6 14
Brief cfinical and laboratory observations
Hirsch and colleagues TM have demonstrated that the increased susceptibility of the n e w b o r n mouse to infection with herpes simplex virus can be corrected by the transfer of macrophages from adult mice. In addition, Blaese 15 noted that the monocyte in the newborn rat is deficient both in host defense against Listeria monocytogenes and in its interaction with lymphocytes in m o u n t i n g a primary antibody response. These findings suggest that rodent monocytes may be functionally less mature than h u m a n monocytes at birth. Alternatively, A D C C effector cell activity may develop earlier in gestational life than do the monocyte functions measured by Blaese 15 and Hirsch and associates.14 Further studies of monocyte function would be helpful in understanding whether monocyte immaturity contributes to the increased susceptibility of the h u m a n neonate to infection.
The Journal of Pediatrics October 1977
5.
6.
7. 8.
9. 10.
11.
REFERENCES 1. Perlmann P, and Holm G: Cytotoxic effects of lymphoid cells in vitro, Adv Immunol ll:117, 1969. 2. MacDonald HR, Bonnard GD, Sordat B, and Zawodnik SA: Antibody-dependent cell-mediated cytotoxicity. Heterogeneity of effector ceils in human peripheral blood, Scand J Immunol 4:487, 1975. 3. Perlmann P, Perlmann H, and Wigzell H: Lymphocyte mediated cytotoxicity in vitro: induction and inhibition by humoral antibody and nature of effector cells, Transplant Rev 13:91, 1972. 4. Wislr F, Frr SS, and Michaelsen TE: Antibodydependent cytotoxicity mediated by human Fc-receptor-
Familial occurrence of the Williams syndrome R. Alan White, M.D., C.M., M. Preus, Ph.D., Gordon V. Watters, M.D., F.R.C.P.(C), and F. Clarke Fraser, Ph.D., M.D.,* Montreal, P. Q., Canada
12.
13.
14.
15.
bearing ceils lacking markers for B- and T-lymphocytes, Int Arch Allergy Appl Immunol 47:139, 1974. Gale RP and Zighelboim J: Modulation of polymorphonuclear leukocyte-mediated antibody-dependent cellular cytotoxicity, J Immunol 113:1793, 1974. Holm G: Lysis of antibody-treated human erythrocytes b.y human leukocytes and macrophages in tissue culture, Int Arch Allergy 43:671, 1972. Harris R, and Ukaejiofo EO: Rapid preparation oflymphocytes for tissue typing, Lancet 2:327, 1969. Shore SL, Melewicz FM, and Gordon DS: The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells: I. Identification of the population of effector cells, J Immunol 118:558, 1977. Milgrom H and Shoa'e SL: Manuscript submitted for publication. Kretschmer RR, Stewardson PD, Papierniak CK, and Gotoff SG: Chemotactic and bactericidal capabilities of human newborn monocytes, J Immunol 117:1303, 1976. Orlowski JP, Sieger L, and Anthony BF: Bactericidal capacity of monocytes of newborn infants, J PEDIATR 89:797, 1976. Weston WL, Carson BS, Barkin RM, and Slater GE: Monocyte-macrophage function in the newborn, Clin Res 24:182A, 1976. Klein RB, Rich KC, Biberstein M, and Stiehm ER: Defective mononuclear and neutrophilic phagocyte chemotaxis in the newborn, Clin Res 24:180A, 1976. Hirsch MS, Zisman B, and Allison AC: Macrophages and age-dependent resistence to herpes virus in mice, J Immunol 104:1160, 1970. Blaese, RM: Macrophage function in the development of immunocompetence and in immunodeficiency, J Reticuloendothel Soc 20:67, 1976.
t6tl"k]rk~~ ~ I I 6 r'k'] 1963 1969 9 WILLIAMS SYNDROME Fig. 1. Pedigree of the two patients described in this report.
