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T-and null cell proliferation in a patient with acute infectious lymphocytosis
520
Letters to the Editor
known, that the bacteremia resulted in simultaneous seeding of the organisms into joint and bone? The finding of periosteal elevation has been described with septic arthritis caused by other organisms, but the association with meningococcal joint infections has apparently not been recorded previously. ~ Margaret R. Hammersch[ag, M.D. Pediatric Service and Channing Laboratory Boston City Hospital Departments of Pediatrics and Medicine Harvard Medical School Boston, Mass. 02118 Carol J. Baker, M.D. Department of Pediatrics Baylor College of Medicine Houston, Texas 77025 REFERENCES
1. Nelson JD: The bacterial etiology and antibiotic management of septic arthritis in infants and children, follow-up, Pediatrics 50:437, 1972. 2. Trueta J: The three types of acute haematogenous osteomyelitis: A clinical and vascular study, J Bone Joint Surg (Br) 41:671, 1959. 3. Leibel RL, Fangmen JJ, and Ostrovsky MC: Chronic meningococcemia in childhood, Am J Dis Child 127:94, 1974. 4. Pinals RS, and Ropes MW: Meningococcal arthritis, Arthritis Rheum 7:241, 1964.
T- and null cell proliferation in a patient with acute infectious lyrnphocytosis To the Editor: Acute infectious lymphocytosis, a benign viral disorder, may be associated with mild respiratory illness, diarrhea, exanthematous rash, or aseptic meningitis, and is invariably characterized by a marked increase in the number of circulating lymphocytes. 1 The nature of these lymphocytes is not yet known. A patient recently seen by us provided an opportunity to examine the subpopulation of these lymphocytes. CASE REPORT
A 15-month-old boy was referred to us because of fever, conjunctivitis, macular rash, and lymphocytosis of 18.3 x 103/ mm 3. At the time of admission, the physical examination was completely normal. The initial hemogram revealed a leukocyte count of 178 • 103/mm 3 with 96% small lymphocytes, 3% neutrophils, and 1% eosinophils. A bone marrow examination was within normal limits. Virus cultures of the stool, urine, and
Supported in part by grant CA-O743 from National Cancer Institute, United States Public Health Service grant RR-05370, and a grant from Leukemia Research Foundation, Inc.
The Journal of Pediatrics March 1976
throat swab were all negative. Acute and convalescent sera showed no rise in antibody titers against following viral agents: influenza virus types A and B, para-influenza types 1, 2 and 3, adenovirus, respiratory synctial virus, mumps, herpes simplex, varicella-zoster, cytomegalovirus, rubella, poliovirus, and coxsackie viruses. Results of complement fixation tests for Mycoplasma, heterophil antibody titer, and Epstein-Barr virus antibody were all negative. The circulating lymphocyte count gradually returned to normal over the next two months. The peripheral lymphocytes were isolated by Ficoll-Hypaque density gradient and studied using the technique of sheep erythrocyte (E) rosette formation for identification of thymusderived T-cells and immunofluorescent staining of surface immunoglobulins for identification of bone marrow derived B-cells, as described previously. 2 The results (Table I) indicate that about half of the proliferating lymphocytes were T-cells and the other half of the proliferating cells were null cells without detectable markers for either T- or B-cells. The absolute number of B-cells showed unremarkable changes. DISCUSSION
An increase in circulating T-cells during viral infection has been well documented in infectious mononucleosis. Since Epstein-Barr virus, the causative agent of infectious mononucleosis, has been found to infect only B-cells, it is postulated that the T-cells proliferate in an effective immune response to EpsteinBarr virus infection of the B-cells? Many viruses such as enteroviruses and adenoviruses have been implicated in acute infectious lymphocytosis. Because ceUmediated immune response is an important mode of host defense against virus infections, it appears likely that the T-cell proliferation in acute infectious lymphocytosis also reflects a successful host immune reaction toward the infectious virus agent. However, the T-cell increase in infectious mononucleosis and in acute infectious lymphocytosis may not be completely analogous, in view of differences in the morphology of the proliferating lymphocytes. In the former condition, the cells are large and atypical, whereas in the latter condition the cells are small lymphocytes, indistinguishable from normal small lymphocytes in stained blood smears? The marked increase in circulating null cells is difficult to interpret because of diverse findings regarding their origin. They may consist of immature B-cells,4 immature T-cells) and a third population of lymphocytes which executes antibody-dependent lymphocyte-mediated cytotoxieity. 