British Journal of Dermatology (1975) 93, 353.
Correspondence ERYTHROCYTE GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN LICHEN PLANUS SIR, Cotton et al. (1972) studied glucose-6-phosphate dehydrogenase (G-6PD) activity in biopsies of lesions from patients with lichen planus and suggested that this skin condition might be associated with a congenital abnormality of the enzyme in the skin. It has been shown that in subjects whose erythrocytes have deficient G-6PD activity, cultured skin cells are also deficient (Gartler et al., 1962; Davidson et al., 1963). The increased incidence of lichen planus in the tropics (Shrank & Harman, 1966) coincides with the prevalence of erythrocyte G-6PD deficiency in the same geographic areas. There appear to be no publications on the incidence of lichen planus in patients with erythrocyte G-6PD deficiency or on the frequency of this enzyme abnormality among lichen planus patients. The intent of this study was to record the incidence of erythrocyte G-6PD deficiency in a group of patients with lichen planus. Haemoglobin electrophoretic pattern was simultaneously determined following the observation of Smits et al. (1969) that sickle cell crises may be more frequent in individuals with concomitant G-6PD deficiency.
TABLE I. The composition of G-6PD activity and Hb electrophoretic pattern in patients with lichen planus and in control group H b electrophoretic pattern
G-6PD activity Group Lichen planus Controls
Normal activity
Partial deficiency
Complete deficiency
24
3 5
4
21
I*
AA
AS
AC
23 24
6 6
I 0
* Female, the remaining subjects with partial or complete G-6PD deficiency were males.
Erythrocyte G-6PD activity was estimated by the semiquantitative method of Motulsky using SIGMA kit (Berger, 1971). Estimations have been performed in thirty Nigerian patients (23 males and 7 females) with lichen planus and thirty controls. Control patients were matched for age and sex and included persons suffering from scabies and acute skin pyogenic infections. All patients showed typical lesions of lichen planus and in twenty-two cases the diagnosis had been confirmed histologically. The pattern of haemoglobin was estimated electrophoretically. There was no difference in incidence of erythrocyte G-6PD deficiency and haemoglobin patterns between lichen planus and control subjects (Table i). This study demonstrates that there was no difference in the activity of erythrocyte G-6PD between a group of patients with lichen planus and a control group in an area with a frequent incidence of this enzyme deficiency. Similarly, no cases of lichen planus have been observed in a large series of G-6PD deficient patients seen in Zaria and Kaduna Hematologic Clinics (Fleming, 1975). Obviously the results only show that the activity of the enzyme is within normal limits in erythrocytes of patients with lichen planus and this does not disagree with the concept of Cotton et al. (1972) suggesting G-6PD deficiency in the skin. This is a preliminary investigation using a relatively insensitive method and a study of quantitative estimation of G-6PD in red cells of lichen planus patients is now in course. 353
354
Correspondence ACKNOWLEDGMENTS
Thanks are due to Professors A.F.Fleming and E.H.O.Parry (Ahmadu Bello University Zaria) for their advice and encouragement. The skilled technical assistance of Mr S.D.Jikeme and Mr Y.A.Ogunfunmilade is gratefully acknowledged. Department of Skin and Venereal Diseases, Ahmadu Bello University Hospital, Kaduna, Nigeria
W.K.JACYK
REFERENCES BERGER, L . (197 I) Sigma Technical Bulletin, 400. COTTON, D.W.K., VAN DEN HUKK, J.J.M.A. & VAN DER STAAK, W.B.J.M. (1972) Lichen planus: an inborn error of metabolism. British Journal of Dermatology, 87, 341. DAVIDSON, R.G., NITOWSKY, H.M. & CHILDS, B . (1963) Demonstration of two populations of cells in the human
heterozygous for glucose-6-phosphate dehydrogenase variants. Proceedings of the National Academy of Sciences of the United States of America, 50, 481. FLEMING, A.F. (1975) Personal communication. GARTLER, S.M., GANDINI, E . & CEPPELINI, R . (1962) Glucose-6-phosphate dehydrogenase deficient mutant in
human cell culture. Nature, 193, 602. HARRIS, H . (1970) The principles of human biochemical genetics. North-Holland, Amsterdam. SHRANK, A.B. & HARMAN, R.R.M. (1966) The incidence of skin diseases in a Nigerian teaching hospital dermatological clinic. British Journal of Dermatology, 78, 235. SMITS, H.L., OSKI, F.A. & BRODY, J.I. (1969) The hemolytic crisis of sickle cell disease: the role of glucose-6phosphate dehydrogenase deficiency. Journal of Pediatrics, 74, 544. A reply
SIR, the observations reported by Dr Jacyk are very interesting and concern a problem that we have been wondering about for some time. Most of the data in the literature indicate that the G-6PD in the skin is the same as that in the erythrocytes since, among other things, skin biopsies can be used to diagnose favism (Gartler et al., 1962). However, it is also known that there are various isozymes of G-6PD in the skin (Davidson et al., 1963) and the possibility remains that one or more of these isozymes may be quantitatively or even qualitatively peculiar to the skin and be coded for independently of the erythrocyte isozyme responsible for favism. We have examined a few electrophoretic patterns of G-6PD in the skin of lichen planus patients but could find no differences between these and similar extracts from the skin of normal subjects (Mier & van den Hurk, unpublished observations). But there is, of course, no a priori reason why a functional enzyme abnormality should always be reflected in a changed electrophoretic