Sinus histiocytosis

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noglobulin synthesis. 12 The association of antibody to E N A and a n SLE-like syndrome appears to be equally rare in children; the youngest case reported thus far is in a child 9 years of age. 13No complement studies were reported in this patient. It would seem that our patient has a unique SLE-like disorder characterized by Clq deficiency, persistently low total hemolytic complement, high antibody titer to ENA, minimal evidence of renal disease, and onset of disease at an extremely early age. Recognition of SLE-like disorders associated with comp l e m e n t deficiencies a s s u m e s great i m p o r t a n c e in determining the activity of disease, therapeutic trials, and subsequent prognosis. REFERENCES 1. Sharp GC, Irvin WS, La.Rogue RL, Velez C, Daley V, Kaiser AD, and Holman HR: Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy, J Clin Invest 50:350, 1971. 2. Sharp GC, Irvin WS, Tan EM, Gould RG, and Holman HR: Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA), Am J Med 52:148, 1972. 3. Epstein WV: Immunologic events preceding clinical exacerbation of systemic lupus erythematosus, Am J Med 54:631, 1973. 4. Koher PF, and Muller-Eberbard HJ: Immunochemical quantitation of the third, fourth and fifth components of human complement: Concentrations in the serum of healthy adults, J Immunol 99:1211, t967.

S&us histiocytosis Larry K. Piekering, M.D.,* Houston, Texas, and Elna Phelan, M.D, St. Louis, Mo. SINUS HISTIOCYTOSIS with l y m p h a d e n o p a t h y is a b e n i g n c o n d i t i o n characterized by painless, massive lymphadenopathy which has a microscopic appearance of sinusoidal dilatation with proliferation of foamy histiocytes and multinucleated giant cells within the siFrom the Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and Divisions of lnfeetious Disease and Hematology at St. Louis Children's Hospital. *Reprint address: The University of TexasHealth Science Center, MedicalSchool, 6400 W. CullenSt., Houston, Texas 77025.

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5. Ammann AJ, Wara D, Salmon S, and Perkins H: Thymus transplantation: Permanent reconstitution of cellular immunity in a patient with sex-linked combined immunodeficiency, N Engl J Med 289:5, 1973. 6. Grossman J, Callerame ML, and Condemi J J: Skin immunofluorescence studies on lupus erythematosus and other antinuclear-antibody-positive diseases, Ann Intern Med 80:496, 1974. 7. Gyorkey F, Min KW, Sincovics JG, and Gyorkey P: Systemic lupus erythematosus and myxovirus, N Engl J Med 280:333, 1969. 8. Goodman JR, Sylvester RA, Talal N, and Tuffanelli DL: Virus-like structures in lymphocytes of patients with systemic and discoid lupus erythematosus, Ann Intern Med 79:396, 1973. 9. Day NK, Geiger H, McLean R, Michael A, and Good RA: C2 deficiency. Development of lupus erythematosus, J Clin Invest 52:1601, 1973. 10. Day NK, Geiger SR, deBracco M, Moncada B, Windhorst D, and Good RA: Clr deficiency: An inborn error associated with cutaneous and renal disease, J Clin Invest 51:1102, 1972. 11. deBracco MME, Windhorst D, Stroud RM, and Moncada B: The autosomal recessive mode of inheritance of Clr deficiency in a large Puerto Rican family, Clin Exp Immunol 16:183, 1974. 12. Gewurz H, Picketing RJ, Christian CL, Synderman R, Mergenhagen SE, and Good RA: Decreased Clq protein concentration and agglutination activity in agammaglobulinemia syndromes: an inborn error reflected in the complement system, Clin Exp Immunol 3:437, 1968. 13. Sanders DY, Huntley CC, and Sharp GC: Mixed connective tissue disease in a child, J PEDIATR83:642, 1973.

nuses. The cervical lymph nodes usually are involved, b u t other lymph nodes may be affected. The etiology is u n k n o w n and no specific treatment is required. Abbreviations used NBT: nitroblue tetrazolium HMPS: hexose monophosphate shunt We report two cases of sinus histiocytosis presenting with different clinical manifestations. Extensive evaluation of the i m m u n e systems of these children in addition to complete bacterial, fungal, acid-fast, and viral cultures failed to yield additional etiologic information. CASE R E P O R T S Case I. Patient M~ S., a 3-year-old black boy, was in good health until several weeks prior to admission, when bilateral,

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The Journal of Pediatrics May 1975

Fig. 2. Anterioposterior chest radiograph of patient W. W. showing bilateral hilar and paratracheal adenopathy with clear lung fields.

