Abstract
A 21-month-old boy presented with a papular rash, lymphadenopathy, and splenomegaly. He developed symmetric polyarthritis, fever, and progressive glomerulonephritis. Serologies for viral agents including HIV were negative. Antinuclear antibody was transiently positive, but no anti-DNA antibodies were present. CH50 and serum C3 values were low. Biopsies of skin, kidney, bone marrow, and lymph node were obtained. There was a perivascular and periadnexal lymphocytic infiltrate in the skin, with a normal epidermis. Renal biopsy showed proliferative mesangial glomerulonephritis. Bone marrow showed an increased number of plasma cells. Lymph node showed histologic changes described in multicentric Castleman's disease including marked follicular hyperplasia, vascular proliferation, and interfollicular expansion with numerous plasma cells. IL-6 mRNA was demonstrated in cells in the marginal zone and interfollicular regions of the node byin situ hybridization. Likewise, the serum IL-6 level was elevated during a clinical exacerbation of the patient's nephritis. These data suggest an underlying lymphoproliferative disorder, such as Castleman's disease, with overproduction of IL-6 resulting in systemic features of the disease, including glomerulonephritis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Castleman B, Iverson L, Menendez VP: Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer 9:822–830, 1956
Flendrig JA, Schillings PHM: Benign giant lymphoma: The clinical signs and symptoms. Folia Med Neerl 12:119–120, 1969
Keller AR, Hochholzer L, Castleman B: Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 29:670–683, 1972
Bartoli E, Massarelli G, Soggia G, Tanda F: Multicentric giant lymph node hyperplasia. A hyperimmune syndrome with a rapidly progressive course. Am J Clin Pathol 73:423–426, 1980
Frizzera G, Banks PM, Massarelli G, Rosai J: A systemic lymphoproliferative disorder with morphologic features of Castleman's disease. Am J Surg Pathol 7:211–231, 1983
Kessler E: Multicentric giant lymph node hyperplasia. A report of seven cases. Cancer 56:2446–2451, 1985
Weisenberger DD: Membranous nephropathy. Its association with multicentric angiofollicular lymph node hyperplasia. Arch Pathol Lab Med 103:591–594, 1979
Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW: Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice. J Clin Invest 86:592–599, 1990
Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno T, Miyazaki J-I, Yamamura K-I, Hirano T, Kishimoto T: IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 86:7547–7551, 1989
Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T, Kishimoto S, Hirano T, Kishimoto T: Pathogenic significance of interleukin 6 (IL-6/BSF-2) in Castleman's disease. Blood 74:1360–1367, 1989
Leger-Ravet MB, Peuchmaur M, Devergne O, Audouin J, Raphael M, Van Damme J, Galanaud P, Diebold J, Emilie D: Interleukin-6 gene expression in Castleman's disease. Blood 78:2923–2930, 1991
Hsu S-M, Waldron JA, Xie S-S, Barlogie B: Expression of interleukin 6 in Castleman's disease. Hum Pathol 24:833–839, 1993
Mandler RN, Kerrigan DP, Smart J, Kuis W, Villiger P, Lotz M: Castleman's disease in POEMS syndrome with elevated interleukin-6. Cancer 69:2697–2703, 1992
Hirano T, Akira S, Taga T, Kishimoto T: Biological and clinical aspects of interleukin 6. Immunology Today 11:443- 449, 1990
Glick AD, Paniker K, Flexner JM, Graber S, Collins RD: Acute leukemia of adults: Ultrastructural, cytochemical, and histological observations in 100 cases. Am J Clin Pathol 73:459–470, 1980
Pinkus GS, Thomas P, Said JW: Leu-M1—a marker for Reed-Sternberg cells in Hodgkin's disease: An immunoperoxidase study of paraffin-embedded tissues. Am J Pathol 119:244–252, 1985
Nordan RP: Measurement of mouse and human IL-6.In Current Protocols in Immunology, JE Coligan, AM Kruisbeek, DH Margulies, EM Shevach, W Strober (eds). New York, Green Publishing Associates and Wiley-Interscience, 1991, Vol. 1, p 661
Villiger PM, Cronin MT, Amenomori T, Wachsman W, Lotz M: IL-6 production by human T lymphocytes. Expression in HTLV-1-infected but not in normal T cells. J Immunol 146:550–559, 1991
Gabay C, Roux-Lombard P, de Moerloose P, Dayer J-M, Vischer T, Guerne P-A: Absence of correlation between interleukin 6 and C-reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis. J Rheumatol 20:815–821, 1993
Cohen PL, Eisenberg RA:Lpr andgld: Single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269, 1991
d'Agay MF, Miclea JM, Clauvel JP, Schaison G, Brocheriou C: Castleman's disease: A well-defined histological pattern for a widely divergent clinical spectrum. Nouv Rev Fr Hematol 31:145–148, 1989
Steinberg JJ, Huang PL, Ljubich P, Lee-Huang S: Antierythropoietin antibodies in hyperviscosity syndrome associated with giant lymph node hyperplasia (GLNH; Castleman's disease). Br J Haematol 74:543–544, 1990
