Aust. N.Z. J. hled. (19i91, 9, pp 3 4 4 -147
CASE REPORT
Disseminated Cryptococcosis with Ocular Involvement R. K. Kumar* and A. W. J. Lykket From the School of Pathology. University of New South Wales, Sydney
SUmmat'y: Disseminated cryptococcosis with ocular involvement. R. K. Kurnar and A. W. J. Lykke, Aust. N.Z. J. Med., 1979, 9, pp. 444-447.
A case of disseminated cryptococcosis with extensive ocular involvement is reported. The patient had pulmonary, meningeal, cerebral, cutaneous, lymph node, renal, adrenal and thyroid lesions, as well as granulomatous endophthalmitis.
Disseminated cryptococcosis is a wellrecognised, albeit uncommon, malady in man. The organs most frequently involved are the brain and meninges, lungs, kidneys and spleen. Less commonly affected sites include skin, liver, lymph nodes, pancreas, thyroid, adrenals, heart. great vesscls, bone, bone marrow and testes.',' Ocular involvement is relatively rare.3This paper reports a case of disseminated cryptococcosis with ocular lesions as well as involvement of a number of other unusual sites. Case Re por t A 67-yen-old woman first presented seven years previously with a nine-month history of frontal headaches, episodes of diplopia and blurred vision in the right eye. She had suffered three episodes of transient ataxia and weakness of the left side prior to admission; on examination there was evidence of left hemiparesis. A diagnosis of a mild right cerebrovascular accident precipitated by transient ischaemic attacks was made. Her condition improved considerably during her stay in hospital. She was readmitted two years later complaining of right hemicranial headache of sudden onset. Examination revealed a blood pressure of 180;llO mmHg, marked neck stiffness and signs of left hemiplegia. A provisional diagnosis of subarachnoid haemorrhage was confirmed by lumbar puncture; carotid angiography was normal. A further admission to hospital seven months later was necessitated when she developed impairment of higher cerebral functions and bilateral lower limb weakness. Ventriculography revealed a communicating hydrocephalus, for which a 'Senior Tutor in Pathology. ?Professor of Pathology. Correspondence: Dr. R . K. Kumar, School of Pathology, The University of New South Wales. PO Box 1, Kensington, NSW 2033 Accepted for publication: 23 December, 1978
ventriculoatrial shunt was inserted, following which the patient improvcd remarkably. Eighteen months ago she was found to be suffering from adrenocortical insufficiency and was treated with cortisone acetate (37.5 mg;day) and fluorocortisol (0.1 nig,;day). On her final admission she presented with pain in the right eye and blurring of vision of three weeks' duration. Ocular examination suggested a posterior uveitis. Examination of the central nervous system revealed impairment of various higher functions, especially memory, together with residual haemiplegia. Other systems were normal. She failed to respond to therapy and apparently suffered yet another cerebrovascular accident while in hospital. which evoked a right-sided hemiparesis. Two weeks later she developed what was thought to be aspiration pneumonia. Lumbar puncture now revealed xanthochrornic cerebrospinal fluid containing numerous 5 -1 2 pm diameter ovoid budding organisms which had a demonstrable capsule in Indian ink preparations and were identified as cryptococci. A quantitative latex agglutination test for Cryptococcus izeojormans antigen in the cerebrospinal fluid was positive in a high titre. A presumptive diagnosis of disseminated cryptococcosis involving the central nervous system and lungs was made. She was treated with amphotericin but her condition continued to deteriorate. She developed ulcerative nodular lesions on the face, from which Ciyptococcus neofornians, sensitive to 5fluorocytosine, was cultured. She also developed lesions of herpes simplex on the buttocks. She died eight weeks after admission. Autopsy Findings Macroscopic
Both lungs were congested, ocdematous and riddled with multiple solid whitish lesions, 4 8 mm in diameter, distributed throughout the pulmonary parenchyma. Tracheobronchial lymph nodes were grossly enlarged and appeared white and necrotic. Macroscopically, the kidneys appeared normal. The adrenals were both markedly atrophic. Both lobes of the thyroid were enlarged, firm and pale. The brain showed minimal hydrocephalus and mild cortical atrophy. The cerebral vessels exhibited only minimal atherosclerosis. There was meningeal thickening in the interpeduncular fossa and over the crebellar hemispheres. Clusters of minute (1- 3 mm) grey gelatinous lesions were observed in the cerebral grey matter on the left side. Microscopic Both lungs contained numerous circumscribed lesions each ing of several alveolar sacs distended with eryptococci. In some areas these focal lesions were confluent. There was little tissue destruction nor was there any surrounding inflammatory reaction. The tracheobronchial lymph nodes exhibited almost complete replacement of lymphoid tissue by innumerable organisms. There was patchy tubular necrosis in both kidneys and scattered fungal lesions similar to those in
FIGURE 1. Skin biopsy showing numerous cryptococci in t h e dermis; note absence of inflammatory response. Silver rnethenamine X 100
the lungs were noted. The thyroid was diffusely infiltrated by cryptococci. Both adrenals exhibited extensive scarring and virtually complete destruction of cortical tissue. Numerous organisms were identified throughout the adrenal cortex. No significant abnormalities were detected in the liver and spleen. A bone marrow biopsy was normal. Antemortern skin biopsies from the facial lesions showed proliferating masscs of fungi, again nith a notable lack of surrounding inflamination (Fig. 1). A skin biopsy from the buttock was histologically a typical herpetic vesicle. The meninges overlying the cerebral and cerebellar hemispheres were diffusely infiltrated with cryptococci (Fig. 2). There was no invasion of the cerebellar cortex and no evidence of inflammation. The cerebral grey matter exhibited numerous focal lesions consisting of proliferating inasses of organisms. Histopathological examination of the eye revealed a granulomatous endophthalmitis with numerous cryptococci identifiable; organisms were noted in the vitreous, retina, subretinal space and choroid (Fig. 3). A scanty lymphocytic inflammatory response was present and occasional giant cells were seen. The anterior segment ofthe eye was normal. as was the optic nerve.
