335
comparison of mean peak-flow readings in the intervention periods with those obtained during the initial observation period suggests that the "placebo" procedure had little or no effect. An
important difference between this study and that et al. was that their subjects were children
of Sarsfield
whereas ours were adults. These measures may well have different effects at different ages, and it is intended that a controlled trial be conducted among children. Furthermore, the subjects in this trial represented the whole range of asthma in the community, so that in
the disease was quite mild. Perhaps mite-eradication is helpful only to patients with severe asthma. Finally, it is possible that these anti-mite measures have a beneficial effect which is too small to have been detected in this trial. If so it seems unlikely that they are of much value or that patients will persevere with them for any length of time. some
-
REFERENCES 1
Maunsell, K., Wraith, D. G., Cunnington, A. M. Lancet, 1968, ii, 1267. 2. Sarsfield, J. K. Archs. Dis. Childh. 1974, 49, 711. 3. Rao, V. R. M., Dean, B. V., Seaton, A., Williams, D. A. Clin. Allergy, 1975, 5, 209. 4. Sarsfield, J. K., Gowland, G., Toy, R., Norman, A. L. E. Archs. Dis. Childh. 1974,49,716. 5. Blythe, M. E., Al Ubaydi, F., Williams, J. D., Smith, J. M. Br. med. J. 1975, i, 62. 6. Maunsell, K., Hughes, A. M., Wraith, D. C. Practitioner, 1970, 205, 779. 7. Burr, M. L., St. Leger, A. S., Bevan, C., Merrett, T. G. Thorax, 1975, 30, 1663. 8. Bhoomkar, A., Davies, S., 9. Lancet, 1974, ii, 1492.
SECOND CASE
A 22-year-old male college student was examined because of 3-week history of 4 to 8 watery diarrhoea movements daily which were not associated with cramps, blood, or mucus. He denied recent ingestion of antibiotics. Physical examination was normal. Laboratory studies included normal hacmatocrit, total and differential white-blood-cell counts, liver-function tests, and serum-calcium. Stool culture was negative for enteric pathogens. Three separate stool specimens were negative for ova and parasites, but large numbers of yeast forms, consistent with Candida species, were seen on each occasion. After 5 days of therapy with ’Lomotil’ no improvement was noted and he was put on nystatin, 500 000 units orally three times daily. Symptoms subsided within 48 hours. Treatment was continued for 7 days. No recurrence was noted in 6 months of follow-up. a
THIRD CASE
A
abdominal cramping and 6-8 times daily. She had been given tetracycline a week earlier for symptoms of an upper-respiratory-tract infection. For the past 2 years she had been taking oral contraceptives and had been treated successfully a year before for a vaginal infection with Candida albicans. No blood or mucus was noted in her stools and she denied nausea or vomiting. Physical examination was unremarkable except for mild lower abdominal tenderness. Laboratory studies included a normal blood-count, liver-function tests, glucose-tolerance test, and erythrocyte-sedimentation rate. Stool culture was negative for enteric pathogens. Tetracycline was discontinued and she was treated with lomotil, but abdominal cramps and diarrhoea persisted for a total of 12 days. Repeat stool culture was again negative for enteric pathogens. Microscopic examination of three stool specimens for ova and parasites showed numerous yeast forms per high-power field, consistent with Candida species. The patient was put on nystatin, 500 000 units orally three times daily, with rapid resolution of symptoms. There has been no recurrence in 3 years of follow-up.
20-year-old
watery bowel
Geary, M., Hills, E. A. ibid. p. 225.
DIARRHŒA CAUSED BY CANDIDA
JAMES G.
for 3 weeks and an associated weight loss of 3 kg. Physical examination was unremarkable and laboratory studies were normal. Sigmoidoscopy was normal to 22 cm. Three stool cultures were negative for enteric pathogens but grew predominantly Candida albicans. There was no history of antibiotic ingestion. Treatment was instituted with nystatin, 500 000 units orally three times daily, and the diarrhoea resolved within 72 hours. After 3 months of follow-up there was no recurrence.
