“The path to CFS Patients’ Hell is paved with physician’s best intentions”. A few days ago, I was pinged by an old friend who was working with Rich Van Konynenburg, Ph.D, before his sudden death in 2012. In the subsequent years, she has suffered ‘consequences’ from some physicians who attempted to treat her.

This post looks at why CFS patients should ask for (demand) evidence based studies behind any recommendations from physicians.

Her current state:

• Low serum immunoglobulin M  (Igm) – aka  hypogammaglobulinemia (almost 8000 articles on PubMed)
  • “The spleen, where plasmablasts responsible for antibody production reside, is the major site of specific IgM production.”
• Low B cells (a lymphocyte not processed by the thymus gland, and responsible for producing antibodies.)
  • ” cells mature in the bone marrow, which is at the core of most bones.”
• And to add severe pain to the mixture — shingles that is not responding to antivirals.
  • The two items above results in patients catching infections easily (unlike the typical CFS patient who almost never get sick)

How much of this is seen with CFS?

The answer is a big yes — for those CFS patients that have had rituximab therapy. Whether this person had this therapy, or some other treatment that caused the same consequence is immaterial

• “We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study [for CFS]. ” [2016]
  • Diagnostic and therapeutic considerations in patients with hypogammaglobulinemia after rituximab therapy [2017].
    • “infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. “
  • Suppression of normal immune responses after treatment with rituximab. [2016]
    • “we recommend that all patients who undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also have immunoglobulin levels monitored periodically during treatment.”
  • “We investigated whether B cell depletion and hypogammaglobulinemia that occur during  rituximab RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, ” [2015]

CFS Literature on rituximab

• “Unless there is enough evidence for neuroinflammation, aggressive immunotherapies like rituximab should not be considered. ” [2017]
• ” The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited.” [2017]
• “Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. ” [2015] – so the improvement is temporary!
• “defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003).  Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). ” [2011]  so the improvement is temporary!
• ” Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. ” [2009]

Recovery Options

• “Intravenous immunoglobulin (IVIG) replacement therapy is the treatment of choice for most primary B-cell disorders with hypogammaglobulinemia,” [emedicine] duration is often for 1 year…
• Going back over a half century, I found the “old treatment”
  • • Hypogammaglobulinaemia, steatorrhoea and megaloblastic anaemia. Response to gluten-free diet and folic acid. [1962]
      • “Thus it seems probable that the gluten-induced enteropathy and perhaps folic acid deficiency rather than simple
        lack of vitamin B12 were the factors responsible in this instance.” Recovery duration was about 2 years.

Bottom Line

This is one example of a sad pattern that I have seen time and again. Treatment is advocated with a blinkered happy outlook (at work, we say “we’ve been popping happy (case) pills!”) ignoring the adverse cases. Often it ends up being viewed as 6 improved (statistically), 3 had no effect and 1 is worse.  How much worse is immaterial when physicians are popping optimistic pills. A marginal improvement of 6 people seems to be more important than severe long term damage to just 1 patient.

This problem is made far worse because patients are suffering from brain fog. Asking the physicians to produce the studies that they are basing their protocol on is essential. The studies should be on humans and clear. If you cannot understand the studies, feel free to forward them to me for an independent opinion.