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ASCORBIC ACID FOR PRICKLY HEAT
1347
ASCORBIC ACID FOR PRICKLY HEAT T. C. HINDSON M.A., M.B. Cantab., M.R.C.P., M.R.C.P.E,, D.T.M. & H. DERMATOLOGIST, BRITISH MILITARY HOSPITAL, SINGAPORE
A chance observation led to the use of ascorbic acid, 15 mg. per kg., in a doubleblind trial in 30 children who had had repeated attacks of prickly heat. Of 15 children given ascorbic acid for two weeks, 14 improved or were free from lesions compared with 4 out of 15 given placebo. All 30 were then given ascorbic acid: no further lesions were seen after one and two months. Only a few patients reported lesions during that time. No unwanted side-effects have been seen.
Sum ary
Singapore is 130 km. (80 miles) north of the equator. The climate is hot and humid and there is little seasonal variation with temperatures around 80°F (26°C) and humidity 84—85%. The average annual rainfall is 88 in. (220 cm.). The effective temperature (Stephenson 1963) calculated by taking into account humidity, dry bulb temperature, and wind speed, exceeds 78 °F (25 °C), the accepted comfort zone, for much of April and May. The work of Griffin et al. (1967) suggests that the primary event in the genesis of prickly heat is cessation of sweatgland activity which they termed " sweat gland fatigue ", and they were able to demonstrate, in individuals in whom prickly heat was artificially induced by occlusion with polyethylene, that areas of sweat-gland fatigue ex-
Introduction first drawn to the
My attention was efficacy of high doses of ascorbic acid in the treatment of prickly heat after interviewing an Australian Air Force officer who had an acute intertriginous dermatitis (see figure). This rash is very common in the tropics and Monilia can be isolated from it on microscopy and culture. However, it does not respond satisfactorily to local nystatin and it is suspected that it is a manifestation of prickly heat secondarily infected with Monilia. This patient said that he had had the rash for one year previously and that it had resisted all topical therapy, but that it suddenly cleared in the course of a week when he ’ was taking ascorbic acid 1 g. daily (’ Redoxon Effervescent ’ Roche Products) because he believed it beneficial for a cold which he had at that time. I put him on ascorbic acid 1 g. daily as the sole treatment, and when re-examined ten days later his groin was normal. Ascorbic acid was then tried in the treatment of five children who had recurrent severe prickly heat. They were given a dose proportional to their weight, and no further attacks of prickly heat presented while they were taking it. Subsequently I carried out a double-blind trial of ascorbic acid in the treatment of 30 cases of prickly heat.
Abele, D. C., Tobie, J. E., Hill, G. J., Contacos, P. G., Evans, C. B. (1965) Am. J. trop. Med. Hyg. 14, 191. Burkitt, D. P., Wright, D. H. (1966) Br. med. J. i, 569. Cohen, S., McGregor, A. I. (1964) in Immunity to Protozoa (edited by P. C. C. Garnham, A. E. Pierce, and I. Roitt); p. 123. Oxford. Coons, A. H., Kaplan, M. H. (1950) J. exp. Med. 91, 1. Curtain, C. C., Baumgarten, A., Kidson, C., Gajdusek, D. C., Gorman, J. G., Rodrique, R., Champness, L. (1965) Br.J. Hœmat. 11, 471. Kidson, C., Gorman, J. G., Parkinson, D. (1965) Trans. R. Soc. trop. Med. Hyg. 59, 415. Dalldorf, G., Linsell, C. A., Barnhart, F. E., Martyn, R. (1964) Perspect. Biol. Med. 7, 435. Gilles, H. M., Hendrickse, R. G. (1963) Br. med. J. ii, 27. Houba, V., Allison, A. C. (1966) Lancet, i, 848. Kaplan, M. H., Meyserian, M., Kushner, I. (1961) J. exp. Med. 113, 17. Kibukamusoke, J. W., Hutt, M. S. R., Wilks, N. E. (1967) Q. Jl Med. 36, —
Typical groin lesion of prickly heat in the tropics
tended considerably beyond areas of prickly heat apparent on examination. This would explain the prevalence of prickly heat in Singapore where, because of the climate, sweat glands are always active. Patients and Methods who had been in Singapore
longer than six they came through the cash desk of the main service grocery store (N.A.A.F.I.). 73 described rashes developing intermittently in their children, which corresponded to a clinical picture of prickly heat: 52 had sought medical advice because of it on one occasion and 17 100
mothers, months, were interviewed consecutively
as
than one occasion. 30 cases were selected; the criterion being that all patients should have suffered continuously from prickly heat for a period of eight weeks, immediately before the date of initial interview. Ages ranged from four months to eight years. There were 18 boys and 12 girls. The sites affected were as follows: on more
393.
