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Amyloidosis: A Brief Overview

 

Amyloidosis is a “group of diseases” that have the common feature where abnormal proteins (or in some cases normal proteins) behave abnormally, and the breakdown product of these proteins fold upon themselves, creating amyloid” fibrils” which deposit in various organs throughout the body. This potentially life-threatening disease can affect the heart, kidneys, liver, spleen, nervous system and digestive tract. (Falk, R., MD, 2018) A basic illustration of the creation of amyloid “fibrils” is shown below.

(Cleveland Clinic, 2020)

 

There are different types of the disease including AL or Light Chain Amyloidosis, AA Amyloidosis, Transthyretin Amyloidosis (referred to as TTR amyloidosis), and Localized Amyloidosis. TTR amyloidosis includes a hereditary type and a non-hereditary type. (Falk, R, MD, 2018)

 

Common symptoms of amyloidosis are shown in the following figure.

(The Canadian Amyloidosis Support Network)

 

Light Chain (AL) Amyloidosis

AL amyloidosis is the most common type of amyloidosis in developed countries, accounting for approximately 85% of all cases. There are approximately 3,000-5,000 new AL amyloidosis cases a year in the United States. (Falk, R., MD, 2018)  

 

The disease usually affects the heart, kidneys, liver and nerves. This type of amyloidosis is blood related, associated with the abnormality of proteins from plasma cells associated with bone marrow. Plasma cells normally create antibodies, known as immunoglobulins, that serve to combat bacteria and viruses. Antibodies are made up of “heavy chains” and “light chains.” AL amyloidosis stems from an abnormal expansion of plasma cells. The abnormal plasma cells secrete abnormal “free light chains” (FLCs) into the bloodstream. These abnormal light chain mutations become “sticky.” The sticky light chains bind together to form amyloid fibrils which can then accumulate in various body organs, as shown below. (Sherwood, A.L.)

(Cleveland Clinic, 2020)

 

Diagnostic testing for AL amyloidosis includes blood testing, urine tests and biopsies. Blood and/or urine tests are used to indicate the presence of amyloid protein, however bone marrow tests or other small biopsy samples of tissue or organs are needed to positively confirm the diagnosis of amyloidosis. Specific types of blood/urine testing include:

  • A 24-hour urine collection to look at the level of protein in your urine sample. Excess protein in the urine may be an indication of kidney involvement.
  • The level of ALP (an enzyme called “alkaline phosphatase”) in your regular blood workup.
  • Blood tests to look for stress and strain on the heart. Cardiac biomarkers that are used include troponin T or troponin I, and NT-proBNP (which stands for N-terminal pro-brain natriuretic peptide) or BNP (brain natriuretic peptide). 
  • Tests for abnormal antibody (immunoglobulin) proteins in the blood include the Free Light Chain Assay, which shows the level of kappa and lambda light chains in a separate blood test. The Free Light Chain Assay test is often referred to as FLC, which is an abbreviation for free light chains.
  • Another test for abnormal immunoglobulin can be done with blood and/or urine. It is called “immunofixation electrophoresis.”

 

Echocardiogram and imaging are performed so that the doctor can look for amyloid deposits in the heart, while viewing the size and shape of it and the location and extent of any impact of amyloid.

 

Tissue biopsy are performed to identify evidence of amyloid deposits. Tissue samples are sent to a lab for microscopic examination, where the tissue is stained with a dye called “Congo-red.”  After putting it under a microscope, amyloid protein is discovered if it turns an apple-green color, resulting in a diagnosis of amyloidosis. The most common tissue sample, which is almost always involved in generating an AL diagnosis, is called a fat-pad biopsy. Fat-pad biopsies are taken from the stomach. Biopsy samples may also be taken from the liver, kidney, nerves, heart, stomach, or intestines.

 

Bone marrow tests are also performed. These involve the removal of some liquid bone marrow and/or the removal of bone tissue. These samples can help to determine the percentage of amyloid producing plasma cells, and when tested in the lab they can assist in identifying whether the abnormal plasma cells are producing kappa or lambda light chains. (Amyloidosis Foundation, 2021)

 

If treatment begins during the early onset of clinical symptoms, the overall success rate is higher, so early detection is essential.

 

Patients with AL amyloidosis have benefited from the recent development of new drugs for myeloma, many of which work effectively on the plasma cells that cause AL amyloidosis. In addition, the FDA approved the first drug treatment specifically for AL amyloidosis in January 2021, called DARZALEX (daratumumab). Drug combinations are more effective than single drugs in attacking the abnormal plasma cells. Drugs that may be useful include traditional chemotherapy drugs (such as melphalan, and cyclophosphamide), as well as “proteasome inhibitor” and “immunomodulator” drugs. (Amyloidosis Foundation, 2021)

 

Stem cell transplant is also a preferred therapy, as it can provide long-term control of the underlying disease. However, only a minority of AL patients (typically less than 25%) are eligible. (Amyloidosis Foundation, 2021)

 

AA Amyloidosis

AA amyloidosis results from increased levels of the circulating serum “amyloid A protein.” Amyloid A protein levels normally elevate in the bloodstream as a response to infection and inflammation. If a patient has an infection or inflammatory condition for an extended period of time (six months or more) they would be at risk for developing AA amyloidosis. The amyloidosis can arise due to chronic inflammatory and infectious conditions, including rheumatic disease, inflammatory bowel disease, tuberculosis, osteomyelitis, lupus, and hereditary fever syndromes. Amyloid deposition usually begins in the kidneys, but the liver, spleen, lymphnodes, and intestines are also commonly affected.

 

If a patient has been diagnosed with a chronic inflammatory disease or chronic infection and they develop high levels of protein in the urine or other associated AA symptoms, then the physician should test for AA amyloid deposition. When kidney damage occurs, it can be clinically shown as protein found in the urine (nephrotic syndrome) or impairment of kidney function.

 

A test involving a 24-hour urine collection can be performed to look at the level of protein in the patient’s urine. If amyloidosis is suspected in most cases a biopsy of the kidney tissue performed.

 

In order to identify AA amyloid, the most common diagnostic test is staining the tissue sample with antibodies that are specific to AA amyloid, the “anti-AA serum.” If the anti-AA serum result is positive then AA amyloidosis is diagnosed. Once AA amyloidosis is confirmed the primary underlying inflammatory condition should then be identified.  

 

With AA amyloidosis it is most important to treat the underlying infection or inflammation in order to reduce the level of the precursor for the AA amyloid deposits.  These treatments vary depending on the underlying condition. Some treatments that exist for inflammatory diseases include surgery on the infection or tumor, drug therapies for rheumatoid arthritis, antibiotics for chronic infection, among others.

