Complex regional pain syndrome type II arising from a gunshot wound (GSW) associated with infective endocarditis and aortic valve replacement

Abstract

A 34-year-old man with a history of gunshot wound (GSW) to the right upper chest developed secondary aortic valve endocarditis (AVE) and was treated with an artificial valve placement (AVP). Three months after, he presented to an outpatient pain management clinic right arm pain and was diagnosed with complex regional pain syndrome type II (CRPS II). The patient underwent a diagnostic sympathetic ganglion block, before undergoing endoscopic thoracic sympathectomy surgery. Successful outcomes revealed decreased pain, opioid utilisation and improved tolerance to therapy and activities of daily living. To our knowledge, this is the first case reporting CRPS II arising from a GSW complicated by AVE followed by AVP, which emphasises how unforeseen syndromes can arise from the management of seemingly unrelated pathology. This case demonstrates the importance of timely and proper diagnosis of uncharacterised residual pain status post-trauma and differential diagnosis and management of chronic pain syndromes.

Background

Complex regional pain syndrome (CRPS) is a debilitating condition and is most likely induced after traumatic events, such as surgery, crushing injury or a gunshot wound (GSW).¹ CRPS is estimated to affect 2%–5% of individuals¹ who have suffered a peripheral nerve injury, and symptoms may vary from self-limiting to debilitating, causing severe impairment of a patient’s quality of life and function.^{2 3} Reflex sympathetic dystrophy is the first type of CRPS, which is usually the result of a noxious triggering event. Causalgia, the previous name for CRPS II, is characterised by continuing pain and allodynia after a peripheral nerve injury, with characteristic oedema and skin blood flow changes of the extremity involved, including altered sudomotor activity, and without any other existing prior condition that would account for these symptoms.^{2 3} The extremities and chest are the most common locations for a GSW, which often lead to peripheral nerve injuries. Due to the complexity of CRPS, several specialties are involved in clinical management, including: anaesthesiology, trauma surgeons, orthopaedics, internal medicine and rehabilitation physicians.^{3 4} Here, we present a case report that highlights the important role of multidisciplinary management of CRPS II, as well as the critical role a physiatrist can play in the coordination and management of CRPS.

Case presentation

A 34-year-old man was brought to the emergency department in December of 2017 by ambulance with a right-sided upper chest region GSW. The patient underwent trauma surgery; however, the ballistic projectile was not removed due to its complicated location, with fragments being located within his right flank and upper chest. In January, 2 weeks after discharge, the patient returned to another hospital with acute-onset dyspnoea, chest pain, fever and chills. Examination and diagnostic studies revealed severe aortic regurgitation with hypokalaemia and a left ventricular volume overload pattern, with prominent Q waves in leads I, aVL and VIII–VI on ECG. He was diagnosed by the cardiology team with aortic valve endocarditis (AVE) and started on antibiotics. The patient failed medical therapy for his AVE, which led to artificial valve placement (AVP) surgery. The patient was discharged 1 month after surgery in stable postoperative condition; however, he had residual pain, which was thought to be a surgical pain in the right upper chest (GSW site), and generalised anxiety, which was not addressed by the hospital team. Approximately 2 months postsurgery, the patient’s chronic pain exacerbated into an acute presentation of right upper extremity (RUE) pain, swelling, erythema and weakness. His primary care provider, who had been managing his opioids and anticoagulants, referred him to our outside pain management clinic for specialised workup of his exacerbated right arm pain, status post-GSW. The patient presented to our clinic with right arm weakness 3/5, especially on abduction, and generalised swelling from his deltoid region to the wrist and mild erythema. He denied new trauma to the area and reported that his symptoms had progressively worsened since last surgery for AVP.

Investigations

This patient timeline of events was quite unique and rare, as described above. Since his surgery, the patient followed up with his primary care provider for anticoagulation management and postoperative pain control; however, his pain was never properly assessed, to differentiate it from simple postsurgery pain or a more complex, acute-onset syndrome, until the referral to our outside pain management clinic. He presented to us 3 months after initial injury with an acute exacerbation of this right chest/upper arm pain with right arm weakness, mild erythema, swelling from the deltoid to the wrist and generalised pain and allodynia. After a thorough history and physical was complete, as well as an extensive chart review, the diagnosis of CRPS II involving the RUE was established. The patient was then referred to interventional physiatry (interventional pain management), for confirmatory diagnosis with electrodiagnostic testing, which revealed abnormal peripheral nerve conduction and subsequent sympathetic ganglion block (SGB). Findings were then discussed with the primary care team, cardiologist and interventional physiatry. He was placed on continuous opioid therapy and warfarin therapy, managed by the primary team, and was referred by our clinic for a surgical sympathectomy for definitive management with interventional physiatry.

