Infection, foreign body, sarcoidosis, Crohn disease and vasculitis
Mnemonic
Group them by mechanism:
Infective
- Tuberculosis and atypical mycobacteria, with caseation
- Leprosy, syphilis (gummata), brucellosis
- Fungal: histoplasmosis, cryptococcus
- Cat scratch disease, schistosomiasis
Non-infective
- Sarcoidosis, non-caseating
- Crohn’s disease, non-caseating and typically sparse
- Granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis
- Foreign body, including suture material and talc
- Berylliosis, silicosis
- Primary biliary cholangitis, de Quervain’s thyroiditis
- Drug reactions
“Caseation means tuberculosis until proven otherwise; non-caseating means sarcoid or Crohn’s.”
A granuloma is a collection of epithelioid macrophages, often with Langhans giant cells (nuclei arranged peripherally in a horseshoe), and it forms when the immune system cannot eliminate a stimulus, so it walls it off instead. It is a type IV process.
Expansion
A granuloma is a focal collection of activated epithelioid macrophages, often with multinucleate giant cells and a rim of lymphocytes. It forms when an agent resists elimination, walling it off instead.
Caseating
- Tuberculosis (the archetype), atypical mycobacteria, some fungi
Non-caseating
- Sarcoidosis
- Crohn disease
- Foreign body, including suture material and talc
- Berylliosis
- Granulomatosis with polyangiitis and other vasculitides
- Primary biliary cholangitis, cat scratch disease, leprosy, syphilis, schistosomiasis
- Drug reactions
Giant cell types offer clues: Langhans cells with a horseshoe of peripheral nuclei in tuberculosis, foreign body giant cells with haphazard nuclei, and Touton cells in xanthomas.
Formation requires T helper 1 cells and interferon gamma to activate macrophages, with TNF-alpha maintaining the structure. This is precisely why anti-TNF biologics cause reactivation of latent tuberculosis, and why screening is mandatory before starting them.