Abstract In this systematic review, we aimed to assess the sensitivity of serum immunofixation (SIFE), urine immunofixation (UIFE), and serum free light chain (sFLC) in detecting plasma cell dyscrasia associated with light chain (AL) amyloidosis. We searched the literature using PubMed, Embase, and CENTRAL databases since inception through March 2024. We included studies reporting the diagnostic accuracy of immunofixation and/or sFLC in patients with AL amyloidosis. We used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of the evidence and QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) to assess the risk of bias. After deduplication, 29 237 records were screened, and 44 studies (n = 18 071) were included. For the meta-analysis, 28 studies reported sensitivity for SIFE (n = 3390), 24 studies for UIFE (n = 2830), 19 studies for SIFE and UIFE (n = 2819), 21 studies for sFLC ratio (n = 3678), 6 studies for SIFE and sFLC ratio (n = 372), 3 studies for UIFE and sFLC ratio (n = 242), and 10 studies for all 3 tests (n = 1430). Pooled sensitivities were as follows: SIFE, 0.68 (95% confidence interval [CI], 0.62-0.73); UIFE, 0.77 (95% CI, 0.72-0.81); SIFE and UIFE, 0.89 (95% CI, 0.84-0.93); and sFLC ratio, 0.82 (95% CI, 0.78-0.86). When SIFE, UIFE, and sFLC ratio were combined, the sensitivity reached 0.99 (95% CI, 0.96-1.00). The high sensitivity of combining SIFE, UIFE, and sFLC ratio supports their use as a reliable initial testing strategy to raise suspicion for AL amyloidosis and guide decisions regarding future diagnostic modalities.
Clinical features of systemic amyloidosis: a scoping review
Abstract Systemic amyloidosis is a rare, multisystem disorder that is often challenging to diagnose due to vague and nonspecific symptoms that frequently overlap with other disorders. By the time patients are diagnosed, irreversible organ impairment from amyloid deposition occurrs, contributing to substantial morbidity and mortality. Although developing the American Society of Hematology (ASH) guidelines on systemic amyloidosis, we identified a critical knowledge gap in the recognition of the clinical presentation of its most common subtypes. Therefore, we conducted a scoping review of 117 studies following PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines to identify clinical “red flags” for light chain (AL) and transthyretin (ATTR; wild-type [ATTRwt] and hereditary [ATTRv]) amyloidosis. Studies were identified from the comprehensive systematic review through the ASH amyloidosis diagnosis guideline panel, data mining, and gray literature review. Data were extracted and synthesized by systems to characterize the earliest and most frequently overlooked clinical red flags for the different types of amyloidosis. Shortness of breath and fatigue, the earliest symptoms of AL amyloidosis, contrast with the carpal tunnel syndrome occurring years before ATTRwt cardiac amyloidosis is diagnosed. Weight loss, unexplained abdominal pain, and early satiety were overlooked red flags for AL amyloidosis, compared to the preceding arrhythmias often missed in evaluation for ATTRwt amyloidosis. Sensory loss was the predominant neuropathic presentation for AL amyloidosis compared to the painful length-dependent neuropathy of ATTRv amyloidosis. Awareness of the early symptoms and distinct patterns across subtypes can enhance cross-specialty awareness and support earlier diagnosis and intervention of AL and ATTR amyloidosis.