Participant characteristics
Table 1 shows patient participant demographics. Out of the 12 patients interviewed, 58% (n = 7) were women. The average age of participants was 40 years, and the average age at diagnosis was 23 years (22.75, range 6–48 years). Most of the sample were White (n = 10), and an estimated 20% of the sample were being treated in a COE. Patient quotes are labeled with ID number, gender, and age.
Table 1
– Patient participant characteristics (n = 12)
| Age, years | |
|---|
| Average (range) | 40 (19–72) |
| Age at diagnosis (years) | |
| Average (range) | 22.75 (6–48) |
| Gender, n (%) | |
| Men | 5 (42) |
| Women | 7(58) |
| Ethnicity | |
| White | 10 (83) |
| Hispanic | 1(8) |
| Native American | 1(8) |
Seven physicians were interviewed: 4 hepatologists (2 of whom were pediatric hepatologists) and 3 neurologists. Most physicians (5/7) were based in a COE specializing in WD, and the remainder were based at academic medical centers and transplant units. On average, the physicians saw 12 (11.57) patients with WD in the last year (Table 2). Physician quotes are labeled with ID number and discipline.
Table 2
Physician participant characteristics
| Specialty, n (%) | |
|---|
| Pediatric hepatologist | 1 (14) |
| Hepatologist | 2 (29) |
| Neurologist | 3 (43) |
| Pediatric transplant hepatologist | 1 (14) |
| Total | 7 (100) |
| No. of patients with WD seen in the last year | |
| Average (range) | 11.57 (3–24) |
Categories and themes
The analysis resulted in 5 overarching categories, each comprising a set of main themes (n = 18) and subthemes (n = 23) (Table 3).
Table 3
– Categories, themes, and subthemes
| Category 1: Diagnosis journey |
|---|
| Theme 1: Early presentation | Theme 2: Physician involvement & communication | Theme 3: Extensive testing | Theme 4: Patient emotions & intuition |
| Subthemes | Age of diagnosis | First doctor approached | Prediagnosis testing | Sense of something not right |
| Symptoms prior to diagnosis | Specialists’ involvement prior to diagnosis | Screening | Emotional response |
| Early suspected diagnosis | Doctor who first identified WD | Diagnosis confirmation testing | |
| Time frames from symptoms or clinical presentation to diagnosis | Explanation of diagnosis | Poking and prodding — excessive testing | |
| Category 2: Multidisciplinary approach |
| | Theme 1: Treatment management | Theme 2: Collaboration | Theme 3: Views on physician treatment |
| Multiple specialists | Joint working | Positive |
| Time frames | Data sharing | Negative |
| Testing | | |
| Pregnancy | | |
| Lack of access | | |
| Category 3: Medication |
| Theme 1: Types of medication | Theme 2: Side effects | Theme 3: Adherence | Theme 4: Cost of medication | Theme 5: Improvement | Theme 6: Ongoing symptoms and concerns |
| Category 4: The role of insurance |
| Theme 1: Comprehensive insurance | Theme 2: Limited insurance |
| Category 5: Education, awareness, and support |
| Theme 1: Family support | Theme 2: Awareness in the medical community | Theme 3: Information sources |
Category 1: Diagnosis Journey
This category comprises 4 themes outlining the procedural aspects of the diagnosis experience as reported by both patients and physicians, in addition to the patient emotional experiences associated with them.
Theme 1: Early presentation
The age at diagnosis varied widely (range 6–48 years); however, the patient’s age did not seem to influence their subsequent experience in terms of the speed of reaching diagnosis and the initiation of treatment. Patients presenting with predominantly psychiatric or neurological symptoms reported longer diagnosis journeys (range 1–16 years) than those presenting with hepatic symptoms or diagnosed through genetic screening (range 2 weeks-3 years). Presenting symptoms varied greatly (see Table 4). Some patients talked about early suspected diagnoses that included leukemia, thyroid issues, degenerative brain disease, and stroke.
Table 4
Codes in symptoms prior to diagnosis
| Subtheme: Symptoms prior to diagnosis |
|---|
| Physical/Biological | Neurological | Emotional/Psychological |
| • Liver issues • Fatigue or tiredness • Eye problems • Abnormal blood test results • Pain or bodily discomfort • Vomiting • Inconsistent menstrual cycle • Nosebleeds • Fever • Skin discoloration/jaundice • Eye problems • Swelling | • Tremors • Drooling • Dysphagia • Poor memory • Coordination or motor skills • Cognitive • Balance or gait • Speech problems • Dizziness • Weakness | • Affective disorders • Managing emotions • Other psychological issues |
Theme 2: Physician involvement and communication
The first doctor approached by patients for their presenting symptoms was generally a primary care physician; however, some patients reported presenting at the emergency room (ER) or via an allied healthcare professional (HCP) such as a speech therapist. Patients discussed seeing multiple specialists prior to receiving the diagnosis of WD (Table 5).