Fig. 1. Two (100x) photomicrographs demonstrating increased pericapsular fibrosis and thickening with sinusoidal areas occupied by large histiocytes with decrease of lymphoid follicular size and loss of lymphoid follicles.

rubbery masses were noted in both upper eyelids. No fever, rash, pharyngitis, or visual difficulty were present. Growth and development were normal. He had received all required immunizations without sequelae, and past medical history did not suggest unusual susceptibility to infection. Physical examination revealed a well-developed black boy with normal vital signs. Positive physical findings included bilateral, rubbery masses in the upper eyelids and posterior cervical and submandibular lymphadenopathy. Results of the ophthalmologic examination was normal. Laboratory data included: hemoglobin, 11 gm/dl; hematocrit, 31%; platelet count, 300,000/mm3; reticulocyte count, 1%; leukocyte count, 10,600 cells/mm 3 with a normal differential. Radiographs of the chest, skull, and orbits were normal, and a skeletal survey revealed no evidence of destructive bone disease. Additional normal laboratory data included urinalysis, erythrocyte sedimentation rate, heterophile agglutination titer, Fransicella tularensis, and brucella titers, bilirubin, alkaline phosphatase, SGOT, SGPT, creatinine phosphokinase, lactic dehydrogenase, uric acid, and an antinuclear antibody determination. The results of a PPD skin test were nonreactive. A bone marrow aspirate revealed normal cellularity and morphology. There was no apparent immunologic deficiency as evidenced by an unstimulated 1 and stimulated 2 nitroblue tetrazolium dye reduction tests, unstimulated and stimulated hexose monop h o s p h a t e s h u n t ( H M P S ) activity of l e u k o c y t e s , 3 total hemolytic complement, third complement component, serum immunoglobulins, and lymphocyte responses to phytohemag-

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glutinin.4 A monilia skin test revealed 7 mm of induration 48 hours after placement. Biopsies of the left eyelid mass and of a posterior cervical lymph node were obtained and found to be consistent with sinus histiocytosis (Fig. 1). No bacterial, fungal, viral, or acidfast organisms were seen on stains or isolated from cultures of the eyelid mass, lymph node biopsy, bone marrow, or blood. Follow-up examination one year after hospitalization revealed no significant change. Growth and development continued to be normal. Case II. Patient W. W., a 3-year-old white boy, was hospitalized for evaluation of neck masses of six weeks' duration with no associated systemic or respiratory symptoms. Past medical.history suggested no unusual susceptibility to infections or adverse affects from any immunizations. Physical examination revealed a well-developed white boy with normal vital signs. Height, weight, and head circumference measurements were all at the fiftieth percentile. Soft, mobile, nontender, 3 x3 cm masses were p~.lpablein the left and right submandibular areas. No hepatosplenomegaly or additional lymphadenopathy was present. Similar laboratory and immune evaluations performed in the previous patient were also within normal limits in this patient. Radiographs of the chest showed bilateral hilar and right paratrac heal adenopathy with clear lung fields (Fig. 2). Films of the mandibles revealed no bony abnormalities, but soft tissue swelling was noted in the areas of the neck masses. A skeletal survey was normal. A bone marrow aspirate revealed normal cellularity and morphology. A left submandibular lymph node biopsy was performed and microscopic examination was consistent with sinus histiocytosis. Bacterial, fungal, acid-fast, and viral cultures of the lymph node and bone marrow aspirate were unrevealing..Gram and acid-fast stains of the material were negative. The child was seen fo~" follow-up examination ten weeks after discharge at which time a slight regression in the size of the cervical adenopathy was noted. Ih the interim period no fever, weight loss, decrease in activity, or development of other lymphadenopathy or hepatosplenomegaly was noted. DISCUSSION The clinical and pathologic findings in the two patients presented are consistent with a diagnosis of sinus histiocytosis. I n 1969, Rosai and Dorfman 5 reported four cases of this syndrome and in 1972 thirty additional cases were described. 6 The disease usually becomes manifest in the first decade of life with the appearance of massive, painless l y m p h a d e n o p a t h y involving the cervical lymph nodes and occasionally the axiliary and inguinal nodes. The involved lymph nodes characteristically enlarge minimally or remain stable in size o v e r a period of several years with subsequent gradual remission. Various treatment regimens have had little or no effect on the course of this benign disease.

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Laboratory evaluation of patients with this syndrome have not been uniform b u t anemia, neutrophil leukocytosis, an increase in the erythrocyte sedimentation rate, and an elevated level of serum IgG have been commonly noted. Minimal elevations of serum IgG concentrations were documented by quantitative immunodiffusion in both of our patients, b u t anemia, leukocytosis, and an increased erythrocyte sedimentation rate were not present. Extensive serologic and radiographic evaluations of both patients were normal, except for the hilar adenopathy that was found in Patient W.W. The etiology of the condition is u n k n o w n , b u t a deficiency of the i m m u n e system or an infectious process has been postulated. Immunologic evaluation of patients previously reported with sinus histiocytosis is scant. For this reason, we investigated the humoral and cellular i m m u n e systems of the patients described. Both had morphologically normal appearing leukocytes on peripheral and bone marrow smears. The resting and s t i m u l a t e d HMPS values were w i t h i n n o r m a l limits w h e n c o m p a r e d to similar d e t e r m i n a t i o n s m a d e on blood obtained from 30 healthy children. These normal values for HMPS activity and NBT dye reduction contrast with the depressed stimulated HMPS activity and stimulated NBT dye reduction reported in 106 children with malignancies.7 Lymphocyte function was evaluated in our patients by absolute lymphocyte counts, delayed hypersensitivity skin tests, and lymphocyte response to phytohemagglutinin. All of these determ i n a t i o n s s u b s t a n t i a t e d n o r m a l T cell f u n c t i o n . Humoral lmmunity appeared to be intact as manifest by the presence of IgG, IgA, IgM, BIC, and total hemolytic complement in adequate quantities in serum. The patients presented have been free of recurrent or serious bacterial infections and have had no abnormal reactions to live viral vaccines. A n i m m u n e deficiency in h u m o r a l , leukocyte f u n c t i o n , or cellular i m m u n e mechanisms as either the etiology or consequence of this condition seems unlikely. The possibility cannot be excluded that a breakdown in host defenses might involve a specific failure in either recognition of an antigen as foreign or the production of one or more of the lymphocyte mediators, with subsequent production of this disease. The patients described illustrate two of the clinical presentations of this benign condition and stress the importance of early and proper differentiation of sinus histiocytosis from the more m a l i g n a n t l y m p h o m a s which often require more drastic and sustained treatment.

