Volume 95 Number 4
B r i e f clinical and laboratory observations
produced coagulopathy, renal microangiopathy, and hemolytic anemia. ~ Our patient did not have the usual prodromal symptoms (diarrhea, vomiting, and blood stools) commonly seen in HUS of a presumed viral etiology. The features of HUS developed during acute pneumococcal sepsis, suggesting that the sepsis was causally related to the HUS. It is unlikely that the infant had two separate diseases at the same time. Pneumococcal sepsis is not rare, and why no other cases of HUS associated with it have been reported is not clear. It is possible that a genetic predisposition to HUS existed in this infant and was precipitated by pneumococcal sepsis, particularly since such predisposition has been observed in some families. ~ However, no other siblings in this family have developed HUS in the last 37 months. The histologic findings in the kidney were typical of those seen two weeks after the onset of the diseaseY S i n c e - n o deposits of immunoglobulins or complement were seen, it it unlikely that the renal damage was secondary to an immune-complex induced post-pneumococcal glomerulonephritis, although the biopsy was performed late in the course and it is possible that the deposits had disappeared. However, the finding of fibrin thrombi and platelets in capillaries is more in favor of HUS. Rarely, disseminated intravascular coagulation has occurred in pneumococcal sepsis:" Rytel e t al ~ have described two fatal cases in elderly patients, one of them asplenic. It could be argued that our patient had DIC, but
559
absence of a diffuse bleeding tendency and normal coagulation studies and fibrinogen levels are not in favor of DIC. Moreover. some intravascular coagulation does occur in patients with HUS." REFERENCES
1. Gasser VC, Gautier E~ Steck A, et al: H~imolytischUr~imiche Syndrome, Schweiz Med Wochenscbr 85:905, 1955. 2. Ray CG, Tucker VL, and Harris DJ: Enteroviruses associated with hemolytic uremic syndrome, Pediatrics 46:378, 1970. 3. Mettler NE: Isolation of microtatibote from patients with hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and from mites in the United States, N Engl J Med 281:1023, 1969. 4. Baker NM, Mills AE, and Rachman 1: Hemolytic uremic syndrome in typhoid fever, Br Med J 2:84, 1974. 5. Koster F, Levin J, Walker L, Tung KSK, Gilman RH, Rahaman MM, Majid MA, Islam S, and Williams RD: Hemolytic uremic syndrome after shigellosis: Relations to endotoxemia and circulating immune complexes, N Engl J Med 298:927, 1978. 6. Gianantonia CA: Hemolytic uremic syndrome, in Edelmann CM, editor: Pediatric kidney disease, vol 2, Boston, 1978, Little, Brown & Company, pp 724-736. 7. Kaplan ItS, Chesney RW, and Drummond KN: Hemolytic uremic syndrome in families, N Engl J Med 292:1090. 1975. 8. Rytel MW, Dee TH, Fenstenfeld JE, and Hensley CaT: Possible pathogenetic role of capsular antigens in fulminant pneumococcal disease with disseminated intravascular coagulation, Am J Med 57:889, 1974.
Pneumocystis carinii pneumonia as the presenting infection in congenital hypogammaglobulinemia Frank T. Saulsbury, M.D., Michael T. Bernstein, M.D., and Jerry A. Winkelstein, M.D.,* Baltimore, Md.
CHILDREN with congenital hypogammaglobulinemia are usually asymptomatic during the first several months of life, owing to the protection afforded by passively transferred maternal IgG. As this protection wanes, the From the Howard Hughes Medical Institute Laboratory of the Departments of Pediatrics and Microbiology, The Johns Hopkins University School of Medicine. Supported by United States Public Health Service Grant No. A1-07007. *Reprint address: Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, MD 21205.
0022-3476/79/100559 +03500.30/0 9 1979 The C. V. Mosby Co.
underlying hypogammaglobulinemia most commonly becomes manifest by an increased susceptibility to infection. Typical presenting infections in these children include pneumonia, otitis media, sepsis, and meningitis, all caused primarily by pyogenic bacteria. 1 Patients with hypogammaglobulinemia are also at risk for Pneumocystis carinii pneumonia-'; however, these children only rarely present with P. carinii pneumonia as their initial infection. This report describes two infants with congenital hypogammaglobulinemia and normal T-cell function in whom the initial infection was P. carinii pneumonia.