Table 5
Examples of physicians involved prior to diagnosis, as reported by patients
| First doctor approached | Specialist involvement prior to diagnosis | Doctor who suspected WD |
|---|
| • Primary care doctor • ER doctor • Pediatrician • Speech therapist • First-year resident • Ophthalmologist • College health office • Cardiopulmonary specialist (family friend) | • Infectious disease doctor • Oncologist • Gastroenterologist • Nursing assistant • Ophthalmologist • Primary care doctor • Psychiatrist • Neurologist • Pediatric gastroenterologist • Intensive care staff | • Gastroenterologist • ER doctor • Primary care doctor • First-year resident • Pathologist • Ophthalmologist • Hepatologist • Cardiopulmonary specialist (family friend) |
While some patients described receiving discouraging comments from their physician with regard to their prognosis and WD’s likely impact on their quality of life (e.g., ability to bear children), the physicians typically reported describing WD to their patients as something treatable but not something to be solved overnight.
“I mean especially in children, I usually say, Well, we have a treatment, so we have a treatment that works pretty well, we can get you to take it and consistently take it and continue monitoring like you’re supposed to, show up for labs etc., then we can usually manage it.” Physician WD06, pediatric hepatologist
Theme 3: Extensive testing
Patients described the burden of ongoing testing throughout their diagnosis journey and the constant “poking and prodding,” including investigatory blood tests, urine samples, eye tests, procedures (i.e., surgery or biopsy), and imaging (i.e., magnetic resonance imaging or computed tomography scans). Physicians were consistent in their report of the tests employed to confirm diagnosis, specifying ceruloplasmin tests, 24-hour urine copper, and an eye exam for Kayser-Fleischer rings. All physicians reported that patients undergo genetic testing as part of the diagnostic process.
“The pediatric GI [gastroenterologist] person will send a bunch of additional labs and find out the ceruloplasmin’s low, then they’ll send them to us, we’ll do the biopsy….” Physician WD06, hepatologist
Theme 4: Patient emotions and intuition
Those patients diagnosed as children described a parent who pushed for tests due to an intuition that there was a deeper problem not yet identified by medical professionals. When receiving the diagnosis, some patients reported feeling negative emotions, such as being afraid. In contrast, others reported feelings of relief to finally receive an explanation as to what was wrong, following a complex journey.
“It was just a weight off my shoulders, finally knowing what was wrong, and there was an answer to what was happening. It was like when it’s all raining and all of a sudden, the sun opens up and the clouds clear and you can see the sky; that was basically what it felt like.” Patient WD12, man, 19
Category 2: Multidisciplinary approach
This category contains data on the ongoing management of WD, as experienced by patients with WD and physicians managing them.
Theme 1: Treatment management
Physicians emphasized the importance of a multidisciplinary team including hepatology, neurology, and psychiatry and supported by social work, physiotherapy, and psychology to manage care after diagnosis. Patients similarly reported engagement with gastroenterologists or hepatologists alongside their primary care physician but did not typically receive support from psychiatry or wider allied HCPs such as physical therapists. Some patients described a lack of access to WD specialists due to geographical distance.
“All of those providers would be optimal, even in terms of a one-time assessment to understand that they do or do not need additional assistance. So really a hepatologist, neurologist, psychiatrist, and…or physical therapist to have a more holistic evaluation of their needs would be optimal.” Physician WD05, neurologist
Regular testing was discussed by both patients and physicians as a large part of WD management. Physicians emphasized the importance of specific tests, such as liver function, ceruloplasmin, and 24-hour urine copper tests. One physician talked about the difficulties a patient had accessing these tests due to geographical distance.
“I’ve had one that I’m really struggling with that 24-hour urine collection…the mom really pushed out to at least yearly. But I was doing, every six months, ideally, I would want a 24-hour urine collection, and his hepatologist was recommending every three months.” Physician WD07, neurologist
Two patients had 2 successful pregnancies each, despite 1 patient being told that it would not be possible. The patients outlined the changes in management during this time, such as increased monitoring and meeting frequency.