6 Further study is needed to elucidate the nature of null cells in acute infectious lymphocytosis. Mahboubeh Dadash-Zadeh, M.D. Division of Hematology Department of Pediatrics Clement C. S. Hsu, M.D. Samuel 3. Sackett Research Laboratories Section of Infectious Diseases-Hypersensitivity Department of Medicine Allen D. Schwartz, M.D. Division of Hematology Department of Pediatrics Northwestern University Medical Center Chicago, Ill. 60611
Volume 88 Number 3
Letters to the Editor
52 1
Table I. Results of T- a n d B-cell studies o f the p a t i e n t d u r i n g t h e acute phase (15 m o n t h s o f age) a n d after the recovery (25 m o n t h s o f age); m e a n values a n d s t a n d a r d deviations (SD) o f 13 n o r m a l individuals are also included
Age of patient
(mo)
15 25 Normal values Mean _+
% Stained cells with antisera against
Peripheral lymphocyte counts (lOS~ram~) 59.3 4.9
46 61
2 17
2 6
0 13
2 8
0 7
0 1
2 12
2 7
2.5 0.8
60 8
13 6
6 3
5 3
7 6
4 2
1 1
8 5
5 2
REFERENCES
1. Wintrobe MM, editor: Clinical hematology, 7 ed, Philadelphia, 1974, Lea & Febiger, p 1289. 2. Hsu CCS, Marti GE, Schrek R, and Williams RC Jr: Lymphocyte bearing B- and T-cell markers in patient with Iymphosarcoma cell leukemia, Ctin Immunol Immunopathol 3:385, 1975. 3. Pattengale PK, Smith RW, Perlin E: Atypical lymphoeytes in acute infectious mononucleosis, N Engl J Med 291:1145, 1974. 4. Wernet P, Siegal FP, Dickler H, Bentwich Z, Fu S, arid Kunkel HG: B and T cells in various disease states: Immature B cells in the blood of certain patients with immune deficiency, Ado Biosci 12:169, 1974. 5. Scheinberg MA, Cathcart ES, and Goldstein AL: Thymosin-induced reduction of "null cells" in peripheral blood lymphocytes of patients with systemic lupus erythematosus, Lancet 1:424, 1975. 6. Jondal M. Wigzeil H, and Aiuti F: Human lymphocyte subpopulations: classification according to surface markers and/or functional characteristics, Transpl Rev 16:163, 1973.
On admission, inspiration was stridulous and prolonged, but expiration was even more affected and characterized by wheezhag. The infant had two respiratory arrests, which responded to intubation. Radiographs of the lateral neck demonstrated no abnormality. An esophagram obtained to exclude tracheal compression by a vascular ring revealed an intrinsic mass of the intrathoracic trachea almost totally obliterating the tracheal air shadow (Fig. 1). The esophagus was normal. Bronchoscopy was then performed; a cyst was seen approximately 2 cm below the glottis. The cyst was ruptured during the procedure, and cloudy fluid was aspirated. The infant was later extubated without recurrence of respiratory distress. Repeat bronchoscopies four days and six weeks later, respectively, revealed no reaccumulation of fluid; the margins of the old cyst were open. DISCUSSION Airway obstruction in infants characterized predominantly by inspiratory stridor is usually indicative of an extrathoracic lesion
Intraluminal tracheal cyst producing airway obstruction in the newborn infant To the Editor: Laryngeal cysts in the newborn infant have been reported as a cause of airway obstructionr but no reports of intraluminal cysts of the trachea could be found upon review of the literature. CASE REPORT
Patient D. L., a male infant, was born after an uncomplicated pregnancy. Delivery was spontaneous, but the amnionic fluid was meconium stained. Respiratory distress with inspiratory stridor and prolonged expiration was noted immediately after delivery. The infant became hypoxemic and hypercapneie and was initially treated for meconium aspiration. A subsequent bronchoscopy was reported as negative. The infant was then referred to the Arizona Medical Center.
Fig. 1. This view of the esophagram demonstrates the smgoth, rounded contour of the intrathoracic tracheal mass. Note tha'~ the tracheal air shadow is nearly completely obliterated by the intrinsic mass. The trachea is not shifted. The esophagus is normal.