KANE JANE H. CHRETIEN VINCENT F. GARAGUSI
Infectious Disease Service, Department of Medicine, Georgetown University Hospital, Washington D. C. 20007, U.S.A. Candida proliferation in the gastrointestinal tract was responsible for diarrhœa in six patients. Their common presentation was multiple loose or watery bowel movements, without blood or mucus but sometimes associated with abdominal cramps, and lasting as long as 3 months. Yeast cells were most easily identified by direct microscopic examination of
Summary
stool specimens. Symptoms disappeared in all after 3 to 4 days of oral nystatin therapy.
patients
Introduction THE clinical entity of intestinal candidiasis has received scant attention. Even reviews of candida infections of the gastrointestinal tract fail to mention the symptom of diarrhoea.’ Since candida can frequently be isolated from the gastrointestinal tract of normal individuals, its presence does not necessarily signify disease.2 However, the candida organism may occasionally proliferate in the gastrointestinal tract to produce symptoms. We describe here six patients in whom candida was implicated as a cause of diarrhoea and who responded promptly to oral nystatin therapy.
developed
woman
movements
FOURTH CASE
A 19-year-old male college student presented with a 3-month history of diffuse abdominal cramps relieved by bowel movements. He was having 3-4 bowel movements daily without blood or mucus, and denied nausea, vomiting, weight loss, or anorexia. Two separate stool examinations were negative for ova and parasites but both specimens revealed many yeast forms per high-power field. He was treated symptomatically with liquids and antispasmodics for 10 days, at which time he returned with persistent complaints of diffuse abdominal discomfort, again relieved by bowel movements. The frequency of bowel movements remained unchanged, but they had become quite watery. No blood or mucus was seen in the specimens. Stool culture was negative for enteric pathogens but large numbers of Candida species were noted. He was put on nystatin, 500 000 units orally three times daily, and the diarrhoea stopped within 72 hours. The abdominal cramping gradually subsided over the 10-day course of therapy. There has been no recurrence in 18 months of follow-up.
Case-reports FIFTH CASE
FIRST CASE
A
46-year-old
man
complained
of loose bowel
movements
A
63-year-old woman underwent parathyroidectomy for pri-
336
hyperparathyroidism. 4 days after surgery she developed hypocalcsemia with serum-calcium values ranging from 6.7to 7.3mg/dl and was placed on oral replacement therapy. She developed a low-grade fever beginning on the first postoperative day; and on the 6th postoperative day she was put on ampicillin 500 mg orally every 6 hours, for a suspected urinarytract infection. The same day the patient developed diarrhoea! stools 3-4 times daily not associated with nausea or vomiting. The low-grade fever and diarrhoea persisted for the next 4 days. Stool cultures on three successive specimens yielded no enteric pathogens but "significant growth of Candida albicans". Stool examination for ova and parasites was negative. Blood-cultures were negative. Ampicillin was discontinued and nystatin, 1 000 000 units orally three times daily, was begun. Within 24 hours the patient became afebrile and the diarrhoea subsided. Therapy was continued for 10 days. The remainder of her hospital course was uneventful and there has been no recurrence after cessation of therapy. mary
SIXTH CASE
A 21-year-old man reported loose bowel movements, three times daily, of 3 months’ duration. Although he did not have cramps, he complained of a "queasy" abdominal sensation during this time. His symptoms were unresponsive to selftherapy with yogurt. He had received clindamycin and tetracycline at various times in the past because of acne, but had last taken tetracycline a month before the diarrhoea began.
tatin, and
none
relapsed
after
completing
7-10 days of
treatment.
In these six cases the clinical presentation was indistinguishable from that of "non-specific" gastroenteritis in that the patients felt well except for diarrhrea and occasional cramps. The diarrhoea was not bloody and ranged from several soft bowel movements to multiple watery episodes daily. In general, fever, nausea, vomiting, and anorexia were absent. One distinguishing feature was the rather protracted course of diarrhoea in patients 1, 2, 4, and 6, which is uncharacteristic of viral gastroenteritis.