“I knew that penicillamine could cause disruption in collagen formation, so I knew that if I had a C-section, it might not heal as well, that’s why they dropped down my dose, for that reason. I was able to breastfeed.” Patient WD11, woman, 52
Some of the physicians discussed the additional monitoring and professional involvement required, such as a perinatologist and a high-risk obstetric clinic, alongside promoting good adherence to the low-copper diet and having the patient take zinc and avoid chelators.
“I think ideally we’d talk with our patients of childbearing potential about that and make some decisions about treatment based on that, and so zinc is probably a safer agent, and so getting someone on zinc and getting someone stable on that would be ideal before they get pregnant. I think most of our Wilson’s patients we suggest being cared for by a high-risk OB/GYN [obstetrician-gynecologist], and then again it just depends a little bit on distance.” Physician WD04, hepatologist
Theme 2: Collaboration
Most physicians discussed the importance of co-managing patients with professionals from other disciplines. Some physicians described challenges with local HCPs. Patients had mixed experiences; while the majority were aware that their physicians were working together and communicating, some felt the different HCP involvement was too isolated. Physicians, in particular those from COEs, believed that shared electronic medical records among HCPs supported multidisciplinary collaboration.
“So, one of the things is also to co-follow patients with the local gastroenterologist, so on one hand to empower them, but it becomes sometimes very, very tricky to do so.” Physician WD01, hepatologist
Theme 3: Views on physician treatment
Patients expressed varying opinions on their physicians. Most of the patient respondents had positive views of their physicians, describing them as being supportive, providing good advice on adherence to diet and medication, and managing side effects.
“He was a very good doctor, he explained everything. And then I remember leaving the room and I’m guessing they talked seriously with my parents about the impact that it would have on my life and on their life.” Patient WD05, woman, 20
Some patients described more negative experiences, such as impersonal interactions where they did not feel heard, in addition to receiving discouraging comments around the time of their diagnosis. This occurred both for those diagnosed decades ago and those diagnosed more recently.
“Well, he said I might die — he said by my next birthday, I’d be dead in a year. He told me all his patients had died — so he told me by my next birthday, I’d be dead by 20 years old, but I sure fooled him.” Patient WD08, man, 73
Category 3: Experience with medication
Medication was discussed as a crucial part of management for WD; both patients and physicians described a range of experiences, outlined in the themes below.
Theme 1: Types of medication
Zinc was widely discussed by both patients and physicians, with most of the patients solely using zinc, which required a regime that they described as “onerous.” Physicians recommended a combination of a chelator and zinc as the best practice, even for maintenance. Some patients and physicians also talked about their experience of experimental medication in clinical trials, antidepressants, and movement disorder medications.
“The first medication I was on was tetrathiomolybdate… I was guinea pig Number 11.” Patient WD10, woman, 51
Theme 2: Side effects
Half the patients recalled issues with side effects from medication. A commonly reported side effect was nausea and vomiting, relating to zinc. Side effects to chelators were reported, such as rashes, and 1 patient experienced a tightness in their throat. Similarly, physicians spoke about how zinc causes gastrointestinal upset. Physicians theorized this could be why some stable patients were using only a chelator because zinc was not well tolerated.
"With taking a lot of zinc, you get a lot of stomach aches and once or twice a month you have serious gastro problems that include diarrhea. That is the most serious side effect of taking a lot of zinc." Patient WD04, man,19
Theme 3: Adherence
Adherence to the medication and dietary regimen was described as challenging, by both patients and physicians, particularly in childhood. Some methods such as pill boxes, alarms, and printouts of high-copper foods were offered by physicians; however, some patients said they were not offered support for adherence challenges. Physicians also discussed using urine and blood tests to monitor adherence. Some physicians suggested that non-adherence to medication was due to their side effects, with 1 also highlighting cases whereby loss of insurance due to life events such as job loss also contributed.
“…trying to get them to adhere to a low-copper diet and take their zinc every day or their trientine…there’s people that scrap this…It can be difficult, I’ve had… teenagers in college and their labs are completely out of whack, and they swear they’re taking their medication.” Physician WD06, pediatric hepatologist
Theme 4: Cost Of Medication
Patients understood the cost of medication, particularly chelators, and discussed the barriers this presented. Generally, physicians viewed zinc as a cheap and accessible medication option for all patients. Physicians acknowledged that chelators, such as trientine, are not affordable to many patients, which perhaps explains why only half of the patients interviewed were using them. One patient expressed fear about the potential prohibitive costs of new treatments when they reach the market.
