Dr David L. J. Freed, MB, MD, MIBiol
CASE STUDY published in the Journal of Nutritional & Environmental Medicine
(September 2003) 13(3), pages 185–194, Taylor & Francis Ltd
INTRODUCTION
‘PIMS’ is an acronym coined originally by McEwen [1] to describe the triad of psychological symptoms, irritable bowel and migraine, which he (as well as Birtwistle and Lunardi) recognized as occurring together so often as to constitute a syndrome. Indeed, the classic descriptions of each individual condition usually mention the other two as ‘minor’ concomitants, sometimes accompanied by dark hints as to a likely psychogenic origin [2]. Wessely et al. [3] almost agreed with McEwen in proposing a category of ‘functional somatic syndromes’, including migraine’s close cousin tension headache, together with premenstrual tension (PMT), globus syndrome, various unexplained pain syndromes and (interestingly) multiple chemical sensitivity. Most clinical ecologists would probably agree with both McEwen and Wessely insofar as these syndromes are, in the main, not different conditions, but different aspects of the same underlying process (except probably for globus, which few of us have experience of), and can all be successfully treated by the same overall strategy, albeit physical not psychological.
CASE HISTORY
A 28-year-old female nurse consulted me in November 1998 with an appalling but sadly not uncommon history. Recurrent ‘ear infections’ began in early childhood, leading to repeated courses of antibiotics throughout her teens and a tonsillectomy aged 25 years, during the course of which she suffered an anaphylactoid reaction, apparently to the anaesthetic. She had also had one diagnosed anaphylactic reaction in her teens, to an unidentified food. Migraines began at age 12 years, shortly before the menarche, sometimes being severe enough to require hospital admission.
On leaving school she trained and qualified as a nurse, in spite of repeated absences because of illness. At age 21 years she was told that she had irritable bowel syndrome. While on holiday at age 22 years she was smitten with severe loin pains and passed urinary gravel. This episode was followed by repeated ‘urinary infections’ which again triggered numerous and repeated courses of antibiotics over the next 2 years.
Aged 22 years, while training in psychiatric nursing and working with eating-disorder patients, she was herself diagnosed as suffering from an eating disorder. She had become tired of the constant abdominal bloating associated with the ‘irritable bowel’ and sharply reduced her overall food intake. This policy alleviated the abdominal problems but caused her weight to decline in step, and her periods stopped. Her doctors persuaded her to start eating again and the ‘irritable bowel syndrome’ returned as her weight went back up.
Aged 27 years she was told that she had pelvic inflammatory disease, although she was in a monogamous relationship and had never had a sexually transmitted disease. For this she was again given numerous courses of antibiotics.
By this stage she had herself noticed the relationship between eating, particularly starchy foods, and the various symptoms, and she persuaded her general practitioner to refer her to an allergist.
Her symptoms on presentation were multiple, including recurrent urticaria, alternating constipation and diarrhoea, abdominal pains and bloating, especially post-prandially, dysmenorrhoea, backache, headaches, catarrh, various psychological symptoms, fatigue, general malaise, and severe pre-menstrual syndrome with mastalgia. She certainly, therefore, satisfied McEwen’s case definition criteria for ‘PIMS’ [1]; in fact, I counted 41 separate symptoms on her questionnaire. Her bowel frequency was three to four times daily. She had been conventionally treated with appropriate medications but without benefit, and had abandoned all of her medications except for dicyclomine (Merbentyl) for the irritable bowel syndrome. Unusually, she was not using oral contraception. I recommended my standard treatment package of rotating ‘stone age’ diet (Appendix 1), together with low-dose desensitization (neutralization) sufficient to cover a restricted but adequate and healthful range of ‘safe’ foodstuffs, as well as a range of environmental substances that I judged she was likely to encounter (Appendix 2). After some months of negotiation with her Health Authority she obtained funding for this and she started treatment with the diet and seven daily neutragen injections (containing a total of 91 ingredients) in May 1999.