Although it has been suggested that the diagnosis of candida enteritis requires barium studies and sigmoidoscopy to rule out other causes,3 the rapid response to nystatin therapy may serve as a diagnostic tool. The artiology may be suggested by stool cultures containing candida, but, as a rule, the media used routinely for the isolation of intestinal bacteria do not favour growth of candida. Certain intestinal flora, especially Enterobacteriaceae and lactobacilli, inhibit the growth of candida4 Also, routine cultures may be discarded before significant candida growth occurs. Direct microscopic examination of the stool, susin saline or iodine, gives more precise information. In all cases from the present report, yeast forms, with budding and often mycelial forms, were predominant. Although Kozinn et awl. suggest mycelial fomation should be present if pathogenicity is to be assumed, candida may be parasitic in the yeast phase, and mycelial-phase growth is not always evidence of pathogenicity.6 In fact, in both manand laboratory animals,’ a large quantity of yeast when swallowed can infiltrate to the bloodstream via persorption and cause symptoms of fungaemia before tissue invasion and subsequent multiplication would have time to occur. The serological evidence for tissue invasion by candida-the presence of
pended PATIENTS WITH DIARRHOEA CAUSED BY OVERGROWTH OF CANDIDA
*
precipitin or agglutinin antibodies,9 was negative in two of our patients tested. Although not a significant number, this suggests that actual tissue invasion may
N.D.=not done.
not
examination was normal. Stool culture was negative for enteric pathogens but Candida albicans grew. A stool specimen examined for ova and parasites contained numerous yeast cells per high-power field. On the 4th day of a 1-week course of nystatin, 500 000 units orally three times daily, symptoms
Physical
disappeared.
be necessary for the
occurrence
cases, stools must be examined for
tured for enteric pathogens before dida as the aetiological agent.
of diarrhoea. In all parasites and cul-
incriminating
can-
Nystatin, 500 000 - 1000 000 units by mouth three times daily, should cause regression of symptoms within 72 hours. Treatment should then be continued for 7-10 If nystatin has no effect on the diarrhoea, then other causes should be more fully explored.
days. Data
on
these six
cases are
summarised in the
accom-
panying table. Discussion The presence of candida in faeces of persons with no underlying disease has invariably been considered nonpathogenic. The present six cases, however, seem to confirm the entity of "candida diarrhoea" in adults. The patients were not debilitated; five of the six had no underlying disease; stool cultures were negative for enteric pathogens; and no parasites were found on multiple examinations. Their rapid response to nystatin treatment was most striking. Despite the duration of symptoms before therapy, all had a return to normal bowel movements within 3-4 days of receiving oral nys-
Requests for reprints should be addressed to V. F. G., Georgeto-Ar, University Hospital 3800 Reservoir Road NW, Washington D.C 20007, U.S.A. REFERENCES 1. 2.
Eras, P., Goldstein, M. J., Sherlock, P. Medicine, Baltimore, 1972, 51, 367 Cohen, R., Roth, F. J., Delgado, E., Ahearn, D. G., Kaiser, M. N. New Engl,
J. Med. 1969, 280, 638. 3. Brabander, J. O., Blank, F., Butas, C. A. Can. med Ass.J. 1957, 77, 478 4. Holt, R. J., Newman, R. L. J. clin. Path. 1967, 20, 80. 5. Kozinn, P. J., Taschdjian, C. L. Pediatrics, Springfield, 1962, 30, 71 6. Winner, H. I. Br. J. Derm. 1969, 81, suppl. 1, p. 62. 7. Krause, W., Matheis, H., Wulf, K. Lancet, 1969, i, 598. 8. Stone, H. H., Kolb, L. D., Currie, C. A., Geheber, C. E., Cuzzell, J. Z Ann. Surg. 1974, 179, 697. 9. Taschdjian, C., Kozinn, P. J., Cuesta, M. B., Toni, E. F. Am. J. clin Path. 1972, 57, 195.