 

With effective treatment of the underlying inflammation amyloid deposits have been known to reduce and nephrotic syndrome can improve. If the kidney function has become significantly impaired, it rarely recovers. 

 

Supportive treatment is very important, including nephrology, cardiology, and neurology. (Amyloidosis Foundation, 2021)

 

TTR (Transthyretin) Amyloidosis

As stated earlier, TTR amyloidosis includes a hereditary type and a non-hereditary type.

 

Hereditary (Familial) Amyloidosis, also referred to as ATTRv amyloidosis, is associated with an inherited genetic mutation. There are various subtypes of familial amyloidosis that are associated with specific demographic groups including Portuguese, Irish, Swedish, Afro-American, and Japanese lineage. 

 

The non-hereditary type of TTR amyloidosis, known as Wild Type Amyloidosis is a disorder predominately of older men in their 70s and beyond. This form of the disease may actually be responsible for up to 10% of male patients having heart failure due to stiff heart tissue. (Falk, R., MD, 2018)  

 

As with AL and AA Amyloidosis, TTR Amyloidosis can manifest itself with a multitude of symptoms. In a vast majority of cases the resultant symptoms are cardiological and/or neuropathic in nature. A basic illustration of the production method for TTR amyloid fibrils is shown below.

Early diagnosis if TTR amyloidosis is essential so as to help minimize the extent of bodily tissue or system damage. First, a patient is tested to determine if they have amyloid proteins in their body. The main diagnostic testing is similar to that described above for AL Amyloidosis, including blood tests, urine tests and biopsies. If amyloidosis is confirmed but the type is not initially identified, additional tests are performed to determine the existence and variation of ATTR.

 

Once it is determined that there is transthyretin amyloid protein (via biopsy and Congo red staining), the specific protein needs to be identified by protein sequence analysis and DNA sequencing. A blood sample is sent to a lab where the DNA chains are analyzed. Sections of the DNA chain are checked for genetic markers of the DNA defect. Hereditary amyloidosis variations affect patients differently. It is critical to establish which variation exists in order to identify a tailored treatment plan.

 

Treatment of TTR amyloidosis include treating the source and symptoms. Source treatment involves slowing down, or stopping, the overproduction of amyloid at the source of the disease. Historically, liver transplant has been helpful, however, the statistics vary as to who can benefit from these transplants, with the outcome dependent largely on the specific mutation that exists in the patient. In some situations, combined heart and liver transplants have helped patients with an ATTR variant that produces cardiac problems. 

 

In 2019, two drugs were approved for treatment of ATTR polyneuropathy associated with TTR amyloidosis in adults.  The first was ONPATTRO (patisiran), a first of its kind RNA interference therapeutic drug which aims to silence the gene expression for patients with the hereditary type TTR.  The second drug approved is TEGSEDI (inotersen), which reduces the production of TTR protein. Also, in 2019, VYNDAQEL and VYNDAMAX (tafamidis) were approved by the FDA for ATTR cardiomyopathy.  (Amyloidosis Foundation, 2021)

 

There is supportive treatment for the various symptoms associated with TTR Amyloidosis, possible symptoms include peripheral neuropathy, autonomic neuropathy, cardiac and kidney problems. There are medications that can be prescribed to treat the effects of peripheral neuropathy, such as tingling or burning sensations. Many patients experience autonomic neuropathy and may require treatment for blood pressure, heart rate, digestion, and perspiration, depending on the location of the damage to the nerves. Other gastrointestinal dysfunctions may require treatment for symptoms that include poor nutritional health, diarrhea or constipation, and nausea or vomiting. (Amyloidosis Foundation, 2021)

 

Localized Amyloidosis

Localized amyloidosis often has a better prognosis than the types that affect one or more organ systems. Typical sites for localized amyloidosis include the bladder, skin, throat or lungs. Correct diagnosis is important so that treatments that affect the entire body can be avoided. (Mayo Clinic. 2021)

 

Summary

Amyloidosis is a complex multi-systemic disease where no two patients are alike. Symptoms are often vague and vary from patient to patient, even within the same disease type, making diagnosis one of the biggest hurdles for the medical community. It is not uncommon to hear from patients that it took multiple years and multiple doctors to ultimately arrive at a correct diagnosis, all the while the disease continued to progress. While treatment is type-specific, it is individualized from patient to patient depending on organ involvement. 

 

In the words of Morie A. Gertz, M.D., M.A.C.P., of the Mayo Clinic and regarded as a leading world expert on amyloidosis.

 

“Thanks to the Amyloidosis Speakers Bureau, providers across the country are being instructed on techniques to suspect and recognize amyloidosis and how to efficiently make the diagnosis in a timely fashion.  Incorporating testing for amyloidosis into the work flow of patients with cardiomyopathy, proteinuria, peripheral neuropathy, unexplained weight loss, and smoldering multiple myeloma has been successful. 

Comprehensive education remains the best strategy to save lives for this rare disorder.”

 

 

 

Sources
Falk, Rodney, MD, Understanding Amyloidosis. (2018).https://www.youtube.com/watch?v=bE68vvDtnyM&t=134s. 
Cleveland Clinic. (2020, June 2). Amyloidosis: AL (Light Chain). https://my.clevelandclinic.org/health/diseases/15718-amyloidosis-al-amyloid-light-chain. 
Sherwood, A. L. (n.d.). Understanding Freelite®, the lab test for serum free light chains. Lecture. 
The Canadian Amyloidosis Support Network. (n.d.). About Amyloidosis. http://thecasn.org/home-2/what-is-amyloidosis/al-amyloidosys/al-amyloidosis-symptoms/
Mayo Clinic. 2021. Amyloidosis – Symptoms and causes. [online] Available at: <https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178> [Accessed 14 July 2021].
Amyloidosis Foundation. 2021. AL – Amyloidosis Foundation. [online] Available at: <https://amyloidosis.org/facts/al/#diagnosis> [Accessed 14 July 2021].

 

A Clinical & Patient Perspective of Wild-Type Amyloidosis

Wild-type ATTR is also referred to as ATTRwt. It is not caused by any known genetic mutations, such as in the case of hereditary forms of the disease (hATTR). This disease used to be called SSA or SCA, which stood for Senile Systemic Amyloidosis and Senile Cardiac Amyloidosis, respectively, which are now outdated terminologies. The disease is not known to be directly related to dementia, but it is related to aging.

