Refer to: Hallett JJ, Fickenscher LG, Ablin AR: Pneumocystis carinii pneumonia in children. West J Med 126:441-444, Jun 1977
Pneumocystis Carinii Pneumonia in Children JOSEPH J. HALLETT, MD; LAWRENCE G. FICKENSCHER, MD, and ARTHUR R. ABLIN, MD, San Francisco
From a retrospective study at the University of California, San Francisco, Medical Center, it is evident that pneumocystic carinii pneumonia is being seen more frequently as a secondary complication to the use of immunosuppressive drugs. This disease presents with nonspecific respiratory symptoms, therefore a high degree of suspicion and knowledge of the population at risk are necessary for an early diagnosis. Except for x-ray films of the chest, physical and laboratory studies are of minimal diagnostic value. In a patient with compromised immune defenses and respiratory distress, bilateral diffuse reticular infiltrates seen on a film of the chest are highly suggestive of pneumocystis carinii pneumonia. The diagnosis should be confirmed histologically because a variety of pathogens can cause these findings and each requires a specific treatment. At our institution, open thoracotomy is the method of choice for obtaining a lung biopsy specimen. Pentamidine isothionate is moderately effective against this usually fatal disease, but its effectiveness depends on beginning treatment early in the illness. PNEUMOCYSTIS CARINII is an opportunistic protozoan which causes interstitial pneumonia. Originally, it was described as a disease of premature and marasmic infants, but it is now being reported with increasing frequency in patients who have been immunosuppressed and are immunodeficient.'-4 With the rise in transplantation and use of chemotherapy, the number of immunosuppressed patients residing in local communities will increase. There they will run the risk of the initial symptoms of pneumocystis carinii pneumonia developing. Our particular concern is for the pediatric age group, in which the incidence of this disease is highest.5 Since successful treatment depends on early diagnosis, it is important From the Department of Pediatrics, University of California, San Francisco. Submitted September 20, 1976. Reprint requests to: Arthur R. Ablin, MD, Department of Pediatrics, Room 650 M, University of California, San Francisco, San Francisco, CA 94143.
that clinicians be aware of this growing problem. This report of 13 pediatric cases emphasizes those factors that may aid in early diagnosis.
Patients and Results of Therapy Patients From a search of medical records at the University of California, San Francisco, Medical Center from October 1971 to February 1975, we found 13 patients (nine boys, four girls), ranging in age from 6 months to 17 years, in whom the diagnosis of pneumocystis carinii pneumonia had been made (Table 1). Seven of eight patients with acute lymphoblastic leukemia were in hematologic remission when pneumocystis carinii pneumonia developed; five of them were in the oneto two-week period following prophylactic central nervous system treatment by irradiation or intra-
thecally given methotrexate (or both) and predTHE WESTERN JOURNAL OF MEDICINE
441
PNEUMOCYSTIS CARINII PNEUMONIA
nisone withdrawal; two were within one week of termination of central nervous system prophylaxis; one had just finished a six-week course of vincristine and prednisone which did not produce remission. In two patients renal transplants had been carried out and immunosuppressive drugs were being given; one was doing well eight months after transplant when pneumocystis carinii pneumonia developed, in the other it developed two weeks after treatment was given for rejection of the transplant. One patient with systemic lupus erythematosus had been receiving steroids for ten years before development of the disease, another with combined immunodeficiency had been treated with antibiotics for frequent infections. A patient with neuroblastoma was in remission while on intensive chemotherapy but died suddenly at home following a short febrile illness. Postmortem examination established pneumocystis as the cause of death.
Deaths Of the three patients who died (Table 1), one died unexpectedly at home two days after an intensive chemotherapy regimen for neuroblastoma was completed. In the two patients in hospital, the time between symptoms and therapy was 10 and 12 days. There was an initial improvement with pentamidine therapy, but on the fifth and seventh days of treatment, respectively, the patients became febrile and tachypneic again. No improvement at any time during treatment was shown on x-ray studies of the chest. Admission to Hospital At the time of admission to hospital (Table 2) all patients were febrile (median temperature, 38.80C) and had elevated respiratory rates (median, 48 per minute). Rales, nasal flaring and intercostal retractions were present in three. Neither the leukocyte count (600 to 7,400 cells per cu mm; median 4,900 cells per cu mm) nor the
TABLE 2.-Concurrent Findings on Admission in 13 Patients with Pneumocystis Carinii Number Patients
Findings
Clinical Fever ............ ....... Nonproductive cough ............ Tachypnea ................... Laboratory Chest roentgenograph ............ Bilateral infiltrates ......... 10 Bronchial thickening ........ 1 1 Normal ................. Leukocyte count normal ..........
Acute lymphoblastic leukemia Renal transplantation .........
1-5
5
.
..
Systemic lupus erythematosus ... Combined immunodeficiency .. 1 Neuroblastoma ............1 TOTAL
442
.........
JUNE 1977 * 126 * 6
......
1
10
Symptoms The most common symptoms were fever, tachypnea and a nonproductive cough which occurred from one to seven days before admission to hospital. Anorexia, diarrhea, vomiting and listlessness were reported in younger children, whereas older children presented with dyspnea and substernal pain. Tachycardia and signs of respiratory distress (nasal flaring, intercostal or suprasternal retractions) were also present, cyanosis less commonly. In spite of respiratory distress, there were no physical findings on auscultation of the chest in ten patients, although in three rales were present.
