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Ultrastruktur und Pathogenese der BCG-Histiocytose (sog. BCG-Granulomatose)

Ultrastructure and pathogenesis of the BCG-histiocytosis (BCG-granulomatosis)

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Summary

After BCG-vaccination of a newborn girl, some enlarged regional lymph-nodes were noticed at the age of ten months. Light-microscopically the lymph nodes showed the typical histological pictures of “BCG-granulomatosis”. The acid-fast bacilli, cultured from fresh lymph node tissue were shown by bacteriological tests to be indistinguishable from BCG. During the investigation period intradermal tuberculin reactions remained negative. Serum immunoglobulins showed deficiency of IgA level.

In vitro responses of leukocytes to tuberculin were depressed, whereas PHA-stimulation revealed normal values. During the investigation period of two years no generalized tuberculosis was observed.

The normal architecture of the enlarged lymph-nodes was obscured by a diffuse overgrowth of macrophages, which had ingested myriads of acid-fast bacilli. Epithelioid-cells were present only in a small number; there were no Langhans giant cells and no tubercles had developed. The phagocytic ability of the macrophages appeared to be fairly well-preserved. Accordingly, these cells showed a high activity of acid-phosphatase and non-specific esterase. Nevertheless, it was observed electron-microscopically that bacterial breakdown was very slight. It also seems likely that there was a marked reduction in bacteriocidal activity. The ultrastructural appearance of the macrophages did not indicate they were abnormal.

Impairment of cell-mediated immunity, as evidenced by the negative tuberculin reaction and the depressed stimulation of cultured leukocytes, may have caused the pathologic alteration of “BCG-granulomatosis” in this case, whereas IgA deficiency is probably without pathogenetic significance. To that extent these pathogenetic factors are similar to those that occur in Lepra lepromatosa.

We suggest that instead of the misleading expression “BCG-granulomatosis” the term “BCG-histiocytosis” be used.

Zusammenfassung

Bei einem 10 Monate alten Mädchen trat nach einer im Neugeborenenalter durchgeführten BCG-Impfung eine Vergrößerung der regionären Leistenlymphknoten auf. Hier konnte bioptisch eine „BCG-Granulomatose“ diagnostiziert werden. Bakteriologisch wurde aus dem Lymphknoten BCG gezüchtet. Die Tuberkulinreaktion war negativ. Im Serum waren die IgA-Globuline ständig deutlich vermindert. Blutlymphocyten des Kindes ließen sich durch PHA regelrecht stimulieren, dagegen war die Blastentransformation durch Tuberkulin vermindert. In einer insgesamt zweijährigen Beobachtungszeit gedieh das Kind gut, es zeigte keine tuberkulöse Generalisation.

Histologisch bestand das typische Bild einer diffusen, retikuloseartigen Makrophagenvermehrung mit weitgehender Zerstörung der Lymphknotenstruktur. In den Makrophagen lagen Myriaden säurefester Stäbchen. Epitheloidzellen wurden in kleiner Zahl, Langhanssche Riesenzellen nicht gebildet. Zu einer Formation von Tuberkeln kam es nicht. Elektronenmikroskopisch konnten nur geringe Abbauerscheinungen an den Mykobakterien beobachtet werden, wobei die Makrophagen regelhaft entwickelt schienen. Enzymcytochemisch ließen sich sehr reichlich saure Phosphatase und unspezifische Esterase in den Makrophagen nachweisen. Ein primärer Defekt der Makrophagen dürfte also nicht vorliegen. Dagegen halten wir die nachgewiesene Störung der zellgebundenen Immunität (cell mediated immunity) für die Ursache der abartigen Reaktion, wogegen der IgA-Mangel wahrscheinlich keine pathogenetische Bedeutung hat. Insofern liegen bei der „BCG-Granulomatose“ ganz ähnliche pathogenetische Mechanismen vor wie bei der Lepra lepromatosa.

Wir schlagen vor, anstelle des mißverständlichen Begriffes „BCG-Granulomatose“ die Bezeichnung „BCG-Histiocytose“ anzuwenden.

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Literatur

  • Allen, J. M., Brieger, E. M., Rees, R. J. W.: Electron microscopy of the host-cell parasite reaction in murine leprosy. J. Path. Bact.89, 301–306 (1965).

    Google Scholar 

  • Ammann, A. J., Hong, R.: Selective IgA deficiency: Presentation of 30 cases and a review of the literature. Medicine (Baltimore)50, 223–236 (1971).

