Volume 88 Number 2
Brief clinical and laboratory observations
ment of Hemophilus influenzae meningitis: A comparison of chloramphenicol and tetracycline, J Inf Dis 125:459, 1972.
263
19. Emerson BB, Smith AL, Harding AL, and Smith DH: H. influenzae b susceptibility to 17 antibiotics, J PEDIATR 86:617, 1975.
Laryngeal obstruction in childhood sarcoidosis Barbara S. Kirschner, M.D.,* and Paul H. Holinger, M.D., Chicago, 111. MORE THAN 230 CHILDREN with sarcoidosis have been described in the pediatric literature, but none had recognized laryngeal involvement resulting in significant respiratory impairment. The present c o m m u n i c a t i o n describes a 14-year-old boy who developed almost complete airway obstruction secondary to extensive laryngeal infiltration at a time when his p u l m o n a r y parenchymal disease had improved. CASE REPORT Patient R. S., a 14-year-old black male, was well until nine years of age, when he developed progressive dyspnea, cough, and anorexia. Physical findings included respiratory distress at rest, perioral cyanosis, granulomatous uveitis, cervical adenopathy, and digital dubbing, but no hepatosplenomegaly. Chest roentgenogram showed bilateral hilar and right paratracheal adenopathy, with diffuse bilateral nodular infiltrations. Results of fungal complement fixation titers, skin tests for fungi, and purified protein derivative were negative. Noncaseating, epithelioid granulomas were observed in a paratracheal lymph node biopsy; stains and cultures for acid-fast bacilli and fungi were negative. The patient received prednisone 20 mg daily for seven months followed by alternate-day therapy. Four months later, in March, 1971, hoarseness developed; on indirect laryngoscopy, vocal cords and epiglottis were normal but mild inflammation of the left arytenoid was noted. Pulmonary function studies and blood gas determinations were within normal limits. Prednisone dosage was decreased gradually, but exertional dyspnea recurred. In February, 1973, increasing dyspnea, cough, and hoarseness occurred with no evidence of increasing pulmonary disease radiologically or by pulmonary function studies. In June, 1973, swelling of the nasal turbinates ensued; biopsy showed noncaseating granulomas. Indirect laryngoscopy demon-
From the Department of Pediatrics, Michael Reese Hospital, and the Department of Laryngology and Bronchoesophagology, University of lllinois Hospital. *Reprint address: Departmentof Pediatrics, Universityof Chicago, 5825 MarylandA re., Chicago, Ill. 60637.
Fig. 1. Lateral xeroradiogram of the neck, demonstrating epiglottic edema, subglottic polypoid masses, and tracheal stenosis. strated edema of the uvula, epiglottis, and aryepiglottic folds; a chest roentgenogram was unchanged. The sudden onset of stridor in August, 1973, necessitated immediate hospitalization. The epiglottis and arytenoids were enlarged and the glottis was 80% narrowed. Soft tissue swelling in the subglottic region and narrowing in the midtrachea were apparent on the roentgenogram. A tracheotomy was planned, but was cancelled because of rapid improvement of laryngeal edema within 48 hours after 60 mg daily of prednisone. Alternate-day prednisone (80 mg) therapy was started, but within three months there was increasing hoarseness, exertional dyspnea, and mouth breathing. Xeroradiograms of the head and neck demonstrated epiglottic edema, large polypoid subglottic masses, and circumscribed stenosis of the
264
Brief clinical and laboratory observations
The Journal of Pediatrics February 1976
Fig. 2. Photographs obtained during direct laryngoscopy, a, Normal larynx; note clear view of true vocal cords, b and c, Extensive granulomatous tissue and edema of laryngeal tissue prior to the surgical procedure, September, 1973. b, Photographs above level of false cords showing severe stenosis; vocal cords not visible, c, Laryngoscope has been advanced but vocal cords only barely visible beyond diseased tissues, d, Fibrotic changes present in December, 1974.