Deposits of TTR amyloid can be found throughout the body, so it is a systemic amyloidosis disease.  The most common place it is found is in the heart. Wild-type ATTR is also known to cause some cases of carpal tunnel syndrome, which can be the first (early) symptom. Recent data suggests that lumbar spine involvement as well as a rupture of the biceps tendon in the forearm can precede cardiac involvement by many years.

This is a disease that has traditionally been found mostly in men, originally reported in those aged 80 and over. As awareness of the disease increases, wild-type ATTR average age at diagnosis is 75. It is often overlooked as an amyloidosis disease because so many people experience heart problems in their later years.

As with hereditary forms of the disease (hATTR), wild-type ATTR causes problems due to the breaking apart, misfolding and deposition of amyloid protein fibrils in healthy tissue. “Wild-type” refers to this form of the disease because it is the natural form of this protein, without genetic mutation. These deposits can interfere with the heart’s normal function, by causing stiffness of the heart tissue, making it more difficult for the heart to fill, leading to heart rhythm problems and heart failure.

 

In this special video, hear world-renowned expert Dr. Mathew S. Maurer and his patient John Basdavanos presenting to a group of medical students. Dr. Maurer provides a brief overview of ATTRwt, while John provides the patient perspective. Together, these insights offer a compelling story about battling a life threatening disease.

 

AI, Protein Folding & Amyloidosis

The Protein Folding Problem

Proteins are the building blocks of life. They are large complex molecules, made up of chains of amino acids, and what a protein does largely depends on its unique 3D structure. Figuring out what shapes proteins fold into is known as the “protein folding problem.”  For decades and decades, one of biology’s biggest challenges has been finding a solution for the “protein folding problem” and is explained in the linked video below.

AI, DeepMind and Google Find Answers

Founded in 2010, DeepMind researches and builds safe AI (Artificial Intelligence) systems that learn how to solve problems and advance scientific discovery for all. They joined forces with Google in 2014 to accelerate their work. They’re a team of scientists, engineers, machine learning experts and more, working together to advance the state of the art in AI.

In a major scientific breakthrough, DeepMind’s AI system AlphaFold has been recognized as a solution to this grandest of all biological problems – the “protein folding problem.”  Here is an excellent video explaining AlphaFold and the making of a scientific breakthrough.

According to Professor Venki Ramakrishman, Nobel laureate and President of the Royal Society,

This computational work represents a stunning advance on the protein-folding problem, a 50-year-old grand challenge in biology.  It has occurred decades before many people in the field would have predicted. It will be exciting to see the many ways in which it will fundamentally change biological research.

 

Potential Impact for Amyloidosis

For diseases which originate with misfolded proteins, such as amyloidosis, “investigators have been doing this exercise by ‘brute force’ until now,” according to Dr. Angela Dispenzieri from the Mayo Clinic.  This AI research is likely to open a whole new world of insight and answers, from which new and more effective treatments can be developed.

Marina Ramirez-Alvarado, Ph.D., whose research laboratory at the Mayo Clinic studies misfolding and amyloid formation in light chain amyloidosis, had this to say.

The protein folding problem, one of the most important scientific questions of the 20th century is making headlines today with the artificial intelligence work from DeepMind. It is clear that DeepMind will provide important basic understanding of the folding process and will significantly benefit those amyloidosis diseases that involve secreted, folded proteins, such as light chain (AL), and Transthyretin (ATTR) amyloidosis.

Dr. Morie Gertz, a hematologist/oncologist from the Mayo Clinic who has decades of clinical experience with amyloidosis, weighs in on some of the possible outcomes from this ground-breaking research.

The ability to predict protein folding in three dimensions may result in the ability to predict which protein sequences are likely to form amyloid fibrils. In light chain amyloidosis this could allow for long-term monitoring of selected patients likely to develop amyloidosis. This would permit extremely early diagnosis long before symptoms developed. It would also allow for the exploration of why wild-type TTR amyloidosis forms amyloid fibrils in the heart in some patients but not in others.

 

However, it won’t answer all questions …

Dr. Vaishali Sanchorawala, director of Boston University’s Amyloidosis Center offers these words of perspective.

The “protein folding problem” that DeepMind’s AlphaFold is designed to solve is predicting the native, functional state of a protein from just its amino acid sequence. Amyloidosis, though, is caused by our bodies’ failure to solve that problem, resulting in misfolded and aggregated proteins. AlphaFold’s remarkable achievement can definitely help to better understand native structure of amyloidogenic light chain proteins. However, amyloid fibrils are different from the native states of their precursor proteins and therefore the adaptation of AlphaFold to study protein misfolding and aggregation, perhaps by predicting the structures of complex amyloid fibrils, might be better able to predict the effects of mutations that alter people’s risk of developing amyloidosis.

 

In closing …

AI is rapidly advancing the knowledge of protein misfolding, unlocking answers for amyloidosis which should lead to earlier diagnosis, improved treatment, and better patient survival.

 

 

———————————————————-

 

Sources:

Angela Dispenzieri, M.D.

Morie A. Gertz, M.D., M.A.C.P.

Vaishali Sanchorawala, M.D.

Marina Ramirez-Alvarado, Ph.D.

 

High Accuracy Protein Structure Prediction Using Deep Learning

John Jumper, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Kathryn Tunyasuvunakool, Olaf Ronneberger, Russ Bates, Augustin Žídek, Alex Bridgland, Clemens Meyer, Simon A A Kohl, Anna Potapenko, Andrew J Ballard, Andrew Cowie, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Jonas Adler, Trevor Back, Stig Petersen, David Reiman, Martin Steinegger, Michalina Pacholska, David Silver, Oriol Vinyals, Andrew W Senior, Koray Kavukcuoglu, Pushmeet Kohli, Demis Hassabis.

 

In Fourteenth Critical Assessment of Techniques for Protein Structure Prediction (Abstract Book), 30 November – 4 December 2020. Retrieved from here.

 

 

ASB: 2020 Year-End Review

 

What a year it has been for everyone!  Year-end 2020 brings us nearly two years since launch, and includes one and a half school years (or three semesters) of medical school.  During that time we have established our mission, pivoted from in-person to virtual thanks to COVID-19, achieved 92% of our presentation goal for 2020, and are excited for 2021!

Our mission is to educate future doctors about amyloidosis, with the belief that heightened awareness will lead to earlier diagnosis and ultimately improve patient survivorship. We know that the level of medical school education about amyloidosis runs the gamut, from a small mention in textbooks to classroom discussions with medical professionals, although the bias is overwhelmingly towards the “minor mention.” As a result, we are confident our efforts will provide students with a valuable enriched exposure to this disease to augment the medical school curriculum.

