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Intriguing Cases

Synergistic (Necessary but Insufficient) Causes of Arthritis

Dr David L. J. Freed, MB, MD, MIBiol

Intriguing Case 14 (part 2 of 3)

In the last instalment I outlined the phenomenon of allergic illnesses caused by combinations of allergens with other factors, when neither alone causes trouble. Now to pick up the tale of my various arthritides over the years.

Apart from the “growing pains” that my GP sagely diagnosed at the age of about 10 (leaving none of us any wiser), I never experienced arthritis until my first term at University (the first time I ever lived away from home).

One morning at the age of 18, I noticed that my first metatarso-phalangeal joint (I forget which foot) was rather painful. I assumed I must have stubbed the toe but it got steadily worse and on the third night I was in such great pain that I couldn’t sleep. No position in bed was comfortable and even the weight of the blankets on my foot was excruciating. I hobbled next morning to the Student Health Service where a nurse diagnosed gout. The blood test revealed a serum urate at the upper end of normal though the 24-hour urine showed a normal urate excretion. That attack lasted about a week and I don’t remember receiving any treatment. But once in a while over the next few years the familiar pain returned and the rheumatologist advised me to take phenylbutazone during the attack. Incredible relief! The pain magically vanished, each time within a couple of hours. When the pattern began repeating itself too often, daily allopurinol was added and that stopped the problem completely (although the urate level, curiously, never rose above the upper limit of normal). I continued taking daily prophylactic allopurinol until about age 35, when I started experimenting with dietary eliminations.

Before we go further I had better explain, for those who don’t know, that the pain of gout is about the worst pain there is. Those who have suffered labour pains and heart attacks will tell you that gout is worse than both , and I can tell you from experience that it is also worse than a compound fracture of the tibia. Gout puts a stop to you, not even bed-rest brings relief. I’m pretty stoic and can cope with most pain, but gout frightens me.

By the age of 35 I had been free of gout for a decade (thanks to allopurinol) but had instead started to get mysterious knee and back pains. I remember waking every morning finding my body stiff, yet alive with electric tingling pains. Stepping on the first stair to go up or downstairs sometimes made me yelp. I started going up and down stairs one step at a time, like a toddler. I made another appointment with the rheumatologist.

By that stage I had been in the allergy business for a few years and I had heard Len McEwen lecturing to the BSACI about the role of food intolerance in arthritis. So before embarking on a lifetime of NSAIDs, steroids and other ghastly things, I decided to try the experiment of avoiding wheat, since that seemed to be the commonest rheumatogenic food, and at the same time I eliminated peanuts as my wife informed me that I was addicted to them (an allegation that I hotly denied, thus unwittingly reinforcing the diagnosis). Within a few days I was running freely up and down stairs again (and I didn’t notice until my wife pointed out the change). I lost a stone in weight, stopped the allopurinol, and cancelled my appointment with the rheumatologist. No more arthralgia and no more gout – wonderful! And so it remained for twenty years, although the range of food eliminations, and later the neutralising jabs, had gradually to be extended to keep me pain-free.

In my fifties I started experiencing occasional backaches, and occasional arthralgias in the ankles or feet. By this time phenylbutazone had been banned so I took indomethacin instead, which was also rapidly effective. Over a few years the attacks of pain in the feet gradually became more frequent and severe until I realised, after a year or two in strenuous denial, that I was actually taking a lot more indomethacin that I liked.

Finally at the age of 54 I had another full-blown, unmistakable attack of gout, simultaneously in the left ankle and the right great toe. Before that attack had fully subsided I had another, something that had never happened before, and this dual attack grumbled on for about four months, up and down (forcing me onto crutches at one stage), until an intra-articular steroid injection put a stop to it. (My rheumatolgist told me initially that it couldn’t be gout, because gout never lasts more than a few weeks, but he changed his mind when he saw my foot doing its imitation of a hot overstuffed salami). But of course the effects of the steroid wore off in due course and the gout returned.

