Complex Regional Pain Syndrome Type I: Stepping Stone Toward a Diagnostic End Point
Current CRPS Diagnostic Criteria
Numerous criteria for CRPS exist, but one of the most commonly used is the Budapest Research Diagnostic Criteria for CRPS, which was codified in 2012 by the International Association for the Study of Pain (IASP), replacing the IASP’s old criteria.<sup>2</sup> In addition to CRPS I and II, the Budapest criteria add a CRPS-NOS (not otherwise specified) type for patients who partially meet CRPS criteria.<sup>2</sup> The Budapest criteria attempt to be objective by requiring physician-observed signs at the time of clinical evaluation, rather than relying solely on patient-reported symptoms; however, the diagnosis remains one of exclusion and there are no guidelines as to the extent to which differential diagnoses should be explored to ensure no better explanation for a patient’s signs and symptoms exists.<sup>1</sup> Additionally, as with other guidelines, they lack specific or objective criteria and continue to rely on the presence of nonspecific signs and symptoms for diagnosis.<sup>1</sup> <br><i>Photo credit: SPL / Science Source </i>
Differential Diagnosis of CRPS I
Numerous underlying conditions in patients with a CRPS I have been uncovered, and when properly managed, have resulted in complete or partial resolution of CRPS signs and symptoms. Therefore, physicians should carefully rule out a variety of other diseases and disorders before making or accepting a diagnosis of CRPS I.<sup>1</sup> As Borchers and Gershwin state, “there is no substitute for a complete history and physical examination and for appropriate laboratory, neurologic and imaging evaluations.”<sup>1</sup> Based on currently available information, they recommend the following conditions be ruled out: bone or soft tissue injuries, neuropathies, thoracic outlet syndrome, traumatic/disease-related vascular disorders, compartment syndrome, inflammatory/autoimmune disorders, infectious diseases, tumors, rare diseases (eg, Gardner-Diamond syndrome), exposure to toxins (eg, heavy metals), and psychological disorders, including malingering and factitious disorder.<sup>1</sup> <br><i> Photo credit: Phanie / Science Source </i>
The Danger of Overdiagnosis
Borchers and Gershwin note that even people who continue to believe in CRPS acknowledge it is overdiagnosed, and they cite 2 studies that demonstrate the magnitude of overdiagnosis.<sup>1</sup> In the first study, 39 of 54 patients (72%) who were given a diagnosis of CRPS did not fulfill Budapest clinical criteria, with 32 found to have another clearly diagnosable biomedical pathology and 7 found to have psychiatric disorders.<sup>3</sup> In the second study, 77% of patients with suspected CRPS I did not fulfill Budapest criteria and 70% went on to have the underlying cause of their signs and symptoms identified.<sup>4</sup> Overdiagnosis of CRPS prevents the true cause of patients’ symptoms from being discovered. In many cases, this leads to overuse of narcotics and other pain medications, which can lead to addiction, increased risk of adverse events, and subpar resolution of symptoms, compromising quality of life. As Borchers and Gershwin state, “a proper diagnosis is important to help patients.”<sup>1</sup><br> <i> Photo credit: Spencer Sutton / Science Source </i>
Accounting for Posttraumatic Healing
Although the signs and symptoms of CRPS are nonspecific, similar manifestations can occur early or late during the healing process from surgery or a traumatic injury. In the case of limb fractures, for example, patients may first experience symptoms fulfilling CRPS I criteria, such as spontaneous and movement-induced pain, sensitization to a variety of mechanical and thermal stimuli, edema, vasomotor instability, and joint stiffness up to 25 weeks after the fracture.<sup>1</sup> Healthcare providers should remember that patients can have great variability in recovery, including recovery time and expression and severity of individual signs and symptoms.<sup>1</sup> In some cases, immobilization, whether by medical device (eg, cast) or from guarding to avoid pain exacerbation, can induce or contribute to CRPS-like manifestations. Therefore, patients experiencing CRPS-like symptoms following a fracture or other injury should be referred to physical therapy to improve their outcomes.<sup>1</sup> <br><i> Photo credit: John T. Alesi / Science Source </i>
