Table 1.

Pragmatic differential diagnosis of generalized lymphadenopathy

Generalized lymphadenopathy
InflammatoryAutoimmuneInfectiousNeoplastic/clonalMiscellaneous/other
iMCD-TAFRO/iMCD-NOS/iMCD-IPL SLE Bacterial BCL IgG4-RD 
HLH ALPS M. tuberculosis and other Mycobacterium species TCLs, including AITL Serum sickness 
MIS-C/A RA (majority localized) Secondary syphilis (early primary is often localized) Hodgkin lymphoma Drug-induced hypersensitivity syndrome 
Kawasaki disease (children) SS (majority localized) Atypical infections POEMS and POEMS-MCD Amyloidosis 
Kikuchi-Fujimoto disease sJIA, AOSD Bacterial sepsis Metastatic carcinomas Sarcoidosis 
Kimura disease Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) Lymphogranuloma venereum (Chlamydia trachomatisLeukemias (ALL/AML/CML/CLL) Lipid storage diseases 
VEXAS syndrome  Chancroid (often localized) Rosai-Dorfman disease Chronic granulomatous diseases 
Inflammatory pseudotumor Typhoid fever Erdheim-Chester disease Angioimmunoblastic lymphadenopathy with dysproteinemia 
Viral LCH Other granulomatous diseases (silicosis, berylliosis) 
HIV Kaposi's sarcoma  
Acute hepatitis (HBV, HCV)  
CMV, EBV 
HHV8 and HHV8-MCD 
HHV6 
HSV 
Adenovirus 
Dengue fever 
Measles, mumps (often localized), and rubella viruses 
Other 
Toxoplasma gondii (toxoplasmosis), Leishmania (leishmaniasis) 
Histoplasmosis, coccidioidomycosis, cryptococcosis 
Generalized lymphadenopathy
InflammatoryAutoimmuneInfectiousNeoplastic/clonalMiscellaneous/other
iMCD-TAFRO/iMCD-NOS/iMCD-IPL SLE Bacterial BCL IgG4-RD 
HLH ALPS M. tuberculosis and other Mycobacterium species TCLs, including AITL Serum sickness 
MIS-C/A RA (majority localized) Secondary syphilis (early primary is often localized) Hodgkin lymphoma Drug-induced hypersensitivity syndrome 
Kawasaki disease (children) SS (majority localized) Atypical infections POEMS and POEMS-MCD Amyloidosis 
Kikuchi-Fujimoto disease sJIA, AOSD Bacterial sepsis Metastatic carcinomas Sarcoidosis 
Kimura disease Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) Lymphogranuloma venereum (Chlamydia trachomatisLeukemias (ALL/AML/CML/CLL) Lipid storage diseases 
VEXAS syndrome  Chancroid (often localized) Rosai-Dorfman disease Chronic granulomatous diseases 
Inflammatory pseudotumor Typhoid fever Erdheim-Chester disease Angioimmunoblastic lymphadenopathy with dysproteinemia 
Viral LCH Other granulomatous diseases (silicosis, berylliosis) 
HIV Kaposi's sarcoma  
Acute hepatitis (HBV, HCV)  
CMV, EBV 
HHV8 and HHV8-MCD 
HHV6 
HSV 
Adenovirus 
Dengue fever 
Measles, mumps (often localized), and rubella viruses 
Other 
Toxoplasma gondii (toxoplasmosis), Leishmania (leishmaniasis) 
Histoplasmosis, coccidioidomycosis, cryptococcosis 

Atypical infections: Rickettsia, Leptospira, Bartonella, Brucella (brucellosis), Francisella tularensis (tularemia, often localized), diphtheria (often localized), Yersinia pestis (often localized, buboes), and Ehrlichia.

AITL, angioimmunoblastic T-cell lymphoma; ALL, acute lymphoid leukemia; ALPS, autoimmune lymphoproliferative syndrome; AML, acute myeloid leukemia; AOSD, adult-onset Still's disease; BCL, B-cell lymphoma; CML, chronic myeloid leukemia; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HBV, hepatitis B; HCV, hepatitis C; HHV8, human herpesvirus 8; HHV8-MCD, human herpesvirus 8-associated multicentric Castleman disease; HHV6, human herpesvirus 6; HLH, hemophagocytic lymphohistiocytosis; HSV, herpes simplex virus; IgG4-RD, immunoglobulin G4-related disease; iMCD-TAFRO/NOS/IPL, idiopathic multicentric Castleman disease-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis/renal insufficiency, organomegaly)/NOS (not otherwise specified)/IPL (idiopathic plasmacytic lymphadenopathy); LCH, Langerhans cell histiocytosis; MIS-C/A, multisystem inflammatory syndrome in children and adults; RA, rheumatoid arthritis; sJIA, systemic juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; SS, Sjögren's syndrome; TCL, T-cell lymphoma.

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