560
B r i e f cfinical and laboratory observations
CASE REPORTS Patient 1. The patient was the 3,240 gm male product of an uneventful gestation. He was the first born child to unrelated parents with no family history of immunodeficiency. He was well until 7 months of age when he developed a cough and intermittent fever, and was admitted to the Johns Hopkins Hospital two weeks later with severe cough, tachypnea, and cyanosis. Physical examination revealed an acutely ill, cyanotic child in respiratory distress. No rales were detected on auscultation of the lungs. A chest roentgenograln demonstrated diffuse, bilateral infiltrates. The hemoglobin was 14.6 gm/dl and the white blood cell count was 28,800/mm ~with 49% segmented neutrophils, 44% lymphocytes, and 5% monocytes. Quantitative serum immunoglobulin studies revealed an IgG of 20 mg/dl and undetectable IgA and lgM. The patient's serum contained no diphtheria or tetanus antitoxin in spite of prior immunizations; serum isoagglutinins were also absent. The patient had normal delayed-type reactivity to intradermal Candida antigen and to dinitrofluorobenzene. The response of his lymphocytes to phytohemagglutinin in vitro was normal. Microscopic examination of lung tissue obtained by needle aspiration revealed Pneumocystis carinii. The patient was treated with gamma globulin and pentamidine isethionate, and recovered. IgM was first detected in his serum at two years of age; by age 5 years, his serum IgM was 280 mg/dl with no evidence of endogenous IgG or IgA production. He is currently 12 years of age. His neutrophil counts have remained normal and he has been free of serious infections on monthly gamma globulin replacement therapy. A male sibling was born three years following the birth of this patient. Subsequent immunologic evaluation of this child revealed absent serum IgG and IgA with normal to increased lgM values, and normal T-cell function. Patient 2. The patient was the 3,150 gm male product of an uneventful gestation. He was the first born child to unrelated parents with no family history of immunodeficiency. He was well until 4 months of age, at which time he d eveloped an intermittent cough. He was admitted to the Johns Hopkins Hospital at age 6 months because of a sudden increase in his cough and the onset of respiratory distress. Physical examination revealed a cyanotic child in respiratory distress. Lymph nodes were not palpable a n d n o tonsillar tissue could be seen. Diffuse rales were noted on auscultation of the lungs. A chest roentgenogram demonstrated diffuse, bilateral infiltrates. The hemoglobin was 12.4 gm/dl, and the white blood cell count was 21,000/ram ~ with 47% segmented neutrophils, 46% lymphocytes, and 7% monocytes. Quantitative serum immunoglobulin studies revealed an IgG of 67 mg/dl and undetectable IgA and IgM. In spite of prior immunization, serum diphtheria and tetanus antitoxin titers were not detected, and his serum contained no isoagglutinins. The patient's in vitro lymphocyte responses to phytohemagglutinin and to allogeneic lymphocytes were normal. Microscopic examination of tissue obtained at open lung biopsy revealed P. carinii. The patient was treated with gamma globulin and a two-week course of trimethoprini:-sulfamethoxazole, and recovered. Trimethoprim-sulfamethoxazole was continued in prophylactic doses ~ for an additional two months and was then discontinued.
