Complex Regional Syndrome of the Foot

and Ankle and Leg.

Recopilacion Dr. Cesar V Fernandez R

Articulos en Linea

08-2020
How Can Healthcare Providers Better
Advocate for Patients With CRPS?
An interview with Jim Broatch, executive vice president and director of the
Reflex Sympathetic Dystrophy Syndrome Association.
By Kristin Della Volpe
Mr. Broatch: First, healthcare providers must believe that the patient’s pain is real.
In some patients, the pain severity may be higher than that conferred by amputation,
cancer pain, or childbirth. Thus, complex regional pain syndrome (CRPS) can be an
incredibly debilitating disease.

Second, multidisciplinary treatment of CRPS is essential for optimal outcomes.

Therefore, healthcare providers must work with each other, and the patient, as a
team.

Whether you are an anesthesiologist, neurologist, pain specialist, or primary care

physician, you should also include a physical therapist, occupational therapist, pain
psychologist, and possibly a vocational specialist on your management team.

Unfortunately, medical care often is fragmented in the United States. People with
CRPS often tell us that physicians don’t spend the time to educate them and that
they feel dismissed. In addition, many of the treatments considered effective for
CRPS (eg, biofeedback, acupuncture, psychotherapy) typically are not covered by
health insurance.

This may be the reason why we see a lot of patients with CRPS taking long-term
opioid therapy, even though opioids are not considered a first-line option for this
condition. If patients cannot afford treatment, what are we going to do to treat their
pain?
While we know opioids may not be the best treatment option for these patients,
unfortunately, following release of the Centers for Disease Control and Prevention
guidelines,1 we saw many patients summarily removed from opioid therapy but not
given an adequate alternative therapy. This is not responsible prescribing.
Why is mental health an important component of treatment?
Mr. Broatch: Patients with CRPS have high rates of psychiatric comorbidity. A
survey hosted on the Reflex Sympathetic Dystrophy Syndrome Association
(RSDSA) website found that 77.2% of patients reported feelings of depression and
78.2% reported periods of anxiety.2 Alarmingly, half of the patients (438/888)
reported having considered suicide at some point during the course of their illness,
with 66 (15.1%) of these patients attempting suicide.2
If a patient does not have access to a pain psychologist, how can healthcare
providers help?
Mr. Broatch: If mental health is not included in a patient’s treatment plan, the
healthcare provider should assist the patient in establishing a social support.
Patients suffering from chronic pain frequently find that their social network becomes
tattered. Some people cannot return to work or may have to cancel social
engagements so often that friends eventually go away.
The RSDSA has a small patient assistance fund that we have used in the past to
help patients with CRPS pay for counseling. In addition, we can use our social
network to help physicians identify a pain psychologist in their local area.

In addition, the RSDSA helps patients find support groups in their area or helps
patients start a new support group. Our conferences also provide patients with social
support as well as education about CRPS and its treatments. Often, patients with
CRPS have never met another person with this condition before coming to our
conference.
What other services does the RSDSA provide?
Mr. Broatch: We publish an electronic and print newsletter to keep patients informed
of the latest CRPS advances. Also, we provide referrals to physicians who specialize
in treating CRPS. Not only do we offer conferences for people with CRPS and their
caregivers, but we also hold scientific conferences for healthcare providers. Our
most recent conference focused on the use of ketamine for the management of
treatment-refractory CRPS
pdates in Management of Complex
Regional Pain Syndrome
The most significant way to improve care of patients with complex regional
pain syndrome is with an early diagnosis.
By Gary W. Jay, MD

Complex regional pain syndrome (CRPS) is a heterogeneous group of disorders that

generally develop after trauma to soft tissue but also may develop after visceral
diseases or nerve lesions, or rarely without an obvious antecedent event. This
debilitating neurologic syndrome is characterized by pain and hypersensitivity,
vasomotor skin changes, and functional impairment. Structural changes in both the
deep and superficial tissues may occur.

The precise cause of the syndrome is not known, and treatments are not curative.
However, emerging research is helping to further understanding of the pathogenesis
and treatment of this challenging syndrome.

