670 because their extracts are unstable and because the protein ingested is often modified by cooking. All this information was set out in 1931 in Coca, Walzer, and Thommen’s book Asthma and Hayfever in Theory and Practice IgE-mediated reactions apart, I agree that elimination diets offer the best means to detect the allergen, combined with the history. I find the Alvarez diet (lamb, rice, canned pears, sugar, salt, and water and nothing else for 3 days) to be most ’. valuable. Your editorial covers well the wide range of tissue injury that may result from food ingestion, but several conditions mentioned would not be considered "food allergy" by many
allergists. Veterans
Hospital, Buffalo, N.Y., U.S.A.
VICTOR L. COHEN
came to see us some
years
later, all of them did satisfy Thorn’s
"three considerations"’ (not "criteria" as stated by Edwards and Dent). These are excessive weight gain and/or fluid retention, with a diurnal gain in weight in general of more than 1.4 kg, exclusion of organic disease, and psychological or emotional disturbance. While on diuretics our patients were having diurnal swings’in weight, sometimes associated with large ftuctuations in carbohydrate and sodium intake. When the diuretics were stopped under controlled conditions in hospital, oedema developed in nine out of the ten patients. In the paper by Thorn,’ cited by Edwards and Dent, it is not clear whether the diurnal fluctuations in weight are while the patients are on diuretics or after diuretics have been stopped, and in particular, if they have been stopped, how long after. This is an important point which is relentlessly confusing in published
of observations made on patients with "idiopathic" oedema. For instance, Edwards and Dent’s letter adds to the confusion by stating that in their published paper2"... diuretic therapy had been discontinued for at least one month prior to investigation". But the paper itself states that "... none of the patients took diuretics or other therapy for at least a week before being studied". In any case the results presented in our paper suggest that even one month after stopping diuretics many of the observations described by Edwards and Dent would be influenced by the previous administration of these drugs. Edwards and Dent then state that the cardinal feature of "idiopathic" oedema is an excessive fall in blood volume on standing. They state that the evidence in support of this speculation is contained in two of their papers, one of which is unpublished.3 There is no evidence in the published paper2 to justify this statement, though it is true that the summary claims that, "The rate of loss of isotopically labelled 1’ albumin from the intravascular compartment was greater in patients with ’idiopathic’ oedema than in control subjects". But in the body of the paper there are no results of administering 125I-albumin to controls. The reason is revealed in the sion : "... for ethical reasons we did not give isotopically labelled albumin to our control subjects". The results that are described, show that in the patients the rate of loss of 125I-albumin was less in the upright position (5.6% per hour compared to 10. 1 % per hour when supine). This anomalous finding was attributed to "technical difficulties of blood sampling in the upright position when tilted". It is clear therefore, that this paper2 does not support the contention that 1251-albumin leaks more freely from the capillaries of patients with "idiopathic" oedema. The additional claim that there was a fall in blood volume upon standing, which was greater in the patients than in tlie controls, was based on increases of packed-cell volume of 10.3% in 11 patients and 7.9% in an unspecified number of controls. In view of the difficulties of blood-sampling which occurred in the upright posture in six of the patients, these results, though they are significant, should perhaps be interpreted with some caution. We must also point out that Edwards and Dent’s statement in their letter that there was a good correlation between 125I-albumin loss from the circulation and packed-cell volume is contrary to the results detailed in the paper. The good correlation that did occur was between the rise in packed-cell volume and the increase in concentration of
accounts
IDIOPATHIC ŒDEMA
SIR,-Dr MacGregor and his co-workers (Feb. 24, p. 397)
’idiopathic’ oedema is idiopathic" and suggested that a principal cause was diuretic abuse, abetted in some patients by self-imposed fluctuations of sodium and carbohydrate intake. There are several aspects of’this study we would like to comask if"
ment on.