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REFERENCES 1. Park BH, Fikrig SM, and Smithwick EM: Infection and nitroblue tetrazolium reduction of neutrophils, Lancet 2:532, 1968. 2. Gifford RH, and Malawista SE: A simple rapid micromethod for detecting chronic granulomatous disease of childhood, J Lab Clin Med 75:511, 1970. 3. Keusch GT, Douglas SD, and Mildvan D: 14C-glucose oxidation in whole blood: A clinical assay for phagocytic dysfunction, Infect Immunol 5:414, 1972. 4. Park BH, and Good RA: A new micromethod for evaluating lymphocyte responses to phytohemagglutinin: Quan-

Occult neuromuscular disease in 100 consecutive patients with scoliosis A. David Rothner, M.D.,* Cleveland, Ohio, Hugo Keim, M.D., and Abe M. Chutorian, M.D., New York, N. Y.

SCOLIOSIS is k n o w n to be a s s o c i a t e d with a wide variety of neurologic disorders. 1"7 Unfortunately, patients with scoliosis are usually seen by neurologists only when obvious neurologic dysfunction is evident or postoperative complications occur. W e have suspected that occult neuromuscular disorders might on occasion be present in a subclinical or subtle fashion and escape detection by the pediatrician and by the orthopedist. To test this supposition a prospective neurologic evaluation of children with scoliosis was undertaken. MATERIALS

AND METHODS

P a t i e n t s e x a m i n e d at t h e C o l u m b i a - P r e s b y t e r i a n Medical Center from July, 1971, to April, 1972, with the chief complaint of scoliosis were included in this study. Sixty-six were inpatients and 34 were outpatients. Patients suspected of having neuromuscular disorders by From the Division of Child Neurology, Department of Neurology, Neurological Institute, College of Physicians and Surgeons of Columbia University. Supported in part by National Institutes of Health Special Fellowship 5 FII NS 2302-03 NSRA. Presented in part at the American Academy of Neurology, Boston, April, 1973. *Reprint address: Section of Child Neurology, The Cleveland ClinicFoundatlon, 9500EuclidAve., Cleveland, Ohio 44106.

The Journal of Pediatrics May 1975

titative analysis of the function of thymus-dependent cells, Proc Natl Acad Sci USA 69:371, 1972. 5. Rosai J, and Dorfman RF: Sinus histiocytosis with massive lymphadenopathy: A newly recognized benign clinicopathological entity, Arch Pathol 87:63, 1969. 6. Rosai J, and Dorfman RF: Sinus histiocytosis with massive lymphadenopathy: A pseudolymphomatous benign disorder, Cancer 30:1174, 1972, 7. Pickering LK, Anderson DC, Choi S, and Feigin RD: Leukocyte function in children with malignancies, Cancer (in press).

their referring physicians or by the Orthopedic Staff were excluded. There were 12 children in this category; their diagnoses included: muscular dystrophy, anterior horn cell disease, cerebral palsy, and meningomyelocele. Detailed medical and family histories were obtained and general orthopedic and neurologic examinations were conducted on all patients. Outpatients had only roentgenographic examinations of the entire spine, unless other diagnostic measures seemed to be indicated. Inpatients h a d the following laboratory studies: complete blood cell counts, SMA 12-60, creatine phosphokinase, coagulation studies, urinalyses, electrocardiograms, pulmonary function studies, and roentgenograms of the entire spine. The following special procedures were performed when indicated; laminography, myelography, spinal arteriography, electromyography, nerve conduction velocities, and muscle biopsies. RESULTS The patients were broadly classified into four groups: idiopathic (genetic), congenital, neuromuscular, and miscellaneous. Group I. Seventy-two patients composed the idiopathic group. N o cause could be found for their curvatures. The inpatients and outpatients in this group were compared with regard to sex, age, duration of scoliosis, and type and degree of curvature. The inpatients and outpatients did not differ significantly and were therefore considered as a single group. The features of this group did not differ from those of previously reported patients with idiopathic scoliosis. The female to male ratio was five to one. Forty-one percent of the patients had a family history of scoliosis. Forty-seven patients in this group had surgical correction of scoliosis and no complications occurred. The other 25 patients in this group either received no specific therapy because