All this time I had of course been pondering my lifestyle and particularly diet to try to spot the triggers that I was sure must exist. For the last 20-odd years I have adhered fairly conscientiously to a rotating stone-age diet with only rare “cheats”, so after a while I was able to notice (retrospectively) a pattern. Each attack had been preceded by a precise combination of three factors, namely:

· grape wine (home-made, additive-free), preceded precisely three days beforehand by

· eating nuts (tree nuts that is, not peanuts), while at the same time

· incubating a URTI.

All three factors had to be there, and the timing was crucial: having wine and nuts on the same day or in reverse order was never followed by an attack.

If a certain symptom is preceded on three separate occasions by particular food(s), that until recently was conventionally taken as proof of causation, and was used (when I was young) for the diagnosis of gluten enteropathy (see the Bellman’s rule enunciated by 19th century mathematician Charles Dodgson [1]). Nowadays food-challenge experts insist on more challenges, intermingled with ‘placebo’ challenges [2], so I have not proved causation in my case although the Bellman’s rule gives strong reason for suspicion. The main reason I write this anecdote is to emphasise the three-day gap between two of the three triggers. We know that combinations of foods can sometimes cause symptoms when the individual foods do not (see Part 1 of this epic, last newsletter), but in my case the combination only works if the two trigger foods are ingested with that three day gap, in that order and not the reverse, and then only when I am incubating a virus at the same time.

How can that be? The hypothesis that comes to my mind, as you may have guessed, lies in some of the manifold actions of dietary lectins.

Edible seeds such as grains, legumes and nuts contain lectins which bind to the mucous membrane of the gut and in many cases are partially taken up into the circulation [3]. They are often toxic and inflammatory, and interfere with the barrier function of the gut mucosa and with the cell-membrane functions of any cell to which they become attached. Their effects are slow, and highly likely to be apparent only after a delay of some days (sometimes months later). The alcohol of wine, on the other hand, increases intestinal permeability in the short term, allowing the wine congeners and whatever else happens to be in the small bowel fast access to the circulation – but only for about an hour or so after alcohol ingestion. Clearly I have an intolerance to my home-made wine (commercial wine is even worse), but apparently this remains subclinical unless the connective tissues have been prepared in advance for damage, presumably by lectins. With the wisdom of hindsight, a three day summative effect in precisely that order – food lectins first then short-term alcohol-facilitated allergy after three days – is exactly what our laboratory knowledge would have predicted (had I had the wit to think of it). Consuming nuts and wine on the same day, or in the reverse order, achieves nothing because the lectins haven’t had time to get the target tissues prepared.

And the third factor, the viral/bacterial URTI? Several bacteria and viruses including pneumococci, some streptococci, staphylococci and influenzaviruses possess the enzyme neuraminidase which strips the terminal sialic acid molecules from cell-surface glycoconjugates, thus increasing lectin binding. This may actually be the explanation for post-streptococcal diseases [3].

Lectins and viruses have several different types of interaction, and can either cancel out or multiply each other’s effects on cells depending on dose and timing, like some nightmare quadrille [4]. It is highly likely that micro-organisms and diet-derived lectins sometimes join together in unholy partnership to prepare the luckless connective tissues (of susceptible people) for acute damage by allergens – but not every time that combination is encountered. (See next newsletter for the exciting denouément!)

References to part 2

1) Just the place for a snark! I have said it twice:
That alone should encourage the crew!
Just the place for a snark! I have said it thrice:
What I tell you three times is true!
(Lewis Carroll, The Hunting of the Snark)

2) Pearson DJ. (1987) Problems with terminology and with study design in food sensitivity. In (ed) Dobbing J. Food Intolerance, Wyeth, London, 1-23.

3) Freed DLJ (2002). Dietary lectins and disease In Food Allergy and Intolerance, 2nd edn (eds Brostoff J, Challacombe SJ) Saunders/Elsevier, London, pp 479-495.

4) Sharon N. Carbohydrate-lectin interactions in infectious disease (1996). Adv Exp Med Biol, 408: 1-8.

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