Differential diagnosis

CRPS II is a diagnosis of exclusion that demonstrates evidence of peripheral nerve injury, which may be confirmed by electrodiagnostic testing.^1–3 According to most studies,^{1 2} when considering the diagnosis of CRPS II, the following differential diagnoses could be included: brachial plexus neuropathy, infection, vasculitis, carpal tunnel syndrome, cervical radiculopathy and Guillain-Barré syndrome. Chart review excluded the above causes quickly. The patient had no risk factors for most of these and the symptomatic presentation of RUE allodynia, muscle weakness and erythematous change followed by the traumatic sequence of events placed CRPS II on the top of the differential. A gold-standard diagnosis for CRPS II has not yet been established. Imaging studies, thermography, sudomotor measures and SGB are diagnostic options, but results are inconclusive in the majority of patients.^5–7 Particularly, SGB has a limited role for diagnosing sympathetic mediated CRPS II. CRPS II is a diagnosis of exclusion, and there should be evidence of three out of the following four symptoms: allodynia, decreased range of motion, motor weakness of the extremity and vasomotor evidence of >1°C temperature asymmetry with skin colour change.^1–4 Prior to establishing the diagnosis of CRPS II, the patient presented to an outside facility with fever, chest pain and shortness of breath and was eventually diagnosed with AVE. Regarding these initial presenting symptoms, our chart review concluded that the outside hospital’s team had likely considered the following differential diagnosis: cardiac tamponade, viral endocarditis, acute coronary syndrome, acute decompensated heart failure, mitral valve pathology, pulmonary oedema and embolism; however, ultrasonography and electrocardiogram, as well as complete blood count with differential, prothrombin time and activated partial thromboplastin time confirmed the AVE diagnosis. Brain natriuretic peptide (BNP) levels were sharply increased, which is a common finding in patients with aortic regurgitation, with the severity of regurgitation being correlated to the degree of rise in BNP concentration.

Treatment

On recognising the diagnosis of AVE by the outside hospital team, medical management was initiated; however, it was found to be ineffective, which led to AVP surgery successfully being performed. Most studies suggest that early surgical intervention is recommended in cases of severe aortic regurgitation,⁴ especially if caused by infective endocarditis, such as in this case. Current guidelines for the treatment for CRPS are inconclusive, suggesting a limited role of SGB for the diagnosis of sympathetically mediated pain.^4–7 In this case, our pain management team recognised the potential aetiology of CRPS II as the patient’s source of pain, and referred him to interventional physiatry for Electromyography and Nerve Conduction Velocity studies (EMG/NCV) followed by SGB to confirm the diagnosis. The patient responded appropriately to the SGB with improvement of symptoms, suggesting the CRPS II aetiology. However, some studies^4–7 have suggested that less than one in three patients with CRPS are likely to respond to a diagnostic SGB. Specifically, if the SGB is effective, then it may be followed by endoscopic thoracic sympathectomy (ETS), which appears to decrease pain levels and analgesic requirements, as well as improve sleep and overall quality of life.⁸ In this case, our outside pain management clinic was able to successfully diagnose, manage and coordinate with multiple medical specialties the complexities of CRPS II for this patient and improve his quality of life.

Outcome and follow-up

This is a very rare case that started with one injury (GSW) that subsequently evolved into a multiorgan system clinical picture, with AVE, followed by AVP and CRPS managed with a multidisciplinary approach (cardiothoracic surgery, cardiology and interventional physiatry). We were not able to find any available data regarding the incidence or prevalence of such sequence events in the general population; however, CRPS II affects only an estimated 0.002% of individuals. The patient remained on chronic opioid therapy, physical rehabilitation/therapy, anticoagulation and psychological care before eventually undergoing ETS by an outside interventional physiatry, which improved his CRPS II symptoms. These procedures were performed to substantially decrease his pain and to facilitate his transition to ongoing active physical rehabilitation therapy and decrease his reliance on chronic opioids. Chronic opioid therapy was decreased from 105 mEq morphine (Morphine Miliequivalents - MME) daily, prior to intervention, to 50 mEq morphine (MME) daily, postintervention. The dosage of other medications, including antibiotics and anticoagulants, is outside the scope of this manuscript to discuss, as these were managed by the primary care and cardiology teams. Due to the complexities of his clinical picture, he remained under the care of cardiology, primary care, psychology and pain management teams after ETS. Our physical medicine and rehabilitation (PM&R) clinic was responsible for the diagnosis of CRPS II and interdisciplinary care coordination. His outcome was successful; improving his pain, qualify of life and tolerance to activities of daily living.