EXECUTIVE SUMMARY

  • Last year, we set our 2020 goal at 60 presentations, not knowing what was ahead. We gave 22 presentations in the Spring, and 33 presentations this Fall.  So while we didn’t quite reach our goal, we are super proud that we did achieve 92% of our goal!  Go us!
  • We are thrilled that our activities are expanding – not only are we returning to medical schools we presented to last year, but we are adding new schools to the roster. A long way to go, but still positive direction. A full list can be found at the end of this update.
  • Our agility in shifting last Spring to a virtual platform served us well. This rapid shift minimized the impact to our operations and, as a result, we were suspended for only a few months. By April, operations had resumed on a minimal basis. By August, operations were back to full swing, with everything being virtual since then.
  • We average around 45 speakers, which allows for diversity in our speaker population’s disease state and flexibility in their availability. This has served us well.
  • Our additional resources to develop speakers, their presentation styles, their stories, and their virtual audio/video capabilities has been well-received and we believe is translating to a higher quality offering.
  • We are particularly delighted that our medical school student mailing list – those interested post-presentation in continuing to receive information about amyloidosis – keeps growing and we will be at 100 in the near future! Content is pulled from experts and other trusted organizations with the intention to offer brief insights into the disease. 
  • This year, with the help of one of our speakers who is a professor/Ph.D. in social science, we will be investigating how we can better ascertain and improve our speaker/ASB effectiveness in the eyes of the medical students.
  • Each Spring and Fall we reach out to medical school deans, updating them on our activities.

 

THE 2020 NUMBERS

  • We reached out to nearly all 160 continental U.S.-based medical schools and student interest groups, met with varying degrees of interest (or no response and/or no interest in some cases).
  • We made 55 presentations in 2020, and have 10 already booked for Spring 2021. Since the ASB started, we now have 89 presentations logged. A complete list of schools we have presented to since we began can be found at the end of this email.
  • Roughly 20% of the presentations are within the curriculum; 80% are to student interest groups. Identifying the appropriate professor(s) and establishing a dialogue continues to be a big challenge.
  • Our educational materials, per the organizers, reached over 16,400 medical students, pushing us over 25,000 since we began.

 

SPEAKERS

The cornerstone of our effort is our group of wonderful patient speakers, who passionately volunteer their time to give back and share their stories of life with amyloidosis.

On average, we have around 45 active speakers, diversified by geography across the continental U.S., by amyloidosis type, by organ involvement, by gender and age. This is a rather deep bench, but we have found it both helpful and necessary. Helpful in that we can maximize attendance if we work around the preferred dates and times suggested by the schools. Helpful in that we can match specific disease states with audience focus (e.g., a cardiac amyloidosis patient speaker to a cardiology student interest group). Necessary in that periodically, a speaker’s personal situation may change and they need to step back either temporarily, or permanently. We are fortunate to have a steady pipeline of new speaker interest, which we spend time screening, qualifying and training. At present, we feel this is an appropriate number of speakers for our current and anticipated growth. 

One area we have added resources to is training and presentation development for our speakers. Thanks to one of our speaker volunteers who has extensive experience, we offer in-depth guidance for new speakers in the development of their presentation outline and rehearsal training for their delivery. In addition, prior to every virtual presentation we rehearse and test the speakers’ audio and video technology. For those partaking, it has been an appreciated additional level of support and we believe is translating to a higher quality offering.

We are saddened that one of our speakers, Mark Stinehour, succumbed to this disease at the age of 56. He was passionate about giving back and leaving a lasting legacy to make a difference for those to come. Our hearts and prayers go out to Mark’s family.

 

ADVISORS

We are proud to have an impressive group of medical experts and influencers in the world of amyloidosis, some of whom are also patients, as advisors to support our initiative. Our advisors are active in our efforts and contribute their specialized expertise in a variety of ways, such as medical school introductions, grant requests, educational development, and patient speaker assessment/development. We are extremely grateful for their assistance and believe that, thanks to their contribution, the ASB will make an even bigger difference in the diagnoses of this disease.  You can see our prestigious list of advisors on our website page www.mm713.org/speakers-bureau/ 

We are sad to share that one of our advisors, Dr. Janice Wiesman, passed away from COVID-19. Janice was an ardent and active supporter of our efforts and passionate about the world in which she lived. Our hearts and prayers go out to Janice’s family.

 

TESTIMONIALS – OUR TRUE REPORT CARD

Feedback from students and medical school professors has been extraordinarily positive. It reinforces to us that candid and authentic patient stories are a valuable complement to the medical school curriculum, strengthening the learning and deepening the durability for these future doctors about this disease. This is exactly why we do what we do. Here are just a few of the testimonials from this year.

 

The opportunity for second year medical students to hear the story of a patient with amyloid is invaluable. The presentation addressed aspects of pathophysiology they are learning and the human side of medicine. This presentation format offered an excellent teaching opportunity to inform doctors-in-training about this serious disease. Our students gained insight into the patient’s journey through diagnosis, treatment and the challenges ahead. We all appreciated the patient’s generosity in sharing her experiences. Having patients teaching medical students about amyloidosis will have a lasting impact on our future doctors with increasing awareness of this disease and ultimately will help future patients.  Theresa Kristopaitis, M.D., Professor, Assistant Dean for Curriculum Integration, Loyola University Stritch School of Medicine

 

Such a powerful presentation that I will carry with me throughout my whole career, no matter what specialty I go into! I not only learned the importance of keeping amyloidosis on my differential, but also the importance of really listening to your patients and working through the hard diagnoses together.   Solana Archuleta, MD Candidate, University of Colorado School of Medicine

 

I had several students make comments after the conclusion of the presentation that it was the best, one even said ‘exceptional,’ presentations given at our school from a patient.  The materials gave all of the students, including myself, a great introduction to some of the pertinent findings in patients with amyloidosis. Co-President of the Internal Medicine Interest Group, University of Arizona College of Medicine, Phoenix

 

Hearing Ed talking about his journey with Amyloidosis was an incredible experience that only further inspired me to want to be a better physician for my future patients. It is one thing to learn about a condition in the classroom, but hearing the real-world struggles with it from another human being provides a whole new perspective. Ed was open about his journey and shared his feelings during each step, giving us insight into what it is like to be a patient with Amyloidosis. I will take what I learned from this presentation and apply it in order to ensure that patients I see in the future do not have to deal with the same issues that Ed had to deal with.   Gurkaran Singh, MD Candidate, University of Arizona College of Medicine, Tucson

 

Diseases such as amyloidosis are often managed by specialists, but it is important for primary care physicians to recognize these signs and direct these patients to these specialists. Increasing awareness of these diseases among all physicians will help patients reach an answer sooner and can have a significant impact on their lives.  Yue Zhang, MD Candidate, Northwestern Feinberg School of Medicine

 

Looking ahead to 2021 we again will target 60 presentations, and seek to expand the list of schools we present to. We are pleased with all we have accomplished thus far, energized by the feedback, cognizant that we have much ahead, and hope we have made you proud. As always, we welcome any comments you may have.

