Infections and AA amyloidosis: An overview

Abstract

Background Amyloidoses are a heterogeneous group of systemic diseases characterised by extracellular accumulation of insoluble amyloid fibrils derived from unfolded proteins. Inflammatory (AA) amyloidosis can complicate various inflammatory disorders that are associated with a sustained acute phase response and serum amyloid A (SAA) protein overproduction. Chronic infections were the first recognised cause of amyloidoses. However, with the better management of underlying diseases, the frequency of AA amyloidosis is decreasing. Purpose The aim of this overview was to discuss the several infections associated with AA amyloidosis and the relative frequency of infections as aetiological factors. Methods A search of the literature was performed using the PubMed database using the MeSH terms “Amyloidosis” and “Infections,” from inception to December 31st, 2019. Articles written in other languages than English or French were excluded. Results The frequency of AA amyloidosis secondary to infections decreased from more than 50% to less than 20% after the 2000s, with a parallel increase in the frequency of AA amyloidosis secondary to inflammatory diseases and to an unknown cause. Conclusion Whereas new antibiotics have been developed and sanitary conditions are better, infections still represent 5%‐30% of the causes of AA amyloidosis, including in developed countries. These data argue for better screening of chronic infections to prevent AA amyloidosis and the development of new strategies to manage recurrent infections.

Systemic Amyloid A Protein Amyloidosis With Gastrointestinal Involvement

“…AA amyloidosis is a result of overproduction of serum AA in response to inflammation. 4,7,10 Reported causes of AA amyloidosis in developed countries, such as the United States, have been associated with chronic inflammatory conditions-rheumatoid arthritis, juvenile idiopathic arthritis, ankylosis spondylitis, familial Mediterranean fever, inflammatory bowel disease, chronic infection, and some malignancies. 3,5,6,8 AA amyloidosis is an unrecognized complication among PWIDs.…”

“…2,3 Systemic AA amyloidosis is characterized by the deposition of serum amyloid A (SAA) protein in tissues/organs in response to inflammation or infection. 4,5 The SAA protein is an acute-phase reactant produced by hepatocytes during inflammation, and its deposition levels in tissue are associated with the chronicity of the inciting factor. 6,7 Although AA amyloidosis is less prevalent in developed countries possibly due to good access to effective treatment of inflammatory conditions, several chronic inflammatory conditions have been associated with AA amyloidosis, with rheumatoid arthritis been recognized as the most common etiology in the developed countries.…”

Therapeutic effects of biological treatments on AA amyloidosis associated with inflammatory bowel disease: a case report and literature review

“…In the vast majority of cases, AA amyloidosis is discovered many years after IBD, only one case was discovered before IBD [30]. Serum AA is an acute phase reactant and precursor protein of AA amyloidosis, the pathophysiology includes the accumulation of SAA protein in the organs [39], such as the kidney, gastrointestinal tract, liver, lungs, skin, peripheral nerves, and soft tissue [40], while tumor necrosis factor (TNF), IL-1, and IL-6 all have a role in its synthesis by hepatocytes; thus, inhibition of previous cytokines may help in management [11]. The presentations differ depending on the organ involved; cardiac infiltration has been well reported in other kinds of amyloidosis, while the frequency and clinical relevance are much lower in AA amyloidosis [41].…”

Serum Amyloid A Protein–Associated Kidney Disease: Presentation, Diagnosis, and Management

“…Systemic AA amyloidosis has been demonstrated to have multiorgan involvement, with biopsy-proven disease in the kidney, liver, gastrointestinal tract, peripheral nerves, lungs and skin, and soft tissue. 11 Presentations vary depending on specific organ involvement; however, new-onset proteinuria and progressive decreased kidney function appear to be by far the most commonly involved organ system, in some cases at over 90% of patients at presentation. 2 Lung involvement, presenting as a bilateral interstitial pattern and nerve involvement presenting as peripheral neuropathy appears to be less common.…”