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. 1978 Jun;91(3):545–570.

Chronic cutaneous graft-versus-host disease in man.

H M Shulman, G E Sale, K G Lerner, E A Barker, P L Weiden, K Sullivan, B Gallucci, E D Thomas, R Storb
PMCID: PMC2018320  PMID: 26221

Abstract

This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BILLINGHAM R. E., BROWN J. B., DEFENDI V., SILVERS W. K., STEINMULLER D. Quantitative studies on the induction of tolerance of homologous tissues and on runt disease in the rat. Ann N Y Acad Sci. 1960 May 31;87:457–471. doi: 10.1111/j.1749-6632.1960.tb23213.x. [DOI] [PubMed] [Google Scholar]
  2. Campbell P. M., LeRoy E. C. Pathogenesis of systemic sclerosis: a vascular hypothesis. Semin Arthritis Rheum. 1975 May;4(4):351–368. doi: 10.1016/0049-0172(75)90017-7. [DOI] [PubMed] [Google Scholar]
  3. Elbadawi A. Hexachrome modification of Movat's stain. Stain Technol. 1976 Sep;51(5):249–253. doi: 10.3109/10520297609116713. [DOI] [PubMed] [Google Scholar]
  4. Fleischmajer R., Damiano V., Nedwich A. Scleroderma and the subcutaneous tissue. Science. 1971 Mar 12;171(3975):1019–1021. doi: 10.1126/science.171.3975.1019. [DOI] [PubMed] [Google Scholar]
  5. Fleischmajer R., Nedwich A. Generalized morphea. I. Histology of the dermis and subcutaneous tissue. Arch Dermatol. 1972 Oct;106(4):509–514. doi: 10.1001/archderm.106.4.509. [DOI] [PubMed] [Google Scholar]
  6. Fleischmajer R., Perlish J. S., Shaw K. V., Pirozzi D. J. Skin capillary changes in early systemic scleroderma. Electron microscopy and "in vitro" autoradiography with tritiated thymidine. Arch Dermatol. 1976 Nov;112(11):1553–1557. [PubMed] [Google Scholar]
  7. Glucksberg H., Storb R., Fefer A., Buckner C. D., Neiman P. E., Clift R. A., Lerner K. G., Thomas E. D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295–304. doi: 10.1097/00007890-197410000-00001. [DOI] [PubMed] [Google Scholar]
  8. Hassell T. M., Page R. C., Narayanan A. S., Cooper C. G. Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2909–2912. doi: 10.1073/pnas.73.8.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hood A. F., Soter N. A., Rappeport J., Gigli I. Graft-versus-host reaction. Cutaneous manifestations following bone marrow transplantation. Arch Dermatol. 1977 Aug;113(8):1087–1091. [PubMed] [Google Scholar]
  10. Johnson R. L., Ziff M. Lymphokine stimulation of collagen accumulation. J Clin Invest. 1976 Jul;58(1):240–252. doi: 10.1172/JCI108455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Krüger G. R., Berard C. W., DeLellis R. A., Graw R. G., Jr, Yankee R. A., Leventhal B. G., Rogentine G. N., Herzig G. P., Halterman R. H., Henderson E. S. Graft-versus-host disease. Morphologic variation and differential diagnosis in 8 cases of HL-A matched bone marrow transplantation. Am J Pathol. 1971 May;63(2):179–202. [PMC free article] [PubMed] [Google Scholar]
  12. Lawley T. J., Peck G. L., Moutsopoulos H. M., Gratwohl A. A., Deisseroth A. B. Scleroderma, Sjögren-like syndrome, and chronic graft-versus-host disease. Ann Intern Med. 1977 Dec;87(6):707–709. doi: 10.7326/0003-4819-87-6-707. [DOI] [PubMed] [Google Scholar]
  13. LeRoy E. C. Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast. J Clin Invest. 1974 Oct;54(4):880–889. doi: 10.1172/JCI107827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leevy C. M., Cardi L., Frank O., Gellene R., Baker H. Incidence and significance of hypovitaminemia in a randomly selected municipal hospital population. Am J Clin Nutr. 1965 Oct;17(4):259–271. doi: 10.1093/ajcn/17.4.259. [DOI] [PubMed] [Google Scholar]
  15. Lerner K. G., Kao G. F., Storb R., Buckner C. D., Clift R. A., Thomas E. D. Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc. 1974 Dec;6(4):367–371. [PubMed] [Google Scholar]
  16. Meuwissen H. J., Rodey G., McArthur J., Pabst H., Gatti R., Chilgren R., Hong R., Frommel D., Coifman R., Good R. A. Bone marrow transplantation. Therapeutic usefulness and complications. Am J Med. 1971 Oct;51(4):513–532. doi: 10.1016/0002-9343(71)90257-9. [DOI] [PubMed] [Google Scholar]
  17. Norton W. L., Nardo J. M. Vascular disease in progressive systemic sclerosis (scleroderma). Ann Intern Med. 1970 Aug;73(2):317–324. doi: 10.7326/0003-4819-73-2-317. [DOI] [PubMed] [Google Scholar]
  18. Otani A. Lupus erythematosus hypertrophicus et profundus. Br J Dermatol. 1977 Jan;96(1):75–78. doi: 10.1111/j.1365-2133.1977.tb05189.x. [DOI] [PubMed] [Google Scholar]
  19. Pinkus H. Lichenoid tissue reactions. A speculative review of the clinical spectrum of epidermal basal cell damage with special reference to erythema dyschromicum perstans. Arch Dermatol. 1973 Jun;107(6):840–846. doi: 10.1001/archderm.107.6.840. [DOI] [PubMed] [Google Scholar]