trachea at the level of C6 and C7 (Fig. 1). Direct laryngoscopy disclosed a markedly thickened epiglottis, nodular infiltration of both false cords, and erythematous vocal cords, which were confluent with the subglottic tissue and almost completely obstructed the airway (Fig. 2). Bronchoscopy was not performed for fear it might precipitate further obstruction. Excisional biopsies taken from both false cords in essence removed the obstructive tissue overhanging the true cords. Histologic study of this tissue showed noncaseating granulomas. Prednisone therapy was continued on alternate days, with no evidence of recurrent obstruction. Currently (July 1975), there is persistent involvement of the soft palate, uvula, epiglottis, arytenoids, and aryepiglottic folds. Cystic lesions are present in the small bones of the hands and feet and skin nodules have appeared on the left arm. There is no significant adenopathy or hepatosplenomegaly. Serologic tests are normal, except for mild eosinophilia (9%). In 1970, a sister was proved to have sarcoidosis with involvement of the parotid gland, cervical and hilar lymph nodes, and minimal pulmonary parenchymal infiltrations. She received 20 months of prednisone therapy and now has no signs of active disease.
DISCUSSION Jasper and Denny ~ recently reported a series o f 25 children with sarcoidosis, one of w h o m had a vocal cord nodule which was not biopsied. M c G o v e r n and Merritt, 2 in an extensive review o f 113 cases of childhood sarcoidosis, did not mention direct laryngeal involvement but reported peripheral and cranial nerve lesions, which resulted in paralysis of the soft palate and vocal cord dysfunction. Kendig 3 and Siltzbach and Greenberg ' in their discussions of organs affected by sarcoidosis did not include the larynx. Reisner 5 described a 17-year-old girl with diffuse infiltration of the larynx and epiglottis. Biopsies of these tissues were not obtained and reexamination seven years later disclosed no signs of respiratory or vocal cord impairment. Devine 6 reviewed the literature concerning infiltration of the larynx in adults with sarcoidosis. The incidence varied from 1.2% to 5%. The epiglottis, aryepiglottic tblds, and arytenoids were most commonly affected and appeared either thickened
Volume 88 Number 2
and edematous or nodular. The vocal cords were rarely abnormal, which explains why airway obstruction rather than vocal changes usually occurs. In a few patients, laryngeal sarcoidosis was observed in the absence of other systemic manifestations of the disease. It is noteworthy that progression of the extrathoracic manifestations of our patient's disease occurred at a time when pulmonary involvement appeared to be stable. This coincides with the experience previously reported in adults. 6 Recognition of this phenomenon should encourage upper airway examination of children with increasing respiratory distress associated with sarcoidosis. Diminution of t h e laryngeal edema by large dose prednisone therapy prevented an anticipated tracheotomy. The recurrence of dyspnea while on a high-dose, alternate-day prednisone regimen, however, necessitated surgical excision of polypoid granulomatous tissue to prevent upper respiratory tract obstruction. Localization of the subglot-
Isolation of varicellazoster virus from blood Sandor Feldman, M.D.,* and Elizabeth Epp, B.A., Memphis, Tenn. V A R I C E L L A is a common childhood infection, manifest as cutaneous lesions, little is known about the hematogenous dissemination of v-z virus. The frequent occurrence of viscerally disseminated lesions in the immunosuppressed host 1 indicates that varicella has a viremic phase; however, antemortem isolation of v-z virus from blood has been reported only once. In 1966 Gold ~ isolated this virus from the blood of a child with hepatoma and varicella but further attempts to isolate bloodborne v-z virus in this and other patients were unsuccessful. Gold's report does not state the type of blood specimen used, the culture technique, or the relationship of blood cultures to the clinical status of the patient. A simple and reliable method for isolating v-z virus ALTHOUGH
From the Infectious Diseases Service, St. Jude Children's Research Hospital. Supported by Cancer Research Center Grant CA 08480from the National Cancer Institute, by a grant from the Washington County, Tennessee Cancer Society, and by A LSA C. *Reprint address: Infectious Diseases Service, St. Jude Children's Research Hospital, P.O. Box 318, Memphis, Tenn. 38101.
