Generalised Lymphadenopathy

Generalised lymphadenopathy is enlargement of lymph nodes in two or more non-contiguous regions, and it indicates systemic disease until proven otherwise.

• Causes: infection (HIV, tuberculosis, infectious mononucleosis, cytomegalovirus, toxoplasmosis, syphilis, brucellosis, typhoid, measles, rubella, visceral leishmaniasis, malaria, schistosomiasis), malignancy (lymphoma, leukaemia, metastatic cancer), autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, sarcoidosis), drugs (phenytoin, allopurinol, carbamazepine, hydralazine) and storage or histiocytic disorders.
• In sub-Saharan Africa, HIV infection, tuberculosis and Burkitt or other lymphomas are leading causes.
• Nodes are significant when over 1 cm (epitrochlear over 0.5 cm, inguinal over 1.5 cm).
• Malignancy is more likely with hard, fixed, matted, rapidly enlarging, or supraclavicular nodes, and with B symptoms.

History and examination point to the cause.

• Count and map nodal groups. Record size, consistency, tenderness, mobility, matting and overlying skin changes.
• Constitutional symptoms: fever, night sweats, weight loss (B symptoms), fatigue.
• Pharyngitis, rash and splenomegaly suggest infectious mononucleosis. Rash and joint symptoms suggest autoimmune disease.
• Hepatosplenomegaly suggests leukaemia, lymphoma, HIV, mononucleosis or storage disease.
• Soft, tender nodes suggest infection. Rubbery, painless nodes suggest lymphoma. Hard, fixed nodes suggest metastasis.
• Oral candidiasis, parotid enlargement and chronic diarrhoea suggest HIV.
• Differential diagnosis: reactive lymphadenopathy, localised lymphadenopathy with regional drainage, lipoma, branchial cleft cyst, parotid or thyroid mass, and hernia in the groin.
• Complications: those of the underlying disease, including superior vena cava obstruction, airway compression, tumour lysis, and secondary infection.

Investigation is directed by clinical findings.

• Full blood count with film (blasts, atypical lymphocytes, eosinophilia, cytopenia), erythrocyte sedimentation rate and C-reactive protein.
• HIV test, tuberculosis assessment (chest X-ray, sputum or gastric aspirate Xpert, tuberculin or interferon-gamma release assay), syphilis serology, Epstein-Barr virus serology (monospot), cytomegalovirus, toxoplasma, hepatitis B and C.
• Liver and renal function, lactate dehydrogenase, uric acid, antinuclear antibody and rheumatoid factor if autoimmune disease is suspected.
• Chest X-ray and abdominal ultrasound for mediastinal or abdominal nodes and organomegaly.
• Lymph node excision biopsy (preferred over fine needle aspiration for lymphoma): histology, immunohistochemistry, culture and acid-fast stain, flow cytometry.
• Bone marrow aspirate and trephine if cytopenia or blasts.
• Computed tomography of chest, abdomen and pelvis for staging.
• Avoid corticosteroids before biopsy as they may mask lymphoma.

Treat the underlying cause after diagnosis.

• Supportive: antipyretics, fluids and nutrition. Avoid empirical corticosteroids before a tissue diagnosis.
• Pharmacological: antiretroviral therapy for HIV (in adults, tenofovir 300 mg, lamivudine 300 mg and dolutegravir 50 mg once daily); antituberculosis therapy for tuberculosis (isoniazid, rifampicin, pyrazinamide and ethambutol for 2 months, then isoniazid and rifampicin for 4 months); penicillin G benzathine 2.4 million units intramuscularly for syphilis; supportive care for infectious mononucleosis (avoid ampicillin and contact sports for 4 weeks in splenomegaly).
• Chemotherapy and radiotherapy for lymphoma and leukaemia, by haematology or oncology specialists. Burkitt lymphoma: rapid chemotherapy (cyclophosphamide-based regimens) with rasburicase or allopurinol and hydration for tumour lysis prevention.
• Autoimmune disease: immunosuppression directed by a rheumatologist.
• Stop offending drugs.
• Procedures: lymph node biopsy, bone marrow biopsy, and drainage of abscess.
• Special groups: children with HIV need cotrimoxazole prophylaxis and growth monitoring. Pregnant women need adjusted regimens.
• Red flags: nodes over 2 cm, supraclavicular or hard nodes, B symptoms, hepatosplenomegaly, cytopenias, mediastinal mass with airway symptoms, and persistence beyond 4 to 6 weeks.
• Follow-up: re-examine in 2 to 4 weeks if the cause is not obvious and the child is well. Persistent or progressive nodes need biopsy.