Stay safe, happy holidays, and all the best for a new 2021!

Mackenzie, Charolotte, and Deb

Operating Committee of the Amyloidosis Speakers Bureau, sponsored by Mackenzie’s Mission

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Since inception in 2019, the Amyloidosis Speakers Bureau has presented to medical students of the following medical schools.

California University of Science & Medicine, School of Medicine, San Bernardino

Central Michigan University College of Medicine

Chicago Medical School, Rosalind Franklin University of Medicine and Science

Cleveland Clinic Lerner College of Medicine

Columbia University Vagelos College of Physicians and Surgeons

Drexel University College of Medicine

Florida Atlantic University Charles E. Schmidt College of Medicine

Florida International University Herbert Wertheim School of Medicine

Florida State University College of Medicine

Geisinger Commonwealth School of Medicine

George Washington School of Medicine

Icahn School of Medicine at Mt. Sinai

Lewis Katz School of Medicine at Temple University

Loyola University Chicago Stritch School of Medicine

Mayo Clinic Alix School of Medicine, Rochester

Mayo Clinic Alix School of Medicine, Scottsdale

Northeast Ohio Medical University College of Medicine

Northwestern University Feinberg School of Medicine

NYU Grossman School of Medicine

Oakland University William Beaumont School of Medicine

Quinnipiac University Frank H Netter MD School of Medicine

Stanford University School of Medicine

Tufts University School of Medicine

University of Arizona College of Medicine, Phoenix

University of Arizona College of Medicine, Tucson

University of Chicago Pritzker School of Medicine

University of Colorado School of Medicine

University of Connecticut School of Medicine

University of Florida College of Medicine

University of Illinois College of Medicine, Chicago

University of Illinois College of Medicine, Peoria

University of Illinois College of Medicine, Rockford

University of Iowa Carver College of Medicine

University of Kansas School of Medicine, Wichita

University of Maryland School of Medicine

University of Massachusetts Medical School

University of Minnesota Medical School

University of Missouri Kansas City School of Medicine

University of Nevada Reno, School of Medicine

University of Pittsburgh School of Medicine

University of South Alabama College of Medicine

University of South Carolina School of Medicine, Columbia

University of Toledo College of Medicine

UNLV School of Medicine

Virginia Commonwealth University School of Medicine

Wayne State University School of Medicine

Wright State University Boonshoft School of Medicine

Yale School of Medicine

 

Spinal Stenosis & Amyloidosis

WHAT IS SPINAL STENOSIS?

Spinal stenosis is narrowing of the spinal column that causes pressure on the spinal cord, or narrowing of the openings (called neural foramina) where spinal nerves leave the spinal column.

This can develop as you age from drying out and shrinking of the disk spaces. (The disks are 80% water.) The narrowing can cause compression on nerve roots resulting in pain or weakness of the legs. If this happens, even a minor injury can cause inflammation of the disk and put pressure on the nerve. You can feel pain anywhere along your back or leg(s) that this nerve supplies.1

 

SYMPTOMS1

Symptoms often get worse slowly over time. Most often, symptoms will be on one side of the body, but may involve both legs.  Symptoms include:

  • Numbness, cramping, or pain in the back, buttocks, thighs, or calves, or in the neck, shoulders, or arms
  • Weakness of part of a leg or arm

Symptoms are more likely to be present or get worse when you stand or walk. They often lessen or disappear when you sit down or lean forward. Most people with spinal stenosis cannot walk for a long period. More serious symptoms include:

  • Difficulty or poor balance when walking
  • Problems controlling urine or bowel movements

 

A POTENTIAL CLUE TO AMYLOIDOSIS?

Amyloid is a very common finding in cartilage and ligaments of elderly subjects, and transthyretin has been demonstrated in some deposits. Lumbar spinal stenosis is also a condition of usually elderly individuals in whom narrowing of the lumbar spinal canal leads to compression of nerves to the lower limbs.

“Another very important historical clue is spinal stenosis, and actually that’s much more commonly seen in patients with ATTR than AL, and in fact, again, almost exclusively in wild type,” according to Dr. Mazen Hanna2

 

WHAT IS SENILE, AKA WILD-TYPE, AMYLOIDOSIS (ATTRwt)?

Amyloidosis is a generic name for a very diverse group of protein folding disorders, all characterized by creation of cross-beta-sheet fibrils. At least 30 different human proteins have been shown to form amyloid fibrils in vivo (). Two main groups of amyloid conditions exist: systemic and localized. In the systemic conditions, deposits occur in many organs and tissues, and the diseases are usually life-threatening; in each of these diseases one out of at least 15 plasma proteins forms amyloid fibrils far from the place of parent protein synthesis. In the localized conditions, the proteins are expressed at the site of deposition (). In both groups, fibrils usually deposit extracellularly and can form conspicuous masses that deform a tissue and interfere with its normal functions.5

Senile systemic amyloidosis (SSA), derived from wild-type transthyretin (TTR), is common in association with aging, although symptom-giving disease usually is comparably rare and affects males at least 10 times more often than women. Restrictive cardiomyopathy is the main clinical expression. However, carpal tunnel syndrome is common in SSA, and widely spread wild-type ATTR amyloid deposits at other connective tissue sites have been demonstrated ().5

Joint cartilage and ligaments are targets of both localized and systemic amyloid. Of the systemic forms, Aβ2-microglobulin [for nomenclature, see ()] amyloidosis is well-known to engage skeletal and joint structures in patients under hemodialysis due to renal insufficiency (). Also, immunoglobulin light chain (AL) amyloidosis is known to generate a variety of symptoms from joints and skeleton, sometimes with neural lesions. Carpal tunnel syndrome is often noted in transthyretin (ATTR) and Aβ2-microglobulin amyloidosis ().5

 

CONCLUSION

From the studies referenced therein, results suggest that transthyretin-derived amyloid deposits may occur more frequently in various ligaments and tendons than originally expected3 and that lumbar spinal stenosis quite frequently may be a consequence of senile systemic amyloidosis [also known as wild-type amyloidosis; ATTRwt]5.

