Week 2: granulomatous lung disease

Question 1

Pathophysiology of granulomas

Answer 1

• compact aggregates of epitheloid cells
• form to confine pathogens, restrict inflammation and protect surrounding tissues
  1. antigen initiates immune response
  2. APCs produce immune mediators: TNF-a, Il12, 15,18, MIP-1, GM-CSF
  3. activated CD4+ T cells differentiate into Th1-like helper cells, secrete Il-2 and IFN-y. Macrophages become activated and transformed to become epithelioid cells
  4. Some cases have activation of T cells to Th2 helper cells, producing Il-4,10,13, fibroblast proliferation and collagen production. Fibrosis.

Question 2

Variations in pulmonary granulomas: Sarcoidosis, hypersensitivity pneumonitis, cryptococcal pneumonia, polyangiitis

Answer 2

1. Sarcoidosis: non necrotizing granuloma with epithelioid cells and giant cells surrounded by lymphocytes
2. Hypersensitivity pneumonitis: loosely formed granulomas in interstitium
3. Cryptococcal pneumonia: granulomatous inflammation with cryptococcal spore phagocytosed by giant cels
4. Granulomatosis with polyangiitis (GPA): granulomatous inflammation with vasculitis

Question 3

Sarcoidosis

Answer 3

1. multi-organ systemic disease that can affect anyone
2. lung and skin commonly involved
   - Lofgren’s syndrome: arthritis, erythema nodosum, bilateral hilar adenopathy (BHA)
   - Heerfordt’s syndrome: uveitis, parotid gland inflammation, fever, may have facial nerve involvement
3. clinical diagnosis
4. radiograph: most common see bilateral hilar adenopathy
5. can treat with steroids, long term treatment benefits are unclear. many resolve spontaneously

Question 4

Hypersensitivity pneumonitis

Answer 4

1. immunological reaction in inhaled organic antigen
   - farmer’s lung: thermophilic actinomycete in moldy hay
   - pigeon-breeder’s lung
   - mapel bark lung
   - suberosis or cork workers
2. Type III or IV immune reactions
3. Acute/subacute
   - cough, fever, chest tightness, malaise
   - loosely formed granulomas
   - diffuse nodular on x-ray
4. chronic
   - progressive dyspnea over years, wt. loss, may have cough

Question 5

Chronic beryllium disease (berylliosis)

Answer 5

1. clinically indistinguishable form sarcodosis
2. dx made with beryllium lymphocyte proliferation test
3. treat with corticosteroids

Question 6

ANCA associated granulomatous vasculitis

Answer 6

1. formerly called wegener’s
2. unknown cause
3. typically involvement
   - URT: sinusitis, saddle nose, epistaxis
   - lungs: alveolar hemorrhage, hemoptysis
   - kidney: glomerulonephritis, hematuria
4. dx: requires biopsy
   - ANCA test, but negative test doesn’t exclude
5. immunosuppressive therapy with corticosteroids and cyclophosphamide or other agents