mobility. There are two specific objections to our previous work (Cotton et al., 1972) which mature reflection has made apparent. Thefirstis that we took full depth punch biopsies which, in the case of lichen planus lesions, would include the characteristic band-like infiltrate. Thus if the infiltrate cells contained an unusual G-6PD isozyme this could result in an apparent KM change. The second objection is that some of our patients had been taking oral steroids and we now find that some steroids can inhibit G-6PD. According to our calculations the quantity of steroids in the patients was too low to produce a significant inhibition but since accumulation of steroids in the skin cannot be ruled out such an effect must remain a possibility. As Dr Jacyk remarks, the test that he used was only semiquantitative and presumably measured some function of the VMAX- It is well established that many G-6PD variants have a normal VMA.\ but an altered KM (Harris, 1970). Since we reported a normal VMAX and an altered G-6PD KM we would not expect a semiquantitative test to reveal this difference.
Corresportdence
355
Nevertheless it is very interesting to see that there is no overlap between favism and lichen planus biochemically, in spite of what might be expected on the basis of theory and the geographical distribution of both diseases. Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands
D.W.K.COTTON W.B.J.M.VAN DER STAAK
Book Reviews The Structure and Function of Skin. WILLIAM MONTAGNA and edn. London: Academic Press. Pp. 433,162 figures. Price £12.95.
PAUL F.PARAKKAL
(1974) 3rd
I do not think it is too much of an exaggeration to suggest that if embryonic dermatologists were to read this and no other book during gestation, there still would be an overall improvement in the level of understanding of the skin as a functioning organ. If these dermatological fetuses were also to consult the 52 odd pages containing references and then actually read some of the references therein, I predict that at term we would have a group of very well educated dermatological neonates indeed. This book is a concise and scholarly work. It neatly summarizes present knowledge concerning the various cutaneous nuts and bolts, the way these fit together and the way that cutaneous structures work. It is extremely well illustrated and some of its figures grab the imagination and stimulate the wondering gland. For example, some of the remarkable photomicrographs of histochemical preparatipns of the innervation and blood supply to the pilosebaceous follicle excite many questions concerning the growth interrelationships between the mesodermal and ectodermal components of this very complex structure. However, although the figures promote questions the text rarely does. The information perhaps underlines too sharply what is known and not what we need to know. I suppose the requirements of brevity dictated that the authors could not devote a great deal of space to speculation on for example, the function of Langerhans cells, or on the control mechanisms for epidermopoiesis. This criticism aside, I think that it is an excellent book. It is one that should be read by all dermatologists in training as well as by all others who retain a lively interest in the nature of the organ whose diseases they treat. R.MARKS
Sunlight and Man. Normal and abnormal photobiologic responses. T.B.FITZFATRICK (Consulting Ed.), M.PATHAK, L.HABER, M.SEIJI & A.KUKITA (Eds.) (1974) Tokyo: University of Tokyo Press. Pp. 870. Price £31.80. The clinician is concerned with trying to classify forms of reaction of the skin to ultraviolet radiation (UVR) and to visible light so that common ground will exist for the discussion of what is known of these various 'photodermatoses'. At the same time, he tries to assess the importance of photoactive substances whether derived from exogenous or endogenous sources, and to understand whether immunological processes are involved or whether it is just a matter of too much substance and/or too much radiation. He wants to know how to confirm 'photosensitivity' and to define, where possible, the responsible wavelengths and what equipment he requires for this and what he needs to do to ensure its reliability. This information is necessary to allow him to diagnose, advise, and treat the patient. The experimental photobiologist is also concerned with these problems, but is at the same time involved in the study of the
Correspondence ERYTHROCYTE GLUCOSE-6-PHOSPHATE DEHYDROGENASE IN LICHEN PLANUS SIR, Cotton et al. (1972) studied glucose-6-phosphate dehydrogenase (G-6PD) activity in biopsies of lesions from patients with lichen planus and suggested that this skin condition might be associated with a congenital abnormality of the enzyme in the skin. It has been shown that in subjects whose erythrocytes have deficient G-6PD activity, cultured skin cells are also deficient (Gartler et al., 1962; Davidson et al., 1963). The increased incidence of lichen planus in the tropics (Shrank & Harman, 1966) coincides with the prevalence of erythrocyte G-6PD deficiency in the same geographic areas. There appear to be no publications on the incidence of lichen planus in patients with erythrocyte G-6PD deficiency or on the frequency of this enzyme abnormality among lichen planus patients. The intent of this study was to record the incidence of erythrocyte G-6PD deficiency in a group of patients with lichen planus. Haemoglobin electrophoretic pattern was simultaneously determined following the observation of Smits et al. (1969) that sickle cell crises may be more frequent in individuals with concomitant G-6PD deficiency.
