Servier – Phlebolymphology

Nathaniel Cleri, MD
Department of Surgery,
Northwell Health, New Hyde Park,
New York, USA

Mohsen Bannazadeh, MD
Department of Surgery,
Northwell Health, New Hyde Park,
New York, USA
Department of Vascular Surgery,
Northwell Health, New Hyde Park,
New York, USA

Antonios Gasparis, MD
Department of Surgery,
Northwell Health, New Hyde Park,
New York, USA
Department of Vascular Surgery,
Northwell Health, New Hyde Park,
New York, USA

ABSTRACT

Chronic venous disease (CVD) signs and symptoms include heaviness, aching, swelling, throbbing, and itching (HASTI). Advanced stages of CVD include swelling, hyperpigmentation, and venous ulcer. Treatment improves most of the signs and symptoms including healing of venous ulcers. Resolution of swelling is often not achieved and can be due to a variety of reasons. After venous intervention, inconsistent rates of reduction in swelling can be due to misdiagnosis, persistent venous disease, and burnout of the lymphatic system. Patients require comprehensive evaluation to identify potential treatment options. Failure to identify other causes of swelling after venous intervention should prioritize lymphatic health using conservative therapies like compression, exercise, and, potentially, venoactive drugs. The addition of lymphedema management techniques such as manual lymphatic drainage and intermittent pneumatic compression are recommended. Further research is needed to clarify the factors influencing swelling resolution, optimize treatment strategies, and establish evidence-based guidelines for post-intervention care, ultimately improving patient outcomes and quality of life.

Introduction

Chronic venous disease (CVD) is caused by reflux or obstruction in the superficial or deep venous system, resulting in venous hypertension. In advanced stages (chronic venous insufficiency [CVI]), the pathology may cause lower-extremity edema, lipodermatosclerosis, and ulceration. Conservative treatment of CVD includes compression therapy, weight loss, exercise, and venotonic drugs. Persistent symptoms despite conservative therapy may lead to treatment of the underlying venous pathology.

Patients who present with disease of CEAP clinical score 3 (based on the clinical-etiological-anatomical-pathophysiological classification system) are often challenging, as resolution of their swelling is not always achieved after venous intervention. This can occur because of failure to identify the underlying cause of swelling, failure to carry out complete treatment of the venous pathology, a multifactor origin of the swelling, or a compromised lymphatic system due to overwhelm by long-standing venous hypertension.

Patients who have residual edema after venous interventions require reevaluation of the causes of leg swelling, careful investigation for residual or undiagnosed superficial or deep disease, and treatment of their lymphatic system.

Residual edema after venous interventions

Venous interventions are considered safe and have been shown to overall significantly improve clinical symptoms and quality of life.¹ There are limited data available on improvement of edema after venous intervention. Most papers that report on results of treatment for clinical symptoms of CVD include patients with disease graded as CEAP C2-C6, with the majority being CEAP C2. Improvement in edema in these studies is usually not a primary end point and not reported in an objective manner, therefore not well documented.

In evaluating outcomes after endovenous ablation in patients with leg swelling, Shutze et al² identified CEAP C3 patients in a database of 1634 limbs treated with endovenous ablation. There were 528 limbs that were treated for edema with an average follow-up of 1494 days (range, 562–2795 days). Patients were surveyed on the amount of edema (current and immediately post procedure), the use of compression stockings, and current satisfaction with the procedure. In this group, 40% of patients had residual swelling after endovenous ablation.² Korany et al³ retrospectively reviewed 80 patients with edema and combined those with superficial reflux and segmental deep venous reflux who underwent endovenous ablation. On follow-up, all patients had no signs of residual superficial reflux, whereas deep venous segment reflux was corrected in 36 (45%) patients after treating the superficial reflux. Edema improved in 45%, whereas 55% showed no improvement after treatment. Similar results were seen at 3, 6, and 12 months. Adherence to compression stocking therapy was high up to 6 months postoperatively, at which point adherence began to drop.³ This study suggests that patients with combined superficial and deep reflux may have a higher failure rate in resolving their edema even with use of compression therapy.

In patients with iliac vein obstruction, percutaneous venous stenting has been reported to reduce edema, although not significantly. Neglén et al⁴ reported on 982 chronic nonmalignant obstructive lesions of the iliac vein that were stented. There was no improvement in swelling in 38% of the patients, 30% had partial relief, and only 32% had complete relief of swelling.⁴ This group of patients with long-standing disease and high venous hypertension due to venous outflow obstruction seem to have the lowest improvement in swelling after intervention, with 68% having residual edema.

