Metal sensitisation and chronic fatigue syndrome?

I have to admit that I pondered longer than usual over whether I should talk about the paper by Vera Stejskal [1] (open-access here) and the idea that: "Patients with CFS [chronic fatigue syndrome] and fibromyalgia are frequently sensitized to metals found in the environment or used in dentistry and surgery."

It was't that I doubted that metals - certain types present in the wrong place or wrong concentration - can affect physical and psychological health and wellbeing as per the example of lead (see here). I was even happy to accept some mention of ASIA (‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’) in the Stejskal paper given my previous exploration of this potentially tricky concept with chronic fatigue syndrome in mind (see here) and some more recent data [2]. The editor-in-chief of the publishing journal, I should add, knows a little more about this than I.

It's just that when I read the paper in its entirety and then googled the analytical weapon of choice - MELISA (Memory Lymphocyte ImmunoStimulation Assay) or rather the lymphocyte transformation test (LTT) - I couldn't help but be a little unsettled at some of the results displayed. When I also found that Dr Stejskal "is the inventor of the MELISA test and holder of trademarks" (see here) without however seemingly any mention of this as a potential conflict of interest on her paper, my brow furrowed a little more.

Putting those issues to one side and hopefully avoiding any terse replies from proponents of MELISA, I am actually quite interested in the findings reported as they were in a peer-reviewed journal. A paper by Kern and colleagues [3] potentially intersecting with the Stejskal results bolstered my decision to blog about this issue and the potential to offer something important for at least some people falling onto the ME/CFS spectrum, subject to further inquiry. Oh, and by the way, when I say ME/CFS I mean SEID...

The Stejskal paper is open-access but that's never stopped me before...

• Based on a very, very small participant number - three subjects with CFS and two with fibromyalgia - where metal exposure was "as a trigger for their ill health", MELISA testing was undertaken to measure "delayed-type hypersensitivity to metals (metal allergy)".
• The assay involves culturing lymphocytes (white blood cells) with selected metals at various concentrations and then measuring lymphocyte proliferation and using something called the Stimulation Index (SI) to describe "reactivity to metals". Just in case you might be querying the method, it has been validated by others as per the paper from Valentine-Thon and colleagues [4].
• Results are presented in a case-by-case format. Control participant data (n=9) based on MELISA testing is also provided: "In the majority of controls, MELISA was negative, indicating non-responsiveness to metals at the lymphocyte level." The same could not however be said for the symptomatic participants who presented with a range of results suggestive of issues with metal allergy. Interestingly, data is presented at both initial testing and "follow-up" after removal of various metal sources and is also complemented in some cases by more traditional patch testing results.
• The author concludes: "In this study, reduction of inflammation-causing metals resulted in an alleviation of symptoms and long-term health improvement. The decrease of metal-specific lymphocyte responses in vitro after removal of sensitizing metals supports the clinical relevance of these findings."

As per other discussions on this blog, CFS/ME is a condition which has seen it's fair share of discussion and debate down the years (see here). A few weeks back, part of those discussions 'kicked off' again focused on the paper by Chalder and colleagues [5] and headlines about 'fear of exercise'. I might also draw your attention to a pretty good critique on that Chalder paper too (see here) alongside what the Cochrane Library recently said about exercise 'therapy' and CFS [6]. In this context, the Stejskal paper talking about metals potentially perpetuating symptoms and even the notion that something else - "As a child she had received at least eight thimerosal and aluminium-containing vaccines" - *might* be implicated in cases, is never going to be particularly well-received in some quarters.

I'm not falling hook, line and sinker for the Stejskal results by the way, based as they were, on case reports and with very little discussion of objective measures of symptom profiles for example, outside of sentences like: "Rapid health improvement followed and she became symptom free." I am however interested in research which talks about clinical improvement in cases of ME/CFS recognising how destructive an illness this can be and the stigma which still pervades some discussions of the condition. The Stejskal paper perhaps offers a template for the consideration of further, more controlled study is this area, expanding on our current understanding of metal allergy [7] outside of just a generalised reaction to jewellery and possibly contributing further to some of the biology potentially involved in at least some CFS/ME [8].

Music then... One by Johnny Cash. Oh and happy birthday Questioning Answers (4 today and therefore ready for reception!)

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[1] Stejskal V. Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment. Isr Med Assoc J. 2014 Dec;16(12):753-8.

[2] Somers EC. et al. Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES. Environ Health Perspect. 2015. Feb 10.

[3] Kern JK. et al. Evidence supporting a link between dental amalgams and chronic illness, fatigue, depression, anxiety, and suicide. Neuro Endocrinol Lett. 2014 Dec 24;35(7):537-552.

[4] Valentine-Thon E. et al. LTT-MELISA is clinically relevant for detecting and monitoring metal sensitivity. Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:17-24.

[5] Chalder T. et al. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. The Lancet Psychiatry. 2015. Jan 13.

[6] Larun L. et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2015 Feb 10;2:CD003200.

[7] Thyssen JP. & Menné T. Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications. Chem Res Toxicol. 2010 Feb 15;23(2):309-18.

[8] Morris G. & Maes M. Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Curr Neuropharmacol. 2014 Mar;12(2):168-85.

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Stejskal V (2014). Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment. The Israel Medical Association journal : IMAJ, 16 (12), 753-8 PMID: 25630203