Are Fluoroquinolones Causing Connective Tissue Disorders that are Leading to ME/CFS?

The symptoms of fluoroquinolone toxicity often mimic those of ME/CFS (Myalgic encephalomyelitis/chronic fatigue syndrome). Many people suffering from fluoroquinolone toxicity experience debilitating fatigue, and some are bed-bound and permanently disabled from this symptom, along with all the others that come along with fluoroquinolone toxicity. Both fluoroquinolone toxicity and ME/CFS are multi-symptom, chronic syndromes that are poorly understood and often disregarded by those in the medical community. Research into the mechanisms behind both fluoroquinolone toxicity and ME/CFS show that mitochondria (the energy centers of our cells) are likely related to both diseases, and so is autonomic nervous system dysfunction, mast cell activation, metabolomics, epigenetics, immune system dysfunction, hormonal imbalances, and other areas of human biology. Both fluoroquinolone toxicity and ME/CFS also have significant overlap with other diseases such as Ehlers-Danlos syndromes (EDS), Postural orthostatic tachycardia syndrome (POTS), and fibromyalgia.

The similarities between fluoroquinolone toxicity and ME/CFS may mean that they have a similar root mechanism…. or they may not. The root cause of fluoroquinolone toxicity is, of course, fluoroquinolones. (The mechanism behind fluoroquinolone toxicity is much more complex and the answer to the question of HOW fluoroquinolones hurt people is still being uncovered.) Most people who have ME/CFS don’t report that their symptoms started with fluoroquinolone exposure (though there is almost certainly some overlap, and there are likely some people who have been diagnosed with ME/CFS whose disease started with a fluoroquinolone prescription). There seem to be a variety of triggers that set off ME/CFS in previously healthy individuals, including, but not limited to, mold exposure and sensitivity, and exposure to a viral infection that the body never fully recovers from.

While it is possible that there are many cases of ME/CFS that were brought on by fluoroquinolones, and thus are “actually” fluoroquinolone toxicity (labels, shmables), it is also possible that both diseases/syndromes have a similar underlying mechanism despite different causes, and it is also possible that though the symptoms and features of both diseases are similar, they are actually different on a mechanistic and/or cellular level.

Though the possibilities for differences between fluoroquinolone toxicity and ME/CFS are potentially significant, the similarities are obvious, and it is likely that research that helps ME/CFS sufferers will help fluoroquinolone toxicity sufferers.

There is a theory about the mechanism behind ME/CFS that has recently come to my attention that could, potentially, tie it more directly to fluoroquinolone toxicity. The theory, in a nutshell, is this:

Some people with ME/CFS have an underlying predisposition for EDS, and thus collagen synthesis is disordered and connective tissues are weakened. The ligaments of the craniocervical junction (where your skull meets your first vertebra) become weak and this leads to craniocervical instability (CCI) and atlantoaxial instability (AAI) (together, CCI/AAI). When people suffer from CCI/AAI their neck ligaments don’t sufficiently hold up their head and their brain stems are compressed into their spines. This causes many symptoms of ME/CFS. (I’m not sure exactly how – ask someone who has done far more research into ME/CFS and/or CCI/AAI than me.)

You can read about how CCI/AAI relates to ME/CFS in these two links:

1. MEchanical Basis
2. A new diagnosis to add to the list: I have craniocervical and atlantoaxial instability

How does this relate to fluoroquinlones?

It is well known that fluoroquinolone antibiotics (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin, Floxin/ofloxacin, and a few others) damage connective tissues–including musculoskeletal connective tissues like tendons, cartilage, bone, and muscle, as well as other connective tissues such as ocular tissue (including the retina), eardrums, and cardiac/heart tissue. Multiple studies have found that fluoroquinolones are toxic and damaging to connective tissues. Given the wide differences in tissues that fluoroquinolones have been shown to deleteriously affect–from cartilage to cardiac tissue–it is reasonable to assert that they damage all connective tissues throughout the body. (Read any of the articles in the citations listed below for information about how fluoroquinolones damage connective tissues.)

Given that fluoroquinolones damage connective tissues (probably all connective tissues – see links below), it is possible that they weaken the tendons of the neck and thus lead to CCI/AAI. CCI/AAI then leads to multi-symptom chronic illness including all the symptoms of ME/CFS (which are too numerous to count).

This weakening of tendons and subsequent CCI/AAI likely occurs more often in people with underlying connective tissue disorders like EDS. I suspect (though I have no proof of this) that there are many kinds of EDS that have not yet been identified, and that more people have the genes for a variation of EDS than those who can currently be diagnosed with the disease. It’s also possible that a genetic predisposition toward EDS is not necessary for fluoroquinolones to cause extensive connective tissue damage, and that they do so in everyone who is exposed to them (at varying levels, of course). Fluoroquinolones have been shown to damage dog and rat connective tissues, especially tendons, and human connective tissues exposed to fluoroquinolones have also shown extensive damage both in-vitro and through analysis of people exposed to fluoroquinolones. I have a hard time believing that all the rats, puppies, and people whose tissues were sampled all had underlying EDS prior to their tissues being destroyed by fluoroquinolones. However, it’s possible that underlying genetic predispositions, including those for EDS, determine how severely people are affected by fluoroquinolones. More research is, of course, needed.

Are fluoroquinolones causing CCI/AAI? And is CCI/AAI leading to ME/CFS? Given the large number of studies showing that fluoroquinolones destroy connective tissues and interfere with collagen synthesis, it’s quite plausible (even likely) that they cause CCI/AAI. How, and if, CCI/AAI is connected with ME/CFS is another question. But given the experiences of the authors of MEchanical Basis and A new diagnosis to add to the list: I have craniocervical and atlantoaxial instability, it’s a possibility that is certainly worth exploring.

Sources for the assertion that fluoroquinolones cause connective tissue destruction and disordered collagen synthesis:

Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population. Hall, Mederic M. et al. PM&R , Volume 3 , Issue 2 , 132 – 142

Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral Fluoroquinolones and the Risk of Retinal Detachment. JAMA. 2012;307(13):1414-1419. doi:10.1001/jama.2012.383

Tsai WC, Hsu CC, Chen CP, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res. 2011;29(1):67-73

Lee C, Lee MG, Chen Y, Lee S, Chen Y, Chen S, Chang S. Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847. doi:10.1001/jamainternmed.2015.5389

Kaleagasioglu F, Olcay E. Fluoroquinolone-induced tendinopathy: etiology and preventive measures. Tohoku J Exp Med. 2012;226(4):251-258.

Adel Alrwisan, Patrick J. Antonelli, Almut G. Winterstein; Quinolone Ear Drops After Tympanostomy Tubes and the Risk of Eardrum Perforation: A Retrospective Cohort Study. Clin Infect Dis 2017; 64 (8): 1052-1058. doi: 10.1093/cid/cix032