Dr David L. J. Freed, MB, MD, MIBiol
This is probably the case of greatest intrigue for me. Apart from its intrinsic interest, I am the patient.
She looks pretty well to you. In fact she’s attractive; a woman in her mid-to-late childbearing years, educated, articulate and clearly intelligent, possibly overweight but otherwise completely healthy as far as you can see. Investigation of heart and kidneys – n.a.d. Menstrual/reproductive history unremarkable except for premenstrual syndrome. Yet she complains bitterly of something that you can’t even see - periodic or fluctuating fluid retention. Too much water.
Her waist band and bra feel uncomfortably tight, her ankles, face and fingers get distended with water, she feels pressure in the head and behind the eyes, she may have a constant headache. She dreads looking in the mirror in the mornings (when her fluid retention is worst) because her face looks like someone else’s, the bags under her eyes are huge and the leakage of tears from the corners of the eyes make her mascara run. The whites of her eyes balloon with fluid (it’s termed chemosis, and by the time she gets to you, later in the day, it has mostly disappeared).
The problem fluctuates from day to day and sometimes from hour to hour. It might be worse premenstrually but it might not be. She steps on the scales and is horrified to find that she has gained half-a-stone overnight. She frequently describes herself as the “Michelin Man”, although she doesn’t look it to you.
You press the ankles with a thumb - no pitting. No itch, no angioedema, no urticaria, Nothing to explain these bitter complaints. What do you do? Either you throw her out, or you prescribe a diuretic in the hope that it keeps her satisfied, and then you throw her out. If you had taken the time to question her more deeply you would also probably have elicited a history of fatigue, sleep disturbance, mood-swings, aches and pains, binge eating, panic attacks, and other nonspecific symptoms that make you want to reach for the script pad for tranx (for her) and the whisky bottle (for yourself).
Some psychiatrists have indeed claimed the syndrome for themselves on the grounds of these various psychological symptoms [1,2]. Psychiatrists of this persuasion occupy the fortunate territory of plausible hypothesis, guesswork, and descriptive epithets dressed up as “diagnoses” that cannot be confirmed by any diagnostic test. Apparently they have never tried the simple experiment of measuring and weighing the patient repeatedly over time. Fortunately we need not devote too much time to considering psychiatric attributions because there is quite a bit of hard science available that will be rather more helpful (see below).
Every now and then one of these waterlogged women notices that certain foods or smells aggravate her fluid problem, and she will persuade her doctor to refer her to an allergist. The allergist, if conventionally trained in immunology, will test her for IgE antibodies, find her negative, and inform the doctor that she does not have allergies. But there is much more that he could, and should, have said.
Intriguing Case 12
One of these ladies came my way in 1976, when I was at Manchester Royal Infirmary learning the allergy trade (my chief Geoff Taylor was abroad, or he’d have crucified me for what I did). I brought her into hospital, weighed and measured her day and night, then gave her a slice of bread to eat (one of the trigger-foods she had described). To my fascination, I saw with my own eyes that she gained eight pounds overnight, and the waist and neck circumferences both went up by half an inch. I visited her next morning, in her side-room off the main ward, while she was lying quietly in bed. After a few moments I became aware of a strange rhythmic squeaking - the bed-springs. Her heart was pounding so forcefully that it was shaking the bed. I was convinced by now of the reality of the syndrome but still baffled.
Two days later she had a spontaneous diuresis, she lost eight pounds of weight over half-a-day, and she had a miserable attack of migraine. Hourly blood tests (my chief, who was responsible for the laboratory costs, would have had apoplexy) showed steep consumption of complement for about four hours following the bread meal, but it was normal again an hour later - obviously a laboratory error (although strange that the same phenomenon occurred, at the same moment after challenge, in two other similar patients that I subsequently investigated). Overall I wasn’t able to help her very much (apart from believing her, for which she remained ever grateful) but I have now seen scores of similar patients and I feel I am groping towards some understanding.
