- Email: [email protected]
Severe infections in splenectomized infants and children
Comments
o n C u r r e n t Literature
S E V E R E I N F E C T I O N S IN SPLENECTOMIZED I N F A N T S AND C H I L D R E N HE spleen in some respects still remains an organ of mystery; howT ever, recent developments in tlle field of hematology have brought about a better understanding and a more satisfactory classification of the blood dyscrasias in their relation to the spleen. Increased knowledge of splenic function has served to refine the indications for splenectomy. Indications and contraindieations for spleneetomy with their qualifications were summarized in a review article by Sanders and Kinnaird 1 in 1956: " . . . trauma to the spleen heads the list of indications for splenectomy both in urgency and frequency. Fifty-five years of clinical trial and error have shown that idiopathic thrombocytopenic purpura and hereditary hemoiytic anemia share the honors in scarcely subordinate fashion to trauma as prime indications for splenectomy. ''1 In Banti's disease and splenic anemia, indications for splenectomy require individual evaluation, "so that today, splenectomy is rarely advocated for 'splenic anemia' and splenomegaly in the absence of significant hemolysis or hypersplenism, and is avoided in Banti's syndrome except as a part of a vascular shunting procedure. ,,1 In a recent clinical study Carl H. Smith and his associates2 point out that, while increasing experience with splenectomy has emphasized the therapeutic value and relative safety of this procedure, attention should be focused on an appreciable number of recorded cases in which serious, recurrent or fatal infection has occurred in the spIenectomized patient. In this article, 223
which appears in the American Journal of Medicine for March, 1957, Smith, Erlandson, Sehuhnan, and Stern 2 refer to the cases recorded in the literature, two of which were their own, and extend their "initial observation indicating a heightened susceptibility to severe infection in a group of infants and children in whom the spleen had been removed for a variety of conditions mostly of a hematologic nature. ''2 Findings on nineteen eases, six of which terminated fatally, are given in this report, the eases falling into several categories: "those associated with meningitis, acute pericarditis and sepsis, and a group consisting of acutely ill children in whom the course was so fulminating as to preclude the detection of a specific etiologic agent." Case histories on all nineteen patients are summarized; complete laboratory studies were not always possible for the fulminating cases, some of the patients having died a few hours after admission. The previous publication by Smith and his colleaguesa concerned a study of Cooley's anemia; two of the children reported experienced an overwhelming fatal illness with high fever, prostration, and coma, sixteen months and t w o weeks, respectively, following splenectomy performed for Cooley's anemia. Examination of the literature at that time by these authors revealed other recorded eases, notably five infants under the age of 6 months with congenital spherocytic anemia reported by King and ShumackeP in 1952. In four of these five infants fulminating infection, either meningitis or
224
THE JOURNAL
meningocoeeemia, developed w i t h i n five weeks to three years after splenect o n y , and one of the five children died a few days after discharge following surgery from a rapidly fatal febrile illness of unknown etiology. In the nineteen cases presently reported by Smith and his associates, the range in age was from 2 to 17 years, some of the patients experieneing repeated episodes of severe infection over a period of years. These authors include ease histories, tabular information concerning time relationships, indication for spleneetomy in their own and recorded cases, and an analysis of the type of infection, as well as a discussion of the spleen's contribution to natural resistance and body defenses. The infections fall into a number of well-defined groups: meningitis (seven eases), acute periearditis (five), a e u t e endoearditis (one), sepsis (three) and three acutely ill patients in whom the course of the infection was so fulminating that specific etiologic detection was not possible. In eleven of the eases bacteriologic diagnosis w a s accomplished, pneumoeoeeus being the most frequent offender (six cases). Other organisms incriminated included Escherichia coli (two eases), Salmonella typhimurium (one ease), alpha streptococcus (one), and Hemophilus influenzae (one). In the m~ningitis group of patients pneumoeoeeus was the predominant organism, isolated in five of seven eases of meningitis. I n one of the patients with meningitis r e c u r r e n t attacks occurred which were caused by different strains of pneumoeoeeus. This situation also obtained, as the authors point out, in some of a group of patients reported by Gofstein and Gellis 5 in 1956. A study of the individual case histories in these nineteen cases revealed t h a t in most instances an apparently well child became seriously ill after a short prodromal period. In a few instances the child had been' somewhat susceptible to recurrent infection before spleneetomy; in some patients, notably those with meningitis, the ful-
