Complex regional pain syndrome
Complex regional pain syndrome

Definition

Complex Regional Pain Syndrome (CRPS) consists of persistent pain that is disproportionally severe relative to the event that has triggered it in association with auronomic disturbance. CRPS was previously known as:

reflex sympathetic dystrophy 

causalgia

Sudeck's atrophy 

algoneurodystrophy 

Pain circuit in a healthy individual

Pathology

Complex regional pain syndrome begins as ongoing pain following an injury, bone fracture or surgery and continues despite the recovery of the initial injury. CRPS affects the extremities, particularly the upper limbs, with higher incidence in women. The condition is usually resolved within 12 months with exceptions where pain develops into a debilitating, chronic disorder impairing daily living activities and quality of life.

The pain is initially localised to the area of trauma but may subsequently spread to the entire limb and even to the opposite limb. In 

‍Pathway of CRPS with onset at local sensory nerves sending stimuli to the brain in turn aggravating nerve stimulation and neurogenic pain

CRPS the sensation of pain is intensified by minor, non-noxious stimuli:

clothing touching the skin (allodynia

noxious stimulus like pinprick (hyperalgesia).

The aetiology of CRPS is unknown and it is believed to be a multifactorial process. Both, the nervous system as well as the immune system contribute. Normally, a pain stimulus travels from the periphery to the dorsal horn of the spinal cord and then to the thalamus in the brain, where it is transferred to the cortex. In the thalamus, the pain sensation is transformed into perception followed by the release of hormones to suppress pain. The somatosensory cortex helps localise pain and process pain into consciousness. 

However, an ongoing noxious stimulus leads to increased excitability of nociceptive neurons in the spinal cord, thus enhancing the response to pain in the brain and reducing the thresholds to non-noxious stimuli (sensitisation).

The stimulation of sensory nerves and the sympathetic nervous system leads to release of tissue damaging neuropeptides (excitatory neurotransmitters, substance P, serotonin) and other chemicals (potassium, bradykinin, histamine, prostaglandins, leukotrienes) resulting in vasodilation, local inflammation (neurogenic inflammation) and swelling. These processes exacerbate nerve stimulation and neurogenic pain, creating a vicious cycle.

Persistent activation of the immune system, after tissue injury or ischaemic-reperfusion injury and consequent vascular damage, seem to play a significant role. Detection of autoantibodies against neuronal antigens substantiate the development of autoimmunity, a hypothesised contributing factor to CRPS.

Neuroimaging studies of patients with CRPS have demonstrated brain changes, with a reduction of the somatosensory cortex area of the affected limb, indicating the pathology has a structural impact on the brain altering the perception of pain, a fact debunking the theory of CRPS being a psychological disease.

The concept of CRPS progression divided into three stages (acute, dystrophic, atrophic) has now been essentially abandoned due to the wide variability of the symptom patterns among the patient population.

Stage I: Evident oedema of the hand compared to the healthy hand due to CRPS

Classification

There are two types of CRPS:

Type I occurs after trauma and causes sensory, motor, autonomic and skin / bone changes in 95% of cases.

Type II also occurs after trauma but in the presence of a major nerve injury. 

Possible complications that may arise in long-standing CRPS include:

Swelling, atrophy, osteoporosis, pseudo-arthrosis, joint stiffness and tendon adhesions which may lead to permanent functional disability. Secondary psychological complications include opiate drug dependence, depression and rarely suicide.

 

Left: Distal radius intraarticular, displaced fracture; Middle: Older distal radius fracture with callus formation; Right: Distal radius and ulna fracture, extraarticular and displaced

No 2.

Intra-articular fracture extends to the wrist joint (or articulation)

Extra-articular fracture is located outside of the wrist joint

Open fracture when bone fragments perforate the skin

Comminuted fracture when the bone breaks into multiple fragments

Non-displaced when the anatomical alignment of the bone is maintained or displaced when the bone fragments move apart.

Melone’s classification describes the characteristics of intra-articular fractures of the radius:

i    Stable fracture

ii    Unstable "die-punch"

iii   "Spike" fracture

iv Split fracture

v   Explosion injuries

Acetabular fracture of the pelvis

Acetabular fractures

These fractures are divided into:

Anterior pillar (not weight bearing part of joint)

Posterior pillar (often associated with dislocation of the hip including the weight bearing part of joint)

Transverse

Comminuted involving both column type 

Sacral / coccygeal fractures

The sacrum is a triangular-shaped bone formed by 5 fused vertebrae, which provide a posterior wall to the pelvic ring. At each side of the sacrum, the ala structures articulate with the ilium bones forming the sacro-iliac joints. Sacral fractures are usually parallel to the spine and can involve the ala. Less frequently sacral fractures may display an “H” shape, including a transversal fracture uniting both sides of the sacrum. Three zones are described where sacral fractures can occur that are along vertical lines relative to the alignment of the foramina. Sacral fractures may result in sacral instability and require treatment via sacroplasty (injection of bone glue into the fracture). Surgery is necessary in case of associated neurological symptoms.

Fractures of the coccyx involve the tailbone, the terminal portion of the spine situated below the sacrum formed by 3 to 5 fused vertebrae. Coccyx fractures occur when falling on a seated position. They are more common in elderly women and seldom require surgical treatment.

Surgical treatment of a distal radius fracture triggered the development of CRPS

Causes

The exact causes of CRPS remain unknown. Trauma has to be present to make the diagnosis of CRPS, most commonly after surgery or major interventions, fractures, prolonged limb immobilisation or even following minor surgery. 

Psychological factors per se do not seem to trigger CRPS. However, there may be an association of CRPS with depression and anxiety when patients suffer from chronic pain.

