Systemic amyloidosis: a challenge for the rheumatologist

Abstract

Amyloidosis comprises a group of diseases characterized by the extracellular deposition of insoluble fibrillar proteins. This mechanism generates different clinical syndromes depending on the site and extent of organ involvement. Amyloidosis is classified into categories of systemic and localized disease. Systemic amyloidosis is further subdivided into a hereditary familial form (for example, ATTR amyloidosis), a reactive form (AA amyloidosis), dialysis-related (Aβ2M) amyloidosis and immunoglobulin light chain (AL) amyloidosis. Treatment can be symptomatic, directed at the affected organ, or can be directed at reducing the production of the abnormal proteins with different strategies. Despite advances in treatment, the prognosis is still poor and depends on the underlying disease as well as the type and degree of dysfunction in involved organs. Early diagnosis is essential because patients with advanced disease are generally unable to undergo intensive therapy. Patients with systemic amyloidosis often present to a rheumatologist not only because the disease can include musculoskeletal and articular symptoms but also because it can be associated with chronic rheumatic diseases. This Review discusses the clinical features of amyloidosis and its rheumatic manifestations. The various types of amyloidosis, as well their prognosis and treatment, are also presented.

Key Points

  • Amyloidosis describes a heterogeneous group of diseases in which normally soluble plasma proteins are deposited in the extracellular space in an abnormal, insoluble, fibrillar form

  • Rheumatic diseases constitute the most frequent cause of AA amyloidosis in Western countries, and AL amyloidosis should be considered in patients with proteinuria, cardiomyopathy, hepatomegaly, neuropathy, gastrointestinal and musculoskeletal symptoms

  • Diagnosis of amyloidosis requires a multidisciplinary approach, including clinical examination, biochemical tests, imaging and genetic analysis, and should be confirmed in a tissue sample by use of Congo red staining in polarized light

  • Fine-needle aspiration of abdominal fat is an easy, noninvasive, safe, fast, and inexpensive technique that demonstrates amyloid deposits in approximately 80–88% of patients

  • Early diagnosis and unequivocal typing of the amyloid deposits are crucial for prognosis and therapy, and age of onset, the type of amyloidosis and cardiac involvement are the main negative prognostic factors

  • Current therapies center on reducing the supply of the amyloid precursor protein to decrease new amyloid formation and perhaps facilitate regression of existing deposits

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Figure 1: Appearance of amyloid protein deposit on microscopic examination.
Figure 2: Pathophysiology of amyloidosis.
Figure 3: Clinical features of AL amyloidosis.
Figure 4: Aβ2M amyloid arthropathy of the shoulder and wrist in a patient undergoing long-term hemodialysis.
Figure 5: Minor salivary gland biopsy of a patient with AL amyloidosis.
Figure 6: Flow diagram outlining the evaluation of a patient with suspected amyloidosis.

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Correspondence to Federico Perfetto.

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Perfetto, F., Moggi-Pignone, A., Livi, R. et al. Systemic amyloidosis: a challenge for the rheumatologist. Nat Rev Rheumatol 6, 417–429 (2010). https://doi.org/10.1038/nrrheum.2010.84

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