The Journal o f Pediatrics October 1979
The patient remained free of infection on monthly gamma globulin replacement therapy until age 15 months, when he was readmitted to the hospital with a two-week history of increasing cough and tachypnea. A chest roentgenogram revealed diffuse interstitial infiltrates. Numerous P. carinii were demonstrated by toluidine blue O stain of material obtained by tracheal aspiration. Repeat immunologic investigation revealed a serum lgG level of 71 mg/dl three weeks after intramuscular administration of gamma globulin, and undetectable IgA and IgM. The patient's in vitro lymphocyte responses to phymhemagglutinin and to allogeneic lymphocytes were again normal, as was the T-cell rosette quantitation. He was treated with trimethoprim-sulfamethoxazole and increased doses of gamma globulin, and recovered. His current therapy consists of biweekly gamma globulin injections and trimethoprim-sulfamethoxazole prophylaxis. DISCUSSION The present report describes two patients with congenital h y p o g a m m a g l o b u l i n e m i a in w h o m the initial infection was P. carinii p n e u m o n i a . Patient 1 a p p e a r s to have X-linked i m m u n o d e f i c i e n c y with increased IgM, 4 whereas Patient 2 has a form o f congenital h y p o g a m m a g l o b u l i n e m i a which c a n n o t be classified, since there is n o family history o f immunodeficiency. A l t h o u g h P. carinii p n e u m o n i a has b e e n associated with a variety o f p r i m a r y i m m u n o d e f i c i e n c y diseases, 2 ~ it has b e e n reported in only 13 patients with congenital h y p o g a m m a g l o b u l i n e m i a or d y s g a m m a g l o b u l i n e m i a in w h o m n o r m a l T-cell function was d o c u m e n t e d : , a-~ O f these, P. carinii p n e u m o n i a was specifically m e n t i o n e d as the initial infection in only three patients. 6-~ O n e o f these patients has s u b s e q u e n t l y h a d at least two recurrences of P. carinii p n e u m o n i a 2 The present report, a l o n g with the previously reported cases, d e m o n s t r a t e s t h a t children with congenital h y p o g a m m a g l o b u l i n e m i a m a y p r e s e n t with P. carinii p n e u m o n i a as their initial infection, a n d that they are also at risk for recurrent infections with this organism. ,~;7 The i m p o r t a n c e of a n t i b o d y in the host's defense against this o r g a n i s m is further illustrated by reports o f P. carinii p n e u m o n i a in other i m m u n o d e f i c i e n t patients. A l t h o u g h severe c o m b i n e d i m m u n o d e f i c i e n c y has b e e n r e p o r t e d to be the most c o m m o n p r i m a r y i m m u n o d e f i ciency disease associated with P. carinii p n e u m o n i a , ~~ this infection has been reported in association with virtually every p r i m a r y i m m u n o d e f i c i e n c y disease with the exception o f ataxia telangiectasia. 2 a However, P. carinii p n e u m o n i a has b e e n reported only once in association with the DiGeorge s y n d r o m e : 6 Thus h y p o g a m m a g l o bulinemia, e i t h e r alone or in concert with deficient T-cell function, is present in the o v e r w h e l m i n g m a j o r i t y of patients with i m m u n o d e f i c i e n c y a n d P. carinii p n e u m o nia. It would appear, therefore, that intact antibody-
Volume 95 Number 4
Brief clinical and laboratory observations
mediated immunity is one of the important determinants in the host's defense against P. carinii. The present report emphasizes that children with congenital h y p o g a m m a g l o b u l i n e m i a are at risk for P. carinii pneumonia and that this may be the initial infection which brings these children to medical attention. This organism must therefore be considered, along with the usual bacterial pathogens, in a child with hypogammaglobulinemia who presents with his first pneumonia. These children are also at risk for recurrent P. carinii pneumonia. Since trimeth0prim-sulfamethoxazole prophylaxis has been shown to be effective in preventing P. carinii pneumonia in cancer patients, 3 consideration should be given to the use of this drug for prophylaxis in children wi,h hypogammaglobulinemia who have recovered from an episode of P. carinii pneumonia. REFERENCES 1. Rosen FS, and Janeway CA: The gamma globulins III. The antibody deficiency syndromes, N Engl J Med 275:709, 1966. 2. Burke BA, and Good RA: Pneumocystis carinii infection, Medicine 52:23, 1973.
