Patients with light chain (AL) amyloidosis often experience a complex, lengthy, and ambiguous journey to diagnosis, which can affect their emotional well-being. |
Older patients may delay seeking medical help because they attribute early, common symptoms, such as fatigue or changes in appetite, to the aging process or to other chronic, more common conditions. |
Clinicians face diagnostic challenges due to lack of awareness of AL amyloidosis, the non-specific symptoms of the disease, and the heterogeneity of the condition. |
1 Introduction
2 Methods
2.1 Qualitative Interviews
2.1.1 Recruitment and Procedures
2.1.2 Data Coding and Analysis
2.2 Quantitative Survey
3 Results
3.1 Study Participants
Clinician research [n (%)] | Patient research [n (%)] | ||
---|---|---|---|
Qualitative study (n = 10)a
| Qualitative study (n = 10)b
| Quantitative study (n = 341)c
| |
Gender | |||
Female | 2 (50.0) | 6 (60.0) | 180 (52.9) |
Male | 2 (50.0) | 4 (40.0) | 160 (47.1) |
Age (years) | |||
Mean (range) | 57 (43–76) | 60 (23–85) | |
Highest level of education completed | |||
<4-year college degree | 0 (0.0) | 4 (40.0) | 144 (38.8) |
College degree (BA/BS) | 0 (0.0) | 3 (30.0) | 109 (33.9) |
Advanced degree (MA, PhD, MD) | 4 (100.0) | 3 (30.0) | 88 (27.3) |
Region (in USA) | |||
Northeast | 2 (50.0) | 2 (20.0) | 68 (19.9) |
Midwest | 1 (25.0) | 3 (30.0) | 80 (15.8) |
South | 0 (0.0) | 4 (40.0) | 80 (23.5) |
West | 0 (0.0) | 1 (10.0) | 81 (23.8) |
Other (including international) | 1 (25.0) | 0 (0.0) | 58 (17.0) |
Time since diagnosis (years) | |||
Mean (range) | 2.3 (4 months–8 years) | 4.5 (1 month–28 years) | |
Organ(s) affected by ALd
| |||
Heart | 6 (60.0) | 178 (52.2) | |
Kidney | 5 (50.0) | 214 (62.8) | |
GI | 3 (30.0) | 148 (43.4) | |
Nervous system | 2 (20.0) | 126 (37.0) | |
Number of organs affected | |||
One | 5 (50.0) | 95 (27.9) | |
Two or more | 5 (50.0) | 246 (72.1) | |
Hematologic response to treatment (remission status) | |||
Complete hematologic response | 5 (50.0) | 141 (41.3) | |
Partial hematologic response | 1 (10.0) | 126 (37.0) | |
No response/disease progressing | 4 (40.0) | 23 (6.7) | |
Do not know | 0 (0.0) | 51 (15.0) |
3.2 Journey to Diagnosis
Quantitative study: survey participants | ||
---|---|---|
n
| % | |
Time between onset of symptoms and diagnosis | ||
<6 months | 96 | 28.2 |
Between 6 months and 1 year | 97 | 28.4 |
Between 1 and 2 years | 76 | 22.3 |
Between 2 and 3 years | 31 | 9.1 |
>3 years | 41 | 12.0 |
Number of doctors seen before diagnosis | ||
One | 11 | 3.2 |
Two | 57 | 16.7 |
Three | 60 | 17.6 |
Four | 68 | 19.9 |
Five | 50 | 14.7 |
Six or more | 95 | 27.9 |
Number of specialty types seen before diagnosis | ||
One | 21 | 6.2 |
Two | 70 | 20.5 |
Three | 97 | 28.4 |
Four | 58 | 17.0 |
Five | 43 | 12.6 |
Six or more | 52 | 15.2 |
3.2.1 Barriers to an Early Diagnosis
3.2.1.1 Interpretation of Signs and Symptoms by Patients Seeking Medical Help
“I’ve always had problems with statins, so I’ve always had joint and muscle pain, because statins have always bothered me. So, I didn’t think much about it when my hands started tingling and I had neck pain.” (Patient 003)
“It was things like being a little more tired, and I was suddenly, and I don’t know how this fits in, but I had been a vegetarian or semi-vegetarian for quite some time, and all of a sudden I would have these horrible cravings for meat, and I thought it had something to do with iron, being of a certain age or whatever.” (Patient 010)
“As part of that whole screening process [screening for eligibility for a stem cell transplant] questions were asked did you have any experience with this or that or the other thing. Then it became evident to me I was seeing some minor symptoms. Nothing I would have said caused me to go to see a doctor.” (Patient 002)
“And it was unusual. I never had shortness of breath. And then it wasn’t every single time. You know, I’d also notice things like I’d finish dinner and I’d go out and play catch with my son and I’d get out of breath. And it was a bunch of unusual circumstances like that. And finally I – the final thing that got me into the doctor was I went for a walk with my daughter, made it about a half mile and had to stop and rest. Like, okay, that’s definitely not normal.” (Patient 004)
3.2.1.2 Patient Characteristics Associated with Delayed Diagnoses
Characteristics | Time between onset of symptoms and receipt of a confirmed diagnosis |
p value | |||
---|---|---|---|---|---|
Early diagnosis (<6 months) (n = 96) | Delayed diagnosis (≥6 months) (n = 245) | ||||
