“In the midst of my journey from one doctor to another, I found myself at a place where the straight path was lost.” These words from a patient resonate deeply with me each time I see someone new with amyloidosis.
For those affected by this rare disease, the journey to diagnosis and treatment is often a winding road filled with unexpected detours, one-way streets, and U-turns — each representing the unique challenges posed by this rare disease. Without clear guidance or a GPS to navigate these obstacles, patients and clinicians alike can find themselves lost in the process.
On Sunday, experts gathered to discuss the much-needed ASH Clinical Practice Guidelines on Amyloidosis. Developed by a diverse, multidisciplinary panel — including patient advocates — these diagnostic guidelines are the result of a thorough scoping review and provide evidence-based, high-quality recommendations.
During the presentation, session Chair Vishal Kukreti, MD, MSc, highlighted key topics such as risk factors, the decision-making process for selecting a target site versus a surrogate site for diagnostic biopsies, and the role of Congo red stain screening in amyloid light-chain (AL) amyloidosis. He underscored that this effort is a crucial step forward, providing tools for early and accurate diagnosis of a disease that has long been under-recognized and underdiagnosed.
The median delay from symptom onset to diagnosis of AL amyloidosis is more than two years. During this time, patients move from provider to provider searching for answers, with 50% seeing five or more specialists before receiving a definitive diagnosis. Amyloidosis is seldom encountered by clinicians, including hematologists, making it challenging to suspect, recognize, and diagnose. Its symptoms are often vague and nonspecific and mimic those of other conditions, leading to misdiagnosis and significant delays in diagnosis.
Session speaker Joselle Cook, MBBS, of Mayo Clinic, reviewed the clinical red flags for systemic amyloidosis to help identify at-risk patients and guide appropriate diagnostic testing. She emphasized key “signals” that should raise suspicion for systemic amyloidosis, such as differentiating early signs from more common symptoms and recognizing red-flag clinical clues that are often masked — insights derived from a scoping review conducted by the panel.
Once amyloidosis is suspected, a tissue biopsy is necessary to confirm the diagnosis. This can be performed either from the target organ (the suspected site) or from a surrogate site (more accessible tissue, such as a fat pad). Hira Shaikh, MD, of the University of Iowa Carver College of Medicine, discussed how and when to choose between target site and surrogate site biopsy.
“During the development of these guidelines, we recognized the need for well-conducted studies to compare the utility of surrogate biopsies with that of target organ biopsies,” Dr. Shaikh said in an interview ahead of the session. “Furthermore, additional research is essential to validate screening tools and identify the appropriate target population for amyloidosis screening.”
Congo red stain is a standard agent for identifying amyloid deposits in tissues, with the type of amyloid confirmed through additional techniques like mass spectrometry. Dr. Naresh Bumma, MD, of Ohio State University, discussed the role of Congo red staining as a screening tool for AL amyloidosis in bone marrow biopsies, noting that it should only be done in biopsies that have already been performed for multiple myeloma or smoldering multiple myeloma. Dr. Bumma also advised not to screen for AL amyloidosis in asymptomatic patients.
“The core message to clinicians is to maintain a high level of suspicion by staying alert to the key clinical red flags of amyloidosis,” Dr. Bumma shared before his presentation. "These guidelines are designed to help hematologists identify the condition early and conduct timely, thorough testing. A prompt diagnosis can lead to earlier treatment, significantly improving patient outcomes. Our goal is to enhance access to care for these patients, both in the U.S. and globally."
The diagnostic guidelines will be published in Blood Advances, and the companion paper on scoping review will also be published. Additionally, another expert panel has already been selected by ASH to develop the treatment guidelines. Looking ahead, ongoing collaborative research will be essential in refining and updating these recommendations. The goal is to drive meaningful changes in clinical practice and eliminate significant delays in the diagnosis and treatment of AL amyloidosis.
By turning uncertainty into clarity, these efforts will provide trusted guidance to both clinicians and patients, steering them toward more effective and timely care pathways.