Discussion
A case of disseminated cryptococcosis is presented, with multi-visceral and ocular involvement. Though the microbiological diagnosis in this patient was established late, retro-
spective cvaluation of the clinical history suggests that she contracted a primary cryptococcal infection which predominantly involved the central nervous system. The pathological lesions exhibited in the CNS adequately explain her neurological symptoms and signs. Symptomatic involvement of the eye was also prominent from the early stages. Late in the course of her illness, dissemination occurred. This may have been precipitated by the use of corticosteroids in therapy after adrenocortical insufficiency had been identified. Though cryptococcal invasion of the adrenals is demonstrable, it is difficult to ascertain whether this was primarily responsible for adrenal destruction since there was considerable adrenal scarring evident, which might indicate that auto-immune adrenal atrophy was supcrimposcd on her earlier illness. The first detailed account of cryptococcosis in Australia was provided by Cox and Tolhurst4 who documented thirteen cases. Several recent reviews of cryptococcosis are availabkP8 and the infection is now widely recognised as being
FIGURE 2.
Micrograph showing diffuse infiltration of the meninges by cryptococci. PAS
FIGURE 3.
Low-power micrograph of the eye, showing extensive destruction. especially of the retina. PAS x 2 5
X
160
bvorldwide. An antecedent disease is identifiable in up to 5O",, ofcases9; malignancies. especially of the lymphoreticular system'. autoimmune diseases'", l 1 and steroid therapy12 arc important predisposing factors. Ocular involvement is rare: Staib ~f d.13 reported a case and reviewed 20 previously documented instances in the literature and a further single case has since been This patient exhibited many of the classic features of disseminated cryptococcosis, especially with regard to the behaviour of the central nervous system lesions8, although several unusual sites are involved. The striking absence of an inflammatory response is often a feature of disseminated cryptococcosis.2 The ocular infection is noteworthy: chorioretinitis is the usual form of ocular involvement in cryptoc o c c o ~ i s .This ~ case, however, exhibits more florid and widespread ocular lesions.
wish to thank Ihe staff of the Department of Morbid Anatomy. St. Vincent's Hospital, Sydncy. for their assistance with this case. as well as Dr. M. IYipic of the Sydney Eye Hospital for histopathological examination of the eye, and Miss L. Goldacre for photographic assistance.
References !.
CASE REPORT
Disseminated Cryptococcosis with Ocular Involvement R. K. Kumar* and A. W. J. Lykket From the School of Pathology. University of New South Wales, Sydney
SUmmat'y: Disseminated cryptococcosis with ocular involvement. R. K. Kurnar and A. W. J. Lykke, Aust. N.Z. J. Med., 1979, 9, pp. 444-447.
A case of disseminated cryptococcosis with extensive ocular involvement is reported. The patient had pulmonary, meningeal, cerebral, cutaneous, lymph node, renal, adrenal and thyroid lesions, as well as granulomatous endophthalmitis.