Marsden, P. D., Connor, D. H., Voller, A., Kelly, A., Schofield, F. D., Hutt, M. S. R. (1967) Bull. Wld. Hlth Org. 36, 901. Richards, A. I. (1954) Economic Development and Tribal Change: a Study of Immigrant Labour in Buganda. Cambridge. Rowe, D. S., McGregor, I. A., Smith, S. J., Hall, P., Williams, K. (1968) Clin. exp. Immun. 3, 63. Shaper, A. G. (1968) Trans. R. Soc. trop. Med. Hyg. (in the press). Coles, R. M. (1965) Br. Heart J. 27, 121. Kaplan, M. H., Foster, W. D., Macintosh, D. M., Wilks, N. E. (1967) Lancet, i, 598. Soothill, J. F., Hendrickse, R. G. (1967) ibid. ii, 629. Stiehm, E. R., Fudenberg, H. H. (1966) Pediatrics, Springfield, 37, 715. Uriel, J. (1958) Clin. Chimica. Acta, 3, 234. van der Geld, H., Peetom, F., Somers, K., Kanyerezi, B. R. (1966) Lancet, ii, 1210. van Tongeren, J. M. (1966) ibid. i, 1266. Voller, A., Bray, R. S. (1962) Proc. Soc. exp. Biol. 110, 907. Webster, D. (1962) Clin. Chimica. Acta, 7, 277. —
—
The 30
patients were divided into two equal groups. Half given ascorbic acid and half a placebo. Patients were allotted to each group by the pharmacist without my knowledge. The dosage of ascorbic acid was based on the observation of the original patient, who weighed 154 lb. (70 kg.) and was taking 1 g. daily. It was assumed therefore that 1 g. was necessary for a patient of 150 lb. weight and the dosage for the were
children
was
calculated
to
the
nearest
25 mg.,
on a
dose-for-
1348
weight basis. parents
were
GRANULOMATOUS HEPATITIS ACCOMPANYING A SELF-LIMITED
Where a child was too young to take tablets instructed to administer them crushed with food.
FEBRILE DISEASE
Results
The table shows the results after two weeks. The 11 patients from the placebo group whose lesions had either not improved or had worsened were given ascorbic acid; after a further two-week interval 6 had no lesions and 5 had improved. None were recorded as unchanged or worse. All 30 patients were then given RESULTS AFTER TWO WEEKS
S. EISENBERG Jerusalem T. G. SACKS
M. ELIAKIM
M.D.
M.D. Jerusalem
I. S.
LEVIJ
M.D. Utrecht
M.B. Pretoria,
M.Med.(Path.)
Cape Town, M.C.Path.