Given the poor results for improvement in swelling after venous interventions, it is paramount to discuss patient expectations prior to treatment. Patients with CVD may present with many clinical symptoms, and those who have a main clinical concern about swelling need to understand that improvement in swelling may or may not occur and that, in some instances, they may have no improvement. The severity, location, and duration of venous disease seem to have an impact on improvement in edema after intervention.^2-4 This may relate to burnout of the lymphatic system over time and its inability to recover even after the venous hypertension is addressed. If that is the case, early intervention in CEAP C3 patients may result in improvement in resolution of symptoms.

Potential reasons for residual leg swelling after venous interventions was nicely reviewed in a previous article in this issue and include residual venous disease in the superficial or deep veins, undiagnosed disease in the superficial or deep veins, nonvenous causes, and dysfunction of the lymphatics. A comprehensive evaluation of these patients is required to offer proper treatment.

Treatment of persistent edema after venous
interventions

The first step in the evaluation of a patient with persistent swelling is to start from the beginning and do a complete history, physical, and evaluation. Whereas venous disease is a common cause of edema, the differential diagnoses are broad and may be multifactorial.⁵ Below are potential causes of swelling and treatment approaches for each.

Systemic causes. Edema can be caused by systemic causes (eg, heart failure, cirrhosis, renal failure, and endocrine disorders). In this case, patients will have bilateral swelling, although rarely they may present with unilateral edema. Evaluation and treatment of systemic causes is critical in these patients to improve their edema. More often than not, the above conditions can be optimized but not cured. Therefore, some degree of edema will most often be present.

Medications. Medications are one of the most common causes of swelling, and such cases typically also present with bilateral edema. All patients with leg swelling should have their medications reviewed, looking for drugs that can cause leg swelling (eg, calcium channel blockers, nonsteroidal anti-inflammatory drugs [NSAIDs], and oral hypoglycemic agents). Discontinuation of such medications will improve their swelling.

Musculoskeletal causes. Immobility and gait disturbances can contribute to lower-limb edema. A sedentary lifestyle, where the lower limbs remain stationary for extended periods without active movement, can also contribute. Additionally, static foot disorders can be an important risk factor that adversely affects edema. Patients should be encouraged to walk, exercise, and undergo physical therapy, all of which help improve calf muscle pump function, enhance venous and lymphatic flow, and reduce edema.

Obesity. One of the major causes of leg swelling is obesity. Patients present with signs and symptoms of venous disease and bilateral swelling. They also tend to present with more advanced stages of venous disease.⁶ This is due to underlying central venous obstructions from the high intra-abdominal pressure. Patients should be encouraged to follow a healthy diet, lose weight, and exercise. In cases of morbid obesity, patients may be candidates for medical or surgical weight loss interventions.

Venous disease. When the above potential causes of leg swelling have been excluded, detailed venous imaging should be done. If swelling after the intervention worsens, ultrasound should be done to evaluate for postoperative deep venous thrombosis. Imaging should also evaluate for residual untreated disease, new venous disease, or unrecognized deep venous disease.^7-9 Not all CEAP C3 patients with superficial disease undergo deep venous imaging, and a proximal obstruction may have been missed. Treatment of residual superficial venous disease or treatment of proximal obstruction can help improve residual swelling. Residual and recurrent vein disease are fairly common; thus, treatment of all possible pathology will further reduce edema. Patients with deep infrainguinal reflux or obstruction do not have many treatment options. However, they should be encouraged to be physically active, exercise, and wear elastic compression stockings.

Pharmacological interventions, such as venotonic drugs, may also be considered as part of the comprehensive management strategy. There are several studies that have shown venotonic drugs to improve signs and symptoms of venous disease and specifically to improve leg edema and circumference.^10-12

Treatment of the lymphatic system

Effective postoperative management is crucial for addressing residual edema and optimizing patient comfort after venous interventions. In CVD patients who present with edema secondary to venous hypertension, treatment may or may not improve the edema. If CVD is the inherent cause of edema, early treatment of the venous pathology may improve the edema. However, if chronic venous hypertension is long-standing and damages the lymphatics, the edema may be irreversible. Patients with residual edema should be offered treatment of their lymphatics.

Patients with persistent swelling should be offered lymphedema treatment that includes lifestyle modifications and medical interventions. This is known as complete decongestive therapy, and it all starts with patient education. Patients are encouraged to elevate their legs and engage in regular leg exercises to promote calf muscle pump function. Maintaining a healthy diet and managing weight are crucial, as is promoting physical activity.