OF P E D I A T R I C S
minating clinical features followed several days of illness during which antibiotics were administered with apparent improvement. Periearditis oeeurred in eight instances: eight attacks in five children, all of whom had severe Cooley's anemia; no specific etiologic agent could be identified. Clinical manifestations and laboratory findings were eompatible with the recognized features of acute benign or idiopathic periearditis which have been described in adults. Each of these patients experienced substernal pain which appeared to be sudden and intense across the u p p e r and lower anterior chest radiating to the back and shoulders. The pain was aggravated by breathing or motion and was somewhat relieved by the sitting position. Leukocytosis, fever, and perieardial friction rub with some evidence of effusion were prominent findings. The electrocardiogram showed eharacteristie changes. Tendency for this eondition to recur was apparent in two cases, one patient suffering two and the other three such attacks, followed in every instance by recovery. The major indication for spleneet o n y in these eases was referable to conditions associated with an established blood dyserasia, and the proeedure was undertaken as a means of reducing transfusion requirements and improving patient status. The interval between the surgical procedure and infection ranged from one day to twelve years, with the m a j o r i t y of episodes (80 per cent) occurring within two years or less. The shortest periods (24 hours and 13 days) were in t w o patients with fulminating course and fatal outcome. In two of the children, each 6 years of age, splenectomy was carried out because of traumatic r u p t u r e of the spleen. F r o m the standpoint of infection susceptibility in relation to spleneetomy, these two essentially normal children are of special interest. One of them experienced two episodes of pneumocoecal meningitis (type 23 and type 12) in a period of eighteen months
COMMENTS ON CURRENT LITERATURE
postoperatively, and the other alpha streptococcal sepsis at 1 year following removal of the spleen. Both patients recovered. Electrophoretic studies of serum proteins were carried out in the case of eight of these splenectomized patients, and no diminution in the concentration of gamma globulin was detected, suggesting that the lowered resistance to serious infection following splenectomy was not associated with a deficiency in serum gamma globulin. I n this connection the authors discuss the rather extensive clinical and experimental evidence concerning the contribution made by the spleen to defense mechanisms of the body. They quote from the Ludwig Kast Lecture given by Dubos 6 before the New York A c a d e m y of Medicine in 1954, which deals with the biochemical determinants of infection: " . . . m a n y types of substances, procedures or accidents have been found capable of bringing about conditions under which latent microorganisms can manifest their potential pathogenicity and cause overt disease." While the number of pertinent cases recorded is relatively small in proportion to the over-all number of splenectomies performed, these authors suggest that the few are of considerable significance, and that removal of the spleen may very well foster vulnerability to infection. I n addition to c]ini-
225
eal observations such as theirs, extensive experimental evidence "implicates the spleen in fundamental processes relating to resistance to infection. ''2 Thus in summary, they emphasize that "the young sp]eneetomized patient requires c 1 o s e supervision for several years postoperatively so that immediate and energetic treatment may be instituted in the event of sudden or severe illness. ''z ]~USSELL J . BLATTNER REFERENCES
1. Sanders, George B., and Kinnaird, David W.: Splenectomy: Indications and Contraindications, Old and New, South. M. J. 49: 142, 1956. 2. Smith, Carl It., Erlandson, Marion, Schulman, Irving, and Stern~ Gertrude: }Iazard of Severe Infections in Sp]enectomized Infants and Children, Am. J. ~/Ied. 22: 390, 1957. 3. Smith, C. I~., Schulman, I., Ando, R. E., and Stern, G.: Studies in Mediterranean (CooleSs) Anemia. I. Clinical a n d
I~Iematologie Aspects of Spleneetomy, With Special Reference to Fetal tIemog]obin Synthesisj Blood 10: 582, ]955. 4. King, H., and Shumacker, I-I. B., Jr.: Splenic Studies. I. Susceptibility to Infection After Splenectomy Performed in Infancy, Ann. Surg. 136: 239, 1952. 5. Gofstein~ Ralph, and Gellis, Sydney, S.: Sp]enectomy in Infancy and Childhood: The Question of Overwhelming Infection Following Operation, A. IV[. A. Am. J. Dis. Child. 91: 566, 1956. 6. Dubos, Rene J.: Biochemical Determinants of Infection, Ludwig Kast Lecture, 27th Graduate Fortnight, New York Academy of Medicine, Oct. 18~ ]954, Bull. New York Acad. 1V~ed. 31: 5, 1955.