 

Stay suspicious.

 

 

 

 

Sources:

1 https://www.mountsinai.org/health-library/diseases-conditions/spinal-stenosis

2 https://www.neurologylive.com/view/cardiac-amyloidosis-management

3 https://pubmed.ncbi.nlm.nih.gov/21334722/

Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, Ando Y, Mizuta H. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011 Sep;42(9):1259-64. doi: 10.1016/j.humpath.2010.11.017. Epub 2011 Feb 21. PMID: 21334722.

4 https://pubmed.ncbi.nlm.nih.gov/14640042/

Westermark P, Bergström J, Solomon A, Murphy C, Sletten K. Transthyretin-derived senile systemic amyloidosis: clinicopathologic and structural considerations. Amyloid. 2003 Aug;10 Suppl 1:48-54. PMID: 14640042.

5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116761/

Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. doi:10.3109/03009734.2014.895786

6 https://en.wikipedia.org/wiki/Spinal_stenosis

 

 

Macroglossia & Amyloidosis

 

WHAT IS IT?

According to the NIH (1), macroglossia is the abnormal enlargement of the tongue in proportion to other structures in the mouth. It usually occurs secondary to an underlying disorder that may be present from birth (congenital) or acquired.

 

SYMPTOMS

Symptoms associated with macroglossia may include drooling, speech impairment, difficulty eating, noisy, high-pitched breathing (stridor), snoring, airway obstruction, abnormal growth of the jaw and teeth, and ulceration. In some cases, the tongue may protrude from the mouth. (1) (3)

Talking may be affected. The large size of the tongue may also cause abnormal development of the jaw and teeth, resulting in misaligned or protruding teeth. Ulceration and dying tissue on the tip of the tongue may be other symptoms of the disorder. (3)

In addition to an enlarged tongue it is common to see indentations around the tongue perimeter from the constant pressure against the teeth.

Patients who graciously offered their picture for this blog reinforce many of these symptoms, including TMJ, difficulty swallowing, and breathing. Reiterated almost unanimously, eating is a problem – chewing and swallowing, clearing food from their mouth. Food gets stuck in front of their teeth. Speech is affected, and they often sound “slushy.” Snoring can get so bad it wakes them (and partners) up during the night. In addition, sometimes, their tongue gets sore from rubbing against their teeth.

 

WHAT CAUSES IT?

Macroglossia can be associated with a wide range of congenital (present from birth) and acquired conditions (e.g., malignancies, metabolic/endocrine disorders, inflammatory or infectious diseases; amyloidosis), or it can occur as an isolated feature (with no other abnormalities). In most cases, it is due to vascular malformations (blood vessel abnormalities) and muscular hypertrophy (an increase in muscle mass). (1)

Macroglossia, while occurring much more frequently in AL amyloidosis, can also accompany ATTR amyloidosis. (2)   

 

HOW IS IT TREATED?

Treatment depends upon the underlying cause and severity and may range from speech therapy in mild cases, to orthodontic procedures, to surgical reduction in more severe cases. (1) (3)

 

Sources

  1. National Institutes of Health
  2. NIH National Library of Medicine
  3. National Organization for Rare Disorders

 

Carpal Tunnel & Amyloidosis

Cardiac Amyloidosis: Look to the Wrist for an Early Diagnostic Clue

Tissue samples from carpal tunnel surgery hold screening utility

According to the Cleveland Clinic, tenosynovial tissue biopsy at the time of carpal tunnel surgery can be a useful tool for detecting cardiac amyloidosis at an earlier stage, suggests a recent Cleveland Clinic study in the Journal of the American College of Cardiology (JACC) (2018;72:2040-2050).

“We found that 1 in 10 older patients who underwent carpal tunnel release surgery for idiopathic carpal tunnel syndrome had either ATTR [transthyretin] or AL [light chain] amyloidosis in a sample of patients who had tenosynovial tissue removed,” says Cleveland Clinic cardiologist Mazen Hanna, MD, the study’s primary investigator. “This may be an early marker or precursor of amyloid heart disease.”

An accompanying editorial in JACC (2018;72:2051-2053) calls the investigation “a well-conducted pilot study that should be seen as a justification for larger screening efforts.”

Better defining the amyloid/carpal tunnel connection

The study was prompted by recognition that, despite the classic association of amyloidosis with carpal tunnel syndrome, the frequency of cardiac involvement at the time of carpal tunnel release surgery had never been established.

“The index patient that got us thinking about this project was operated on by Cleveland Clinic orthopaedic surgeon William Seitz, MD, a key collaborator on the study, who noted thickened tenosynovial tissue and astutely asked for a Congo red stain,” Dr. Hanna explains. “In the wake of that, we decided to undertake this study to determine the prevalence and type of amyloid deposits in carpal tunnel surgery patients and assess for cardiac involvement.”

So Drs. Hanna and Seitz, together with colleagues from Cleveland Clinic’s Heart & Vascular and Orthopaedic & Rheumatologic Institutes, ended up prospectively studying consecutive men aged 50 or older and women aged 60 or older undergoing carpal tunnel release surgery at Cleveland Clinic over a one-year period. They stained samples of tenosynovial tissue from all patients; those with confirmed amyloid deposits were typed with mass spectrometry and the patients underwent cardiac evaluation consisting of electrocardiography, echocardiography with longitudinal strain, technetium pyrophosphate scintigraphy and blood tests for biomarkers.

Findings prompt therapy initiation in three patients

Of the 98 patients enrolled, 10 (10.2 percent) had a positive biopsy for amyloid — seven ATTR, two AL and one untyped. Two of these patients were diagnosed with hereditary ATTR, two were determined to have cardiac involvement (one AL, one ATTR wild-type) and three were started on pharmacologic therapy.

Notably, patients with ATTR demonstrated no difference in plasma transthyretin concentration or tetramer kinetic stability, which indicates that these measures likely cannot serve to detect cardiac amyloidosis on their own.

Low-cost method of early detection

“Amyloid cardiomyopathy is an underrecognized cause of heart failure with preserved ejection fraction,” Dr. Hanna observes. “We believe that screening patients for amyloidosis when they have carpal tunnel surgery can be an inexpensive way to diagnose cardiac involvement early and help avert progressive heart failure.”

This is particularly true, he notes, with the advent of the first effective therapies for cardiac amyloidosis, which recently have rendered the condition medically treatable for the first time.