n
| % |
n
| % | ||
Age [mean years (SD)] | 61.3 (10.3) | 60.2 (10.2) | 0.388 | ||
Gender | 0.356 | ||||
Male | 49 | 51.0 | 111 | 45.5 | |
Female | 47 | 49.0 | 133 | 54.5 | |
Race | 0.583 | ||||
White/Caucasian | 87 | 90.6 | 217 | 88.6 | |
Other | 9 | 9.4 | 28 | 11.4 | |
Educational attainment | 0.343 | ||||
<4-year college degree | 30 | 33.0 | 95 | 41.1 | |
College degree (BA/BS) | 32 | 35.2 | 77 | 33.3 | |
Advanced degree (MA, PhD, MD) | 29 | 31.9 | 59 | 25.5 | |
Initial symptoms (% yes)a
| |||||
Shortness of breath | 48 | 52.7 | 168 | 71.8 | 0.001 |
Fatigue | 66 | 70.2 | 211 | 86.8 | <0.001 |
Edema (swelling of ankles and legs) | 58 | 61.1 | 163 | 67.9 | 0.232 |
Dizziness upon standing | 37 | 41.1 | 135 | 57.9 | 0.007 |
A feeling of fullness in the stomach/early satiety | 36 | 38.7 | 136 | 56.7 | 0.003 |
Alternating bouts of constipation or diarrhea | 25 | 27.8 | 79 | 32.6 | 0.395 |
Weight loss | 33 | 35.1 | 99 | 41.3 | 0.301 |
Enlarged tongue | 13 | 13.8 | 54 | 23.1 | 0.060 |
Numbness of the legs/arms | 19 | 20.0 | 114 | 47.9 | <0.001 |
Purpura (raccoon eyes) | 17 | 18.3 | 65 | 27.3 | 0.087 |
Number of organs involved | 0.137 | ||||
One | 34 | 35.4 | 61 | 24.9 | |
Two | 21 | 21.9 | 68 | 27.8 | |
Three or more | 41 | 42.7 | 116 | 47.3 | |
Organ most affected by AL amyloidosis | <0.001 | ||||
Heart (cardiac) | 18 | 18.8 | 85 | 34.7 | |
Kidney | 61 | 63.5 | 83 | 33.9 | |
Other | 17 | 17.7 | 77 | 31.4 | |
Types of organs/systems impacted (% yes)a
| |||||
Heart (cardiac) | 45 | 46.9 | 133 | 54.3 | 0.218 |
Kidney | 69 | 71.9 | 145 | 59.2 | 0.029 |
Liver | 16 | 16.7 | 33 | 13.5 | 0.449 |
Nervous system | 26 | 27.1 | 100 | 40.8 | 0.018 |
Gastrointestinal | 32 | 33.3 | 116 | 47.3 | 0.019 |
3.2.1.3 Challenges of a Differential Diagnosis
Patienta
| Organ involvement | Physician specialists consulted | |||||||
---|---|---|---|---|---|---|---|---|---|
Cardiologist | Gastroenterologist | Hematologist | Nephrologist | Oncologist | Primary care physician | Pulmonology | Other | ||
001 | K | ✓ | ✓ | ✓ | ✓ | ||||
002 | K | ✓ | ✓ | ✓ | ✓ | ||||
003 | L, NS, O | ✓ | ✓ | ✓ | |||||
004 | H, GI | ✓ | ✓ | ||||||
005 | H | ✓ | |||||||
006 | K, H, GI, O | ✓ | ✓ | ||||||
008 | K, H, NS | ✓ | ✓ | ✓ | ✓ | ✓ | |||
009 | GI | ✓ | ✓ | ✓ | ✓ | ||||
010 | H | ✓ | ✓ | ||||||
011 | H, O | ✓ | ✓ |
“He started talking about; he didn’t say amyloidosis at that time but he said you know could be some variant of leukemia in your blood system. Could be myeloma.” (Patient 002)
“At that point the diagnosis was still cardiomyopathy … hypertrophic cardiomyopathy. When I was in the hospital to get the defibrillator pacemaker a team came in and basically just shook their heads and said, you know, something’s not right with this diagnosis so we’re going to do a biopsy. They did a biopsy and the next day installed the defibrillator. I went back for a check on the silver bandage the week after that where they advised me that I had cardiac amyloidosis.” (Patient 005)
“And when she came back, she said, ‘Oh, you have got something called pre-leukemia, MDS, myelodysplastic syndrome.’ She said that ‘That’s MDS, which is a form of cancer.’” (Patient 008)
“I think the asthma [diagnosis] absolutely was incorrect and going through all of the asthma medications, of course, did not help.” (Patient 010)
3.2.2 Emotional Toll of the Diagnostic Process
“… the longer it went the more and more frightened I got because they couldn’t identify it … when they finally said it’s amyloidosis, it’s almost a relief because I finally knew what it was.” (Patient 001)
“At the same exact moment [when I received the diagnosis] I feel relieved that actually I had a diagnosis, that I wasn’t crazy. I mean there was something wrong with me that wasn’t medically identifiable because, if not relief, there was a certain sense of justification that it is all good. And then it hit me when they started saying, yes, but there is no cure for AL.” (Patient 008)
“I can tell you the exact date when it happened, I know it was probably about 4:00 and I remember exactly where I was standing because I was at work, and I had gone into a stairwell to take his call, and I can remember in detail most of the conversation so in terms of feelings, it’s not exactly a feeling but it was life-changing, I knew that. I remember being distressed and wondering really what was going to happen to me, and it was a little bit of a shock, so I didn’t necessarily cry or anything at that moment, I just remember being kind of overwhelmed, which is probably the word.” (Patient 010)