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Pneumocystis carinii pneumonia despite prophylaxis in children with human immunodeficiency virus infection
992
Clinical and laboratory observations
The Journal of Pediatrics December 1991
Pneumocystis carinii pneumonia despite prophylaxis in children with human immunodeficiency virus infection Brigitta U. Mueller, MD, Karina M. Butler, MB,BCh,Robert N. Husson, MD, and Philip A. Pizzo, MD From the Pediatric Branch of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Before the widespread use of prophylaxis against Pneumocystis carinii infection and antiretroviral treatment, almost two thirds of the children infected with the human immunodeficiency virus eventually had P. carinii pneumonia, and the mortality rate in children under the age of 1 year exceeded 60%. 1, 2 The National Pediatric H I V Resource Center Working Group, in conjunction with the Centers for Disease Control and U.S. Public Health Service, has recently published guidelines for PCP prophylaxis based on age-dependent changes in the patients' CD4 count or percentage. 3"6 Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis, with pentamidine and dapsone as alternatives for patients unable to tolerate T M P / S M X . 3, 7 Although these agents are highly effective, clinical failures can occur. We highlight one case and note six additional "breakthrough" infections, underscoring the need for physicians to continue to include PCP in the differential diagnosis of a child with respiratory compromise, even though the patient may be receiving PCP prophylaxis. CASE REPORT
A 20-month-old white girl was hospitalized for tachypnea and increasing lethargy. She had been born to an intravenous drug-using mother and had been placed in a foster home within 5 days of birth. At the age of 9 months she had persistent oral candidiasis and began to lose developmental milestones. Human immunodeficiency virus antibody was detected by enzyme-linked immunosorbent assay and Western blot, the CD4 count was 0.571 x 10 9 cells/mm 3, and serum p24 antigen was 773 pg/ml. The patient was given PCP prophylaxis with TMP/SMX (tr!metboprim, 150 mg/m 2 per day, and sulfamethoxazole, 750 mg/m 2 per day, given orally in two divided doses on 3 consecutive days each week). At 13 months of age she was referred to the National Cancer Institute and enrolled in a previously described phase I/II study of dideoxyinosine, 8 at a dosage of 120 mg/m 2 per day given orally in three divided doses. After 4 months of treatment, the dose of ddI was increased to 360 mg/m 2 per day because of progressive encephalopathy, including increased spasticity and right arm weakness. The patient continued
Submitted for publication May 13, 199l; accepted June 20, 1991. Reprint requests: P. A. Pizzo, MD, Pediatric Branch, National Cancer Institute, Bldg. 10, Room 13N240, Bethesda, MD 20892. 9/26/31949
to receive prophylactic TMP/SMX therapy. During a routine clinic visit, after 24 weeks of ddI therapy, her foster parents reported an increase in lethargy during the preceding days. Physical examination revealed tachypnea, which led to hospitalization. The child was afebrile and alert but somewhat fatigued and listless, and a radiograph of the chest showed an interstitial process that was unchanged from previous examinations. The patient had received the third day of the 3-days-per-week TMP/SMX prophylaxis on the day of admission. She was given ceftriaxone (100 mg/kg per day intravenously), and an induced sputum specimen was obtained within 24 hours. Toluidine blue stain revealed the presence of pneumocysts. Arterial blood gas values were as follows: pH 7.41; ddI HIV PCP TMP/SMX
Dideoxyinosine Human immunodeficiency virus Pneumocystis carinii pneumonia Trimethoprim-sulfametb oxazole
partial pressure of carbon dioxide, 32 mm Hg; partial pressure of oxygen, 59 mm Hg; and oxygen saturation, 91%. The patient was given pentamidine (4 mg/kg per day intravenously) and placed under an oxygen tent with 50% oxygen. The sulfamethoxazole level of a serum specimen drawn approximately 24 hours after the last oral dose was 47 /xg/ml, confirming recent compliance with the prophylactic regimen. The patient received intensive supportive care but had progressive respiratory deterioration and required ventilatory support. Pneumocysts were detected in a tracheal aspirate obtained 7 days after pentamidine therapy was started. The patient's pulmonary status did not improve despite the addition of trimetrexate, maximal ventilatory support, and a 48-hour course of dexamethasone. After 26 days of treatment, the patient died. At autopsy, extensive and diffuse alveolar damage was noted, but no pneumocysts or other infectious agents were demonstrated. RESULTS In addition to the patient described above, we have observed five other children who had PCP while receiving prophylaxis (Table). Some children had had previous episodes of P C P but were not given prophyIaxis because either it Was not known, at the time they were being treated, to be beneficial or because their enrollment in a phase I study did not allow for concurrent medications. Nonetheless, three of seven episodes of PCP occurred despite prophylaxis with orally administered T M P / S M X , two others during monthly
Volume 119 Number 6
Clinical and laboratory observations
993
Table. PCP while receiving prophylaxis Age (yr)
CD4 count (cells/mm 3)
0.5 (9/87) 1.2 (06/88) 2.1 (6/89)
100 6 5
2.8 (1/90)
10
7.5 (5/88)
0
8 (11/88)
14
8.8 (09/89)
0
10.4 (4/91)
0
3 Vertical
1.2 (6/89)
372
4 Vertical
1.7 (10/89)
217
5 Transfusion
18 (5/90)
3
9 (9/89)
4
No.