B r i e f clinical and laboratory observations
265
tic lesions by xeroradiography 7 prior to surgery facilitated therapy by accentuating the margins of nodular masses accessible to extirpation. REFERENCES 1. Jasper PL, and Denny FW: Sarcoidosis in children, J PEDIATR73:499, 1968. 2. McGovern JP, and Merritt DH: Sarcoidosis in children, Adv Pediatr 8:97, 1956. 3. Kendig EL: Sarcoidosis among children, J PEDIATR61:269, 1962. 4. Siltzbach LE and Greenberg GM: Childhood sarcoidosis: A study of 18 patients, N Engl J Med 279:1239, 1968. 5. Reisner D: Boeck's sarcoid and systemic sarcoidosis: A study of 35 cases, Am Rev Tuberc 49:437, 1944. 6. Devine KD: Sarcoidosis and sarcoidosis of the larynx, Laryngoscope 55i533, 1965. 7. Holinger PH, Lutterbeck EF, and Bulger R: Xeroradiography of the larynx, Ann Otol Rhinol Laryngol 81:1, 1972.
from blood would be useful in studying the pathogenesis of variceUa as well as evaluating the efficacy of antiviral agents in treatment of the infection. Such a method is reported here. MATERIALS
AND METHODS
Clinical specimens. Specimens for the isolation of virus were obtained from two children with acute leukemia and varicella. These patients developed varicella pneumonitis on days 2 and 4 of infection, respectively; both were treated with IDUR and survived. Abbreviations used: v-z virus: varicella-zoster virus IDUR: idoxuridine PBS: phosphate-buffered saline CPE: cytopathic effect BHK: baby hamster kidney From each patient approximately 0.1 ml of vesicle fluid was aseptically aspirated with a sterile, disposable 27gauge needle attached to a 1.0 ml syringe. Two to 3 ml of blood, obtained by venipuncture, were drawn into a syringe containing 0.1 m l of heparin (1,000 units/ml). All specimens were inoculated into tissue cultures within 2 hours. Culture system. Human embryonic lung fibroblasts were used to isolate v-z virus from clinical specimens. Fibroblasts were prepared from the lungs of a spontaneously aborted fetus of less than 20 weeks' gestation; the procedure was similar to that of Lennette and Schmidt. 3
Brief clinical and laboratory observations
ment of Hemophilus influenzae meningitis: A comparison of chloramphenicol and tetracycline, J Inf Dis 125:459, 1972.
263
19. Emerson BB, Smith AL, Harding AL, and Smith DH: H. influenzae b susceptibility to 17 antibiotics, J PEDIATR 86:617, 1975.
Laryngeal obstruction in childhood sarcoidosis Barbara S. Kirschner, M.D.,* and Paul H. Holinger, M.D., Chicago, 111. MORE THAN 230 CHILDREN with sarcoidosis have been described in the pediatric literature, but none had recognized laryngeal involvement resulting in significant respiratory impairment. The present c o m m u n i c a t i o n describes a 14-year-old boy who developed almost complete airway obstruction secondary to extensive laryngeal infiltration at a time when his p u l m o n a r y parenchymal disease had improved. CASE REPORT Patient R. S., a 14-year-old black male, was well until nine years of age, when he developed progressive dyspnea, cough, and anorexia. Physical findings included respiratory distress at rest, perioral cyanosis, granulomatous uveitis, cervical adenopathy, and digital dubbing, but no hepatosplenomegaly. Chest roentgenogram showed bilateral hilar and right paratracheal adenopathy, with diffuse bilateral nodular infiltrations. Results of fungal complement fixation titers, skin tests for fungi, and purified protein derivative were negative. Noncaseating, epithelioid granulomas were observed in a paratracheal lymph node biopsy; stains and cultures for acid-fast bacilli and fungi were negative. The patient received prednisone 20 mg daily for seven months followed by alternate-day therapy. Four months later, in March, 1971, hoarseness developed; on indirect laryngoscopy, vocal cords and epiglottis were normal but mild inflammation of the left arytenoid was noted. Pulmonary function studies and blood gas determinations were within normal limits. Prednisone dosage was decreased gradually, but exertional dyspnea recurred. In February, 1973, increasing dyspnea, cough, and hoarseness occurred with no evidence of increasing pulmonary disease radiologically or by pulmonary function studies. In June, 1973, swelling of the nasal turbinates ensued; biopsy showed noncaseating granulomas. Indirect laryngoscopy demon-
From the Department of Pediatrics, Michael Reese Hospital, and the Department of Laryngology and Bronchoesophagology, University of lllinois Hospital. *Reprint address: Departmentof Pediatrics, Universityof Chicago, 5825 MarylandA re., Chicago, Ill. 60637.