The patient is almost always female (I’ve seen two men with it in 30 years). They look healthy, indeed bonny, which adds to their frustration because doctors and friends don’t take their complaints seriously. They may or may not be obese as well, that is the body may contain excess fat as well as water, and it seems to be that uneasy combination that gives the lumpy appearance of cellulite. Conventional medical examination discovers no abnormality other than perhaps some hyperperistalsis of the abdomen.
It is however worthwhile doing two less common examinations. Firstly, ask her to lie quietly on the examination couch, head propped up and arms by sides, looking at the ceiling and thinking peaceful calming thoughts. Sit beside the couch and after a couple of minutes look for hyperventilation - the upper chest moving with each breath instead of the abdominal wall. (Chaps: resist the temptation to gaze at her bosom, it won’t help you much. The bosom can rise and fall in acute hyperventilation but not usually in chronic. It’s the upper chest you want). Chronic hyperventilation is common in these patients and makes its own contribution to the symptoms. It is worthwhile identifying (although I think it is more a result of the illness than its cause) because it is at least partly amenable to conscious override and training, and gives you a much calmer patient to work with. McEwen offers an excellent diagnostic questionnaire with useful breathing exercises [3].
The other examination that usually yields positive results is to squeeze skinfolds gently in any painful areas, searching for rheumatic patches [4] (rheumatic patches are virtually universal in these patients). The calves often feel firm, almost woody in texture, pumped up with excess water. There is no true oedema, although the soft tissues are definitely waterlogged. The water seems to be concentrated in the connective tissues and is palpable in the superficial fascia, especially in the legs where there may be some telltale cellulite.
A certain amount of fluid retention is healthful, indeed essential for life – without it we would all evaporate to dryness. It is enhanced by oestrogen so women of child-bearing age tend to retain more water than men, and that is responsible for the lusciousness of body than men find attractive. What we are talking about here though is an exaggerated form of this normal phenomenon, and it has causes. To make a start on those we need to know four facts.
First, connective tissues are composed of carbohydrate (glycosaminoglycans), protein (collagen and elastin) and cells, together with about 80% of water [5]. Second, the glycosaminoglycans have many sulphate groups which attract clouds of cations to maintain electrical neutrality and therefore also water through osmosis (the Donnan effect [6]). Third, the foodstuffs most commonly implicated by these patients as causes of fluid retention are bread, potatoes and other starchy foods - if they keep to a low-carb diet the fluid often improves or goes away (although they get tetchy and miserable, and the aches and pains get worse initially). And fourth, these starchy foods, almost without exception, contain proteins called lectins which exert many effects on living tissues because they bind with antibody-like strength to carbohydrates, and carbohydrates are universal on all body cell surfaces and most plasma proteins [7,8]. Lectins, particularly wheat lectin, bind avidly to the connective tissue that coats and intermingles with muscles. Among the many effects of lectins on the body is inflammation, and inflammation causes swelling of the inflamed area. Lectins also bind to glycosaminoglycans and I strongly suspect that they thereby attract extra water into the tissue, though that remains unproven for the time being. Inflammation also, perhaps surprisingly, is associated with deposition of excessive fat in that organ and surrounding it [9], though fat is slower, in both coming and going, than water.
At around the same time as my original 1976 patient, Prof HE de Wardener and his team of London nephrologists were studying the same syndrome, which they termed idiopathic oedema or (because of the episodic nature of the problem) cyclical oedema. They discovered about 30 years ago that in many cases this fluid retention, or even true oedema, is aggravated in women (paradoxically) by taking diuretics – the very drugs that we use to drain excess water from the tissues [10,11].
Long-term use of diuretics causes the body to become dependent on more and more diuretics, as happens so often with any long-term medicine (habituation or tachyphylaxis). Any attempt to stop the drugs causes ferocious rebound oedema, which can be avoided only by equally ferocious sodium restriction. I remember one woman who could not pass water at all in the mornings – her bladder was simply not filling – until she took her regular diuretic. That part of de Wardener’s hypothesis is certainly true, but I don’t believe it’s the whole answer because (a) I see it often in women who don’t take diuretics, (b) people don’t take medicines for no reason, there must have been some excess fluid there first, and (c) because carbohydrate elimination usually stops the problem. Nor do I agree that oedema is a good term, because there is no pitting of the ankles. Rather it is as if the connective tissues are sucking in water like a sponge.