Departments of Internal Medicine B, Pathology, and Microbiology, Hadassah University Hospital and Hadassah Medical School, Jerusalem, Israel From the
Five
patients with
a
self-limited febrile
Summary disease resembling infectious
ascorbic-acid therapy and re-examined after a further one and two months. At neither examination were lesions visible on any of the 30 patients. After one month 5, and after two months 4 reported that they had had occasional lesions during the
period. Thus it seems that ascorbic acid, when given in high doses, is effective in the treatment and prevention of prickly heat. No unwanted side-effects have been recorded from such doses to date. The exact mechanism of action of ascorbic acid in prevention of prickly heat is not yet established, although I have found that it reduces the area of experimentally induced sweat-gland fatigue and its subsequent duration. Ascorbic acid is known to act as a hydrogen-ion carrier for the intracellular redox enzyme systems (Mapson 1954) and Shamin Ara and Pakis (1953) postulated that in conditions of profuse sweating significant amounts of ascorbic acid might be lost by this route, but Sargent et al. (1944) doubted whether any loss of the vitamin in this way would be significant. Ascorbic-acid levels in sweat collected from individuals on high ascorbic-acid intake have not yet been carried out. That sweat glands, hyperactive in a tropical atmosphere, might selectively become short of this vitamin, or that the vitamin in large doses might take over the action of, or replenish some essential, but fatigued enzyme system such as the succinic-dehydrogenase system-which Dobson at el. (1958) showed was the first to disappear on excess sweating-is an attractive hypothesis which needs further
investigation. I thank Lieut.-Colonel H. S. Moore, Prof. C. D. Calnan, Colonel W. J. Irwin, and Lieut.-Colonel S. E. M. Jarvis for their help and encouragement, the R.A.F. Metereology Section, Changi, for climate data, and Dr. A. J. F. Eberle and the staff of Roche Pharmaceuticals Ltd. for professional and financial assistance.
Requests for reprints should be addressed to T. Military Hospital, c/o G.P.O. Singapore
C. H.,
R.A.M.C.,
British
REFERENCES
L., Foronisano, V., Lotitz, W. C. (1958) J. invest. Derm. 31, 147. Griffin, T. B., Maiback, H. I., Sulzberger, M. B. (1967) ibid. 49, 379. Mapson, M. A., (1954) The Vitamins, Chemistry, Physiology and Pathology, New York. Sargent, F., Robinson, P., Johnson, R. E. (1944) J. biol. Chem. 158, 285. Shamin Ara, Pakis, J. (1953) Sci. res. 5, 61. Stephenson, P. M. (1963) Meteorol. Mag. 92, 338. Dobson,
R.
mononu-
cleosis are described. The main manifestations of the disease included fever, cough, a slight enlargement of the spleen, and peripheral lymphocytosis. Gross lymphadenopathy was absent, abnormal lymphocytes were not found, and the Paul-Bunnell test was negative in all cases. Hepatocellular function tests were slightly impaired but jaundice was absent. Liver-biopsy specimens which were performed in three of the cases, revealed lesions resembling granulomas. The course of the disease was not influenced by antibiotics, and complete recovery ensued within 3 to 4 weeks. Subsequent biopsy specimens showed no abnormalities. The cause of the disease remained obscure in spite of an extensive search for ætiological factors. Introduction DURING the spring of 1966 we saw five patients with a disease resembling infectious mononucleosis but lacking some of its typical features. An extensive search for aetiological factors was fruitless. The cases represented
diagnostic challenge, and there were several interesting features, notably evidence of liver involvement. a
Case-reports FIRST CASE
30-year-old civil-servant was admitted to the hospital in May, 1966, because of malaise, fever, severe headache, and non-productive cough of 6 day’s duration. The temperature was intermittent and rose to 39°C (1024°F) in the evenings, A
without chills. He was in excellent general state, temperature 38°C
(1006°F), pulse-rate 100 per minute, blood-pressure 130/70 mm.Hg. No jaundice. The pharynx showed slight congestion. A soft, grade-2, blowing. systolic murmur (known to exist since childhood) was heard at the 4th left intercostal space. Liver was neither tender nor palpable; spleen palpable 2-3 cm. below the costal margin; no lymphadenopathy. Laboratory data Erythrocyte-sedimentation rate (Westergren) 10 mm. in lst hour, 22 mm. in 2nd hour; Hb 16-3 g. per 100 ml. White blood-cells 7100-11,500 per c.mm. The differential count revealed 55-65% lymphocytes, 8-10% monocytes, and 32-46°. segmented cells (five counts). Urinalysis normal. Multiple blood and urine cultures sterile. Sputum grew Hœmophilus influenzœ. Thick blood preparations revealed no malaria parasites or Borrelia. Serological tests for Salmonella infections, typhus fever, brucellosis, infectious mononucleosis, and Q fever all negative. Wassermann reaction was negative; no L.E. cells. Many stool examinations revealed no ova or parasites. Liver-function tests are listed in table I. X-ray of the chest showed slight enlargement of the left atrium and ventricle; lungs normal. The temperature remained elevated for 18 days after admission and was not affected by the oral administration of
ASCORBIC ACID FOR PRICKLY HEAT T. C. HINDSON M.A., M.B. Cantab., M.R.C.P., M.R.C.P.E,, D.T.M. & H. DERMATOLOGIST, BRITISH MILITARY HOSPITAL, SINGAPORE
A chance observation led to the use of ascorbic acid, 15 mg. per kg., in a doubleblind trial in 30 children who had had repeated attacks of prickly heat. Of 15 children given ascorbic acid for two weeks, 14 improved or were free from lesions compared with 4 out of 15 given placebo. All 30 were then given ascorbic acid: no further lesions were seen after one and two months. Only a few patients reported lesions during that time. No unwanted side-effects have been seen.
