- Email: [email protected]
Multicentric reticulohistiocytosis in a child
266
Clinical and laboratory observations
diagnosis would allow for more effective management of anticipated problems such as cholelithiasis and its complications, the need for splenectomy, and the examination of family members for the disease. REFERENCES
1. Hereditary spherocytosis and other hemolytic anemias associated with abnormalities of the red cell membrane. In: Wintrobe MM, Lee GR, Boggs DR, et al., eds. Clinical hematology. Philadelphia: Lea & Febiger, 1981:747-8. 2. Fukagawa N, Friedman S, Gill FM, et al, Hereditary spherocytosis with normal fragility after incubation. JAMA 1979;242:63-4. 3. Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anemia. QJ Med 1953;22:79-99. 4. Zail SS, Krawitz P, Viljoen E, et al. Atypical hereditary spherocytosis: biochemical studies and sites of erythrocyte destruction. Br Med J 1967;13:323-34.
The Journal of Pediatrics February 1989
5. Lefrere J J, Courouce AM, Girot R, et al. Six cases of hereditary spherocytosis revealed by human parvovirus infection. Br J Haematol 1986;62:653-7. 6. Dameshek W, Bloom ML. The events in the hemolytic crisis of hereditary spherocytosis, with particular reference to the reticulocytopenia, pancytopenia and abnormal splenic mechanism. Blood 1948;3:1381-409. 7. Paolino W. Variations of the mean diameter in the ripening of the erythrocyte. Acta Med Scand 1949;136:141-7. 8. Griggs RC, Weisman R, Harris JW. Alterations in osmotic fragility related to in vivo erythrocyte aging and splenic sequestration in hereditary spherocytosis. J Clin Invest 1960;39:89-101. 9. Crosby WH, Conrad ME. Hereditary spherocytosis: observations on hemolytic mechanisms and iron metabolism. Blood 1960;15:662-74. 10. Lux SE. Disorders of the red cell membrane. In: Nathan D, Oski F, eds. Hematology of infancy and childhood. Philadelphia: WB Saunders, 1987:488-9.
Multicentric reticulohistiocytosis in a child Stephen A. Raphael, MD, Susan L. Cowdery, MD, Eric N. Faerber, MD, Harold W. Lischner, MD, H. Ralph Schumacher, MD, and Charles D. Tourtellotte, MD From the Section of Immunology and Rheumatology, Department of Pediatrics, the Department of Radiology, and the Section of Rheumatology, Department of Internal Medic!ne, Temple University School of Medicine and St. Christopher's Hospital for Children; the Department of internal Medicine, Section of Rheumatology, Albert Einstein Medical Center-Northern Division; and the Section of Rheumatology, Department of Internal Medicine, University of Pennsylvania School of Medicine and Veterans Administration Hospital of Philadelphia
Multicentric reticulohistiocytosis is a rare, easily misdiagnosed, systemic disorder of unknown cause, characterized by papulonodular skin lesions, potentially destructive arthritis, a tendency to involve multiple organs, and histopathologic studies that show large mononuclear and multinucleated giant cell infiltrations. 1-7 There is a possible association with malignancy, diabetes, hypothyroidism, hyperlipidemia, and tuberculosis.i, 2,6,8,9 All fully described cases have been in adults. W e present the first clinically described case of M R H in a child.
symmetric swelling of several distal interphalangeal joints, and nonpainful, hypopigmented wartlike intracutaneous nodules over the distal ends and periungual areas of several fingers. Subsequently, she experienced easy fatigability, increased numbers of skin nodules, and bilateral painful knee swelling. Fever, unexplained weight loss, anorexia, adenopathy, rash, signs of the Raynaud phenomenon, photosensitivity, mouth ulcers, chest pain, neurologic problems, myalgia, abdominal pain, eye irritation, loss of scalp hair, and intolerance to cold were denied. There was no MRH
Multicentric reticulohistiocytosis
[
CASE REPORT The patient, a black girl almost 14 years old, was well until 1ly2 years of age, when she noticed the simultaneous occurrence of early morning stiffness, loss of grip strength, right elbow pain,
Submitted for publication July 18, 1988; accepted Sept. 20, 1988. Reprint requests: Stephen A. Raphael, MD, St. Christopher's Hospital for Children, Section of Immunology and Rheumatology, 5th and Lehigh Ave., Philadelphia, PA 19133.