CRPS Definition
CRPS is grouped into 2 categories (CRPS type I and CRPS type II) based on the
absence or presence, respectively, of peripheral nerve damage. The International
Association for the Study of Pain (IASP) defines CRPS type I as “a syndrome that
usually develops after an initiating noxious event, is not limited to the distribution of
a single peripheral nerve, and is apparently disproportionate to the inciting event. It
is associated at some point with evidence of edema, changes in skin blood flow,
abnormal sudomotor activity in the region of the pain, or allodynia or
hyperalgesia.”1 CRPS type II is characterized by clinical signs of peripheral nerve
injury, such as abnormalities found on nerve conduction study. 2
Signs and Symptoms
CRPS is a spectrum disorder with clinical features varying in intensity and clinical
presentation. The symptoms and diagnostic features of CRPS types I and II are
identical. They include severe pain or uncomfortable sensations, as well as limb
swelling, hair growth changes (most typically hair falling out, as well as possible
development of coarser, darker hair and/or rapid hair growth), nail changes (faster
growth, distorted shape), as well as muscle atrophy, increased sweating, and skin
changes (thin and shiny, or skin lesions). 3 Symptoms may be acute or last for many
years.

In addition, patients may experience a spreading of symptoms to other parts of the

body—most commonly in a contralateral or ipsilateral pattern. Diagonal spread is
rare but also may occur.4 Spread of symptoms typically occurs spontaneously
without a secondary trauma, except in the case of diagonal spread, which generally
occurs in the context of a new trauma and is more common in patients with a younger
age at onset of CRPS and a more severely affected phenotype. 4 Although the cause
of spreading CRPS symptoms is not clear, researchers have speculated that CRPS
may spread by spinally or cortically mediated mechanisms. 4

Patient Characteristics
A recent study examining the clinical characteristics of patients with CRPS found
that approximately 73% of CRPS patients were female, and the mean age at onset
of symptoms was 43 years.5 The investigators also found a greater predominance of
left-handedness (21.8% vs 10% in the general population) and multiple limb
involvement (13%, 83% of whom had contiguous spread). The median time from
symptom onset to diagnosis was 6 months, but ranged up to 129 months.

Warm and Cold Subtypes

Bruehl et al recently provided evidence to support the concept of warm and cold
subtypes of CRPS in an international, multicenter study.6 Their evaluation of the
signs and symptoms of CRPS in 152 patients revealed a warm CRPS patient cluster
characterized by a warm, red, edematous, and sweaty extremity, and a cold CRPS
patient cluster characterized by a cold, blue, and less edematous extremity.

Median pain duration was significantly shorter in the warm subtype than in the cold
subtype (4.7 vs 20 months; P < 0.001), but pain intensity was comparable. 6 A
measure of inflammation was significantly elevated in the warm subtype (P < 0.001),
but this measure decreased significantly the first year after injury (P < 0.001). The
investigators suggested that inflammatory mechanisms may contribute most
prominently to the acute phase of the warm subtype but diminish over time.
 Mood Symptoms
Pain catastrophizing, depression, and anxiety are commonly found in patients with
CRPS and are linked with poorer outcomes. 7,8 Notably, patients are at high risk for
suicidal ideation (74%), underscoring the need for psychiatric evaluation and early
intervention for psychiatric disorders in the overall management of
CRPS.9 (see Patient Advocacy for Complex Regional Pain Syndrome.)
Pathophysiology of CRPS
The origins of the disease remain largely unclear. CRPS most likely is developed
and maintained by both the central and peripheral nervous system. Possible
contributors to CRPS include:

 Ischemic reperfusion injury or oxidative stress10-13

 Peripheral and central sensitization 14-18
 Altered sympathetic nervous system function or sympatho-afferent coupling19-23
 Nerve injury24-26
 Neurogenic inflammation and autoimmune dysfunction, including activated glial
cells27-31
 Brain plasticity32-35
 Genetic and psychological factors/disuse36-40

The Role of Glial Cells

Over the past decade, research on CRPS has focused on the role of glial
cell activation in the perpetuation of CRPS. Increased glial cell activation has been
demonstrated in patients with CRPS.30,31 In addition, data from animal studies
supports the hypothesis that limb fracture triggers afferent C-fiber substance P
release, which signals chronic neuroglial activation. That glial activation, in turn, may
contribute to the ongoing central nociceptive sensitization in CRPS. 41 Evidence
suggests that microglial activation triggers proinflammatory responses—including
release of cytokines—that leads to neuronal hyperexcitability, neurotoxicity, and
chronic inflammation.42
This research has led to investigation of pharmacotherapies to block glial cell
activation in CRPS, including use of low-dose naltrexone and minocycline.