TABLE I. The composition of G-6PD activity and Hb electrophoretic pattern in patients with lichen planus and in control group H b electrophoretic pattern
G-6PD activity Group Lichen planus Controls
Normal activity
Partial deficiency
Complete deficiency
24
3 5
4
21
I*
AA
AS
AC
23 24
6 6
I 0
* Female, the remaining subjects with partial or complete G-6PD deficiency were males.
Erythrocyte G-6PD activity was estimated by the semiquantitative method of Motulsky using SIGMA kit (Berger, 1971). Estimations have been performed in thirty Nigerian patients (23 males and 7 females) with lichen planus and thirty controls. Control patients were matched for age and sex and included persons suffering from scabies and acute skin pyogenic infections. All patients showed typical lesions of lichen planus and in twenty-two cases the diagnosis had been confirmed histologically. The pattern of haemoglobin was estimated electrophoretically. There was no difference in incidence of erythrocyte G-6PD deficiency and haemoglobin patterns between lichen planus and control subjects (Table i). This study demonstrates that there was no difference in the activity of erythrocyte G-6PD between a group of patients with lichen planus and a control group in an area with a frequent incidence of this enzyme deficiency. Similarly, no cases of lichen planus have been observed in a large series of G-6PD deficient patients seen in Zaria and Kaduna Hematologic Clinics (Fleming, 1975). Obviously the results only show that the activity of the enzyme is within normal limits in erythrocytes of patients with lichen planus and this does not disagree with the concept of Cotton et al. (1972) suggesting G-6PD deficiency in the skin. This is a preliminary investigation using a relatively insensitive method and a study of quantitative estimation of G-6PD in red cells of lichen planus patients is now in course. 353
354
Correspondence ACKNOWLEDGMENTS
Thanks are due to Professors A.F.Fleming and E.H.O.Parry (Ahmadu Bello University Zaria) for their advice and encouragement. The skilled technical assistance of Mr S.D.Jikeme and Mr Y.A.Ogunfunmilade is gratefully acknowledged. Department of Skin and Venereal Diseases, Ahmadu Bello University Hospital, Kaduna, Nigeria
W.K.JACYK
REFERENCES BERGER, L . (197 I) Sigma Technical Bulletin, 400. COTTON, D.W.K., VAN DEN HUKK, J.J.M.A. & VAN DER STAAK, W.B.J.M. (1972) Lichen planus: an inborn error of metabolism. British Journal of Dermatology, 87, 341. DAVIDSON, R.G., NITOWSKY, H.M. & CHILDS, B . (1963) Demonstration of two populations of cells in the human
heterozygous for glucose-6-phosphate dehydrogenase variants. Proceedings of the National Academy of Sciences of the United States of America, 50, 481. FLEMING, A.F. (1975) Personal communication. GARTLER, S.M., GANDINI, E . & CEPPELINI, R . (1962) Glucose-6-phosphate dehydrogenase deficient mutant in
human cell culture. Nature, 193, 602. HARRIS, H . (1970) The principles of human biochemical genetics. North-Holland, Amsterdam. SHRANK, A.B. & HARMAN, R.R.M. (1966) The incidence of skin diseases in a Nigerian teaching hospital dermatological clinic. British Journal of Dermatology, 78, 235. SMITS, H.L., OSKI, F.A. & BRODY, J.I. (1969) The hemolytic crisis of sickle cell disease: the role of glucose-6phosphate dehydrogenase deficiency. Journal of Pediatrics, 74, 544. A reply
SIR, the observations reported by Dr Jacyk are very interesting and concern a problem that we have been wondering about for some time. Most of the data in the literature indicate that the G-6PD in the skin is the same as that in the erythrocytes since, among other things, skin biopsies can be used to diagnose favism (Gartler et al., 1962). However, it is also known that there are various isozymes of G-6PD in the skin (Davidson et al., 1963) and the possibility remains that one or more of these isozymes may be quantitatively or even qualitatively peculiar to the skin and be coded for independently of the erythrocyte isozyme responsible for favism. We have examined a few electrophoretic patterns of G-6PD in the skin of lichen planus patients but could find no differences between these and similar extracts from the skin of normal subjects (Mier & van den Hurk, unpublished observations). But there is, of course, no a priori reason why a functional enzyme abnormality should always be reflected in a changed electrophoretic mobility. There are two specific objections