Fig. 1. Lateral xeroradiogram of the neck, demonstrating epiglottic edema, subglottic polypoid masses, and tracheal stenosis. strated edema of the uvula, epiglottis, and aryepiglottic folds; a chest roentgenogram was unchanged. The sudden onset of stridor in August, 1973, necessitated immediate hospitalization. The epiglottis and arytenoids were enlarged and the glottis was 80% narrowed. Soft tissue swelling in the subglottic region and narrowing in the midtrachea were apparent on the roentgenogram. A tracheotomy was planned, but was cancelled because of rapid improvement of laryngeal edema within 48 hours after 60 mg daily of prednisone. Alternate-day prednisone (80 mg) therapy was started, but within three months there was increasing hoarseness, exertional dyspnea, and mouth breathing. Xeroradiograms of the head and neck demonstrated epiglottic edema, large polypoid subglottic masses, and circumscribed stenosis of the
264
Brief clinical and laboratory observations
The Journal of Pediatrics February 1976
Fig. 2. Photographs obtained during direct laryngoscopy, a, Normal larynx; note clear view of true vocal cords, b and c, Extensive granulomatous tissue and edema of laryngeal tissue prior to the surgical procedure, September, 1973. b, Photographs above level of false cords showing severe stenosis; vocal cords not visible, c, Laryngoscope has been advanced but vocal cords only barely visible beyond diseased tissues, d, Fibrotic changes present in December, 1974.
trachea at the level of C6 and C7 (Fig. 1). Direct laryngoscopy disclosed a markedly thickened epiglottis, nodular infiltration of both false cords, and erythematous vocal cords, which were confluent with the subglottic tissue and almost completely obstructed the airway (Fig. 2). Bronchoscopy was not performed for fear it might precipitate further obstruction. Excisional biopsies taken from both false cords in essence removed the obstructive tissue overhanging the true cords. Histologic study of this tissue showed noncaseating granulomas. Prednisone therapy was continued on alternate days, with no evidence of recurrent obstruction. Currently (July 1975), there is persistent involvement of the soft palate, uvula, epiglottis, arytenoids, and aryepiglottic folds. Cystic lesions are present in the small bones of the hands and feet and skin nodules have appeared on the left arm. There is no significant adenopathy or hepatosplenomegaly. Serologic tests are normal, except for mild eosinophilia (9%). In 1970, a sister was proved to have sarcoidosis with involvement of the parotid gland, cervical and hilar lymph nodes, and minimal pulmonary parenchymal infiltrations. She received 20 months of prednisone therapy and now has no signs of active disease.
