The following letter, which appeared in the February 1992 issue of AJDC, was mistakenly published without the table. It appears in its entirety below.—
Intravenous Immune
Globulin and
Meningitis
Aseptic
Sir.\p=m-\We report the case of a patient with aseptic meningitis that was probably caused by the administration of intravenous immune globulin (IVIG). Patient Report.\p=m-\A9-year-old boy was admitted to the hospital 1 day after the development of epistaxis and hematemesis. Results of physical examination were unremarkable except for petechiae on the palate. A complete blood cell count revealed a hemoglobin level of 99 g/L and a white blood cell count of 7.2 \m=x\109/L, with 0.24 segmented neutrophils, 0.68 lymphocytes, 0.05 monocytes, and 0.03 eosinophils. His platelet count was 16 \m=x\109/L, and a peripheral blood smear showed a decreased number of platelets and giant platelets. A clinical diagnosis of immune
thrombocytopenic purpura
was
made. Intravenous immune globulin (400 mg/kg of body weight; Sandoglobulin IV, Sandoz Pharmaceuticals, East
Hanover, NJ)
was infused over 4 hours for 2 days. His platelet count increased to 69 \m=x\109/L within 48 hours of starting infusion. Approximately 12 hours after completion of the second dose of IVIG, the patient complained of head¬ ache. He also developed fever and vom¬ ited once. Results of neurologic examina¬ tion revealed the patient to be lethargic, with normal fundi but a stiff neck. A computed tomogram of the head was normal. Lumbar puncture revealed cloudy cerebrospinal fluid. Analysis of the cerebrospinal fluid revealed the fol¬ lowing values: white blood cell count,
daily
2.5X107L (0.98
segmented neutrophils
and 0.02 lymphocytes); protein, 0.60 g/L; and glucose, 4.1 mmol/L. A gram stain of the sediment was negative for bacteria, and viral (enteroviruses and herpes sim¬ plex) and bacterial cultures of cerebrospi¬ nal fluid were negative. Results of tests of renal and hepatic function were normal. Results of tests to detect antinuclear anti¬ bodies and anti-DNA were negative, and his C3 serum complement was normal. Administration of IVIG was discontinued after the second dose, and the patient began a short course of prednisone ther¬ apy (3 mg/kg of body weight per day for
4
days). The
became completely within 24 to 48 hours of the onset of neurologic symptoms. His platelet count was normal 4 days after
patient
asymptomatic
hospitalization, writing.
and he
was
well at this
Comment. —The clinical presenta¬ tion and course of aseptic meningitis in this patient are similar to those in pre¬ viously described patients.13 Six epi¬ sodes of aseptic meningitis, two in each of three patients, have been re¬ ported (Table). In four of these epi¬ sodes, including that of our patient, headache, fever, and neck stiffness de¬ veloped within 48 hours of administra¬ tion of IVIG. In one patient, both epi¬ sodes occurred 7 days after IVIG ther¬ apy, despite using a different IVIG preparation the second time. The white blood cell count in cerebrospinal fluid
ranged
from 0.18xl07L to
2.45X107L, with greater than 0.90
neutrophils, an unusual finding in aseptic meningitis. All patients had rapid and complete recoveries. The development of aseptic menin¬ gitis after IVIG administration in sev¬
eral
patients with similar clinical adds supportive evidence to a
courses
causal relationship between the two; the mechanism ofsuch a relationship is unknown. While headache, fever, and vomiting are reported to be frequent side effects of therapy with IVIG, what
Episodes of Aseptic Meningitis After IVIG Administration* Time Between Administration
Source, y Jayabose et al,1 1990
Age of Patient, y
of IVIG and
Diagnosis Acute ITP
IVIG Dose 1 1
Symptoms of
Meningitis
White Blood Cell Count, xlOVL (Proportion of Segmented
NeutrophilsJt
Protein,
grit
Comment
gm/kg
10 h after
gm/kg
Within 24 h of second dose
0.18
(.85)
0.27
3-wk interval between the
36 h after first
2.45 (.88)
0.45
Similar
7 d after first
0.45
dose 7d
(.90)
0.15
None
0.31 (.90)
0.21
3-wk interval
(two doses)
a
0.35
single dose
(.94)
0.20
None
two
Kats et
al,31988
Chronic ITP
400
Acute ITP
400
mg/kg
(two doses) Casteels-Van Daele et al,3 1990
mg/kg per day (five doses) 400 mg/kg
dose
15
episodes episode
mo
earlier*
between the two
Present
study
Acute ITP
400
mg/kg
(two doses)
36 h after the
first dose
2.50 (.98)
0.60
*IVIG indicates intravenous immune globulin; ITP, immune thrombocytopenic purpura. Viral and bacterial cultures in all studies, tin cerebrospinal fluid. ^Patient's white blood cell count in cerebrospinal fluid was 1.55x109/L during the first episode of meningitis.