MoA
1 Vertical
2 Vertical
6 Vertical
Prophylaxis*
Antiretroviral therapy*
Outcome comments
None None AZT orally (since 9/88) IV pentamidine ddI orally Survived PCP; (since 8/89) died of sepsis 1/91 None ddC orally (since 4/88) None ddC/AZT orally PCP not proved (since 12/88) Oral TMP/SMX ddI orally (since 10/89) IV pentamidine AZT continuous Died of PCP infusion (since 11/90) ddI orally Alive Oral TMP/SMX (since 9/89) ddI orally Died of severe PCP Oral TMP/SMX (since 4/89) (see text for details) Monthly aerosolized AZT orally Alive pentamidine (since 3/89) Alive; started AZT; Monthly aerosolized None pentamidine switched later to ddI
Subsequent prophylaxis
None None None
Monthly IV pentamidine; started TMP/SMX
TMP/SMX; IV pentamidine
TMP/SMX
Dapsone/pyrimethamine Aerosolized pentamidine
MoA, Mode of acquisition;AZT, zidovudine;IV, intravenous;ddC, dideoxycytidine.
*At PCP diagnosis. aerosolized pentamidine therapy, and two during intravenous treatment with pentamidine every 4 weeks. DISCUSSION The most commonly recommended prophylactic regimen or PCP is T M P / S M X (trimethoprim, 150 m g / m 2 per day, and sulfamethoxazole, 750 m g / m 2 per day) given orally twice daily on 3 consecutive days, 3, 7, 9 a schedule that has been used successfully for patients with cancer. Although some studies support the efficacy of T M P / S M X with virtually no occurrences of PCP, 1~ our experience demonstrates that breakthroughs can occur. Although the data on patients with cancer did not show any difference in the incidence of PCP between patients receiving T M P / S M X daily and patients being treated only three times a week, 9 all three of our patients with PCP who were given T M P / SMX prophylaxis received the drug on 3 consecutive days weekly, There is always a question of compliance with an oral drug regimen, but in the patient reported above we were able to demonstrate an adequate drug level 24 hours after the last dose was reportedly given by the foster parents, who were also known to be very compliant with treatment. Although the numbers are too small to compare incidence rates of different regimens, these examples show that PCP can occur despite standard prophylactic regimens. The clinical presentation of PCP differs markedly be-
tween patients with acquired immune deficiency syndrome and other patients with immunosuppression. 11, 12 In patients with acquired immune deficiency syndrome it is not uncommon to see an insidious and prolonged onset with nonspecific symptoms such as mild cough, dyspnea on exertion, fatigue, and weight loss. Children are often restless, have tachypnea and tachycardia, and sometimes have fever and a dry, nonproductive cough. Chest pain was the only clinical symptom in one of our patients. As the disease progresses, children often have rapidly increasing evidence of cyanosis, hypoxemia, intercostal and subcostal retractions, nasal flaring, and rales) 3 Studies of healthy children have shown that there is a marked age-dependent difference in CD4 lymphocyte number, with much higher normal values in young children than in adults. 5 This may explain why PCP can occur in children with CD4 counts greater than 200 cells/ram3, 4, 6, 14the level associated with an increased risk in adults.iS Therefore new guidelines for children with HIV infections have been developed recently) As the group of patients receiving prophylactic agents becomes larger, it is likely that the incidence of atypical presentations or breakthrough infections will increase. The clinician taking care of a child with an HIV infection who has respiratory symptoms must maintain a high index of suspicion for the possibility of PCP, even in children who are receiving PCP prophylaxis.