    Google Scholar 

  • Armstrong, J. A., d'Arcy Hart, P.: Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J. exp. Med.134, 713–740 (1971).

    Google Scholar 

  • Bang, J., Engbaek, H. C., Nielsen, E.: Osteomyelitis following BCG-vaccination. Acta tuberc. scand.38, 206–208 (1960).

    Google Scholar 

  • Brown, C. A., Draper, P., d'Arcy Hart, P.: Mycobacteria and lysosomes: a paradox. Nature (Lond.)221, 658–660 (1969).

    Google Scholar 

  • Bullock, W. E., Fasal, P.: Studies of immune mechanism in leprosy. III. The role of cellular and humoral factors in impairment of the in vitro immune response. J. Immunol.106, 888–899 (1971).

    Google Scholar 

  • Carlgren, L. E., Hansson, C. G., Henricsson, L., Whålén, P.: Fatal BCG infection in an infant with congenital, lymphocytopenic agammaglobulinaemia. Acta paediat. scand.55, 636–644 (1966).

    Google Scholar 

  • Carlgren, L. E., Henricsson, L., Hansson, G., Whålén, P.: A case of agammaglobulinaemia and fatal BCG dissemination. Acta paediat. scand.54, 631 (1965).

    Google Scholar 

  • Chapman, G. B., Hanks, J. H., Wallace, J. H.: An electron microscope study of the disposition and fine structure of Mycobacterium lepraemurium in mouse spleen. J. Bact.77, 205–211 (1959).

    Google Scholar 

  • Draper, P., Rees, R. J. W.: Electron-transparent zone of mycobacteria may be a defense system. Nature (Lond.)228, 860–861 (1970).

    Google Scholar 

  • Drescher, J., Müller, M.: Morphologische, zytochemische und autoradiographische Untersuchungen an Drüsenfieberzellen in vitro. Blut21, 315–330 (1970).

    Google Scholar 

  • Drescher, J., Rüssler, P.: In Vorbereitung.

  • Dumont, A., Sheldon, H.: Changes in the fine structure of macrophages in experimentally produced tuberculous granulomas in hamsters. Lab. Invest.14, 2034–2055 (1965).

    Google Scholar 

  • Falkmer, S., Lind, A., Ploman, L.: Fatal tuberculosis from BCG vaccination. Acta paediat. scand.44, 219–236 (1955).

    Google Scholar 

  • Felländer, M.: Tuberculous osteitis following BCG vaccination. Acta orthop. scand.33, 116–126 (1963).

    Google Scholar 

  • Foucard, T., Hjelmstedt, Å.: BCG-osteomyelitis and -osteoarthritis as a complication following BCG-vaccination. Acta orthop. scand.42, 142–151 (1971).

    Google Scholar 

  • Gardborg, O., Iversen, O. H., Torheim, B. J., Hesselberg, I.: Generalized BCG infection with fatal course in an infant. Acta paediat. scand.52, 293–303 (1963).

    Google Scholar 

  • Glauert, A. M., Glauert, R. H.: Araldite as an embedding medium for electron microscopy. J. biophys. biochem. Cytol.4, 191–194 (1958).

    Google Scholar 

  • Gormsen, H.: On the occurrence of epitheloid cell granulomas in the organs of BCG-vaccinated human beings. Acta path. microbiol. scand., Suppl.111, 117–120 (1956).

    Google Scholar 

  • Guld, J., Magnus, K., Tolderlund, K., Biering-Sørensen, K., Edwards, Ph. Q.: Suppurative lymphadenitis following intradermal BCG vaccination of the newborn. Brit. med. J.1955 II, 1048–1054.

    Google Scholar 

  • Gusek, W.: Histologische und vergleichende elektronenmikroskopische Untersuchungsergebnisse zur Cytologie, Histogenese und Struktur des tuberkulösen und tuberculoiden Granuloms. Med. Welt (Stuttg.)15, 850–866 (1964).

    Google Scholar 

  • Haensch, R., Schmalbruch, H.: Zur Morphologie der Leprazelle. Arch. Derm. Forsch.241, 179–187 (1971).

    Google Scholar 

  • Hanson, L. A.: Aspects of the absence of the IgA system. In: Immunologic deficiency diseases in man, eds. R. A. Good, P. Miescher and R. T. Smith. Birth defects Orig. Art. Series, vol. IV, 1, 292–297. New York: Nat. Found. 1968.