Al-Jabi M, Tolnai G, McCaughey WTE: Angiofollicular lymphoid hyperplasia in an angiolipomatous mass. Arch Pathol Lab Med 104:313–315, 1980
Radaszkiewicz T, Hansmann M-L, Lennert K: Monoclonality and polyclonality of plasma cells in Castleman's disease of the plasma cell variant. Histopathology 14:11–24, 1989
Hall PA, Donaghy M, Cotter FE, Stansfeld AG, Levison DA: An immunohistological and genotypic study of the plasma cell form of Castleman's disease. Histopathology 14:333–346, 1989
Isaacson PG: Castleman's disease. Histopathology 14:429- 432, 1989
Sherman D, Ramsay B, Theodorou NA, Woodrow D, Paradinas FP, Cream JJ, Murray-Lyon IM: Reversible plane xanthoma, vasculitis, and peliosis hepatis in giant lymph node hyperplasia (Castleman's disease): A case report and review of the cutaneous manifestations of giant lymph node hyperplasia. J Am Acad Dermatol 26:105–109, 1992
Horii Y, Muraguchi A, Iwano M, Matsuda T, Hirayama T, Yamada H, Fujii Y, Dohi K, Ishikawa H, Ohmoto Y, Yoshizaki K, Hirano T, Kishimoto T: Involvement of interleukin-6 in mesangial proliferative glomerulonephritis. J Immunol 143:3949–3955, 1989
Humphreys SR, Holley KE, Smith LH, McIlrath DC: Mesenteric angiofollicular lymph node hyperplasia (lymphoid hamartoma) with nephrotic syndrome. Mayo Clin Proc 50:317–321, 1975
Ruggieri G, Barsotti P, Coppoia G, Spinelli C, Balducci A, Ventola FR, d'Adamo G, Tata MV, Marinozzi V: Membranous nephropathy associated with giant lymph node hyperplasia: A case report with histological and ultrastructural studies. Am J Nephrol 10:323–328, 1990
Said R, Tarawneh M: Membranoproliferative glomerulonephritis associated with multicentric angiofollicular lymph node hyperplasia. Case report and review of the literature. Am J Nephrol 12:466–470, 1992
Kishimoto T: The biology of interleukin-6. Blood 74:1–10, 1989
Bosseloir A, Hooghe-Peters EL, Heinen E, Cormann N, Kinet-Denoel C, Vanhaelst L, Simar L: Localization of interleukin 6 mRNA in human tonsils by in situ hybridization. Eur J Immunol 19:2379–2381, 1989
Salisbury JR: Castleman's disease in childhood and adolescence: Report of a case and review of the literature. Pediatr Pathol 10:609–615, 1990
Hunt SJ, Anderson WD: Giant lymph node hyperplasia of the hyaline vascular type with plasmacytoid T-cells and presentation in infancy. Am J Clin Pathol 91:344–347, 1989
Futrell JW, McKillop DB, Izant RJ Jr: Angiomatous lymphoid hamartoma in an infant. Am J Dis Child 128:96–99, 1974
Hung I-J, Kuo T-T, Lin J-N: New observations in a child with angiofollicular lymph node hyperplasia (Castleman's disease) originated from the mesenteric root. Am J Pediat Hematol Oncol 14:255–260, 1992
Lee SL, Rosner F, Rivero I, Feldman F, Hurwitz A: Refractory anemia with abnormal iron metabolism: Its remission after resection of hyperplastic mediastinal lymph nodes. N Engl J Med 272:761–766, 1965
Shohat B, Cohen I, Fogel R, Zaizov R: Suppressor mono-nuclear cells in giant lymph node hyperplasia and thymoma. Cancer 48:923–926, 1981
Neerhout RC, Larson W, Mansur P: Mesenteric lymphoid hamartoma associated with chronic hypoferremia, anemia, growth failure, and hyperglobulinemia. N Engl J Med 280: 922–925, 1969
Burgert EO, Jr., Gilchrist GS, Fairbanks VF, Lynn HB, Dukes PP, Harrison EG Jr: Intra-abdominal angiofollicular lymph node hyperplasia (plasma-cell variant) with an antierythropoietic factor. Mayo Clin Proc 50:542–546, 1975
Bjarnason I, Cotes PM, Knowles S, Reid C, Wilkins R, Peters TJ: Giant lymph node hyperplasia (Castleman's disease) of the mesentery. Observations on the associated anemia. Gastroenterology 87:216–223, 1984
Powell RW, Lightsey AL, Thomas WJ, Marsh WL: Castleman's disease in children. J Pediat Surg 21:678–682, 1986
Miller JS, Miller JJ, III: Benign giant lymph node hyperplasia presenting as fever of unknown origin. J Pediat 87:237–239, 1975
Boxer LA, Boxer GJ, Flair RC, Engstrom PF, Brown GS: Angiomatous lymphoid hamartoma associated with chronic anemia, hypoferremia, and hypergammaglobulinemia. J Pediat 81:66–70, 1972
Buchanan GR, Chipman JJ, Hamilton BL, Daughaday WH: Angiomatous lymphoid hamartoma: Inhibitory effects on erythropoiesis, growth, and primary hemostasis. J Pediat 99:382–388, 1981
Author information
Authors and Affiliations
Additional information
These authors contributed equally to the manuscript.
Rights and permissions
About this article
Cite this article
Kinney, M.C., Hummell, D.S., Villiger, P.M. et al. Increased interleukin-6 (IL-6) production in a young child with clinical and pathologic features of multicentric Castleman's disease. J Clin Immunol 14, 382–390 (1994). https://doi.org/10.1007/BF01546323
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01546323