- Email: [email protected]
TOPICAL STEROIDS
758
** The following letter from Sir Eric Scowen, on behalf of the Committee on Safety of Medicines, was sent to doctors in the U.K. on Oct. 6.-ED. L "The Committee on Safety of Medicines has considered the two reports on mortality among women using oral contraceptives, published in The Lancet of October 8, 1977. The first described the results of a study by the Royal College of General Practitioners (R.C.G.P.) and the second a study conducted by the Oxford Department of Social and Community Medicine in collaboration with the Family Planning Association. The numbers in the studies are too small to allow precise conclusions to be reached about the over-all risk of using oral contraceptives or any residual risk which may remain from previous use. However, the findings in both studies are in line with the trend noted in earlier investigations that the risk of arterial thrombosis with oral contraceptives increases with age-particularly in the later part of reproductive life-and that this risk is aggravated by cigarette smoking. In one study the figures show an excess mortality from subarachnoid haemorrhage both in users and in ex-users of oral contraceptives. There is no similar finding in the other study. Further studies will therefore be needed before any conclusion can be reached. During the course of these studies major changes have occurred in the composition of oral contraceptive products due to a progressive reduction in their oestrogen content. In addition, some preparations containing the progestogen, megestrol acetate, in use at the start of the investigations have been removed from the market. It is therefore impossible at present to make any reasonable assessment of the findings discussed in the two reports in relation to the oral contraceptives now currently in use. In the view of the Committee of Safety of Medicines the present studies do not indicate the necessity for any change in the warnings and precautions for oral contraceptives, except to emphasise the importance of the increased risk for women in the later age group, especially those who are cigarette smokers.""
expected superiority of a corticosteroid in
by
our
group in Cardiff confirms
eczema, and
a
trial
that, for chronic hand
no active ingredients as effective 0.025% betametha("unguentum Merck") isone valerate over a one-month period. Clearly, the use of topical corticosteroids should be critically assessed by the prescriber who should realise that he is only temporarily damping down inflammation and that simpler (and cheaper) materials may be as effective. Pharmaceutical houses are similarly addicted. It is not their fault: they produce compounds which appear effective and which are prescribed extensively. Because topical corticosteroids have to be used over long periods and because the prescribers are hooked on them, large amounts are sold (sales of plain corticosteroid preparations in 1976-77 amounted to approximately LI0 million). For these reasons the pharmaceutical industry has been slow to realise that these products are far from ideal for the patient, and we are still some way off the production of compounds that have a more fundamental action than the suppression of inflammation. eczema at
least,
a
material
containing
was as
of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN
Department
R. MARKS
SIR,-In your excellent editorial (Sept. 3, p. 487) you review the various undesirable effects of fluorinated steroids and conclude: "the hope must be that powerful anti-inflammatory agents can be developed which do not have ’fluorinated problems’ ". At the same time I read an equally authoritative article on corticosteroids in skin diseases by Dr D. D. Munro in the August issue of the Prescribers’ Journal. Munro states: "Most potent preparations are halogenated steroids, usually with one or more fluorine atoms, but neither the potency nor any complications are directly related to the fluorination, and equally potent non-halogenated compunds give rise to the same local and systemic side-effects". I am confused about these fundamentally opposite views on structure-activity relationships among the topical steróids. Elmdene Alcoholic Treatment Unit,
TOPICAL STEROIDS
SIR,-The "jungle topical steroids" is more hazardous than your editorial (Sept. 3, p. 487) suggests. Although masked infection, skin atrophy, pituitary-adrenal axis suppression, and habituation have all correctly been highlighted, other dangers exist. It is not only patients and their dermatoses who become "hooked" on steroids; doctors are also easily addicted to prescribing them. They see the rapid effects of the corticosteroids on their patient’s abnormal skin and vicariously experience the relief of symptoms. Topical corticosteroids suppress the inflammatory response of skin disease although we are not sure how.’ They do not fundamentally influence the natural history of skin disease. Consequently, relief lasts only as long as the application. The dramatic response of acutely inflamed skin to topical corticosteroids causes prescribers to forget the mild (but safe and useful) anti-inflammatory effects of simple bland creams and other preparations containing materials such as zinc and tar. How such bland preparations work is as mysterious as the mode of action of corticosteroids but some placebo preparations have an antimitotic effect for inflamed epidermis2 and others seem to have a vasoconstrictor action.3 There have been few studies contrasting the action of corticosteroids with simpler remedies. However, one such trial4 failed to show the
Bexley Hospital, Bexley, Kent DA5
2BW
SISIR K. MAJUMDAR
of
Wilson, L. C., Marks, R. in Mechanisms of Topical Corticosteroid Activity (edited by L. Wilson, and R. Marks). Edinburgh, 1976. 2. Tree, S., Marks, R. Br. J. Derm. 1975, 92, 195. 3. Woodford, R., Barry, B. W. ibid. 1973, 98, 53. 4. Medansky, R. S., Handler, R. M. Clin. Med. 1974, 81, 27. 1.