“The early recognition made possible by tenosynovial tissue biopsy is critical, since current treatment strategies suppress the production of precursor protein or prevent protein misfolding but do not directly target current amyloid deposits,” Dr. Hanna explains. “This allows for implementation of disease-modifying therapy prior to development of cardiac symptoms.”

He adds that the detection of AL in two of the 10 patients with biopsy-diagnosed amyloidosis is especially notable since AL cardiac amyloidosis tends to progress more rapidly and has a poor prognosis once cardiac involvement advances.

Time for a screening algorithm

Dr. Hanna and his colleagues are continuing to follow up the study cohort to observe and report additional noteworthy findings. In the meantime, these initial results, together with emerging data related to soft tissue amyloidosis, have prompted implementation of a new screening algorithm at Cleveland Clinic.

The algorithm, available as a supplementary online figure to the JACC study report, guides hand surgeons on the appropriateness of tenosynovial biopsy at the time of carpal tunnel release surgery. If Congo red staining is positive, typing with mass spectrometry and referral to an amyloidosis specialist is indicated.

The authors of the accompanying JACC editorial note that while the best screening methodology remains to be determined, “a screening algorithm will likely be incorporated into everyday clinical practice in the near future.”

Closing Words



Adapting During COVID-19

While our amyloidosis patient presentations have always been in-person, whether in class or over lunch, during this unusual time surrounding the COVID-19 pandemic we are offering two excellent virtual alternatives, each accompanied by a presentation by one of our advisors. These virtual packages have already been shared with hundreds of medical students across the country and have been well received.

1a)  Live webinar. Hosted by the medical school on their platform, our patient speaker provides a live presentation of their journey with this disease, from symptoms through diagnosis and treatment, and life today, followed by real-time Q&A. Typically one hour in length, we are very flexible and work with the school’s desired date and time.

OR

1b)  Pre-taped patient video presentation.  Jessica, one of our patient speakers, shares her journey with cardiac AL amyloidosis with medical students at the University of Colorado School of Medicine. She takes the audience through her early symptoms, diagnosis, treatment, and her “new normal” life today, offering her perspective as a patient with a rare disease. Her emotional and compelling story is about 30 minutes long, followed by 10 minutes of Q&A from the students.

PLUS

2)  Clinical PDF on Diagnosing Amyloidosis.  An excellent powerpoint presentation “Diagnosing Amyloidosis: From Cardiology to Neurology” by Dr. J. Mark Sloan from Boston University’s Amyloidosis Center, including patient and pathology pictures, and clinical diagnostic information.

We believe, and feedback confirms, these virtual packages are a compelling alternative to in-person that advances students’ knowledge of amyloidosis while sharing valuable insights from both the patient and clinical perspectives.  These virtual packages can be customized to focus on other types of amyloidosis, organ involvement, and expert medical presentation topics to meet specific audience interests.

If interested in learning more, please contact us at asb.mm713@gmail.com.

Periorbital Purpura & Amyloidosis

Most of the symptoms and signs of AL amyloidosis are non-specific and usually caused by a number of other common conditions.  But a few rare complaints are very suggestive of a diagnosis of AL amyloidosis.  Bruising of the skin around the eyes is one of these.  This is known as periorbital purpura in medical terminology, and may also be referred to as raccoon eyes or panda eyes.

 

Although less than 15% of patients with AL amyloidosis experience this problem, it is hardly ever caused by anything else, so it should certainly prompt doctors to investigate the possibility of AL amyloidosis.

 

Periorbital purpura is dark, usually appears quite suddenly, and is quite different from the common phenomenon of shadows under the eyes.  The appearance is usually that of quite severe bruising.  Sometimes the bruising fades or even disappears during or after chemotherapy treatment, but this may take months.  Some patients with AL amyloidosis also experience easy bruising in other parts of the body.  Any rubbing of the skin can cause these to appear and they may then fade.  However the bruising round the eyes usually lasts for much longer.  It does not cause any pain or irritation and is only a cosmetic issue.

It is quite often the trigger for a doctor to check for the possibility of amyloidosis.

 

Source: National Amyloidosis Centre

Amyloidosis: The Road to Diagnosis

As a rare disease with a wide range of symptoms, Amyloidosis can be difficult for doctors to recognize. The disease presents itself differently depending on the type of Amyloidosis and which organs are affected. Delays in diagnosis are common, and some suffer for years while seeking answers. As a result, the road to diagnosis is often too long and winding, resulting in serious consequences for patients.

According to a survey of 575 patients conducted by Mackenzie’s Mission in 2019, over 60% of patients surveyed saw between two and four doctors before receiving a diagnosis, and another 24% saw five or more.

 

We reached out to our Amyloidosis community and asked them to share their road to diagnosis. Hear from Lisa, Len, Jan, Janet, and Laura, as they share their unique symptoms and struggles in receiving their Amyloidosis diagnosis.

 

Lisa

Lisa was diagnosed with Tracheobronchial Amyloidosis in 2011. She was 41 years old and had only 39% lung function. After working as a first responder for ASPCA in post-Katrina New Orleans, Lisa began having breathing problems. She assumed it was a reaction to the dust and debris she was exposed to in the hurricane zone.

In 2006 she was diagnosed as being severely asthmatic and was treated with inhalers and nebulizers. None of the treatments improved her symptoms and caused multiple side effects, including manic episodes and weight gain. Her health continued to decline.

Now unable to work due to her breathing problems, Lisa moved back home with her elderly mother in New York. She continued to seek treatment while rapidly losing lung function.

Finally, in 2011, she once again switched pulmonologists in her search for answers. Lisa’s new doctor took her off the steroids and did a bronchoscopy. They found a 2cm mass in her trachea, a mass so big it prevented the scope from going into her lungs. A biopsy, including congo red stain, revealed a diagnosis of Amyloidosis. Lisa’s was the first case of Tracheobronchial Amyloidosis diagnosed at the Albany Medical Centre in New York.

Thankfully, Lisa’s pulmonologist referred her to Dr.Berk at the Boston Medical Centre. After treatment with low dose radiation and chemotherapy, including Velcade, she has been steady since 2014.

Lisa, at the age of 49, is now reliant on a scooter to get around and is on oxygen 24/7. Despite her battles, she has a beautiful attitude towards life, facing her troubles with grace and bravery. In Lisa’s words: “Life is always an adventure, right?”

 

Len

Len suffered from symptoms for two years before receiving a diagnosis in 2012. After not feeling well, he visited a naturopath who helped alleviate some of his symptoms. He was having issues with his heart, and blood work showed a problem with his kidneys.