After a vicious withdrawal phase lasting about a week she began to feel better and by the time I saw her next, 6 weeks later for the first follow-up visit, she reckoned she was overall 75% better; on some days ‘like a new woman’. She was still experiencing problems (itchy skin) after eating fruits and had, therefore, stopped all fruits about a week previously. She was still taking dicyclomine, mainly, she confessed, because she was psychologically addicted to it—she had come to rely on it heavily over the years and did not dare to be without it.
The emergent problem with fruits, plus her nursing career, suggested a latex allergy (see Discussion), so my next step was to neutralize her also for latex. At the same time I made dilutions of dicyclomine and neutralized her for that, as neutralization has an anecdotal reputation for being helpful with addiction (the physical part of addiction) [4]. I thought that she might now be well enough to reduce the frequency of her neutragen injections to alternate days.
At the second follow-up visit in August that year (3 months after starting treatment) she reported feeling very well indeed provided she kept to the dietary regimen, with the exception of five foods which had initially been safe but had now started causing symptoms. On re-testing those five foods, three of the end-points had indeed changed and I adjusted her neutragen accordingly. At the same time I tested her for some extra foods from the ‘less safe’ range (root vegetables and legumes but not grains), in the hope that she would in due course be able to expand her diet (although the ‘stone age’ range that she already had was fully nutritious).
She was still avoiding fruits, but a few days previously she had succumbed to temptation at a party and had eaten some corn chips. Two days later she had developed an upper respiratory infection and had bronchitis. I congratulated her on confirming that my dietary advice had been based on clinical reality rather than an allergist’s whim, and advised her not to get the chest infection treated but to wait for it to pass (as it did). The only real remaining problem at this stage was PMT, which was not quite as bad as previously but still there. Overall she had lost about 1.5 stone in weight and was slim but not wasted. I directed her to a nutritional practitioner for the PMT, but when I saw her a month later she reported failure; she had been unable to tolerate the supplements and the PMT had still occurred. On this visit she was complaining of acute-onset vomiting and diarrhoea, occasioned, she suspected, by some organic chicken, but already getting better. She also reported that she had tried the experiment of reducing the neutragen injections to alternate days, but that on the days without them she felt worse, so had gone back to daily shots. I made no changes other than recommending oral nystatin (pure powder), the minimum effective dose of which I asked her to discover by experiment. She eventually settled on half a teaspoon three times a day.
Three months later (December, 7 months from the beginning of treatment) she returned. She was now very well indeed except for the PMT, which she was suffering on that day. Nutritional supplements had not been tolerated so I attempted neutralization for oestrogen and progesterone. The former gave negative results but the latter gave the appearance of neutralizing on the third dilution. Within 10 min of injecting this apparent neutralizer the PMT had gone. A daily injection of this dilution for 10 days before each period served to hold the PMT at bay until the following June when it returned.
Re-testing the hormones at this stage showed a reversal of pattern: progesterone gave negative results whereas oestrogen was showing positive. Neutralizing that was followed by instant relief and the next month she became pregnant. I advised her to stop the nystatin but to continue with the neutragen injections. She battled mightily with carbohydrate cravings throughout her pregnancy, with variable success, and felt predictably rotten for a few days after any dietary indulgence, but the following March she gave birth to a healthy boy who has remained well since. On my advice she breast-fed him exclusively for several months until he was able to indicate his interest in the foods on her plate.
She wrote to me several times while pregnant, mainly seeking reassurance. She mentioned various psychological problems including past abusive relationships, for which she had had counselling without benefit. Once the baby was born, however, she stopped worrying about all that and blossomed into motherhood.
On the last telephone contact before she moved and was lost to follow-up (June 2002) she reported being in excellent physical and emotional condition. She was far better able to cope with the diet, which she knew to be essential for the long term and to which she was reconciled. She was still ‘cheating’ from time to time and suffering consequences every time, but she was philosophical about that, as from experience she knew that she would then recover as long as she reverted straight away to a strict diet. She was still taking occasional small doses of dicyclomine, but only as a ‘psychological crutch’. The PMT returned when her periods returned, but she could no longer make the journey, with a baby in tow, for hormone re-testing. She still required regular neutragen injections, although only two to three times weekly, and somewhat to my surprise the original recipe (now over 3 years since testing) was still working for her.
