After asking you to do all the work for a couple weeks (answering my questions), I’m back to my usual pontificating. This week it’s a collection of interesting journal articles.
The first is a somewhat unusual case report about chronic hypophosphatemia caused by an iron infusion. Hypophosphatemia is always a risk with these infusions, but it’s acute (meaning sudden and temporary), not chronic. For a few patients, however, the hypophosphatemia becomes chronic and can last for years. The title pretty much says it all: “An Unusually Prolonged Case of FGF23-mediated Hypophosphatemia Secondary to Ferric Carboxymaltose Use.” What’s interesting is that apparently in these patients, once the body is triggered by the iron infusion to over-produce FGF23, it keeps doing it, long after the infusion stops. And, as far as I can tell, no one knows why. It seems likely that if we knew more about what triggers FGF23 (the exact pathway, not just “something in the PHEX gene”), we might be able to develop a treatment that gets even closer to the source of the problem than we currently have with burosumab. And that treatment might also help the infusion-caused chronic hypophosphatemia patients, who currently don’t have a definitive treatment regimen when the symptoms last more than a few weeks.
The beginning of the abstract for “Switching to burosumab from conventional therapy in siblings with relatively well-controlled X-linked hypophosphatemia” made me cringe a little (suggesting that only children with severe symptoms should receive burosumab), but the authors go on to talk about the benefits of burosumab beyond what’s accomplished by the old (terrible) phos/calcitriol treatment. They talk about two siblings who’d had “effective treatment” with the phos/calcitriol (not exactly sure what “effective” means here), but were switched to burosumab, and (no surprise) “Both patients showed further improvement in radiographic and laboratory findings ….” I also like the conclusion about the importance of “monitoring not only rickets and calcium/phosphate metabolism but all symptoms of XLH after initiating burosumab.” The other symptom they’re talking about is pain, and too often the value of an expensive treatment is measured only in its effects on visible/measurable symptoms, excluding the very real but intangible symptoms of pain and fatigue.
Another interesting observation by these authors is somewhat buried in the abstract (and that’s all I have access to). One of the patients reported pain the back of the knees after switching to burosumab, which went away when the phosphorus levels normalized. I experienced a brief period of increased pain (in my spine) on starting burosumab, and I’ve heard about assorted locations of increased pain from others, but I haven’t seen it discussed much in literature. It’s important to prepare patients for the possibility that what’s often considered a life-changing treatment (I do believe that myself) may not be immediately life-changing, and may even feel like a step backwards initially, but most patients find that it’s worth that temporary setback. Otherwise, an unprepared patient may think it’s a permanent setback and stop the treatment that would, in time, offer benefits that vastly outweigh the initial challenges.
“Rare Causes of Musculoskeletal Pain: Thinking beyond Common Rheumatologic Diseases” is a small but necessary advance in educating the clinicians who may see XLH patients. Most continuing education is addressed to endocrinologists who already know their patients have XLH but may not have treated an XLHer before. The truly massive challenge is in educating the non-endocrinologists who might see a misdiagnosed XLHer, and that’s what this article is trying to do for rheumatologists. The article also confirms (anecdotally) something I’ve observed, that significant numbers of XLHers are misdiagnosed with ankylosing spondylitis. In this case report, three brothers had that misdiagnosis, when all three actually had XLH. The article also provides some concrete ways in which the two conditions (along with DISH — Diffuse Idiopathic Skeletal Hyperostosis) can be differentiated. There’s even a test I’d never heard of, called HLA-B27, which, if positive, means the patient is at risk of developing an autoimmune disorder (which Ankylosing Spondylitis is, and XLH is not). A negative result is not definitive, but it’s a pretty good indication that the patient does not have Ankylosing Spondylitis or DISH, and a better diagnosis should be sought. The article doesn’t say it outright, but the misdiagnosis didn’t matter so much before burosumab, because there really wasn’t much that could be offered to treat any of the three conditions. It’s different now, since XLH, unlike the other two diagnoses, does have an effective treatment, so misdiagnosis isn’t just an annoyance, but a potential tragedy.
That’s a lot to absorb, so I’ll stop here.
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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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