THE
VAR| OU S P ATT ER N S
of abnormalities in patients
with the Williams syndrome have recently been reviewed From the Department of Medical Genetics, Paediatrics, and Neurology, The Montreal Children's Hospital Publication No. 449from the McGill University-Montreal Children's Hospital Research Institute. *Reprint address: Department of Medical Genetics, The Montreal Children's Hospital, 2300 Tupper St. Montreal, P.Q., H3H 1P3, Canada.
in THE JOURNAL? The constellation of features'-' has been expanded to include patients without infantile hypercalcemia or supravalvular aortic stenosis. 1 The syndrome is usually sporadic in occurrence. Two patients are reported here who are second cousins.
CASE REPORTS The first patient (L,K.) was referred at 13 years of age to the Department of Medical Genetics; the tentative diagnosis was Williams syndrome. At that time she was attending a special
Volume 91 Number 4
Brief clinical and laboratory observations
6 15
Fig. 2. The facies of A, Patient L.K., and B, Patient R.B., which are characteristic of Williams syndrome.
school; her IQ (Stanford-Binet) was 70. The family pedigree is depicted in Fig. 1. Patient L.K.'s gestation period was 40 weeks; birth weight, 2.1 kg (less than the third percentile for gestational age). She was fetally malnourished and remained in hospital for two weeks because of feeding difficulties and "jitteriness." The serum calcium concentration at that time was normal. At two years of age she was readmitted to hospital for evaluation of motor, mental, and growth retardation. The characteristics noted at the time of referral are presented in Table I. The electroencephalogram was abnormal. The second patient (R.B.) was referred at 3 years of age with a tentative diagnosis of Smith-Lemli-Opitz syndrome. He was a second cousin of L.K. (Fig. 1). The gestation was 43 weeks; the birth weight, 2.5 kg (less than the third percentile for age). In the neonatal period he had meconium aspiration, hypoglycemia, and feeding difficulties that were attributed to palatopharyngeal incoordination. The serum calcium level was normal. The head circumference at birth was at the fiftieth percentile, but at 2 years of age it was below the third percentile. The characteristics noted at the time of referral are presented in Table 1. In addition, there were dolichocephaly, epicanthal folds, grade I hypospadias, and bilateral high axial triradii. Each of the children has a normal karyotype on orcein staining. DISCUSSION T h e p h e n o t y p e s o f t h e two patients, as s h o w n in T a b l e I a n d in Fig. 2, are c h a r a c t e r i s t i c o f the W i l l i a m s s y n d r o m e . As in o u r two patients, i n f a n t i l e h y p e r c a l c e m i a a n d c a r d i o v a s c u l a r a b n o r m a l i t i e s m a y b e a b s e n t in c h i l d r e n w i t h the s y n d r o m e . ~ T h e W i l l i a m s s y n d r o m e is usually s p o r a d i c in occurrence, 1 b u t h a s b e e n r e p o r t e d in b o t h m o n o z y g o t i c a n d dizygotic twins, :~. ~ in siblings, ''-" a n d in t h e s e c o n d cousins
T a b l e I. C h a r a c t e r i s t i c s o f the s y n d r o m e 1 n o t e d in the p r e s e n t cases
Patient Patient L.K. R.B.
%*
Prenatal growth deficiency Postnatal growth deficiency
+ +
+ +
80 89
Microcephaly Mental deficiency Unusual personality Mild neurologic dysfunction Median eyebrow flare Ocular hypotelorism Depressed nasal bridge Periorbital fullness Strabismus Blue eyes Stellate (lacy) pattern of irides Anteverted nares Long philtrum Prominent lips with open mouth
+ + + + + + + + + + + -+
+ + + + + + + + + + +
67 94 67 57 81 53 68 56 35 74 72 74 56 89
Cardiovascular abnormality
-
-
*Percentage of findings in previously recorded patients. r e p o r t e d here. Since t h e s y n d r o m e is rare, t h e o c c u r r e n c e in s e c o n d cousins is u n l i k e l y to b e c o i n c i d e n t a l . A n o c c a s i o n a l o c c u r r e n c e in relatives, h o w e v e r , m i g h t b e a c c o u n t e d for b y r e d u c e d p e n e t r a n c e , d e l a y e d m u t a t i o n , a f a m i l i a l e n v i r o n m e n t a l factor, or g e n e t i c h e t e r o g e n e i t y . E v e n t h o u g h the r e c u r r e n c e risk is low, t h e c l i n i c i a n o u g h t to e n q u i r e a b o u t a n d i n v e s t i g a t e o t h e r f a m i l y m e m b e r s with m e n t a l deficiency a n d g r o w t h r e t a r d a t i o n w h e n e v e r this c o n d i t i o n is d i a g n o s e d . It is o n l y i n this w a y
6 16
B r i e f clinical and laboratory observations
that accurate recurrence risks may be defined and the genetic pathogenesis clarified.