*** It is the fluorinated steroid that has mostly been misused, and it so happens it is only the fluorinated steroid that has a high inherent potency, interfering with the H.P.A. axis. Certainly, non-fluorinated steroids if used wrongly—e.g., with prolonged occlusion-have produced side-effects. For simplicity, all the difficulties were labelled "fluorinated problems", though it is not the fluorine component per se that is to blame.-ED.L. GLYCOSYLATED HÆMOGLOBIN IN DIABETES AND RENAL FAILURE your editorial (July 2, p. 22) you draw attention the increase of the glycosylated haemoglobin HbAlc in diabetes mellitus and the risk of reduced oxygen supply to the tissues. In renal failure, most patients have impaired glucose tolerance and those on chronic dialysis are usually dialysed against fluid with a high glucose content. It seems important therefore to study the level of HbA1c in patients on chronic dialysis in relation to their glucose metabolism. HbA1c was measured by the method of Trivelli et al, with minor modifications.1,2 In 18 normal subjects the HbAlc level
SIR,-In
to
1. Trivelli, L.
A., Ranney, H. M., Lai, H. T. New Engl. J. Med. 1971, 284,
353. 2.
Ranney,
H. M
Unpublished.
** The following letter from Sir Eric Scowen, on behalf of the Committee on Safety of Medicines, was sent to doctors in the U.K. on Oct. 6.-ED. L "The Committee on Safety of Medicines has considered the two reports on mortality among women using oral contraceptives, published in The Lancet of October 8, 1977. The first described the results of a study by the Royal College of General Practitioners (R.C.G.P.) and the second a study conducted by the Oxford Department of Social and Community Medicine in collaboration with the Family Planning Association. The numbers in the studies are too small to allow precise conclusions to be reached about the over-all risk of using oral contraceptives or any residual risk which may remain from previous use. However, the findings in both studies are in line with the trend noted in earlier investigations that the risk of arterial thrombosis with oral contraceptives increases with age-particularly in the later part of reproductive life-and that this risk is aggravated by cigarette smoking. In one study the figures show an excess mortality from subarachnoid haemorrhage both in users and in ex-users of oral contraceptives. There is no similar finding in the other study. Further studies will therefore be needed before any conclusion can be reached. During the course of these studies major changes have occurred in the composition of oral contraceptive products due to a progressive reduction in their oestrogen content. In addition, some preparations containing the progestogen, megestrol acetate, in use at the start of the investigations have been removed from the market. It is therefore impossible at present to make any reasonable assessment of the findings discussed in the two reports in relation to the oral contraceptives now currently in use. In the view of the Committee of Safety of Medicines the present studies do not indicate the necessity for any change in the warnings and precautions for oral contraceptives, except to emphasise the importance of the increased risk for women in the later age group, especially those who are cigarette smokers.""
