PHENOTHIAZINE PIGMENTATION
1
854 hydroxycorticosteroids after corticotrophin stimulation, 6 and the measurement of plasma-steroid levels.’ Robson and Kilborn 8 have described 34 patients with con- tinuous asthma who had received no treatment with corticosteroids or corticotrophin. Like earlier workers, they found that the urinary steroid metabolites were mostly in the normal range. They also found that, al- though the resting production of cortisol by these patients was normal, the production of cortisol after corticotrophin stimulation was below normal in about two-thirds of the asthmatics studied. A functional abnormality of the adrenals has been postulated on this evidence, but the problem of comparing one group of patients with " normals " is nowhere greater than in assessing adrenal function. A relation between corticosteroid production and body-size has been demonstrated.9-11 The possible influence of age and sex also needs to be taken into account in comparing such groups. Some of these difficul- ties might be resolved by relating plasma-cortisol produc- tion rates to body-weight or surface area. Even when carefully matched groups are compared, the influence of repeated stress, such as might result from asthmatic attacks, on adrenocortical reserves cannot be disregarded. PHENOTHIAZINE PIGMENTATION LAST year we discussed 12 a new side-effect attributed to chlorpromazine; and the first cases in this country have since been reported.13 Patients on long-continued high doses may get a bluish or slate-grey colour on exposed areas of skin, ’particularly the face. Sometimes ocular deposits also appear and they may impair vision. Chlor- promazine, in widest use, has been incriminated most often, but other phenothiazines can be responsible.14 The effect of the drug is cumulative and pigmentation appears gradually, especially during the summer. A dose of over 300 mg. a day for three years or more is usual, but shorter periods on higher doses may suffice. The pigmentation has been studied in the uveal tract of animals 15 and by histological techniques in the skin of patients.14 It is probable that phenothiazines accumulat- ing in the skin absorb wavelengths of light which cause an inflammatory reaction and an increase in melanin. At the same time phenothiazine is broken down and its metabolites combine with melanin to form a blue pig- ment. This product is refractory to further degradation and is disseminated throughout the reticuloendothelial system, causing a diffuse melanosis of the viscera, which has been seen post mortem.16 Endocrine or autonomic as well as local factors may be involved. Almost all reported cases were in women, many with amenorrha:a,17 suggesting a pituitary influence; -, and several phenothiazines are known to release melanin- stimulating hormone from the hypophysis in animals.18 Another contributory cause may be diminished secretion of pigment-lightening factor, melatonin, from the pineal gland, the result of an action of phenothiazines on the 6 Kass, I., Appleby, S. Amer. J. med. Sci. 1960, 240, 213. 7 Siegel, S. C., et al. J. Allergy, 1956, 27, 504. 8. Robson, A. O., Kilborn, J. R. Thorax, 1965, 20, 93. 9. DeMoor, P., et al. J. clin. Endocr. 1963, 23, 677. 10. Migeon, C. J. Metabolism, 1963, 12, 718. 11 Dunkleman, S. S. J. clin. Endocr. 1964, 24, 832. 12. Lancet, 1964, i, 1206. 13. Cairns, R. J., Capoore, H. S., Gregory, I. D. R. ibid. Jan. 30, 1965, p. 239 14. Satanove, A. J. Amer. med. Ass. 1965, 191, 263. 15. Potts, A. M. Trans. Amer. ophthal. Soc. 1962, 60, 517. 16. Greiner, A. C., Nicholson, G. A. Canad. med. Ass. J. 1964, 91, 627 17. Greiner, A. C., Berry, K. ibid. 1964, 90, 663. 18. Scott, G. T., Nading, L. K. Proc. Soc. exp. Biol., N Y 1961, 106, 88 sympathetic reflex control of the gland.16 Phenothiazine pigmentation is not reversed after treatment stops, but melanin formation has been successfully blocked by the chelating agent, D-penicillamine.19 The full significance and severity of this side-effect is still doubtful. Whilst the cosmetic blemish may be an acceptable price to pay for behavioural control in severe schizophrenia, more serious effects due to visceral involve- ment remain possible. Greiner and Nicholson fi reported sudden unexplained death in 12 physically healthy young adults taking phenothiazines, and all of them had visceral pigmentation. Tests in surviving patients with skin pigmentation have sometimes shown slight impairment of hepatic and renal function. STEPPING-STONE OR SHELTERED LIVING? SINCE the Ministry of Health in 1959 directed local authorities to provide hostels for patients who have lately left mental hospitals, there has been, with some honourable exceptions, a tardy response. Last year 20 we reviewed some of the different kinds of accommodation that had proved useful, and Dr. Peter Morgan 21 has now reported another successful enterprise at Newcastle upon Tyne. The hostel, a former commercial hotel, was opened in January, 1963, by the local authority for discharged women patients. Half came from a nearby hospital, and the other half from outpatient departments and other extramural sources. The hostel was renovated and has 25 single