1217
Category 1 included wounds without clinical evidence of inflammation; category 2 those with visible swelling in the skin and subcutaneous tissues; category 3 those with swelling and and category 4 those with pus visible to the naked eye. A PDP-11computer system was used to analyse the data.
erythema;
RESULTS
478 wounds were sutured with P.G.A. and 522 with silk. The comparative assessment of wounds is summarised in table I, including all four categories. Wounds sutured with P.G.A. showed a significantly lower incidence of inflammatory reaction (categories 2-4), particularly noticeable in category 4 (infection with pus), the most readily assessed grade. Both comparisons give a value of X2 which is highly significant (PO-01). Regional variations.-The proportion of wounds in
compared with 19p for a corresponding silk suture of 45 cm length. Moreover, children are saved the psychological trauma of suture removal.
We are grateful to the nursing staff of the accident service of the Luton and Dunstable Hospital for their cooperation in this trial.
Requests for reprints should be addressed to M.S.B. REFERENCES 1. Anscombe, A. R., Hira, N., Hunt, B. Br. J. Surg 1970, 57, 2. Echeverria, E., Jimenez, J. Surgery Gynec. Obstet. 1970, 131, 3. Solhaug, J. H., Heimann, P. Acta chir. scand. 1975, 141, 326. 4. Mouzas, G. L., Pompa, P. Br. J. Surg. 1974, 61, 313. 5. Postlethwait, R. W. Archs Surg. 1970, 101, 489. 6. Olerud, S. Lancet, 1970, i, 1060. 7. Clough, V., Alexander-Williams, J. ibid. 1975, i, 194.
which
an inflammatory reaction developed (categories 2-4) varied considerably with the site of the wound (table II). P.G.A. gave better results in all sites, particularly in wounds of the hand. When category 4 alone was considered, P.G.A. was again found to give better results in all sites, particularly in the lower limb and hand. In the lower limb, none of the 46 wounds sutured with
showed pus; whereas 9 put of 71 sutured with silk did so. The corresponding figures for the hand were 4 out of 149 (P.G.A.) and 13 out of 191 (silk). Where the incidence of suppuration was highest, the superiority of P.G.A. was most clearly shown. Sex differences.-In each sex 21% of wounds were adjudged unsatisfactory (categories 2-4), but the difference between P.G.A. and silk was greater for women than men (table III). Women had a higher incidence of suppuration, particularly where silk was used. This may well be associated with a greater number of lower-limb wounds in women, a region with a high infection-rate (table II). Age differences.-Comparison of silk and P.G.A. for different age-groups showed consistently lower figures for P.G.A., especially for suppuration. This feature was P.G.A.
pronounced in the 41-60 age-group, a group with large proportion of limb and hand wounds where the risk of suppuration is particularly high (table II). most a
DISCUSSION
The most important conclusion is that P.G.A. is superior to silk as a suture material in the treatment of wounds in an accident service. A number of experimental,6 have shown that the inflammatory response of tissues to P.G.A. is less than that to silk or catgut. In clinical practice one would thus expect a lower wound infection-rate with P.G.A. than with silk; our results support this. Of the criteria used (categories 1-4) for assessment the presence of pus in the wound is obviously the most incontrovertible, and here the statistical significance of the results is high. The superiority of P.G.A. is particularly notable in wounds of the hand, which accounted for 34% of all wounds with a suppuration rate of 5%. The rate of wound healing was not assessed; but total wound dehiscence in the absence of infection was recorded and found to be commoner in the silk group. A further advantage of P.G.A. is that removal of the suture is not required. The saving of time for general practitioners,’ community nurses, and patients themselves is substantial. There is no significant difference in cost. A metric 2 P.G.A. suture of 75 cm length cost 35p,
-
917. 1.
Occupational Health OCCUPATIONAL VITILIGO INDUCED BY p-tert-BUTYLPHENOL, A SYSTEMIC DISEASE? OLIVER
JAMES Department of Medicine (Geriatrics), University of Newcastle upon Tyne
R. W. MAYES I.C.I. Agricultural Division, Billingham
C.
J. STEVENSON
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon
Summary
Tyne NE1 4LP
Vitiligo, morphologically indistinguishable from true vitiligo, was detected in men exposed to p-tert-butylphenol (P.T.B.P.)