Letters to the Editor
known, that the bacteremia resulted in simultaneous seeding of the organisms into joint and bone? The finding of periosteal elevation has been described with septic arthritis caused by other organisms, but the association with meningococcal joint infections has apparently not been recorded previously. ~ Margaret R. Hammersch[ag, M.D. Pediatric Service and Channing Laboratory Boston City Hospital Departments of Pediatrics and Medicine Harvard Medical School Boston, Mass. 02118 Carol J. Baker, M.D. Department of Pediatrics Baylor College of Medicine Houston, Texas 77025 REFERENCES
1. Nelson JD: The bacterial etiology and antibiotic management of septic arthritis in infants and children, follow-up, Pediatrics 50:437, 1972. 2. Trueta J: The three types of acute haematogenous osteomyelitis: A clinical and vascular study, J Bone Joint Surg (Br) 41:671, 1959. 3. Leibel RL, Fangmen JJ, and Ostrovsky MC: Chronic meningococcemia in childhood, Am J Dis Child 127:94, 1974. 4. Pinals RS, and Ropes MW: Meningococcal arthritis, Arthritis Rheum 7:241, 1964.
T- and null cell proliferation in a patient with acute infectious lyrnphocytosis To the Editor: Acute infectious lymphocytosis, a benign viral disorder, may be associated with mild respiratory illness, diarrhea, exanthematous rash, or aseptic meningitis, and is invariably characterized by a marked increase in the number of circulating lymphocytes. 1 The nature of these lymphocytes is not yet known. A patient recently seen by us provided an opportunity to examine the subpopulation of these lymphocytes. CASE REPORT
A 15-month-old boy was referred to us because of fever, conjunctivitis, macular rash, and lymphocytosis of 18.3 x 103/ mm 3. At the time of admission, the physical examination was completely normal. The initial hemogram revealed a leukocyte count of 178 • 103/mm 3 with 96% small lymphocytes, 3% neutrophils, and 1% eosinophils. A bone marrow examination was within normal limits. Virus cultures of the stool, urine, and
Supported in part by grant CA-O743 from National Cancer Institute, United States Public Health Service grant RR-05370, and a grant from Leukemia Research Foundation, Inc.
The Journal of Pediatrics March 1976
throat swab were all negative. Acute and convalescent sera showed no rise in antibody titers against following viral agents: influenza virus types A and B, para-influenza types 1, 2 and 3, adenovirus, respiratory synctial virus, mumps, herpes simplex, varicella-zoster, cytomegalovirus, rubella, poliovirus, and coxsackie viruses. Results of complement fixation tests for Mycoplasma, heterophil antibody titer, and Epstein-Barr virus antibody were all negative. The circulating lymphocyte count gradually returned to normal over the next two months. The peripheral lymphocytes were isolated by Ficoll-Hypaque density gradient and studied using the technique of sheep erythrocyte (E) rosette formation for identification of thymusderived T-cells and immunofluorescent staining of surface immunoglobulins for identification of bone marrow derived B-cells, as described previously. 2 The results (Table I) indicate that about half of the proliferating lymphocytes were T-cells and the other half of the proliferating cells were null cells without detectable markers for either T- or B-cells. The absolute number of B-cells showed unremarkable changes. DISCUSSION
An increase in circulating T-cells during viral infection has been well documented in infectious mononucleosis. Since Epstein-Barr virus, the causative agent of infectious mononucleosis, has been found to infect only B-cells, it is postulated that the T-cells proliferate in an effective immune response to EpsteinBarr virus infection of the B-cells? Many viruses such as enteroviruses and adenoviruses have been implicated in acute infectious lymphocytosis. Because ceUmediated immune response is an important mode of host defense against virus infections, it appears likely that the T-cell proliferation in acute infectious lymphocytosis also reflects a successful host immune reaction toward the infectious virus agent. However, the T-cell increase in infectious mononucleosis and in acute infectious lymphocytosis may not be completely analogous, in view of differences in the morphology of the proliferating lymphocytes. In the former condition, the cells are large and atypical, whereas in the latter condition the cells are small lymphocytes, indistinguishable from normal small lymphocytes in stained blood smears? The marked increase in circulating null cells is difficult to interpret because of diverse findings regarding their origin. They may consist of immature B-cells,4 immature T-cells) and a third population of lymphocytes which executes antibody-dependent lymphocyte-mediated cytotoxieity. 