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
Volume 91 Number 4
Brief clinical and laboratory observations
6 17
Table I. D i s s e m i n a t e d W e g e n e r g r a n u l o m a t o s i s in c h i l d r e n 16 years o f age or y o u n g e r
No.
Reference
Sex Age onsetat
1 Case Records of M Mass Gen Hosp, 195F 2 Fahey et al, 1954~ F
i2
12
Systems involved Heart, lungs, kidney, central nervous system Nasopharynx, lung, kidney, joints middle ear Nasopharynx, lung, kidney
3 Feldman et al, 1966~,
F
13
4 Roback et al, 1969'~
M
16
5 Lancos et al, F 19717 6 Isaeva et al, 1972~ M
9
Lung, kidney
8
Nasopharynx, lung, kidney
7 Hu et al, 1977~'
M
8 Present report Case 1 9 Present report Case 2
F F
14
Nasopharynx, lung, joints kidney, skin
Nasopharynx, lung, kidney, skin 10 Eye, nasopharynx, kidney, skin 12 Eye, nasopharynx. 6/12 lung, kidney larynx, joints, skin
Tissue diagnosis
Treatment
I
Course
Cause of death
Kidney, lung, brain
Symptomatic
Death in 2 years
Cardiopulmonary failure
Lung, spleen, kidney, heart
Symptomatic
Death in 1 mo
Respiratory failure
Heart, lung spleen, kidney Maxillary sinus mucosa, kidney lung
Symptomatic
Death in 7 wk
Respiratory failure
Prednisone, azathioprine (short course before death) Symptomatic, hemodialysis Prednisone
Death in 5 mo
Renal failure and bleeding diathesis
Death in 3 mo
Renal failure
Death in 2 wk
Respiratory failure, bleeding, diathesis Respiratory and renal failure
Lung and kidney Pharynx, kidney, lung Skin, kidney
Death in 6 wk
Orbital tissue, kidney, skin Nasal mucosa, skin
cyclophosphamide 50 mg/day and prednisone 20 mg on alternate days produced a second remission. Renal function is stable, serum creatinine is 1.3 mg/dl, and she excretes 900 mg of protein daily. Case 2. Patient C. J., born in 1959, was seen in February, 1972, after seven weeks of a purulent and sanguinous nasal discharge, fever, blurred vision, and a dry, nonproductive cough. The nasal mucosa was swollen, granular appearing, and extremely friable. A roentgenographic examination disclosed marked thickening of the mucosa of paranasal sinuses. She had bilateral optic papillitis; vision in the right eye was 20/800 and in the left was 20/200. A chest roentgenogram demonstrated multiple right-sided round densities from 3 to 8 cm in diameter. Urinalysis revealed 15 to 20 red blood cells/high-powered field, 100 mg/dl protein, and cellular casts. The serum creatinine concentration was 0.7 mg/dl. Serum antinuclear antibodies were negative and the serum complement (C3) 130 mg/dl. The serum IgE level was 120 IU/ml. A biopsy of the mucosa of the right maxillary sinus had histologic features characteristic of Wegener granulomatosis. Initial treatment consisted of 60 mg prednisone and 250 mg azathioprine per day. Since the nasal discharge persisted and she developed a bilateral painful serosanguinous otitis media, azathioprine was discontinued and cyclophosphamide, 100 mg/ day (2 mg/kg body weight), was begun. A stormy course characterized by recurrent pulmonary granulomata with bilateral pleural effusions, cutaneous nodular lesions, polyarthralgias, microangiopathic hemolytic anemia, neutropenia, and staphylococcal facial cellulitis followed which required discontinuation of
Prednisone, cyclophosphamide Prednisone, cyclophosphamide (Azathioprine chlorambucil)
Good response with relapse Good response with many relapses