DISCUSSION
This case illustrates several points, starting with the recurrent ‘infections’ of childhood. Unless there is a true immunodeficiency syndrome, recurrent respiratory or ear (and possibly urinary) inflammations are usually caused not primarily by infections but by allergy or intolerance (although secondary infection may supervene on mucous membranes already inflamed by allergy), and the allergen most frequently incriminated is cow’s milk [5, 6]. We still have a long way to go in educating the paediatric, general practice and nursing communities about what can be achieved by simple dietary manoeuvres. Almost certainly, the multiple courses of antibiotics and the tonsillectomy were all unnecessary, and the antibiotics may also have contributed to her later ill-health by disrupting the intestinal flora, by allergy to the antibiotics themselves, and possibly by other pathways. Within the last 5 years, numerous research groups world-wide have confirmed the initially surprising finding that the exhibition of antibiotics during infancy is associated with a raised risk of asthma and other atopic conditions in later life [7–12], and the link appears to be causal, as predicted decades ago by Fox [13]. This risk of provoking atopy should be added to the list of known antibiotic hazards.
With this childhood history it is almost predictable that the next ‘diagnoses’ to be given were irritable bowel syndrome and migraine. These, of course, are not true diagnoses, but descriptive epithets, telling us nothing that we did not already know, but giving the comforting illusion that the doctor is in control. Migraine and irritable bowel syndrome run alongside psychological symptoms (non-psychotic anxiety and depression as well as chronic hyperventilation) to comprise the syndrome designated by McEwen [1] as ‘PIMS’. My experience leads me, in part agreement with Wessely et al. [3], to expand the syndrome to include at least soft-tissue rheumatism and fibromyalgia, making ‘PRIMS’ (psychological symptoms, rheumatism, irritable bowel, migraine syndrome).
Again, the causal link is likely to be the numerous childhood antibiotics causing disruption to both the gut flora and the Th1/Th2 axis [7–12], plus, of course, the initial childhood allergic diathesis which started the whole cursed antibiotic cascade in the first place.
PRIMS responds well to low-dose desensitization against multiple foods and inhalants with either neutralization or enzyme-potentiated desensitization, in both cases usually coupled with appropriate dietary modification and sometimes oral antifungals [1]. I have discussed neutralization in detail elsewhere [14]. This clinical response is seen whether or not the patient initially gave a history suggestive of specific ‘reactions’. Reasoning backwards, therefore, clinical success presumably means that it was an allergy or intolerance that caused the syndrome, or at least made a material contribution to it. But conventional allergy tests of the IgE-associated variety (type I or type A) [15] are usually negative, so it is safer to attribute the condition to intolerance of unspecified mechanism rather than to an allergy in the immunological sense.
This patient was somewhat unusual in that she also had recurrent urticaria and a previous history of reliably diagnosed anaphylaxis. I thought it possible, therefore, that she had an IgE-type diathesis over and above her PRIMS. It is not my normal practice to order serum IgE estimations, as the skin testing I do for neutralization can also be relied upon to show up any weal-and-flare (type I) reactions. But few chronic urticarias are associated with type I reactions [16] and this patient displayed them to only six foods out of the 58 tested (salmon, celeriac, duck, hen’s egg, cumin and sheep feta cheese—not the traditionally allergenic foods).
As a side issue, cow’s milk cheese (cheddar) did not evoke a type I skin reaction, whereas sheep’s milk cheese did. All ungulate milks share numerous common antigens and although goat and sheep milks have a folklore reputation for healing, in practice a child allergic to cows’ milk will often also be allergic to those, or soon will become so if they are introduced as substitutes [5]. All milks are routinely banned by the stone age diet [17]. Cheese making, however, destroys and/or modifies some milk antigens, while new antigens are also acquired from the rennet and/or micro-organisms used, and cheeses can sometimes be tolerated when the parent milks are not. I therefore followed my standard practice in this case, and after the patient had become reasonably well on the strictest dietary regimen, I performed a second round of neutralization testing to cover a further range of foods that had initially been forbidden, including root crops and cheeses (but not grains, which are reserved until the end for the really successful cases).