994
Clinical and laboratory observations
REFERENCES
1. Bernstein LJ, Bye MR, Rubinstein A. Prognostic factors and life expectancy in children with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia. Am J Dis Child 1989;143:775-8. 2. Scott GB, Hutto C, Makuch RW, et al. Survival in children with perinatally acquired human immunodeficiencyvirus type 1 infection. N Engl J Med 1989;32l:1791-6. 3. Centers for DiseaseControl. Guidelinesfor prophylaxisagainst Pneumocystis carinii pneumonia for children with human immunodefieiencyvirus infection/exposure. MMWR 1991;40:t13. 4. Kovacs A, Frederick T, Church J, et al. CD4 T-lymphocsee counts and Pneumocystis carinii pneumonia in pediatric HIV infection. JAMA 1991;265:1698-703. 5. Yanase Y, Tango T, Okumura K, et al. Lymphocyte subsets identifiedby monoclonalantibodies in healthy children. Pediatr Res 1986;20:1147-51. 6. Connor E, Bagarazzi M, McSherry G, et al. Clinical and laboratory correlates of Pneumocystis carinii pneumonia in children infected with HIV. JAMA t991;265:1693-7. 7. Masur H. Preventionof Pneumocystis carinii pneumonia.Rev Infect Dis 1989;11:S1664-8. 8. Butler KM, Husson RN, Balis FM, et al. Dideoxyinosinein children with symptomatic human immunodeficiencyvirus infection. N Engl J Med 1991;324:137-44.
The Journal of Pediatrics December 1991
9. Hughes WT, Rivera GK, Schell MJ, et al. Successful intermittent chemoprophylaxisfor Pneumocystis carinii pneumonitis. N Engl J Med 1987;316:1627-32. 10. Fischl MA, Dickinson GM, LaVoie J. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988; 259:1185-9. 1l. Kovacs JA, Hiemenz JW, Maeher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiencysyndrome and patients with other immunodeficiencies.Ann Intern Med 1984;100:663-71. 12. DeLorenzo LJ, Huang CT, Maguire GP, Stone DJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987;91:323-7. 13. Hughes WT. Pneumocystis carinii pneumonia. In: Pizzo PA, Wilfert CA, eds. Pediatric AIDS. Baltimore: Williams & Wilkins, 1991:288-98. 14. LeibovitzE, Rigaud M, Pollack H, et al. Pneumocystis carinii pneumonia in infants infected with the human immunodeficiency virus with more than 450 CD4 T-lymphocytes per cubic millimeter. N Engl J Med 1990;323:531-3. 15. Phair J, Munoz A, Detels R, et aL The risk of Pneumocystis earinii pneumonia among men infected with human immunodeficiency virus type 1. N Engl J Med 1990;322:161-5.
Cyclosporine treatment of severe ulcerative colitis in children W. R. Treem, MD, P. M. Davis, RN, a n d J. S. Hyams, MD From the Division of Pediatric Gastroenterology and Nutrition, Hartford Hospital, Hartford, Connecticut, and the Department of Pediatrics, University of Connecticut School of Medicine, Farmington
Immunosuppressive therapy has been used in patients with inflammatory bowel disease refractory to corticosteroids and in those who are dependent on high doses of corticosteroids for adequate control of symptoms. Immunosuppressire agents used in children with inflammatory bowel disease include azathioprine and 6-mercaptopurine, but their therapeutic effects take weeks to months.1 In patients with severe ulcerative colitis, this delay abrogates the potential usefulness of these agents. Recent reports have described a beneficial response to cyclosporine in adults with Crohn disease or ulcerative cotitis. 2, 3 Six children with Submitted for publication June 14, 1991; accepted Aug. 8, 1991. Reprint requests: William R. Treem, MD, Division of Pediatric Gastroenterology, Hartford Hospital, 80 Seymour St., Hartford, CT 06115. 9/26/33005
severe ulcerative colitis refractory to standard medical management, including two children previously described, 4 were treated with cyclosporine. We describe their early and long-term responses. METHODS Six children (four boys) aged 10 to 17 years (mean age 14.3 years) were judged to have severe ulcerative colitis5 on the basis of the following criteria documented at the time of admission to the hospital: (1) more than five grossly bloody diarrheal stools per day, (2) hematocrit value less than 32%, (3) serum albumin concentration less than 3.0 gm/dl, (4) oral temperature greater than 38 ~ C, and (5) resting pulse rate more than 90 beats/rain. Three of the children had a history of mild episodes of bloody diarrhea and had ulcerative colitis diagnosed 4 to 24 months before this episode of severe colitis; in the three other children, the
Clinical and laboratory observations
The Journal of Pediatrics December 1991