    Google Scholar 

  • Haraldsson, S.: Osteitis tuberculosa fistulosa following vaccination with BCG strain. Acta orthop. scand.29, 121–133 (1960).

    Google Scholar 

  • Haworth, J. C., Dilling, L.: Concentration of γA-globulin in serum, saliva and nasopharyngeal secretions of infants and children. J. Lab. clin. med.67, 922–933 (1966).

    Google Scholar 

  • Hollström, E., Hård, S.: A fatality from BCG vaccination. Acta derm.-venereol. (Stockh.)33, 159–160 (1953).

    Google Scholar 

  • Horwitz, O., Meyer, J.: The safety record of BCG vaccination and untoward reactions observed after vaccination. Fortschr. Tuberk.-Forsch.8, 245–271 (1957).

    Google Scholar 

  • Hsu, H. S.: The fate of Mycobacterium tuberculosis with in macrophages of guinea pigs. Amer. Rev. resp. Dis.103, 607–611 (1971).

    Google Scholar 

  • Imerslund, O., Jonsen, T.: Lupus vulgaris and multiple bone lesions caused by BCG. Acta tuberc. scand.30, 116–123 (1955).

    Google Scholar 

  • Karnovsky, M. J.: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell Biol.27, 137A-138A (1965).

    Google Scholar 

  • Leake, E. S., Evans, D. G., Myrvik, Q. N.: Ultrastructural patterns of bacterial breakdown in normal and granulomatous rabbit alveolar macrophages. J. reticuloendoth. Soc.9, 174–199 (1971).

    Google Scholar 

  • Leder, L.-D.: Der Blutmonocyt. Berlin-Heidelberg-New York: Springer 1967.

    Google Scholar 

  • Leder, L.-D., Crespin, S.: Fermenthistochemische Untersuchungen zur Genese der Hautfenstermakrophagen. Frankfurt. Z. Path.73, 611–628 (1964).

    Google Scholar 

  • Lennert, K: Handbuch der speziellen pathologischen Anatomie und Histologie. Lymphknotendiagnostik in Schnitt und Ausstrich. Cytologie und Lymphadenitis, Bd. I, 3. Berlin-Göttingen-Heidelberg: Springer 1961.

    Google Scholar 

  • Lennert, K., Löffler, H., Leder, L.-D.: Fermenthistochemische Untersuchungen am lymphoretikulären Gewebe. Cytologie und Histochemie in der Haematologie. 9. Freiburger Symposion (1962), S. 363–383. Berlin-Göttingen-Heidelberg: Springer 1963.

    Google Scholar 

  • MacKaness, G. B.: Cellular immunity. The monocyte in delayed-type hypersensitivity. In: Mononuclear phagocytes, p. 461–485, ed. R. Van Furth, Oxford and Edinburgh: Blackwell scientific publications 1970.

    Google Scholar 

  • Merckx, J. J., Brown, A. L., Karlson, A. G.: An electron-microscopic study of experimental infections with acid-fast bacilli. Amer. Rev. resp. Dis.89, 485–496 (1964).

    Google Scholar 

  • Meyer, J., Jensen, K. A.: A fatal case of tuberculosis produced by BCG. Amer. Rev. Tuberc.70, 402–412 (1954).

    Google Scholar 

  • Mori, Y., Lennert, K.: Electron microscopic atlas of lymph node cytology and pathology. Berlin-Heidelberg-New York: Springer 1969.

    Google Scholar 

  • Nitsch, K.: In Druck.

  • North, R. J., Mackaness, G. B.: Electron microscopical observations on the peritoneal macrophages of normal mice and mice immunised with Listeria monocytogenes. Brit. J. exp. Path.44, 601–611 (1963).

    Google Scholar 

  • Reid, J. D.: The pathogenesis of the immunologic granuloma. N.Z. med. J.71, 375–378 (1970).

    Google Scholar 

  • Rockey, J. H., Hanson, L. A., Heremans, J. F., Kunkel, H. G.: Beta-2-A-agammaglobulinemia in two healthy men. J. Lab. clin. Med.63, 205 (1964).

    Google Scholar 

  • Sato, M., Fujiwara, A., Takahashi, K.: A case of lupus vulgaris following BCG vaccination. Kekkaku37, 36–40, 73–79 (1962) [in Japanisch].

