not-yet-known not-yet-known not-yet-known unknown Title Page Rare presentation of severe recurrent upper extremity deep vein thrombosis (UEDVT) in a young male Zurwa Nishat1, Neha Patel MD2 1Rowan-Virtua School of Osteopathic Medicine, Email: [email protected] 2Department of Internal Medicine, AtlantiCare Regional Medical Center, Email: [email protected] Author For Correspondence: Zurwa Nishat OMS-IV, Rowan-Virtua SOM 113 Laurel Rd, Stratford, NJ 08084 E-mail: [email protected] The authors declare they have no relevant or material financial interests related to the research described in this article. No funding was received for the submitted work. Written informed consent and permission from the patient for publication was obtained. Introduction Upper extremity deep vein thrombosis (UEDVT) is a relatively rare condition, making up about 6% of total venous thrombosis cases.1 These cases occur without predisposing factors and can be idiopathic or due to anatomical abnormalities such as thoracic outlet syndrome (TOS).2 Idiopathic UEDVT can occur in otherwise young healthy individuals, particularly males, who partake in strenuous physical activity.3 Conversely, TOS is caused by a compression of the brachial plexus or subclavian vasculature as it courses from the cervical region to the arm. TOS is split into neurogenic, vascular, and non-specific-type forms.4 Up to 90% of TOS cases tend to be neurogenic, wherein patients present with symptoms of pain, numbness, tingling, and weakness of the upper extremity, whereas vascular TOS can lead to swelling and thrombus formation.5 Anatomical anomalies precipitating TOS can originate from the soft-tissue, such as the scalene muscle, or from the bone, such as the cervical ribs.6 Incidence rates lie between 0.3 to 8%, but remain controversial since there is no objective diagnostic modality used to confirm TOS. Patients suspected to have TOS may undergo nerve conduction studies and electromyography as well as imaging studies of the cervical spine with chest x-rays. Treatment is initiated with conservative measures such as physical therapy, but in vascular and true neurogenic forms of TOS, surgery remains the definite solution.4 UEDVT can exist in a primary or secondary form. Primary UEDVT, a subtype of venous TOS, also known as Paget Schroetter syndrome, comprises up to one third of UEDVT cases. Unlike secondary UEDVT, which is caused most commonly by central lines, tumors, and surgery, primary UEDVT may not have any precipitating factors. Symptomatic UEDVT usually involves the thrombosis of the subclavian, axillary, and brachial veins. Specifically, Paget Schroetter syndrome (PSS) is caused by thrombosis of the subclavian or axillary veins. PSS is associated with anatomical anomalies within the brachiocephalic area, including a more lateral insertion of the costoclavicular ligament to the first rib and hypertrophy of the scalene. These abnormalities create a narrowed venous thoracic outlet, which in combination with repetitive movements, lead to thrombus formation due to microtrauma of the vasculature and elicitation of the coagulation cascade.1 Patients present with swelling, discomfort, pain, paresthesia, weakness, and heaviness of the upper limb. On examination, calor, edema, and erythema are usually present.3 Treatment is pertinent for symptomatic relief and for reduction of recurrence and complications such as pulmonary emboli and post-thrombotic syndrome. Preferred diagnostic tests include compression and/or duplex ultrasonography since contrast venography, the gold standard, tends to be more invasive and expensive.1,2 Treatment of UEDVT remains elusive and controversial due to limited randomized controlled trials and tends to be an application of modalities used for lower extremity DVT. Current treatment is typically comprised of thrombolysis with unfractionated low molecular weight heparin and transition to oral anticoagulants for at least three months.3 After initial treatment, one-third of patients will have clot recurrence unless the anatomic issue is surgically resolved.7 Case History The patient was a 37-year-old male who presented to the emergency room with left arm swelling, erythema, and pain with associated heaviness in his shoulders and neck, which progressively worsened over the span of two months. He reported severe pain radiating to his left shoulder and scapula. He also experienced numbness and tingling in his fourth and fifth fingers. The patient began noticing red