REFERENCES 1. Jones KL, and Smith DW: The Williams elfin facies syndrome, J PEDIATR86:718, 1975. 2. Williams JCP, Barratt-Boyes BC, and Lowe JB: Supravalvular aortic stenosis, Circular 24:1311, 1961. 3. Wiltse HE, Goldbloom RB, Antia AU, Ottesen OE, Rowe RO, and Cooke RE: Infantile hypercalcemia syndrome in twins, N Engl J Med 275:1157, 1966. 4. Illig R, and Prader A: Kasuistische Beitrage zur Idiopath-
Wegener granulomatosis in childhood: Prolonged survival following cytotoxic therapy A. Vishnu Moorthy, M.D.,* Russell W. Chesney, M.D., William E. Segar, M.D., and Ted Groshong, M.D.,** Madison, Wis.
WEGENER GRANULOMATOSIS is characterized by a widespread necrotizing and granulomatous vasculitis of small arteries and veins o f the upper and lower respiratory tracts and kidneys? The disseminated form of the disease may involve the eyes, middle ear, larynx, skin, joints, heart, and central and peripheral nervous systems in this necrotizing process? Treatment with cytotoxic agents, particularly cyclophosphamide, has altered the m e a n survival of what was a rapidly fatal disease 2 to the point that remission and survival for several years have now been reported? A limited form of the disease is known; pathologic changes are limited to the respiratory tract? To our knowledge only seven cases of disseminated Wegener granulomatosis have been reported under the age of From the Departments of Pediatrics, Medicine, and Pathology, The Nephrology Program, University of Wisconsin Center for Health Sciences. *Supported in part by a United States Public Health Service training grant No. AM 05582-08. Reprint address: Dr. A.V. Moorthy~ Department of Pediatrics, University of Wisconsin, 1300 UniversityAve., Madison, W1 53706. **Recipient of the John Orton Watkins Research Fellowship in Medical Sciences.
The Journal of Pediatrics October 1977
ischen Hypercalcemie und Vitamin D Intoxication, Helv Paediatr Acta 14:618, 1959. 5. Forfar JO: Clinical and metabolic studies in idiopathic hypercalcemia of infancy, M.D. Thesis, Scotland, 1958, University of St. Andrews, p 78 (cited in reference 6). 6. Kenny FM, Aceto T Jr, Purisch M, Harrison HE, Harrison HC, and Blizzard RM: Metabolic studies in a patient with idiopathic hypercalcemia of infancy, J P~DIATR 62:531, 1963. 7. Antia AU, Wiltse HE, Rowe RD, Pitt EL, Levin S, Ottesen OE, and Cooke RE: Pathogenesis of the supravalvular aortic stenosis syndrome, J PEDIATR61:431, 1967.