56 1
3. Hughes WT, Kuhn S, Chaudhary S, et ah Successful chemoprophylaxis for Pneumocystis carinii pneumonitis, N Engl J Med 297:1419, 1977. 4. Fudenberg H, Good RA, Hitzig W, et al: Primary immunodeficiencies, Report of a World Health Organization Committee, Pediatrics 47:927, 1971. 5. Walzer PD, Schultz MG, Western KA, and Robbins JB: Pneumocystis carinii pneumonia and primary immune deficiency diseases, Natl Cancer Inst Monogr 43:65, 1976. 6. Gentry LO, and Remington JS: Pneumocystis carinii pneumonia in siblings, J PEDIATR76:769, 1970. 7. Jose DG, Gatti RA, and Good RA: Eosinophilia with Pneumocystis carinii pneumonia and immune deficiency syndromes, J PEDIATR79:748, 1971. 8. Whisnant JK, and Buckley RH: Successful pyrimethaminesulfadiazine therapy of pneumocystis pneumonia in infants with X-linked immunodeficiency with hyper-IgM, Natl Cancer Inst Monogr 43:211, 1976. 9. Richman DD, Zamvil L, and Remington JS: Recurrent Pneumocystis carinii pneumonia in a child with hypogammaglobulinemia, Am J Dis Child 125:102, 1973. 10. DiGeorge AM: Congenital absence of the thymus and its immunologic consequences: Occurrence with congenital hypoparathyroidism, in Good RA, and Bergsma D, editors: Birth Defects, Original Article Series, New York, 1968, National Foundation Press, p 116.
Hepatic irradiation and adriamycin cardiotoxicity Pardeep Bhanot, M.D., Barbara Cushing, M.D.,* Arvin Philippart, M.D., Lakshmi Das, M.D., and Zia Farooki, M.D., Detroit, Mich.
T H E C A R D I O T O X I C I T Y of
adriamycin is well
known
to
be cumulative and dose d e p e n d e n t > ~-Concomitant irradiation of the mediastinum or administration of cyclophosphamide potentiates this toxicity. The incidence of congestive heart failure due to adriamycin cardiotoxicity is very low if the total cumulative dose is limited to 550 m g / m -~, or 450 m g / m ~ when one of the potentiating factors is present.'-' We have recently observed a patient who had received liver irradiation for hepatoblastoma, in w h o m congestive heart failure developed after a total cumulative dose of 303 m g / m ~. We believe hepatic dysfunction secondary to irradiation interfered with the elimination of adriamycin and was instrumental in causing adriamycin cardiotoxicity at a much lower dose. Such a sequence of events leading to increased risk of adriamycin cardiotoxicity has not been reported previously. From the Divisions of Hematology/Oncology and Cardiology, Children's Hospital of Michigan; the Departments of Pediatrics and Surgery, Wayne State University School of Medicine. *Reprint address: Children's Hospital of Michigan, 3901 Beaubien Blvd., Detroit, M1 48201. 0022-3476/79/100561 +03500.30/0 9 1979 The C. V. Mosby Co.
CASE R E P O R T A hepatoblastoma involving both the right and left lobes of the liver was diagnosed in a 31A-year-old black girl. At the time of diagnosis the hemoglobin was 7.4 gm/dl, WBC 13,900/mm ,', bilirubin 0.25 mg/dl, alkaline phosphatase 390 IU, SGPT 26 units, SGOT 62 units, total protein 6.9 gm/dl (albumin 2.6, globulin 4.3), and the alpha fetoprotein was strongly positive. A Abbreviations used DTIC: dimethyltriazeno-imidazole-carboxamide ECG: electrocardiogram BSP: Bromsulphalein 99mTcsulphur colloid liver scan revealed a large defect in the right lobe of the liver. On exploratory laparotomy a nodular tumor mass was found in the right lobe of the liver, with some extension into the left lobe. On the basis of these findings as well as the evidence of involvement of both lobes of the liver on an arteriogram, the tumor was thought to be unresectable. The patient was treated with 2,500 rads (125 rads daily) by linear accelerator by a port encompassing both lobes of the liver and three-fourths of the abdomen, including the inferior border of the cardiac silhouette. During irradiation (after 11 days of treatment) the bilirubin concentration was 2.4 mg/dl, total protein 7.2
B r i e f clinical and laboratory observations