discoloration and swelling of his left arm three months prior and initially attributed it to his chronic neck and shoulder pain he has had for four years. The patient was engaging in upper-body physical activity daily, in the form of virtual reality training. His occupation required little to no strenuous activity and minimal repetitive movements. The patient denied injuries or any other trauma to the upper extremities or trunk. The patient had no significant past medical history and was not taking any medications for the past year. Family history was negative for cancer, coagulopathies, deep venous thrombosis, and pulmonary embolism. The patient did not smoke or drink alcohol. He used marijuana often for sleep and pain relief. On presentation, the patient was afebrile, nonhypoxic on room air, slightly tachycardic with a heart rate reaching 102, and normotensive. His left upper extremity was noted to be diffusely edematous and erythematous with reduced range of motion and strength. Methods While in the hospital, the patient underwent left upper extremity duplex ultrasonography and was found to have nonocclusive thrombus of the subclavian vein as well as multiple occlusive thrombi of the axillary, brachial, and basilic veins. The patient was started on intravenous heparin and transitioned to apixaban. He was started on cephalexin for possible cellulitis. Patient was advised to follow-up with hematology and vascular surgery in the outpatient setting. Upon one month follow-up in the primary care office, the patient noted drastic improvement of left arm swelling, pain, and paresthesia within a few days after hospital discharge. He still had residual heaviness and pain in his shoulder and neck, only in certain arm positions and worsened with immobility. On physical examination, the patient exhibited proper posture without thoracic kyphosis. His arterial pulses were palpable and equal bilaterally with normal capillary refill. His extremities had normal tone and range of motion, with strength and sensation intact. The Adson test did not lead to a diminished pulse while a Roos test exacerbated soreness and heaviness in the upper limb. X-ray of the cervical spine was unremarkable, while MRI showed central disk herniation at C2-3, without any other abnormalities. The patient had a negative hematology and vascular work-up, with no preceding event or causative factor being identified. The patient was advised to continue anticoagulation and follow-up with a venogram to assess for venous compression if symptoms recurred. Conclusion This case report illustrates the longitudinal management of a rare UEDVT presentation. It highlights the significance of and challenges associated with identifying the etiology of UEDVT, especially in otherwise young and healthy patients without any risk factors. The challenges with patient management are partly due to variability in patient presentation and lack of standardized treatment due to infrequency of primary UEDVT in the general population. Since UEDVT are associated with high morbidity and complications, it is imperative to expand research on this subject beyond extrapolating from what is known about lower extremity DVT. Discussion Unlike DVT of the lower extremities, cases in the upper extremities are far less common. Moreover, up to 90% of UEDVT cases involve a secondary cause, including indwelling venous catheters and malignancy. In this case, we observed a young, healthy, physically active male without any of these risk factors or a history of hospitalization, injury, past DVT, cardiac disease, or recent surgery, present with UEDVT.1 Further hematology and vascular work-up was unable to delineate an underlying cause. There is a strong clinical suspicion for PSS since the patient was taking part in upper body exercises daily through a virtual reality program, which required arm abduction and other repetitive movements. This microtrauma about an already narrowed thoracic outlet most likely led to multiple thrombi forming in the upper extremity. The patient also exhibited localized pain to the neck and shoulder, which points specifically to thrombosis of the subclavian or axillary vein.8 The ulnar distribution of paresthesia can be explained by the lower trunk (C8-T1) residing adjacent to the tendinous portion of the scalenes and hard surface of the rib, leading to obstruction.4 The patient’s history provides further clues for possible TOS since he suffered from persistent chronic neck and shoulder pain for