Sum ary
Singapore is 130 km. (80 miles) north of the equator. The climate is hot and humid and there is little seasonal variation with temperatures around 80°F (26°C) and humidity 84—85%. The average annual rainfall is 88 in. (220 cm.). The effective temperature (Stephenson 1963) calculated by taking into account humidity, dry bulb temperature, and wind speed, exceeds 78 °F (25 °C), the accepted comfort zone, for much of April and May. The work of Griffin et al. (1967) suggests that the primary event in the genesis of prickly heat is cessation of sweatgland activity which they termed " sweat gland fatigue ", and they were able to demonstrate, in individuals in whom prickly heat was artificially induced by occlusion with polyethylene, that areas of sweat-gland fatigue ex-
Introduction first drawn to the
My attention was efficacy of high doses of ascorbic acid in the treatment of prickly heat after interviewing an Australian Air Force officer who had an acute intertriginous dermatitis (see figure). This rash is very common in the tropics and Monilia can be isolated from it on microscopy and culture. However, it does not respond satisfactorily to local nystatin and it is suspected that it is a manifestation of prickly heat secondarily infected with Monilia. This patient said that he had had the rash for one year previously and that it had resisted all topical therapy, but that it suddenly cleared in the course of a week when he ’ was taking ascorbic acid 1 g. daily (’ Redoxon Effervescent ’ Roche Products) because he believed it beneficial for a cold which he had at that time. I put him on ascorbic acid 1 g. daily as the sole treatment, and when re-examined ten days later his groin was normal. Ascorbic acid was then tried in the treatment of five children who had recurrent severe prickly heat. They were given a dose proportional to their weight, and no further attacks of prickly heat presented while they were taking it. Subsequently I carried out a double-blind trial of ascorbic acid in the treatment of 30 cases of prickly heat.
Abele, D. C., Tobie, J. E., Hill, G. J., Contacos, P. G., Evans, C. B. (1965) Am. J. trop. Med. Hyg. 14, 191. Burkitt, D. P., Wright, D. H. (1966) Br. med. J. i, 569. Cohen, S., McGregor, A. I. (1964) in Immunity to Protozoa (edited by P. C. C. Garnham, A. E. Pierce, and I. Roitt); p. 123. Oxford. Coons, A. H., Kaplan, M. H. (1950) J. exp. Med. 91, 1. Curtain, C. C., Baumgarten, A., Kidson, C., Gajdusek, D. C., Gorman, J. G., Rodrique, R., Champness, L. (1965) Br.J. Hœmat. 11, 471. Kidson, C., Gorman, J. G., Parkinson, D. (1965) Trans. R. Soc. trop. Med. Hyg. 59, 415. Dalldorf, G., Linsell, C. A., Barnhart, F. E., Martyn, R. (1964) Perspect. Biol. Med. 7, 435. Gilles, H. M., Hendrickse, R. G. (1963) Br. med. J. ii, 27. Houba, V., Allison, A. C. (1966) Lancet, i, 848. Kaplan, M. H., Meyserian, M., Kushner, I. (1961) J. exp. Med. 113, 17. Kibukamusoke, J. W., Hutt, M. S. R., Wilks, N. E. (1967) Q. Jl Med. 36, —
Typical groin lesion of prickly heat in the tropics
tended considerably beyond areas of prickly heat apparent on examination. This would explain the prevalence of prickly heat in Singapore where, because of the climate, sweat glands are always active. Patients and Methods who had been in Singapore
longer than six they came through the cash desk of the main service grocery store (N.A.A.F.I.). 73 described rashes developing intermittently in their children, which corresponded to a clinical picture of prickly heat: 52 had sought medical advice because of it on one occasion and 17 100
mothers, months, were interviewed consecutively
as
than one occasion. 30 cases were selected; the criterion being that all patients should have suffered continuously from prickly heat for a period of eight weeks, immediately before the date of initial interview. Ages ranged from four months to eight years. There were 18 boys and 12 girls. The sites affected were as follows: on more
393.
