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lymphadenopathy

Etiology: 1) systemic infection - scarlet fever (Streptococcus pyogenes) - cat scratch disease (Bartonella henselae & Bartonella quintana) - secondary syphilis (Treponema pallidum) - Herpes simplex I & II - human immunodeficiency virus (HIV) - toxoplasmosis - brucellosis - rubella - rubeola (measles) - histoplasmosis - dengue fever - leptospirosis - leishmaniasis - trypanosomiasis (Trypanosoma rhodesiense & gambiense) - Chagas' disease (Trypanosoma cruzi) - disseminated tuberculosis - Castleman's disease 2) head & neck infection - reactive - diphtheria (Corynebacterium diphtheriae) - Streptococcus pyogenes - Archanobacterium haemolyticus - herpangina (Coxsackie A virus) - oral Herpes (Herpes simplex I & II) - necrobacillosis (Fusobacterium necrophorum) - dental abscess (mixed anaerobes/aerobes) - infectious mononucleosis (EBV) - cytomegalovirus (CMV) - toxoplasmosis - scrofula (Mycobacterium tuberculosis) - Kawasaki disease - Kikuchi's disease - cat-scratch fever 3) axillary infection - tuberculosis - pneumonia - upper extremity cellulitis - sporotrichosis (Sporothrix schenckii) - tularemia (Francisella tularensis) 4) abdominal infection - mesenteric lymphadenitis (Yersinia enterocolitica) - mycobacteriosis (Mycobacterium avium) 5) inguinal infection - chancroid (Haemophilus ducreyi) - syphilis - Herpes simplex (Herpes virus I & II) - lower extremity cellulitis (Streptococcus, Staphylococcus) - plague (Yersinia pestis) - Lyme disease (Borrelia burgdorferi) - tularemia (tick-borne) (Francisella tularensis) - lymphogranuloma venereum 6) immunologic disease - rheumatoid arthritis - systemic lupus erythematosus - dermatomyositis - serum sickness - drug reactions - phenytoin - hydralazine - allopurinol - silicone implants - angioimmunoblastic lymphadenopathy - Sjogren's syndrome - primary biliary cirrhosis - chronic autoimmune hepatitis 7) malignancies - hematologic - Hodgkin's lymphoma - acute leukemias (T-cell, B-cell, myeloid & monocytoid) - chronic leukemias (T-cell, B-cell, myeloid & monocytoid) - lymphomas - malignant histiocytosis - metastatic tumors to lymph nodes - melanoma - seminoma - lung cancer - breast cancer - prostate cancer - kidney cancer - head & neck cancer - gastrointestinal cancer 8) endocrine diseases - hyperthyroidism 9) lipid storage diseases - Gaucher's disease - Niemann-Pick disease 10) miscellaneous & idiopathic diseases - giant follicular lymph node hyperplasia (Castleman's disease) - sinus histiocytosis - dermatopathic lymphadenitis - sarcoidosis - amyloidosis - mucocutaneous lymph node syndrome (Kawasaki disease) - lymphomatoid granulomatosis - multifocal Langerhans cell (eosinophilic) granulomatosis - familial Mediterranean fever - Kikuchi's histiocytic necrotizing lymphadenitis 11) differential by location of adenopathy* - suboccipital - scalp infections - mononucleosis - toxoplasmosis - tick bites - lymphoma - anterior auricular - ocular infections - cat-scratch fever - posterior auricular - rubella - cervical - head or neck cancer - head or neck infection - infectious mononucleosis - Epstein-Barr virus - cytomegalovirus - toxoplasmosis - rubella - tuberculosis - lymphoma - metastatic cancer - submandibular/submental - neoplasms of the larynx or oropharynx - dental disease - thyroid cancer - supraclavicular - lymphoma - breast cancer - lung cancer - gastrointestinal (GI) cancer - infection - lungs - retroperitoneal space - axillary - infection - trauma - insect bites of hand or arm - cat-scratch fever - breast cancer - lymphoma - melanoma - brucellosis - epitrochlear - hand infection - lymphoma - sarcoidosis - tularemia - secondary syphilis - rheumatoid arthritis - mediastinal/hilar/thoracic - lymphoma - lung infection - lung cancer - sarcoidosis - infectious mononucleosis - tuberculosis - histoplasmosis - retroperitoneal - lymphoma - tuberculosis - germ-cell tumors - seminoma - prostate cancer - inguinal - lymphoma - pelvic cancer - sexually transmitted disease - foot & leg infection & trauma - Pasteurella pestis - generalized (> 2 sites) - infection: - Epstein-Barr virus - cytomegalovirus - toxoplasmosis - tuberculosis - hepatitis - syphilis - HIV/AIDS - histoplasmosis - measles - rubella - varicella - malignancy - lymphoma - leukemia 12) uncommon causes - amyloidosis - sarcoidosis - mucocutaneous lymph node syndrome (Kawasaki's syndrome) - lymphomatoid granulomatosis - angioimmunoblastic lymphadenopathy 13) iatrogenic - serum sickness - drug reaction - silicone - graft vs host disease * < 1% of lymphadenopathy in primary care due to malignancy * risk of malignancy increases with age & chronicity * younger persons are more likely to have infectious cause Pathology: 1) lymphocyte proliferation & hyperplasia of non lymphoid cells in response to antigen exposure - size of the lymph node increases - nodal architecture is preserved 2) entrapment of malignant cells* within lymph nodes results in malignant cells taking residence in lymph nodes, proliferating & causing nodal enlargement with destruction of nodal architecture Clinical manifestations: 1) size: a lymph node larger than 1 cm in diameter is considered enlarged. 2) location: see differential diagnosis 3) mobility - freely mobile lymph nodes are generally benign - lymph nodes fixed to underlying tissue are generally malignant 4) consistency - infection - tender - asymmetric - matted - may have inflamed, red overlying skin - lymphoma: - large - symmetric - firm - mobile; - non tender - rubbery - metastatic tumor - fixed - hard - discrete - non tender 5) temporal course - constant - intermittent 6) associated signs/symptoms: - cough - fever suggests infection vs malignancy - weight loss - night sweats - pruritus - fatigue - arthralgia - myalgia - hepatomegaly - splenomegaly - abdominal masses Laboratory: 1) malignancy suspected (fevers, night sweats, weight loss) - excisional lymph node biopsy* - histologic examination - culture - antigenic typing - chromosomal analysis - molecular studies 2) infection suspected - complete blood count (CBC) - peripheral blood smear - markers of inflammation - erythrocyte sedimentation rate (ESR) - serum C-reactive protein (CRP) - tuberculin skin test (PPD) - coccidioidomycosis serology if indicated - serum protein electrophoresis - heterophile antibodies - serum transaminases - antibodies to Toxoplasmosis - HIV testing - Bartonella hensellae serology 3) autoimmune disease or connective tissue disease suspected - see more specific disease * NEJM knowledge+ seems to endorse fine needle aspiration followed by a core biopsy (maybe not) [7] Radiology: 1) chest X-ray 2) ultrasound 3) computed tomography (CT) Differential diagnosis: 1) cysts 2) abscess Management: 1) infection a) empiric treatment with antibiotics for no more than 1-2 weeks b) observation for 15-30 days after appropriate treatment 2) other specifically directed therapy 3) 50% of lymph node biopsies are non diagnostic 4) 25% of patients with non-diagnostic biopsies develop disease in 1 year 5) observation (without laboratory testing or imaging) for - otherwise asymptomatic patients with - cervical or inguinal lymphadenopathy and - small, mobile lymph nodes of short duration (< several months) [2] - small, soft, freely mobile lymph nodes limited to adjacent sites [2]

Related

differential diagnosis of regional lymphadenopathy & acute encephalitis lymph node

Specific

cervical lymphadenopathy hilar lymphadenopathy inguinal lymphadenopathy lymphadenitis mediastinal lymphadenopathy sinus histiocytosis sinus histiocytosis with massive lymphadenopathy; Rosai-Dorfman disease tonsillar hypertrophy

General

lymphoid tissue disease; lymphoid disorder sign/symptom

Properties

ETIOLOGY: infection inflammation malignant neoplasm

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 603-604
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 10. American College of Physicians, Philadelphia 1998, 2012, 2015, 2022
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 324
  4. Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol. 1993 Dec;20(6):570-82. PMID: 8296196
  5. Sahai S. Lymphadenopathy. Pediatr Rev. 2013 May;34(5):216-27. PMID: 23637250
  6. Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg. 1999 Oct;34(10):1447-52. PMID: 10549745
  7. NEJM Knowledge+ Complex Medical Care