Pneumocystis carinii pneumonia despite prophylaxis in children with human immunodeficiency virus infection Brigitta U. Mueller, MD, Karina M. Butler, MB,BCh,Robert N. Husson, MD, and Philip A. Pizzo, MD From the Pediatric Branch of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Before the widespread use of prophylaxis against Pneumocystis carinii infection and antiretroviral treatment, almost two thirds of the children infected with the human immunodeficiency virus eventually had P. carinii pneumonia, and the mortality rate in children under the age of 1 year exceeded 60%. 1, 2 The National Pediatric H I V Resource Center Working Group, in conjunction with the Centers for Disease Control and U.S. Public Health Service, has recently published guidelines for PCP prophylaxis based on age-dependent changes in the patients' CD4 count or percentage. 3"6 Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis, with pentamidine and dapsone as alternatives for patients unable to tolerate T M P / S M X . 3, 7 Although these agents are highly effective, clinical failures can occur. We highlight one case and note six additional "breakthrough" infections, underscoring the need for physicians to continue to include PCP in the differential diagnosis of a child with respiratory compromise, even though the patient may be receiving PCP prophylaxis. CASE REPORT
A 20-month-old white girl was hospitalized for tachypnea and increasing lethargy. She had been born to an intravenous drug-using mother and had been placed in a foster home within 5 days of birth. At the age of 9 months she had persistent oral candidiasis and began to lose developmental milestones. Human immunodeficiency virus antibody was detected by enzyme-linked immunosorbent assay and Western blot, the CD4 count was 0.571 x 10 9 cells/mm 3, and serum p24 antigen was 773 pg/ml. The patient was given PCP prophylaxis with TMP/SMX (tr!metboprim, 150 mg/m 2 per day, and sulfamethoxazole, 750 mg/m 2 per day, given orally in two divided doses on 3 consecutive days each week). At 13 months of age she was referred to the National Cancer Institute and enrolled in a previously described phase I/II study of dideoxyinosine, 8 at a dosage of 120 mg/m 2 per day given orally in three divided doses. After 4 months of treatment, the dose of ddI was increased to 360 mg/m 2 per day because of progressive encephalopathy, including increased spasticity and right arm weakness. The patient continued
Submitted for publication May 13, 199l; accepted June 20, 1991. Reprint requests: P. A. Pizzo, MD, Pediatric Branch, National Cancer Institute, Bldg. 10, Room 13N240, Bethesda, MD 20892. 9/26/31949
to receive prophylactic TMP/SMX therapy. During a routine clinic visit, after 24 weeks of ddI therapy, her foster parents reported an increase in lethargy during the preceding days. Physical examination revealed tachypnea, which led to hospitalization. The child was afebrile and alert but somewhat fatigued and listless, and a radiograph of the chest showed an interstitial process that was unchanged from previous examinations. The patient had received the third day of the 3-days-per-week TMP/SMX prophylaxis on the day of admission. She was given ceftriaxone (100 mg/kg per day intravenously), and an induced sputum specimen was obtained within 24 hours. Toluidine blue stain revealed the presence of pneumocysts. Arterial blood gas values were as follows: pH 7.41; ddI HIV PCP TMP/SMX
Dideoxyinosine Human immunodeficiency virus Pneumocystis carinii pneumonia Trimethoprim-sulfametb oxazole
partial pressure of carbon dioxide, 32 mm Hg; partial pressure of oxygen, 59 mm Hg; and oxygen saturation, 91%. The patient was given pentamidine (4 mg/kg per day intravenously) and placed under an oxygen tent with 50% oxygen. The sulfamethoxazole level of a serum specimen drawn approximately 24 hours after the last oral dose was 47 /xg/ml, confirming recent compliance with the prophylactic regimen. The patient received intensive supportive care but had progressive respiratory deterioration and required ventilatory support. Pneumocysts were detected in a tracheal aspirate obtained 7 days after pentamidine therapy was started. The patient's pulmonary status did not improve despite the addition of trimetrexate, maximal ventilatory support, and a 48-hour course of dexamethasone. After 26 days of treatment, the patient died. At autopsy, extensive and diffuse alveolar damage was noted, but no pneumocysts or other infectious agents were demonstrated. RESULTS In addition to the patient described above, we have observed five other children who had PCP while receiving prophylaxis (Table). Some children had had previous episodes of P C P but were not given prophyIaxis because either it Was not known, at the time they were being treated, to be beneficial or because their enrollment in a phase I study did not allow for concurrent medications. Nonetheless, three of seven episodes of PCP occurred despite prophylaxis with orally administered T M P / S M X , two others during monthly
Volume 119 Number 6
Clinical and laboratory observations
993
Table. PCP while receiving prophylaxis Age (yr)
CD4 count (cells/mm 3)
0.5 (9/87) 1.2 (06/88) 2.1 (6/89)
100 6 5
2.8 (1/90)
10
7.5 (5/88)
0
8 (11/88)
14
8.8 (09/89)
0
10.4 (4/91)
0
3 Vertical
1.2 (6/89)
372
4 Vertical
1.7 (10/89)
217
5 Transfusion
18 (5/90)
3
9 (9/89)
4
No.