produced coagulopathy, renal microangiopathy, and hemolytic anemia. ~ Our patient did not have the usual prodromal symptoms (diarrhea, vomiting, and blood stools) commonly seen in HUS of a presumed viral etiology. The features of HUS developed during acute pneumococcal sepsis, suggesting that the sepsis was causally related to the HUS. It is unlikely that the infant had two separate diseases at the same time. Pneumococcal sepsis is not rare, and why no other cases of HUS associated with it have been reported is not clear. It is possible that a genetic predisposition to HUS existed in this infant and was precipitated by pneumococcal sepsis, particularly since such predisposition has been observed in some families. ~ However, no other siblings in this family have developed HUS in the last 37 months. The histologic findings in the kidney were typical of those seen two weeks after the onset of the diseaseY S i n c e - n o deposits of immunoglobulins or complement were seen, it it unlikely that the renal damage was secondary to an immune-complex induced post-pneumococcal glomerulonephritis, although the biopsy was performed late in the course and it is possible that the deposits had disappeared. However, the finding of fibrin thrombi and platelets in capillaries is more in favor of HUS. Rarely, disseminated intravascular coagulation has occurred in pneumococcal sepsis:" Rytel e t al ~ have described two fatal cases in elderly patients, one of them asplenic. It could be argued that our patient had DIC, but
559
absence of a diffuse bleeding tendency and normal coagulation studies and fibrinogen levels are not in favor of DIC. Moreover. some intravascular coagulation does occur in patients with HUS." REFERENCES
1. Gasser VC, Gautier E~ Steck A, et al: H~imolytischUr~imiche Syndrome, Schweiz Med Wochenscbr 85:905, 1955. 2. Ray CG, Tucker VL, and Harris DJ: Enteroviruses associated with hemolytic uremic syndrome, Pediatrics 46:378, 1970. 3. Mettler NE: Isolation of microtatibote from patients with hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and from mites in the United States, N Engl J Med 281:1023, 1969. 4. Baker NM, Mills AE, and Rachman 1: Hemolytic uremic syndrome in typhoid fever, Br Med J 2:84, 1974. 5. Koster F, Levin J, Walker L, Tung KSK, Gilman RH, Rahaman MM, Majid MA, Islam S, and Williams RD: Hemolytic uremic syndrome after shigellosis: Relations to endotoxemia and circulating immune complexes, N Engl J Med 298:927, 1978. 6. Gianantonia CA: Hemolytic uremic syndrome, in Edelmann CM, editor: Pediatric kidney disease, vol 2, Boston, 1978, Little, Brown & Company, pp 724-736. 7. Kaplan ItS, Chesney RW, and Drummond KN: Hemolytic uremic syndrome in families, N Engl J Med 292:1090. 1975. 8. Rytel MW, Dee TH, Fenstenfeld JE, and Hensley CaT: Possible pathogenetic role of capsular antigens in fulminant pneumococcal disease with disseminated intravascular coagulation, Am J Med 57:889, 1974.
Pneumocystis carinii pneumonia as the presenting infection in congenital hypogammaglobulinemia Frank T. Saulsbury, M.D., Michael T. Bernstein, M.D., and Jerry A. Winkelstein, M.D.,* Baltimore, Md.
CHILDREN with congenital hypogammaglobulinemia are usually asymptomatic during the first several months of life, owing to the protection afforded by passively transferred maternal IgG. As this protection wanes, the From the Howard Hughes Medical Institute Laboratory of the Departments of Pediatrics and Microbiology, The Johns Hopkins University School of Medicine. Supported by United States Public Health Service Grant No. A1-07007. *Reprint address: Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, MD 21205.
0022-3476/79/100559 +03500.30/0 9 1979 The C. V. Mosby Co.
underlying hypogammaglobulinemia most commonly becomes manifest by an increased susceptibility to infection. Typical presenting infections in these children include pneumonia, otitis media, sepsis, and meningitis, all caused primarily by pyogenic bacteria. 1 Patients with hypogammaglobulinemia are also at risk for Pneumocystis carinii pneumonia-'; however, these children only rarely present with P. carinii pneumonia as their initial infection. This report describes two infants with congenital hypogammaglobulinemia and normal T-cell function in whom the initial infection was P. carinii pneumonia.
