When to Suspect a Diagnosis of Amyloidosis

Abstract

Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe organ dysfunction. Despite the etiological heterogeneity of systemic amyloidosis, the clinical manifestations of the different forms of amyloidosis largely overlap and depend upon the effected organ. The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific; therefore, establishing the diagnosis is difficult, and early diagnosis requires clinical suspicion. Light chain (AL) amyloidosis may present with highly specific signs such as macroglossia and periorbital purpura, but these signs are insensitive. Amyloidosis is still underdiagnosed, even though treatments are now available and are effective in improving patient's survival and quality of life. Cardiac amyloidosis is the major determinant of survival, and the earlier it is detected the better the survival. All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin. The aim of this review is to provide clinicians with knowledge about the signs and symptoms that raise the suspicion of amyloidosis, bearing in mind the importance of early diagnosis of this disease.

Immunoglobulin light chain amyloidosis

“…In the light of these findings, bone scintigraphy with a 99mTc-labelled pyrophosphate or DPD tracer may be of future interest for definitive exclusion of ATTRwt or suspicion of coexisting ATTRwt in patients with AL. These new insights will clearly influence the diagnostic work up for AL and ATTR in the near future [8].…”

“…The pattern and intensity of organ involvement determines the clinical presentation. Symptoms are often very unspecific, especially at the beginning and may include the following: fatigue, dyspnea, ankle and leg edema, weight loss, diarrhea, obstipation and orthostatic hypotension [8]. However, there are some specific but very rare signs suggesting the presence of amyloidosis like periorbital ecchymosis, enlargement of the tongue, bilateral carpal tunnel syndrome and a typical form of nail dystrophy (Table 1; Fig.…”

Worldwide Perspectives of Amyloidosis

“…The review "When to suspect amyloid?" [1] emphasizes the warning signs that should alert a physician evaluating a patient. Hematologists following monoclonal gammopathy of undetermined significance and smoldering multiple myeloma should be alert to the possibility of the development of amyloidosis even if light chains are not rising and they must monitor clinical signs and symptoms, 24-h urinary protein, alkaline phosphatase, and cardiac biomarkers.…”

“…The prognosis of AL patients is determined by the biology of the underlying clonal disease, the pattern and extent of organ involvement at baseline, and the response to treatment. New systems for BMPC ≥10% or CRAB or high risk FISH CyBorD ± daratumumab × 4-6 cycles 1,2,3 No CyBorD ± daratumumab × 6-12 cycles 1,2,3 Fig. 1.…”

“…BMPC, bone marrow plasma cells; CyBorD, cyclophosphamide, bortezomib, and dexamethasone; VGPR, very good partial response. 1 Or BMel-Dex. 2 If < partial response at 2 months, consider changing the therapy.…”