54 of 198 during its manufacture. There is evidence that P.T.B.P. caused vitiligo by a systemic mechanism and that the severity of the disease was related to the intensity of exposure. No association with autoimmune disease was found. Screening for other possible associated disorders revealed mildly abnormal liver-function tests in 6 workers: liver biopsy confirmed liver damage. Of the 144 men exposed to P.T.B.P. who did not have vitiligo, only 2 had any abnormal liver-function test. It seems possible that the liver damage is related to P.T.B.P. INTRODUCTION
THE main use of p-tert-butylphenol (P.T.B.P.) is the production of resins for adhesives used in the car industry. It is a white crystalline solid which melts at 97-98 °C to a clear, colourless liquid, and vaporises at 260 °C. It is produced by reacting isobutene with phenol in the presence of a catalyst; the crude P.T.B.P. is purified by distillation, allowed to cool, pastillated and packed into bags. This process began in 1958 in the factory where our investigation was conducted. Workers were exposed to the vapour in the distillation stage and to dust in the pastillating and packing sheds where the background dust level was 10 parts per million (p.p.m.) with occasional peaks of 100 p.p.m. P.T.B.P. is absorbed readily through the skin and also from P.T.B.P. by inhalation. Occupational vitiligo was first reviewed by
Malten
et
al.’ in 1971 who drew attention
to cases
in
1218 TABLE III-DEGREE OF EXPOSURE TO P.T.B.P.
Russiaand Japan.3 In the car industry, Calnan and Cooke4 found that vitiligo usually developed at sites in contact men
with
working
P.T.B.P.-containing adhesive, in confined spaces had
more
but that
widespread
involvement. In 1975 we started a thorough survey of vitiligo and possible associated systemic disorders in workers at a
factory manufacturing P.T.B.P. SURVEY METHODS
In 1974 the number of men who had reported depigmentation had reached double figures. Production of P.T.B.P. was stopped and the full extent of the problem was assessed by screening the whole workforce exposed to P.T.B.P., and also men who had previously been exposed but had moved to other sites. The screening programme was designed to identify the extent of depigmentation, to relate this to the degree of exposure, and to investigate possible systemic effects with particular reference to liver and thyroid disturbance and autoimmune disease. The programme comprised: (1) a questionnaire to establish length and severity of occupational exposure, to record the medical and family history with particular reference to liver and thyroid disease and autoimmune disease, and to record alcohol consumption and details of drugs taken; (2) a general clinical examination for evidence of hepatic,s thyroid, or autoimmune disease; (3) detailed examination of the skin by Wood’s lamp to detect the severity and distribution of depigmentation ; and (4) serological investigation (biochemical profile, immunological profile, and antibody estimation). RESULTS
Clinical Findings: Skin
Of the 198 workers who had been exposed to P.T.B.P. and were examined, 54 had vitiligo, presumed to be occupational, and 144 men were unaffected. In 7 of the 54 men the extent of depigmentation was very slight and could be seen only by Wood’s light. Clinically the condition was indistinguishable from true vitiligo; skin from a matching depigmented area from the hand of 1 of the 54 men and from the hand of a patient with true vitiligo showed identical histological features. Unlike true vitiligo,6 there was no clinical evidence of an association TABLE I-OCCUPATIONAL VITILIGO: SITES AFFECTED PATIENTS
IN 54
TABLE IV-DURATION AND INTENSITY OF EXPOSURE TO P.T.B.P.
RELATED TO SEVERITY OF VITILIGO
with autoimmune disease in the 54 men or their families, or in the unaffected but exposed men. Partial resolution of depigmentation has been seen in 16 of 35 men re-examined a year after the survey. The sites affected (table i) suggest that depigmentation was induced by systemic absorption of P.T.B.P. and not by skin contact. When affected and unaffected workers were compared, it seemed that the occurrence of vitiligo was related to the duration of exposure to P.T.B.P. (table n), and, even more, to the intensity of exposure in particular jobs (tables in and iv). 14 of the 54 men had been exposed for five years or less. In the remainder, exposure had been for between six and twenty years. All 9 men with very extensive vitiligo were in high or medium exposure occupations, but 2 had been exposed for less than five years.