560
B r i e f cfinical and laboratory observations
CASE REPORTS Patient 1. The patient was the 3,240 gm male product of an uneventful gestation. He was the first born child to unrelated parents with no family history of immunodeficiency. He was well until 7 months of age when he developed a cough and intermittent fever, and was admitted to the Johns Hopkins Hospital two weeks later with severe cough, tachypnea, and cyanosis. Physical examination revealed an acutely ill, cyanotic child in respiratory distress. No rales were detected on auscultation of the lungs. A chest roentgenograln demonstrated diffuse, bilateral infiltrates. The hemoglobin was 14.6 gm/dl and the white blood cell count was 28,800/mm ~with 49% segmented neutrophils, 44% lymphocytes, and 5% monocytes. Quantitative serum immunoglobulin studies revealed an IgG of 20 mg/dl and undetectable IgA and lgM. The patient's serum contained no diphtheria or tetanus antitoxin in spite of prior immunizations; serum isoagglutinins were also absent. The patient had normal delayed-type reactivity to intradermal Candida antigen and to dinitrofluorobenzene. The response of his lymphocytes to phytohemagglutinin in vitro was normal. Microscopic examination of lung tissue obtained by needle aspiration revealed Pneumocystis carinii. The patient was treated with gamma globulin and pentamidine isethionate, and recovered. IgM was first detected in his serum at two years of age; by age 5 years, his serum IgM was 280 mg/dl with no evidence of endogenous IgG or IgA production. He is currently 12 years of age. His neutrophil counts have remained normal and he has been free of serious infections on monthly gamma globulin replacement therapy. A male sibling was born three years following the birth of this patient. Subsequent immunologic evaluation of this child revealed absent serum IgG and IgA with normal to increased lgM values, and normal T-cell function. Patient 2. The patient was the 3,150 gm male product of an uneventful gestation. He was the first born child to unrelated parents with no family history of immunodeficiency. He was well until 4 months of age, at which time he d eveloped an intermittent cough. He was admitted to the Johns Hopkins Hospital at age 6 months because of a sudden increase in his cough and the onset of respiratory distress. Physical examination revealed a cyanotic child in respiratory distress. Lymph nodes were not palpable a n d n o tonsillar tissue could be seen. Diffuse rales were noted on auscultation of the lungs. A chest roentgenogram demonstrated diffuse, bilateral infiltrates. The hemoglobin was 12.4 gm/dl, and the white blood cell count was 21,000/ram ~ with 47% segmented neutrophils, 46% lymphocytes, and 7% monocytes. Quantitative serum immunoglobulin studies revealed an IgG of 67 mg/dl and undetectable IgA and IgM. In spite of prior immunization, serum diphtheria and tetanus antitoxin titers were not detected, and his serum contained no isoagglutinins. The patient's in vitro lymphocyte responses to phytohemagglutinin and to allogeneic lymphocytes were normal. Microscopic examination of tissue obtained at open lung biopsy revealed P. carinii. The patient was treated with gamma globulin and a two-week course of trimethoprini:-sulfamethoxazole, and recovered. Trimethoprim-sulfamethoxazole was continued in prophylactic doses ~ for an additional two months and was then discontinued.
