While rituximab is often seen as a “wonder drug” for IgG4-RD patients, Dr. Michael Bamber, who lives with IgG4-RD, shared a sobering story about his recent episode of sepsis. He was left to wonder, “Could rituximab somehow have played a role?”
Dr. Michael Bamber, a member of the IgG4ward! Foundation Advisory Board, provides the QOW this week. The Foundation is grateful to him and his wife, Dr. Linda Bamber – also an Advisory Board member – for sharing his story and allowing us to reflect on its lessons.
MB:
“Many of us on rituximab think of it as something of a wonder drug. It appears to control IgG4-RD in most cases, often with few apparent side-effects – at least not immediate ones. As the pandemic showed, however, there can be serious consequences to immune suppression, and B cell depletion is a form of immunosuppression. I had an experience recently that taught me another lesson about rituximab – one that is worth discussing with the IgG4-RD Community.
I developed severe sepsis – a condition in which bacteria enter the bloodstream and cause a potentially life-threatening situation. The sepsis happened seemingly “out of the blue” – a couple of weeks after I had undergone a prostate biopsy. I went from feeling perfectly well at home to a fever of 104 degrees in the Emergency Room in a time interval that seemed like a blur. The organism isolated from my blood – E. coli – suggested that the prostate biopsy likely set me up for the sepsis.
Fortunately, I was diagnosed promptly and started treatment with antibiotics and fluids within an hour and a half of my first symptoms. Ultimately, I walked out of the hospital after five days – a tribute to prompt diagnosis and the swift institution of antibiotics and fluids. Though the biopsy may have triggered the entire episode, I have to wonder: did my rituximab treatment somehow play a role in this?”
IgG4ward!:
Thank you, Michael, for sharing your story and letting us discuss this event. The short answer to your question – “Could rituximab somehow play a role in this?” – is YES. Rituximab treatment may well have contributed to what happened and although sepsis is not a common complication of B cell depletion, it is difficult to say that it was not partly responsible for your experience.
The human immune system is a complex and redundant “shield,” designed to protect us from the world of microorganisms – bacterial, viral, fungal, etc. – that surround us. Microorganisms fill not only our environments but also reside on and in us: on our skin, in our respiratory system, and in our gastrointestinal tracts. To protect us against these organisms, our immune systems consist of many cell types and an impressive array of proteins and signaling molecules that work in harmony to prevent infection – the breach of these normal protective mechanisms. Most of the time, the immune system does an astonishingly good job: 24 hours a day, 7 days a week, without disruption.
In order to treat an immune-mediated disease such as IgG4-RD, a condition in which part of the immune system has gone awry and begun attacking the patient’s own body, we must slow down parts of the immune system through treatment. The purpose of such treatment is to control inflammation to prevent organ damage and other injuries that may even lead to death in the absence of appropriate intervention. In doing so, however, we remove or partially disable a portion of the protective mesh that is the immune system, inevitably weakening it at some spot(s).
Our current therapies, including B cell depletion, permit us to alter the immune system in ways that are much more targeted than ever before. This targeting results in treatment strategies that – in general – are substantially safer than the shotgun approaches of previous eras that led almost inevitably to the risk of substantial collateral damage. When one pauses to think about what we do with B cell depletion – removing all circulating B cells from the blood for many months – it is remarkable that we are usually able to do this with relatively few side-effects compared to older therapies. The older therapies are both less effective in most cases and substantially more dangerous overall.
Even so, no lunch is entirely free all the time. Sometimes, by removing a portion of the immune system’s redundancy, we weaken areas of defense. These become vulnerabilities that microorganisms can breach, leading to infections. It is frequently the case that two or more “hits” are required to permit an infection to develop and cause big problems. In Michael’s case, a reasonable explanation is that the wound resulting from the prostate biopsy created a foothold for the organism, which was then able to flourish in an environment of depleted B cells. This does not happen in all patients who undergo such procedures, but in Michael’s case it did. Only the alert recognition of a potential problem by Linda, a fast ambulance, and timely Emergency Room care prevented an outcome that could have been much worse.
The biggest lesson here is that people living with IgG4-RD (and their caregivers) must be vigilant to the possibility of swift changes in their health status and ask questions quickly. A fever or other abrupt change in condition should not wait until morning without some discussion of whether or not something worrisome might be afoot.
Michael and Linda, as strong supporters and advocates of the IgG4ward! Foundation’s mission, understand that major goals of research in IgG4-RD now include the development of safer and more effective diagnostic and treatment strategies than we have today. We move steadily toward those goals. Until we “get there”, Michael has the final word:
“A serious drug like rituximab comes with potential risks.”
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