The most important point is that MacGregor et al. have studied a group of patients who would not be generally accepted as idiopathic oedema. Most investigators have taken their definition from Thorn,’ who stated that the condition was one of intermittent affecting adult females without evidence of cardiac, renal, hepatic, allergic, hypoproteinwmic, obstructive veqous, or lymphatic disease, or taking drugs known to cause sodium retention. We would addthat premyxoedema should also be excluded. Furthermore, we have followed the criterion of Thorn that to be considered a case of idiopathic oedema the patient must have diurnal weight gains in excess of 1.4 kg. None of the patients studied by et al. satisfied these criteria-indeed only three presented with oedema. Their findings are important but the title of their article should have been "A study of oedema in diuretic abusers". The cardinal feature of idiopathic oedema, as defined by Thorn and confirmed by us,2.3 is the excessive fall in blood volume on standing, with compensatory renal reabsorption of salt and water. In both these studies there was good correlation between measurements of 121 I-albumin loss from the circulation and packed-cell volume is assessing changes in blood volume on tilting, and in both any diuretic therapy had been discontinued for at least one month before the investigation. In our experience, in who fit the diagnostic criteria of idiopathic oedema, as outlined above, the discontinuation of diuretic therapy does not lead to a disappearance of the symptoms and signs of the syndrome. We do not feel that maintenance diuretics are the appropriate therapy for this syndrome since they will lead to a further reduction of an already low blood volume. The ideal treatment should be directed at the cause of the excessive capillary leak, and this remains unknown. i OWEN M. EDWARDS Addenbrooke’s Hospital, RICHARD G. DENT Cambridge CB2 2QQ
having
swelling,
MacGregor
patients
discus-
1211-albumin. await Edwards and Dent’s second paper with instill maintain that intermittent oedema of unknown cause in most if not all women is due to their use of diuretics, possibly abetted on some occasions by self-imposed fluctuations in sodium and carbohydrate intake-in other words, their oedema is not idiopathic.
Whilst
***This letter has been shown to Dr MacGregor and Professor de Wardener, whose reply follows.-ED.L
SIR,-Dr Edwards and Dr Dent do not accept that our patients had "idiopathic" oedema because a careful history of the initial cause for their taking diuretics did not always reveal that it was oedema; more usually it was concern for their weight and appearance. However, by the time the patients 1. Thorn, G. W. J. Am. med. Ass. 1968, 206, 333. 2. Edwards, O. M., Bayliss, R. I. S. Q. Jl Med., 1976, 45, 125. 3. Dent, R. G., Edwards, O. M. Clin. Endocr. (in the press).
terest,
we
we
Charing Cross Hospital Medical School, Department of Medicine, London W6 8RF
G. G. A. A. MacGREGOR
MACGREGOR H. E. DE WARDENER
1. Thorn, G. W. J. Am. med. Ass. 1968, 206, 333 2. Edwards, O. M., Bayliss, R. I. S. Q.Jl Med. 1976, 45, 125. 3. Dent, R. G., Edwards, O. M. Clin. Endocr. (in the press).
allergists. Veterans
Hospital, Buffalo, N.Y., U.S.A.
VICTOR L. COHEN
came to see us some
years
later, all of them did satisfy Thorn’s
"three considerations"’ (not "criteria" as stated by Edwards and Dent). These are excessive weight gain and/or fluid retention, with a diurnal gain in weight in general of more than 1.4 kg, exclusion of organic disease, and psychological or emotional disturbance. While on diuretics our patients were having diurnal swings’in weight, sometimes associated with large ftuctuations in carbohydrate and sodium intake. When the diuretics were stopped under controlled conditions in hospital, oedema developed in nine out of the ten patients. In the paper by Thorn,’ cited by Edwards and Dent, it is not clear whether the diurnal fluctuations in weight are while the patients are on diuretics or after diuretics have been stopped, and in particular, if they have been stopped, how long after. This is an important point which is relentlessly confusing in published
of observations made on patients with "idiopathic" oedema. For instance, Edwards and Dent’s letter adds to the confusion by stating that in their published paper2"... diuretic therapy had been discontinued for at least one month prior to investigation". But the paper itself states that "... none of the patients took diuretics or other therapy for at least a week before being studied". In any case the results presented in our paper suggest that even one month after stopping diuretics many of the observations described by Edwards and Dent would be influenced by the previous administration of these drugs. Edwards and Dent then state that the cardinal feature of "idiopathic" oedema is an excessive fall in blood volume on standing. They state that the evidence in support of this speculation is contained in two of their papers, one of which is unpublished.3 There is no evidence in the published paper2 to justify this statement, though it is true that the summary claims that, "The rate of loss of isotopically labelled 1’ albumin from the intravascular compartment was greater in patients with ’idiopathic’ oedema than in control subjects". But in the body of the paper there are no results of administering 125I-albumin to controls. The reason is revealed in the sion : "... for ethical reasons we did not give isotopically labelled albumin to our control subjects". The results that are described, show that in the patients the rate of loss of 125I-albumin was less in the upright position (5.6% per hour compared to 10. 