Clinical Findings: Systemic Thyroid enlargement or signs
of thyroid disease were found in any of the 54 men with vitiligo. There were no signs of other chronic systemic diseases; in particular, there were no signs of chronic liver disease; significant liver enlargement and splenomegaly were not detected. not
Laboratory Findings abnormalities in the full blood-count, urea, electrolytes except where they could be accounted for by intercurrent and independent illness (e.g., known hypertension). None of the workers had glycosuria. 20 men were patch tested with 2% P.T.B.P. and all were negative. Autoimmune disease and immunology.-The immunoglobulin profile in 54 men with vitiligo revealed a few minor abnormalities compatible with intercurrent disease, (e.g., asthma). A weakly positive antinuclear factor in 1 man was associated with intercurrent illness. Smooth-muscle antibody was present at low titre (1/20) in 1 man. Thyroid antibodies (T.R.C., cytoplasmic, microsomal) were strongly positive in 2 men, 1 of whom also had gastric parietal antibodies. Of the 144 workers exposed to P.T.B.P. who did not have vitiligo, 2 had a weak positive thyroid-antibody titre, and 1 had a weak There
or
TABLE II-DURATION OF EXPOSURE TO P.T.B.P.
*
(no. with vitiHgo)—(no. in exposure group).
were no
1219
positive gastric parietal antibody. Thus, in the 54 men with vitiligo and the 144 men without vitiligo there was association with autoimmune disease. Liver.--6 of the 54 men with vitiligo had an increase of aspartate aminotransferase (A.S.T.) on two or more occasions. 3 of these also showed an increase in serumbilirubin, although none had overt jaundice; in every case liver-function tests returned to normal within 6 months. Liver biopsy was done on clinical grounds and with their informed consent, in all 6 men with raised A.S.T. values but after their liver-function tests had returned to normal. In all 6 men liver-biopsy findings were abnormal, the main histological features being moderate or severe focal fatty change (in all 6); portal tracts with collagenous septal formation (4) and fibrosis amounting to probable macronodular cirrhosis in a fifth; and spotty, hepatocellular necrosis with mild lymphocytic infiltration (4). No abnormality of autoantibodies or immunoglobulins was found in these patients. HBsAg was negative in all 6. None had a history of liver disease. While none of the 6 was teetotal only 2 admitted to a consumption of more than ten pints of beer (200 g alcohol) a week. 2 of the 144 workers exposed to P.T.B.P. with no vitiligo also had minor abnormalities of liver function; both admitted drinking more than ten pints of beer a week. The difference between 6/54 vitiligo patients and 2/144 non-vitiligo patients is statistically no
significant (P
Category 1 included wounds without clinical evidence of inflammation; category 2 those with visible swelling in the skin and subcutaneous tissues; category 3 those with swelling and and category 4 those with pus visible to the naked eye. A PDP-11computer system was used to analyse the data.
erythema;
RESULTS
478 wounds were sutured with P.G.A. and 522 with silk. The comparative assessment of wounds is summarised in table I, including all four categories. Wounds sutured with P.G.A. showed a significantly lower incidence of inflammatory reaction (categories 2-4), particularly noticeable in category 4 (infection with pus), the most readily assessed grade. Both comparisons give a value of X2 which is highly significant (PO-01). Regional variations.-The proportion of wounds in
compared with 19p for a corresponding silk suture of 45 cm length. Moreover, children are saved the psychological trauma of suture removal.
We are grateful to the nursing staff of the accident service of the Luton and Dunstable Hospital for their cooperation in this trial.
Requests for reprints should be addressed to M.S.B. REFERENCES 1. Anscombe, A. R., Hira, N., Hunt, B. Br. J. Surg 1970, 57, 2. Echeverria, E., Jimenez, J. Surgery Gynec. Obstet. 1970, 131, 3. Solhaug, J. H., Heimann, P. Acta chir. scand. 1975, 141, 326. 4. Mouzas, G. L., Pompa, P. Br. J. Surg. 1974, 61, 313. 5. Postlethwait, R. W. Archs Surg. 1970, 101, 489. 6. Olerud, S. Lancet, 1970, i, 1060. 7. Clough, V., Alexander-Williams, J. ibid. 1975, i, 194.
which
an inflammatory reaction developed (categories 2-4) varied considerably with the site of the wound (table II). P.G.A. gave better results in all sites, particularly in wounds of the hand. When category 4 alone was considered, P.G.A. was again found to give better results in all sites, particularly in the lower limb and hand. In the lower limb, none of the 46 wounds sutured with
showed pus; whereas 9 put of 71 sutured with silk did so. The corresponding figures for the hand were 4 out of 149 (P.G.A.) and 13 out of 191 (silk). Where the incidence of suppuration was highest, the superiority of P.G.A. was most clearly shown. Sex differences.-In each sex 21% of wounds were adjudged unsatisfactory (categories 2-4), but the difference between P.G.A. and silk was greater for women than men (table III). Women had a higher incidence of suppuration, particularly where silk was used. This may well be associated with a greater number of lower-limb wounds in women, a region with a high infection-rate (table II). Age differences.-Comparison of silk and P.G.A. for different age-groups showed consistently lower figures for P.G.A., especially for suppuration. This feature was P.G.A.