history of recent immunizations, antecedent illness, tick bite, or travel. The patient was taking no long-term medications. She was not sexually active. Growth and development had been normal. Family history revealed two well siblings and a history of intravenous drug abuse in the patient's father. Initial physical examination revealed an anxious 1l~(2-year-old pubertal black girl in no acute physical distress. Height and weight were appropriate for age. Vital signs were normal. The patient had multiple 2 to 3 mm wartlike nodules along the dorsal
Volume 114 Number 2
Clinical and laboratory observations
267
Fig. 1. Periungual wartlike nodules on the fingers, arranged in a "coral bead" formation.
aspects of her fingers with a "'coral bead" formation around the nail folds (Fig. 1). Several larger 5 mm nodules were palpable along the flexor tendon sheaths of the hands, over the wrists, along the extensor surface of the right elbow, and on the dorsum of the left foot. The patient had bilateral elbow contractures, fullness of both wrists with loss of full extension, minimally tender second metacarpophalangeal joints, bony deformities of several distal interphalangeal joints, marked bilateral knee swelling and tenderness (with associated 10-degree extension lags), and mild bilateral ankle swelling and tenderness. Grip strength was poor. The other findings of the examination, including those of a complete ophthalmologic examination, were within normal limits. One of us (C.D.T.), a rheumatologist for adults, made the diagnosis of MRH at this time. Laboratory data included normal values for hemoglobin, hematocrit, total leukocyte count, platelet count, erythrocyte sedimentation rate, C-reactive protein, sickle cell preparation, antinuclear antibodies, rheumatoid factor, serum lgA and IgM, C l q binding activity, urinalysis, cholesteroll and liver function. Abnormal results included increased values for serum IgG (1760 mg/dl), circulating immune complexes by Raji cell assay (168 ]xg antihemophilic globulin Eq/ml) without demonstrable antilymphocyte cytotoxic antibodies, triglycerides (189 mg/dl [2.15 mmol/L]), blood glucose (114 mg/dl [6.3 mmol/Ll), and 9% eosinophils on peripheral blood smear. A purified protein derivative test had a negative result. Conventional x-ray studies revealed a normal chest, multiple joint effusions with juxtaarticular soft tissue swelling and hyperemic changes, and generalized bone demineralization. There was no evidence of joint destruction. A skin biopsy specimen of one of the nodules showed, by light microscopy, infiltrations of mononuclear and multinucleated giant
cells (Fig. 2). Electron microscopy revealed scattered small monocytes and many larger cells with single or multiple nuclei containing little heterochromatinr profuse cytoplasmic mitochondria, dilated cisterns of smooth or rough endoplasmic reticulum, and laminated inclusions. With the recommended therapy of 75 mg/kg/day of aspirin, the patient had less pain and morning stiffness, but 21/2 months later, physical examination findings were unchanged except for less pain on joint movement. Laboratory data included normal values for reticulocyte count, triiodothyronine, thyroxine, thyroidstimulating hormone, lgG subclasses, and total numbers of T, B, CD4+, and CD8+, cells. A repeat total serum IgG test showed a normal level (1400 mg/dl). For better definition of the extent of joint involvement, a needle biopsy of the synovium, with aspiration of fluid from the left knee, was performed. Analysis of joint fluid revealed an erythrocyte count of 6700/mm 3, leukocyte count of 1200/mm 3 (2% polymorphonuclear leukocytes, 8% lymphocytes, 90% unidentified mononuclear), glucose level of 98 mg/dl (5.4 mmol/L), and total protein level of 4.7 gm/dl (47 gm/L). Gram stain and cultures were negative. Synovial biopsy showed a mild mononuclear infiltration with absence of histiocytes positive for periodic acid-Schiff reagent; no large cells were seen. Electron microscopy showed some proliferating type B (fibroblast-like) lining cells, scattered monocytes, and perivascular fibrosis. On magnetic resonance imaging scan of the knees, bilateral intraarticular effusions were again demonstrated. A small, discrete area of decreased signal intensity measuring 1 cm was found in the subcutaneous fat, posterior to the popliteal vessels of the left knee. Ten months later the patient returned. Aspirin therapy had been discontinued for 2 months, and she had minimal pain. There
268
Clinical and laboratory observations
The Journal of Pediatrics February 1989
Fig. 2. Skin biopsy specimen of one of the nodules pictured in Fig. 1, which shows mononuclear infiltrations and scattered multinucleated giant cells.
