What are the extrapulmonary manifestations of Asthma, Tuberculosis (TB), Interstitial Lung Disease (ILD), Bronchiectasis, and Sarcoidosis?

Extrapulmonary Manifestations of Respiratory Diseases

Asthma

Asthma is primarily a pulmonary disease with minimal true extrapulmonary manifestations. The disease process is confined to the airways, though systemic inflammation may be present in severe cases. There is an epidemiological association with inflammatory bowel disease, where patients with IBD have increased risk of developing asthma (HR 1.83-2.72), but this represents comorbidity rather than direct extrapulmonary involvement 1.

Tuberculosis

Tuberculosis is a systemic disease that can affect virtually any organ system beyond the lungs. The extrapulmonary manifestations include:

• Lymphatic involvement: Extrathoracic lymph node disease is common, particularly cervical and mediastinal nodes 2
• Cutaneous manifestations: Skin involvement occurs through hematogenous spread or direct extension 2
• Skeletal disease: Bone and joint tuberculosis, most notably Pott's disease (spinal TB) 2
• Genitourinary involvement: Renal and genital tract disease from hematogenous dissemination 2
• Central nervous system: Tuberculous meningitis and tuberculomas represent severe extrapulmonary disease 2
• Gastrointestinal: Peritoneal and intestinal tuberculosis 2

The challenge lies in distinguishing TB from sarcoidosis, as both can trigger similar immunological responses and have overlapping clinical presentations 2.

Interstitial Lung Disease (ILD)

ILD frequently presents with significant extrapulmonary manifestations, particularly when associated with connective tissue diseases. The systemic involvement varies by underlying etiology:

Connective Tissue Disease-Associated ILD

• Musculoskeletal: Joint pain, swelling, muscle weakness, and fatigue are common in CTD-ILD 1, 3
• Dermatologic: Photosensitivity, rashes, and Raynaud's phenomenon occur frequently 1
• Rheumatologic: Pleuritis, dry eyes (sicca symptoms), and dry mouth suggest underlying autoimmune disease 1
• Vascular: Pulmonary hypertension develops in advanced disease, reflecting pulmonary vascular dysfunction and right ventricular compromise 1

Systemic Lupus Erythematosus-ILD

• Multisystem involvement: Cutaneous, musculoskeletal, renal, neurologic, and hematological manifestations are characteristic 1
• Pleural disease: The most common pulmonary manifestation in SLE 1
• Gastroesophageal reflux: Associated with increased ILD risk 1

Idiopathic Inflammatory Myopathy-ILD

• Muscle involvement: Proximal muscle weakness and elevated muscle enzymes 1
• Autoantibody profiles: Anti-MDA5 and anti-synthetase antibodies predict rapidly progressive ILD 1

Cardiovascular Complications

• Right ventricular dysfunction: Common across all ILD types, with reduced O2 pulse and elevated heart rate at submaximal exercise 1
• Pulmonary hypertension: A predictor of poor prognosis requiring specific evaluation 1

Constitutional Symptoms

• Weight loss, malaise, and fatigue may occur, though fever is rare in IPF and suggests alternative diagnosis 1

Bronchiectasis

Bronchiectasis in the context of inflammatory bowel disease represents the most well-documented extrapulmonary connection. The manifestations include:

• IBD-associated bronchiectasis: The inflammatory lesions mirror those in the digestive tract, suggesting shared mucosal immune dysfunction 1
• Airway inflammation: Involves the bronchial tree from glottis to small airways 1
• Progressive airway destruction: Can lead to subglottic/tracheal strictures, chronic bronchitis, and bronchiolitis obliterans 1
• Post-surgical timing: More frequently observed after colonic surgery in IBD patients 1
• Systemic associations: Patients with COPD have significantly elevated risk of both UC (HR 1.83) and CD (HR 2.72) 1

The gastrointestinal and respiratory tracts share components of the common mucosal immune system, explaining the epithelial and mucosal immune defects that link these conditions 1.

Sarcoidosis

Sarcoidosis is fundamentally a multisystem granulomatous disease with extrapulmonary involvement in approximately 40% of patients with pulmonary disease. The extrapulmonary manifestations are diverse and clinically significant:

Most Common Sites

• Extrathoracic lymph nodes: The most frequent extrapulmonary site (detected in 147 of 258 patients with extrapulmonary involvement) 4
• Cutaneous involvement: Second most common site (86 of 258 patients), including erythema nodosum, lupus pernio, and papular lesions 4

Organ-Specific Manifestations

• Ocular disease: Requires baseline eye examination once diagnosis is established 1
• Cardiac involvement: Myocardial sarcoidosis can cause disproportionate cardiovascular abnormalities affecting both left and right ventricles; baseline electrocardiogram is recommended 1
• Neurologic: Central and peripheral nervous system involvement 1
• Renal: Can cause hypercalcemia and direct renal parenchymal disease 1

Clinical Indicators of Extrapulmonary Disease

• Fatigue: Significantly more common in patients with extrapulmonary involvement (16.6% vs 8.3%) 4
• Elevated serum ACE levels: Higher in extrapulmonary disease (79.0±46.9 IU/L vs 69.7±38.7 IU/L) 4
• More severe HRCT findings: Patients with extrapulmonary involvement show more deteriorating radiographic patterns 4
• Fever: Can occur as part of systemic inflammatory presentation, though bilateral hilar adenopathy without B symptoms is more typical 5

Critical Organ Involvement Requiring Treatment Modification

Immunotherapy should be withheld in patients with extensive disease (stage ≥2), extrapulmonary disease involving critical organ systems (ocular, myocardial, neurologic, renal), or sarcoid-related hypercalcemia 1.

Common Pitfall

The presence of fever and productive cough should trigger infectious disease consultation, as these atypical symptoms may indicate competing diagnoses rather than sarcoidosis itself 5, 6. Fiberoptic bronchoscopy with bronchoalveolar lavage may be necessary to exclude infections 6.