Volume 92 Number 6
nephroblastoma occurring in children who have a sibling or parent with this disease. Kamran Tebbi, M.D. Assistant Professor Samuel Gross, M.D. Professor Department o f Pediatrics Case Western Reserve University Rainbow Babies & Childrens Hospital 2101 A delbert Rd. Cleveland, OH 44106 REFERENCES 1.
Knudson A G Jr, and Strong LC: Mutation and cancer: A model for Wilms' tumor of the kidney, J Natl Cancer Inst 48"313, 1972. 2. Brown TW, Puranik SR, Altman DH, and Hardin HC Jr: Wilms' tumor i n t h r e e successive generations, Surgery 72:756, 1972. 3. Kaufman RL, Vietti TJ, and Wabner CJ: Wilms' tumor in father and son: Birth Defects, 10(10): 191, 1974. 4. Kontras SB, and Newton WA Jr: Familial Wilms' tumor, Birth Defects 10(4): 187, 1974. 5. Meadows TA, Lichtenfeld JL, and Koop CE: Wilms' tumor in three children of a woman with congenital hemihypertropby, N E n g l J Med 291:23, 1974. 6. Juberg RC, St. Martin EC, and Hundley JR: Familial occurrence of Wilms' tumor: Nephroblastoma in one of monozygous twins and in another sibling, Am J Human Genet 27:155, 1975. 7. Bond JV: Wilms' tumour, hypospadia s and cryptorchidism in twins, Arch Dis Child 52:243, 1977.
A possible early example of mucocutaneous lymph node syndrome In recent years an interesting pediatric disorder has been described w h i c h is becoming widely known as the mucocutaneous lymph node syndrome (MCLNS), or Kawasaki disease. Kawasaki ~himself thought that this disease was a new entity, and this opinion is shared by other workers. There is, however, reason to doubt whether we are in fact dealing with a really new disease, 2 or merely with an entity that has recently been rediscovered. Some of this doubt is based on the study o f one of the most striking characteristics of the disease-the occurrence o f aneurysms of the coronary arteries in a proportion o f patients. Instances Of this salient feature had been reported long before Kawasaki delineated the MCLNS. ~ One of the earliest of these descriptions is in the report published bY Samuel Gee ~ in 1871. Since Gee's contribution appears to have been largely overlooked, it was thought desirable to pay tribute to this astute early observer by quoting in full his description:
0022-3476/78/0692-1027500.20/0 9 1978 The C. V. Mosby Co.
Clinical notes
10 2 7
The peculiarity of the following case lies in the age of the patient. William Shrosbree, act. 7, died in Mark on October 20, 1870, in consequence of scarlatinal dropsy with intercurrent pneumonia and meningitis. The pericardium was natural. The heart natural in size, and the valves healthy. The coronary arteries were dilated into aneurysms at three places, namely, at the apex of the heart a small aneurysm the size o f a pea; at the base of the right ventricle, close to the tip of the right auricular appendix, and near to the mouth o f one o f the coronary arteries, another aneurysm of the same size; and at the back of the heart, at the base o f the ventricles, and in the sulcus between the ventricles, a third aneurysm the size o f a horse bean. These aneurysms contained small recent clots, quite loose. The aorta near the valves, and the aortic cusp of the mitral valve, presented specks o f atheroma. The heart is preserved in the museum. Aneurysms o f the coronary arteries in children are an important component of the MCLNS. It is very likely that the so-called congenital aneurysms o f the coronary arteries are in fact only expressions of a previous attack o f this disease which may or may not have been recognized. 2 There are no other known causes o f this striking pathologic change, which had been considered to be an expression of infantile polyarteritis nodosa. Japanese pathologists, who had t h e opportunity of examining necropsy material from fatal instances of Kawasaki disease, were impressed by the similarity of the changes in this disorder with those reported in infantile polyarteritis nodosa; Fetterman and Hashida' and Landing and Larson ~ also thought that there were no significant pathologic differences. Gee's ~ report o f coronary aneurysms, probably one o f the earliest recorded instances, must be viewed in this light. If one then adds some of the other features of the mucocutaneous lymph node syndrome-fever, changes of the lips and the "strawberry-like" tongue, the swollen shiny skin and edema of the extremities, the macular skin rash o f the trunk and head, and the characteristic peeling of the skin o f the extremities-Gee's a impression o f "scarlatina! dropsy" in his patient becomes more intelligible, and suggests that in fact Gee may well have described one of the earlies t , perhaps even the first, example of Kawasaki disease. These considerations are not intended to detract in any way from Kawasaki's merit in having outlined the features of MCLNS and in having drawn the modern clinicians' attention to this disorder. K. Aterman, M.D., D.Sc., F.R.C. Path. Department of Pathology Dalhousie University Izaak Walton Killam Hospital for Children P.O. Box 3070 Halifax, Nova Scotia, Canada B3J 3G9
REFERENCES 1. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, and Yanagawa J: A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan, Pediat 54:271, 1974. 2. Aterman K, Dische MR, Franke J, Fraser GM, and Meyer WW: Aneurysms of the coronary arteries in infants and
10 2 8
Clinical notes
children. A Review, and report of six cases, Virchows Arch [Pathol Anat] 374:27, 1977. 3. Gee SJ: Cases of morbid anatomy: Aneurysms of coronary arteries in a boy, St. Barthlomew's Hospital Reports, vol 7, 1871. 4. Fetterman GH, and Hashida Y: Mucocutaneous lymph node syndrome (MLNS): A disease widespread in Japan which demands our attention, Pediatrics 54: 268, 1974. 5. Landing BH, and Larson EJ: Are infantile periarteritis nodosa with coronarY artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan, Pediatrics 59:651, t977.
Infantile genetic agranulocytosis and acute lymphocytic leukemia in two sibs In 1956, Kostmann 1 described a condition of agranulocytosis in a Swedish family. The patients had a severe disease characterized by chronic and recurrent pyogenic infections with onset during the first year of life, associated with severe neutropenia, monocytosis, and eosinophilia. Bone marrow morpfiology demonstrated normal myeloid precursors with the absence of mature neutrophiis.
CASE R E P O R T Patient S.H. (age 11) had had repeated life-threatening pyogenic infections since age 6 months involving her skin, umbilicus, lung, and brain. Peripheral blood and bone marrow aspiration showed persistent neutropenia with maturation arrest of the myeloid precursors in her bone marrow. (The marrow differential count showed no neutrophils or bands: promyelocytes 24%, myelocytes I0%, metamyelocytes 1%, !ymphocytes 2%, plasma cells 8%, eosinophils 28%, and normoblasts 27%.) Her neutrophil counts ranged from 0 to900/m a with no tendency to cycle while eosinophil counts were elevated (440 to 1,665/m3). Her older sister developed acute lymphocytic leukemia when she Was 6 years of age and died two years later. COLONY-FORMING CELLS AND COLONYSTIMULATING ACTIVITY Patient S.H. produced a normal number of colony-forming cells (CFU-C) in her bone marrow culture (77/10 a vs. 36/10 ~
0022-3476/78/0692-1028500.10/0 9 1978 The C. Y. Mosby Co.
The Journal of Pediatrics June 1978
nucleated cells plated in normal children). The colonies were aspiratedand stained; no mature neutrophils were observed. Monocytes from Patient S.H. also produced adequate amounts of colony-stimulating activity in vitro. Studies of her serum for inhibitors to normal marrow CFU-C production were negative. DISCUSSION Our patient, as well as those described by Parmley et aU had a normal number of CFU-C but the cells failed to mature, both in viyo and in vitro, to bands and neutrophis. Olofsson et al, 3 on the other hand, showed normal maturation in vitro of the marrow cells. The defect in acute leukemia is proposed by MetcaW to be a maturation defect of normal cells rather than the result of abnormal proliferation of a done of abnormal cells. Thus, the defect in one sister may have resulted in the development of acute lymphocytic leukemia, whereas the maturation defect in the pr0positus resulted in agranulocytosis. We thank Dr. Joel Shavin and Dr. Edward Rainey for aUowing us to investigate this patierft. Victor Lui, M.D. Abdelsalam H. Ragab, M.D. Harry Findley, M.S. Barbara Frauen, B.S. Emory University School of Medicine 69 Butler St., S.E. Atlanta, GA 30303
REFERENCES 1. Kostmann R; Infantile genetic agranulocytosis (agranulocytosis infantilis hereditaria): a new recessive lethal disease of man, Acta Pediatl: 45: (Suppl 105):1, 1956. 2. ParmleyRT, Ogawa M, Darby CP Jr, and Spicer SS: Congenital neutropenia: neutrophi! proliferation with abnormal maturation, Blood 46:723, 1975. 3. Olofsson T, Olsson I, Kostmann R, Malmstrom S, and Thilen A: Granulopoiesis in infantile genetic agranulocytosis: in vitro cloning of marrow ceils in agar culture, Scand J Haematol 16:18, 1976. 4. MetcalfD: The nature of leukemia: neoplasm or disorder of hemopoietic regulation, Med J Aust 2:739, 1971.
nephroblastoma occurring in children who have a sibling or parent with this disease. Kamran Tebbi, M.D. Assistant Professor Samuel Gross, M.D. Professor Department o f Pediatrics Case Western Reserve University Rainbow Babies & Childrens Hospital 2101 A delbert Rd. Cleveland, OH 44106 REFERENCES 1.
Knudson A G Jr, and Strong LC: Mutation and cancer: A model for Wilms' tumor of the kidney, J Natl Cancer Inst 48"313, 1972. 2. Brown TW, Puranik SR, Altman DH, and Hardin HC Jr: Wilms' tumor i n t h r e e successive generations, Surgery 72:756, 1972. 3. Kaufman RL, Vietti TJ, and Wabner CJ: Wilms' tumor in father and son: Birth Defects, 10(10): 191, 1974. 4. Kontras SB, and Newton WA Jr: Familial Wilms' tumor, Birth Defects 10(4): 187, 1974. 5. Meadows TA, Lichtenfeld JL, and Koop CE: Wilms' tumor in three children of a woman with congenital hemihypertropby, N E n g l J Med 291:23, 1974. 6. Juberg RC, St. Martin EC, and Hundley JR: Familial occurrence of Wilms' tumor: Nephroblastoma in one of monozygous twins and in another sibling, Am J Human Genet 27:155, 1975. 7. Bond JV: Wilms' tumour, hypospadia s and cryptorchidism in twins, Arch Dis Child 52:243, 1977.
A possible early example of mucocutaneous lymph node syndrome In recent years an interesting pediatric disorder has been described w h i c h is becoming widely known as the mucocutaneous lymph node syndrome (MCLNS), or Kawasaki disease. Kawasaki ~himself thought that this disease was a new entity, and this opinion is shared by other workers. There is, however, reason to doubt whether we are in fact dealing with a really new disease, 2 or merely with an entity that has recently been rediscovered. Some of this doubt is based on the study o f one of the most striking characteristics of the disease-the occurrence o f aneurysms of the coronary arteries in a proportion o f patients. Instances Of this salient feature had been reported long before Kawasaki delineated the MCLNS. ~ One of the earliest of these descriptions is in the report published bY Samuel Gee ~ in 1871. Since Gee's contribution appears to have been largely overlooked, it was thought desirable to pay tribute to this astute early observer by quoting in full his description:
0022-3476/78/0692-1027500.20/0 9 1978 The C. V. Mosby Co.
Clinical notes
10 2 7
The peculiarity of the following case lies in the age of the patient. William Shrosbree, act. 7, died in Mark on October 20, 1870, in consequence of scarlatinal dropsy with intercurrent pneumonia and meningitis. The pericardium was natural. The heart natural in size, and the valves healthy. The coronary arteries were dilated into aneurysms at three places, namely, at the apex of the heart a small aneurysm the size o f a pea; at the base of the right ventricle, close to the tip of the right auricular appendix, and near to the mouth o f one o f the coronary arteries, another aneurysm of the same size; and at the back of the heart, at the base o f the ventricles, and in the sulcus between the ventricles, a third aneurysm the size o f a horse bean. These aneurysms contained small recent clots, quite loose. The aorta near the valves, and the aortic cusp of the mitral valve, presented specks o f atheroma. The heart is preserved in the museum. Aneurysms o f the coronary arteries in children are an important component of the MCLNS. It is very likely that the so-called congenital aneurysms o f the coronary arteries are in fact only expressions of a previous attack o f this disease which may or may not have been recognized. 2 There are no other known causes o f this striking pathologic change, which had been considered to be an expression of infantile polyarteritis nodosa. Japanese pathologists, who had t h e opportunity of examining necropsy material from fatal instances of Kawasaki disease, were impressed by the similarity of the changes in this disorder with those reported in infantile polyarteritis nodosa; Fetterman and Hashida' and Landing and Larson ~ also thought that there were no significant pathologic differences. Gee's ~ report o f coronary aneurysms, probably one o f the earliest recorded instances, must be viewed in this light. If one then adds some of the other features of the mucocutaneous lymph node syndrome-fever, changes of the lips and the "strawberry-like" tongue, the swollen shiny skin and edema of the extremities, the macular skin rash o f the trunk and head, and the characteristic peeling of the skin o f the extremities-Gee's a impression o f "scarlatina! dropsy" in his patient becomes more intelligible, and suggests that in fact Gee may well have described one of the earlies t , perhaps even the first, example of Kawasaki disease. These considerations are not intended to detract in any way from Kawasaki's merit in having outlined the features of MCLNS and in having drawn the modern clinicians' attention to this disorder. K. Aterman, M.D., D.Sc., F.R.C. Path. Department of Pathology Dalhousie University Izaak Walton Killam Hospital for Children P.O. Box 3070 Halifax, Nova Scotia, Canada B3J 3G9
REFERENCES 1. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, and Yanagawa J: A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan, Pediat 54:271, 1974. 2. Aterman K, Dische MR, Franke J, Fraser GM, and Meyer WW: Aneurysms of the coronary arteries in infants and
10 2 8
Clinical notes
children. A Review, and report of six cases, Virchows Arch [Pathol Anat] 374:27, 1977. 3. Gee SJ: Cases of morbid anatomy: Aneurysms of coronary arteries in a boy, St. Barthlomew's Hospital Reports, vol 7, 1871. 4. Fetterman GH, and Hashida Y: Mucocutaneous lymph node syndrome (MLNS): A disease widespread in Japan which demands our attention, Pediatrics 54: 268, 1974. 5. Landing BH, and Larson EJ: Are infantile periarteritis nodosa with coronarY artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan, Pediatrics 59:651, t977.
Infantile genetic agranulocytosis and acute lymphocytic leukemia in two sibs In 1956, Kostmann 1 described a condition of agranulocytosis in a Swedish family. The patients had a severe disease characterized by chronic and recurrent pyogenic infections with onset during the first year of life, associated with severe neutropenia, monocytosis, and eosinophilia. Bone marrow morpfiology demonstrated normal myeloid precursors with the absence of mature neutrophiis.
CASE R E P O R T Patient S.H. (age 11) had had repeated life-threatening pyogenic infections since age 6 months involving her skin, umbilicus, lung, and brain. Peripheral blood and bone marrow aspiration showed persistent neutropenia with maturation arrest of the myeloid precursors in her bone marrow. (The marrow differential count showed no neutrophils or bands: promyelocytes 24%, myelocytes I0%, metamyelocytes 1%, !ymphocytes 2%, plasma cells 8%, eosinophils 28%, and normoblasts 27%.) Her neutrophil counts ranged from 0 to900/m a with no tendency to cycle while eosinophil counts were elevated (440 to 1,665/m3). Her older sister developed acute lymphocytic leukemia when she Was 6 years of age and died two years later. COLONY-FORMING CELLS AND COLONYSTIMULATING ACTIVITY Patient S.H. produced a normal number of colony-forming cells (CFU-C) in her bone marrow culture (77/10 a vs. 36/10 ~
0022-3476/78/0692-1028500.10/0 9 1978 The C. Y. Mosby Co.
The Journal of Pediatrics June 1978
nucleated cells plated in normal children). The colonies were aspiratedand stained; no mature neutrophils were observed. Monocytes from Patient S.H. also produced adequate amounts of colony-stimulating activity in vitro. Studies of her serum for inhibitors to normal marrow CFU-C production were negative. DISCUSSION Our patient, as well as those described by Parmley et aU had a normal number of CFU-C but the cells failed to mature, both in viyo and in vitro, to bands and neutrophis. Olofsson et al, 3 on the other hand, showed normal maturation in vitro of the marrow cells. The defect in acute leukemia is proposed by MetcaW to be a maturation defect of normal cells rather than the result of abnormal proliferation of a done of abnormal cells. Thus, the defect in one sister may have resulted in the development of acute lymphocytic leukemia, whereas the maturation defect in the pr0positus resulted in agranulocytosis. We thank Dr. Joel Shavin and Dr. Edward Rainey for aUowing us to investigate this patierft. Victor Lui, M.D. Abdelsalam H. Ragab, M.D. Harry Findley, M.S. Barbara Frauen, B.S. Emory University School of Medicine 69 Butler St., S.E. Atlanta, GA 30303
REFERENCES 1. Kostmann R; Infantile genetic agranulocytosis (agranulocytosis infantilis hereditaria): a new recessive lethal disease of man, Acta Pediatl: 45: (Suppl 105):1, 1956. 2. ParmleyRT, Ogawa M, Darby CP Jr, and Spicer SS: Congenital neutropenia: neutrophi! proliferation with abnormal maturation, Blood 46:723, 1975. 3. Olofsson T, Olsson I, Kostmann R, Malmstrom S, and Thilen A: Granulopoiesis in infantile genetic agranulocytosis: in vitro cloning of marrow ceils in agar culture, Scand J Haematol 16:18, 1976. 4. MetcalfD: The nature of leukemia: neoplasm or disorder of hemopoietic regulation, Med J Aust 2:739, 1971.
