Secondary amyloidosis diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]Shyam Patel [3]

Overview

The diagnostic study of choice in amyloidosis is tissue biopsy of the affected organ. Urinary protein measurement followed by renal biopsy is the gold standard of the diagnosis.

Since AA amyloidosis is a condition that occurred due to another illness, the diagnostic study of choice varies according to the primary disorder.^[1]

However, the amyloidosis itself should be confirmed through histologic examination of the affected organs.
A tissue biopsy of the affected organ is the gold standard test for amyloidosis. Particular stains can determine the subtype of amyloidosis.
Kidney is affected to a greater extent compared to other organs. The 24-hour urine collection with the assessment of urinary protein may be useful and in the case of renal involvement, a kidney biopsy is required.
Staining the tissue sample with antibodies that are specific for AA amyloidosis will confirm the final diagnosis.
Organ-specific labs: If a particular organ is affected, laboratory measurements that are specific to that organ can be measured. For example, if there is liver involvement, liver function tests (such as AST, ALT, total bilirubin, and alkaline phosphatase) should be measured.^[2]

Following diagnostic criteria has been used for AL amyloidosis. However, it may be applicable for AA amyloidosis as well.^[3]

The table below adopted from Clinical Epidemiology Journal


Diagnostic Criteria
Organ	Criteria
Kidney	> 0.5 g/day protein loss, predominantly albumin in 24-hour urine collection
Heart	Low voltage (<5mm) in all limb leads on ECG Elevated levels of NT-proBNP Mean wall thickness >12 mm on the echocardiogram, in the absence of other cardiac cause Delay in subendocardial gadolinium enhancement on cardiac MR imaging
Liver	Alkaline phosphatase> 1.5 upper limits of normal Hepatomegaly >15 cm Absence of heart failure
Nerve	Symmetric lower extremity sensorimotor peripheral neuropathy on physical examination Presence of orthostatic hypotension due to autonomic nerve involvement Intestinal dysmotility (gastric emptying disorder, pseudo-obstruction, voiding dysfunction)
Gastrointestinal tract	Histologic examination consistent with amyloidosis histology
Lung	Diffuse bilateral interstitial pattern on the imaging studies Histologic examination consistent with the diagnosis of amyloidosis
Skin and soft tissue	Macroglossia, jaw claudication, skin lesions in physical examination Findings associated with the diagnosis of Carpal tunnel syndrome on EMG Histologic examination consistent with the diagnosis of amyloidosis

↑ Lachmann, Helen J.; Goodman, Hugh J.B.; Gilbertson, Janet A.; Gallimore, J. Ruth; Sabin, Caroline A.; Gillmore, Julian D.; Hawkins, Philip N. (2007). "Natural History and Outcome in Systemic AA Amyloidosis". New England Journal of Medicine. 356 (23): 2361–2371. doi:10.1056/NEJMoa070265. ISSN 0028-4793.
↑ Gertz, Morie A.; Comenzo, Ray; Falk, Rodney H.; Fermand, Jean Paul; Hazenberg, Bouke P.; Hawkins, Philip N.; Merlini, Giampaolo; Moreau, Philippe; Ronco, Pierre; Sanchorawala, Vaishali; Sezer, Orhan; Solomon, Alan; Grateau, Giles (2005). "Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis". American Journal of Hematology. 79 (4): 319–328. doi:10.1002/ajh.20381. ISSN 0361-8609.
↑ Real de Asua, Diego; Galvan, Jose Maria; Filigghedu, Maria Teresa; Trujillo, Davinia; Costa, Ramon; Cadinanos, Julen (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clinical Epidemiology: 369. doi:10.2147/CLEP.S39981. ISSN 1179-1349.