was no morning stiffnessor evidenceof pain on joint motion. Joint contractures were still present, The periuugual rash was almost gone. Roentgenograms of the hands, wrists, elbows, knees, and feet showed bilateral knee effusionsand erosions of almost every interphalangeal joint of the hands. The erythrocyte sedimentation rate was 1 mm/hr. A technetium bone scan showed areas of bone abnormality of almost all phalangeal and carpal bones with little evidence of soft tissue involvement. Because there has been minimal evidenceof inflammation from both the radiologic (repeat radiographs of the hands and wrists were unchanged in 3 months) and clinical (absence of pain) standpoints, therapy has consisted only of symptomatic pain relief with aspirin. DISCUSSION Aside from the inclusion (without clinical description) of an 11-year-old patient in the series of MRH patients reported by Barrow and Holubar, 11we have been unable to locate any reports of patients with MRH younger than 16 years of age. Although at least one textbook ~~ and one review 11of pediatric rheumatology refer to childhood cases of MRH, the article in which these cases are reported 12 states that these patients represent a different clinical and histopathologic entity--termed familial histiocytic dermatoarthritis by the a u t h o r s - - f r o m M R H as reported in adults. The childhood form has a familial component, a marked tendency to involve the eye, and a lack of giant cells in tissue sections; the last of these characteristics is considered an essential feature of MRH. ~,a
The clinical presentation of our patient, including the typical distribution of the skin nodules and the histopathologic characteristics, tends to confirm the diagnosis of MRH as it is described in adults. The spontaneous regression of these skin lesions and clinically detectable synovitis is in keeping with the usually described course in adults~; the disease may wax and wane over many years and finally stop completely. Additional findings described include evidence of abnormal liver function and mildly elevated serum immunoglobulin levels. The discovery of increased levels of circulating immune complexes in our patient (a finding not previously described in MRH) is not surprising. Such complexes are found in many conditions associated with arthritis? 3 Whether these factors play a pathophysiologic role or merely serve as markers r for other immune events is not certain. Most of this patient's joint inflammation probably occurred before or during her initial presentation. The evidence is the dramatic change in radiographic appearance of her joints during a time when she had minimal pain. This delayed appearance, on plain film radiography, of destructive joint change (common to many forms of arthritis) makes therapy decisions difficult, especially when potentially toxic agents (such as cyclophosphamide--which may be the agent of choice in adults with MRH) might be considered. Obviously, in children, the decision can be even more difficult because of the potential
Volume 114 Number 2
short- and long-term side effects of such therapy. TMPerhaps newer procedures such as magnetic resonance imaging, by allowing earlier diagnosis of osseous and cartilaginous damage, will m a k e these decisions easier. We plan to follow this patient with a variety of modalities, including plain film radiography, bone scanning, magnetic resonance imaging, and acute-phase reactant monitoring, the combined results of which may allow identification of future disease progression in a timely manner.