cyclophosphamide therapy for two weeks. Following three months of therapy improvement was observed, and medications were altered to prednisone 20 mg on alternate days and cyclophosphamide 50 mg/day. In July, 1973, cyclophosphamide was discontinued because she developed cystitis and gross hematuria. Over the next three and a half years she received three additional courses of cyclophosphamide to control relapses characterized by blepheroconjunctivitis and otitis media on one occasion and granulomatous ulcerations of the larynx on two occasions. Cyclophosphamide was given for six months at 100 to 125 mg/ day on each occasion. At present she has bilateral scotomata, a mixed restrictive and obstructive pattern in pulmonary function, and a bilateral conductive hearing defect. DISCUSSION W e g e n e r g r a n u l o m a t o s i s is diagnosed b y the criteria o f F a h e y a n d associates ~ which include: (1) necrotizing g r a n u l o m a s o f the respiratory tract; (2) a generalized focal necrotizing vasculitis involving b o t h arteries a n d veins; and (3) a glomerulitis characterized by necrosis a n d thrombosis of loops o f the capillary tuft, c a p s u l a r a d h e sion, a n d a g r a n u l o m a t o u s evolution. Each o f the patients described here h a d the dissemin a t e d form o f the disease exhibiting r h i n o r r h e a , epistaxis, nasal obstruction, chronic sinusitus, fever, malaise, t r a c h e o b r o n c h i a l or n a s o p h a r y n g e a l ulcers with nasal deformation, serous otitis m e d i a with h e a r i n g loss, polyar-
6 18
Brief clinical and laboratory observations
thralgias, decreased vision from optic nerve granuloma, laryngitis with aphonia on several occasions, nodular or infiltrative parenchymal pulmonary lesions, proptosis, pseudotumor of the orbit, cutaneous nodules, and renal lesions. These patients did not appear to have any of the other vasculitic or granulomatous diseases in the differential diagnosis of Wegener granulomatosis. Although 200 cases of this disease had been reported by 1967 and several other large series have recently appeared,1. ,0 to our knowledge only seven cases of disseminated Wegener granulomatosis under the age of 16, each with a fatal outcome, have been described ~-1~ (Table I). Most of these patients had been given either symptomatic treatment or treatment with prednisone alone. Both of our patients have been treated with prednisone and cyclophosphamide. Patient 1 received 18 months of cyclophosphamide therapy. Since then she has experienced clinical improvement and maintained stable renal function. Patient 2 was treated for three months with azathioprine without apparent benefit, but had clinical improvement after cyclophosphamide was substituted. The introduction of cytotoxic therapy for this disorder has vastly improved the previous mean survival rate of five months. 2 Only three deaths have occurred among 47 patients given an adequate therapeutic trial with a variety of immunosuppressive agents, including azathioprine, chlorambucil, or cyclophosphamide.' Cyclophosphamide has been used more frequently than the other agents'. 10at a dose of 1 to 2 mg/kg by mouth or 2 to 4 mg/kg intravenously for the first week in fulminant cases. It is uncertain how long this form of therapy should be used.
Congenital complete heart block associated with hydrops fetalis Karl M. Altenburger, M.D.,* Maryann Jedziniak, M.D., William L. Roper, M.D., and Jacinto Hernandez, M.D., Denver, Colo. From The Department of Pediatrics, University of Colorado Medical Center, and The Children's Hospital. *Reprint address: Department of Pediatrics, Box C-220, University of Colorado Medical Center, Denver, CO 80262.
The Journal of Pediatrics October 1977
Most patients show evidence of remission within several weeks, but relapses are known to occur in patients apparently free of the disease for one year.' Relapses have responded to additional courses o f cyclophosphamide, with lasting improvement for as long as 689 years. We thank Scott Arnold, M.D., of Cuba City, Wis., and Jack Schroeder, M.D., of Beloit, Wis., for referral of these patients, Charles Brandenberg, M.D., for expert otolaryngologic consultation, Thomas France, M.D., for expert opthalmologic consultation, and to Ms. Joyce Bublitz for secretarial assistance. REFERENCES 1. WolffSM, Fauci AS, Horn RG, et al: Wegener's granulomatosis, Ann Intern Med 81:513, t974. 2. Walton EW: Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis), Br Med J 11:265, 1958. 3. Carrington CB, and Liebow AA: Limited forms of angiitis and granulomatosis of Wegener's type, Am J Med 41:497, 1966. 4. Case records of the Mass. General Hospital, Case No. 37511, N Engl J Med 245:978, 1951. 5. Feldman F, Fink H, and Gruezo Z: Wegener's granulomatosis, Am J Dis Child 112:587, 1966. 6. Roback SA, Herdman RC, Hoyer JH, et al: Wegener's granulomatosis in a child: Observations in pathogenesis and treatment, Am J Dis Child 118:608, 1969. 7. LancosF, Erdos Z, Kadar A, et al: Wegenersche granulomatose in kindesalter, Acta Paediatr Acad Sci Hung 12:285, 1971. 8. Fahey J, Leonard E, Churg J, et al: Wegener's granulomatosis, Am J Med 17:168, 1954. 9. Isaeva LA, Fedorova AN, Lysinka GA, et al: Wegener's granulomatosis in children, Pediatriia 51:67, t972. 10. Hu C-H, O'Loughlin S, and Winkelmann RK: Cutaneous manifestations of Wegener granulomatosis, Arch Dermatol 113:175, 1977.
THIS REPORT describes a newborn infant with congenital complete heart block resulting in hydrops retails. CASE R E P O R T A five-hour-old white male infant was admitted to The Children's Hospital intensive care nursery because of severe hydrops and respiratory distress. He was born at 33 weeks' gestation to a healthy 31-year-old mother. At 32 weeks' gestation Abbreviation used ANA: antinuclear antibodies
I
the fetal heart rate was noted to be 40 to 60/minute. Because fetal movement' had continued unchanged, no fetal distress was presumed. One week later the mother noted decreased fetal movement. The fetal heart rate was again regular at 40 to 60 beats/minute. An ultrasound scan showed a "halo" around the fetal head, and an emergency cesarean section was performed for presumed fetal distress.
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
Volume 91 Number 4
Brief clinical and laboratory observations
6 17
Table I. D i s s e m i n a t e d W e g e n e r g r a n u l o m a t o s i s in c h i l d r e n 16 years o f age or y o u n g e r
No.
Reference
Sex Age onsetat
1 Case Records of M Mass Gen Hosp, 195F 2 Fahey et al, 1954~ F
i2
12
Systems involved Heart, lungs, kidney, central nervous system Nasopharynx, lung, kidney, joints middle ear Nasopharynx, lung, kidney
3 Feldman et al, 1966~,
F
13
4 Roback et al, 1969'~
M
16
5 Lancos et al, F 19717 6 Isaeva et al, 1972~ M
9
Lung, kidney
8
Nasopharynx, lung, kidney
7 Hu et al, 1977~'
M
8 Present report Case 1 9 Present report Case 2
F F
14
Nasopharynx, lung, joints kidney, skin
Nasopharynx, lung, kidney, skin 10 Eye, nasopharynx, kidney, skin 12 Eye, nasopharynx. 6/12 lung, kidney larynx, joints, skin
Tissue diagnosis
Treatment
I
Course
Cause of death
Kidney, lung, brain
Symptomatic
Death in 2 years
Cardiopulmonary failure
Lung, spleen, kidney, heart
Symptomatic
Death in 1 mo
Respiratory failure
Heart, lung spleen, kidney Maxillary sinus mucosa, kidney lung
Symptomatic
Death in 7 wk
Respiratory failure
Prednisone, azathioprine (short course before death) Symptomatic, hemodialysis Prednisone
Death in 5 mo
Renal failure and bleeding diathesis
Death in 3 mo
Renal failure
Death in 2 wk
Respiratory failure, bleeding, diathesis Respiratory and renal failure
Lung and kidney Pharynx, kidney, lung Skin, kidney
Death in 6 wk
Orbital tissue, kidney, skin Nasal mucosa, skin
cyclophosphamide 50 mg/day and prednisone 20 mg on alternate days produced a second remission. Renal function is stable, serum creatinine is 1.3 mg/dl, and she excretes 900 mg of protein daily. Case 2. Patient C. J., born in 1959, was seen in February, 1972, after seven weeks of a purulent and sanguinous nasal discharge, fever, blurred vision, and a dry, nonproductive cough. The nasal mucosa was swollen, granular appearing, and extremely friable. A roentgenographic examination disclosed marked thickening of the mucosa of paranasal sinuses. She had bilateral optic papillitis; vision in the right eye was 20/800 and in the left was 20/200. A chest roentgenogram demonstrated multiple right-sided round densities from 3 to 8 cm in diameter. Urinalysis revealed 15 to 20 red blood cells/high-powered field, 100 mg/dl protein, and cellular casts. The serum creatinine concentration was 0.7 mg/dl. Serum antinuclear antibodies were negative and the serum complement (C3) 130 mg/dl. The serum IgE level was 120 IU/ml. A biopsy of the mucosa of the right maxillary sinus had histologic features characteristic of Wegener granulomatosis. Initial treatment consisted of 60 mg prednisone and 250 mg azathioprine per day. Since the nasal discharge persisted and she developed a bilateral painful serosanguinous otitis media, azathioprine was discontinued and cyclophosphamide, 100 mg/ day (2 mg/kg body weight), was begun. A stormy course characterized by recurrent pulmonary granulomata with bilateral pleural effusions, cutaneous nodular lesions, polyarthralgias, microangiopathic hemolytic anemia, neutropenia, and staphylococcal facial cellulitis followed which required discontinuation of
Prednisone, cyclophosphamide Prednisone, cyclophosphamide (Azathioprine chlorambucil)
Good response with relapse Good response with many relapses
cyclophosphamide therapy for two weeks. Following three months of therapy improvement was observed, and medications were altered to prednisone 20 mg on alternate days and cyclophosphamide 50 mg/day. In July, 1973, cyclophosphamide was discontinued because she developed cystitis and gross hematuria. Over the next three and a half years she received three additional courses of cyclophosphamide to control relapses characterized by blepheroconjunctivitis and otitis media on one occasion and granulomatous ulcerations of the larynx on two occasions. Cyclophosphamide was given for six months at 100 to 125 mg/ day on each occasion. At present she has bilateral scotomata, a mixed restrictive and obstructive pattern in pulmonary function, and a bilateral conductive hearing defect. DISCUSSION W e g e n e r g r a n u l o m a t o s i s is diagnosed b y the criteria o f F a h e y a n d associates ~ which include: (1) necrotizing g r a n u l o m a s o f the respiratory tract; (2) a generalized focal necrotizing vasculitis involving b o t h arteries a n d veins; and (3) a glomerulitis characterized by necrosis a n d thrombosis of loops o f the capillary tuft, c a p s u l a r a d h e sion, a n d a g r a n u l o m a t o u s evolution. Each o f the patients described here h a d the dissemin a t e d form o f the disease exhibiting r h i n o r r h e a , epistaxis, nasal obstruction, chronic sinusitus, fever, malaise, t r a c h e o b r o n c h i a l or n a s o p h a r y n g e a l ulcers with nasal deformation, serous otitis m e d i a with h e a r i n g loss, polyar-
6 18
Brief clinical and laboratory observations
thralgias, decreased vision from optic nerve granuloma, laryngitis with aphonia on several occasions, nodular or infiltrative parenchymal pulmonary lesions, proptosis, pseudotumor of the orbit, cutaneous nodules, and renal lesions. These patients did not appear to have any of the other vasculitic or granulomatous diseases in the differential diagnosis of Wegener granulomatosis. Although 200 cases of this disease had been reported by 1967 and several other large series have recently appeared,1. ,0 to our knowledge only seven cases of disseminated Wegener granulomatosis under the age of 16, each with a fatal outcome, have been described ~-1~ (Table I). Most of these patients had been given either symptomatic treatment or treatment with prednisone alone. Both of our patients have been treated with prednisone and cyclophosphamide. Patient 1 received 18 months of cyclophosphamide therapy. Since then she has experienced clinical improvement and maintained stable renal function. Patient 2 was treated for three months with azathioprine without apparent benefit, but had clinical improvement after cyclophosphamide was substituted. The introduction of cytotoxic therapy for this disorder has vastly improved the previous mean survival rate of five months. 2 Only three deaths have occurred among 47 patients given an adequate therapeutic trial with a variety of immunosuppressive agents, including azathioprine, chlorambucil, or cyclophosphamide.' Cyclophosphamide has been used more frequently than the other agents'. 10at a dose of 1 to 2 mg/kg by mouth or 2 to 4 mg/kg intravenously for the first week in fulminant cases. It is uncertain how long this form of therapy should be used.
Congenital complete heart block associated with hydrops fetalis Karl M. Altenburger, M.D.,* Maryann Jedziniak, M.D., William L. Roper, M.D., and Jacinto Hernandez, M.D., Denver, Colo. From The Department of Pediatrics, University of Colorado Medical Center, and The Children's Hospital. *Reprint address: Department of Pediatrics, Box C-220, University of Colorado Medical Center, Denver, CO 80262.
The Journal of Pediatrics October 1977
Most patients show evidence of remission within several weeks, but relapses are known to occur in patients apparently free of the disease for one year.' Relapses have responded to additional courses o f cyclophosphamide, with lasting improvement for as long as 689 years. We thank Scott Arnold, M.D., of Cuba City, Wis., and Jack Schroeder, M.D., of Beloit, Wis., for referral of these patients, Charles Brandenberg, M.D., for expert otolaryngologic consultation, Thomas France, M.D., for expert opthalmologic consultation, and to Ms. Joyce Bublitz for secretarial assistance. REFERENCES 1. WolffSM, Fauci AS, Horn RG, et al: Wegener's granulomatosis, Ann Intern Med 81:513, t974. 2. Walton EW: Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis), Br Med J 11:265, 1958. 3. Carrington CB, and Liebow AA: Limited forms of angiitis and granulomatosis of Wegener's type, Am J Med 41:497, 1966. 4. Case records of the Mass. General Hospital, Case No. 37511, N Engl J Med 245:978, 1951. 5. Feldman F, Fink H, and Gruezo Z: Wegener's granulomatosis, Am J Dis Child 112:587, 1966. 6. Roback SA, Herdman RC, Hoyer JH, et al: Wegener's granulomatosis in a child: Observations in pathogenesis and treatment, Am J Dis Child 118:608, 1969. 7. LancosF, Erdos Z, Kadar A, et al: Wegenersche granulomatose in kindesalter, Acta Paediatr Acad Sci Hung 12:285, 1971. 8. Fahey J, Leonard E, Churg J, et al: Wegener's granulomatosis, Am J Med 17:168, 1954. 9. Isaeva LA, Fedorova AN, Lysinka GA, et al: Wegener's granulomatosis in children, Pediatriia 51:67, t972. 10. Hu C-H, O'Loughlin S, and Winkelmann RK: Cutaneous manifestations of Wegener granulomatosis, Arch Dermatol 113:175, 1977.
THIS REPORT describes a newborn infant with congenital complete heart block resulting in hydrops retails. CASE R E P O R T A five-hour-old white male infant was admitted to The Children's Hospital intensive care nursery because of severe hydrops and respiratory distress. He was born at 33 weeks' gestation to a healthy 31-year-old mother. At 32 weeks' gestation Abbreviation used ANA: antinuclear antibodies
I
the fetal heart rate was noted to be 40 to 60/minute. Because fetal movement' had continued unchanged, no fetal distress was presumed. One week later the mother noted decreased fetal movement. The fetal heart rate was again regular at 40 to 60 beats/minute. An ultrasound scan showed a "halo" around the fetal head, and an emergency cesarean section was performed for presumed fetal distress.