  20. Reed R. J., Ackerman A. B. Pathology of the adventitial dermis. Anatomic observations and biologic speculations. Hum Pathol. 1973 Jun;4(2):207–217. doi: 10.1016/s0046-8177(73)80008-5. [DOI] [PubMed] [Google Scholar]
  21. Reed R. J., Clark W. H., Mihm M. C. The cutaneous collagenoses. Hum Pathol. 1973 Jun;4(2):165–186. doi: 10.1016/s0046-8177(73)80005-x. [DOI] [PubMed] [Google Scholar]
  22. Rowell N. R., Hopper F. E. The periodontal membrane in systemic sclerosis. Br J Dermatol. 1977 Jan;96(1):15–20. doi: 10.1111/j.1365-2133.1977.tb05179.x. [DOI] [PubMed] [Google Scholar]
  23. STASTNY P., STEMBRIDGE V. A., ZIFF M. HOMOLOGOUS DISEASE IN THE ADULT RAT, A MODEL FOR AUTOIMMUNE DISEASE. I. GENERAL FEATURES AND CUTANEOUS LESIONS. J Exp Med. 1963 Oct 1;118:635–648. doi: 10.1084/jem.118.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sale G. E., Lerner K. G., Barker E. A., Shulman H. M., Thomas E. D. The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Am J Pathol. 1977 Dec;89(3):621–636. [PMC free article] [PubMed] [Google Scholar]
  25. Saurat J. H., Didier-Jean L., Gluckman E., Bussel A. Graft versus host reaction and lichen planus-like eruption in man. Br J Dermatol. 1975 May;92(5):591–592. doi: 10.1111/j.1365-2133.1975.tb03131.x. [DOI] [PubMed] [Google Scholar]
  26. Siimes M. A., Johansson E., Rapola J. Scleroderma-like graft-versus-host disease as late consequence of bone-marrow grafting. Lancet. 1977 Oct 15;2(8042):831–832. doi: 10.1016/s0140-6736(77)90772-3. [DOI] [PubMed] [Google Scholar]
  27. Sjögren's syndrome--newer aspects of research, diagnosis, and therapy. Ann Intern Med. 1971 Dec;75(6):937–950. [PubMed] [Google Scholar]
  28. Slavin R. E., Santos G. W. The graft versus host reaction in man after bone marrow transplantation: pathology, pathogenesis, clinical features, and implication. Clin Immunol Immunopathol. 1973 Jul;1(4):472–498. doi: 10.1016/0090-1229(73)90005-6. [DOI] [PubMed] [Google Scholar]
  29. Spielvogel R. L., Ullman S., Goltz R. W. Skin changes in graft-vs-host disease. South Med J. 1976 Oct;69(10):1277–1281. doi: 10.1097/00007611-197610000-00009. [DOI] [PubMed] [Google Scholar]
  30. Stastny P., Stembridge V. A., Vischer T., Ziff M. Homologous disease in the adult rat, a model for autoimmune disease. II. Findings in the joints, heart, and other tissues. J Exp Med. 1965 Oct 1;122(4):681–692. doi: 10.1084/jem.122.4.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Storb R., Thomas E. D., Weiden P. L., Buckner C. D., Clift R. A., Fefer A., Fernando L. P., Giblett E. R., Goodell B. W., Johnson F. L. Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. Blood. 1976 Dec;48(6):817–841. [PubMed] [Google Scholar]
  32. Tan E. M. Immunopathology and pathogenesis of cutaneous involvement in systemic lupus erythematosus. J Invest Dermatol. 1976 Sep;67(3):360–365. doi: 10.1111/1523-1747.ep12514707. [DOI] [PubMed] [Google Scholar]
  33. Thomas E. D., Buckner C. D., Banaji M., Clift R. A., Fefer A., Flournoy N., Goodell B. W., Hickman R. O., Lerner K. G., Neiman P. E. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977 Apr;49(4):511–533. [PubMed] [Google Scholar]
  34. Thomas E. D., Storb R., Clift R. A., Fefer A., Johnson L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895–902. doi: 10.1056/NEJM197504242921706. [DOI] [PubMed] [Google Scholar]
  35. Thomas E., Storb R., Clift R. A., Fefer A., Johnson F. L., Neiman P. E., Lerner K. G., Glucksberg H., Buckner C. D. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975 Apr 17;292(16):832–843. doi: 10.1056/NEJM197504172921605. [DOI] [PubMed] [Google Scholar]
  36. Touraine R., Revuz J., Dreyfus B., Rochant H., Mannoni P. Graft versus host reaction and lichen planus. Br J Dermatol. 1975 May;92(5):589–589. doi: 10.1111/j.1365-2133.1975.tb03130.x. [DOI] [PubMed] [Google Scholar]
  37. Van Vloten W. A., Scheffer E., Dooren L. J. Localized scleroderma-like lesions after bone marrow transplantation in man. A chronic graft versus host reaction. Br J Dermatol. 1977 Apr;96(4):337–341. doi: 10.1111/j.1365-2133.1977.tb07126.x. [DOI] [PubMed] [Google Scholar]
  38. Winkelmann R. K. Classification and pathogenesis of scleroderma. Mayo Clin Proc. 1971 Feb;46(2):83–91. [PubMed] [Google Scholar]
  39. Woodruff J. M., Eltringham J. R., Casey H. W. Early secondary disease in the Rhesus monkey. I. A comparative histopathologic study. Lab Invest. 1969 Jun;20(6):499–511. [PubMed] [Google Scholar]
  40. de VRIES M., CROUCH B. G., van PUTTEN L., van BEKKUM D. Pathologic changes in irradiated monkeys treated with bone marrow. J Natl Cancer Inst. 1961 Jul;27:67–97. [PubMed] [Google Scholar]

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