16r -1~ since the peak incidence of the disease is in.the fourth to fifth decades. Each patient died despite various forms of therapy. W e have observed two children with this disease, 10 and 13 years & a g e , who have survived for two and one-half and five years, respectively, while on prednisone and intermittent cyclophosphamide therapy. CASE REPORTS
Case 1. Patient K.F., a 10-year-old girl, presented in May, 1974, with mucopurulent and sanguinous nasal discharge and bilateral proptosis. A nontender mass measuring 25 x 15 mm was palpable through the right upper eyelid and a smaller mass was palpable in the left orbit. Urinalysis was normal. A diagnosis of pseudotumor of the orbit was made. Granulomatous vasculitis, characterized by inflammation of small arterioles and veins and by paravascular granulomata with chronic inflammatory cells and multinucleated giant cells, was noted on the biopsy of the orbital mass. Prednisone therapy was started. In November, 1974, she developed anemia and azotemia. Urinalysis revealed over 50 red blood cells per high-powered field with many red blood cell and granular casts. Urinary protein excretion was 5 gm/day. Serum creatinine was 2A mg/dl and creatinine clearance 36 rag/minute/1.73 m ~. Hemoglobin was 9.5 gm/dl, serum complement (C3) 105 mg/dl, lgE 100 IU/ ml (normal 50 to 250 IU/ml), and serum antinuclear antibodies and anti-GBM (glomerular basement membrane) antibodies were negative. A percutaneous renal biopsy revealed proliferative glomerulonephritis with epithelial cellular crescents. Many glomeruli were totally sclerosed, while some others had only segmental proliferation. Medium-sized arterioles showed vasculitis. A granular deposition of immunoglobulin G and C3 was seen in the glomeruli. Oral cyclophosphamide, 75 mg/day (2 mg/kg), was started. Over the next two months urine protein excretion decreased to 1.0 gm/day, and creatinine clearafice increased to 61 ml/minute/ 1.73 m 2. Cyclophosphamide, 50 rag/day, and 20 rag/day of prednisone on alternate days were used for the next 16 months. All therapy was discontinued in July, 1976, because she was asymptomatic with stable renal function. However, in November, 1976, she became febrile, developed nasal mucosal ulceration and purulent discharge, and a roentgenographic examination disclosed a maxillary sinusitis with bony erosions. Partial ptosis of the right eye with proptosis recurred. Resumption of therapy with
Brief cfinical and laboratory observations
Hirsch and colleagues TM have demonstrated that the increased susceptibility of the n e w b o r n mouse to infection with herpes simplex virus can be corrected by the transfer of macrophages from adult mice. In addition, Blaese 15 noted that the monocyte in the newborn rat is deficient both in host defense against Listeria monocytogenes and in its interaction with lymphocytes in m o u n t i n g a primary antibody response. These findings suggest that rodent monocytes may be functionally less mature than h u m a n monocytes at birth. Alternatively, A D C C effector cell activity may develop earlier in gestational life than do the monocyte functions measured by Blaese 15 and Hirsch and associates.14 Further studies of monocyte function would be helpful in understanding whether monocyte immaturity contributes to the increased susceptibility of the h u m a n neonate to infection.
The Journal of Pediatrics October 1977
5.
6.
7. 8.
9. 10.
11.
REFERENCES 1. Perlmann P, and Holm G: Cytotoxic effects of lymphoid cells in vitro, Adv Immunol ll:117, 1969. 2. MacDonald HR, Bonnard GD, Sordat B, and Zawodnik SA: Antibody-dependent cell-mediated cytotoxicity. Heterogeneity of effector ceils in human peripheral blood, Scand J Immunol 4:487, 1975. 3. Perlmann P, Perlmann H, and Wigzell H: Lymphocyte mediated cytotoxicity in vitro: induction and inhibition by humoral antibody and nature of effector cells, Transplant Rev 13:91, 1972. 4. Wislr F, Frr SS, and Michaelsen TE: Antibodydependent cytotoxicity mediated by human Fc-receptor-
Familial occurrence of the Williams syndrome R. Alan White, M.D., C.M., M. Preus, Ph.D., Gordon V. Watters, M.D., F.R.C.P.(C), and F. Clarke Fraser, Ph.D., M.D.,* Montreal, P. Q., Canada
12.
13.
14.