MoA
1 Vertical
2 Vertical
6 Vertical
Prophylaxis*
Antiretroviral therapy*
Outcome comments
None None AZT orally (since 9/88) IV pentamidine ddI orally Survived PCP; (since 8/89) died of sepsis 1/91 None ddC orally (since 4/88) None ddC/AZT orally PCP not proved (since 12/88) Oral TMP/SMX ddI orally (since 10/89) IV pentamidine AZT continuous Died of PCP infusion (since 11/90) ddI orally Alive Oral TMP/SMX (since 9/89) ddI orally Died of severe PCP Oral TMP/SMX (since 4/89) (see text for details) Monthly aerosolized AZT orally Alive pentamidine (since 3/89) Alive; started AZT; Monthly aerosolized None pentamidine switched later to ddI
Subsequent prophylaxis
None None None
Monthly IV pentamidine; started TMP/SMX
TMP/SMX; IV pentamidine
TMP/SMX
Dapsone/pyrimethamine Aerosolized pentamidine
MoA, Mode of acquisition;AZT, zidovudine;IV, intravenous;ddC, dideoxycytidine.
*At PCP diagnosis. aerosolized pentamidine therapy, and two during intravenous treatment with pentamidine every 4 weeks. DISCUSSION The most commonly recommended prophylactic regimen or PCP is T M P / S M X (trimethoprim, 150 m g / m 2 per day, and sulfamethoxazole, 750 m g / m 2 per day) given orally twice daily on 3 consecutive days, 3, 7, 9 a schedule that has been used successfully for patients with cancer. Although some studies support the efficacy of T M P / S M X with virtually no occurrences of PCP, 1~ our experience demonstrates that breakthroughs can occur. Although the data on patients with cancer did not show any difference in the incidence of PCP between patients receiving T M P / S M X daily and patients being treated only three times a week, 9 all three of our patients with PCP who were given T M P / SMX prophylaxis received the drug on 3 consecutive days weekly, There is always a question of compliance with an oral drug regimen, but in the patient reported above we were able to demonstrate an adequate drug level 24 hours after the last dose was reportedly given by the foster parents, who were also known to be very compliant with treatment. Although the numbers are too small to compare incidence rates of different regimens, these examples show that PCP can occur despite standard prophylactic regimens. The clinical presentation of PCP differs markedly be-
tween patients with acquired immune deficiency syndrome and other patients with immunosuppression. 11, 12 In patients with acquired immune deficiency syndrome it is not uncommon to see an insidious and prolonged onset with nonspecific symptoms such as mild cough, dyspnea on exertion, fatigue, and weight loss. Children are often restless, have tachypnea and tachycardia, and sometimes have fever and a dry, nonproductive cough. Chest pain was the only clinical symptom in one of our patients. As the disease progresses, children often have rapidly increasing evidence of cyanosis, hypoxemia, intercostal and subcostal retractions, nasal flaring, and rales) 3 Studies of healthy children have shown that there is a marked age-dependent difference in CD4 lymphocyte number, with much higher normal values in young children than in adults. 5 This may explain why PCP can occur in children with CD4 counts greater than 200 cells/ram3, 4, 6, 14the level associated with an increased risk in adults.iS Therefore new guidelines for children with HIV infections have been developed recently) As the group of patients receiving prophylactic agents becomes larger, it is likely that the incidence of atypical presentations or breakthrough infections will increase. The clinician taking care of a child with an HIV infection who has respiratory symptoms must maintain a high index of suspicion for the possibility of PCP, even in children who are receiving PCP prophylaxis.