We thank Gilda Clayborne, Marie Sieck, and Susan Rothfuss for technical assistance with the electron microscopy. REFERENCES
1. Barrow MV, H01ubar K. Multicentric reticuiohistiocytosis: a review Of 33 patients~ Medicine 1969;48:287-305. 2. Orkim M, Goltz RW, Good RA, Fisher MA. A study of multicentric retieulohistiocytosis. Arch Dermatol 1964; 89:640-54. 3. Gold RH, Metzger AL, Mirra JM, Weingerger H J, Kilebrew K. Multicentric reticulohistiocytosis (lipoid dermato-arthritis): an erosive polyarthritis with distinctive clinical, roentgenographic and pathologic features. Am J Rheumatol 1975; 124:610-24. 4. Freemont A J, Jones CJP, Denton J. The synovium and synovial fluid in multicentric reticulohistiocytosis. J Clin Pathol 1983;36:860-6.
Clinical and laboratory observations
269
5. Coode PE, Ridgeway H, Jones DB. Multicentric reticulohistiocytosis: report of two cases with ultrastructure, tissue culture and immunology studies. Clin Exp Dermatol 1980;5:281-93. 6. Catterall MD. Multiceiatric reticulohistiocytosis: a review of eight cases. Clin Exp Dermatol 1980;5:267-9. 7. Heatiacote JG~ Guenther LC, Wallace AC. Multicentric retieulohistiocytosis: a report of a case and review of the Pathology. Pathology 1985;17:60i-8. 8. Lesher JL, Allen BS. Multicentric reficulohistiocytosis. J Am Acad Dermatoi 1984;11:713-23, 9. Nunninck JC, Krusinski PA, Yates JW. Multicentric reticulohistiocytosis and cancer: a case report and review of the literature. Med Pediatr Oncol 1985;13:273-9. 10. Jacobs JC. Pediatric rheumatology for the pracfioner. 1st ed. New york: Springer-Verlag, 1982:145. I1. CassidyJT. Misce!laneouseonditions associated with arthritis in children. In: Miller ML, ed. Pediatric rheumatology. Philadelphia: WB Saunders, 1986:1040-1 (Pediatric Clinics of North America; vol 33.) 12. Zayid I, Farraj J. Familial histiocytic dermatitis: a new syndrome. Am J Med 1973;54:793-800. 13. WMoore TL, Osborn TG, Dorner RW. 19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in sera Of patientswith juvenile rheumatoid arthritis. Pediatr Res 1986;20:977281. 14. Pederson-Bjergaard J, Ersboll J; Hansen VL, et al. Carcin0ma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma. N Engl J Med 1988; 318:1028-32.
Juvenile laryngeal papillomatosis and epidermoid carcinoma Marianne Chaput, MD, Jacques Ninane, MD Serge Gosseye, MD, Didier Mouiin, MD, Marc Hamoir, MD, Dominique Claus, MD, Charles Francis, MD, Fran~oise Richard, MD, Christiane Vermylen, MD, and Guy Cornu, MD From the Departments of Pediatric Hematology and Oncology, Pathology, Pediatric Intensive Care, Otorhinolaryngology, Pediatric Radiology, Pneumology, and Radiotherapy, Cliniques UniversitairesSaint-Luc, Brussels,Belgium
Juvenile laryngeal papillomatosis is characterized by multiple lesions, extensive proliferation, and frequent relapses, but there is a low risk of malignant transformation.! A viral cause has been proved recently by the finding of viral antigen and the identification of human papillomavirus D N A in laryngeal papillomas. 2,3 Although endoscopy with Submitted for publication June 8, 1988; accepted Aug. 1, 1988. Reprint requests: Jacques Ninane, MD, Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
resection or CO2-1aser vaporization relieves the airway obstruction, relapse is unfortunately the rule. We report the case of a child whose first symptoms of laryngeal papillomat0sis appeared at 6 months of age. He was HPV
Human papilloma~,irus
I
treated with repeated endoscopic resections, laser Vaporization, and antiviral chemotherapy but developed laryngeal squamous cell carcinoma when he was 6 years of age.
