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Brief clinical and laboratory observations

REFERENCES 1. Roser F, Kozinn PJ, and Jervis GA: Leukocyte function and serum immunoglobulins in Down's syndrome, N Y State J Med 73:672, 1973. 2. Kretschmer RR, Lopez-Osuna M, De La Rosa and Armendares S: Leukocyte functions in Down's syndrome qualitative NBT reduction and bactericidal capacity, Clin Immunol Immunopathol 2:449, 1974. 3. Boyden SV: The chemotactie effect of mixtures of antibody and antigen on polymorphonuelear leukocytes, J Exp Med 115:453, !962. 4. Baum J, Mowat AG, and Kirk JA: A simiplified method for the measurement of chemotaxis of polymorphonuclear leukocytes from human blood, J Lab Ctin Meal 77:501, 1971. 5. Park BH, Fikfig SM, and Smithwick EM: Infection and nitroblue tetrazolinm reduction by neutrophils: A diagnostic aid, Lancet 2:532, 1968. 6. McKelvey EM, and Fahey JL: Immunoglobulin changes in disease, J Clin Invest 44:1778, 1965.

Recurrent aseptic meningitis without sequelae Wendy S. Coleman, M.D., Harold W. Lischner, M.D., and Warren D. Grover, M.D.,* Philadelphia, Pa.

R E C U R R E N T ASEPTIC M E N I N G I T I S is a rare disease in infancy. The syndrome is characterized by bouts of fever associated with signs of meningeal irritation, increased cell count in cerebrospinal fluid with occasional large endothelial cells, and a self-limited course unaffected by antibiotic therapy? Between attacks, patients are asymptomatic and manifest no a b n o r m a l neurologic signs. The administration of corticosteroids to patients who have this condition has not usually altered the illness? We could find only one report describing a decrease in the number of recurrences of aseptic meningitis in a child 7 years of age who was treated with prednisone? We have observed recurrent aseptic meningitis over a period o f 21

From St. Christopher's Hospital for Children and the Departments of Pediatrics, Neurology, and Immunology, Temple University School of Medicine. Supported in part by Department of Health, Education, and Welfare Training Grant (I TO1 NSlOO72-OIA2, NSRA). *Reprints to: 2600 N. Lawrence St., Philadelphia, Pa. 19133.

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7. Mainland D: Elementary medical statistics, Philadelphia, 1965, WB Saunders Company, p 283. 8. Raab SO, Mellman WJ, Oski FA, and Bake D: Abnormal leukocyte kinetics-an explanation for enzyme abnormalities observed in trisomy 21 (Down's syndrome), J PEDIATR 69:952, 1966. 9. Hsia DYY, Justice P, George F, Smith GF, and Dowben RM: Down's syndrome a critical review of the biochemical and immunological data, Am J Dis Child 121:153, 1971. 10. Hill HR, Saul HS, Dettloff JL, and Quie PG: Impaired leukotactic responsiveness in patients with juvenile diabetes mel!itus, Clin Immunol Immunopathol 2:395, 1974. 11. Miller ME: Chemotaxis and random mobility characterization of two distinct mechanisms of leukocyte movements, their clinical significance and their correlation with neutrophilenia, in Braun W, and Ungar J, editors: Non-specific factors influencing host resistance, Basel, 1973, S. Karger AG, p. 215.

months in an infant one year of age. Therapy with corticosteroids was associated with a decrease in the frequency and severity of attacks.

CASE REPORT Patient M. W. (SCHC No. 70-02-031) was first admitted to St. Christopher's Hospital for Children at the age of one year for evaluation of fever, lethargy, and vomiting. She presented as a fretful, black female infant (weight 9.8 kg, height 82 cm, and temperature 400 C rectally) without evidence of localized infection, nuchal rigidity, or abnormal neurologic signs. The cerebrospinal fluid contained 648 cells (55% mononuclear cells), 50 mg/ dl of protein, and 41 mg/dl of glucose (Fig. 1). No organisms were seen on Grain stain and no aerobic or anaerobic bacteria or fungi were recovered from the cerebrospinal fluid culture. Recovery was apparently complete after 24 hours. A review of the past history indicated no head trauma, exposure to drugs or chemicals, or infection with unusual agents. The mother's pregnancy and delivery had not been unusual; birth weight was 2.4 kg. There was no family history of neurologic or immunologic disease. Abbreviation used CSF: cerebrospinal fluid