6 Further study is needed to elucidate the nature of null cells in acute infectious lymphocytosis. Mahboubeh Dadash-Zadeh, M.D. Division of Hematology Department of Pediatrics Clement C. S. Hsu, M.D. Samuel 3. Sackett Research Laboratories Section of Infectious Diseases-Hypersensitivity Department of Medicine Allen D. Schwartz, M.D. Division of Hematology Department of Pediatrics Northwestern University Medical Center Chicago, Ill. 60611
Volume 88 Number 3
Letters to the Editor
52 1
Table I. Results of T- a n d B-cell studies o f the p a t i e n t d u r i n g t h e acute phase (15 m o n t h s o f age) a n d after the recovery (25 m o n t h s o f age); m e a n values a n d s t a n d a r d deviations (SD) o f 13 n o r m a l individuals are also included
Age of patient
(mo)
15 25 Normal values Mean _+
% Stained cells with antisera against
Peripheral lymphocyte counts (lOS~ram~) 59.3 4.9
46 61
2 17
2 6
0 13
2 8
0 7
0 1
2 12
2 7
2.5 0.8
60 8
13 6
6 3
5 3
7 6
4 2
1 1
8 5
5 2
REFERENCES
1. Wintrobe MM, editor: Clinical hematology, 7 ed, Philadelphia, 1974, Lea & Febiger, p 1289. 2. Hsu CCS, Marti GE, Schrek R, and Williams RC Jr: Lymphocyte bearing B- and T-cell markers in patient with Iymphosarcoma cell leukemia, Ctin Immunol Immunopathol 3:385, 1975. 3. Pattengale PK, Smith RW, Perlin E: Atypical lymphoeytes in acute infectious mononucleosis, N Engl J Med 291:1145, 1974. 4. Wernet P, Siegal FP, Dickler H, Bentwich Z, Fu S, arid Kunkel HG: B and T cells in various disease states: Immature B cells in the blood of certain patients with immune deficiency, Ado Biosci 12:169, 1974. 5. Scheinberg MA, Cathcart ES, and Goldstein AL: Thymosin-induced reduction of "null cells" in peripheral blood lymphocytes of patients with systemic lupus erythematosus, Lancet 1:424, 1975. 6. Jondal M. Wigzeil H, and Aiuti F: Human lymphocyte subpopulations: classification according to surface markers and/or functional characteristics, Transpl Rev 16:163, 1973.
On admission, inspiration was stridulous and prolonged, but expiration was even more affected and characterized by wheezhag. The infant had two respiratory arrests, which responded to intubation. Radiographs of the lateral neck demonstrated no abnormality. An esophagram obtained to exclude tracheal compression by a vascular ring revealed an intrinsic mass of the intrathoracic trachea almost totally obliterating the tracheal air shadow (Fig. 1). The esophagus was normal. Bronchoscopy was then performed; a cyst was seen approximately 2 cm below the glottis. The cyst was ruptured during the procedure, and cloudy fluid was aspirated. The infant was later extubated without recurrence of respiratory distress. Repeat bronchoscopies four days and six weeks later, respectively, revealed no reaccumulation of fluid; the margins of the old cyst were open. DISCUSSION Airway obstruction in infants characterized predominantly by inspiratory stridor is usually indicative of an extrathoracic lesion
Intraluminal tracheal cyst producing airway obstruction in the newborn infant To the Editor: Laryngeal cysts in the newborn infant have been reported as a cause of airway obstructionr but no reports of intraluminal cysts of the trachea could be found upon review of the literature. CASE REPORT
Patient D. L., a male infant, was born after an uncomplicated pregnancy. Delivery was spontaneous, but the amnionic fluid was meconium stained. Respiratory distress with inspiratory stridor and prolonged expiration was noted immediately after delivery. The infant became hypoxemic and hypercapneie and was initially treated for meconium aspiration. A subsequent bronchoscopy was reported as negative. The infant was then referred to the Arizona Medical Center.
Fig. 1. This view of the esophagram demonstrates the smgoth, rounded contour of the intrathoracic tracheal mass. Note tha'~ the tracheal air shadow is nearly completely obliterated by the intrinsic mass. The trachea is not shifted. The esophagus is normal.