comparison of mean peak-flow readings in the intervention periods with those obtained during the initial observation period suggests that the "placebo" procedure had little or no effect. An
important difference between this study and that et al. was that their subjects were children
of Sarsfield
whereas ours were adults. These measures may well have different effects at different ages, and it is intended that a controlled trial be conducted among children. Furthermore, the subjects in this trial represented the whole range of asthma in the community, so that in
the disease was quite mild. Perhaps mite-eradication is helpful only to patients with severe asthma. Finally, it is possible that these anti-mite measures have a beneficial effect which is too small to have been detected in this trial. If so it seems unlikely that they are of much value or that patients will persevere with them for any length of time. some
-
REFERENCES 1
Maunsell, K., Wraith, D. G., Cunnington, A. M. Lancet, 1968, ii, 1267. 2. Sarsfield, J. K. Archs. Dis. Childh. 1974, 49, 711. 3. Rao, V. R. M., Dean, B. V., Seaton, A., Williams, D. A. Clin. Allergy, 1975, 5, 209. 4. Sarsfield, J. K., Gowland, G., Toy, R., Norman, A. L. E. Archs. Dis. Childh. 1974,49,716. 5. Blythe, M. E., Al Ubaydi, F., Williams, J. D., Smith, J. M. Br. med. J. 1975, i, 62. 6. Maunsell, K., Hughes, A. M., Wraith, D. C. Practitioner, 1970, 205, 779. 7. Burr, M. L., St. Leger, A. S., Bevan, C., Merrett, T. G. Thorax, 1975, 30, 1663. 8. Bhoomkar, A., Davies, S., 9. Lancet, 1974, ii, 1492.
SECOND CASE
A 22-year-old male college student was examined because of 3-week history of 4 to 8 watery diarrhoea movements daily which were not associated with cramps, blood, or mucus. He denied recent ingestion of antibiotics. Physical examination was normal. Laboratory studies included normal hacmatocrit, total and differential white-blood-cell counts, liver-function tests, and serum-calcium. Stool culture was negative for enteric pathogens. Three separate stool specimens were negative for ova and parasites, but large numbers of yeast forms, consistent with Candida species, were seen on each occasion. After 5 days of therapy with ’Lomotil’ no improvement was noted and he was put on nystatin, 500 000 units orally three times daily. Symptoms subsided within 48 hours. Treatment was continued for 7 days. No recurrence was noted in 6 months of follow-up. a
THIRD CASE
A
abdominal cramping and 6-8 times daily. She had been given tetracycline a week earlier for symptoms of an upper-respiratory-tract infection. For the past 2 years she had been taking oral contraceptives and had been treated successfully a year before for a vaginal infection with Candida albicans. No blood or mucus was noted in her stools and she denied nausea or vomiting. Physical examination was unremarkable except for mild lower abdominal tenderness. Laboratory studies included a normal blood-count, liver-function tests, glucose-tolerance test, and erythrocyte-sedimentation rate. Stool culture was negative for enteric pathogens. Tetracycline was discontinued and she was treated with lomotil, but abdominal cramps and diarrhoea persisted for a total of 12 days. Repeat stool culture was again negative for enteric pathogens. Microscopic examination of three stool specimens for ova and parasites showed numerous yeast forms per high-power field, consistent with Candida species. The patient was put on nystatin, 500 000 units orally three times daily, with rapid resolution of symptoms. There has been no recurrence in 3 years of follow-up.
20-year-old
watery bowel
Geary, M., Hills, E. A. ibid. p. 225.
DIARRHŒA CAUSED BY CANDIDA
JAMES G.
for 3 weeks and an associated weight loss of 3 kg. Physical examination was unremarkable and laboratory studies were normal. Sigmoidoscopy was normal to 22 cm. Three stool cultures were negative for enteric pathogens but grew predominantly Candida albicans. There was no history of antibiotic ingestion. Treatment was instituted with nystatin, 500 000 units orally three times daily, and the diarrhoea resolved within 72 hours. After 3 months of follow-up there was no recurrence.