“I am not taking penicillamine, I am not taking trientine. I guess I could get funding for that. If I don’t have funding for that, those medicines are real expensive. Basic things that are cheaper.” Patient WD03, woman, 53
Theme 5: Improvement
Many patients experienced improvement in their symptoms due to the medication, including reduction in liver cirrhosis or tremors. The most reported improvement was the disappearance of Kayser-Fleisher rings in the eyes.
Patients also reflected on how the improvements made them feel, and how they were able to progress in their life despite having WD. For a few patients, they were also able to reduce their medication once symptoms had improved.
“… in 14 years, my liver has not had any more cirrhosis because of my medicine.” Patient WD05, woman, 20
Theme 6: Ongoing Symptoms And Concerns
Some patients reported a range of ongoing symptoms, some still linked to their initial presentation and others that had emerged since diagnosis. The most common ongoing symptoms were tremors, fatigue, and depression/low mood. However, the reason for these ongoing symptoms and their relationship to the patient’s medication regimen are unclear.
Neurologists spoke about the ongoing management of movement-related symptoms and stressed that patients can still experience some of these manifestations despite being on the optimal treatment for the movement disorder.
“If people have more manifestations, kind of a combination of the things we talk about tremor or Parkinsonism, dystonia, those people have a tendency to get better if they’re on medicine, but they might also continue to have residual symptoms, even with the optimal treatment after time, and then people who are severely affected often remain severely affected, even with treatment.” Physician WD04, neurologist
Category 4: Influence of insurance
Participants described a range of insurance providers from private insurance through family and work, to federal health insurance programs for those with lower income or disability.
Theme 1: Comprehensive Insurance
Some patients spoke about their insurance covering a large part of their tests and treatment for WD. Patients who reported having private or comprehensive insurance tended to be on chelators, whereas patients with less comprehensive insurance were on zinc.
“It covers everything…They started me with penicillamine because it was a lot less money; the medicine I’m on now is $50,000 a month per my insurance, and so they didn’t want to put me on that immediately without trying penicillamine first.” Patient WD05, woman, 20
Theme 2: Limited Insurance
Patients reported not getting tests, treatments, or prescription zinc and chelators due to limited insurance. All physicians talked about experiencing insurance barriers, both for approving chelation therapy and prescription zinc.
“It is good that I have insurance, but X is the worst insurance if you are American because it is for lower income. They are helping me with the basic things, but since that insurance isn’t very good, they are not helping me with more expensive [things]…” Patient WD03, woman, 53
Category 5: Education, awareness & support
This category comprised elements of support and knowledge that both patients and physicians believed contributed to the good clinical management of WD.
Theme 1: Family Support
Patients spoke about the various ways their family had supported them throughout their journey, from advocating with physicians to offering support with the medication regimen and dietary restrictions, particularly those who were diagnosed in childhood. Physicians also acknowledged that family support is as important as having good insurance. One physician stated that family support was particularly helpful in cases where there is non-adherence to medication and where more severe presentations involve neurological issues.
“Well, we try, education is a big part of it, and getting the family, if there is family and friends to be part of the equation for trying to get someone compliant.” Physician WD04, neurologist
Theme 2: Awareness In The Medical Community
Patients spoke about encountering HCPs at all stages of their journey who knew little to nothing about WD. The physicians interviewed were not surprised by this due to the rarity of the disease and most HCPs’ lack of exposure to it. They emphasized the importance of having a WD specialist involved in some way in the management of patients with WD.
“…because it is a rare disease…it needs to be brought to attention that there are things out of the norm, and people have these situations. Doctors are busy; they can’t think of absolutely everything, but the awareness does kind of need to be there.” Patient WD08, woman, 40
Theme 3: Information Sources
Patients discussed drawing on a variety of sources for information and education. This included Facebook groups and rare disease websites and forums; however, 1 physician expressed some concerns over the reliability of these sources. Some patients reported their physician as the principal source of information. But physicians did feel there was a need for more information, with 1 stressing the need for patients to self-educate and self-advocate.
“We certainly point people to the Wilson’s Disease Association for education and support, and it’s often a good way for them to continue to read about the illness and connect with other patients because it’s a rare condition and being part of that community can often be helpful in terms of understanding where they are and not being on their own as much.” Physician WD05, neurologist