    Google Scholar 

  • Saúl, A.: The response of the patient with leprosy toward M. leprae injected with lepromin. International Leprosy Colloquium, Borstel 1970.

  • Seifert, K.: Zur Orientierung inhomogener Gewebseinbettung für die Ultramikrotomie. Mikroskopie17, 231–234 (1962).

    Google Scholar 

  • Sinios, A., Swoboda, W., Meissner, G., Stur, D.: Osteomyelitis als Folge der BCG-Impfung. Mschr. Kinderheilk.113, 605–609 (1965).

    Google Scholar 

  • South, M. A.: IgA in neonatal immunity. Ann. N.Y. Acad. Sci.176, 40–48 (1971).

    Google Scholar 

  • South, M. A., Cooper, M. D., Wollheim, F. A., Good, R. A.: The IgA system. II. The clinical significance of IgA deficiency. Studies in patients with agammaglobulinemia and ataxia teleangiectasia. Amer. J. Med.44, 168–178 (1968).

    Google Scholar 

  • Spiess, H.: Chemo- und Impfprophylaxe. In: Handbuch der Kinderheilkunde, Bd. V, S. 807–834, Hrsg. H. Opitz u. F. Schmidt. Berlin-Göttingen-Heidelberg: Springer 1963.

    Google Scholar 

  • Stojanov, D. P., Zagurov, G. P.: Über die mikroskopischen Veränderungen bei BCG-geimpften Kindern. Zbl. allg. Path. path. Anat.104, 486–494 (1963).

    Google Scholar 

  • Suter, E.: The multiplication of tubercle bacilli within normal phagocytes in tissue culture. J. exp. Med.96, 137–150 (1952).

    Google Scholar 

  • Thrap-Meyer, H.: Generalized BCG infection in man. Acta tuberc. scand.29, 173–179 (1954).

    Google Scholar 

  • Turk, J. L.: Granuloma formation in lymph nodes. Proc. roy. Soc. Med.64, 2–4 (1971).

    Google Scholar 

  • Turk, J. L., Oort, J.: The production of sensitized cells in cell-mediated immunity. In: Handbuch der allgemeinen Pathologie, Bd. VII/3, S. 392–435. Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Ustvedt, H. J.: Usual and unusual reactions to BCG inoculation in children. Amer. Rev. Tuberc.74, 32–42 (1956).

    Google Scholar 

  • Virtanen, S., Lindgren, I.: Osteomyelitis of the femur caused by BCG. Acta tuberc. scand.41, 260–267 (1962).

    Google Scholar 

  • Vortel, V.: Der morphologische Ablauf der Reaktion nach BCG-Impfung. Virchows Arch. path. Anat.336, 46–58 (1962).

    Google Scholar 

  • Waaler, E., Oeding, P.: Generalized BCG infection in man. III. Autopsy findings. Acta tuberc. scand.29, 188–192 (1954).

    Google Scholar 

  • Wallerström, A., Enell, H.: Bacterial metastasis following BCG-vaccination. Acta paediat. scand.55, 517–523 (1966).

    Google Scholar 

  • Watanabe, T., Tanaka, K., Hagiwara, Y.: Generalized tuberculosis after BCG-vaccination. Acta path. jap.19, 395–407 (1969).

    Google Scholar 

  • Waters, M. F. R., Turk, J. L., Wemambu, S. N. C.: Mechanisms of reactions in leprosy. International Leprosy Colloquium, Borstel 1970.

  • West, C. D., Hong, R., Holland, N. H.: Immunoglobulin levels from the newborn period to adulthood and in immunoglobulin deficiency states. J. clin. Invest.41, 2054–2065 (1962).

    Google Scholar 

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Authors and Affiliations

  1. Pathologisches Institut der Universität Kiel, Universitäts-Kinderklinik Kiel, Germany

    E. Kaiserling, K. Lennert, K. Nitsch & J. Drescher

  2. Kinderkrankenhaus DRK Cecilienstift Hannover, Germany

    E. Kaiserling, K. Lennert, K. Nitsch & J. Drescher

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  1. E. Kaiserling
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Kaiserling, E., Lennert, K., Nitsch, K. et al. Ultrastruktur und Pathogenese der BCG-Histiocytose (sog. BCG-Granulomatose). Virchows Arch. Abt. A Path. Anat. 355, 333–353 (1972). https://doi.org/10.1007/BF00554322

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