Major causes include:

Injuries: sprains, surgery, arthroscopy, wounds, fractures, crush trauma, burns

Prolonged limb immobilisation

 

Prolonged use of a cast can lead to CRPS

Risk factors

The most commonly recognised risk factors for developing CRPS are:

History of CRPS

Surgery

Bunt trauma

Fractures

Prolonged limb immobilisation with a cast, splint or sling

Genetics (genes of major histocompatibility complex)

Psychological factors (high anxiety, still questioned but possible)

Brittle nails is a symptom of CRPS

Symptoms

Symptomatic manifestations of CRPS apart from pain which is often very severe include elevated or reduced skin temperature, sweating, and oedema due to vascular abnormalities. Additional symptoms are abnormal posture of the limb, tremor and weakness. The common symptoms of CRPS are:

Spontaneous burning or aching pain of the affected extremity

Skin sensitivity

Skin discoloration

Swelling

Sweating

Temperature changes (2/3 warmer, 1/3 colder)

Brittle nails

In chronic CRPS, the main symptoms can become more severe. In the long term, patients may develop non-dermatomal sensory deficits, disturbances of the body perception, and motor deficits leading to:

Pain spread to the entire limb and often to the opposite limb

Severe muscle dystrophy

Limb weakness

Reduced joint motion

Osteoporosis

‍Examiner testing sensory function of the finger tip

Diagnosis

The diagnosis of CRPS is based on medical assessment using both subjective symptom reports and objective signs on clinical assessment. Early diagnosis of CRPS is critical to prevent the transition into a chronic condition. The International Association for the Study of Pain (IASP) has established the Budapest diagnostic criteria of CRPS following the 2004 meeting in Budapest to achieve a higher specificity compared to previous definitions. The main criteria are:

A continuing pain that is disproportionate to the initial pathological event.

The patient must report at least one CRPS symptom in three of the four categories: 

* Sensory symptoms: hyperalgesia (noxious stimulus) and allodynia (non-noxious stimulus)

Vasomotor symptoms: skin temperature asymmetry, skin colour changes, skin colour asymmetry to opposite side

Sudomotor symptoms/oedema: swelling/oedema, sweating changes, sweating asymmetry to opposite side

Motor & trophic symptoms: Reduced range of motion, motor dysfunction (weakness, tremor), trophic alterations of the skin, nail, hair.

At time of clinical evaluation, the patient must display at least one sign in two or more of the above categories.

Diagnosis of CRPS is confirmed if no other diseases fit the array of symptoms identified on clinical examination.

Diagnostic methods may support the findings of clinical examination or be used for differential diagnosis:

Electromyography & nerve conduction studies (CRPS II)

Triple phase bone scintigraphy (increased bone metabolism)

MRI of extremity looking for bone oedema

Quantitative sudomotor axon reflex test

Trial of sympathetic ganglion block

X-rays and MRI to exclude nerve compression at the spine

Other tests to rule out alternative diagnoses such as deep vein thrombosis, arthritis, diabetes or infection.

Treatment

A mirror is used to create a reflective illusion of an affected limb to trick the brain into thinking movement has occurred without pain

Nonoperative treatment

Nonoperative 

The treatment of CRPS remains a challenge. Because of the lack of consensus on a standardised treatment for CRPS, several strategies are currently recommended mostly based on a multidisciplinary management. Some of these are not proven to be efficacious:

Physical/occupational therapy (especially for CRPS Type I)

Oral corticosteroids (acute phase)

NSAIDs

Opioid analgesics (morphine derivatives)

Anti-convulsant drugs (pregabalin, gabapentin, topiramate)

Local injection of anaesthetics early in the disease

Calcitonin (calcium modulation)

Bisphosphonates

Calcium channel blockers

Anaesthetics (ketamine)

Intravenous immunoglobulins

Psychological therapy

Antidepressants

Mirror box therapy (restore correct image of affected limb)

Hyperbaric oxygen therapy (emerging therapy)

Rarely, amputation becomes the last resource for CRPS

Surgical treatment

Surgical intervention is used in case conservative treatment fails but it may not resolve the symptoms. Surgical approaches include:

Spinal  cord stimulation: small electrodes are implanted along the spine with the purpose of delivering mild electric impulses to the affected sensory nerves

Pain pump implantation: it consists of the implantation near the abdomen of a small device that releases analgesic medications directly to the spinal cord

Cross-section of the spinal cord showing the thick nerve ganglia in yellow that are ablated with radiofrequency

Radiofrequency ablation: destruction of the sympathetic ganglion either via radiofrequency ablation or using chemicals

High frequency and repetitive transcranial magnetic stimulation: may reduce pain when combined with medical treatment

Amputation: in rare cases, amputation of the affected limb may be the last option.

Physiotherapist assisting in stretching and gentle wrist-hand exercise

Rehabilitation

Physical and occupational therapy can be very effective in treating pain and reduced function caused by CRPS. Psychological counselling may be recommended if these therapeutic strategies are not successful. Common rehabilitative strategies include:

Hydrotherapy

Mirror therapy

Desensitisation

Weight bearing

Stretching / fine motor exercises

Acupuncture

Pilates / Yoga

Physical activity is efficaceous method to prevent CRPS

Prevention

The main strategy for preventing CRPS is to treat pain at the onset of the first symptoms especially after injury or trauma. It is essential to maintain regular physical activity of the affected limb to avoid muscle wasting, joint stiffness and ultimately disability.

Vitamin C is the most efficacious preventative therapy after a fracture or surgery due to its antioxidant properties, which may reduce inflammation.

Minimising the duration of the tourniquet use to block blood flow during limb surgery to reduce ischaemic-reperfusion injury mediated by oxidative stress when blood flow is restored

Bisphosphonates may help to restore bone metabolism

Topical ketamine as analgesic