Age (years)
Pneumocystis Carinii Pneumonia in Children JOSEPH J. HALLETT, MD; LAWRENCE G. FICKENSCHER, MD, and ARTHUR R. ABLIN, MD, San Francisco
From a retrospective study at the University of California, San Francisco, Medical Center, it is evident that pneumocystic carinii pneumonia is being seen more frequently as a secondary complication to the use of immunosuppressive drugs. This disease presents with nonspecific respiratory symptoms, therefore a high degree of suspicion and knowledge of the population at risk are necessary for an early diagnosis. Except for x-ray films of the chest, physical and laboratory studies are of minimal diagnostic value. In a patient with compromised immune defenses and respiratory distress, bilateral diffuse reticular infiltrates seen on a film of the chest are highly suggestive of pneumocystis carinii pneumonia. The diagnosis should be confirmed histologically because a variety of pathogens can cause these findings and each requires a specific treatment. At our institution, open thoracotomy is the method of choice for obtaining a lung biopsy specimen. Pentamidine isothionate is moderately effective against this usually fatal disease, but its effectiveness depends on beginning treatment early in the illness. PNEUMOCYSTIS CARINII is an opportunistic protozoan which causes interstitial pneumonia. Originally, it was described as a disease of premature and marasmic infants, but it is now being reported with increasing frequency in patients who have been immunosuppressed and are immunodeficient.'-4 With the rise in transplantation and use of chemotherapy, the number of immunosuppressed patients residing in local communities will increase. There they will run the risk of the initial symptoms of pneumocystis carinii pneumonia developing. Our particular concern is for the pediatric age group, in which the incidence of this disease is highest.5 Since successful treatment depends on early diagnosis, it is important From the Department of Pediatrics, University of California, San Francisco. Submitted September 20, 1976. Reprint requests to: Arthur R. Ablin, MD, Department of Pediatrics, Room 650 M, University of California, San Francisco, San Francisco, CA 94143.
that clinicians be aware of this growing problem. This report of 13 pediatric cases emphasizes those factors that may aid in early diagnosis.
Patients and Results of Therapy Patients From a search of medical records at the University of California, San Francisco, Medical Center from October 1971 to February 1975, we found 13 patients (nine boys, four girls), ranging in age from 6 months to 17 years, in whom the diagnosis of pneumocystis carinii pneumonia had been made (Table 1). Seven of eight patients with acute lymphoblastic leukemia were in hematologic remission when pneumocystis carinii pneumonia developed; five of them were in the oneto two-week period following prophylactic central nervous system treatment by irradiation or intra-
thecally given methotrexate (or both) and predTHE WESTERN JOURNAL OF MEDICINE
441
PNEUMOCYSTIS CARINII PNEUMONIA
nisone withdrawal; two were within one week of termination of central nervous system prophylaxis; one had just finished a six-week course of vincristine and prednisone which did not produce remission. In two patients renal transplants had been carried out and immunosuppressive drugs were being given; one was doing well eight months after transplant when pneumocystis carinii pneumonia developed, in the other it developed two weeks after treatment was given for rejection of the transplant. One patient with systemic lupus erythematosus had been receiving steroids for ten years before development of the disease, another with combined immunodeficiency had been treated with antibiotics for frequent infections. A patient with neuroblastoma was in remission while on intensive chemotherapy but died suddenly at home following a short febrile illness. Postmortem examination established pneumocystis as the cause of death.
Deaths Of the three patients who died (Table 1), one died unexpectedly at home two days after an intensive chemotherapy regimen for neuroblastoma was completed. In the two patients in hospital, the time between symptoms and therapy was 10 and 12 days. There was an initial improvement with pentamidine therapy, but on the fifth and seventh days of treatment, respectively, the patients became febrile and tachypneic again. No improvement at any time during treatment was shown on x-ray studies of the chest. Admission to Hospital At the time of admission to hospital (Table 2) all patients were febrile (median temperature, 38.80C) and had elevated respiratory rates (median, 48 per minute). Rales, nasal flaring and intercostal retractions were present in three. Neither the leukocyte count (600 to 7,400 cells per cu mm; median 4,900 cells per cu mm) nor the
TABLE 2.-Concurrent Findings on Admission in 13 Patients with Pneumocystis Carinii Number Patients
Findings
Clinical Fever ............ ....... Nonproductive cough ............ Tachypnea ................... Laboratory Chest roentgenograph ............ Bilateral infiltrates ......... 10 Bronchial thickening ........ 1 1 Normal ................. Leukocyte count normal ..........
Acute lymphoblastic leukemia Renal transplantation .........
1-5
5
.
..
Systemic lupus erythematosus ... Combined immunodeficiency .. 1 Neuroblastoma ............1 TOTAL
442
.........
JUNE 1977 * 126 * 6
......
1
10
Symptoms The most common symptoms were fever, tachypnea and a nonproductive cough which occurred from one to seven days before admission to hospital. Anorexia, diarrhea, vomiting and listlessness were reported in younger children, whereas older children presented with dyspnea and substernal pain. Tachycardia and signs of respiratory distress (nasal flaring, intercostal or suprasternal retractions) were also present, cyanosis less commonly. In spite of respiratory distress, there were no physical findings on auscultation of the chest in ten patients, although in three rales were present.
Age (years)