DISCUSSION Jasper and Denny ~ recently reported a series o f 25 children with sarcoidosis, one of w h o m had a vocal cord nodule which was not biopsied. M c G o v e r n and Merritt, 2 in an extensive review o f 113 cases of childhood sarcoidosis, did not mention direct laryngeal involvement but reported peripheral and cranial nerve lesions, which resulted in paralysis of the soft palate and vocal cord dysfunction. Kendig 3 and Siltzbach and Greenberg ' in their discussions of organs affected by sarcoidosis did not include the larynx. Reisner 5 described a 17-year-old girl with diffuse infiltration of the larynx and epiglottis. Biopsies of these tissues were not obtained and reexamination seven years later disclosed no signs of respiratory or vocal cord impairment. Devine 6 reviewed the literature concerning infiltration of the larynx in adults with sarcoidosis. The incidence varied from 1.2% to 5%. The epiglottis, aryepiglottic tblds, and arytenoids were most commonly affected and appeared either thickened
Volume 88 Number 2
and edematous or nodular. The vocal cords were rarely abnormal, which explains why airway obstruction rather than vocal changes usually occurs. In a few patients, laryngeal sarcoidosis was observed in the absence of other systemic manifestations of the disease. It is noteworthy that progression of the extrathoracic manifestations of our patient's disease occurred at a time when pulmonary involvement appeared to be stable. This coincides with the experience previously reported in adults. 6 Recognition of this phenomenon should encourage upper airway examination of children with increasing respiratory distress associated with sarcoidosis. Diminution of t h e laryngeal edema by large dose prednisone therapy prevented an anticipated tracheotomy. The recurrence of dyspnea while on a high-dose, alternate-day prednisone regimen, however, necessitated surgical excision of polypoid granulomatous tissue to prevent upper respiratory tract obstruction. Localization of the subglot-
Isolation of varicellazoster virus from blood Sandor Feldman, M.D.,* and Elizabeth Epp, B.A., Memphis, Tenn. V A R I C E L L A is a common childhood infection, manifest as cutaneous lesions, little is known about the hematogenous dissemination of v-z virus. The frequent occurrence of viscerally disseminated lesions in the immunosuppressed host 1 indicates that varicella has a viremic phase; however, antemortem isolation of v-z virus from blood has been reported only once. In 1966 Gold ~ isolated this virus from the blood of a child with hepatoma and varicella but further attempts to isolate bloodborne v-z virus in this and other patients were unsuccessful. Gold's report does not state the type of blood specimen used, the culture technique, or the relationship of blood cultures to the clinical status of the patient. A simple and reliable method for isolating v-z virus ALTHOUGH
From the Infectious Diseases Service, St. Jude Children's Research Hospital. Supported by Cancer Research Center Grant CA 08480from the National Cancer Institute, by a grant from the Washington County, Tennessee Cancer Society, and by A LSA C. *Reprint address: Infectious Diseases Service, St. Jude Children's Research Hospital, P.O. Box 318, Memphis, Tenn. 38101.
B r i e f clinical and laboratory observations
265
tic lesions by xeroradiography 7 prior to surgery facilitated therapy by accentuating the margins of nodular masses accessible to extirpation. REFERENCES 1. Jasper PL, and Denny FW: Sarcoidosis in children, J PEDIATR73:499, 1968. 2. McGovern JP, and Merritt DH: Sarcoidosis in children, Adv Pediatr 8:97, 1956. 3. Kendig EL: Sarcoidosis among children, J PEDIATR61:269, 1962. 4. Siltzbach LE and Greenberg GM: Childhood sarcoidosis: A study of 18 patients, N Engl J Med 279:1239, 1968. 5. Reisner D: Boeck's sarcoid and systemic sarcoidosis: A study of 35 cases, Am Rev Tuberc 49:437, 1944. 6. Devine KD: Sarcoidosis and sarcoidosis of the larynx, Laryngoscope 55i533, 1965. 7. Holinger PH, Lutterbeck EF, and Bulger R: Xeroradiography of the larynx, Ann Otol Rhinol Laryngol 81:1, 1972.
from blood would be useful in studying the pathogenesis of variceUa as well as evaluating the efficacy of antiviral agents in treatment of the infection. Such a method is reported here. MATERIALS
AND METHODS
Clinical specimens. Specimens for the isolation of virus were obtained from two children with acute leukemia and varicella. These patients developed varicella pneumonitis on days 2 and 4 of infection, respectively; both were treated with IDUR and survived. Abbreviations used: v-z virus: varicella-zoster virus IDUR: idoxuridine PBS: phosphate-buffered saline CPE: cytopathic effect BHK: baby hamster kidney From each patient approximately 0.1 ml of vesicle fluid was aseptically aspirated with a sterile, disposable 27gauge needle attached to a 1.0 ml syringe. Two to 3 ml of blood, obtained by venipuncture, were drawn into a syringe containing 0.1 m l of heparin (1,000 units/ml). All specimens were inoculated into tissue cultures within 2 hours. Culture system. Human embryonic lung fibroblasts were used to isolate v-z virus from clinical specimens. Fibroblasts were prepared from the lungs of a spontaneously aborted fetus of less than 20 weeks' gestation; the procedure was similar to that of Lennette and Schmidt. 3