1 % per hour when supine). This anomalous finding was attributed to "technical difficulties of blood sampling in the upright position when tilted". It is clear therefore, that this paper2 does not support the contention that 1251-albumin leaks more freely from the capillaries of patients with "idiopathic" oedema. The additional claim that there was a fall in blood volume upon standing, which was greater in the patients than in tlie controls, was based on increases of packed-cell volume of 10.3% in 11 patients and 7.9% in an unspecified number of controls. In view of the difficulties of blood-sampling which occurred in the upright posture in six of the patients, these results, though they are significant, should perhaps be interpreted with some caution. We must also point out that Edwards and Dent’s statement in their letter that there was a good correlation between 125I-albumin loss from the circulation and packed-cell volume is contrary to the results detailed in the paper. The good correlation that did occur was between the rise in packed-cell volume and the increase in concentration of
accounts
IDIOPATHIC ŒDEMA
SIR,-Dr MacGregor and his co-workers (Feb. 24, p. 397)
’idiopathic’ oedema is idiopathic" and suggested that a principal cause was diuretic abuse, abetted in some patients by self-imposed fluctuations of sodium and carbohydrate intake. There are several aspects of’this study we would like to comask if"
ment on.
The most important point is that MacGregor et al. have studied a group of patients who would not be generally accepted as idiopathic oedema. Most investigators have taken their definition from Thorn,’ who stated that the condition was one of intermittent affecting adult females without evidence of cardiac, renal, hepatic, allergic, hypoproteinwmic, obstructive veqous, or lymphatic disease, or taking drugs known to cause sodium retention. We would addthat premyxoedema should also be excluded. Furthermore, we have followed the criterion of Thorn that to be considered a case of idiopathic oedema the patient must have diurnal weight gains in excess of 1.4 kg. None of the patients studied by et al. satisfied these criteria-indeed only three presented with oedema. Their findings are important but the title of their article should have been "A study of oedema in diuretic abusers". The cardinal feature of idiopathic oedema, as defined by Thorn and confirmed by us,2.3 is the excessive fall in blood volume on standing, with compensatory renal reabsorption of salt and water. In both these studies there was good correlation between measurements of 121 I-albumin loss from the circulation and packed-cell volume is assessing changes in blood volume on tilting, and in both any diuretic therapy had been discontinued for at least one month before the investigation. In our experience, in who fit the diagnostic criteria of idiopathic oedema, as outlined above, the discontinuation of diuretic therapy does not lead to a disappearance of the symptoms and signs of the syndrome. We do not feel that maintenance diuretics are the appropriate therapy for this syndrome since they will lead to a further reduction of an already low blood volume. The ideal treatment should be directed at the cause of the excessive capillary leak, and this remains unknown. i OWEN M. EDWARDS Addenbrooke’s Hospital, RICHARD G. DENT Cambridge CB2 2QQ
having
swelling,
MacGregor
patients
discus-
1211-albumin. await Edwards and Dent’s second paper with instill maintain that intermittent oedema of unknown cause in most if not all women is due to their use of diuretics, possibly abetted on some occasions by self-imposed fluctuations in sodium and carbohydrate intake-in other words, their oedema is not idiopathic.
Whilst
***This letter has been shown to Dr MacGregor and Professor de Wardener, whose reply follows.-ED.L
SIR,-Dr Edwards and Dr Dent do not accept that our patients had "idiopathic" oedema because a careful history of the initial cause for their taking diuretics did not always reveal that it was oedema; more usually it was concern for their weight and appearance. However, by the time the patients 1. Thorn, G. W. J. Am. med. Ass. 1968, 206, 333. 2. Edwards, O. M., Bayliss, R. I. S. Q. Jl Med., 1976, 45, 125. 3. Dent, R. G., Edwards, O. M. Clin. Endocr. (in the press).
terest,
we
we
Charing Cross Hospital Medical School, Department of Medicine, London W6 8RF
G. G. A. A. MacGREGOR
MACGREGOR H. E. DE WARDENER
1. Thorn, G. W. J. Am. med. Ass. 1968, 206, 333 2. Edwards, O. M., Bayliss, R. I. S. Q.Jl Med. 1976, 45, 125. 3. Dent, R. G., Edwards, O. M. Clin. Endocr. (in the press).