pronounced in the 41-60 age-group, a group with large proportion of limb and hand wounds where the risk of suppuration is particularly high (table II). most a
DISCUSSION
The most important conclusion is that P.G.A. is superior to silk as a suture material in the treatment of wounds in an accident service. A number of experimental,6 have shown that the inflammatory response of tissues to P.G.A. is less than that to silk or catgut. In clinical practice one would thus expect a lower wound infection-rate with P.G.A. than with silk; our results support this. Of the criteria used (categories 1-4) for assessment the presence of pus in the wound is obviously the most incontrovertible, and here the statistical significance of the results is high. The superiority of P.G.A. is particularly notable in wounds of the hand, which accounted for 34% of all wounds with a suppuration rate of 5%. The rate of wound healing was not assessed; but total wound dehiscence in the absence of infection was recorded and found to be commoner in the silk group. A further advantage of P.G.A. is that removal of the suture is not required. The saving of time for general practitioners,’ community nurses, and patients themselves is substantial. There is no significant difference in cost. A metric 2 P.G.A. suture of 75 cm length cost 35p,
-
917. 1.
Occupational Health OCCUPATIONAL VITILIGO INDUCED BY p-tert-BUTYLPHENOL, A SYSTEMIC DISEASE? OLIVER
JAMES Department of Medicine (Geriatrics), University of Newcastle upon Tyne
R. W. MAYES I.C.I. Agricultural Division, Billingham
C.
J. STEVENSON
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon
Summary
Tyne NE1 4LP
Vitiligo, morphologically indistinguishable from true vitiligo, was detected in men exposed to p-tert-butylphenol (P.T.B.P.)
54 of 198 during its manufacture. There is evidence that P.T.B.P. caused vitiligo by a systemic mechanism and that the severity of the disease was related to the intensity of exposure. No association with autoimmune disease was found. Screening for other possible associated disorders revealed mildly abnormal liver-function tests in 6 workers: liver biopsy confirmed liver damage. Of the 144 men exposed to P.T.B.P. who did not have vitiligo, only 2 had any abnormal liver-function test. It seems possible that the liver damage is related to P.T.B.P. INTRODUCTION
THE main use of p-tert-butylphenol (P.T.B.P.) is the production of resins for adhesives used in the car industry. It is a white crystalline solid which melts at 97-98 °C to a clear, colourless liquid, and vaporises at 260 °C. It is produced by reacting isobutene with phenol in the presence of a catalyst; the crude P.T.B.P. is purified by distillation, allowed to cool, pastillated and packed into bags. This process began in 1958 in the factory where our investigation was conducted. Workers were exposed to the vapour in the distillation stage and to dust in the pastillating and packing sheds where the background dust level was 10 parts per million (p.p.m.) with occasional peaks of 100 p.p.m. P.T.B.P. is absorbed readily through the skin and also from P.T.B.P. by inhalation. Occupational vitiligo was first reviewed by
