What are the sequelae of healed granulomatous disease, such as tuberculosis or histoplasmosis, in the lung?

Sequelae of Healed Granulomatous Disease in the Lung

Healed granulomatous lung disease, such as tuberculosis or histoplasmosis, commonly results in calcified pulmonary nodules (histoplasmomas), mediastinal lymph node calcifications, broncholithiasis, fibrosing mediastinitis, bronchiectasis, and emphysematous changes, with most sequelae being asymptomatic and requiring no treatment.

Benign Calcified Sequelae (No Treatment Required)

Pulmonary Nodules (Histoplasmomas)

• Calcified pulmonary nodules are the most common sequela and represent contracted sites of prior infection that persist indefinitely 1
• Calcification typically appears in the center or in concentric rings and may require years to develop 1
• These nodules are asymptomatic, usually discovered incidentally on chest imaging, and frequently removed surgically only to exclude malignancy 1
• Antifungal treatment is not recommended for isolated pulmonary nodules, as they contain no viable organisms and do not respond to therapy 1
• Histoplasmomas may enlarge slowly and occasionally cavitate, but this does not indicate active infection 1

Calcified Mediastinal Lymph Nodes

• Calcified hilar and mediastinal lymph nodes represent healed granulomatous inflammation 1
• These are nonprogressive in the majority of cases after specific immunity develops 1
• No treatment is indicated for asymptomatic calcified lymphadenopathy 2

Symptomatic Structural Sequelae

Broncholithiasis

• Broncholithiasis occurs when calcified lymph nodes erode into adjacent bronchi, causing hemoptysis, localized wheeze, and obstructive pneumonitis 1
• Patients may expectorate small chalk-like pieces (lithoptysis) 1
• Bronchoscopic or surgical removal of the broncholith is recommended; antifungal treatment is not indicated 1

Fibrosing Mediastinitis

• Fibrosing mediastinitis is characterized by invasive fibrosis that encases mediastinal or hilar structures, causing occlusion of central vessels and airways 1
• Approximately 20% of cases involve bilateral lung involvement and carry high mortality 1
• Most patients have superior vena cava occlusion or single lung dysfunction with significant morbidity but favorable long-term survival 1
• Neither antifungal nor anti-inflammatory treatment ameliorates the outcome of established mediastinal fibrosis 1
• If clinical findings suggest an inflammatory process rather than chronic fibrosis (elevated ESR, positive complement fixation antibodies), a 12-week course of itraconazole 200 mg once or twice daily may be considered 1

Granulomatous Mediastinitis

• This represents a more inflammatory process that may respond to treatment 1
• Itraconazole 200 mg once or twice daily for 6-12 months is recommended for symptomatic granulomatous mediastinitis 1
• Amphotericin B followed by itraconazole may be used for severe cases 1

Pulmonary Parenchymal Sequelae

Bronchiectasis and Emphysema

• Bronchiectasis develops as a consequence of granulomatous inflammation and tissue destruction during active disease 1
• Studies of excised lung tissue suggest that granulomatous inflammation is the etiology for bronchiectasis in many cases 1
• Localized emphysema and bullae formation are common secondary changes 3
• These structural changes predispose to secondary infections including aspergillosis, atypical mycobacteriosis, and bacterial airway infections 4

Atelectatic Induration

• Lobar atelectatic induration forms from organized destructive pneumonia following tuberculous granulomatous pneumonia 3
• This represents permanent scarring and fibrosis that occurs when damage to surrounding tissue is severe 5

Serious Complications Requiring Monitoring

Secondary Fungal Infections

• Residual cavities from healed granulomatous disease are at high risk for Aspergillus colonization and infection 3
• Aspergillus can form fungus balls (aspergillomas) in 7 of 11 cases with cavity colonization 3
• Semi-invasive aspergillosis with necrotizing pneumonia can develop and become a direct cause of death 3

Chronic Respiratory Failure

• Progressive loss of pulmonary function from extensive fibrotic changes can lead to chronic lung failure with cor pulmonale 3
• Mean heart weight increases to 335 grams with decreased left ventricle to right ventricle ratio (1.24) in patients with low lung function from sequelae 3

Risk of Reactivation

• Dormant organisms can remain in healed granulomas and reactivate when cellular immunity wanes, particularly when CD4+ counts fall below 150 cells/μL 6
• Reactivation can occur years after leaving endemic areas 6
• Immunosuppression from any cause (transplantation, autoimmune disease treatment, HIV) increases reactivation risk 6

Key Clinical Pitfalls

• Do not treat asymptomatic calcified nodules, lymph nodes, or splenic lesions with antifungal therapy—they do not contain viable organisms and will not respond 2
• Distinguish between fibrosing mediastinitis (no treatment benefit) and granulomatous mediastinitis (may respond to itraconazole) based on inflammatory markers and imaging characteristics 1
• Monitor residual cavities for secondary fungal colonization, which requires different management than the original granulomatous disease 3
• Patients with extensive bilateral fibrotic changes require long-term monitoring for progressive respiratory failure and cor pulmonale 3