Discussion

CRPS type II is a multifactorial disorder with neurogenic inflammation, nociceptive sensitisation and vasomotor dysfunction. The extremity persistent pain of causalgia has been associated with inflammatory molecules, such as interleukin (IL)-1, Tumor Necrosis Factor - alpha and IL-12.^1–3 This is a very rare syndrome related to peripheral nerve injury with a complex pathophysiology and multifactorial aetiology, and, although incidence and prevalence remain unknown, it has been estimated to affect approximately 0.02% of the general population. CRPS I is more common than type II, with most common precipitating events being trauma and surgical intervention.^1–4 The development of CRPS following traumatic injuries is a major cause of concern; therefore, effective, rapid diagnosis and coordinated clinical management is essential. We highlight the role of interventional physiatry using diagnostic SGBs for select cases of CRPS II. With a diagnostic SGB, results are generally obtained after 3–6 blocks, confirming the diagnosis and resulting in increased range of motion, medication reduction and a less painful window of opportunity to transition into active rehabilitation.^{3 5–7} Clinical guidelines^3–7 suggest a limited role of SGB for diagnosis of sympathetically mediated pain, due to the understanding that less than 33% of patients with CRPS II are likely to respond to it. An adequate response demonstrates an appropriate and sustained increase in skin temperature (≥1.5°C and ≥90 min), without evidence of thermal or tactile sensory deficits. There are no indicators to predict block success, and its use is based on the pathophysiological cause of CRPS II. Several aetiological factors have been associated with the pathophysiology of CRPS, including altered sympathetic function, autoimmune states, central sensitisation, inflammatory states. Following tissue damage or neuronal injury, there is an increase in inflammation and enhanced responsiveness to painful stimuli, as well as excessive sympathetic outflow, leading to adrenergic receptor overexpression on nociceptive fibres. This is also mediated by central and neuronal sensitisation by substance P, bradykinin and glutamate in both the peripheral nerves and spinal cord, resulting in increased pain from both noxious and non-noxious stimuli.² Innovative treatment interventions recently documented the utilisation of botulinum toxin A to treat CRPS II, which demonstrated profound prolonged analgesia in patients with CRPS II, when compared with standard SGB with bupivacaine, with a 60-day analgesia difference being demonstrated between the two modalities.⁹ Other emerging treatments with promising outcomes reported in the literature include: immunomodulation therapy with anti-IL-10, thalidomide, 2 weeks of 90 min hyperbaric oxygen therapy daily and plasma exchange therapy.^3–9 ETS may be performed if the SGB is effective in decreasing sympathetically mediated pain in causalgia. ETS appears to decrease pain levels and analgesic utilisation and improve sleep and overall quality of life.⁹ CRPS as a consequence of GSW was first reported during the American Civil War; however, very few cases^10–12 have been reported in the literature regarding the development of AVE following GSW, and to our knowledge, none have been reported regarding the development of CRPS II associated with AVE followed by AVP, secondary to a GSW in the same patient. This case is an excellent teaching tool and reminder of an important clinical lesson: be mindful and pay attention to how unforeseen syndromes can arise from the management of seemingly unrelated pathology. Additionally, we highlight the important role that PM&R physicians can play for the timely diagnosis, coordination of care and management of CRPS II, which is a very difficult syndrome to diagnose and manage due to its complex presentation.

Learning points.

• This is a very rare case that started with one injury gunshot wound (GSW) and evolved into a multiorgan system clinical picture, managed with a multidisciplinary approach (cardiothoracic trauma surgery, cardiology, primary care, psychology, physical medicine and rehabilitation (PM&R) and interventional physiatry). This case is an excellent teaching tool and reminder of an important clinical lesson for how unforeseen syndromes can arise from the management of seemingly unrelated pathology.

• The patient presented with an acute exacerbation of chronic upper chest and right upper extremity pain with weakness, erythema, allodynia and swelling. After chart review was conducted, highlighting the events of a GSW 3 months prior, followed by aortic valve endocarditis and subsequent artificial valve placement (AVP) surgery in an outside facility, he was referred to our pain management clinic for proper assessment of residual uncharacteristically intense postsurgical pain. After differential diagnosis consideration, complex regional pain syndrome type II (CRPS II) was established with confirmatory NCV/EMG and sympathetic ganglion block (SGB) by outside interventional physiatry. Our PM&R clinic was responsible for the diagnosis, coordination of the specialists involved in managing his complex medical picture and assisted with intercommunication between specialties and continuous physical rehabilitation postprocedure, as well as titration of opioid therapy. His outcome was successful, improving his pain, qualify of life, decreasing opioid reliance and improving adherence to rehabilitation therapy and tolerance to activities of daily living.

• CRPS II has a variety of aetiologies, and in this case, the GSW and peripheral nerve injury, sternotomy for AVP, prolonged immobilisation and heart–lung machinery used during the AVP surgery were all potential predisposing factors. SGB may be used for select cases of CRPS II, although clinical guidelines are inconclusive. SGB has a limited role for diagnosis of sympathetically mediated pain, with the understanding that less than 33% of patients are likely to respond to it. Endoscopic thoracic sympathectomy (ETS) may be performed if the SGB is effective to decrease sympathetic mediated pain in CRPS II.

• We highlight an important clinical lesson and educational message with this case reporting a very rare sequence of symptomatic events leading to a complex diagnosis. We highlight the important role that PM&R physicians can play for the diagnosis, coordination and management of CRPS II with SGB and ETS, as well as the need for proper workup of postsurgical residual pain, which in this case led to the diagnosis of CRPS II. We urge clinicians to consider timely referral to PM&R services in such cases that pain that seems characteristically or categorically different from the expected course for proper evaluation, diagnosis and rehabilitation of injuries that potentially impact’ patients’ quality of life and physical function.