin C - are widely deliverable and remain the backbone of care.