The Journal o f Pediatrics October 1979
The patient remained free of infection on monthly gamma globulin replacement therapy until age 15 months, when he was readmitted to the hospital with a two-week history of increasing cough and tachypnea. A chest roentgenogram revealed diffuse interstitial infiltrates. Numerous P. carinii were demonstrated by toluidine blue O stain of material obtained by tracheal aspiration. Repeat immunologic investigation revealed a serum lgG level of 71 mg/dl three weeks after intramuscular administration of gamma globulin, and undetectable IgA and IgM. The patient's in vitro lymphocyte responses to phymhemagglutinin and to allogeneic lymphocytes were again normal, as was the T-cell rosette quantitation. He was treated with trimethoprim-sulfamethoxazole and increased doses of gamma globulin, and recovered. His current therapy consists of biweekly gamma globulin injections and trimethoprim-sulfamethoxazole prophylaxis. DISCUSSION The present report describes two patients with congenital h y p o g a m m a g l o b u l i n e m i a in w h o m the initial infection was P. carinii p n e u m o n i a . Patient 1 a p p e a r s to have X-linked i m m u n o d e f i c i e n c y with increased IgM, 4 whereas Patient 2 has a form o f congenital h y p o g a m m a g l o b u l i n e m i a which c a n n o t be classified, since there is n o family history o f immunodeficiency. A l t h o u g h P. carinii p n e u m o n i a has b e e n associated with a variety o f p r i m a r y i m m u n o d e f i c i e n c y diseases, 2 ~ it has b e e n reported in only 13 patients with congenital h y p o g a m m a g l o b u l i n e m i a or d y s g a m m a g l o b u l i n e m i a in w h o m n o r m a l T-cell function was d o c u m e n t e d : , a-~ O f these, P. carinii p n e u m o n i a was specifically m e n t i o n e d as the initial infection in only three patients. 6-~ O n e o f these patients has s u b s e q u e n t l y h a d at least two recurrences of P. carinii p n e u m o n i a 2 The present report, a l o n g with the previously reported cases, d e m o n s t r a t e s t h a t children with congenital h y p o g a m m a g l o b u l i n e m i a m a y p r e s e n t with P. carinii p n e u m o n i a as their initial infection, a n d that they are also at risk for recurrent infections with this organism. ,~;7 The i m p o r t a n c e of a n t i b o d y in the host's defense against this o r g a n i s m is further illustrated by reports o f P. carinii p n e u m o n i a in other i m m u n o d e f i c i e n t patients. A l t h o u g h severe c o m b i n e d i m m u n o d e f i c i e n c y has b e e n r e p o r t e d to be the most c o m m o n p r i m a r y i m m u n o d e f i ciency disease associated with P. carinii p n e u m o n i a , ~~ this infection has been reported in association with virtually every p r i m a r y i m m u n o d e f i c i e n c y disease with the exception o f ataxia telangiectasia. 2 a However, P. carinii p n e u m o n i a has b e e n reported only once in association with the DiGeorge s y n d r o m e : 6 Thus h y p o g a m m a g l o bulinemia, e i t h e r alone or in concert with deficient T-cell function, is present in the o v e r w h e l m i n g m a j o r i t y of patients with i m m u n o d e f i c i e n c y a n d P. carinii p n e u m o nia. It would appear, therefore, that intact antibody-
Volume 95 Number 4
Brief clinical and laboratory observations
mediated immunity is one of the important determinants in the host's defense against P. carinii. The present report emphasizes that children with congenital h y p o g a m m a g l o b u l i n e m i a are at risk for P. carinii pneumonia and that this may be the initial infection which brings these children to medical attention. This organism must therefore be considered, along with the usual bacterial pathogens, in a child with hypogammaglobulinemia who presents with his first pneumonia. These children are also at risk for recurrent P. carinii pneumonia. Since trimeth0prim-sulfamethoxazole prophylaxis has been shown to be effective in preventing P. carinii pneumonia in cancer patients, 3 consideration should be given to the use of this drug for prophylaxis in children wi,h hypogammaglobulinemia who have recovered from an episode of P. carinii pneumonia. REFERENCES 1. Rosen FS, and Janeway CA: The gamma globulins III. The antibody deficiency syndromes, N Engl J Med 275:709, 1966. 2. Burke BA, and Good RA: Pneumocystis carinii infection, Medicine 52:23, 1973.