Downloaded From: http://archpedi.jamanetwork.com/ by a Michigan State University User on 06/16/2015
episodes
None were
negative
proportion of patients have laboratory evidence of aseptic meningitis is un¬
known. It is also of interest that all re¬ ported cases of aseptic meningitis oc¬ curred in patients with immune thrombocytopenic purpura and after
improvement in platelet count. Physicians should be aware that this clinical syndrome exists, that re¬ sults of analysis of cerebrospinal fluid may be significantly abnormal in these patients, and that the out¬ comes reported to date have, to our knowledge, been uniformly good. SREEDHAR P. RAO, MD
JEFFREY TEITLEBAUM, MD
SCOTT T. MILLER, MD State University of New York Health Science Center at
Brooklyn
450 Clarkson Ave, Box 49 Brooklyn, NY 11203 1. Jayabose S, Roseman B, Gupta A. Aseptic meningitis syndrome after IV gamma globulin therapy for ITP. Am J Pediatr Hematol
Oncol. 1990;12:117. Abstract. 2. Kats E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA. 1988;259:3269-3270. 3. Casteels\p=n-\Van Daele M, Wijndaele L, Hunnick K, Gillis P. Intravenous immune globulin and acute aseptic meningitis. N Engl J Med. 1990;323:614-615.
A Second Look at
Breast-feeding and
Full-time Maternal
Employment Sir.\p=m-\Iused to be a full-time pedianow I am a full-time mother and a part-time pediatrician. As a member of the "mommy club" (viz, the "old boys' network"), I chuckle at (and am embarrassed by) the advice I used to offer. For example, I used to believe that breast-feeding is, or should be, compatible with full-time maternal employment. Why not, you ask? Everyone does it. Articles and books are filled with advice on pumping and freezing milk, on "role overload," on the joys of "having it all" and of "quality time," and on the nutritional and immunologic benefits of breast milk. Success is measured by "duration of nursing." What could be missing? Discussion of the infant's point of view and of the emotional side of the nursing relationship is usually missing. In fact, the entire mother-child relationship is usually tactfully ig-
trician;
avoiding
nored
or relegated to a final parathat mentions the wonder of the occasional "real" nursing. Any consideration of the infant's feelings and needs is generally absent. Recall that full-time infant day care is a nec¬ essary corollary of full-time maternal employment. Surely who cares for the infant and how are as significant and worthy of discussion as what is placed in the bottle. One might also wonder if breast milk in a bottle from a mother substitute has significance for the in¬ fant as it does for the mother. Does this pattern of feeding permit and help the infant to know and make a relationship with his or her mother? When an infant is nursed, his or her hunger and mother's let-down become synchronized (after about 6 to 8 weeks), forming the physical ba¬ sis for the closeness and gratification of the nursing relationship. It is con¬ fusing and mistaken to use the word breast-feeding for both nursing and for the pairing of lactation (the mainte¬ nance of a milk supply) with breastmilk-in-a-bottle feeding by substitute care-givers. Most published work on combining breast-feeding and em¬ ployment unfortunately neither en¬ tertains these issues nor steps be¬ yond the confines of the technical aspects of the enterprise. I fear my views are so unpopular and are rejected so vehemently be¬ cause they provoke guilt. Finances and careers are usually more flexible and negotiable than we care to admit. What if all this mother-infant separa¬ tion and substitute care (the "hidden" side of "breast-feeding" and working fuU-time) are neither necessary nor best for the infant? We often hear about the busy professional who "has to work." But pumping or no pump¬ ing, saying, "oh, it must be nice to be at home" to an at-home mother im¬ plies a self-sacrifice that simply is not there. In fact, staying home full-time is difficult, does not earn money or build self-esteem like work does, and can regularly make one feel isolated and "stir crazy," longing for the adult world of work where time flies. The gratifications of being at home are pri¬ marily long-term. One hopes that the dependable, consistent, and nurtur¬
graph
ing relationship one provides, though imperfect, is the best building block an
infant can use to become a solid, ma¬ ture person. The end of nursing, too, is a time
