Lymphedema/Phlebolymphedema

Lymphedema is a condition marked by the retention of interstitial fluid (lymph) and edema of surrounding soft tissue, often affecting the extremities. It can lead to chronic inflammation, fibrosis, and significant functional and psychosocial impairment. 

Primary lymphedema results from the abnormal development of the lymphatic system, often from abnormal or missing lymph nodes or channels. Secondary lymphedema is caused by damage to the lymphatic system, such as from lymph nodes having been dissected during cancer surgery, trauma, infection, and even chronic venous insufficiency. Phlebolymphedema results from mixed venous and lymphatic insufficiency. 

Phlebolymphedema, also referred to as combined venous and lymphatic insufficiency, is a chronic and progressive condition resulting from the coexistence of chronic venous insufficiency (CVI) and secondary lymphedema. It represents a severe form of lower extremity edema with a significant impact on skin integrity and wound healing. The overlap of venous hypertension and lymphatic dysfunction creates a compounding effect that increases the risk of ulceration and infection, and impacts the quality of life.

Risk Factors for Lymphedema

Lymphedema can be classified as either primary (congenital or idiopathic) or secondary (acquired). Several risk factors are associated with the development of secondary lymphedema:

Cancer treatment. Surgical lymph node dissection and radiation therapy—especially in breast, gynecological, and genitourinary cancers—can lead to lymphedema.¹

Infection. Recurrent cellulitis or lymphangitis can damage lymphatic vessels, particularly in tropical regions where filariasis is endemic.¹

Obesity. Increased adiposity can compress lymphatic vessels and impair lymphatic flow.²

Chronic venous insufficiency (CVI). Can lead to phlebolymphedema due to venous hypertension affecting lymphatic drainage.¹

Surgical trauma. Orthopedic and vascular surgeries may disrupt lymphatic pathways.¹

Clinical Presentation

Lymphedema and phlebolymphedema typically present with insidious onset of swelling, most often affecting the extremities. Clinical features include:

Edema. This can include distal swelling in the extremities, including the arms, hands, legs, feet; and proximal swelling in the breast, chest, shoulder, pelvis, groin, genitals, face/intraoral tissues.¹ Edema is non-pitting in later stages, often asymmetric and worse distally. Patients may have restricted range of motion due to swelling. 

Skin changes. These can include hyperkeratosis, papillomatosis, ulcers, and lichenification.¹

Recurrent infections. Cellulitis and lymphangitis are common due to compromised local immunity.³
Functional impairment. Reduced limb mobility and heaviness, limiting activities of daily living.¹

Psychosocial impact. Depression, anxiety, and diminished quality of life are frequently reported.⁴

International Society of Lymphology Staging 

Stage 0. A clinically normal extremity, but with abnormal lymph transport (ie, illustrated by lymphoscintigraphy)^5,6

Stage 1. Early edema that improves with limb elevation^5,6

Stage 2. Pitting edema that does not resolve with elevation^5,6 

Stage 3. Fibroadipose deposition and skin changes^5,6

Etiology and Pathophysiology

Lymphedema results from impaired lymphatic drainage, which may arise from aplasia, hypoplasia, obstruction, fibrosis, or valvular incompetence.¹ The persistent accumulation of lymph triggers a cascade of chronic inflammation, adipose tissue deposition, and fibrosis, further compromising lymphatic function. Increased interstitial pressure also contributes to skin breakdown and ulcer formation in advanced cases.

Phlebolymphedema results from the interaction between venous and lymphatic dysfunction. Chronic venous hypertension leads to increased capillary filtration and interstitial fluid accumulation. The lymphatic system, responsible for clearing this excess fluid, becomes overwhelmed or damaged over time, leading to secondary lymphedema.

Diagnosis

Diagnosis is primarily clinical but may be supported by:

Physical examination. Stemmer’s sign (inability to pinch the skin at the base of the second toe or finger) is a hallmark.⁶

Imaging. Lymphoscintigraphy is the gold standard. Indocyanine green (ICG) lymphography, magnetic resonance imaging (MRI) lymphangiography, and ultrasound are also used.⁶

Differential diagnosis. It is important to distinguish lymphedema from CVI, lipedema, deep vein thrombosis (DVT), and renal or cardiac edema.⁶

Treatment for Lymphedema/Phlebolymphedema 

Effective management is multidisciplinary and should begin early to prevent progression.

Complete decongestive therapy (CDT). This consists of manual lymphatic drainage (MLD), a superficial and light massage technique; compression therapy, multi-layer bandaging followed by compression garments; exercise; and skin care.¹

Intermittent pneumatic compression (IPC). Used adjunctively, especially in cases refractory to standard CDT.⁷

Surgical approaches. Physiologic procedures include lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT).^1,8 Excisional procedures include debulking surgeries such as Charles or modified Homans procedures for advanced lymphedema.⁹

References
1.    Sleigh BC, Manna B. Lymphedema. [Updated 2023 Apr 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537239/
2.     Mehrara BJ, Greene AK. Lymphedema and obesity: is there a link?. Plast Reconstr Surg. 2014;134(1):154e-160e. doi:10.1097/PRS.0000000000000268
3.        Grada AA, Phillips TJ. Lymphedema: Pathophysiology and clinical manifestations. J Am Acad Dermatol. 2017;77(6):1009-1020. doi:10.1016/j.jaad.2017.03.022
4.        Fu MR, Ridner SH, Hu SH, Stewart BR, Cormier JN, Armer JM. Psychosocial impact of lymphedema: a systematic review of literature from 2004 to 2011. Psychooncology. 2013;22(7):1466-1484. doi:10.1002/pon.3201
5.        International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology. 2013;46(1):1-11. 
6.        Greene AK, Goss JA. Diagnosis and Staging of Lymphedema. Semin Plast Surg. 2018;32(1):12-16. doi:10.1055/s-0038-1635117
7.        Dunn N, Williams EM, Dolan G, Davies JH. Intermittent pneumatic compression for the treatment of lower limb lymphedema: a pilot trial of sequencing to mimic manual lymphatic drainage versus traditional graduated sequential compression. Lymphat Res Biol. 2022;20(5):514-521. doi:10.1089/lrb.2021.0025
8.        Chang EI, Skoracki RJ, Chang DW. Lymphovenous anastomosis bypass surgery. Semin Plast Surg. 2018;32(1):22-27. doi:10.1055/s-0038-1636510
9.        Kareh AM, Xu KY. Surgical Management of Lymphedema. Mo Med. 2020;117(2):143-148.