994
Clinical and laboratory observations
REFERENCES
1. Bernstein LJ, Bye MR, Rubinstein A. Prognostic factors and life expectancy in children with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia. Am J Dis Child 1989;143:775-8. 2. Scott GB, Hutto C, Makuch RW, et al. Survival in children with perinatally acquired human immunodeficiencyvirus type 1 infection. N Engl J Med 1989;32l:1791-6. 3. Centers for DiseaseControl. Guidelinesfor prophylaxisagainst Pneumocystis carinii pneumonia for children with human immunodefieiencyvirus infection/exposure. MMWR 1991;40:t13. 4. Kovacs A, Frederick T, Church J, et al. CD4 T-lymphocsee counts and Pneumocystis carinii pneumonia in pediatric HIV infection. JAMA 1991;265:1698-703. 5. Yanase Y, Tango T, Okumura K, et al. Lymphocyte subsets identifiedby monoclonalantibodies in healthy children. Pediatr Res 1986;20:1147-51. 6. Connor E, Bagarazzi M, McSherry G, et al. Clinical and laboratory correlates of Pneumocystis carinii pneumonia in children infected with HIV. JAMA t991;265:1693-7. 7. Masur H. Preventionof Pneumocystis carinii pneumonia.Rev Infect Dis 1989;11:S1664-8. 8. Butler KM, Husson RN, Balis FM, et al. Dideoxyinosinein children with symptomatic human immunodeficiencyvirus infection. N Engl J Med 1991;324:137-44.
The Journal of Pediatrics December 1991
9. Hughes WT, Rivera GK, Schell MJ, et al. Successful intermittent chemoprophylaxisfor Pneumocystis carinii pneumonitis. N Engl J Med 1987;316:1627-32. 10. Fischl MA, Dickinson GM, LaVoie J. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988; 259:1185-9. 1l. Kovacs JA, Hiemenz JW, Maeher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiencysyndrome and patients with other immunodeficiencies.Ann Intern Med 1984;100:663-71. 12. DeLorenzo LJ, Huang CT, Maguire GP, Stone DJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987;91:323-7. 13. Hughes WT. Pneumocystis carinii pneumonia. In: Pizzo PA, Wilfert CA, eds. Pediatric AIDS. Baltimore: Williams & Wilkins, 1991:288-98. 14. LeibovitzE, Rigaud M, Pollack H, et al. Pneumocystis carinii pneumonia in infants infected with the human immunodeficiency virus with more than 450 CD4 T-lymphocytes per cubic millimeter. N Engl J Med 1990;323:531-3. 15. Phair J, Munoz A, Detels R, et aL The risk of Pneumocystis earinii pneumonia among men infected with human immunodeficiency virus type 1. N Engl J Med 1990;322:161-5.
Cyclosporine treatment of severe ulcerative colitis in children W. R. Treem, MD, P. M. Davis, RN, a n d J. S. Hyams, MD From the Division of Pediatric Gastroenterology and Nutrition, Hartford Hospital, Hartford, Connecticut, and the Department of Pediatrics, University of Connecticut School of Medicine, Farmington
Immunosuppressive therapy has been used in patients with inflammatory bowel disease refractory to corticosteroids and in those who are dependent on high doses of corticosteroids for adequate control of symptoms. Immunosuppressire agents used in children with inflammatory bowel disease include azathioprine and 6-mercaptopurine, but their therapeutic effects take weeks to months.1 In patients with severe ulcerative colitis, this delay abrogates the potential usefulness of these agents. Recent reports have described a beneficial response to cyclosporine in adults with Crohn disease or ulcerative cotitis. 2, 3 Six children with Submitted for publication June 14, 1991; accepted Aug. 8, 1991. Reprint requests: William R. Treem, MD, Division of Pediatric Gastroenterology, Hartford Hospital, 80 Seymour St., Hartford, CT 06115. 9/26/33005
severe ulcerative colitis refractory to standard medical management, including two children previously described, 4 were treated with cyclosporine. We describe their early and long-term responses. METHODS Six children (four boys) aged 10 to 17 years (mean age 14.3 years) were judged to have severe ulcerative colitis5 on the basis of the following criteria documented at the time of admission to the hospital: (1) more than five grossly bloody diarrheal stools per day, (2) hematocrit value less than 32%, (3) serum albumin concentration less than 3.0 gm/dl, (4) oral temperature greater than 38 ~ C, and (5) resting pulse rate more than 90 beats/rain. Three of the children had a history of mild episodes of bloody diarrhea and had ulcerative colitis diagnosed 4 to 24 months before this episode of severe colitis; in the three other children, the