15.
bearing ceils lacking markers for B- and T-lymphocytes, Int Arch Allergy Appl Immunol 47:139, 1974. Gale RP and Zighelboim J: Modulation of polymorphonuclear leukocyte-mediated antibody-dependent cellular cytotoxicity, J Immunol 113:1793, 1974. Holm G: Lysis of antibody-treated human erythrocytes b.y human leukocytes and macrophages in tissue culture, Int Arch Allergy 43:671, 1972. Harris R, and Ukaejiofo EO: Rapid preparation oflymphocytes for tissue typing, Lancet 2:327, 1969. Shore SL, Melewicz FM, and Gordon DS: The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells: I. Identification of the population of effector cells, J Immunol 118:558, 1977. Milgrom H and Shoa'e SL: Manuscript submitted for publication. Kretschmer RR, Stewardson PD, Papierniak CK, and Gotoff SG: Chemotactic and bactericidal capabilities of human newborn monocytes, J Immunol 117:1303, 1976. Orlowski JP, Sieger L, and Anthony BF: Bactericidal capacity of monocytes of newborn infants, J PEDIATR 89:797, 1976. Weston WL, Carson BS, Barkin RM, and Slater GE: Monocyte-macrophage function in the newborn, Clin Res 24:182A, 1976. Klein RB, Rich KC, Biberstein M, and Stiehm ER: Defective mononuclear and neutrophilic phagocyte chemotaxis in the newborn, Clin Res 24:180A, 1976. Hirsch MS, Zisman B, and Allison AC: Macrophages and age-dependent resistence to herpes virus in mice, J Immunol 104:1160, 1970. Blaese, RM: Macrophage function in the development of immunocompetence and in immunodeficiency, J Reticuloendothel Soc 20:67, 1976.
t6tl"k]rk~~ ~ I I 6 r'k'] 1963 1969 9 WILLIAMS SYNDROME Fig. 1. Pedigree of the two patients described in this report.
THE
VAR| OU S P ATT ER N S
of abnormalities in patients
with the Williams syndrome have recently been reviewed From the Department of Medical Genetics, Paediatrics, and Neurology, The Montreal Children's Hospital Publication No. 449from the McGill University-Montreal Children's Hospital Research Institute. *Reprint address: Department of Medical Genetics, The Montreal Children's Hospital, 2300 Tupper St. Montreal, P.Q., H3H 1P3, Canada.
in THE JOURNAL? The constellation of features'-' has been expanded to include patients without infantile hypercalcemia or supravalvular aortic stenosis. 1 The syndrome is usually sporadic in occurrence. Two patients are reported here who are second cousins.
CASE REPORTS The first patient (L,K.) was referred at 13 years of age to the Department of Medical Genetics; the tentative diagnosis was Williams syndrome. At that time she was attending a special
Volume 91 Number 4
Brief clinical and laboratory observations
6 15
Fig. 2. The facies of A, Patient L.K., and B, Patient R.B., which are characteristic of Williams syndrome.
