Granulomatous diseases of lung

    • Necrotizing lesions:
      • Tuberculosis
      • Necrotizing sarcoidal granulomatosis
    • Non-necrotizing lesions:
      • Sarcoidosis
      • Pneumonitis
      • Fungal infections
      • Eosinophilic granulomatous polyangitis
      • Polyangitis with granulomatosis

Tuberculosis

Etiology:

                Infectious disease caused by mycobacterium Tuberculosis. The pulmonary form occurs by inhalation of droplets containing organisms. The nonpulmonary form most often caused by ingestion of infected milk.

Types of tuberculosis:

    1. Primary tuberculosis:

                It is initial infection, characterized by primary or Ghon complex, the combination of peripheral subpleural parenchymal lesion and involved hilar lymph nodes.

    1. Secondary tuberculosis:

                It results from activation of a prior Ghon complex with spread to a new pulmonary or extrapulmonary site.

Clinical features:

Fever, hemoptysis, progressive disability, pleural effusion and generalized wasting.

Pathological findings:

    • Granulomas: composed of epithelioid histiocytes, multinucleated giant cells and cuff of surrounding lymphocytes
    • Necrosis with caseation
    • Scarring and calcification
    • Zeihl-Nelson stain highlights the organisms

Pathogenesis:

    • Organisms are ingested by macrophages which process the bacterial antigens for presentation to CD4 T-helper 1 cells
    • The CD4+ T cells proliferate and secrete cytokines, attracting lymphocytes and macrophages
    • Macrophages ingest and kill some of the bacilli or are morphologically altered to form epithelioid cells and langhans multinucleated giant cells

Sarcoidosis

It is common multisystem granulomatous disease of unknown etiology . Lung is most commonly involved organ occurring in 90% of cases.

Clinical features:

    • Young ranging from 20-40 years
    • More common in African-Americans
    • Women are affected more
    • Half of the patients are asymptomatic
    • Dyspnea and cough are most common symptoms

Radiographically:

    • Most common abnormality is hilar adenopathy (in around 50% of cases)
    • 30% of cases have both hilar adenopathy and parenchymal infiltrates
    • In 12% cases parenchymal infiltrates only
    • Small nodules are seen on CT scan in almost all cases

Laboratory tests:

    • 80% patients with active sarcoidosis have elevated angiotensin-converting enzyme in the serum
    • TNF concentration in bronchoalveolar fluid

Pathological Findings:

    • Non-necrotizing granulomas involving pleura, connective tissue septa and interstitium around pulmonary vessels and bronchi
    • Granulomas and fibrosis are in lymhangitic distribution
    • Granulomas are small and composed of epithelioid histiocytes and multinucleated giant cells
    • The histiocytes are tightly packed and granulomas are discretely marginated, with few lymphocytes mixed.
    • Outer borders show concentric laminated collagen giving them an onionskin appearance
    • Laminated concretions composed of calcium and proteins known as Schaumann bodies and stellate inclusions known as asteroid bodies.

Pathogenesis:

etiology of sarcoidosis is unknown however it is suggested that it is disease of disordered immune regulation in genetically predisposed individuals

    • Immunological factors:
      • Intra-alveolar and interstitial accumulation of CD4+ T cells, resulting in CD4/CD8 T-cells ratios ranging from 5:1 to 15:1 suggesting pathogenic involvement of CD4+ helper T cells
      • Increased levels of T cell derived TH1 cytokines such as IL-2 and IFN-gamma, which may be responsible for T cell expansion and macrophage activation.
      • Increased levels of T cell derived TH1 cytokines that favour recruitment of additional T cell and monocytes. It contributes in formation of gtranulomas
      • TNF is raised at high levels and TNF concentration in bronchioalveolar fluid is marker of disease activity
      • Impaired dendritic cell function
    • Genetic factors:
      • Association of certain HLA genotypes like HLA-A1 and HLA-B8

Non-necrotizing sarcoidosis

Clinical symptoms:

    • Low grade fever and cough

Radiographically:

    • Single or multiple nodules

Microscopically:

    • Sarcoidal granulomas coalescing to form large nodular collection of granulomatous inflammation
    • Pulmonary arteries show vasculitis
    • Lymphocytic infiltration, mural fibrosis and luminal obliteration
    • Central necrosis can be striking
    • It is diagnosis of exclusion
    • Tuberculosis and fungal infection should be carefully ruled out

Treatment and prognosis:

    • Responds well to steroid therapy
    • Prognosis is excellent

Fungal and fungi-like bacterial infections

    1. Actinomycosis:
    • Gram positive anaerobic filamentous bacteria
    • Abscess and sinus tract formation
    • Exudates contains characteristic sulphur granules
    1. Nocardiosis:
    • Gram positive aerobic filamentous bacteria
    • Weakly acid-fast
    • Opportunistic bacteria
    1. Candidiasis:
    • Caused by candida albicans
    • Budding yeast cells, pseudohyphae and septate hyphae are seen
    1. Cryptococcosis:
    • Caused by Cryptococcus neoformans
    • Encapsulated organisms with narrow based buds
    1. Aspergillosis:
    • Caused by Aspergillus
    • Acutely branching,hyaline, septate fungal hyphae
    1. Histoplasmosis:
    • Organism name is Histoplasma Capsulatum
    • Intracellular budding yeast cells are characteristics
    1. coccidiodomycosis:
    • Coccidioides immitis
    • Fungal spherules containing endospores within granulomas

DR SAADIA HAFEEEZ

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