expected superiority of a corticosteroid in
by
our
group in Cardiff confirms
eczema, and
a
trial
that, for chronic hand
no active ingredients as effective 0.025% betametha("unguentum Merck") isone valerate over a one-month period. Clearly, the use of topical corticosteroids should be critically assessed by the prescriber who should realise that he is only temporarily damping down inflammation and that simpler (and cheaper) materials may be as effective. Pharmaceutical houses are similarly addicted. It is not their fault: they produce compounds which appear effective and which are prescribed extensively. Because topical corticosteroids have to be used over long periods and because the prescribers are hooked on them, large amounts are sold (sales of plain corticosteroid preparations in 1976-77 amounted to approximately LI0 million). For these reasons the pharmaceutical industry has been slow to realise that these products are far from ideal for the patient, and we are still some way off the production of compounds that have a more fundamental action than the suppression of inflammation. eczema at
least,
a
material
containing
was as
of Medicine, Welsh National School of Medicine, Cardiff CF4 4XN
Department
R. MARKS
SIR,-In your excellent editorial (Sept. 3, p. 487) you review the various undesirable effects of fluorinated steroids and conclude: "the hope must be that powerful anti-inflammatory agents can be developed which do not have ’fluorinated problems’ ". At the same time I read an equally authoritative article on corticosteroids in skin diseases by Dr D. D. Munro in the August issue of the Prescribers’ Journal. Munro states: "Most potent preparations are halogenated steroids, usually with one or more fluorine atoms, but neither the potency nor any complications are directly related to the fluorination, and equally potent non-halogenated compunds give rise to the same local and systemic side-effects". I am confused about these fundamentally opposite views on structure-activity relationships among the topical steróids. Elmdene Alcoholic Treatment Unit,
TOPICAL STEROIDS
SIR,-The "jungle topical steroids" is more hazardous than your editorial (Sept. 3, p. 487) suggests. Although masked infection, skin atrophy, pituitary-adrenal axis suppression, and habituation have all correctly been highlighted, other dangers exist. It is not only patients and their dermatoses who become "hooked" on steroids; doctors are also easily addicted to prescribing them. They see the rapid effects of the corticosteroids on their patient’s abnormal skin and vicariously experience the relief of symptoms. Topical corticosteroids suppress the inflammatory response of skin disease although we are not sure how.’ They do not fundamentally influence the natural history of skin disease. Consequently, relief lasts only as long as the application. The dramatic response of acutely inflamed skin to topical corticosteroids causes prescribers to forget the mild (but safe and useful) anti-inflammatory effects of simple bland creams and other preparations containing materials such as zinc and tar. How such bland preparations work is as mysterious as the mode of action of corticosteroids but some placebo preparations have an antimitotic effect for inflamed epidermis2 and others seem to have a vasoconstrictor action.3 There have been few studies contrasting the action of corticosteroids with simpler remedies. However, one such trial4 failed to show the
Bexley Hospital, Bexley, Kent DA5
2BW
SISIR K. MAJUMDAR
of
Wilson, L. C., Marks, R. in Mechanisms of Topical Corticosteroid Activity (edited by L. Wilson, and R. Marks). Edinburgh, 1976. 2. Tree, S., Marks, R. Br. J. Derm. 1975, 92, 195. 3. Woodford, R., Barry, B. W. ibid. 1973, 98, 53. 4. Medansky, R. S., Handler, R. M. Clin. Med. 1974, 81, 27. 1.
*** It is the fluorinated steroid that has mostly been misused, and it so happens it is only the fluorinated steroid that has a high inherent potency, interfering with the H.P.A. axis. Certainly, non-fluorinated steroids if used wrongly—e.g., with prolonged occlusion-have produced side-effects. For simplicity, all the difficulties were labelled "fluorinated problems", though it is not the fluorine component per se that is to blame.-ED.L. GLYCOSYLATED HÆMOGLOBIN IN DIABETES AND RENAL FAILURE your editorial (July 2, p. 22) you draw attention the increase of the glycosylated haemoglobin HbAlc in diabetes mellitus and the risk of reduced oxygen supply to the tissues. In renal failure, most patients have impaired glucose tolerance and those on chronic dialysis are usually dialysed against fluid with a high glucose content. It seems important therefore to study the level of HbA1c in patients on chronic dialysis in relation to their glucose metabolism. HbA1c was measured by the method of Trivelli et al, with minor modifications.1,2 In 18 normal subjects the HbAlc level
SIR,-In
to
1. Trivelli, L.
A., Ranney, H. M., Lai, H. T. New Engl. J. Med. 1971, 284,
353. 2.
Ranney,
H. M
Unpublished.