Downloaded From: http://archpedi.jamanetwork.com/ by a Michigan State University User on 06/16/2015
when it is difficult not to "need to be back at work." Weaning is a special and challenging period for mother and infant. It marks the end of a spe¬ cial closeness and the emergence of the infant as a person. Perrnitting the infant to reject the breast and support¬ ing his or her growing away are ex¬ traordinarily difficult for most moth¬ ers. Pumping milk until one is either tired of it or until the infant is a certain age both sadly bypass an entire devel¬ opmental step for both partners. Unfortunately, breast milk cannot substitute for parenting (I can hear the cries of indignation already) and our current enthusiasm for combining lac¬ tation and separation may serve to di¬ vert attention from more substantive issues. For example, how can we as professionals and as individuals better support mothering, parenting, and the mother-child relationship? What economic incentives, from paid mater¬ nity leaves to child allowances to flex¬ ible hours with job security, would be most workable? What program of emotional supports (for mothers of all socioeconomic groups) from home visiting to parenting centers, would be best, and how could it be funded? I am certainly a strong advocate of nursing, but until our discussions move be¬ yond breast milk to the mother-child relationship, I fear we are missing the forest for the trees. LYDIA FURMAN, MD 2256 N St James Pkwy Cleveland Heights, OH 44106
Fluid
Management and Arginine Vasopressin in Bacterial
Meningitis
Sir.\p=m-\Padilla and colleagues1 recently reported that urine vasopressin concentrations fell during the first 3 days of treatment of bacterial meningitis when patients received maintenance
fluid requirements containing a mean of 5.6 mEq/kg per day of ionized sodium. In a similar series of patients,2 plasma arginine vasopressin normalized within 24 hours when maintenance plus replacement fluids (the mean volume of fluid administered in a 24-hour period was 1.5 \m=x\ maintenance and contained 7.8 mEq/kg per day ofionized sodium) were given, but remained elevated when fluids were restricted (the mean volume of fluid administered in a 24-hour period was
Intravenous Immune
Globulin and
Meningitis
Aseptic
Sir.\p=m-\We report the case of a patient with aseptic meningitis that was probably caused by the administration of intravenous immune globulin (IVIG). Patient Report.\p=m-\A9-year-old boy was admitted to the hospital 1 day after the development of epistaxis and hematemesis. Results of physical examination were unremarkable except for petechiae on the palate. A complete blood cell count revealed a hemoglobin level of 99 g/L and a white blood cell count of 7.2 \m=x\109/L, with 0.24 segmented neutrophils, 0.68 lymphocytes, 0.05 monocytes, and 0.03 eosinophils. His platelet count was 16 \m=x\109/L, and a peripheral blood smear showed a decreased number of platelets and giant platelets. A clinical diagnosis of immune
thrombocytopenic purpura
was
made. Intravenous immune globulin (400 mg/kg of body weight; Sandoglobulin IV, Sandoz Pharmaceuticals, East
Hanover, NJ)
was infused over 4 hours for 2 days. His platelet count increased to 69 \m=x\109/L within 48 hours of starting infusion. Approximately 12 hours after completion of the second dose of IVIG, the patient complained of head¬ ache. He also developed fever and vom¬ ited once. Results of neurologic examina¬ tion revealed the patient to be lethargic, with normal fundi but a stiff neck. A computed tomogram of the head was normal. Lumbar puncture revealed cloudy cerebrospinal fluid. Analysis of the cerebrospinal fluid revealed the fol¬ lowing values: white blood cell count,
daily
2.5X107L (0.98
segmented neutrophils
and 0.02 lymphocytes); protein, 0.60 g/L; and glucose, 4.1 mmol/L. A gram stain of the sediment was negative for bacteria, and viral (enteroviruses and herpes sim¬ plex) and bacterial cultures of cerebrospi¬ nal fluid were negative. Results of tests of renal and hepatic function were normal. Results of tests to detect antinuclear anti¬ bodies and anti-DNA were negative, and his C3 serum complement was normal. Administration of IVIG was discontinued after the second dose, and the patient began a short course of prednisone ther¬ apy (3 mg/kg of body weight per day for
4
days). The
became completely within 24 to 48 hours of the onset of neurologic symptoms. His platelet count was normal 4 days after
patient
asymptomatic
hospitalization, writing.
