What are the symptoms and diagnostic investigations for primary lymphoedema?

From the Guidelines

Primary lymphoedema is diagnosed based on a combination of clinical presentation, physical examination, and imaging studies, with lymphoscintigraphy being a key diagnostic tool to visualize lymphatic flow 1. The symptoms of primary lymphoedema include progressive swelling, typically affecting the limbs, that results from congenital abnormalities in the lymphatic system. The main symptoms include:

• Persistent swelling (often in one or both legs, though arms can be affected)
• A feeling of heaviness in the affected limb
• Restricted range of motion
• Recurrent skin infections
• Thickened or hardened skin
• Appearance changes like square toes or deep skin creases Diagnostic investigations begin with a thorough clinical history and physical examination, including palpation of the upper quadrant for fibrosis, pitting, and overall tissue quality 1. Additional diagnostic tools include:
• Bioimpedance analysis to detect lymphatic transport impairments and diagnose subclinical and early stage lymphedema
• Circumferential measurement to diagnose upper extremity lymphedema
• Water displacement to diagnose lymphedema with volumetry >200 mL when compared to the contralateral arm
• Ultrasound to identify tissue changes
• Magnetic Resonance Imaging (MRI) to assess tissue changes and rule out other causes of swelling
• Computed Tomography (CT) scans to assess tissue changes and rule out other causes of swelling
• Lymphoscintigraphy to detect lymphatic system impairment
• Lymphography to detect lymphatic system impairment Early diagnosis is crucial as lymphoedema is progressive and irreversible, though it can be managed with compression therapy, manual lymphatic drainage, exercise, and meticulous skin care to prevent complications like cellulitis and lymphangitis 1.

From the Research

Symptoms of Primary Lymphoedema

• Primary lymphoedema is a hereditary genetic disorder of the lymphatic system, resulting in malformation or dysfunction of the lymphatic system, leading to an accumulation of fluid in the tissue and the formation of oedema 2
• The most common form is peripheral lymphoedema of the lower limbs, but systemic manifestations such as intestinal lymphangiectasia, ascites, chylothorax or hydrops fetalis may also occur 2
• The clinical presentation and the degree of lymphoedema varies depending on the causative gene and the specific gene alteration 2
• Primary lymphoedema is divided into five categories: (1) disorders with somatic mosaicism and segmental growth abnormality, (2a) syndromal disorders, (2b) disorders with systemic involvement, (2c) congenital lymphoedema and (2d) disorders that occur after the first year of life (late onset lymphoedema) 2
• Lymphoedema is the swelling of one or several parts of the body owing to lymph accumulation in the extracellular space, often chronic, worsens if untreated, predisposes to infections and causes an important reduction in quality of life 3
• The lower extremities are more commonly affected than the arms or genitalia, and the disease can be syndromic 4
• Morbidity includes decreased self-esteem, infections, and reduced function of the area 4

Diagnostic Investigations for Primary Lymphoedema

• Diagnosis relies on clinical presentation, imaging of the structure and functionality of the lymphatics, and in genetic analyses 3
• Targeted genetic diagnosis is based on the patient's clinical presentation and classification into one of the five categories 2
• Basic diagnostics include cytogenetic and molecular genetic testing, followed by molecular genetic diagnosis through single-gene analyses, gene panel examinations, exome sequencing or whole genome sequencing 2
• Lymphoscintigraphy is a critical diagnostic tool to confirm the diagnosis of lymphedema 4, 5
• Other imaging modalities, including CT or MRI, can also be used to visualize lymphatic dysfunction 5
• A thorough evaluation of patients presenting with extremity swelling should include identification of prior surgical or radiation therapy for malignancy, as well as documentation of other risk factors for lymphedema 5
• Physical examination should focus on differentiating signs of lymphedema from other causes of systemic or localized swelling 5