I

Six weeks later similar signs and symptoms recurred. Examination at this time revealed an irritable child with fever (40 ~ C) and nuchal stiffness. A small sacral sinus tract was noted; there was no evidence of inflammation. The CSF contained 3,400 cells (64% mononuelear cells), a protein level of 128 mg/dl, and a glucose level of 42 mg/dl (Fig. 1) Intravenous therapy with ampicillin (300 mg/kg/24 hr) was started. After 24 hours the CSF contained 1,364 cells (5% mononuclear cells), a protein level of 62 mg/dl, and a glucose level of 48 mg/dl. Defervescence occurred during the next three days. Exploration and removal of the

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Briefclinical and laboratory observations

The Journal ofPediatrics July1975

3500--

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TOTAL CELL COUNT % MONONUCLEAR CELLS l~ CSF PROTEIN mg/dL [ ] CSF GLUCOSE mg/dl

2500-2000-1500-i 1000--

u

100--

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1

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~ ~ ~2 rP,

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Fig. 1. Serial CSF data and response to therapy. dermal sinus tract were performed after the acute episode had resolved. At the time of surgery, no connection between the sinus tract and the spinal canal was found. No neurologic abnormalities were observed at the time of discharge from the hospital. Between the ages of 13 and 23 months, she had seven similar episodes (Fig. 1). Each was characterized by fever, irritability, vomiting, and nuchal rigidity. Recovery was spontaneous within 48 to 72 hours. An increased cell count was noted at the time of each spinal fluid analysis. Large fragile endothelial cells were observed in the CSF during the third hospitalization. Intravenous therapy with ampicillin and gentamicin was given during the first three of these episodes, without apparent effect. Cultures for bacteria, viruses, and fungi and serologic tests including immunoglobulin levels in the serum and CSF, hemolytic complement assay (CH 50), assays of complement factors 3 and 4, and lupus erythematosus preparations were normal. Antinuclear antibody, rheumatoid factor, cold agglutinins, and cryoglobulins could not be detected in serum. Other negative results included roentgenographs of the skull (with temporal bone tomograPhY ), paravertebral spine, and chest as well as pneumoencephalography, myelography, technetium and mercury brain scan, intrathecal RISA scan, carotid angiography, and repeated electroencephalograms. A second lumbar exploration with laminectomy was performed at 16 months of age; no cause for the repeated episodes of meningitis was found. Her mental and motor development continued to progress normally. During the ninth episode, when the patient was 23 months of age, the administration of prednisone was started (2 mg/kg/day). The daily dose was decreased to 2.5 mg every other day during the next three months. During the time of corticosteroid therapy the patient was asymptomatic. Administration of prednisone was discontinued after a period of five months; aseptic meningitis recurred two days later. Prednisone therapy (2 mg/kg/day) was started at 28 months of age, and the, dose was gradually decreased to 5 mg every other day over the next three months. With the exception of brief episodes of fever and irritability lasting up to

ten hours, when there was a minimal increase in the CSF cells, the patient has remained asymptomatic. At 40 months of age the neurologic examination was normal and motor and mental abilities appear advanced for her age. DISCUSSION The signs and symptoms demonstrated by our patient were unique in respect to the age o f onset, repeated occurrences of meningitis over a 21-month period without detectable etiology or sequelae, and the response to corticosteroid therapy. Recurrent meningitis in infancy suggests a congenital or traumatic defect in the meninges or a parameningeal focus of infection. ~ Other causes ~, 3 of recurrent meningitis in the pediatric age group include spinal or intracranial dermoid cyst, craniopharyngioma, neurenteric cysts, meningeal dissemination of posterior fossa neoplasms, unusual infections (leptospiral, fungal, viral), leukemia, i m m u n e defects, and collagen diseases. In our patient n o abnormalities were found in roentgenographic studies, surgical exploration, or laboratory examinations to identify other causes of recurrent meningitis. Mollaret' described a disease in adults which included short periods of meningitis without apparent cause. Typical cerebrospinal fluid findings included an increased n u m b e r of cells with a predominance of lymphocytes and occasional large, fragile endothelial ceils. The patients were asymptomatic between attacks. This disease is rare in childhood; we could find no reports of patients under five years of age 2 and only one report o f a child seven years of age who responded to therapy. 3 The empiric use of prednisone in our patient was associated with a decreased frequency of attacks and an exacerbation of the disease process when therapy was discontinued. The

