Demystifying CRPS: What Clinicians Need to Know
Complex regional pain syndrome (CRPS) is a debilitating neurologic syndrome characterized by pain and hypersensitivity, vasomotor skin changes, and functional impairment. The condition also is marked by various degrees of trophic changes, including alternations in hair pattern and in nail consistency.
CRPS generally follows a fracture, but also can be triggered by other types of trauma—surgery, inflammation, stroke, crush injury, myocardial infarction, neoplasms, immobilization, and sprains.1 Psychological stressors and poor coping skills can influence the natural history and severity of CRPS.
At least 50,000 new cases of CRPS occur annually in the United States, although the true incidence of CRPS is uncertain. A 2003 study of residents in Olmsted County, Minnesota, found an incidence of 5.46 per 100,000 person years.1 However, a 2007 study by de Mos et al found an incidence of 26.2 per 100,000 person years.2 In both studies, females were 3 to 4 times more likely than males to be affected with the condition. Upper extremities are more likely than lower extremities to be implicated in CRPS, with fractures often precipitating the onset of the syndrome.
Studies have identified potential links between CRPS and several other conditions, including asthma, migraine, and osteoporosis among patients who develop the pain syndrome later in life. A significant association exists between concurrent use of angiotensin converting enzyme (ACE) inhibitors and the risk for CRPS, although the relationship has not been proven to be causal.
What is CRPS?
In 1994, a panel working for the International Association for the Study of Pain (IASP) developed the umbrella term CRPS encompassing 2 conditions: reflex sympathetic dystrophy (RSD) and causalgia. Under the new classification, RSD became CRPS Type I and causalgia, CRPS Type II.
Although the IASP definition of CRPS is extremely sensitive, it has been criticized for leading to over diagnosis of the condition. Recognizing this problem, a panel of experts met in Budapest, Hungary, in 2003 to resolve the issue. Their modified criteria, published in 2007, are generally considered to have improved the diagnosis of CRPS (Table).3
Both forms of CRPS include an initial “warm” phase, which likely is due to extravasation of plasma and protein in the affected area, followed by vasodilation. The etiology of this phenomenon, while uncertain, may be the release of pro-inflammatory cytokines (interleukins [IL] and tumor necrosis factor [TNF]-alpha) and neuropeptides (calcitonin gene-related peptide and substance P). Tests of blister fluid, plasma, and cerebrospinal fluid of patients with CRPS have revealed elevated levels of these cytokines.
Patients with either form of CRPS also experience hyperesthesia, allodynia, and/or hyperalgesia. Hyperesthesia is the increased sensitivity to stimulation; allodynia is the pain associated with stimulus that normally provokes no pain; hyperalgesia is an exaggerated painful response to a painful stimulus.
CRPS Type I is marked by a lack of a specific nerve lesion. Patients with Type II CRPS, on the other hand, have clear evidence of nerve injury (causalgia), although symptoms may extend beyond the course of the affected peripheral nerve, differentiating the injury from isolated mononeuropathy.
Patients with Type I (but not Type II) CRPS sometimes experience spreading of their pain to areas beyond the intial locus of pain; in order of prevalence, this spreading can be contiguous (enlargement of the affected area), independent (symptoms in a distant non-contiguous location), or mirror-image (symptoms in a region opposite of the area of the initial presentation).4
There is no medical cure for CRPS. The vast majority of CRPS patients have some degree of pain and dysfunction for greater than 5 years after onset, whereas approximately 15% of CRPS patients develop intractable pain and physical impairment that impacts their ability to work and function normally.5 As with other chronic conditions, patients with CRPS commonly experience psychological symptoms related to their condition that clinicians also must address. These include depression, anxiety, fear, disuse of the affected body part, and social withdrawal.
The value of CRPS staging has become a matter of dispute among pain specialists, and clinicians tend to ignore them in practice. Further, a prospective study involving more than 800 patients with CRPS failed to cinform a sequential progression of the syndrome.6
Stage I CRPS traditionally has been thought to manifest as acute symptoms marked by sensory and/or vasomotor changes, and possibly sudomotor changes. Stage II involves increased pain, as well as vasomotor, motor, and trophic changes. Patients in Stage III experience a diminution in pain, significantly increased motor and/or trophic changes, and continued changes in vasomotor activity.
How to Diagnose CRPS
Because no definitive test exists for CRPS, the diagnosis must be made by exclusion. The list of conditions with symptoms that overlap with those of CRPS is long, and includes entrapment neuropathies, thoracic outlet syndrome, discogenic disease, deep vein thrombosis, cellulitis, vascular insufficiency, lymphedema, and erythromelalgia.7
The hallmark of diagnosis is a thorough clinical evaluation of symptoms and signs. A variety of laboratory and vascular studies can be helpful in excluding other pain diagnoses. These tests including electromyelography and nerve conduction testing to rule out peripheral neuropathy; magnetic resonance imaging (MRI) and x-rays to identify any soft tissue trauma, disc disease, central canal stenosis, or bone disorders; vascular testing to rule out deep vein thrombosis; and blood testing to rule out infectious causes of pain, cellulitis, and rheumatologic disease. However, outcomes studies have failed to support the value of such testing.