and he
was
well at this
Comment. —The clinical presenta¬ tion and course of aseptic meningitis in this patient are similar to those in pre¬ viously described patients.13 Six epi¬ sodes of aseptic meningitis, two in each of three patients, have been re¬ ported (Table). In four of these epi¬ sodes, including that of our patient, headache, fever, and neck stiffness de¬ veloped within 48 hours of administra¬ tion of IVIG. In one patient, both epi¬ sodes occurred 7 days after IVIG ther¬ apy, despite using a different IVIG preparation the second time. The white blood cell count in cerebrospinal fluid
ranged
from 0.18xl07L to
2.45X107L, with greater than 0.90
neutrophils, an unusual finding in aseptic meningitis. All patients had rapid and complete recoveries. The development of aseptic menin¬ gitis after IVIG administration in sev¬
eral
patients with similar clinical adds supportive evidence to a
courses
causal relationship between the two; the mechanism ofsuch a relationship is unknown. While headache, fever, and vomiting are reported to be frequent side effects of therapy with IVIG, what
Episodes of Aseptic Meningitis After IVIG Administration* Time Between Administration
Source, y Jayabose et al,1 1990
Age of Patient, y
of IVIG and
Diagnosis Acute ITP
IVIG Dose 1 1
Symptoms of
Meningitis
White Blood Cell Count, xlOVL (Proportion of Segmented
NeutrophilsJt
Protein,
grit
Comment
gm/kg
10 h after
gm/kg
Within 24 h of second dose
0.18
(.85)
0.27
3-wk interval between the
36 h after first
2.45 (.88)
0.45
Similar
7 d after first
0.45
dose 7d
(.90)
0.15
None
0.31 (.90)
0.21
3-wk interval
(two doses)
a
0.35
single dose
(.94)
0.20
None
two
Kats et
al,31988
Chronic ITP
400
Acute ITP
400
mg/kg
(two doses) Casteels-Van Daele et al,3 1990
mg/kg per day (five doses) 400 mg/kg
dose
15
episodes episode
mo
earlier*
between the two
Present
study
Acute ITP
400
mg/kg
(two doses)
36 h after the
first dose
2.50 (.98)
0.60
*IVIG indicates intravenous immune globulin; ITP, immune thrombocytopenic purpura. Viral and bacterial cultures in all studies, tin cerebrospinal fluid. ^Patient's white blood cell count in cerebrospinal fluid was 1.55x109/L during the first episode of meningitis.
Downloaded From: http://archpedi.jamanetwork.com/ by a Michigan State University User on 06/16/2015
episodes
None were
negative
proportion of patients have laboratory evidence of aseptic meningitis is un¬
known. It is also of interest that all re¬ ported cases of aseptic meningitis oc¬ curred in patients with immune thrombocytopenic purpura and after
improvement in platelet count. Physicians should be aware that this clinical syndrome exists, that re¬ sults of analysis of cerebrospinal fluid may be significantly abnormal in these patients, and that the out¬ comes reported to date have, to our knowledge, been uniformly good. SREEDHAR P. RAO, MD
JEFFREY TEITLEBAUM, MD
SCOTT T. MILLER, MD State University of New York Health Science Center at
Brooklyn
450 Clarkson Ave, Box 49 Brooklyn, NY 11203 1. Jayabose S, Roseman B, Gupta A. Aseptic meningitis syndrome after IV gamma globulin therapy for ITP. Am J Pediatr Hematol
Oncol. 1990;12:117. Abstract. 2. Kats E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA. 1988;259:3269-3270. 3. Casteels\p=n-\Van Daele M, Wijndaele L, Hunnick K, Gillis P. Intravenous immune globulin and acute aseptic meningitis. N Engl J Med. 1990;323:614-615.