Endometriosis, pre-menstrual syndrome, menstrual irregularities and dysmenorrhoea are common concomitants of PRIMS, and these conditions improve in step with the main symptoms once allergies/intolerances and nutrient deficiencies are dealt with [18]. The diagnostic label of ‘pelvic inflammatory disease’ is not so commonly encountered, but not unexpected against this background of general gynaecological dysfunction, while the further courses of unnecessary antibiotics will have added their own fuel to the existing fire.
I am unable to propose any coherent hypothesis to explain the clinical association between PRIMS and gynaecological problems (noted also by Wessely et al. [3]), but perhaps both are related to the disordered bowel flora, allowing abnormal micro-organisms (including yeasts such as the famous Candida albicans) to colonize the vagina and perhaps invade the other pelvic organs. On the other hand, fever is rare in these patients, so a genuine infective pathogenesis would seem less likely and antibiotics should be contraindicated. Nutritional supplementation is usually helpful for gynaecological symptoms but this woman could not tolerate any of the supplements suggested by my normally successful nutritionist. This intolerance of nutritional supplements is not uncommon in the patients I see, but fortunately she got better in spite of it, presumably because once she was no longer ‘fighting against her food’, as it were, she extracted her nutrients effectively from it. As in this case, fruits often remain problematic after other foods have been well tolerated for weeks or months. Patients often ask why this is, and I do not know how to answer. Plausible hypotheses include the fruit sugar which would encourage fermentative gut micro-organisms and/or the latex cross-reacting allergens responsible for fruit–latex syndrome [19]. Neutralizing this patient for rubber latex was indeed followed by an improvement in her fruit tolerance, although interestingly there was no type I skin reaction to latex.
Elimination dieting is commonly accompanied in the first week by a ‘withdrawal syndrome’, both physical and psychological, similar to that seen during tobacco or opiate withdrawal. The physical symptoms include worsening of the original symptoms as well as headaches and severe depression, and usually last no more than 5–10 days. It is this physical withdrawal that demonstrates the existence of food addiction, a state conventionally associated with chocolate and other caffeinated ingestants but not staples like wheat and milk. Actually, many plant compounds are potentially addictive, in particular the exorphins and many of the alkaloids of food crops [20], so the concept of food addiction need not be as revolutionary as it seems. Wheat withdrawal is every bit as severe as caffeine withdrawal. A physical withdrawal syndrome can be interpreted hopefully, as a sign that the patient is working on the right lines.
Psychological withdrawal follows the classic grief pattern, may last for months or years, and, as with tobacco, causes much recidivism. The memory of how nice that food used to be is never lost. As with tobacco, the first taste of the longed-for food after months of abstention is usually a flat anticlimax, but after two or three tastes the addiction is back in full force. This patient experienced both types of withdrawal and her pattern of repeated backsliding for the first year or two is unfortunately common. Eventually she learned how to handle it, but some of her experiences are illuminating.
Succumbing to temptation at a party is, of course, classic for all addicts and in our patient the addictant was maize, in the form of corn chips. This was followed a couple of days later by acute bronchitis, not perhaps what one would have expected as an allergy symptom. Maize, in common with all grains, contains a group of natural toxins called lectins, which are carbohydrate-binding proteins present in many food crops. Many are resistant to cooking and digestion and can pass through the gut wall unchanged, attaching themselves to the glycoconjugates present on most cell surfaces. They have numerous biological actions, the most relevant in this context being their propensity to strip away the mucus from mucous membranes, allowing micro-organisms to attach to the membrane, when they would otherwise have been trapped and carried away by the mucus [21, 22]. Lectins are frequently allergenic as well as toxic, so their effects can be compounded by IgE symptoms. Patients on stone age diets, which automatically exclude most dietary lectins as these are mainly found in carbohydrate-rich foods, have been anecdotally noted to suffer far fewer respiratory tract infections than normal healthy people [23].