Clinical and laboratory observations
diagnosis would allow for more effective management of anticipated problems such as cholelithiasis and its complications, the need for splenectomy, and the examination of family members for the disease. REFERENCES
1. Hereditary spherocytosis and other hemolytic anemias associated with abnormalities of the red cell membrane. In: Wintrobe MM, Lee GR, Boggs DR, et al., eds. Clinical hematology. Philadelphia: Lea & Febiger, 1981:747-8. 2. Fukagawa N, Friedman S, Gill FM, et al, Hereditary spherocytosis with normal fragility after incubation. JAMA 1979;242:63-4. 3. Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anemia. QJ Med 1953;22:79-99. 4. Zail SS, Krawitz P, Viljoen E, et al. Atypical hereditary spherocytosis: biochemical studies and sites of erythrocyte destruction. Br Med J 1967;13:323-34.
The Journal of Pediatrics February 1989
5. Lefrere J J, Courouce AM, Girot R, et al. Six cases of hereditary spherocytosis revealed by human parvovirus infection. Br J Haematol 1986;62:653-7. 6. Dameshek W, Bloom ML. The events in the hemolytic crisis of hereditary spherocytosis, with particular reference to the reticulocytopenia, pancytopenia and abnormal splenic mechanism. Blood 1948;3:1381-409. 7. Paolino W. Variations of the mean diameter in the ripening of the erythrocyte. Acta Med Scand 1949;136:141-7. 8. Griggs RC, Weisman R, Harris JW. Alterations in osmotic fragility related to in vivo erythrocyte aging and splenic sequestration in hereditary spherocytosis. J Clin Invest 1960;39:89-101. 9. Crosby WH, Conrad ME. Hereditary spherocytosis: observations on hemolytic mechanisms and iron metabolism. Blood 1960;15:662-74. 10. Lux SE. Disorders of the red cell membrane. In: Nathan D, Oski F, eds. Hematology of infancy and childhood. Philadelphia: WB Saunders, 1987:488-9.
Multicentric reticulohistiocytosis in a child Stephen A. Raphael, MD, Susan L. Cowdery, MD, Eric N. Faerber, MD, Harold W. Lischner, MD, H. Ralph Schumacher, MD, and Charles D. Tourtellotte, MD From the Section of Immunology and Rheumatology, Department of Pediatrics, the Department of Radiology, and the Section of Rheumatology, Department of Internal Medic!ne, Temple University School of Medicine and St. Christopher's Hospital for Children; the Department of internal Medicine, Section of Rheumatology, Albert Einstein Medical Center-Northern Division; and the Section of Rheumatology, Department of Internal Medicine, University of Pennsylvania School of Medicine and Veterans Administration Hospital of Philadelphia
Multicentric reticulohistiocytosis is a rare, easily misdiagnosed, systemic disorder of unknown cause, characterized by papulonodular skin lesions, potentially destructive arthritis, a tendency to involve multiple organs, and histopathologic studies that show large mononuclear and multinucleated giant cell infiltrations. 1-7 There is a possible association with malignancy, diabetes, hypothyroidism, hyperlipidemia, and tuberculosis.i, 2,6,8,9 All fully described cases have been in adults. W e present the first clinically described case of M R H in a child.
symmetric swelling of several distal interphalangeal joints, and nonpainful, hypopigmented wartlike intracutaneous nodules over the distal ends and periungual areas of several fingers. Subsequently, she experienced easy fatigability, increased numbers of skin nodules, and bilateral painful knee swelling. Fever, unexplained weight loss, anorexia, adenopathy, rash, signs of the Raynaud phenomenon, photosensitivity, mouth ulcers, chest pain, neurologic problems, myalgia, abdominal pain, eye irritation, loss of scalp hair, and intolerance to cold were denied. There was no MRH
Multicentric reticulohistiocytosis
[
CASE REPORT The patient, a black girl almost 14 years old, was well until 1ly2 years of age, when she noticed the simultaneous occurrence of early morning stiffness, loss of grip strength, right elbow pain,
Submitted for publication July 18, 1988; accepted Sept. 20, 1988. Reprint requests: Stephen A. Raphael, MD, St. Christopher's Hospital for Children, Section of Immunology and Rheumatology, 5th and Lehigh Ave., Philadelphia, PA 19133.
