Summary
In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory brust required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic rsonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, “burnt out” white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.
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References
Balfour HH, Shehan JJ, Speicher CE, Kauder E (1971) Chronic granulomatous disease of childhood in a 23-year-old man. JAMA 217: 960–961
Bartman J, Van de Velde RL, Friedman F (1967) Pigmented lipid histiocytosis and susceptibility to infection: ultrastructure of splenic histiocytes. Pediatrics. 1967: 40: 100–1002
Bridges RA, Berendes H, Good RA (1959) A fatal granulomatous disease of childhood. The clinical, pathological and laboratory features of a new syndrome. J Dis Child 97: 387–408
Dilworth JA, Mardel GL (1967) Adults with chronic granulomatous disease of “childhood” Clin Res 24: 452A
Donowitz GR, Mandell GL (1983) Clinical presentation and unusual infections in chronic granulomatous disease. In: Gallen JI, Fauci AS (eds) Advances in Host Defense Mechanisms, vol 3. Raven Press, New York, pp 65-
Evans HE, Edgcomb JH (1962) Unexplained granulomatosis in childhood: a clinicopathological dilemma. Arch Pathol 74: 360–366
Fleischmann J, Church JA, Lehrer RI (1986) Primary candida meningitis and chronic granulomatous disease. Am J Med Sci 29: 334–341
Garel D, Devictor D, Tchernia G, Pham T, Dommergues JP (1989) Streptococcus group B tardive meningitis revealing chronic septic granulomatosis. Ann Pediatr 36: 35–37
Harada T, Sugihara H, Tsuchiyama H, Noda H (1977) Histochemical and ultrastructural observation of the pigment in pigmented lipid histiocytes of chronic granulomatous disease. Acta Histochem Cytochem 10: 500–507
Hotchi M, Fujiwara M, Nasu T (1980) Chronic granulomatous disease associated with peculiar aspergillus lesions, pathoanatomical report based on two autopsy cases and a brief review of all autopsy cases reported in Japan. Virchows Arch [A] 387: 1–15
Johnston RB, Newman SL (1977) Chronic granulomatous disease. Pediatr Clin North Am 24: 365–376
Kobayashi S, Ichinohe S, Okabe N, Tatsuzawa O (1988) Varicella-zoster virus infection in chronic granulomatous disease. Pediatr Infect Dis J 7: 809–810
Landing BH, Shirkey HS (1957) A syndrome of recurrent infection and infiltration of viscera by pigmented lipid histiocytes. Pediatrics 20: 431–438
Quie PG, White JG, Holmes B, Good RA (1967) In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest 46: 668–679
Riggs JE, Quaglieri FC, Schochet SS Jr, Dove DJ (1989) Pigmented, lipid-laden histiocytes in the central nervous system in chronic granulomatous disease of childhood. J Child Neurol 4: 61–63
Segal AW (1985) Variations on the theme of chronic granulomatous disease. Lancet I: 1378–1383
Smith TW, DeGirolami U, Henin D, Bolgert F, Hauw J-J (1990) Human immunodeficiency virus (HIV) leukoencephalopathy and the Microcirculation. J Neuropathol Exp Neurol 649: 357–370
Tanaka T, Takahashi K, Morita H,-(19) Chronic granulomatous disease of childhood and sea-blue histiocytosis, a pathologic study of an autopsy case. Acta Pathol Jpn 34: 1385–1401
Tauber AI, Borregaard N, Simons E, Wright J (1983) Chronic granulomatous disease: a syndrome of phagocyte oxidase deficiencies. Medicine 61: 286–309
Ulshafer RJ, Allen CB, Rubin ML (1990) Distributions of elements in the human retinal pigment epithelium. Arch Ophthalmol 108: 113–117
Vichi GF, Jenuso R, de Martino M, Vierucci A (1986) Unusual evolution of chronic granulomatous disease with mediastinum localization and diffusion into vertebrae, ribs and vertebral canal. ROFO 145: 109–111
Walker DH, Okiye G (1957) Chronic granulomatous disease involving the central nervous system. Pediatr Pathol 1: 159–167
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Hadfield, M.G., Ghatak, N.R., Laine, F.J. et al. Brain lesions in chronic granulomatous disease. Acta Neuropathol 81, 467–470 (1991). https://doi.org/10.1007/BF00293469
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DOI: https://doi.org/10.1007/BF00293469