Welcome Back Rheumatology Fans,
Another week, another podcast, another new subject to learn all about and this time it is SUPER relevant to us as Physiotherapists and MSK Therapists seeing patients with Lupus.
You can listen to the podcast here, it is 12 mins long but I struggled a little with the accents of the guests, there is a full transcript to download (which I did) which solved that very minor issue. Be aware, it is heavily medical, I had to look up quite a few terms!
I have sorted some takeaways below which you all seem to be finding useful!
For tons of info on Lupus and Connective Tissue Disorders (as well as all the other Rheum disorder) enroll in my online course. Just FYI changes are coming to this in 2026 but currently if you enroll you get lifetime access so do it NOW.
Preload deficiency may explain fatigue and exercise intolerance in SLE - even when disease is controlled
Clinicians at Johns Hopkins observed a subset of SLE patients whose lupus was well controlled yet who continued to report profound fatigue, dyspnea, heat intolerance, and markedly reduced exercise capacity. These symptoms were not due to active inflammation, cardiac structural abnormalities, or pulmonary disease. Careful haemodynamic testing - including exercise right-heart catheterisation - revealed that these patients failed to generate adequate preload during exertion, limiting cardiac output. This is “functional dehydration” phenomenon and reframes persistent fatigue in SLE.
Exercise intolerance in these patients is posture-dependent and quantifiable
Patients described a distinctive pattern: they tolerated exercise better lying flat than standing, and they exhibited elevated baseline heart rates. Cardiopulmonary exercise testing (CPET) confirmed objectively reduced exercise capacity despite structurally normal hearts on CT, echocardiography with strain imaging, and MRI. This demonstrates that the limitation is physiologic rather than subjective, separating preload deficiency from nonspecific fatigue. Recognising this pattern - orthostatic worsening, normal imaging, elevated resting HR - can guide clinicians toward targeted evaluation rather than attributing symptoms to deconditioning or psychological causes.
Undetectable NT-proBNP levels help rule out other causes and support the diagnosis
Across the cohort, NT-proBNP levels were low or undetectable. While not diagnostic of preload deficiency by itself, an undetectable NT-proBNP carries a ~99% negative predictive value for structural heart disease associated with heart failure. This biomarker therefore helps eliminate common cardiac explanations for exercise intolerance. In the appropriate clinical context - controlled SLE, normal structural imaging, reduced exercise tolerance - very low BNP levels increase confidence that the issue is inadequate cardiac filling rather than pressure overload.
Treatment focuses on restoring functional blood volume and controlling heart rate
Many patients demonstrated “functional dehydration,” meaning that despite drinking normally, they could not retain enough intravascular volume to support preload during exertion. Treatment therefore parallels POTS (postural orthostatic tachycardia syndrome) management: high fluid intake (1–3 gallons/day) and increased sodium consumption (up to 5 g/day). Some patients benefited from electrolyte solutions like Gatorade or Liquid IV to maintain volume.
DO NOT DO THIS WITHOUT MEDICAL SUPPORT
The pathophysiology remains unknown
Though preload deficiency has now been documented, its underlying mechanism is unclear. Dysautonomia was suspected, but formal autonomic testing did not reach diagnostic thresholds.
The next steps include determining prevalence, defining risk factors, and pursuing mechanistic studies to identify the affected biological pathways.
Further Resources