school; her IQ (Stanford-Binet) was 70. The family pedigree is depicted in Fig. 1. Patient L.K.'s gestation period was 40 weeks; birth weight, 2.1 kg (less than the third percentile for gestational age). She was fetally malnourished and remained in hospital for two weeks because of feeding difficulties and "jitteriness." The serum calcium concentration at that time was normal. At two years of age she was readmitted to hospital for evaluation of motor, mental, and growth retardation. The characteristics noted at the time of referral are presented in Table I. The electroencephalogram was abnormal. The second patient (R.B.) was referred at 3 years of age with a tentative diagnosis of Smith-Lemli-Opitz syndrome. He was a second cousin of L.K. (Fig. 1). The gestation was 43 weeks; the birth weight, 2.5 kg (less than the third percentile for age). In the neonatal period he had meconium aspiration, hypoglycemia, and feeding difficulties that were attributed to palatopharyngeal incoordination. The serum calcium level was normal. The head circumference at birth was at the fiftieth percentile, but at 2 years of age it was below the third percentile. The characteristics noted at the time of referral are presented in Table 1. In addition, there were dolichocephaly, epicanthal folds, grade I hypospadias, and bilateral high axial triradii. Each of the children has a normal karyotype on orcein staining. DISCUSSION T h e p h e n o t y p e s o f t h e two patients, as s h o w n in T a b l e I a n d in Fig. 2, are c h a r a c t e r i s t i c o f the W i l l i a m s s y n d r o m e . As in o u r two patients, i n f a n t i l e h y p e r c a l c e m i a a n d c a r d i o v a s c u l a r a b n o r m a l i t i e s m a y b e a b s e n t in c h i l d r e n w i t h the s y n d r o m e . ~ T h e W i l l i a m s s y n d r o m e is usually s p o r a d i c in occurrence, 1 b u t h a s b e e n r e p o r t e d in b o t h m o n o z y g o t i c a n d dizygotic twins, :~. ~ in siblings, ''-" a n d in t h e s e c o n d cousins
T a b l e I. C h a r a c t e r i s t i c s o f the s y n d r o m e 1 n o t e d in the p r e s e n t cases
Patient Patient L.K. R.B.
%*
Prenatal growth deficiency Postnatal growth deficiency
+ +
+ +
80 89
Microcephaly Mental deficiency Unusual personality Mild neurologic dysfunction Median eyebrow flare Ocular hypotelorism Depressed nasal bridge Periorbital fullness Strabismus Blue eyes Stellate (lacy) pattern of irides Anteverted nares Long philtrum Prominent lips with open mouth
+ + + + + + + + + + + -+
+ + + + + + + + + + +
67 94 67 57 81 53 68 56 35 74 72 74 56 89
Cardiovascular abnormality
-
-
*Percentage of findings in previously recorded patients. r e p o r t e d here. Since t h e s y n d r o m e is rare, t h e o c c u r r e n c e in s e c o n d cousins is u n l i k e l y to b e c o i n c i d e n t a l . A n o c c a s i o n a l o c c u r r e n c e in relatives, h o w e v e r , m i g h t b e a c c o u n t e d for b y r e d u c e d p e n e t r a n c e , d e l a y e d m u t a t i o n , a f a m i l i a l e n v i r o n m e n t a l factor, or g e n e t i c h e t e r o g e n e i t y . E v e n t h o u g h the r e c u r r e n c e risk is low, t h e c l i n i c i a n o u g h t to e n q u i r e a b o u t a n d i n v e s t i g a t e o t h e r f a m i l y m e m b e r s with m e n t a l deficiency a n d g r o w t h r e t a r d a t i o n w h e n e v e r this c o n d i t i o n is d i a g n o s e d . It is o n l y i n this w a y
6 16
B r i e f clinical and laboratory observations
that accurate recurrence risks may be defined and the genetic pathogenesis clarified.
REFERENCES 1. Jones KL, and Smith DW: The Williams elfin facies syndrome, J PEDIATR86:718, 1975. 2. Williams JCP, Barratt-Boyes BC, and Lowe JB: Supravalvular aortic stenosis, Circular 24:1311, 1961. 3. Wiltse HE, Goldbloom RB, Antia AU, Ottesen OE, Rowe RO, and Cooke RE: Infantile hypercalcemia syndrome in twins, N Engl J Med 275:1157, 1966. 4. Illig R, and Prader A: Kasuistische Beitrage zur Idiopath-
Wegener granulomatosis in childhood: Prolonged survival following cytotoxic therapy A. Vishnu Moorthy, M.D.,* Russell W. Chesney, M.D., William E. Segar, M.D., and Ted Groshong, M.D.,** Madison, Wis.