Food poisoning after organic chicken is not that unusual, because many patients equate organic with healthful, forgetting that Salmonella, Campylobacter, etc. are also ‘organic’.
Organic chicken needs just as much care in cooking as any other chicken, and organic vegetables actually need greater care in preparation than their regular supermarket equivalents. This is because, without the use of pesticides, there is a greater likelihood of pests, and the patient is desensitized for cabbage, not caterpillar!
The use of nystatin is based on the empirical observations of Truss, Crook and others that polysymptomatic food-intolerant patients often show good clinical response to the exhibition of oral antifungals and low sugar diet [24]. From this observation grew the ‘candida hypothesis’ which proposes that the normal intestinal commensal Candida albicans, if it multiplies beyond a certain level, enters a mycelial phase of growth in which hyphae penetrate the intestinal wall making it ‘leaky’ to undigested dietary toxins.
Although this hypothesis as presented in popular paperbacks is simplistic and not altogether accurate, the existence of the clinical phenomenon of response to antifungals is not in doubt [24]. I am most accustomed to using simple nystatin BP, and as in this case I usually neutralize polysymptomatic patients for nystatin in the first round of testing, in case I decide to prescribe it later on.
Neutralization for progesterone and oestrogen has an anecdotal reputation among neutralizers for success in PMT. Twenty years ago, when I first heard this described, it was attributed to the patient being ‘allergic to her own progesterone’. I still find that concept difficult to understand and I am not aware of any clinical trials, but again, in practice, my experience has been favourable. Steroids are not water soluble but I simply make up a suspension in aqueous medium and dilute from that; after a couple of dilutions the liquid turns clear. Perhaps traces do in fact dissolve and one is simply replenishing a deficient hormone. On the other hand, my experience with this woman, of PMT symptoms resolving within minutes once the apparent ‘neutralizer’ is reached, has been seen repeatedly [25], and that does suggest true neutralization rather than hormone replenishment. Neutralizing dilutions (end-points) do change with the passage of time, as with this woman’s hormones, but even so her main treatment (neutragens for foods and inhalants) still remains effective years later, as is often the case.
Although most allergists who use neutralization recommend patients to tail off treatment after a few months, in the expectation of having achieved full desensitization, not all patients achieve this and have to continue with neutralization (as this patient did) long term.
Since the thalidomide disaster of the 1960s, doctors are terrified of giving any medicine to pregnant women, so there is little information available on neutralization in pregnancy. There is, however, quite a lot of experience from the earlier decades of the twentieth century of classic hyposensitization in pregnancy, and the overall conclusion is that this is not dangerous and may indeed improve the health of both mother and baby [26, 27].
Because neutralization is far safer than classic hyposensitization in all other respects, it should be safe in pregnancy also, and I have therefore (albeit with some trepidation) sanctioned continuation of neutralization into pregnancy for several of my female patients (including both of my own daughters when pregnant) and so far have not encountered problems. I doubt whether a controlled trial of neutralization in pregnancy could ever be ethically done, so this is a question that will never be answered by science. Clinical experience—the oldest clinical science of all—will have to suffice.
The same remark applies to my recommendations on weaning the babies of allergic women. Normal healthy human breast milk contains trace amounts of all the mother’s ingestants, usually accompanied by secretory IgA antibodies against them. In principle, this seems to be nature’s way of gently introducing the baby to the antigenic foods which it will have to encounter in a few months’ time. My advice to all nursing allergic women is to wean first on to those foods and drinks that the mother herself has been consuming throughout lactation, unless there is reason to suspect specific reactions [28]. Lastly, what can we say about the venerable mind–body debate with which we began?
