PA3.3 | Chronic & Granulomatous Inflammation — Summary & Reflection

REFLECT

Consider a 45-year-old woman with a 6-month history of progressive breathlessness, bilateral hilar lymphadenopathy on CXR, and a serum ACE level of 180 U/L. Lymph node biopsy reveals non-caseating granulomas with no organisms on special stains.

1. What is the most likely diagnosis, and what cells would you expect to predominate in the granuloma?
2. If she were started on an anti-TNF agent for a co-existing autoimmune condition, what complication would you anticipate and why?
3. How would the histological picture differ if this were tuberculosis rather than the suspected diagnosis?

Write 3–5 sentences addressing each question before reviewing your answers with your tutor.

KEY TAKEAWAYS

Chronic inflammation is defined by simultaneous active inflammation, tissue destruction, and repair — not just duration. The dominant cells are macrophages, lymphocytes, and plasma cells (not neutrophils).

Key causes: persistent infection, foreign body, autoimmunity, unresolved acute inflammation.

Macrophage polarisation determines outcome: M1 (IFN-γ driven) destroys tissue; M2 (IL-4/IL-13 driven) repairs it. When macrophages cannot eliminate the agent, they transform into epithelioid histiocytes and fuse into Langhans (peripheral horseshoe nuclei) or foreign-body (random nuclei) giant cells, forming a granuloma.

Granuloma formation requires IFN-γ (Th1) + TNF-α — disrupting TNF-α (anti-TNF drugs) dissolves granulomas and reactivates latent TB.

Caseating granulomas (cheesy necrosis) → TB, fungal infections. Non-caseating granulomas → sarcoidosis, Crohn, foreign body, tuberculoid leprosy.

Systemic effects — fever (endogenous pyrogens/PGE2), ↑CRP, ↑ESR (via fibrinogen), leucocytosis — reflect sustained cytokine release and are the bedside and laboratory correlates of ongoing chronic inflammation.