XLH (and to a lesser extent the other chronic hypophosphatemias) has been well-represented in medical journals in the last ten years or so, in the run-up to the clinical trials and eventual approvals of burosumab both XLH and TIO. The articles tend to fall into one of three categories: pure science at the molecular level (e.g., mouse models and bone analysis), more immediately practical science (e.g., clinical trial results, retrospective reviews of patient data, surveys), and everything else (opinions and case studies).
The category I don’t understand in the XLH context is case studies. According to the National Institutes of Health, a case study is “a research approach that is used to generate an in-depth, multi-faceted understanding of a complex issue in its real-life context.” That makes sense when there is very little available information on a medical condition or subset of symptoms, and the article is written by someone who has solid expertise in that subject, if not the particular angle addressed in the case report. .For instance, case reports made sense in the early days of COVID-19, when very little was known about it, and every scrap of information was useful. Or with the new bird flu that’s begun infecting humans, and again, very little is known about its potential effects on humans.
But what I’m seeing in the XLH context is articles written by authors who, as best I can tell, have only treated the one patient who is the example used in the case study. (or perhaps a handful of patients, as opposed to dozens or hundreds of us). It feels as if the clinicians are writing the article to justify all the work they put into learning about the disorder by reading the articles by actual experts.
As a patient reading these case reports, it often feels like the patients’ suffering was viewed, first and foremost, as a career opportunity for the clinicians, rather than as patients who needed help. The articles make me think of the ICU doctor who, on meeting me minutes after I’d been diagnosed with a heart attack, greeted me with, “Ooh, you have XLH. That’s so exciting.” And then wanted to talk about that instead of whether I was going to die from heart disease, pretending to be an expert in XLH when it was immediately obvious that all he knew about it he’d learned from two minutes with Dr. Google, and he’d remembered at least half of it wrong.
A lot of the case studies on XLH feel like a written variation on that experience: the authors happened to run into a patient with a rare disorder, one that’s gotten a fair bit of interest from journal editors lately due to there actually being a treatment for it (unlike the majority of rare disorders), so it’s an opportunity for them to show off the superficial knowledge they’ve acquired.
I’m not even sure there’s much benefit to this sort of article to the medical community. How does it make sense for someone who’s only treated one patient (or a small number of us) with the disorder to then be the one teaching everyone else about it? Especially in a disorder like XLH, where there is a wide range of symptoms and severity, how does it make sense for someone who has mostly a theoretical understanding of the disorder to be pontificating about it? In what other area of science does a single experiment (treatment of the case study’s one patient) make someone an expert, when there are many other scientists who have done the same experiment multiple times (treatment of a wide range of patients)?
I can understand the appeal of case studies for a condition that has NOT been widely studied or reported on. In that setting, every little bit of information is important, so the case study fills a gap, with most of the focus on the featured patient, rather than summarizing the literature. But there have been over 200 journal articles about XLH (or the other FGF23-mediated hypophosphatemias) in the past few years. Many of them, like this one, written by clinicians who have seen many patients with XLH, across most of its variations, rather than just a single patient whose presentation may be atypical. And most of the expert articles will mention the wide range of symptoms and severity, which suggests that the experience of just one patient is not particularly useful to a broader understanding of the disorder.
I just don’t see any real benefit to these case studies for either patients or the medical community at large. If forced to name one benefit, I’d say that at least the articles raise awareness of the condition. But I think that’s outweighed by the potential drawbacks, mostly related to the authors not knowing what they don’t know, and therefore passing along misinformation (or at least incomplete information). Many of the XLH case studies I’ve read perpetuate old myths, because the clinicians don’t have the necessary experience to avoid them. The biggest problem areas involve claiming that males are more seriously affected than females, believing that it’s possible to distinguish between “severe” and “mild” cases during childhood (without considering the progressive nature of the disease and the consequences in adulthood), and thinking chronic hyposphosphatemia is primarily about the bones/teeth, rather than a whole-body, whole-life disorder.
Sometimes I have to laugh at how clueless the author is, like when a case study mentions that something is surprising to the author, when in fact, it’s extremely common and well known among both patients and expert clinicians (like the article author who was shocked to find that XLHers are often misdiagnosed with ankylosing spondylitis, something I’ve known for more than twenty years, when it happened to me and I heard other patients mentioning the same misdiagnosis).
In other cases, I just want to bang my head against my desk in despair, like with the recent case study (not linking to it, because it doesn’t deserve the traffic) that resurrected the old “vitamin D resistant rickets” terminology, clearly unaware that the usage is both wrong and harmful. I’m just guessing, but from the footnotes in the article, it looks like, in the authors’ attempt to be comprehensive in their literature search, they unearthed a lot of older journal articles that used that terminology in the titles, and so these non-experts assumed that it was legitimate terminology, rather than something developed more than fifty years ago, based on a totally wrong view of XLH. Context matters, and these non-expert authors don’t know the context.
A lesser problem is that I worry that these case studies serve as noise that drowns out the really good information that’s available. Yes, the case studies purport to be sharing, in a single, concise article, the gist of all the other articles, but it defeats the purpose when, in fact, the clinician needs to follow all those footnote links to see if the author actually understood the referenced article. Who has time for that?
If a clinician goes to Pubmed and searches “XLH,” they’ll get an overwhelming number of results: 613 as I write this, with more added every month. Sorting the results by “best match” does a pretty good job of pushing the case studies to the bottom, but I often sort by “most recent,” and a clinician who’s aware of the rapidly evolving understanding of XLH might choose that sorting option too, to be sure of getting the most current information, and then it becomes more likely that there will be case studies in the first page or two of results.
Maybe I’m just overly sensitive about non-experts purporting to lecture others about XLH, and there is some benefit to greater awareness, but what I’ve seen of XLH case studies, most of them are doing far more harm than good, and editors and peer reviewers don’t seem to have the expertise to figure out which ones might actually be useful to the medical community without harming patients. Just one more reason why there really ought to be an affected patient/caregiver on the review panel, especially when the subject is a rare disorder.
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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