Approach to a patient with lymphadenopathy

The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people. Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged in two or more noncontiguous areas or “localized” if only one area is involved. Distinguishing between localized and generalized lymphadenopathy is important in formulating a differential diagnosis. In primary care patients with unexplained lymphadenopathy, approximately three-fourths of patients will present with localized lymphadenopathy and one fourth with generalized lymphadenopathy

HISTORY

  • How long the swelling has been noticed and how it progressed:
    • Shorter duration:
      • Infectious: Bacterial (strep/staph)
      • Viral ( EBV, Rubella, Rubeola, HZV, CMV )
      • Acute Leukemia
      • Kawasaki
      • Drug reactions
    • Insiduous onset:
      • Toxoplasmosis, HIV, CSD
      • CML
      • SLE, JRA, JDM, sarcoidosis
      • Gauchers, Neiman Pick
    • Chronic Lymphadenopathy:
      • Tuberculosis, Ch. Otitis media, Tinea capitis, Seborrhoea, Head Lice
    • Age of onset: ALL (2-6y), Lymphoma (15-19y), Kawasaki <5yrs
    • Sex: Male: Trauma and wound infection, leukemia, lymphoma
      • Female: SLE, JRA
    • Progression: Rapidly increasing in size: Acute Leukemia, Metastasis Variable duration with increasing in size: Lymphomas
  • Tenderness present:
    • Bacterial adenitis,
    • Malignancy with rapid growth and necrosis or with hemorrhage
  • Discharge present: Bacterial adenitis, TB

GENERALIZED LYMPHADENOPATHY

Infections: TB, Rubella, rubeola, CMV, HIV, HTLV, Histoplasmosis, EBV, HZV, Toxoplasmosis
Malignancy:
  • Primary: Hodgkin disease, non-Hodgkin lymphoma, histiocytic disorders, lymphoproliferative disease.
  • Metastatic: Leukemia, neuroblastoma, rhabdomayosarcoma
Autoimmune diseases: Lupus erythematosis, Rhumatoid arthritis, Dermatomyositis.
Lipid storage disease: Gaucher disease, Niemann-Pick disease
Drug reaction: Carbamazepine, phenytoin, penicillin, sulphonamides, captopril
Others: Castleman disease, sarcoidosis, serum sickness

 

REGIONAL LYMPHADENOPATHY

Cervical:
  • Strep/staph adenitis, Mycobacterial infections, IMN, Kawasaki disease, cat scratch disease, malignancies, sinus histiocytosis
Occipital: Roseola, rubella, scalp infections ( tinea)
Preauricular: Eye infections, cat scratch disease
Submaxillary: TB, Lymphoma, Histoplasmosis
Axillary:
  • Infections of the arm/ chest wall, cat scratch disease, malignancies
  • Mediastinal:
    • TB, malignancies (teratoma, T cell lymphoma, leukemia), sarcoidosis, Histoplasmosis.
  • Abdominal:
    • TB, Mesenteric adenitis, Malignancies
  • Ilioinguinal:
    • Infections of the leg or groin