history of recent immunizations, antecedent illness, tick bite, or travel. The patient was taking no long-term medications. She was not sexually active. Growth and development had been normal. Family history revealed two well siblings and a history of intravenous drug abuse in the patient's father. Initial physical examination revealed an anxious 1l~(2-year-old pubertal black girl in no acute physical distress. Height and weight were appropriate for age. Vital signs were normal. The patient had multiple 2 to 3 mm wartlike nodules along the dorsal
Volume 114 Number 2
Clinical and laboratory observations
267
Fig. 1. Periungual wartlike nodules on the fingers, arranged in a "coral bead" formation.
aspects of her fingers with a "'coral bead" formation around the nail folds (Fig. 1). Several larger 5 mm nodules were palpable along the flexor tendon sheaths of the hands, over the wrists, along the extensor surface of the right elbow, and on the dorsum of the left foot. The patient had bilateral elbow contractures, fullness of both wrists with loss of full extension, minimally tender second metacarpophalangeal joints, bony deformities of several distal interphalangeal joints, marked bilateral knee swelling and tenderness (with associated 10-degree extension lags), and mild bilateral ankle swelling and tenderness. Grip strength was poor. The other findings of the examination, including those of a complete ophthalmologic examination, were within normal limits. One of us (C.D.T.), a rheumatologist for adults, made the diagnosis of MRH at this time. Laboratory data included normal values for hemoglobin, hematocrit, total leukocyte count, platelet count, erythrocyte sedimentation rate, C-reactive protein, sickle cell preparation, antinuclear antibodies, rheumatoid factor, serum lgA and IgM, C l q binding activity, urinalysis, cholesteroll and liver function. Abnormal results included increased values for serum IgG (1760 mg/dl), circulating immune complexes by Raji cell assay (168 ]xg antihemophilic globulin Eq/ml) without demonstrable antilymphocyte cytotoxic antibodies, triglycerides (189 mg/dl [2.15 mmol/L]), blood glucose (114 mg/dl [6.3 mmol/Ll), and 9% eosinophils on peripheral blood smear. A purified protein derivative test had a negative result. Conventional x-ray studies revealed a normal chest, multiple joint effusions with juxtaarticular soft tissue swelling and hyperemic changes, and generalized bone demineralization. There was no evidence of joint destruction. A skin biopsy specimen of one of the nodules showed, by light microscopy, infiltrations of mononuclear and multinucleated giant
cells (Fig. 2). Electron microscopy revealed scattered small monocytes and many larger cells with single or multiple nuclei containing little heterochromatinr profuse cytoplasmic mitochondria, dilated cisterns of smooth or rough endoplasmic reticulum, and laminated inclusions. With the recommended therapy of 75 mg/kg/day of aspirin, the patient had less pain and morning stiffness, but 21/2 months later, physical examination findings were unchanged except for less pain on joint movement. Laboratory data included normal values for reticulocyte count, triiodothyronine, thyroxine, thyroidstimulating hormone, lgG subclasses, and total numbers of T, B, CD4+, and CD8+, cells. A repeat total serum IgG test showed a normal level (1400 mg/dl). For better definition of the extent of joint involvement, a needle biopsy of the synovium, with aspiration of fluid from the left knee, was performed. Analysis of joint fluid revealed an erythrocyte count of 6700/mm 3, leukocyte count of 1200/mm 3 (2% polymorphonuclear leukocytes, 8% lymphocytes, 90% unidentified mononuclear), glucose level of 98 mg/dl (5.4 mmol/L), and total protein level of 4.7 gm/dl (47 gm/L). Gram stain and cultures were negative. Synovial biopsy showed a mild mononuclear infiltration with absence of histiocytes positive for periodic acid-Schiff reagent; no large cells were seen. Electron microscopy showed some proliferating type B (fibroblast-like) lining cells, scattered monocytes, and perivascular fibrosis. On magnetic resonance imaging scan of the knees, bilateral intraarticular effusions were again demonstrated. A small, discrete area of decreased signal intensity measuring 1 cm was found in the subcutaneous fat, posterior to the popliteal vessels of the left knee. Ten months later the patient returned. Aspirin therapy had been discontinued for 2 months, and she had minimal pain. There
268
Clinical and laboratory observations
The Journal of Pediatrics February 1989
Fig. 2. Skin biopsy specimen of one of the nodules pictured in Fig. 1, which shows mononuclear infiltrations and scattered multinucleated giant cells.
