The pattern of amyloidosis in Malaysia.

Congo red screening of routine biopsies at the University Hospital Kuala Lumpur revealed the following categories of amyloidosis: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). Unlike in the West, AA amyloidosis in this population was usually secondary to leprosy or tuberculosis. Liver involvement in AL amyloidosis was shown to exhibit a sinusoidal pattern and differed from the vascular pattern of AA amyloidosis. Within the category of AA amyloidosis, there were two patterns of renal involvement--glomerular and vascular, with the glomerular pattern carrying a more ominous clinical picture. Notable among the localized amyloidoses were isolated atrial amyloidosis complicating chronic rheumatic heart disease, intratumour amyloidosis within nasopharyngeal carcinomas and dystrophic amyloidosis which occurred in fibrotic tissues.

The pattern of amyloidosis in a Malaysian patient population.

Congo red screening of 27,052 routine biopsy specimens from 22,827 patients over a 5 1/2-year period in the Department of Pathology, University of Malaya detected 186 cases of amyloidosis. The categories of amyloidosis encountered and their prevalences in relation to each other were: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). A third of patients with systemic AL amyloidosis had coexistent immunocyte abnormality. The commonest underlying pathology for systemic AA amyloidosis was leprosy. Notable among the types of localized amyloidosis revealed by this study were isolated atrial amyloidosis, which appeared to complicate chronic rheumatic heart disease, and intratumour amyloidosis complicating nasopharyngeal carcinoma. Other tumours in which amyloid deposits were observed included basal cell carcinoma, islet cell tumour and medullary carcinoma of the thyroid. Dystrophic amyloidosis was observed in fibrotic tissues, such as damaged cardiac valves and osteoarthritic joints. Heredofamilial amyloidosis, senile systemic amyloidosis and degenerative cerebral amyloidosis were notably absent from this study.

Autopsy findings in 35 cases of leprosy in Malaysia.

The findings of autopsies performed on 35 leprosy subjects in the University Hospital, Kuala Lumpur, between January 1981 and December 1985 are presented. This is the first report based on autopsy findings from Malaysia. The patients were elderly subjects with a mean age of 74 years. Sixty-six percent had lepromatous leprosy. None had active skin lesions. The most common cause of death was pyogenic infection, particularly bronchopneumonia. Tuberculosis was noted in 25% of the cases. The other important causes of death included cardiac and renal failure. Renal lesions were evident in 71% of the cases, and the most common pathology was interstitial nephritis. Generalized amyloidosis complicated six (17%) patients.

Serum amyloid protein SAA, C-reactive protein and lysozyme in leprosy.

Serum amyloid protein (SAA) appears to be the precursor of amyloid protein AA, the non-immunoglobulin fibril protein of secondary amyloidosis. Since amyloidosis is known to occur in high frequency associated with lepromatous leprosy (LL), we have examined the SAA levels in untreated LL patients and compared them to the levels observed in patients with tuberculoid leprosy (TT) and a large number observed in healthy controls. We found that SAA is markedly elevated in LL when compared to TT and controls. No clear correlation could be established with C-reactive protein, a well-documented acute phase reactant, or serum lysozyme levels that reflect the presence of monocyte activity. This study showed that SAA levels in leprosy do not appear to be a reflection of inflammatory activity or monocyte turnover. Whether amyloidosis will be more prevalent in patients who have higher SAA levels remains to be determined.

Amyloid fibril proteins found in Papua New Guinean and other amyloidoses.

Recent studies have established that amyloid fibrils found in different clinical conditions differ in the nature of their constituent proteins. In primary amyloidosis and in amyloidosis associated with multiple myeloma or macroglobulinaemia the amyloid fibrils are usually largely composed of fragments of immunoglobulin light chains. In secondary amyloidosis, protein AA, a unique protein unrelated to immunoglobulins, is the major component of the fibrils. Other chemical types of amyloid have been described in primary medullary carcinoma of the thyroid and in senile cardiac amyloidosis. In Papua New Guinea amyloidosis is seen secondary to chronic infections such as leprosy and tuberculosis as well as in patients without an apparent predisposing disease. The amyloid proteins obtained from a representative range of Papua New Guinean patients have been characterised and in all cases examined the amyloid was found to be of the protein AA or secondary type. Current research into the pathogenesis of secondary amyloidosis centres on the mechanisms whereby protein AA is derived from the presumed precursor molecule, protein SAA, which is a normal acute-phase reactant.

Secondary amyloidosis and the serum amyloid precursor in leprosy: geographical variation and association with leukocytosis.

The prevalence of the amyloid-related serum component, protein SAA, was investigated in two groups of leprosy patients from different areas of Papua New Guinea. Protein SAA was more prevalent in coastal leprosy patients (49% positive) than in highland patients (21% positive). Paradoxically, many more cases of amyloidosis were diagnosed in the highland group (17 of 199) than in the coastal group (3 of 112). In the highland patient group, SAA was found to correlate with the leprosy disease spectrum, being more prevalent in patients toward the lepromatous pole. Borderline and tuberculoid patients who had detectable SAA usually had neurotrophic ulcers. No such relationships were observed in the coastal patient group, probably because other infections, more common on the coast, were also responsible for causing increased concentrations of SAA which is known to behave as an acute phase reactant. A correlation was observed between SAA positivity and neutrophil leukocytosis. This suggests that various inflammatory stimuli such as erythema nodosum leprosum reactions, neurotrophic ulcers and intercurrent infections, all contribute to the prevalence of SAA in leprosy patients.

Amyloid fibril protein AA in Papua New Guinean amyloidosis.

In this study of protein composition of amyloid fibrils isolated from eight patients representative of the spectrum of amyloidosis found in Papua New Guinea has been investigated. All fibril preparations, including three from patients with amyloidosis secondary to lepromatous leprosy and one from an unusual juvenile case of primary amyloidosis, contained the non-immunogobulin amyloid protein, protein AA. However, only 44% of thirty-six amyloid patients had detectable levels of the protein AA-related serum component, protein SAA. Alkali-degraded material from each of the fibril preparations failed to react in double immunodiffusion test with antiserum to the amyloid-related light chain VgammaV, but evidence was found for this immunoglobulin light chain-specificity in the serum of one patient.