Another point missing from de Wardener’s hypothesis is the effect of specific allergies, which also cause fluid retention. My original 1976 patient complained not only about certain foods but also about chemical pollutants and even her husband’s semen (he was forced to use a condom, which annoyed him mightily as he had recently had a vasectomy). If simple carbohydrate restriction fails in these patients, there is always, in my experience, some allergy or intolerance that has not been spotted – usually to a foodstuff that is unsuspectingly consumed daily. I cannot remember a case in which allergy treatment with specific avoidance and desensitisation has failed to solve the problem, provided there is no kidney or heart problem (and any such condition would normally have been spotted by conventional medicine, long before the patient got to me).
My usual approach to allergic fluid retention is dual: a strict rotating stone-age diet eliminating all high-carbohydrate foods as well as dairy products and additives, plus desensitisation for (a) all foodstuffs that the patient will be permitted, and (b) a wide range of environmental allergens and toxicants. So far I have used neutralisation as the desensitisation method and I have no experience of EPD in this condition – anyone out there got views? The first half-stone of fluid is lost within the first week, during which time the patient feels awful and the aches and pains get much worse (the excess water was distending and softening the rheumatic patches and now it’s gone). After that she usually starts getting steadily better. After three months she will be 2-3 stones lighter, slimmer, and minus those awful bags under the eyes. The cellulite has quietly dissolved away. Any residual rheumatism or headache can then generally be resolved by intradermal injection of 0.7% sodium salicylate into the relevant rheumatic patches [4], which are almost invariably found overlying the trapezii and the 7th cervical spine.
I usually use this injection technique only after the dietary phase, but it can also be used as first aid, when the patient needs to look her best for an urgent appointment. Injecting the patch overlying C7 usually causes a considerable loss of fluid from the face, as the chelating effect of the salicylate removes the cations that were attracting the water. Electrical neutrality will however always eventually be re-established, so the benefit will be short-lived until the dietary approach has done its job.
A final word about diuretics. Faithful readers of my rantings will have gathered by now that I have a general prejudice against conventional medications, and this is no exception. The kidneys in this syndrome are functioning as they should, it is the connective tissues that are at fault. By exhibiting diuretics to these women we are not “flogging a dying horse” – we are flogging a healthy horse until it dies.
References
1) Pelosi AJ et al: A psychiatric study of idiopathic oedema. Lancet, 1986, ii: 999-1002
2) Pelosi AJ et al: Psychological disturbances in indiopathic oedema. Lancet 1987, I: 658.
3) McEwen LM: EPD and Allergy (2003) McEwen Laboratories, 12 Horseshoe Park, Pangbourne, RG8 7JW, section B12
4) Freed, DLJ, Chattopadhyay C, Gupta I. Intradermal salicylate injections for fibromyalgia.
J Orthopaed Med (2001), 23: 12-15.
5) Bayliss MT. Proteoglycans: structure and molecular organisation in cartilage.
In Hukins DWL (ed) Connective Tissue Matrix, (1984) pp55-88
6) Myers ER, Armstrong CG, Mow VC. Swelling pressure and collagen tension. Ibid, 161-186.
7) Freed, DLJ: Lectins in the food: their importance in health and disease. Journal of Nutritional Medicine. (1991) 2: 45-64.
8) Freed DLJ: Do dietary lectins cause disease? Br Med J (1999) 318: 1023-4
9) Pond CM. Interactions of adipose and lymphoid tissues.
In Fantuzzi G, Mazzone T (2007), Adipose Tissue and Adipokines in Health and Disease, Humana, New Jersey, pp133-150.
10) MacGregor GA, Markandu ND, Roulston JE, Jones JC, de Wardener HE. Is "idiopathic" edema idiopathic? Lancet (1979) i:397-400
11) de Wardener HE. Idiopathic edema – role of diuretic abuse. Kidney International 1981, 19: 397-400.