was no morning stiffnessor evidenceof pain on joint motion. Joint contractures were still present, The periuugual rash was almost gone. Roentgenograms of the hands, wrists, elbows, knees, and feet showed bilateral knee effusionsand erosions of almost every interphalangeal joint of the hands. The erythrocyte sedimentation rate was 1 mm/hr. A technetium bone scan showed areas of bone abnormality of almost all phalangeal and carpal bones with little evidence of soft tissue involvement. Because there has been minimal evidenceof inflammation from both the radiologic (repeat radiographs of the hands and wrists were unchanged in 3 months) and clinical (absence of pain) standpoints, therapy has consisted only of symptomatic pain relief with aspirin. DISCUSSION Aside from the inclusion (without clinical description) of an 11-year-old patient in the series of MRH patients reported by Barrow and Holubar, 11we have been unable to locate any reports of patients with MRH younger than 16 years of age. Although at least one textbook ~~ and one review 11of pediatric rheumatology refer to childhood cases of MRH, the article in which these cases are reported 12 states that these patients represent a different clinical and histopathologic entity--termed familial histiocytic dermatoarthritis by the a u t h o r s - - f r o m M R H as reported in adults. The childhood form has a familial component, a marked tendency to involve the eye, and a lack of giant cells in tissue sections; the last of these characteristics is considered an essential feature of MRH. ~,a
The clinical presentation of our patient, including the typical distribution of the skin nodules and the histopathologic characteristics, tends to confirm the diagnosis of MRH as it is described in adults. The spontaneous regression of these skin lesions and clinically detectable synovitis is in keeping with the usually described course in adults~; the disease may wax and wane over many years and finally stop completely. Additional findings described include evidence of abnormal liver function and mildly elevated serum immunoglobulin levels. The discovery of increased levels of circulating immune complexes in our patient (a finding not previously described in MRH) is not surprising. Such complexes are found in many conditions associated with arthritis? 3 Whether these factors play a pathophysiologic role or merely serve as markers r for other immune events is not certain. Most of this patient's joint inflammation probably occurred before or during her initial presentation. The evidence is the dramatic change in radiographic appearance of her joints during a time when she had minimal pain. This delayed appearance, on plain film radiography, of destructive joint change (common to many forms of arthritis) makes therapy decisions difficult, especially when potentially toxic agents (such as cyclophosphamide--which may be the agent of choice in adults with MRH) might be considered. Obviously, in children, the decision can be even more difficult because of the potential
Volume 114 Number 2
short- and long-term side effects of such therapy. TMPerhaps newer procedures such as magnetic resonance imaging, by allowing earlier diagnosis of osseous and cartilaginous damage, will m a k e these decisions easier. We plan to follow this patient with a variety of modalities, including plain film radiography, bone scanning, magnetic resonance imaging, and acute-phase reactant monitoring, the combined results of which may allow identification of future disease progression in a timely manner.
