CRPS New Review- May 2023

CRP a painful neurologic condition that is characterised by the presence of

- Autonomic dysfunction
- Persistent regional inflammatory changes
- Immune and autoimmune dysfunction
- Symptoms located in non-dermatomal distribution.
- The pain is out of proportion to the inciting event both in intensity and
temporality.

Risk factors:

- Female gender, up to four-fold increased risk, particularly during menopause

- Being Caucasiona
- Having a higher income
- Comorbid conditions: headache/migraine, depression, asthma, drug abuse,
preexisting osteoporosis, myofascial pain, anxiety and neuropathy
Definitions and diagnosis of CRPS

CRPS 1 accounts for the majority of CRPS cases.

CRPS 2 previously know as causalgia, presence of a prior nerve injury

CRPS- NOS( not otherwise specified) refers to patients that display some features of
CRPS without fully satisfying diagnostic criteria and without another disease process
that fully explains their symptoms

There is no single diagnostic test that establishes the diagnosis of CRPS.

- In the acute or “warm” phase, patients report intense, burning pain, typically
out of proportion to that expected for their injury (if associated with an inciting
injury).
- As the disease progresses to the chronic or ‘“cold” phase, hair and nail growth
slows down, skin temperature decreases, and the limb becomes atrophied and
mottled, often with a marked decrease in range-of-motion.
CRPS Syndrome Severity Score was developed to help track the progression of the
syndrome. Updated version has 8 signs and 8 symptoms.
Inciting Events

Fractures are often an inciting event for the development of CRPS.

Upper extremity fractures and distal fractures in particular are significant risk factors.

More severe fractures (requiring surgical repair), high energy mechanisms of injury, and
prolonged time under anesthesia during surgical repair also increase the risk of
developing CRPS.
Independent of the presence of a fracture, the surgery itself also represents a risk
factor.
Risk factors, inciting events and pre-existing conditions linked to development of
CRPS:
These include (some rarer than others) transradial cardiac catheterization, angiotensin-
converting-enzyme inhibitors, neurovegetative dystonia, hyperparathyroidism, post-
traumatic stress disorder, metabolic syndrome, alcohol abuse, smoking, traumatic brain
injury, rheumatoid arthritis, animal/insect bites, and basal cell carcinoma.

Budapest Criteria: require the presence of 3 of 4 symptoms and 2 of 4 signs in the

following categories: sensory, vasomotor, sudomotor/oedema, motor/trophic
Investigations:
- X-ray: may show demineralization which is nonspecific, but important to exclude
fracture
- MRI may demonstrate spotted bone marrow edema, joint effusion or contrast uptake in
the skin and synovium. High specificity, low sensitivity
- Three-phase bone scintigraphy( particularly phase 3, know as triple phase bone scan)
has been purportedly been the most sensitive test for detecting CRPS. It may have
additional value in predicting response to treatment
- Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, has been
proposed as a possible biomarker for CRPS.
- Reduced levels of IL-37 (has significant immunosuppressive and anti-inflammatory
effects)
- Reduced level of tryptophan (decreased levels are associated with low mood and
depression)
- Increased Treg cell number, CD8+ T cells and GM-CSF
- Analysing microRNA signatures is a newer area of research. miRNA may predict
response to Ketamine
- Skin biopsies of the affected area: decreased intraepidermal nerve fibre density
- The tourniquet ischemia test, poor sensitivity, good specificity (88%)
- Thermography may be useful in monitoring response to treatment
Pathophysiology of CRPS
Current evidence supports a multifactorial etiology with input from the central nervous system,
sympathetic nervous system, peripheral nervous system, and immune system, as well as an
influence from underlying genetic factors.

Central and Peripheral Nervous System

Inflammation
Genetics
Sympathetic Nervous System and Sympatho-afferent Coupling

Autoimmune Component: 70 % of CRPS patients display anti-autonomic

munoglobulin
G antibodies in their serum
Mental Health Component
Treatment of CRPS:

1- Pharmacological therapies
 Gabapentin: does not change disease course
 Antidepressants: TCA, SNRI
 Transdermal/topical agents: Capsaicin, clonidine, buprenorphine
 Opioids: little evidence
 SNRI: limited evidence
 Corticosteroids
2- Physical and occupational therapy
3- Neuromodulation
a. Spinal cord stimulation
b. Dorsal root ganglion stimulation: more precise targeting of painful regions
c. Peripheral nerve stimulation
d. TENS
4- Neural and sympathetic blockade
a. Stellate ganglion block
b. Lumbar sympathetic block
c. Supraclavicular brachia plexus block
 d. T2 Paravertebral block
5- Emerging therapies
 Ketamine
 Intrathecal strategies
 Calcitonin
 Bisphosphonates
 N-acetylcysteine
 Low-Dose naltrexone
 Scrambler therapy
 Mirror box therapy
 Cannabinoids
 Photobiomodulation
 Plasma exchange
 Transcranial Magnetic Stimulation/Transcranial direct current stimulation
 Botulinum toxin
 Immunoglobulin therapy
 Surgical sympathectomy
 Amputation