Disseminated cryptococcosis is a wellrecognised, albeit uncommon, malady in man. The organs most frequently involved are the brain and meninges, lungs, kidneys and spleen. Less commonly affected sites include skin, liver, lymph nodes, pancreas, thyroid, adrenals, heart. great vesscls, bone, bone marrow and testes.',' Ocular involvement is relatively rare.3This paper reports a case of disseminated cryptococcosis with ocular lesions as well as involvement of a number of other unusual sites. Case Re por t A 67-yen-old woman first presented seven years previously with a nine-month history of frontal headaches, episodes of diplopia and blurred vision in the right eye. She had suffered three episodes of transient ataxia and weakness of the left side prior to admission; on examination there was evidence of left hemiparesis. A diagnosis of a mild right cerebrovascular accident precipitated by transient ischaemic attacks was made. Her condition improved considerably during her stay in hospital. She was readmitted two years later complaining of right hemicranial headache of sudden onset. Examination revealed a blood pressure of 180;llO mmHg, marked neck stiffness and signs of left hemiplegia. A provisional diagnosis of subarachnoid haemorrhage was confirmed by lumbar puncture; carotid angiography was normal. A further admission to hospital seven months later was necessitated when she developed impairment of higher cerebral functions and bilateral lower limb weakness. Ventriculography revealed a communicating hydrocephalus, for which a 'Senior Tutor in Pathology. ?Professor of Pathology. Correspondence: Dr. R . K. Kumar, School of Pathology, The University of New South Wales. PO Box 1, Kensington, NSW 2033 Accepted for publication: 23 December, 1978
ventriculoatrial shunt was inserted, following which the patient improvcd remarkably. Eighteen months ago she was found to be suffering from adrenocortical insufficiency and was treated with cortisone acetate (37.5 mg;day) and fluorocortisol (0.1 nig,;day). On her final admission she presented with pain in the right eye and blurring of vision of three weeks' duration. Ocular examination suggested a posterior uveitis. Examination of the central nervous system revealed impairment of various higher functions, especially memory, together with residual haemiplegia. Other systems were normal. She failed to respond to therapy and apparently suffered yet another cerebrovascular accident while in hospital. which evoked a right-sided hemiparesis. Two weeks later she developed what was thought to be aspiration pneumonia. Lumbar puncture now revealed xanthochrornic cerebrospinal fluid containing numerous 5 -1 2 pm diameter ovoid budding organisms which had a demonstrable capsule in Indian ink preparations and were identified as cryptococci. A quantitative latex agglutination test for Cryptococcus izeojormans antigen in the cerebrospinal fluid was positive in a high titre. A presumptive diagnosis of disseminated cryptococcosis involving the central nervous system and lungs was made. She was treated with amphotericin but her condition continued to deteriorate. She developed ulcerative nodular lesions on the face, from which Ciyptococcus neofornians, sensitive to 5fluorocytosine, was cultured. She also developed lesions of herpes simplex on the buttocks. She died eight weeks after admission. Autopsy Findings Macroscopic
Both lungs were congested, ocdematous and riddled with multiple solid whitish lesions, 4 8 mm in diameter, distributed throughout the pulmonary parenchyma. Tracheobronchial lymph nodes were grossly enlarged and appeared white and necrotic. Macroscopically, the kidneys appeared normal. The adrenals were both markedly atrophic. Both lobes of the thyroid were enlarged, firm and pale. The brain showed minimal hydrocephalus and mild cortical atrophy. The cerebral vessels exhibited only minimal atherosclerosis. There was meningeal thickening in the interpeduncular fossa and over the crebellar hemispheres. Clusters of minute (1- 3 mm) grey gelatinous lesions were observed in the cerebral grey matter on the left side. Microscopic Both lungs contained numerous circumscribed lesions each ing of several alveolar sacs distended with eryptococci. In some areas these focal lesions were confluent. There was little tissue destruction nor was there any surrounding inflammatory reaction. The tracheobronchial lymph nodes exhibited almost complete replacement of lymphoid tissue by innumerable organisms. There was patchy tubular necrosis in both kidneys and scattered fungal lesions similar to those in
FIGURE 1. Skin biopsy showing numerous cryptococci in t h e dermis; note absence of inflammatory response. Silver rnethenamine X 100
the lungs were noted. The thyroid was diffusely infiltrated by cryptococci. Both adrenals exhibited extensive scarring and virtually complete destruction of cortical tissue. Numerous organisms were identified throughout the adrenal cortex. No significant abnormalities were detected in the liver and spleen. A bone marrow biopsy was normal. Antemortern skin biopsies from the facial lesions showed proliferating masscs of fungi, again nith a notable lack of surrounding inflamination (Fig. 1). A skin biopsy from the buttock was histologically a typical herpetic vesicle. The meninges overlying the cerebral and cerebellar hemispheres were diffusely infiltrated with cryptococci (Fig. 2). There was no invasion of the cerebellar cortex and no evidence of inflammation. The cerebral grey matter exhibited numerous focal lesions consisting of proliferating inasses of organisms. Histopathological examination of the eye revealed a granulomatous endophthalmitis with numerous cryptococci identifiable; organisms were noted in the vitreous, retina, subretinal space and choroid (Fig. 3). A scanty lymphocytic inflammatory response was present and occasional giant cells were seen. The anterior segment ofthe eye was normal. as was the optic nerve.
Discussion
A case of disseminated cryptococcosis is presented, with multi-visceral and ocular involvement. Though the microbiological diagnosis in this patient was established late, retro-
spective cvaluation of the clinical history suggests that she contracted a primary cryptococcal infection which predominantly involved the central nervous system. The pathological lesions exhibited in the CNS adequately explain her neurological symptoms and signs. Symptomatic involvement of the eye was also prominent from the early stages. Late in the course of her illness, dissemination occurred. This may have been precipitated by the use of corticosteroids in therapy after adrenocortical insufficiency had been identified. