Volume 88 Number 6

involved, abscesses form underneath intact skin. Absence of fluctuation in such lesions may occasionally be due to lack of pus, but more often is due to the deep location of the abscess. We could determine the absence or presence of pus, often in copious amounts, only upon incising lesions. Local treatment recommended in this disease has been limited to the application of gentamicin to necrotic skirt lesions in burned patients? The cases reported here illustrate the importance of local drainage in order to promote rapid healing. We r e c o m m e n d that incision and drainage be routinely incorporated in the therapeutic management of Pseudomonas sepsis with ecthymatous lesions.

We thank Dr. Daniel E. Trophy who referred Case 2 to us, Dr. J. J. Corrigan under whose care Case 3 was hospitalized, Dr. J. Peter Lynch who reviewed the manuscript, and Ms. Jacque Brown who assisted in the preparation of this paper.

Congenital stem cell dysfunction associated with Turner-like phenotype Kenneth W. Feldman, M.D., Hans D. Oehs, M.D.,* Thomas H. Priee, M.D., and

Brief clinical and laboratory observations

979

REFERENCES 1. Markley K, Gurmendi (3, Chavez PM, and Bazan A: Fatal Pseudomonas septicemias in burned patients, Ann Surg 145:175, 1957. 2. Teplitz C: Pathogenesis of Pseudomonas vasculitis and septic lesions, Arch Pathol 80:297, 1965. 3. Hall JH, Callaway JL, Tindall JP, et ah Pseudomonas aeruginosa in dermatology, Arch Dermatol 97:312, 1968. 4. Forkner CE Jr, Frei G I I I , Edgecomb JH, and Utz JP: Pseudomonas septicemia; observations in twenty-three cases, Am J Med 25:877, 1958. 5. Bauer MF, and Hewitt WL: Pseudomonas aeruginosa-contaminant or pathogen7 Arch Dermatol 84:410, 1961. 6. McCracken GH Jr, and Eichenwald HF: Antimicrobial therapy: Therapeutic recommendations and a review of newer drugs, J PEDIATR85:297, 1974. 7. Lund ME, Blazevie DJ, and Matsen JM: Rapid gentamicin bioassay using a multiple-antibiotic-resistant strain of Klebsiella pnemnoniae, Antimicrob Agents Chemother 4:569, 1973. 8. Larter WE, John TJ, Sieber OF, and Johnson H: Granulocytopenia associated with carbenieillin therapy of Pseudomonas sepsis (manuscript).

C O N G E N I T A L BONE MARROW HYPOPLASIA has been associated with several distinct patterns of malformation. 1-7 We report here an additional patient with probable congenital stem cell dysfunction and a phenotype similar to the XO Turner syndrome, but with no demonstrable chromosomal abnormality. Abbreviations used MCV: mean corpuscular volume TIBC: total iron-binding capacity EIT: erythron iron turnover E/M: erythroid/myeloid ratio

Ralph J. Wedgwood, M.D., Seattle, Wash.

CASE REPORT From the Dysmorphology Unit, Division of Developmental Biology and Morphogenesis and the Immunology Unit, Division of Arthritis and Immunology, Department of Pediatrics and the Division of Hematology, Department of Medicine, University of Washington School of Medicine. Supported by a grant (AI 07073)from the National Institute of Allergy and Infectious Diseases, a grant (RR-37) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health, and a grant (1-6-7) from the National Foundation-March of Dimes. Hans D. Ochs, M.D., is an Investigator of the Howard Hughes Medical Institute. *Reprint address: Department of Pediatrics RD-20, University of Washington, Seattle, Wash. 98195.

This 5S-year-old girl is the only child of a 21-year-old gravida 1, para 1 mother and a 23-year-old, unrelated father. Gestation and term delivery were normal. Birth weight was 2.7 kg (tenth percentile); length was 44 cm (less than third percentile). Puffy hands and feet were noted during the first weeks of life. When two days old a heart murmur was heard. At 189 years the hemoglobin concentration dropped to 3 gm/dl, and she required a blood transfusion. Anemia persisted to age 5, but she has required only one subsequent transfusion. During the past 389 years the patient has had five episodes of pneumonia, one episode of pneumococcal septicemia, recurrent otitis media, diarrhea, and several attacks of asthma. At the age of 51/2years, her weight was 13.5 kg (less than third percentile) and her height was 104 cm (third percentile). Psychomotor development was normal. She had prominent, slanted

980

B r i e f clinical a n d laboratory observations

auricles, epicanthal folds, synophrys, high-arched palate, small jaw, webbed neck, low posterior hair line, hypoplastic nipples, short fourth metacarpals, and a normal 10 degree-carrying angle at the elbow. Dermatoglyphic findings included a left transverse palmar crease and a two whorl, eight ulnar loop dermal print. A grade 3/6 systolic ejection murmur was heard at the upper left sternal border, and a grade 1/6 early diastolic murmur at the mid-left sternal border. Blood pressure was 90/60 mm Hg in the arms and 75/45 mm Hg in the legs. These findings were suggestive of mild coarctation of the aorta and a bicuspid aortic valve. The spleen was palpable 2 to 3 cm below the costal margin. Results of an intravenous pyelogram was normal. No evidence of radial hypoplasia was found on roentgenograms. A scan of the 'splenic and hepatic xeticuloendothelial system showed normal uptake of ""Tc. Bone age was slightly below the chronologic age. Conventional chromosomal ,analysis and Giemsa banding of peripheral blood leukocytes revealed a karyotype of 46XX without evidence of structural abnormalities. HEMATOLOGIC STUDIES*

AND IMMUNOLOGIC

Peripheral blood counts obtained during the past two years are summarized in Table I. At four years of age her hematocrit value was 18%, hemoglobin concentration 9.1 g m / d l , M C V 95/~3, and reticulocyte index 0.3%. Peripheral blood smear showed mild poikylocytosis. Bone marrow aspirate appeared hypocellular with a normal E / M ratio (1/3). Bone marrow biopsy was hypocellula r with decreased erythroid and myeloid precursors and normal numbers of megakaryocytes. Serum iron concentration was 100/~g/dl and total iron-binding capacity was 285/zg/dl. Ferrokinetic studies revealed an erythron iron turnover of 0.571 (basal 0.561) indicating a failure of the marrow to respond to the anemia. Radioiron incorporation by cultured marrow cells was low and showed a dosedependent increase to exogenously added erythropoietin but not to 5/3-androgens. Urinary erythropoietin was high (450 units/day; normal less than 1 unit/day), consistent with the degree of anemia. The patient was restudied at the age of 51/2 years at which time her hematocrit value had increased to 33%, M C V decreased to 83/~3, and reticulocyte index was 0.4%. Poikylocytosis was less prominent than previously. Bone marrow biopsy showed normal cellularity. Bone marrow aspirate revealed an E / M ratio o f 1/1-1/2. The erythroid series appeared normal. The myeloid series showed a slight shift toward early forms. Megakaryocytes were normal. Serum iron concentration was 120 /zg/dl and TIBC was 320 /~g/dl. Ferrokinetic studies (EIT 0.87]') indicated improvement over the previous measurefnents but still showed a mild erythroid hypoproliferation. The *Complete hematologic data available on request. ]'Milligrams of iron/dl whole blood/day.

The Journal o f Pediatrics June 1976

Table I. Peripheral blood counts 1973-1975

Date

7/9/73 2/23/731 7/27/731 8/3/73~ 12/18/73 8/15/74 9/29/74~ 10/2/74 4/2/75 4/2/75w 6/10/75 11/11/75

RBC/ mm :~

1.9 x -2.7 x 2.5 x 1.9 •

HCT

Poly- LymphoM C V * morphs/[ cytes/ (%) (~: ) mm mm :~

10~ 18 26 10'~ 26 10~ 22 10" 20 26 -25 2.3 • 10~ 22 4 • l0 G 33 35 4.2 • 10~ 35 -

-

95 -97 96 106 --97 83 --

-

82

800 780 3,600 2,600 560 490 4,400 900 406 1,283 1,300 1,000

3,000 2,800 2,700 2,400 1,900 2,400 680 2,600 1,900 -2,200 1,200

Platelets~ mm

~

370,000

-320,000 420,000 --330,000

*Medium corpuscular volume, tPneumonia. ~Septicemia (pneumococci). w intravenous cortisone (4 mg/kg).

peripheral neutrophil count has often been low, but has n o t shown cyclic fluctuation. With acute illness, granulocyte counts have increased but even with demonstrated bacterial infection the degree of leukocytosis has been minimal. In vitro marrow colony growth was abnormal, resulting in large spreading myeloid colonies of undifferentiated cells in addition to small normal granulocytic colonies. Marrow neutrophil reserve was subnormal as judged by response to intravenous hydrocortisone. Leukocyte migration was normal quantitatively and qualitatively using the Roebuck skin window technique. Granulocytes showed normal nitroblue tetrazolium reduction in the endotoxin-coated slide test and responded adequately to chemotactic factors (C5a, bacterial factor). Serum concentrations of immunoglobulins were elevated compared to age-matched controls~: IgG 1580 m g / d l , IgM 123 mg/dl, and IgA 255 m g / d l . Circulating B- and T-lymphocytes were normal in n u m b e r as estimated by rosette formation (E- and EAC-rosettes). Intravenous immunization with bacteriophage OX 174 resulted in a low primary and a moderately decreased seco,ndary antibody response (Fig. 1). Immunologic memory, however, was intact as indicated by an increase in antibgdy titer during the second and third immunization. Antibody after the secondary immunization consisted of rapidly declining levels of IgM instead of the persistent levels of mainly IgG of normal controls~; after the third phage injection, a reduced proportion (41%) of the rapidly rising antibody titer was of the IgG class. A Schick test was positive at age 5 years (after completed immunizations during infancy), but converted to negative

Volume 88 Number 6

Brief clinical and laboratory observations

$ 2~ immunization

~ 1~ immunization

981

~ 3~immunization

10,000-

1000Patient

K

Z

"~ I00" B

1-

~.IQ.M~Icj61 ~ Patient .1

I'

i

5

i

j /,/~

4

i

2 13 4 Time in weeks

1

[i ~

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Fig. 1. Primary, secondary, and tertiary antibody responses to bacteriophage I~IX 174. For each immunization, 2 x 109 plaque-forming units/kg body weight were given intravenouslyY Antibody titers were determined at different time intervals. The range of antibody titers (Kv) of 20 controls is shown by the stippled area. Geometric means of the Kv are indicated for controls (o--o) and the patient (A----A). Only one control and the patient received a tertiary immunization. Class of antibody was determined two weeks after secondary (A) and tertiary (B) immunization, using column chromatography (Sephadex G-200) and 2-mercapto-ethanol treatment and expressed as IgG/IgM ratio.

after a booster immunization at the age of 51/2 years; low titers of hemagglutinating antibody to diphtheria and tetanus toxin were present at that time. The isohemagglutinin titer (anti-A) was 1:128. Several skin tests for determination of delayed hypersensitivity were positive, and she was successfully sensitized to dinitrochlorobenzene. In vitro lymphocyte transformation was normal, using nonspecific mitogens (PHA, pokeweek mitogen, concanavallin A) and allogeneic cells (mixed lymphocyte culture). Red blood cell adenosine deaminase and nucleoside phosphorylase activity were normal. Serum complement levels were normal. DISCUSSION The resemblance of this patient with the XO Turner syndrome was so striking that several independent observers ordered buccal smears and chromosome studies. No abnormalities could be found; translocations and deletions were not present on Giemsa banding. The dysmorphic features were distinct from those of Noonan syndrome. :~ Thus "Turner-like phenotype" seems appropriate. Abnormalities of three hematopoietic stem cell lines were demonstrated: remittent hypoplastic anemia, intermittent neutropenia, and reduced and delayed humoral immune responses.

The triad of hypoplastic anemia, neutropenia, and deficient antibody production has not been associated with the XO Turner syndrome. It has been suggested that IgM production may be partially controlled by the Xchromosome.: . . . . Individuals with XO Turner syndrome have diminished serum IgM and IgM associated antibody titers. '2 The patient presented here had slightly increased serum IgM levels, and the immunologic abnormality affected the IgG rather than the IgM antibody response. In 1970 Diamond and associatess presented nine patients like ours with "Turner-like phenotype" who had normal chromosomes and in addition developed congenital hypoplastic anemia. All of these patients had normal chromosome analyses. None were reported, however, to have had other hematologic abnormalities, immune deficiency, or unusual susceptibility to infections. Congenital hypoplastic anemia has also been associated with patterns of malformation distinctly different from the Turner syndrome, including the Fanconi syndrome 1~ and triphalangeal thumbs.: 3.6, 7 It has also been associated with first chromosome abnormalities. ~ 4 There is no apparent reason for the association of dysmorphic features and hematopoietic (stem cell) dysfunction. The association of hypoplastic anemia with Turner phenotype does not yet appear to be familial. The organs affected in our patient

982

Brief clinical and laboratory observations

differentiate at different times so that a single prenatal insult is unlikely. The association may, however, provide a future clue to the biologic nature of such congenital defects and thus deserves attention. We are indebted to Drs. John Adamson and Jack Singer who performed the erythropoietin assays and the in vitro studies of marrow colony growth, and to Dr. David W. Smith who gave valuable advice. REFERENCES 1 . Diamond LK, Allen DM, and Magill FB: Congenital (erythroid) hypop!astic anemia: A 25-year study, Am J Dis Child 102:403, 1961. 2. Tartaglia AP, Propp S, Amarose AP, Propp RP, and Hall CA: Chromosome abnormality and hypocalcemia in congenital erythroid hypoplasia, Am J Med 41:990, 1966. 3. Aase JM, and Smith DW: Congenital anemia and triphalangeal thumbs: A new syndrome, J PEDIATR 74:471, 1969. 4. Hayn R, Kurczynski E, and Schmickel R: The association of Blackfan-Diamond syndrome, physical abnormalities and an abnormality of chromosome l, J PEDIATR 85:531, 1974.

T lymphocyte dysfunction, hyperimmunoglobulinemia E, recurrent bacterial infections, and defective neutrophil chemotaxis in a Negro child

The Journal of Pediatrics June 1976

5. Diamond LK, McElfresh AE, Say B, and DiGeorge AM: Turner's phenotype in children with congenital hypoplastic (pure red cell aregenerative) anemia, Program of the American Society of Hematology, Thirtieth Annual Meeting, 1970, p 130. 6. Murphy S, and Lubin B: Triphalangeal thumbs and congenital erythrojd hypoplasia: Report of a case with unusual features, J PEDIATR81:987, 1972. 7. Jones B, and Thompson H: Triphalangeal thumbs associated with hypoplastic anemia, Pediatrics 52:609, 1973. 8. Buckley RH, Dees SC, and O'Fallon WM: Serum immunoglobulins. 1. Levels in norma! children and in uncomplicated childhood allergy, Pediatrics 41:600, 1968. 9. Ochs HD, Davis SD, and Wedgwood R J: Immunologic response to bacteriophage ,OX 174 in immunodeficiency diseases, J Clin Invest 50:2599, 1971. 10. smith DW: Recognizable patterns of human malformation, Philadelphia, 1970, WB Saunders Company. 11. Rhodes K, Markham RL, Maxwell PM, and Monk-Jones ME: Immunoglobulins and the X-chromosome, Br Med J 3:439, 1969. 12. WOod CBS, Martin W, Adinolfi M, and Polani PE: Immunoglobulins and the X-chromosome, Br Med J 4:110, 1969.

IN RECENT -YEARS disorders o f neutrophil mobility associated with recurrent staphylococcal infections h a v e been observed in several clinical entities? In Job syndrome recurrent "cold" abscesses were described in red-haired, fair-skinned females2; more recently, Buckley and associates 3 reported a syndrome in male children in which recurrent pyogenic infections were associated with hyperimmun0globulinemia E. Each of these syndromes has recently been associated with a defect in leukocyte chemotaxis 4. Abbreviations used Ig: immunoglobulin RAST: radioallergosorbent test

Joseph A. Church, M.D., Lawrence D. Frenkel, M.D., Washington, D.C., Daniel G. Wright, M.D., Bethesda, Md., and Joseph A. Bellanti, M.D.,* Washington, D.C. From the Departments of Pediatrics and Microbiology, Georgetown University School of Medicine, and the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health. Supported in part by National Institutes of Health Training Grant HD-O0261. *Reprint address: Georgetown University Medical Center, Gorman Building, Room 130, 3800 Reservoir Road, N.W., Washington, D.C. 20007.

In the present report we describe the results of immunologic studies in a Negro child with clinical features of both entities. We suggest that the two disorders may be related and are not restricted to an isolated kindred or ethnic group. C A S E REPORT Patient C. S., a 12-year-old black girl, was referred to Georgetown University Hospital because of recurrent pyogenic infections. The patient was the product of an uncomplicated pregnancy. She had colic during the first few months of life, and at three months of age developed a generalized eczematoid eruption associated with the first episode of pneumonia. Thereafter, she