o n C u r r e n t Literature
S E V E R E I N F E C T I O N S IN SPLENECTOMIZED I N F A N T S AND C H I L D R E N HE spleen in some respects still remains an organ of mystery; howT ever, recent developments in tlle field of hematology have brought about a better understanding and a more satisfactory classification of the blood dyscrasias in their relation to the spleen. Increased knowledge of splenic function has served to refine the indications for splenectomy. Indications and contraindieations for spleneetomy with their qualifications were summarized in a review article by Sanders and Kinnaird 1 in 1956: " . . . trauma to the spleen heads the list of indications for splenectomy both in urgency and frequency. Fifty-five years of clinical trial and error have shown that idiopathic thrombocytopenic purpura and hereditary hemoiytic anemia share the honors in scarcely subordinate fashion to trauma as prime indications for splenectomy. ''1 In Banti's disease and splenic anemia, indications for splenectomy require individual evaluation, "so that today, splenectomy is rarely advocated for 'splenic anemia' and splenomegaly in the absence of significant hemolysis or hypersplenism, and is avoided in Banti's syndrome except as a part of a vascular shunting procedure. ,,1 In a recent clinical study Carl H. Smith and his associates2 point out that, while increasing experience with splenectomy has emphasized the therapeutic value and relative safety of this procedure, attention should be focused on an appreciable number of recorded cases in which serious, recurrent or fatal infection has occurred in the spIenectomized patient. In this article, 223
which appears in the American Journal of Medicine for March, 1957, Smith, Erlandson, Sehuhnan, and Stern 2 refer to the cases recorded in the literature, two of which were their own, and extend their "initial observation indicating a heightened susceptibility to severe infection in a group of infants and children in whom the spleen had been removed for a variety of conditions mostly of a hematologic nature. ''2 Findings on nineteen eases, six of which terminated fatally, are given in this report, the eases falling into several categories: "those associated with meningitis, acute pericarditis and sepsis, and a group consisting of acutely ill children in whom the course was so fulminating as to preclude the detection of a specific etiologic agent." Case histories on all nineteen patients are summarized; complete laboratory studies were not always possible for the fulminating cases, some of the patients having died a few hours after admission. The previous publication by Smith and his colleaguesa concerned a study of Cooley's anemia; two of the children reported experienced an overwhelming fatal illness with high fever, prostration, and coma, sixteen months and t w o weeks, respectively, following splenectomy performed for Cooley's anemia. Examination of the literature at that time by these authors revealed other recorded eases, notably five infants under the age of 6 months with congenital spherocytic anemia reported by King and ShumackeP in 1952. In four of these five infants fulminating infection, either meningitis or
224
THE JOURNAL
meningocoeeemia, developed w i t h i n five weeks to three years after splenect o n y , and one of the five children died a few days after discharge following surgery from a rapidly fatal febrile illness of unknown etiology. In the nineteen cases presently reported by Smith and his associates, the range in age was from 2 to 17 years, some of the patients experieneing repeated episodes of severe infection over a period of years. These authors include ease histories, tabular information concerning time relationships, indication for spleneetomy in their own and recorded cases, and an analysis of the type of infection, as well as a discussion of the spleen's contribution to natural resistance and body defenses. The infections fall into a number of well-defined groups: meningitis (seven eases), acute periearditis (five), a e u t e endoearditis (one), sepsis (three) and three acutely ill patients in whom the course of the infection was so fulminating that specific etiologic detection was not possible. In eleven of the eases bacteriologic diagnosis w a s accomplished, pneumoeoeeus being the most frequent offender (six cases). Other organisms incriminated included Escherichia coli (two eases), Salmonella typhimurium (one ease), alpha streptococcus (one), and Hemophilus influenzae (one). In the m~ningitis group of patients pneumoeoeeus was the predominant organism, isolated in five of seven eases of meningitis. I n one of the patients with meningitis r e c u r r e n t attacks occurred which were caused by different strains of pneumoeoeeus. This situation also obtained, as the authors point out, in some of a group of patients reported by Gofstein and Gellis 5 in 1956. A study of the individual case histories in these nineteen cases revealed t h a t in most instances an apparently well child became seriously ill after a short prodromal period. In a few instances the child had been' somewhat susceptible to recurrent infection before spleneetomy; in some patients, notably those with meningitis, the ful-