years with positional discomfort. In particular, he had alleviation of pain based on arm, neck, and shoulder position. The patient exhibited a symptom distribution of lower plexus neurogenic TOS including neck, shoulder, and arm pain in addition to paresthesia of the fourth and fifth fingers. Acutely, the patient also had vascular TOS symptoms, specifically the venous form, including swelling, heaviness, discoloration, and severe pain of the upper extremity. In this patient, the neurogenic and vascular subtypes of TOS seem to coexist.5,6 Even with treatment, a thrombus is seldom completely dissolved. Residual thrombi have been observed in 82% of patients with UEDVT post-treatment. This patient experienced a recurrent UE DVT a few months following the initial episode after missing several doses of apixaban, with ultrasound demonstrating significant thrombosis in the axilla. The patient was subsequently switched to rivaroxaban for better adherence to the once daily dosing. A systematic review of case series and cohort studies on UEDVT showed high mortality rates among patients with UEDVT, but it is difficult to elucidate this effect in the setting of preexisting malignancies in this population.9 Because of high morbidity, complications, and loss of occupational productivity, it is important to monitor for UEDVT recurrence. Management is taken from what is known about lower extremity DVT but since primary UEDVT are the rarest subset, no standard modality for management exists. Treatment is instead guided by clinical expertise. Even diagnostic measures commonly used for lower extremity DVT such as Well’s criteria and D-dimer offer limited value in cases of UEDVT, instead, the Constans score is used to risk-stratify patients suspected of having an UEDVT. Additionally, there is controversy regarding the use of thrombolysis and anticoagulation versus anticoagulation alone.1 In the case reported, the patient was treated with thrombolysis and anticoagulation, so the risk of post-thrombotic syndrome and PE is lower than if physical measures such as rest, heat, and elevation were employed, yet recurrent thrombosis poses a higher risk because of this treatment modality.3 Since the patient continues to have neck pain, lidocaine or botulinum toxin injections could aid in relief of tense musculature in conjunction with NSAIDs, muscle relaxants, transcutaneous electrical nerve stimulation, and physical therapy. Patient education on relaxation techniques and limiting repetitive movements that trigger symptoms are pertinent, but more aggressive treatment may be warranted to avoid functional impairment since the patient is relatively young.6 Surgical decompression involving removal of the first rib and costoclavicular ligament, anterior scalenectomy, and venolysis would be indicated with persistence of symptoms and for long-term resolution.10 References Khan, O., Marmaro, A., & Cohen, D. A. (2021). A review of upper extremity deep vein thrombosis. Postgraduate Medicine, 133(sup1), 3–10. doi:10.1080/00325481.2021.1892390 Spiezia, L., & Simioni, P. (2009). Upper extremity deep vein thrombosis. Internal and Emergency Medicine, 5(2), 103–109. doi:10.1007/s11739-009-0320-x Bernardi, E., Pesavento, R., & Prandoni, P. (2006). Upper Extremity Deep Venous Thrombosis. Seminars in Thrombosis and Hemostasis, 32(7), 729–736. doi:10.1055/s-2006-951458 Huang, J. H., & Zager, E. L. (2004). Thoracic Outlet Syndrome. Neurosurgery, 55(4), 897–903. doi:10.1227/01.neu.0000137333.04342.4d Sanders, R. J., Hammond, S. L., & Rao, N. M. (2007). Diagnosis of thoracic outlet syndrome. Journal of Vascular Surgery, 46(3), 601–604. doi:10.1016/j.jvs.2007.04.050 Kuhn, J. E., Lebus, G. F., & Bible, J. E. (2015). Thoracic Outlet Syndrome. Journal of the American Academy of Orthopaedic Surgeons, 23(4), 222–232. doi:10.5435/jaaos-d-13-00215 Illig, K. A., & Doyle, A. J. (2010). A comprehensive review of Paget-Schroetter syndrome. Journal of Vascular Surgery, 51(6), 1538–1547. doi:10.1016/j.jvs.2009.12.02 Heil J, Miesbach W, Vogl T, Bechstein WO, Reinisch A: Deep vein thrombosis of the upper extremity—a systematic review. Dtsch Arztebl Int 2017; 114:244–9. DOI: 10.3238/arztebl.2017.0244 Grant JD, Stevens SM, Woller SC, et al.: Diagnosis and management of upper extremity deep-vein thrombosis in adults. JTH 2012;108: 1097–108. Engelberger, R. P., & Kucher, N. (2012). Management of Deep Vein Thrombosis of the Upper Extremity. Circulation, 126(6), 768–773. doi:10.1161/circulationaha.111