Rare disease patients often face a difficult journey to diagnosis, commonly termed a ‘diagnostic odyssey’. This often involves moving from clinician to clinician, multiple misdiagnosis, unnecessary tests, and incorrect treatments. In this week’s blog, Narmadha Kali Vanan considers the impact of this on patients as well as the perspectives of medical staff.

Before I personally encountered a patient with a rare disease, mentions of rare diseases in medical textbooks led me to naively believe that these diseases would be instantly recognisable since their constellations of symptoms appeared to be so unique. When I encountered a child with Beckwith-Wiedemann Syndrome (BWS) during my paediatrics placement, I was keen to learn more about the condition, which I had never heard of before.

BWS is a congenital overgrowth condition associated with an increased risk of developing tumours (1). With an estimated incidence of 1 in 13 700, BWS satisfies the criteria of a rare disease, which is defined by the European Union as a disease that affects less than 5 in 10,000 of the general population (1, 2). Further research into this condition highlighted the features of BWS which makes it a challenge to diagnose. 85% of BWS cases are sporadic, arising as a result of a random mutation instead of an inherited gene defect. Furthermore, the hallmark features of exomphalos, macroglossia and gigantism are not always present as the clinical presentation of BWS is highly variable (1). The enormity of the diagnostic challenges associated with rare diseases began to dawn on me as I considered the cumulative effect these features would have on the diagnostic process of BWS.

The term ‘diagnostic odyssey’ encompasses the time from initial disease recognition or symptom onset to a final diagnosis as experienced by patients with rare diseases and their families. This usually involves multiple referrals and encounters with specialists and a battery of often unnecessary investigations (2). The average rare disease patient consults five doctors and waits four years before receiving a final diagnosis (3). This prolonged diagnostic journey is bound to have an impact on the patient at the centre of it all, with the right diagnosis and the appropriate treatment being delayed – potentially causing their condition to deteriorate further.

Patients have to face the frustration of attending multiple appointments as they are referred from one specialist to the next, alongside having to take time off work and school. Concerns may be raised about an individual if they miss too much work and this may lead to loss of income. If the patient concerned is a child, having to miss school to attend appointments may leads to feelings of social isolation. These factors can add to the stress of seeking out a diagnosis, alongside not having a named diagnosis to explain the situation to others. The psychological impact of the diagnostic odyssey is undeniable, with the stressors above combined with hopelessness and uncertainty about the future predisposing patients to conditions such as anxiety and depression (4).

Without a named condition, patients in the midst of this diagnostic journey also face issues with accessing coordinated care for themselves. Once the common conditions are ruled out, the diagnostic process can slow down as the patient may not fit into a box for further referral onwards to a certain specialty and the question arises as to who is best placed to care for the patient. This issue is further compounded by the fact that communication between hospital and local health services and even between hospital departments are often fragmented. The burden of ensuring that healthcare professionals have access to investigation results and documents from previous consultations falls to the patient, who often has to bring their own records to appointments or update their primary consultant (if there is one) if needed (3).

The battery of tests that these patients are often subjected to are not without their risks. Patients are bound to experience more anxiety associated with test results considering the high stakes of the situation. False positives and incidental findings that these tests unearth may become red herrings which mislead clinicians who are desperately trying to get to the root of the issue and may further cloud a clinical picture which is likely to be confusing enough as it is.

It is easy to understand how a patient and their family could lose faith in the medical profession while shuttling between specialists without an endpoint in sight. This is further worsened by misdiagnoses – the average rare disease patient receives three misdiagnoses before their final diagnosis (4). The emotional turmoil and unnecessary treatments associated with misdiagnoses add to the notion that the patient-clinician relationship suffers as a result. For example, if a patient has been misdiagnosed in the past, they may be more cynical of their doctor’s suggestions due to past experiences and the doctor then faces an uphill battle in inspiring the patient’s confidence in their diagnostic reasoning. Misdiagnoses may be perceived as ‘time wasted’ by patients as they may have undergone a different treatment pathway than what was required. The sequelae of the disease itself may have progressed further due to the delay in obtaining the correct diagnosis and appropriate treatment than it would have if the diagnosis was made sooner.