Considering Nerve Problems
Nerve problems are frequently misdiagnosed as CRPS I, particularly in the setting of carpal tunnel symptoms (CTS) and negative electromyographic findings.<sup>5</sup> Because false-negative electromyographic studies are not uncommon, the possibility of CTS should not be ruled out solely based on these findings, particularly in patients manifesting symptoms common to CRPS I and CTS, such as allodynia, hyperalgesia, vasomotor instability, sudomotor disturbances, and/or pain. In such patients, further investigation may yield clinical and electrophysiological evidence of CTS, which can often be successfully treated with surgical decompression.<sup>1</sup> Pseudoaneurysms can also compress nerves and lead to a CRPS I misdiagnosis.<sup>1</sup> Such pseudoaneurysms have been reported after transfemoral catheterization and brachial artery angiography,<sup>6,7</sup> indicating procedural complications should not be overlooked as a cause of CRPS-like signs and symptoms. <br><i> Photo credit: Antonia Reeve / Science Source <i>
Ruling Out Infectious Causes
Varicella-zoster infection and reactivation and Lyme disease can cause CRPS-like symptoms. Varicella zoster reactivation has been associated with nerve damage, including neuronal and axonal loss in peripheral nerves, the dorsal root, and the dorsal root ganglia, with postherpetic neuralgia also causing marked atrophy of the spinal cord dorsal horn.<sup>1</sup> In a prospective study, CRPS-like symptoms were common in those with outbreaks affecting an extremity, particularly a distal extremity.<sup>8</sup> Zoster vaccination can help prevent patients from developing CRPS-like symptoms from herpes zoster infection.<sup>1</sup> Lyme disease can cause neuroborreliosis, which has been associated with axonal degeneration in peripheral nerves, indicating nerve damage might be the underlying cause of CRPS-like symptoms in patients with Lyme disease.<sup>1</sup> Initiation, prolongation, or renewal of antibiotic treatment has shown success in eliminating symptoms of Lyme disease and CRPS in patients with Lyme disease.
Numerous tumor types have been associated with CRPS symptoms, including benign and malignant lesions. Cases of glomus tumors of the hand misdiagnosed as CRPS I have been reported, with some patients suffering for almost a decade before the correct diagnosis was made and the tumor excised, providing full relief of CRPS-like symptoms.<sup>1</sup> Love’s pin test and the Hildreth test can detect glomus tumors with high sensitivity and specificity.<sup>1</sup> Patients with other tumor types have also achieved full or partial relief of their CRPS-like symptoms upon treatment of their tumors, including a patient whose lung carcinoma was discovered because of CRPS-like symptoms.<sup>9</sup> It has been suggested that CRPS I might represent a paraneoplastic syndrome in patients with tumors, but the symptoms appear to be more common when tumors invade bone or affect nerve tissue.<sup>1</sup><br><i> Photo credit: ICVI-CCN / Science Source </i>
Evaluating for Psychological Disorders
Somatization disorder, factitious disorder, and malingering have all been identified in patients with CRPS I, with the latter two being reported more frequently than somatoform disorders.<sup>1</sup> It has been observed that many of the “objective signs” of CRPS I can be artificially induced, such as temperature differences simply by keeping one arm dependent and immobile for 30 minutes.<sup>1</sup> In the setting of somatoform disorders, the DSM-5 criteria have shifted from emphasizing the presence of unexplained symptoms to excessive and disproportionate thoughts, feelings, and behaviors concerning these symptoms,<sup>1</sup> which might help clinicians distinguish these patients from those with CRPS-like symptoms from medical causes. Patients with questionable symptoms or who are disproportionately troubled by their symptoms, particularly those with a history of psychological disorders, might benefit from referral to a psychiatric specialist while underlying medical causes continue to be investigated.
