A rare condition characterised by extracellular deposition of abnormal insoluble protein (amyloid) which is relatively resistant to proteolysis.
Pathophysiology:
Amyloid consists of fibrils formed by proteins of different types (the precursor protein). The different proteins that form amyloid fibrils in different types of amyloid have different individual amino acid sequences, size, function and structure and are normally soluble, but within amyloid plaques they form misfolded aggregates of insoluble fibrils with similar structure and the following common appearance and properties:
· amorphous eosinophilic appearance on light microscopy (H&E staining)
· all take up congo red stain and exhibit apple green birefringence under polarized light
· fibrillar pattern on electron microscopy
· B-pleated sheet pattern on x-ray diffraction
Aetiology unknown, possibly due to derangement in autoregulation after protracted antigenic challenge
Amyloidosis can involve any organ. Nodular accumulation within an organ can affect function. Diffuse accumulation within an organ leads to organ failure.
Epidemiology, classsification and and clinical presentation:
Amyloidosis may be familial (very rare), primary (AL, idiopathic) or secondary (AA, secondary to chronic inflammation, infection or chronic renal failure) and is reported to be commoner in males than in females.
Primary amyloidosis may be localised or systemic.
Secondary amyloidosis is invariably systemic.
Historically, amyloidosis has been classified according to anatomic distribution:
· Localized disease (10–20%)1. Locally produced amyloid is deposited focally in a single organ/system. Diagnosis requires the absence of systemic amyloidosis
· Systemic disease (80–90%)1. Systemic amyloid can be diagnosed by the presence of amyloid on renal biopsy, biopsy of subcutaneous fat, rectal biopsy, bone marrow biopsy or serum.
Current WHO classification of amyloidosis is based on the biochemical composition of the fibrillar component. The overwhelming majority of cases are either primary systemic (AL) or secondary systemic (AA) amyloid.
Primary systemic amyloidosis is known within the WHO classification as amyloid light chain amyloidosis (AL amyloid). The fibrillar component is a variable light chain immunoglobulin which is therefore unique to each patient. 30% of patients with primary amyloidosis will progress to multiple myeloma2 and plasma cells involve less than 25% of the bone marrow3.
In secondary systemic amyloidosis, the fibrillar component is part of the acute phase reactant serum amyloid A (SAA) which is secreted by the liver and is elevated in the serum in response to chronic disease states. Amyloid A (AA) is the precipitating protein in amyloid deposits in these patients and is identical in all patients.
Pulmonary amyloidosis:
Pulmonary amyloidosis may be a manifestation of systemic amyloidosis (usually primary systemic/AL amyloidosis) or it may be a localised disease (primary pulmonary/localised amyloidosis). 88% of patients with systemic amyloidosis are found to have pulmonary involvement at autopsy4. Clinically significant pulmonary amyloidosis and radiographic evidence of pulmonary amyloidosis is uncommon5.
Most cases of pulmonary involvement occur in primary systemic (AL amyloidosis)5 and, in fact, pulmonary involvement is almost the rule in primary systemic amyloidosis. The incidence of pulmonary involvement in secondary systemic amyloidosis (due to chronic inflammation, infections or neoplasm) is low. The remaining cases of pulmonary involvement occur as localised primary amyloidosis. Isolated pulmonary amyloidosis is rare and its diagnosis requires the absence of systemic amyloidosis. In localised pulmonary amyloidosis the amyloid may be AM or AL, with most cases being AL.
Pulmonary manifestations of amyloidosis depend on whether the disease is local or systemic and can be parenchymal or tracheobronchial.
Manifestations of pulmonary amyloidosis:
Parenchymal involvement may be diffuse (alveolar septal) or nodular (amyloidomas).
Tracheobronchial amyloidosis may present as intra luminal masses (amyloidomas) or submucoal plaques.
Isolated pulmonary vascular deposition, without clinically significant parenchymal involvement, is a histological finding that occurs to some extent in all forms6 and may be associated with pulmonary hypertension (8 cases)7.
Hilar/mediastinal lymphadenopathy has also been described as a manifestation of pulmonary amyloidosis.