to our previous work (Cotton et al., 1972) which mature reflection has made apparent. Thefirstis that we took full depth punch biopsies which, in the case of lichen planus lesions, would include the characteristic band-like infiltrate. Thus if the infiltrate cells contained an unusual G-6PD isozyme this could result in an apparent KM change. The second objection is that some of our patients had been taking oral steroids and we now find that some steroids can inhibit G-6PD. According to our calculations the quantity of steroids in the patients was too low to produce a significant inhibition but since accumulation of steroids in the skin cannot be ruled out such an effect must remain a possibility. As Dr Jacyk remarks, the test that he used was only semiquantitative and presumably measured some function of the VMAX- It is well established that many G-6PD variants have a normal VMA.\ but an altered KM (Harris, 1970). Since we reported a normal VMAX and an altered G-6PD KM we would not expect a semiquantitative test to reveal this difference.
Corresportdence
355
Nevertheless it is very interesting to see that there is no overlap between favism and lichen planus biochemically, in spite of what might be expected on the basis of theory and the geographical distribution of both diseases. Department of Dermatology, University of Nijmegen, Nijmegen, The Netherlands
D.W.K.COTTON W.B.J.M.VAN DER STAAK
Book Reviews The Structure and Function of Skin. WILLIAM MONTAGNA and edn. London: Academic Press. Pp. 433,162 figures. Price £12.95.
PAUL F.PARAKKAL
(1974) 3rd
I do not think it is too much of an exaggeration to suggest that if embryonic dermatologists were to read this and no other book during gestation, there still would be an overall improvement in the level of understanding of the skin as a functioning organ. If these dermatological fetuses were also to consult the 52 odd pages containing references and then actually read some of the references therein, I predict that at term we would have a group of very well educated dermatological neonates indeed. This book is a concise and scholarly work. It neatly summarizes present knowledge concerning the various cutaneous nuts and bolts, the way these fit together and the way that cutaneous structures work. It is extremely well illustrated and some of its figures grab the imagination and stimulate the wondering gland. For example, some of the remarkable photomicrographs of histochemical preparatipns of the innervation and blood supply to the pilosebaceous follicle excite many questions concerning the growth interrelationships between the mesodermal and ectodermal components of this very complex structure. However, although the figures promote questions the text rarely does. The information perhaps underlines too sharply what is known and not what we need to know. I suppose the requirements of brevity dictated that the authors could not devote a great deal of space to speculation on for example, the function of Langerhans cells, or on the control mechanisms for epidermopoiesis. This criticism aside, I think that it is an excellent book. It is one that should be read by all dermatologists in training as well as by all others who retain a lively interest in the nature of the organ whose diseases they treat. R.MARKS
Sunlight and Man. Normal and abnormal photobiologic responses. T.B.FITZFATRICK (Consulting Ed.), M.PATHAK, L.HABER, M.SEIJI & A.KUKITA (Eds.) (1974) Tokyo: University of Tokyo Press. Pp. 870. Price £31.80. The clinician is concerned with trying to classify forms of reaction of the skin to ultraviolet radiation (UVR) and to visible light so that common ground will exist for the discussion of what is known of these various 'photodermatoses'. At the same time, he tries to assess the importance of photoactive substances whether derived from exogenous or endogenous sources, and to understand whether immunological processes are involved or whether it is just a matter of too much substance and/or too much radiation. He wants to know how to confirm 'photosensitivity' and to define, where possible, the responsible wavelengths and what equipment he requires for this and what he needs to do to ensure its reliability. This information is necessary to allow him to diagnose, advise, and treat the patient. The experimental photobiologist is also concerned with these problems, but is at the same time involved in the study of the