OF P E D I A T R I C S
minating clinical features followed several days of illness during which antibiotics were administered with apparent improvement. Periearditis oeeurred in eight instances: eight attacks in five children, all of whom had severe Cooley's anemia; no specific etiologic agent could be identified. Clinical manifestations and laboratory findings were eompatible with the recognized features of acute benign or idiopathic periearditis which have been described in adults. Each of these patients experienced substernal pain which appeared to be sudden and intense across the u p p e r and lower anterior chest radiating to the back and shoulders. The pain was aggravated by breathing or motion and was somewhat relieved by the sitting position. Leukocytosis, fever, and perieardial friction rub with some evidence of effusion were prominent findings. The electrocardiogram showed eharacteristie changes. Tendency for this eondition to recur was apparent in two cases, one patient suffering two and the other three such attacks, followed in every instance by recovery. The major indication for spleneet o n y in these eases was referable to conditions associated with an established blood dyserasia, and the proeedure was undertaken as a means of reducing transfusion requirements and improving patient status. The interval between the surgical procedure and infection ranged from one day to twelve years, with the m a j o r i t y of episodes (80 per cent) occurring within two years or less. The shortest periods (24 hours and 13 days) were in t w o patients with fulminating course and fatal outcome. In two of the children, each 6 years of age, splenectomy was carried out because of traumatic r u p t u r e of the spleen. F r o m the standpoint of infection susceptibility in relation to spleneetomy, these two essentially normal children are of special interest. One of them experienced two episodes of pneumocoecal meningitis (type 23 and type 12) in a period of eighteen months
COMMENTS ON CURRENT LITERATURE
postoperatively, and the other alpha streptococcal sepsis at 1 year following removal of the spleen. Both patients recovered. Electrophoretic studies of serum proteins were carried out in the case of eight of these splenectomized patients, and no diminution in the concentration of gamma globulin was detected, suggesting that the lowered resistance to serious infection following splenectomy was not associated with a deficiency in serum gamma globulin. I n this connection the authors discuss the rather extensive clinical and experimental evidence concerning the contribution made by the spleen to defense mechanisms of the body. They quote from the Ludwig Kast Lecture given by Dubos 6 before the New York A c a d e m y of Medicine in 1954, which deals with the biochemical determinants of infection: " . . . m a n y types of substances, procedures or accidents have been found capable of bringing about conditions under which latent microorganisms can manifest their potential pathogenicity and cause overt disease." While the number of pertinent cases recorded is relatively small in proportion to the over-all number of splenectomies performed, these authors suggest that the few are of considerable significance, and that removal of the spleen may very well foster vulnerability to infection. I n addition to c]ini-
225
eal observations such as theirs, extensive experimental evidence "implicates the spleen in fundamental processes relating to resistance to infection. ''2 Thus in summary, they emphasize that "the young sp]eneetomized patient requires c 1 o s e supervision for several years postoperatively so that immediate and energetic treatment may be instituted in the event of sudden or severe illness. ''z ]~USSELL J . BLATTNER REFERENCES
1. Sanders, George B., and Kinnaird, David W.: Splenectomy: Indications and Contraindications, Old and New, South. M. J. 49: 142, 1956. 2. Smith, Carl It., Erlandson, Marion, Schulman, Irving, and Stern~ Gertrude: }Iazard of Severe Infections in Sp]enectomized Infants and Children, Am. J. ~/Ied. 22: 390, 1957. 3. Smith, C. I~., Schulman, I., Ando, R. E., and Stern, G.: Studies in Mediterranean (CooleSs) Anemia. I. Clinical a n d
I~Iematologie Aspects of Spleneetomy, With Special Reference to Fetal tIemog]obin Synthesisj Blood 10: 582, ]955. 4. King, H., and Shumacker, I-I. B., Jr.: Splenic Studies. I. Susceptibility to Infection After Splenectomy Performed in Infancy, Ann. Surg. 136: 239, 1952. 5. Gofstein~ Ralph, and Gellis, Sydney, S.: Sp]enectomy in Infancy and Childhood: The Question of Overwhelming Infection Following Operation, A. IV[. A. Am. J. Dis. Child. 91: 566, 1956. 6. Dubos, Rene J.: Biochemical Determinants of Infection, Ludwig Kast Lecture, 27th Graduate Fortnight, New York Academy of Medicine, Oct. 18~ ]954, Bull. New York Acad. 1V~ed. 31: 5, 1955.