KANE JANE H. CHRETIEN VINCENT F. GARAGUSI
Infectious Disease Service, Department of Medicine, Georgetown University Hospital, Washington D. C. 20007, U.S.A. Candida proliferation in the gastrointestinal tract was responsible for diarrhœa in six patients. Their common presentation was multiple loose or watery bowel movements, without blood or mucus but sometimes associated with abdominal cramps, and lasting as long as 3 months. Yeast cells were most easily identified by direct microscopic examination of
Summary
stool specimens. Symptoms disappeared in all after 3 to 4 days of oral nystatin therapy.
patients
Introduction THE clinical entity of intestinal candidiasis has received scant attention. Even reviews of candida infections of the gastrointestinal tract fail to mention the symptom of diarrhoea.’ Since candida can frequently be isolated from the gastrointestinal tract of normal individuals, its presence does not necessarily signify disease.2 However, the candida organism may occasionally proliferate in the gastrointestinal tract to produce symptoms. We describe here six patients in whom candida was implicated as a cause of diarrhoea and who responded promptly to oral nystatin therapy.
developed
woman
movements
FOURTH CASE
A 19-year-old male college student presented with a 3-month history of diffuse abdominal cramps relieved by bowel movements. He was having 3-4 bowel movements daily without blood or mucus, and denied nausea, vomiting, weight loss, or anorexia. Two separate stool examinations were negative for ova and parasites but both specimens revealed many yeast forms per high-power field. He was treated symptomatically with liquids and antispasmodics for 10 days, at which time he returned with persistent complaints of diffuse abdominal discomfort, again relieved by bowel movements. The frequency of bowel movements remained unchanged, but they had become quite watery. No blood or mucus was seen in the specimens. Stool culture was negative for enteric pathogens but large numbers of Candida species were noted. He was put on nystatin, 500 000 units orally three times daily, and the diarrhoea stopped within 72 hours. The abdominal cramping gradually subsided over the 10-day course of therapy. There has been no recurrence in 18 months of follow-up.
Case-reports FIFTH CASE
FIRST CASE
A
46-year-old
man
complained
of loose bowel
movements
A
63-year-old woman underwent parathyroidectomy for pri-
336
hyperparathyroidism. 4 days after surgery she developed hypocalcsemia with serum-calcium values ranging from 6.7to 7.3mg/dl and was placed on oral replacement therapy. She developed a low-grade fever beginning on the first postoperative day; and on the 6th postoperative day she was put on ampicillin 500 mg orally every 6 hours, for a suspected urinarytract infection. The same day the patient developed diarrhoea! stools 3-4 times daily not associated with nausea or vomiting. The low-grade fever and diarrhoea persisted for the next 4 days. Stool cultures on three successive specimens yielded no enteric pathogens but "significant growth of Candida albicans". Stool examination for ova and parasites was negative. Blood-cultures were negative. Ampicillin was discontinued and nystatin, 1 000 000 units orally three times daily, was begun. Within 24 hours the patient became afebrile and the diarrhoea subsided. Therapy was continued for 10 days. The remainder of her hospital course was uneventful and there has been no recurrence after cessation of therapy. mary
SIXTH CASE
A 21-year-old man reported loose bowel movements, three times daily, of 3 months’ duration. Although he did not have cramps, he complained of a "queasy" abdominal sensation during this time. His symptoms were unresponsive to selftherapy with yogurt. He had received clindamycin and tetracycline at various times in the past because of acne, but had last taken tetracycline a month before the diarrhoea began.
tatin, and
none
relapsed
after
completing
7-10 days of
treatment.
In these six cases the clinical presentation was indistinguishable from that of "non-specific" gastroenteritis in that the patients felt well except for diarrhrea and occasional cramps. The diarrhoea was not bloody and ranged from several soft bowel movements to multiple watery episodes daily. In general, fever, nausea, vomiting, and anorexia were absent. One distinguishing feature was the rather protracted course of diarrhoea in patients 1, 2, 4, and 6, which is uncharacteristic of viral gastroenteritis.