Malten
et
al.’ in 1971 who drew attention
to cases
in
1218 TABLE III-DEGREE OF EXPOSURE TO P.T.B.P.
Russiaand Japan.3 In the car industry, Calnan and Cooke4 found that vitiligo usually developed at sites in contact men
with
working
P.T.B.P.-containing adhesive, in confined spaces had
more
but that
widespread
involvement. In 1975 we started a thorough survey of vitiligo and possible associated systemic disorders in workers at a
factory manufacturing P.T.B.P. SURVEY METHODS
In 1974 the number of men who had reported depigmentation had reached double figures. Production of P.T.B.P. was stopped and the full extent of the problem was assessed by screening the whole workforce exposed to P.T.B.P., and also men who had previously been exposed but had moved to other sites. The screening programme was designed to identify the extent of depigmentation, to relate this to the degree of exposure, and to investigate possible systemic effects with particular reference to liver and thyroid disturbance and autoimmune disease. The programme comprised: (1) a questionnaire to establish length and severity of occupational exposure, to record the medical and family history with particular reference to liver and thyroid disease and autoimmune disease, and to record alcohol consumption and details of drugs taken; (2) a general clinical examination for evidence of hepatic,s thyroid, or autoimmune disease; (3) detailed examination of the skin by Wood’s lamp to detect the severity and distribution of depigmentation ; and (4) serological investigation (biochemical profile, immunological profile, and antibody estimation). RESULTS
Clinical Findings: Skin
Of the 198 workers who had been exposed to P.T.B.P. and were examined, 54 had vitiligo, presumed to be occupational, and 144 men were unaffected. In 7 of the 54 men the extent of depigmentation was very slight and could be seen only by Wood’s light. Clinically the condition was indistinguishable from true vitiligo; skin from a matching depigmented area from the hand of 1 of the 54 men and from the hand of a patient with true vitiligo showed identical histological features. Unlike true vitiligo,6 there was no clinical evidence of an association TABLE I-OCCUPATIONAL VITILIGO: SITES AFFECTED PATIENTS
IN 54
TABLE IV-DURATION AND INTENSITY OF EXPOSURE TO P.T.B.P.
RELATED TO SEVERITY OF VITILIGO
with autoimmune disease in the 54 men or their families, or in the unaffected but exposed men. Partial resolution of depigmentation has been seen in 16 of 35 men re-examined a year after the survey. The sites affected (table i) suggest that depigmentation was induced by systemic absorption of P.T.B.P. and not by skin contact. When affected and unaffected workers were compared, it seemed that the occurrence of vitiligo was related to the duration of exposure to P.T.B.P. (table n), and, even more, to the intensity of exposure in particular jobs (tables in and iv). 14 of the 54 men had been exposed for five years or less. In the remainder, exposure had been for between six and twenty years. All 9 men with very extensive vitiligo were in high or medium exposure occupations, but 2 had been exposed for less than five years.
Clinical Findings: Systemic Thyroid enlargement or signs
of thyroid disease were found in any of the 54 men with vitiligo. There were no signs of other chronic systemic diseases; in particular, there were no signs of chronic liver disease; significant liver enlargement and splenomegaly were not detected. not
Laboratory Findings abnormalities in the full blood-count, urea, electrolytes except where they could be accounted for by intercurrent and independent illness (e.g., known hypertension). None of the workers had glycosuria. 20 men were patch tested with 2% P.T.B.P. and all were negative. Autoimmune disease and immunology.-The immunoglobulin profile in 54 men with vitiligo revealed a few minor abnormalities compatible with intercurrent disease, (e.g., asthma). A weakly positive antinuclear factor in 1 man was associated with intercurrent illness. Smooth-muscle antibody was present at low titre (1/20) in 1 man. Thyroid antibodies (T.R.C., cytoplasmic, microsomal) were strongly positive in 2 men, 1 of whom also had gastric parietal antibodies. Of the 144 workers exposed to P.T.B.P. who did not have vitiligo, 2 had a weak positive thyroid-antibody titre, and 1 had a weak There
or
TABLE II-DURATION OF EXPOSURE TO P.T.B.P.
*
(no. with vitiHgo)—(no. in exposure group).
were no
1219
positive gastric parietal antibody. Thus, in the 54 men with vitiligo and the 144 men without vitiligo there was association with autoimmune disease. Liver.--6 of the 54 men with vitiligo had an increase of aspartate aminotransferase (A.S.T.) on two or more occasions. 3 of these also showed an increase in serumbilirubin, although none had overt jaundice; in every case liver-function tests returned to normal within 6 months. Liver biopsy was done on clinical grounds and with their informed consent, in all 6 men with raised A.S.T. values but after their liver-function tests had returned to normal. In all 6 men liver-biopsy findings were abnormal, the main histological features being moderate or severe focal fatty change (in all 6); portal tracts with collagenous septal formation (4) and fibrosis amounting to probable macronodular cirrhosis in a fifth; and spotty, hepatocellular necrosis with mild lymphocytic infiltration (4). No abnormality of autoantibodies or immunoglobulins was found in these patients. HBsAg was negative in all 6. None had a history of liver disease. While none of the 6 was teetotal only 2 admitted to a consumption of more than ten pints of beer (200 g alcohol) a week. 2 of the 144 workers exposed to P.T.B.P. with no vitiligo also had minor abnormalities of liver function; both admitted drinking more than ten pints of beer a week. The difference between 6/54 vitiligo patients and 2/144 non-vitiligo patients is statistically no
significant (P