rooms, with ample space for rest and recreation. It is run by a resident warden, deputy warden, cook, and two maids. There are a visiting psychiatrist, psychiatric social worker, and mental-health officers. Of the 32 resi- dents discharged in the first year, 15 have returned to their own homes, 9 others have gone to lodgings, and 8 to residential work. 6 were readmitted to hospital. The average length of stay in the hostel was about six weeks, which is a good deal less than in other hostels of this kind. This may be partly determined by policy, for it was made clear in the first interview with the patient " that the hostel was a temporary and not a permanent home". The local employment situation and good social services of Newcastle may be other important reasons. The hostel at Newcastle follows the pattern of Cam- bridge 22 and Birmingham 23 hostels. Its purpose is to offer patients support until they are ready to resume inde- pendent lives in the community, and hostel placement is regarded as a phase in treatment. A different pattern is followed in the group of hostels in County Down, North- ern Ireland.z’ There the emphasis is not upon a half-way house, though patients have left the hostels to rejoin the community. The chief purpose of the scheme is to offer a permanent home for suitable long-term patients outside the mental hospital. It seems clear that both kinds of hostel are needed, and that both are an important part of the care of these patients. Dr. GUSTAV NOSSAL has been appointed director of the Walter and Eliza Hall Institute, Melbourne, in succession to Sir Macfarlane Burnet, o.M., who retires on Sept. 1. 19. Greiner, A. C., Nicholson, G. A., Baker, R. A. Canad. med Ass. J. 1964, 91, 636. 20. Lancet, 1964, ii, 398. 21. Morgan, P Mon. Bull. Minist. Hlth Lab. Serv. 1964, 23, 224 22. Clark, D. H., Cooper, L. W. Lancet, 1960, i, 588 23. Harbert, W. B., Taylor, F. J. D. ibid. 1962, ii, 1064. 24. Berrington, W. P., Green, R H. ibid. 1964, ii, 966.
Transcript of PHENOTHIAZINE PIGMENTATION
854
hydroxycorticosteroids after corticotrophin stimulation, 6and the measurement of plasma-steroid levels.’ Robsonand Kilborn 8 have described 34 patients with con-
tinuous asthma who had received no treatment withcorticosteroids or corticotrophin. Like earlier workers,they found that the urinary steroid metabolites were
mostly in the normal range. They also found that, al-though the resting production of cortisol by these patientswas normal, the production of cortisol after corticotrophinstimulation was below normal in about two-thirds ofthe asthmatics studied. A functional abnormality of theadrenals has been postulated on this evidence, but theproblem of comparing one group of patients with" normals " is nowhere greater than in assessing adrenal
. function. A relation between corticosteroid productionand body-size has been demonstrated.9-11 The possibleinfluence of age and sex also needs to be taken intoaccount in comparing such groups. Some of these difficul-ties might be resolved by relating plasma-cortisol produc-tion rates to body-weight or surface area. Even when
carefully matched groups are compared, the influence ofrepeated stress, such as might result from asthmatic attacks,on adrenocortical reserves cannot be disregarded.
PHENOTHIAZINE PIGMENTATION
LAST year we discussed 12 a new side-effect attributed to
chlorpromazine; and the first cases in this country havesince been reported.13 Patients on long-continued highdoses may get a bluish or slate-grey colour on exposedareas of skin, ’particularly the face. Sometimes ocular
deposits also appear and they may impair vision. Chlor-
promazine, in widest use, has been incriminated mostoften, but other phenothiazines can be responsible.14 Theeffect of the drug is cumulative and pigmentation appearsgradually, especially during the summer. A dose of over300 mg. a day for three years or more is usual, but shorterperiods on higher doses may suffice.The pigmentation has been studied in the uveal tract
of animals 15 and by histological techniques in the skin ofpatients.14 It is probable that phenothiazines accumulat-ing in the skin absorb wavelengths of light which causean inflammatory reaction and an increase in melanin. Atthe same time phenothiazine is broken down and itsmetabolites combine with melanin to form a blue pig-ment. This product is refractory to further degradationand is disseminated throughout the reticuloendothelial
system, causing a diffuse melanosis of the viscera, whichhas been seen post mortem.16
Endocrine or autonomic as well as local factors may beinvolved. Almost all reported cases were in women,many with amenorrha:a,17 suggesting a pituitary influence; -,and several phenothiazines are known to release melanin-stimulating hormone from the hypophysis in animals.18Another contributory cause may be diminished secretionof pigment-lightening factor, melatonin, from the pinealgland, the result of an action of phenothiazines on the6 Kass, I., Appleby, S. Amer. J. med. Sci. 1960, 240, 213.7 Siegel, S. C., et al. J. Allergy, 1956, 27, 504.8. Robson, A. O., Kilborn, J. R. Thorax, 1965, 20, 93.9. DeMoor, P., et al. J. clin. Endocr. 1963, 23, 677.