56 1
3. Hughes WT, Kuhn S, Chaudhary S, et ah Successful chemoprophylaxis for Pneumocystis carinii pneumonitis, N Engl J Med 297:1419, 1977. 4. Fudenberg H, Good RA, Hitzig W, et al: Primary immunodeficiencies, Report of a World Health Organization Committee, Pediatrics 47:927, 1971. 5. Walzer PD, Schultz MG, Western KA, and Robbins JB: Pneumocystis carinii pneumonia and primary immune deficiency diseases, Natl Cancer Inst Monogr 43:65, 1976. 6. Gentry LO, and Remington JS: Pneumocystis carinii pneumonia in siblings, J PEDIATR76:769, 1970. 7. Jose DG, Gatti RA, and Good RA: Eosinophilia with Pneumocystis carinii pneumonia and immune deficiency syndromes, J PEDIATR79:748, 1971. 8. Whisnant JK, and Buckley RH: Successful pyrimethaminesulfadiazine therapy of pneumocystis pneumonia in infants with X-linked immunodeficiency with hyper-IgM, Natl Cancer Inst Monogr 43:211, 1976. 9. Richman DD, Zamvil L, and Remington JS: Recurrent Pneumocystis carinii pneumonia in a child with hypogammaglobulinemia, Am J Dis Child 125:102, 1973. 10. DiGeorge AM: Congenital absence of the thymus and its immunologic consequences: Occurrence with congenital hypoparathyroidism, in Good RA, and Bergsma D, editors: Birth Defects, Original Article Series, New York, 1968, National Foundation Press, p 116.
Hepatic irradiation and adriamycin cardiotoxicity Pardeep Bhanot, M.D., Barbara Cushing, M.D.,* Arvin Philippart, M.D., Lakshmi Das, M.D., and Zia Farooki, M.D., Detroit, Mich.
T H E C A R D I O T O X I C I T Y of
adriamycin is well
known
to
be cumulative and dose d e p e n d e n t > ~-Concomitant irradiation of the mediastinum or administration of cyclophosphamide potentiates this toxicity. The incidence of congestive heart failure due to adriamycin cardiotoxicity is very low if the total cumulative dose is limited to 550 m g / m -~, or 450 m g / m ~ when one of the potentiating factors is present.'-' We have recently observed a patient who had received liver irradiation for hepatoblastoma, in w h o m congestive heart failure developed after a total cumulative dose of 303 m g / m ~. We believe hepatic dysfunction secondary to irradiation interfered with the elimination of adriamycin and was instrumental in causing adriamycin cardiotoxicity at a much lower dose. Such a sequence of events leading to increased risk of adriamycin cardiotoxicity has not been reported previously. From the Divisions of Hematology/Oncology and Cardiology, Children's Hospital of Michigan; the Departments of Pediatrics and Surgery, Wayne State University School of Medicine. *Reprint address: Children's Hospital of Michigan, 3901 Beaubien Blvd., Detroit, M1 48201. 0022-3476/79/100561 +03500.30/0 9 1979 The C. V. Mosby Co.
CASE R E P O R T A hepatoblastoma involving both the right and left lobes of the liver was diagnosed in a 31A-year-old black girl. At the time of diagnosis the hemoglobin was 7.4 gm/dl, WBC 13,900/mm ,', bilirubin 0.25 mg/dl, alkaline phosphatase 390 IU, SGPT 26 units, SGOT 62 units, total protein 6.9 gm/dl (albumin 2.6, globulin 4.3), and the alpha fetoprotein was strongly positive. A Abbreviations used DTIC: dimethyltriazeno-imidazole-carboxamide ECG: electrocardiogram BSP: Bromsulphalein 99mTcsulphur colloid liver scan revealed a large defect in the right lobe of the liver. On exploratory laparotomy a nodular tumor mass was found in the right lobe of the liver, with some extension into the left lobe. On the basis of these findings as well as the evidence of involvement of both lobes of the liver on an arteriogram, the tumor was thought to be unresectable. The patient was treated with 2,500 rads (125 rads daily) by linear accelerator by a port encompassing both lobes of the liver and three-fourths of the abdomen, including the inferior border of the cardiac silhouette. During irradiation (after 11 days of treatment) the bilirubin concentration was 2.4 mg/dl, total protein 7.2