We thank Gilda Clayborne, Marie Sieck, and Susan Rothfuss for technical assistance with the electron microscopy. REFERENCES
1. Barrow MV, H01ubar K. Multicentric reticuiohistiocytosis: a review Of 33 patients~ Medicine 1969;48:287-305. 2. Orkim M, Goltz RW, Good RA, Fisher MA. A study of multicentric retieulohistiocytosis. Arch Dermatol 1964; 89:640-54. 3. Gold RH, Metzger AL, Mirra JM, Weingerger H J, Kilebrew K. Multicentric reticulohistiocytosis (lipoid dermato-arthritis): an erosive polyarthritis with distinctive clinical, roentgenographic and pathologic features. Am J Rheumatol 1975; 124:610-24. 4. Freemont A J, Jones CJP, Denton J. The synovium and synovial fluid in multicentric reticulohistiocytosis. J Clin Pathol 1983;36:860-6.
Clinical and laboratory observations
269
5. Coode PE, Ridgeway H, Jones DB. Multicentric reticulohistiocytosis: report of two cases with ultrastructure, tissue culture and immunology studies. Clin Exp Dermatol 1980;5:281-93. 6. Catterall MD. Multiceiatric reticulohistiocytosis: a review of eight cases. Clin Exp Dermatol 1980;5:267-9. 7. Heatiacote JG~ Guenther LC, Wallace AC. Multicentric retieulohistiocytosis: a report of a case and review of the Pathology. Pathology 1985;17:60i-8. 8. Lesher JL, Allen BS. Multicentric reficulohistiocytosis. J Am Acad Dermatoi 1984;11:713-23, 9. Nunninck JC, Krusinski PA, Yates JW. Multicentric reticulohistiocytosis and cancer: a case report and review of the literature. Med Pediatr Oncol 1985;13:273-9. 10. Jacobs JC. Pediatric rheumatology for the pracfioner. 1st ed. New york: Springer-Verlag, 1982:145. I1. CassidyJT. Misce!laneouseonditions associated with arthritis in children. In: Miller ML, ed. Pediatric rheumatology. Philadelphia: WB Saunders, 1986:1040-1 (Pediatric Clinics of North America; vol 33.) 12. Zayid I, Farraj J. Familial histiocytic dermatitis: a new syndrome. Am J Med 1973;54:793-800. 13. WMoore TL, Osborn TG, Dorner RW. 19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in sera Of patientswith juvenile rheumatoid arthritis. Pediatr Res 1986;20:977281. 14. Pederson-Bjergaard J, Ersboll J; Hansen VL, et al. Carcin0ma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma. N Engl J Med 1988; 318:1028-32.
Juvenile laryngeal papillomatosis and epidermoid carcinoma Marianne Chaput, MD, Jacques Ninane, MD Serge Gosseye, MD, Didier Mouiin, MD, Marc Hamoir, MD, Dominique Claus, MD, Charles Francis, MD, Fran~oise Richard, MD, Christiane Vermylen, MD, and Guy Cornu, MD From the Departments of Pediatric Hematology and Oncology, Pathology, Pediatric Intensive Care, Otorhinolaryngology, Pediatric Radiology, Pneumology, and Radiotherapy, Cliniques UniversitairesSaint-Luc, Brussels,Belgium
Juvenile laryngeal papillomatosis is characterized by multiple lesions, extensive proliferation, and frequent relapses, but there is a low risk of malignant transformation.! A viral cause has been proved recently by the finding of viral antigen and the identification of human papillomavirus D N A in laryngeal papillomas. 2,3 Although endoscopy with Submitted for publication June 8, 1988; accepted Aug. 1, 1988. Reprint requests: Jacques Ninane, MD, Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
resection or CO2-1aser vaporization relieves the airway obstruction, relapse is unfortunately the rule. We report the case of a child whose first symptoms of laryngeal papillomat0sis appeared at 6 months of age. He was HPV
Human papilloma~,irus
I
treated with repeated endoscopic resections, laser Vaporization, and antiviral chemotherapy but developed laryngeal squamous cell carcinoma when he was 6 years of age.