Compression therapy is a cornerstone in the management of these patients. Daytime compression therapy for lymphedema management typically involves custom-fitted or over-the-counter compression garments, wrap devices, or bandaging, with a preference for flat knit materials. For patients with stage 2 or 3 lymphedema, nighttime compression garments are also recommended. Manual lymphatic drainage (MLD) should be considered in case of advanced swelling, with transition to self-MLD and intermittent pneumatic compression (IPC) devices, shown to significantly improve quality of life, reduce swelling, and complications.^13,14

A recent Delphi consensus on the management of lymphedema strongly supports the use of compression garments, with 89% agreeing that regular use reduces disease progression; 70.2% agree that MLD is a mandatory component of patient care; and 92% recommend IPC for lymphedema patients.¹⁵ In summary, with persistent edema after venous interventions, treatment should focus on the lymphatic system.

Conclusion

Improvement in swelling after venous interventions varies in the literature. This can be due to misdiagnosis, residual venous disease, or failure of the lymphatic system. Evaluation for other causes of swelling or treatment of residual venous disease is important. If swelling persists or no other causes are identified, treatment of the lymphatic system is necessary. Addressing patients’ expectations ahead of venous interventions for leg swelling is critical given that swelling may persist in 40% to 70% of patients.



CORRESPONDING AUTHOR
Antonios Gasparis, MD
Department of Surgery, Northwell
Health, 1999 Marcus Avenue, New Hyde
Park, NY 11402, USA
EMAIL: agasparis@northwell.edu


References
1. Kim H, Cho S, Lee K, Labropoulos N, Joh JH. Clinical outcomes of nonthermal ablation, thermal ablation, and surgical stripping for varicose veins. J Vasc Surg Venous Lymphat Disord. 2024;12(6):101902.
2. Shutze W, Shutze R, Dhot P, Ogola GO. Patient-reported outcomes of endovenous superficial venous ablation for lower extremity swelling. Phlebology. 2019;34(6):391-398.
3. Korany AO, Ismail AM, ElAskary NA, Kassem AM. The effect of superficial venous incompetence treatment on combined segmental deep venous reflux. Ann Vasc Surg. 2024;100:184-189.
4. Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg. 2007;46(5):979-990.
5. Gasparis AP, Kim PS, Dean SM, Khilnani NM, Labropoulos N. Diagnostic approach to lower limb edema. Phlebology. 2020;35(9):650-655.
6. Burian EA, Rungby J, Karlsmark T, et al. The impact of obesity on chronic oedema/lymphoedema of the leg – an international multicenter cross-sectional study (LIMPRINT). Int J Obes (Lond). 2024;48(9):1238-1247.
7. Puggioni A, Lurie F, Kistner RL, Eklof B. How often is deep venous reflux eliminated after saphenous vein ablation? J Vasc Surg. 2003;38(3):517-521.
8. Mühlberger D, Morandini L, Brenner E. Venous valves and major superficial tributary veins near the saphenofemoral junction. J Vasc Surg. 2009;49(6):1562- 1569.
9. Adler C, Mousa A, Rhee A, Patel MD. Varicose veins of the lower extremity: Doppler US evaluation protocols, patterns, and pitfalls. Radiographics. 2022;42(7):2184-2200.
10. Kakkos SK, Nicolaides AN. Efficacy of micronized purified flavonoid fraction (Daflon®) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Int Angiol. 2018;37(2):143-154.
11. Ulloa JH. Micronized purified flavonoid fraction (MPFF) for patients suffering from chronic venous disease: a review of new evidence. Adv Ther. 2019;36(Suppl 1):20-25.
12. Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, et al. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020;11(11):CD003229.
13. Murray-Ramcharan M, Escurra MF, Donaldson B, Raza Rizvi SA. Patient centered outcomes of a lymphedema pump in patients with symptomatic lower extremity edema. Ann Vasc Surg. 2024;108:333-337.
14. Lerman M, Gaebler JA, Hoy S, et al. Health and economic benefits of advanced pneumatic compression devices in patients with phlebolymphedema. J Vasc Surg. 2019;69(2):571-580.
15. Lurie F, Malgor RD, Carman T, et al. The American Venous Forum, American Vein and Lymphatic Society and the Society for Vascular Medicine expert opinion consensus on lymphedema diagnosis and treatment. Phlebology. 2022;37(4):252- 266.