10. Migeon, C. J. Metabolism, 1963, 12, 718.11 Dunkleman, S. S. J. clin. Endocr. 1964, 24, 832.12. Lancet, 1964, i, 1206.13. Cairns, R. J., Capoore, H. S., Gregory, I. D. R. ibid. Jan. 30, 1965, p. 23914. Satanove, A. J. Amer. med. Ass. 1965, 191, 263.15. Potts, A. M. Trans. Amer. ophthal. Soc. 1962, 60, 517.16. Greiner, A. C., Nicholson, G. A. Canad. med. Ass. J. 1964, 91, 62717. Greiner, A. C., Berry, K. ibid. 1964, 90, 663.18. Scott, G. T., Nading, L. K. Proc. Soc. exp. Biol., N Y 1961, 106, 88
sympathetic reflex control of the gland.16 Phenothiazinepigmentation is not reversed after treatment stops, butmelanin formation has been successfully blocked by thechelating agent, D-penicillamine.19The full significance and severity of this side-effect is
still doubtful. Whilst the cosmetic blemish may be an
acceptable price to pay for behavioural control in severeschizophrenia, more serious effects due to visceral involve-ment remain possible. Greiner and Nicholson fi reportedsudden unexplained death in 12 physically healthy youngadults taking phenothiazines, and all of them had visceralpigmentation. Tests in surviving patients with skin
pigmentation have sometimes shown slight impairmentof hepatic and renal function.
STEPPING-STONE OR SHELTERED LIVING?
SINCE the Ministry of Health in 1959 directed localauthorities to provide hostels for patients who have latelyleft mental hospitals, there has been, with some honourableexceptions, a tardy response. Last year
20 we reviewedsome of the different kinds of accommodation that had
proved useful, and Dr. Peter Morgan 21 has now reportedanother successful enterprise at Newcastle upon Tyne.The hostel, a former commercial hotel, was opened inJanuary, 1963, by the local authority for dischargedwomen patients. Half came from a nearby hospital, andthe other half from outpatient departments and otherextramural sources. The hostel was renovated and has25 single rooms, with ample space for rest and recreation.It is run by a resident warden, deputy warden, cook, andtwo maids. There are a visiting psychiatrist, psychiatricsocial worker, and mental-health officers. Of the 32 resi-dents discharged in the first year, 15 have returned totheir own homes, 9 others have gone to lodgings, and 8to residential work. 6 were readmitted to hospital.The average length of stay in the hostel was about six
weeks, which is a good deal less than in other hostels ofthis kind. This may be partly determined by policy, forit was made clear in the first interview with the patient" that the hostel was a temporary and not a permanenthome". The local employment situation and goodsocial services of Newcastle may be other importantreasons.
The hostel at Newcastle follows the pattern of Cam-
bridge 22 and Birmingham 23 hostels. Its purpose is to
offer patients support until they are ready to resume inde-pendent lives in the community, and hostel placement isregarded as a phase in treatment. A different pattern isfollowed in the group of hostels in County Down, North-ern Ireland.z’ There the emphasis is not upon a half-wayhouse, though patients have left the hostels to rejoin thecommunity. The chief purpose of the scheme is to offera permanent home for suitable long-term patients outsidethe mental hospital. It seems clear that both kinds ofhostel are needed, and that both are an important partof the care of these patients.
Dr. GUSTAV NOSSAL has been appointed director of theWalter and Eliza Hall Institute, Melbourne, in succession toSir Macfarlane Burnet, o.M., who retires on Sept. 1.19. Greiner, A. C., Nicholson, G. A., Baker, R. A. Canad. med Ass. J. 1964,
91, 636.20. Lancet, 1964, ii, 398.21. Morgan, P Mon. Bull. Minist. Hlth Lab. Serv. 1964, 23, 22422. Clark, D. H., Cooper, L. W. Lancet, 1960, i, 58823. Harbert, W. B., Taylor, F. J. D. ibid. 1962, ii, 1064.24. Berrington, W. P., Green, R H. ibid. 1964, ii, 966.
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