He was sent to a kidney specialist who ordered a biopsy. Within 24 hours he was given a diagnosis of Amyloidosis, with further testing showing it was AL. A bone marrow biopsy was also performed to rule out the possibility of multiple myeloma.

Thankfully, Len was admitted into a trial and received chemotherapy with melphalan, dexamethasone, and antibiotics. Within six months, he was in full remission!

Len has a great sense of humor and continues to spend time enjoying the things he loves. In Len’s words, “We power on as life can be short.”

 

Jan

Jan was diagnosed with AL Amyloidosis affecting her heart, skin, autonomic and peripheral nervous systems in 2009 at the Mayo Clinic in Rochester, MN. She visited Mayo after suffering from symptoms for over six years and was diagnosed within days.

Early symptoms included swelling, trouble walking, difficulty swallowing, tingling and numbness. According to Jan, some days, “it felt like her legs didn’t respond to her intentions for them to move.”

As her symptoms progressed, Jan had problems chewing and struggled to even open her mouth wide enough to eat. She was out of breath and lightheaded when standing, sometimes accompanied by lower chest pain. Jan suffered from severe fatigue and some days was unable to move her legs or lift her arms. Everyday activities required extreme concentration. Other symptoms included thinning hair, brittle fingernails, and stiff, painful hands.

She suffered from these symptoms for six years.  She faced x-rays, ultrasounds, MRI’s, CT scans, a stress test, an angiogram, an echocardiogram, and a pulmonary function test. As her health continued to decline, Jan’s doctor assured her things were normal and that she had the heart of a twenty-year-old.  Despite her doctor discouraging her, she decided to head to the Mayo Clinic.

Thank goodness she pushed through and advocated for herself! After four days of testing at Mayo, she was diagnosed with Amyloidosis.  In 2009, she had a partial response to her stem cell transplant. Two years later, after doctors discovered a blockage, she received a pacemaker.

In 2016, her light chains rose high enough that she needed another stem cell transplant. This time it was exceptionally difficult on her body. But after many issues and a lengthy hospitalization, Jan had a complete response. She is still in hematological remission today!

Although she still suffers from symptoms due to damage done to her heart, she is doing her best to lead a full life and is now “feeling back to her new normal.”

 

Janet  (not her real name – the patient asked to remain anonymous)

Janet received a diagnosis of Amyloidosis in June 2019, primarily affecting her kidneys and neurological system.

Her early symptoms included a lack of appetite, problems with bowel movements and sudden weight loss of 30 pounds. As her symptoms progressed, Janet suffered from low blood pressure and dizzy bouts and eventually would pass out upon standing. She had a tingling sensation between her toes, which progressed to constant, excruciating pain on the bottom of her feet.

Throughout the two years she searched for answers Janet visited many specialists. She had a colonoscopy, cardiac catherization, NCV, EMG, adrenal gland imaging, total body x-ray, blood tests, cardiac stress tests, heart monitor, skin biopsy, bone marrow biopsy, and a kidney biopsy.

Janet was dismissed at emergency rooms, with doctors saying her symptoms were either related to orthostatic hypotension or nothing.

She was misdiagnosed with MGUS and was being monitored by a hematologist because she had the markers for Multiple Myeloma.

As her symptoms continued to worsen, she visited her primary care physician who ordered a 24-hour urine sample. Janet was immediately sent to the emergency room when the results showed high amounts of protein in her urine. A kidney biopsy was performed and showed a diagnosis of Amyloidosis.

After facing CyBorD treatment, Janet is now on maintenance. Her neurological pain and weakness has worsened, and she is now using a walker.

She is too weak to be eligible for a stem cell transplant, but in Janet’s words “I’m hoping when I go back in June that this may change. Fingers crossed!”

 

Laura

Laura was diagnosed with AL Amyloidosis in the spring of 2018, at the age of 45. Her initial symptom was a chronic cough, which began six months earlier.  Diagnosed with asthma, Laura was treated with inhalers, nebulizers and steroids. The medications did nothing to improve her symptoms. As these issues continued, new problems emerged. Edema in her legs and ankles and an elevated BNP prompted her doctor to refer her to a cardiologist.

He tested and pursued answers until a diagnosis of Amyloidosis was confirmed. Because the Amyloidosis affects her heart, she has had an EKG, echocardiograms, a cardiac MRI, and a heart biopsy.

Laura’s last treatment was in October 2019. She is now monitored to ensure her levels remain normal. In Laura’s words: “I feel good most days. I know God is in control, so I try not to get too worked up.”

 

Conclusion

Amyloidosis presents itself in different ways with varying symptoms for each patient. Because of these differences, doctors often struggle to find an answer. If you are sick and searching for a diagnosis, please don’t give up. Follow your instincts, switch doctors, get second opinions, and keep going until you find out what is happening.

During my search, I was told it was anxiety and that my symptoms were all in my head. They were NOT. I was made to feel like I was irritating my doctor with my repeat visits. I was embarrassed and made to feel like I was too weak to handle life, that I was seeking attention, and exaggerating my symptoms. None of this was true.

I was sick and I needed help. I remember sitting in the parking lot of the hospital, too embarrassed to go in because I didn’t want to be dismissed and made to feel like I was crazy. So, I sat. I sat in that parking lot and cried because I couldn’t find someone who would help me.

Soon after, I realized that this is MY LIFE and other people’s opinions of me didn’t matter. In my gut I knew I was sick.  I went back to doctors, and clinics and the ER again and again and again and I demanded answers. Until one day, a wonderful hematologist said to me, “It is obvious that you are very sick.”

And with that statement I felt relief. You’d think my first instinct would be fear, but I felt relieved. Because I finally found someone who believed me. And I feel in my heart that this beautiful lady saved my life. I will be forever grateful to her.

If this resonates with you, your answers are out there too. Keep searching.

 

We are thankful to our fellow Amyloidosis patients for sharing their stories with us. Knowing that you are not alone can be an extraordinary help when faced with a scary diagnosis. If you or a loved one has been recently diagnosed with Amyloidosis, reach out to find support in those who genuinely understand your battles. It can make all the difference.

 

 

Lori Grover is a guest blogger for Mackenzie’s Mission. She was diagnosed with AL Amyloidosis in 2016 and writes to share experiences and lessons learned during her journey.  More wonderful blogs by Lori can be found on her page Amyloid Assassin.  Lori is a freelance copywriter, and a mom of two wonderful boys. She loves writing, reading, and all things crafty. 

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