WEGENER GRANULOMATOSIS is characterized by a widespread necrotizing and granulomatous vasculitis of small arteries and veins o f the upper and lower respiratory tracts and kidneys? The disseminated form of the disease may involve the eyes, middle ear, larynx, skin, joints, heart, and central and peripheral nervous systems in this necrotizing process? Treatment with cytotoxic agents, particularly cyclophosphamide, has altered the m e a n survival of what was a rapidly fatal disease 2 to the point that remission and survival for several years have now been reported? A limited form of the disease is known; pathologic changes are limited to the respiratory tract? To our knowledge only seven cases of disseminated Wegener granulomatosis have been reported under the age of From the Departments of Pediatrics, Medicine, and Pathology, The Nephrology Program, University of Wisconsin Center for Health Sciences. *Supported in part by a United States Public Health Service training grant No. AM 05582-08. Reprint address: Dr. A.V. Moorthy~ Department of Pediatrics, University of Wisconsin, 1300 UniversityAve., Madison, W1 53706. **Recipient of the John Orton Watkins Research Fellowship in Medical Sciences.
The Journal of Pediatrics October 1977
ischen Hypercalcemie und Vitamin D Intoxication, Helv Paediatr Acta 14:618, 1959. 5. Forfar JO: Clinical and metabolic studies in idiopathic hypercalcemia of infancy, M.D. Thesis, Scotland, 1958, University of St. Andrews, p 78 (cited in reference 6). 6. Kenny FM, Aceto T Jr, Purisch M, Harrison HE, Harrison HC, and Blizzard RM: Metabolic studies in a patient with idiopathic hypercalcemia of infancy, J P~DIATR 62:531, 1963. 7. Antia AU, Wiltse HE, Rowe RD, Pitt EL, Levin S, Ottesen OE, and Cooke RE: Pathogenesis of the supravalvular aortic stenosis syndrome, J PEDIATR61:431, 1967.
16r -1~ since the peak incidence of the disease is in.the fourth to fifth decades. Each patient died despite various forms of therapy. W e have observed two children with this disease, 10 and 13 years & a g e , who have survived for two and one-half and five years, respectively, while on prednisone and intermittent cyclophosphamide therapy. CASE REPORTS
Case 1. Patient K.F., a 10-year-old girl, presented in May, 1974, with mucopurulent and sanguinous nasal discharge and bilateral proptosis. A nontender mass measuring 25 x 15 mm was palpable through the right upper eyelid and a smaller mass was palpable in the left orbit. Urinalysis was normal. A diagnosis of pseudotumor of the orbit was made. Granulomatous vasculitis, characterized by inflammation of small arterioles and veins and by paravascular granulomata with chronic inflammatory cells and multinucleated giant cells, was noted on the biopsy of the orbital mass. Prednisone therapy was started. In November, 1974, she developed anemia and azotemia. Urinalysis revealed over 50 red blood cells per high-powered field with many red blood cell and granular casts. Urinary protein excretion was 5 gm/day. Serum creatinine was 2A mg/dl and creatinine clearance 36 rag/minute/1.73 m ~. Hemoglobin was 9.5 gm/dl, serum complement (C3) 105 mg/dl, lgE 100 IU/ ml (normal 50 to 250 IU/ml), and serum antinuclear antibodies and anti-GBM (glomerular basement membrane) antibodies were negative. A percutaneous renal biopsy revealed proliferative glomerulonephritis with epithelial cellular crescents. Many glomeruli were totally sclerosed, while some others had only segmental proliferation. Medium-sized arterioles showed vasculitis. A granular deposition of immunoglobulin G and C3 was seen in the glomeruli. Oral cyclophosphamide, 75 mg/day (2 mg/kg), was started. Over the next two months urine protein excretion decreased to 1.0 gm/day, and creatinine clearafice increased to 61 ml/minute/ 1.73 m 2. Cyclophosphamide, 50 rag/day, and 20 rag/day of prednisone on alternate days were used for the next 16 months. All therapy was discontinued in July, 1976, because she was asymptomatic with stable renal function. However, in November, 1976, she became febrile, developed nasal mucosal ulceration and purulent discharge, and a roentgenographic examination disclosed a maxillary sinusitis with bony erosions. Partial ptosis of the right eye with proptosis recurred. Resumption of therapy with