Marsden, P. D., Connor, D. H., Voller, A., Kelly, A., Schofield, F. D., Hutt, M. S. R. (1967) Bull. Wld. Hlth Org. 36, 901. Richards, A. I. (1954) Economic Development and Tribal Change: a Study of Immigrant Labour in Buganda. Cambridge. Rowe, D. S., McGregor, I. A., Smith, S. J., Hall, P., Williams, K. (1968) Clin. exp. Immun. 3, 63. Shaper, A. G. (1968) Trans. R. Soc. trop. Med. Hyg. (in the press). Coles, R. M. (1965) Br. Heart J. 27, 121. Kaplan, M. H., Foster, W. D., Macintosh, D. M., Wilks, N. E. (1967) Lancet, i, 598. Soothill, J. F., Hendrickse, R. G. (1967) ibid. ii, 629. Stiehm, E. R., Fudenberg, H. H. (1966) Pediatrics, Springfield, 37, 715. Uriel, J. (1958) Clin. Chimica. Acta, 3, 234. van der Geld, H., Peetom, F., Somers, K., Kanyerezi, B. R. (1966) Lancet, ii, 1210. van Tongeren, J. M. (1966) ibid. i, 1266. Voller, A., Bray, R. S. (1962) Proc. Soc. exp. Biol. 110, 907. Webster, D. (1962) Clin. Chimica. Acta, 7, 277. —
—
The 30
patients were divided into two equal groups. Half given ascorbic acid and half a placebo. Patients were allotted to each group by the pharmacist without my knowledge. The dosage of ascorbic acid was based on the observation of the original patient, who weighed 154 lb. (70 kg.) and was taking 1 g. daily. It was assumed therefore that 1 g. was necessary for a patient of 150 lb. weight and the dosage for the were
children
was
calculated
to
the
nearest
25 mg.,
on a
dose-for-
1348
weight basis. parents
were
GRANULOMATOUS HEPATITIS ACCOMPANYING A SELF-LIMITED
Where a child was too young to take tablets instructed to administer them crushed with food.
FEBRILE DISEASE
Results
The table shows the results after two weeks. The 11 patients from the placebo group whose lesions had either not improved or had worsened were given ascorbic acid; after a further two-week interval 6 had no lesions and 5 had improved. None were recorded as unchanged or worse. All 30 patients were then given RESULTS AFTER TWO WEEKS
S. EISENBERG Jerusalem T. G. SACKS
M. ELIAKIM
M.D.
M.D. Jerusalem
I. S.
LEVIJ
M.D. Utrecht
M.B. Pretoria,
M.Med.(Path.)
Cape Town, M.C.Path.
Departments of Internal Medicine B, Pathology, and Microbiology, Hadassah University Hospital and Hadassah Medical School, Jerusalem, Israel From the
Five
patients with
a
self-limited febrile
Summary disease resembling infectious
ascorbic-acid therapy and re-examined after a further one and two months. At neither examination were lesions visible on any of the 30 patients. After one month 5, and after two months 4 reported that they had had occasional lesions during the
period. Thus it seems that ascorbic acid, when given in high doses, is effective in the treatment and prevention of prickly heat. No unwanted side-effects have been recorded from such doses to date. The exact mechanism of action of ascorbic acid in prevention of prickly heat is not yet established, although I have found that it reduces the area of experimentally induced sweat-gland fatigue and its subsequent duration. Ascorbic acid is known to act as a hydrogen-ion carrier for the intracellular redox enzyme systems (Mapson 1954) and Shamin Ara and Pakis (1953) postulated that in conditions of profuse sweating significant amounts of ascorbic acid might be lost by this route, but Sargent et al. (1944) doubted whether any loss of the vitamin in this way would be significant. Ascorbic-acid levels in sweat collected from individuals on high ascorbic-acid intake have not yet been carried out. That sweat glands, hyperactive in a tropical atmosphere, might selectively become short of this vitamin, or that the vitamin in large doses might take over the action of, or replenish some essential, but fatigued enzyme system such as the succinic-dehydrogenase system-which Dobson at el. (1958) showed was the first to disappear on excess sweating-is an attractive hypothesis which needs further
investigation. I thank Lieut.-Colonel H. S. Moore, Prof. C. D. Calnan, Colonel W. J. Irwin, and Lieut.-Colonel S. E. M. Jarvis for their help and encouragement, the R.A.F. Metereology Section, Changi, for climate data, and Dr. A. J. F. Eberle and the staff of Roche Pharmaceuticals Ltd. for professional and financial assistance.