Brain Imaging Findings

Brain imaging research had vastly improved our understanding of CRPS and has
demonstrated that CRPS is associated with abnormal brain system morphology.
These morphologic changes result in dysregulation of pain processing in motor,
sensory, affective pain, and autonomic systems.

For example, a 2014 study by Barad et al illustrated that patients with CRPS have a
decreased volume of gray matter in pain-related affect regions in the brain including
the dorsal insula, left orbitofrontal cortex, and several areas of the cingulate
cortex.32 Patients also had a greater volume of gray matter in the bilateral dorsal
putamen and right hypothalamus.

Barad et al32 found that pain duration was associated with decreased gray matter in
the left dorsolateral prefrontal cortex, whereas pain intensity was associated with
increased volume in the left posterior hippocampus and left amygdala and
decreased volume in the bilateral dorsolateral prefrontal cortex. They hypothesized
that the findings may reflect a neurobiological predisposition for central sensitization
or plasticity changes resulting from ongoing neuropathic afferent input.

Diagnosis
CRPS is diagnosed based on clinical signs and symptoms. Table 1 shows what is
commonly referred to as the “Budapest Criteria” for CRPS diagnosis, which was
adopted as the official IASP diagnostic criteria for CRPS in 2012. 3
 Treatment of CRPS
Four general treatment guidelines have been published since 2010. 43-46 Given the
regional differences in the guidelines, this review primarily discusses the 2013
RSDSA guidelines by Harden et al,44 which also were published most recently.
As with patients with other chronic pain conditions, patients with CRPS appear to
derive the greatest improvement in physical function, mood, and ability to cope with
pain when they are treated with an interdisciplinary pain management approach. 47-
49
Such an approach incorporates physical therapy (PT), occupational therapy (OT),
pharmacotherapy, psychotherapy, interventional and neurostimulation techniques,
as well as complementary and alternative approaches.

Functional Restoration
The RSDSA guidelines44 noted that pain management techniques that focus on
functional restoration (ie, PT/OT) are an important aspect of CRPS treatment, with
the goal being gradual desensitization and steady progression to increase strength
and improve flexibility.44 Harden et al suggest a staged approach to PT/OT as shown
in the Figure.44 As part of this algorithm, medications, interventional techniques, and
more intense psychotherapies should be reserved for patients who fail to progress
using functional restoration techniques or who cannot initiate these programs
because of high pain levels.44

Evidence-Based Treatments

Formulating an evidence-based approach to CRPS management is difficult given

the lack of high-quality evidence supporting efficacy of most available therapies.
Cochrane reviews50,51 found low-quality evidence to support the following:
 PT or OT therapy
 Bisphosphonates, calcitonin, or subanesthestic intravenous ketamine
 Graded motor imagery (laterality training, motor imagery, mirror therapy for visual
feedback)
Mirror therapy (use of a mirror box to watch the reflection of the unaffected limb move
as if it were the affected limb). Table 2 presents current evidence on treatments
proposed for CRPS.2,52-90 Notably, many of the commonly used treatments for CRPS
(eg, antidepressants, opioids, and anticonvulsants) have not been evaluated in
randomized controlled trials (RCTs) or have shown equivocal findings. 2
In addition, some treatments, such as sympathetic nerve blocks, have shown
negative findings in RCTs. Future, larger RCTs of these treatments, as well as
results from emerging therapies, such as minocycline, transcranial magnetic
stimulation, real-time neurofeedback, and high-frequency neurostimulation, are
eagerly anticipated.
Conclusion

The most significant way to improve the care of patients with CRPS is to attain early
diagnosis, typically using the Budapest Criteria. Some physicians may choose to use
sympathetic nerve blocks to try to establish the diagnosis and/or confirm the clinical
diagnosis. However, no more than 1 to 3 injections should be used, as per this
author’s protocol. Also, it is important to remember that the “soft tissue trauma” that
may have precipitated the problem may be so insignificant that the patient may not
remember it

Treatment with pharmacotherapy by itself is helpful but is not adequate. Without

question, patients are best treated in an interdisciplinary neurorehabilitation center.
A combination of PT/OT along with appropriate pharmacotherapy can allow patients
to achieve improvement in pain and functioning; however, achieving health
insurance coverage may be an arduous process.

Although significant gains in knowledge have been achieved in the past decade,
more research into the diagnosis and treatment of CRPS is needed urgently. It is the
author’s opinion that experimental studies on the use of minocycline to decrease
glial cell activity is an important avenue of research, and the new research on low-
dose oral naltrexone is extremely exciting.