A Second Look at
Breast-feeding and
Full-time Maternal
Employment Sir.\p=m-\Iused to be a full-time pedianow I am a full-time mother and a part-time pediatrician. As a member of the "mommy club" (viz, the "old boys' network"), I chuckle at (and am embarrassed by) the advice I used to offer. For example, I used to believe that breast-feeding is, or should be, compatible with full-time maternal employment. Why not, you ask? Everyone does it. Articles and books are filled with advice on pumping and freezing milk, on "role overload," on the joys of "having it all" and of "quality time," and on the nutritional and immunologic benefits of breast milk. Success is measured by "duration of nursing." What could be missing? Discussion of the infant's point of view and of the emotional side of the nursing relationship is usually missing. In fact, the entire mother-child relationship is usually tactfully ig-
trician;
avoiding
nored
or relegated to a final parathat mentions the wonder of the occasional "real" nursing. Any consideration of the infant's feelings and needs is generally absent. Recall that full-time infant day care is a nec¬ essary corollary of full-time maternal employment. Surely who cares for the infant and how are as significant and worthy of discussion as what is placed in the bottle. One might also wonder if breast milk in a bottle from a mother substitute has significance for the in¬ fant as it does for the mother. Does this pattern of feeding permit and help the infant to know and make a relationship with his or her mother? When an infant is nursed, his or her hunger and mother's let-down become synchronized (after about 6 to 8 weeks), forming the physical ba¬ sis for the closeness and gratification of the nursing relationship. It is con¬ fusing and mistaken to use the word breast-feeding for both nursing and for the pairing of lactation (the mainte¬ nance of a milk supply) with breastmilk-in-a-bottle feeding by substitute care-givers. Most published work on combining breast-feeding and em¬ ployment unfortunately neither en¬ tertains these issues nor steps be¬ yond the confines of the technical aspects of the enterprise. I fear my views are so unpopular and are rejected so vehemently be¬ cause they provoke guilt. Finances and careers are usually more flexible and negotiable than we care to admit. What if all this mother-infant separa¬ tion and substitute care (the "hidden" side of "breast-feeding" and working fuU-time) are neither necessary nor best for the infant? We often hear about the busy professional who "has to work." But pumping or no pump¬ ing, saying, "oh, it must be nice to be at home" to an at-home mother im¬ plies a self-sacrifice that simply is not there. In fact, staying home full-time is difficult, does not earn money or build self-esteem like work does, and can regularly make one feel isolated and "stir crazy," longing for the adult world of work where time flies. The gratifications of being at home are pri¬ marily long-term. One hopes that the dependable, consistent, and nurtur¬
graph
ing relationship one provides, though imperfect, is the best building block an
infant can use to become a solid, ma¬ ture person. The end of nursing, too, is a time
Downloaded From: http://archpedi.jamanetwork.com/ by a Michigan State University User on 06/16/2015
when it is difficult not to "need to be back at work." Weaning is a special and challenging period for mother and infant. It marks the end of a spe¬ cial closeness and the emergence of the infant as a person. Perrnitting the infant to reject the breast and support¬ ing his or her growing away are ex¬ traordinarily difficult for most moth¬ ers. Pumping milk until one is either tired of it or until the infant is a certain age both sadly bypass an entire devel¬ opmental step for both partners. Unfortunately, breast milk cannot substitute for parenting (I can hear the cries of indignation already) and our current enthusiasm for combining lac¬ tation and separation may serve to di¬ vert attention from more substantive issues. For example, how can we as professionals and as individuals better support mothering, parenting, and the mother-child relationship? What economic incentives, from paid mater¬ nity leaves to child allowances to flex¬ ible hours with job security, would be most workable? What program of emotional supports (for mothers of all socioeconomic groups) from home visiting to parenting centers, would be best, and how could it be funded? I am certainly a strong advocate of nursing, but until our discussions move be¬ yond breast milk to the mother-child relationship, I fear we are missing the forest for the trees. LYDIA FURMAN, MD 2256 N St James Pkwy Cleveland Heights, OH 44106
Fluid
Management and Arginine Vasopressin in Bacterial
Meningitis
Sir.\p=m-\Padilla and colleagues1 recently reported that urine vasopressin concentrations fell during the first 3 days of treatment of bacterial meningitis when patients received maintenance
fluid requirements containing a mean of 5.6 mEq/kg per day of ionized sodium. In a similar series of patients,2 plasma arginine vasopressin normalized within 24 hours when maintenance plus replacement fluids (the mean volume of fluid administered in a 24-hour period was 1.5 \m=x\ maintenance and contained 7.8 mEq/kg per day ofionized sodium) were given, but remained elevated when fluids were restricted (the mean volume of fluid administered in a 24-hour period was