Although it has been suggested that the diagnosis of candida enteritis requires barium studies and sigmoidoscopy to rule out other causes,3 the rapid response to nystatin therapy may serve as a diagnostic tool. The artiology may be suggested by stool cultures containing candida, but, as a rule, the media used routinely for the isolation of intestinal bacteria do not favour growth of candida. Certain intestinal flora, especially Enterobacteriaceae and lactobacilli, inhibit the growth of candida4 Also, routine cultures may be discarded before significant candida growth occurs. Direct microscopic examination of the stool, susin saline or iodine, gives more precise information. In all cases from the present report, yeast forms, with budding and often mycelial forms, were predominant. Although Kozinn et awl. suggest mycelial fomation should be present if pathogenicity is to be assumed, candida may be parasitic in the yeast phase, and mycelial-phase growth is not always evidence of pathogenicity.6 In fact, in both manand laboratory animals,’ a large quantity of yeast when swallowed can infiltrate to the bloodstream via persorption and cause symptoms of fungaemia before tissue invasion and subsequent multiplication would have time to occur. The serological evidence for tissue invasion by candida-the presence of
pended PATIENTS WITH DIARRHOEA CAUSED BY OVERGROWTH OF CANDIDA
*
precipitin or agglutinin antibodies,9 was negative in two of our patients tested. Although not a significant number, this suggests that actual tissue invasion may
N.D.=not done.
not
examination was normal. Stool culture was negative for enteric pathogens but Candida albicans grew. A stool specimen examined for ova and parasites contained numerous yeast cells per high-power field. On the 4th day of a 1-week course of nystatin, 500 000 units orally three times daily, symptoms
Physical
disappeared.
be necessary for the
occurrence
cases, stools must be examined for
tured for enteric pathogens before dida as the aetiological agent.
of diarrhoea. In all parasites and cul-
incriminating
can-
Nystatin, 500 000 - 1000 000 units by mouth three times daily, should cause regression of symptoms within 72 hours. Treatment should then be continued for 7-10 If nystatin has no effect on the diarrhoea, then other causes should be more fully explored.
days. Data
on
these six
cases are
summarised in the
accom-
panying table. Discussion The presence of candida in faeces of persons with no underlying disease has invariably been considered nonpathogenic. The present six cases, however, seem to confirm the entity of "candida diarrhoea" in adults. The patients were not debilitated; five of the six had no underlying disease; stool cultures were negative for enteric pathogens; and no parasites were found on multiple examinations. Their rapid response to nystatin treatment was most striking. Despite the duration of symptoms before therapy, all had a return to normal bowel movements within 3-4 days of receiving oral nys-
Requests for reprints should be addressed to V. F. G., Georgeto-Ar, University Hospital 3800 Reservoir Road NW, Washington D.C 20007, U.S.A. REFERENCES 1. 2.
Eras, P., Goldstein, M. J., Sherlock, P. Medicine, Baltimore, 1972, 51, 367 Cohen, R., Roth, F. J., Delgado, E., Ahearn, D. G., Kaiser, M. N. New Engl,
J. Med. 1969, 280, 638. 3. Brabander, J. O., Blank, F., Butas, C. A. Can. med Ass.J. 1957, 77, 478 4. Holt, R. J., Newman, R. L. J. clin. Path. 1967, 20, 80. 5. Kozinn, P. J., Taschdjian, C. L. Pediatrics, Springfield, 1962, 30, 71 6. Winner, H. I. Br. J. Derm. 1969, 81, suppl. 1, p. 62. 7. Krause, W., Matheis, H., Wulf, K. Lancet, 1969, i, 598. 8. Stone, H. H., Kolb, L. D., Currie, C. A., Geheber, C. E., Cuzzell, J. Z Ann. Surg. 1974, 179, 697. 9. Taschdjian, C., Kozinn, P. J., Cuesta, M. B., Toni, E. F. Am. J. clin Path. 1972, 57, 195.