It is also important to consider the clinician’s perspective in this situation – a clinician may feel inadequate if they are unable to figure out what exactly is this problem and this may translate into them feeling as if they cannot be completely honest with the patient. This may lead to doctors wanting to err on the side of caution and not commit to a single diagnosis alongside referring the patient to another clinician, which may leave patients feeling frustrated. Some clinicians are also likely to seize the diagnostic challenge with zest which can be positive however, the sudden change in the pace and increased interactions with various clinicians may make it easy for patients to feel as if they are curiosities in a museum. As a medical student, I can definitely testify to being encouraged to approach patients with rare diseases to ask them for permission to examine them for interesting signs. Although examining patients and being exposed to rare signs is an essential part of medical education, it is important to consider the impact that this constant and potentially unwanted attention has on a patient. Clinicians may also write patients off as presenting with a psychological condition when confronted with records of multiple consultations without a named diagnosis, leaving patients with a label which is hard to shake off and may also lead to actual psychological conditions being missed (3).

A multifaceted approach is required to deal with the issues associated with a prolonged diagnostic journey. In rare diseases with multisystem involvement such as BWS, the input of various health professionals such as plastic surgeons, renal physicians, oncologists, speech and language therapists and orthodontists need to be drawn upon using a multidisciplinary approach. This approach should be supplemented by the presence of a named care coordinator where possible to ensure that patients and their families are not overly burdened by managing multiple appointments alongside relaying information to various health professionals, all while trying to understand a nameless condition. 5 Having someone who is experienced in rare diseases in this role who can act as a source of reliable information and support for patients would benefit patients greatly by reducing the amount of administration needed to coordinate their care and by staving off feelings of isolation.

A culture of openness and transparency should be encouraged so clinicians can be upfront with their patients about diagnostic uncertainty. Although it might not be what the patient would like to hear at the time, being aware of the reality of the situation is preferable to the patient being in the dark about the direction of their care, allowing them to adjust their expectations accordingly. Increasing access to genetic testing and specialist services so that clinicians are able to refer their patients on with less delay will hopefully speed up diagnosis and also allow differentials to be excluded more efficiently, avoiding the descent into a diagnostic odyssey. Empowering patients who are at the centre of this issue will prove to be the most effective way to improve patients’ experience. This can be done by directing patients to the appropriate support groups where they will be able to share their journey and expertise with others who are facing similar situations. For example, SWAN UK (Syndromes Without A Name) is a support network run by the charity Genetic Alliance UK which supports a community of families of children with undiagnosed conditions by organising free events for them to socialise at and by providing information to these families 24/7. 5 Encouraging patients to participate in research is another way to empower patients – patients and their families may have different priorities with regards to research outcomes and their experiences will add great value to research regarding their condition (3).

The consequences of the ‘diagnostic odyssey’ on rare disease patients and the patient-clinician relationship should be recognised and utilised to drive a shift in how rare disease patients are cared for by healthcare professionals. Empowering patients and encouraging patient-clinician collaboration will hopefully improve patients’ experience as they undergo the process of seeking an elusive explanation for their symptoms.

1. Weksberg R, Shuman C, Beckwith J. Beckwith–Wiedemann syndrome. European Journal of Human Genetics [Internet]. 2009 [cited 15 November 2017];18(1):8-14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987155/

2. Black N, Martineau F, Manacorda T. Diagnostic odyssey for rare diseases: exploration of potential indicators [Internet]. London: Policy Innovation Research Unit (PIRU), Department of Health Services Research & Policy, London School of Hygiene and Tropical Medicine; 2015 [cited 15 November 2017]. Available from: http://www.piru.ac.uk/assets/files/Rare%20diseases%20Final%20report.pdf

3. Muir E. The Rare Reality – an insight into the patient and family experience of rare disease [Internet]. Rare Disease UK; 2016. Available from: https://www.raredisease.org.uk/media/1588/the-rare-reality-an-insight-into-the-patient-and-family-experience-of-rare-disease.pdf

4. Rare Disease Impact Report: Insights from patients and the medical community [Internet]. Shire; 2013. Available from: https://globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf

5. About SWAN UK [Internet]. SWAN UK. [cited 15 November 2017]. Available from: https://www.undiagnosed.org.uk/about-us/