Requests for reprints should be addressed to T. Military Hospital, c/o G.P.O. Singapore
C. H.,
R.A.M.C.,
British
REFERENCES
L., Foronisano, V., Lotitz, W. C. (1958) J. invest. Derm. 31, 147. Griffin, T. B., Maiback, H. I., Sulzberger, M. B. (1967) ibid. 49, 379. Mapson, M. A., (1954) The Vitamins, Chemistry, Physiology and Pathology, New York. Sargent, F., Robinson, P., Johnson, R. E. (1944) J. biol. Chem. 158, 285. Shamin Ara, Pakis, J. (1953) Sci. res. 5, 61. Stephenson, P. M. (1963) Meteorol. Mag. 92, 338. Dobson,
R.
mononu-
cleosis are described. The main manifestations of the disease included fever, cough, a slight enlargement of the spleen, and peripheral lymphocytosis. Gross lymphadenopathy was absent, abnormal lymphocytes were not found, and the Paul-Bunnell test was negative in all cases. Hepatocellular function tests were slightly impaired but jaundice was absent. Liver-biopsy specimens which were performed in three of the cases, revealed lesions resembling granulomas. The course of the disease was not influenced by antibiotics, and complete recovery ensued within 3 to 4 weeks. Subsequent biopsy specimens showed no abnormalities. The cause of the disease remained obscure in spite of an extensive search for ætiological factors. Introduction DURING the spring of 1966 we saw five patients with a disease resembling infectious mononucleosis but lacking some of its typical features. An extensive search for aetiological factors was fruitless. The cases represented
diagnostic challenge, and there were several interesting features, notably evidence of liver involvement. a
Case-reports FIRST CASE
30-year-old civil-servant was admitted to the hospital in May, 1966, because of malaise, fever, severe headache, and non-productive cough of 6 day’s duration. The temperature was intermittent and rose to 39°C (1024°F) in the evenings, A
without chills. He was in excellent general state, temperature 38°C
(1006°F), pulse-rate 100 per minute, blood-pressure 130/70 mm.Hg. No jaundice. The pharynx showed slight congestion. A soft, grade-2, blowing. systolic murmur (known to exist since childhood) was heard at the 4th left intercostal space. Liver was neither tender nor palpable; spleen palpable 2-3 cm. below the costal margin; no lymphadenopathy. Laboratory data Erythrocyte-sedimentation rate (Westergren) 10 mm. in lst hour, 22 mm. in 2nd hour; Hb 16-3 g. per 100 ml. White blood-cells 7100-11,500 per c.mm. The differential count revealed 55-65% lymphocytes, 8-10% monocytes, and 32-46°. segmented cells (five counts). Urinalysis normal. Multiple blood and urine cultures sterile. Sputum grew Hœmophilus influenzœ. Thick blood preparations revealed no malaria parasites or Borrelia. Serological tests for Salmonella infections, typhus fever, brucellosis, infectious mononucleosis, and Q fever all negative. Wassermann reaction was negative; no L.E. cells. Many stool examinations revealed no ova or parasites. Liver-function tests are listed in table I. X-ray of the chest showed slight enlargement of the left atrium and ventricle; lungs normal. The temperature remained elevated for 18 days after admission and was not affected by the oral administration of