CRPS I remains a questionable diagnosis with poorly defined criteria and no truly objective findings, such as specific laboratory or imaging results. The continued overreliance on this diagnosis has led to overuse of narcotics and other pain medications and suboptimal resolution of symptoms. As part of the Budapest criteria, clinicians should ensure other medical diagnoses are sufficiently ruled out, particularly any diseases and disorders that can compromise nerve function, such as injuries, infections, and tumors. In the majority of cases, patients with a CRPS I diagnosis who underwent more exhaustive investigations often had the true cause of their symptoms identified and experienced full or partial resolution of their symptoms upon proper treatment, indicating healthcare professionals should not consider CRPS I a definitive diagnosis.
Identifying the cause of chronic pain can be challenging, particularly because it can have myriad causes, some of which might not be obvious. When the cause of pain is not apparent and proper investigations into its etiology are not conducted, a diagnosis of complex regional pain syndrome (CRPS) might be made. CRPS is divided into types I (CRPS I) and II (CRPS II), depending on the presence of a definable nerve lesion, which is absent in CRPS I and present in CRPS II.
The diagnosis of CRPS I is particularly problematic because it cannot be objectively identified via laboratory or imaging studies. It relies on questionable diagnostic criteria that require the presence of individual or combinations of nonspecific symptoms that are common in other diseases and disorders, which has led many healthcare providers to question the validity of this diagnosis.
In a recently published article in Autoimmunity Reviews, researchers closely examined the clinical relevance of CRPS I, concluding the condition is grossly overdiagnosed, which has led to the overzealous use of narcotics and other pain medications and subpar outcomes for patients.1 Throughout their article, they document many instances where further investigations in patients with a CRPS I diagnosis revealed the true cause of their pain and related symptoms. Subsequently, they suggest CRPS, particularly type I, "should never be considered a diagnostic endpoint, but should instead be an indicator of the urgent need for extensive exploration of the differential diagnosis."1
- Borchers AT, Gershwin ME. The clinical relevance of complex regional pain syndrome type I: The Emperor's New Clothes. [Published online September 23, 2016] Autoimmun Rev. 2016. doi:10.1016/j.autrev.2016.09.024.
- Harden RN, Oaklander AL, Burton AW, et al. Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 4th Edition. http://rsds.org/wp-content/uploads/2014/12/CRPS-guidlines-4th-ed-2013-PM.pdf. Published 2013. Accessed December 15, 2016.
- Mailis-Gagnon A, Lakha SF, Allen MD, Deshpande A, Harden RN. Characteristics of complex regional pain syndrome in patients referred to a tertiary pain clinic by community physicians, assessed by the Budapest clinical diagnostic criteria. Pain Med. 2014;15(11):1965-1974. doi:10.1111/pme.12584.
- Frölke JP, van Rumund A, de Waardt D, et al. Complex regional pain syndrome type 1? In 77% of people had a different diagnosis [in Dutch]. Ned Tijdschr Geneeskd. 2009;153(12):550-553.
- Del Piñal F. Editorial. I have a dream...Reflex sympathetic dystrophy (RSD or complex regional pain syndrome—CRPS I) does not exist. J Hand Surg Eur. 2013;38(6):595-597.
- Saad A, Knolla R, Gupta K. Complex regional pain syndrome following transfemoral catheterization. J Invasive Cardiol. 2011;23(11):E267-E270.
- Gillick JL, Cooper JB, Babu S, Das K, Murali R. Successful treatment of complex regional pain syndrome with pseudoaneurysm excision and median nerve neurolysis. World Neurosurg. 2016;92:582.e5-8. doi:10.1016/j.wneu.2016.06.023.
- Berry JD, Rowbotham MC, Petersen KL. Complex regional pain syndrome-like symptoms during herpes zoster. Pain. 2004;110(1-2):e1-12.
- Prowse M, Higgs CM, Forrester-Wood C, McHugh N. Reflex sympathetic dystrophy associated with squamous cell carcinoma of the lung. Ann Rheum Dis. 1989;48(4):339-341.
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