This case illustrates the frequent tendency of PRIMS patients to dwell on their past histories of abusive relationships or abusive parents, although this patient did not claim to have been sexually abused as PRIMS patients quite often do. A history of childhood sexual abuse is unexpectedly common in PRIMS patients [29], and the association has been interpreted as indicating causation in both directions. The more conventional suggestion is that the physical symptoms represent somatization, whereas I have suggested that exposure of a young girl’s immature genital tract to semen might lead to masked semen allergy in later life, thus explaining the female preponderance (although I concede that this suggestion is not relevant here).
The mind–body debate has been rumbling around the allergy world for many years and is impossible to resolve except by successful treatment. This young lady (in common with most PRIMS patients in my experience) got better using diet and desensitization, even though her psychological stresses were no further towards resolution. They just ceased to matter once she was better. There is no doubt in my mind, after over 30 years of listening to allergy patients, that the symptoms can be aggravated by psychological stresses, but I have yet to see convincing evidence that they have ever been caused by them. Amateur psychoanalysts are free to speculate, as psychological causes are by their nature incapable of being either disproved or proved; we allergists, on the other hand, are one of the few groups of doctors who can actually prove causation [30].
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APPENDIX 1
Four-Day Rotation Diet (‘Stone Age’) © David Freed & Margaret Moss, 2003
Day 1 |
Day 2 |
Day 3 |
Day 4 |
|
SAFE FOODS |
chicken |
guinea fowl |
turkey |
beef/veal |
FUN FOODS |
lemon |
butternut |
red/green/yellow capsicum pepperaubergine (eggplant)tomato, pineapplepersimmon (Sharon)passion fruit, rhubarbchilli pepperpaprika, cayennesavory, rosemarythyme, sageoregano, marjoramspearmintsesame, sesame oilpeppermint teachamomile teadandelion coffee/tea |
fresh figguavakiwihopsbay leafclovechestnutcoffeelemon verbena teacinnamon |
DANGEROUS |
goat milk |
sheep milk |
organic ham |
cows’ milk |
NB Spring or filtered water, sea salt and pepper are permitted on all days.
APPENDIX 2
Specific Neutragen for the Present Case Study
Bottle 1.
Chicken, pork, parsley, fennel, lemon, pineapple, tea, peppercorn mix, lamb,
prawn, spinach, cucumber, courgette, pear, melon, squid, rosehip tea, haddock, salmon,
trout, sardine, plaice, mackerel, tuna, sharon fruit.
Bottle 2.
Sunflower oil, lettuce, tomato, asparagus, chive, cress, capsicum, olive oil,
peppermint tea, beef, cauliflower, broccoli, Brussels sprouts, watercress, kiwi, coffee,
maize*, celeriac, mushroom, duck, mussel, crab, egg, chilli, ginger.
Bottle 3.
Alternaria, Chlorella, Cladosporium, Penicillium, Aspergillus, Candida albicans,
flock, sheep wool, birch pollen**, Dermatophagoides pteronyssinus, leaf mould, influenza
vaccine, dog, crushed grasses, histamine, ethanol, formaldehyde, human semen, gas, diesel
exhaust fumes, swimming pool water mix***, mixed colour print, sodium salicylate,
nystatin, perfume mix.
Bottle 4.
Phenol.
Bottle 5.
Glycerol.
Bottle 6.
Turkey, celery, venison, halibut, cod.
Bottle 7.
Cabbage, burnt gas fumes, cigarette smoke, cumin, St John’s wort, sheep feta,
Martell brandy, cane sugar, brewer’s yeast.
Bottle 8
(added after patient had improved, as noted in text): latex, parsnip, pea, cheddar,
grape, beet sugar, swede, sweet potato, beetroot, dicyclomine.
*Maize is banned from the diet but included in the neutragen in the hope of making
toothpaste, licking stamps, etc. (often hidden sources of maize products) safer.
**Birch pollen is added, although rare as an aeroallergen in the UK, because it cross-reacts
with several vegetable foods, in the hope of making those safer.
***Waters are freeze-dried then the sediments resuspended and diluted in phenol/saline
diluent.