History

  • History of any localizing symptoms or signs:
    • Bacterial Infections: Sore throat, Ear/eye discharge, Trauma/ wound on the body
  • Rash over body
    • Bacterial/viral infections, TB, Kawasaki, malignancy, metabolic diseases, drugs, SLE, JRA, JDM, histoplasmosis
    • Pruritis:
    • Hodgkins, Drug reactions
  • Associated symptoms:
    • Fever: Infections, Leukemia, Lymphoma, other Malignancy, Drug reactions, JRA, SLE, Sarcoidosis.
    • Weight loss: Tuberculosis, HIV, Malignancy, Failure to thrive ( Gaucher's and Nieman Picks)
    • Night sweats: Hodgkins lymphoma
    • Cough: Infections (TB), ALL, Lymphoma, sarcoidosis
    • Bone or joint pains: TB, Reactive arthritis viral infections, bacterial infections, Leukemia, Lymphoma, secondary malignancy (neuroblastoma), JRA, SLE, Kawasaki, Gaucher's.
    • Bleeding from any site: Malignancy, Bacterial sepsis
    • Abdomen distension: TB, HIV, Leukemia, Lymphoma, Systemic onset JRA, SLE, Gaucher's, NPD, Sarcoidosis
    • Jaundice: CMV, HIV, HBV, Lymphoma, Secondary malignancy
    • Altered bowel Habits: TB, HIV, JDM, SLE (male and/diarrhea)
    • SOB or breathing difficulty: Mediastinal mass, cardiac involvement
    • Dysphagia: NHL, TB, rhabdomyosarcoma, histoplasmosis
    • Visual problem: neuroblastoma
    • Hematuria: SLE, TB, rhabdomyosarcoma
  • Past medical history:
    • H/O TB, recurrent or other chronic infection, history of blood transfusion (CMV, HIV)
  • History of contact with TB, pet in the family (Toxoplasmosis, cat scratch disease)
  • Dietary history: intake of undercooked meat (Toxoplasmosis)
  • History of drug ingestion/treatment taken.
  • History of immunization (MMR)
  • Development history ( Gaucher's, NPD)
  • Family history: similar complaints, TB or any chronic Illness. HIV
  • Occupation and Age of parents: HIV, Downs syndrome

General Examination:

  • Anthropometry: Ht, Wt, (TB, malignancy) OFC Downs syndrome
  • Vitals:
    • HR fever, anemia
    • Irregular: viral myocarditis, strep, myocardial infiltration (Hodgkins), SLE, JDM, Kawasaki disease
    • BP: SLE, neuroblastoma

Local Examination:

  • Inspection: Number, position, the surface of LN
  • Palpation: Site, number, local temperature, tenderness, surface and margins, matted +/-, fixidity to surrounding structure or skin
  • Node character
    • Bacterial adenitis: regional, discrete, Tender, overlying erythema, +/- fluctuation
    • TB: nontender matted, +/- draining sinus
    • Hodgkins: Nontender, rubbery in consistency
    • Malignancy: Firm to hard, fixed to an underlying structure or overlying skin
    • Multiple nodes involved: generalized lymphadenopathy

     
    source: AAFP

    General survey

    • Pallor: TB, HIV, CMV, EBV, Bacterial sepsis, CSD malignancy (Leukemia, Lymphoma), JRA, SLE, JDM, Gaucher's, NPD
    • Icterus, Cyanosis, Pedal edema, Clubbing
    • JVP ( Lymphoma)
    • Rash over body
      • Petechiae: Bacterial sepsis, CSD, Viral infections (HIV, EBV, measles), Leukemia, secondary malignancy, SLE, Gaucher's, Neiman Picks disease, Drug.
      • Skin nodules: GAS, TB, AML, CML, Hodgkins, TB, Sarcoidosis, histoplasmosis, Drugs (sulphonamides) neuroblastoma
    • Dysmorphism: Downs syndrome ALL + AML
    • Bony tenderness: Leukemia, Malignancy
    • Oral Examination:
      • Strep pharyngitis,
      • Petechiae in oral mucosa
      • Gum bleeding
      • Gum hypertrophy (AML)
      • Oral ulcers: Leukemia, SLE, JDM
      • Strawberry tongue: Kawasaki
    • Ear examination:
      • Bacterial infections
      • Otorrhoea: TB, rhabdomyosarcoma
    • Eye examination
      • Conjunctivitis: bacterial/viral infection, Kawasaki dis.
    • Phlycten: Tuberculosis
    • Uveitis : JRA
    • Inflammatory reaction: SLE, Sarcoidosis
    • Chorioretinitis: Toxoplasmosis
    • Retinal Hemorrhages: Acute Leukemia
    • Eye lid talangiectasia: JDM
    • Cherry red spot: NPD, Gauchers disease
    • Proptosis: Neuroblastoma
    • Vision: neuroblstoma, rhabdomyosarcomy, JRA

    Systemic Examination:

    • P/A Abd.
      • Distension
      • Hepatosplenomegaly: Tuberculosis, HIV, EBV, Rubella, Leishmaniasis, Bacterial sepsis, Histoplasmosis, Leukemia, Lymphoma, JRA, SLE, Gaucher's, NPD
      • Hepatomegaly: Sarcoidosis
      • Splenomegaly: IMN, massive CML, Gaucher's
      • Abdominal mass or ascites: TB, Malignancy
    • Chest:
    • Tracheal deviation ( Lymphoma)
      • B/L air entry or added sounds
      • Pleural effusion: TB, Bacterial inf, lymphoma, JRA, SLE
      • Infiltrates: Malignancy, NPD
      • Others: Sarcoidosis interstitial fibrosis
    • CVS: any murmurs, pericardial effusion, TB, Viral myocarditis, Kawasaki, lymphoma, JRA, SLE, JDM
    • Nervous System:
      • General or focal neurological signs
    Meningitis: Viral, bacterial, TB
    Infiltration: ALL >AML, Hodgkins disease, NHL, Secondary malignancy neuroblastoma, SLE (memory loss, cognitive impairment, neuropsychiatric) JDM( depression), Gaucher's, NPD (neurodegeneration)

    Investigations

    • CBC
      • Hb: TB, HIV, CSD, Back sepsis, malignancy, SLE, JRA, Gaucher's, NPD
      • TLC: Infections, Leukemia, JRA, HIV, SLE
    • Neutrophils: Bacterial infections, CML ALL, NHL, HIV, drugs (penicillin)
    • Lymphocytes: viral inf, TB, ALL HIV, Hodgkins (advanced), SLE, JDM
    • Eosinophilia: TB, Toxoplasmosis, Hodgkins, sarcoidosis
    • Basophilia: CML
    • ESR: TB, Hodgkins, CSD, JRA
    • Platelet: JRA, CML back. sepsis, HIV, EBV, CSD, Leukemia, 2ยบ malignancy, SLE, JRA, JDM, Gaucher's, NPD
    • P/S: Blast cells +/- ALL, AML, CML
    • Bone marrow examination: Leukemia, Leishmaniasis, Neuroblastoma, Gaucher's, NPD
    • Montoux: TB
    • CXR
      • Pneumonitis: Bact/ viral inf, infiltrates malignancy
      • Hilar Lymphadenopathy: TB, ALL, Hodgkins, NHL, Sarcoidosis, HIV
      • Cardiomegaly: TB, HIV, rubella, HZV, EBV, GAS, Kawasaki, SLE, JRA, JDM, Drugs( sulphonamides)
    • Echocardiography: Kawasaki disease
    • C/S Blood, Pus, Throat
    • Biopsy of Lymph node: Indicated if
      • Persistent or unexplained fever, weight loss, night sweats, hard nodes or fixation to surrounding tissue
      • Increase in size over baseline in 2 Wks
      • No decrease in size in 4-6 Wks
      • No regression to normal in 8-12 Wks
      • Development of new signs and symptoms
    • Serology: HIV, HBV, EBV
    • ANA: JRA, SLA
    • dsDNA: SLE
    • Uric acid malignancy
    • Calcium: sarcoidosis, Tumour lysis syndrome (P, K) NHL
    • Cu & ferritin: Hodgkins lymphoma
    • LFT: HBV, EBV, Malignancy
    • RFT: Before chemotherapy JDM, Sarcoidosis, sepsis, HIV
    • CT/MRI: Malignancy
    • Bone scan: Malignancy

    Management

    • General management:
      • Stabilize patient:
        • Maintain airway
        • Establish circulation
        • Blood / platelet transfusion
        • Fluid and electrolyte balance
      • Supportive care
        • Antibiotics prophylactic if neutropenia +
        • Pain management
        • Nutritional management
        • Psychological support
      • Specific management:
        • Antibiotics for bacterial infections
        • Antiviral if indicated HIV, HZV
        • Malignancy: chemotherapy, surgery or radiation as indicated
        • Collagen vascular disease: NSAID, steroids

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