What are infiltrative diseases?

Infiltrative Diseases: Definition and Types

Infiltrative diseases are characterized by the deposition of abnormal substances or infiltration of inflammatory cells in tissues, resulting in organ dysfunction through impaired cellular function, necrosis, fibrosis, or disruption of normal architecture. 1

Cardiac Infiltrative Diseases

Infiltrative heart diseases are a subgroup of restrictive cardiomyopathies characterized by:

• Deposition of abnormal substances in the myocardium, resulting in myocardial thickening or dilation and restricted ventricular filling 1
• Disease progression that can lead to heart failure, conduction abnormalities, arrhythmias, and sudden death if left untreated 1
• Variable presentation depending on the specific disorder and stage of disease, ranging from minimal cardiac abnormalities to advanced restrictive and/or dilated cardiomyopathy 2

Common Cardiac Infiltrative Diseases

1. Amyloidosis

   • Characterized by deposition of amyloid protein fibrils in the myocardium 1
   • Most common types: AL (light chain) amyloidosis and ATTR (transthyretin-related) amyloidosis 1
   • Results in myocardial and valvular thickening, presenting with heart failure or arrhythmia 1

2. Sarcoidosis

   • Characterized by myocardial infiltration with noncaseating granulomas 1
   • Cardiac involvement occurs in 25% of patients with systemic sarcoidosis in the United States 1
   • Presents with conduction abnormalities, arrhythmias, sudden cardiac death, heart failure, pericardial effusion, or ventricular aneurysms 1

3. Hemochromatosis (Siderotic Cardiomyopathy)

   • Characterized by iron deposition from frequent blood transfusions and altered iron hemostasis 1
   • Presents in advanced stages with heart failure, conduction abnormalities, or sudden death 1
   • Highly treatable when diagnosed early 1, 3

4. Other Cardiac Infiltrative Diseases

   • Anderson-Fabry disease: glycosphingolipid deposition 1
   • Endomyocardial fibrosis: part of hypereosinophilic syndrome 1
   • Oxalosis: oxalate deposition causing LV thickening and conduction abnormalities 1
   • Friedrich ataxia: mitochondrial iron accumulation 1
   • Mucopolysaccharidoses: variable phenotypic expression 1

Pulmonary Infiltrative Diseases

Infiltrative lung diseases involve accumulation of inflammatory cells or substances in the lung parenchyma:

• Characterized by bilateral parenchymal infiltrates with variable degrees of tissue inflammation and fibrosis 1
• Present with exertional dyspnea, abnormal pulmonary physiology, and abnormal gas transfer 1
• May be acute or chronic in nature 1

Types of Pulmonary Infiltrative Diseases

1. Known Causes

   • Pneumoconioses (occupational lung diseases) 1
   • Connective tissue disease-associated ILD (CTD-ILD) 1
   • Hypersensitivity pneumonitis (HP) 1

2. Unknown Causes

   • Sarcoidosis: noncaseating granulomas in multiple organs 1
   • Idiopathic interstitial pneumonias (IIP) 1:
     • Idiopathic pulmonary fibrosis (IPF)
     • Nonspecific interstitial pneumonia (NSIP)
     • Desquamative interstitial pneumonia (DIP)
     • Respiratory bronchiolitis with interstitial lung disease (RBILD)
     • Acute interstitial pneumonia (AIP)
     • Cryptogenic organizing pneumonia (COP)
     • Lymphoid interstitial pneumonia (LIP)

3. Invasive Fungal Infiltrative Disease

   • Defined as fungal hyphae present 'within' the mucosal tissue 1
   • Common pathogens include Zygomycetes (Rhizopus, Mucor) and Aspergillus species 1
   • Characterized by angioinvasion of fungal hyphae producing thrombosis and tissue necrosis 1

Other Systemic Infiltrative Diseases

1. Niemann-Pick Disease

   • Characterized by foam cells (histiocytic cells swollen with stored lysosomal lipid) 1
   • Infiltration of foam cells into tissues leads to visceromegaly, pulmonary compromise, and marrow dysfunction 1
   • Types include NPA (severe neurologic involvement) and NPB (primarily visceral) 1

2. Langerhans Cell Histiocytosis

   • Characterized by abnormal proliferation of Langerhans cells 4
   • Can affect multiple organs including endocrine glands 4

Diagnosis of Infiltrative Diseases

• Clinical suspicion based on systemic manifestations and organ dysfunction 1, 3
• Laboratory tests: serum biomarkers specific to the suspected disease 1
• Imaging studies: echocardiography, cardiac MRI, CT, nuclear imaging 1, 2
• Tissue biopsy: often required for definitive diagnosis 1

Treatment Approaches

• Disease-specific therapies targeting the underlying pathological process 1, 3
• Supportive care for organ dysfunction 1
• Advanced therapies including organ transplantation in select cases 3
• Early diagnosis is critical for initiating therapy to mitigate deleterious effects 5, 3

Infiltrative diseases represent a diverse group of disorders that can affect multiple organ systems, with significant morbidity and mortality if not diagnosed and treated promptly. A high index of suspicion and appropriate diagnostic workup are essential for early intervention.