Disorders of the Lymphatic System

Complete clinical notes covering the classification, pathophysiology, and management of lymphadenitis and Hodgkin Lymphoma.

1. Lymphadenitis

Lymphadenitis is the inflammation of the lymph nodes, usually secondary to infection, immune activation, or malignancy in the drainage territory. It represents a localized immune response and is one of the most common clinical presentations in primary care and general medicine.

1.1 Definition and Classification

• Acute lymphadenitis: Rapid onset; tender, warm, enlarged nodes; typically bacterial.
• Chronic lymphadenitis: Persistent enlargement (>4 weeks); often granulomatous or neoplastic.
• Suppurative lymphadenitis: Progression to abscess formation with central necrosis and pus.
• Generalized lymphadenitis: Involvement of multiple non-contiguous node groups; suggests systemic disease.
• Localized lymphadenitis: Confined to a single regional group; indicates local infection or malignancy.

1.2 Causes and Risk Factors

1.3 Pathophysiology

1. Infection or antigenic stimulus in the drainage area triggers immune cell recruitment to the regional node.
2. Hyperplasia of germinal centers (B-cell proliferation) and paracortical expansion (T-cell response).
3. Increased blood flow and vascular permeability cause redness, warmth, and swelling.
4. Pressure on the capsule and surrounding tissues produces pain.
5. In bacterial infections, neutrophil infiltration may lead to suppuration and abscess formation.
6. In granulomatous infections (TB, fungi), epithelioid macrophages and giant cells form caseating granulomas.

1.4 Clinical Features

• Local signs: Enlarged, tender lymph node(s); overlying skin may be erythematous and warm.
• Systemic signs: Fever, malaise, anorexia; severity correlates with the underlying infection.

1.7 Management

• Supportive care: Rest, hydration, analgesia (paracetamol or NSAIDs), warm compresses.
• Antibiotics: Empirical therapy targeting likely pathogens.
  — Community-acquired: amoxicillin-clavulanate or cephalexin for 7–10 days.
  — MRSA risk: clindamycin or trimethoprim-sulfamethoxazole.
  — Cat-scratch disease: azithromycin if severe; usually self-limiting.
  — TB lymphadenitis: standard anti-TB regimen (RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol for 2 months, then rifampicin + isoniazid for 4 months).
• Surgical drainage: Incision and drainage for fluctuant abscesses; needle aspiration may suffice for small collections.
• Treatment of underlying cause: Antivirals where indicated, antiretroviral therapy for HIV, immunosuppressants for autoimmune disease.
• Follow-up: Reassess at 2–4 weeks; persistent or enlarging nodes require further investigation.

2. Hodgkin's Disease (Hodgkin Lymphoma)

Hodgkin lymphoma (HL) is a malignant neoplasm of the lymphatic system characterized by the presence of Reed-Sternberg cells in a background of inflammatory cells. It accounts for approximately 10% of all lymphomas and has a bimodal age distribution with peaks in young adulthood and after age 55.

2.1 Epidemiology and 2.2 Etiology

• Incidence: 2–3 per 100,000 annually in developed countries. Slight male predominance (M:F ratio 1.3:1).
• Infectious: Epstein-Barr virus (EBV) implicated in 40–50% of cases; HIV increases risk 10-fold.
• Genetic: Familial clustering suggests genetic susceptibility; HLA associations identified.
• Immunodeficiency: Congenital immunodeficiency, post-transplant immunosuppression.
• Environmental: No strong environmental carcinogen identified; smoking may be a minor risk factor.

2.3 Pathophysiology

1. Originates from germinal center B cells that have undergone failed apoptosis.
2. The neoplastic cell is the Reed-Sternberg (RS) cell or its variant, the Hodgkin cell.
3. RS cells are large, binucleated or multinucleated cells with prominent eosinophilic nucleoli ('owl-eye' appearance).
4. RS cells constitute <1% of the tumor mass; the majority is a reactive inflammatory infiltrate.
5. RS cells express CD30 and CD15; they are usually negative for CD20 and CD45 (LCA).
6. Cytokine production (IL-5, IL-10, TGF-beta) by RS cells contributes to the inflammatory background and systemic symptoms.

2.4 Classification (WHO 2016)

2.6 Staging (Ann Arbor System)

2.7 Investigations

• Laboratory: Full blood count (anemia, leukocytosis, eosinophilia, or thrombocytosis); ESR and LDH (elevated levels correlate with disease burden); Liver and renal function tests; Serum albumin (low albumin is a poor prognostic factor); HIV and hepatitis B/C serology.
• Imaging: CT neck/chest/abdomen/pelvis (defines nodal and organ involvement); PET-CT (Gold standard for initial staging and response assessment).
• Biopsy: Excisional lymph node biopsy is mandatory; fine needle aspiration is insufficient for diagnosis. Immunohistochemistry: CD30+, CD15+, PAX5+ (weak), CD20 variable, CD45 negative.
• Bone Marrow Biopsy: Required in selected cases (stage IV, cytopenias, or if PET-CT is unavailable).

2.8 Differential Diagnosis

2.9 Treatment and 2.10 Prognosis

Advanced Stage (Stages III-IV) typically requires 6–8 cycles of ABVD chemotherapy. Escalated BEACOPP is used for high-risk patients.

Prognosis: Overall 5-year survival exceeds 85%. International Prognostic Score (IPS) for advanced HL includes seven factors: Male sex, age >45 years, stage IV, albumin <40 g/L, hemoglobin <105 g/L, leukocytosis >15,000/µL, lymphocytopenia <600/µL or <8% of WBC. Each factor reduces freedom from progression by approximately 7–8%.

3. Key Points Summary