Volume 87 Number 1

response to corticosteroid therapy might represent an effect upon a still undetected immunologic process or simple suppression of an inflammatory process initiated by some undetected infectious agent.

REFERENCES 1. Bruyn GW, Staathof LJA, and Raymakers GMJ: Mollaret's meningitis: Differential diagnosis and diagnostic pitfalls, Neurology 12:745, 1962.

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2. Hermans PE, Goldstein MP, and Wellman WE: Mollaret's meningitis and differential diagnosis of recurrent meningitis, Am J Med 52:128, 1972. 3. Swartz MN and Dodge PR: Bacterial meningitis: a review of selected aspects, N Engl J Med 272"898, 1965. 4. Mollaret P: La meningite endothelio-leuco-cytaire multirecurrente benigne: syndrome nouveau ou maladie nouvelle? Presentation de deux malades, Bull Soc Med Hosp Paris p 121, March 1944.

Hypergammaglobulinemic purpura in a child Jerry C. Jacobs, M.D., N e w York, N.Y.

I N 1 9 4 3 W A L D ~ N ST R O M 1 described three women with chronic relapsing purpura of the lower extremities. A n elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and mild anemia were characteristic of the syndrome. The purpura was not u n u s u a l except for a marked orthostatic tendency (carrying heavy things with outstretched arms could produce it in the arms of one lady). Although the purpuric lesions disappeared after each episode, small pigmented spots remained. After m a n y episodes these coalesced resulting in a permanently mottled appearance with brown patches which has been considered diagnostic (Fig. 1). Of the more than 100 patients reported, ~ ~ only three girls, two of Greek origin, had the onset in childhood. However, 90% of all reported cases have been women and the few m e n who have had the disorder have been middle aged. We have recently seen an 8-year-old boy with a definitive diagnosis of hypergammaglobulinemic purpura whose disease started at age 3 years.

CASE REPORT Patient G. P., an 8-year-old Greek boy, was first seen at the Columbia-Presbyterian Medical Center in August, 1973, for evaluation of chronic generalized lymphadenopathy and varying swelling of the lower extremities with dependent purpura. He had been well until age 3 years when these same symptoms first appeared. Repeated studies in Greece revealed hypergammaFrom the Department o f Pediatrics, College o f Physicians & Surgeons o f Columbia University, The Edward Daniels Faulkner Arthritis Clinic, and the Babies Hospital, the Children's Medical & Surgical Center, Columbia-Presbyterian Medical Center. Reprint address: Babies Hospital, The Children's Medical & Surgical Center, 3975 Broadway, New York, N. Y. 10032.

Fig. 1. Characteristic purpuric spots, permanent brown pigmentation, and brawny swelling of legs in hypergammaglobulinemic purpura. globulinemia, nonspecific lymphadenitis on lymph node biopsy, and slight eosinophilia in bone marrow aspirations. Despite these complaints, he had remained generally healthy and led a normal life, although at times leg pain prevented running and playing. Physical examination was otherwise normal. Abnormal laboratory studies included: hemoglobin, 10.0 gm/ dl; reticulocyte count, 1.6%; erythrocyte sedimentation rate, 125 mm/hr (Westergren); serum haptoglobin, decreased; gamma-2 globulin, 3.6 gm/dl; IgG, 3,000 mg/dl; IgA, 420 mg/dl; IgM, 315 mg/dl (normal ranges: IgG, 400-1,435 mg/dl; IgA, 35-215 mg/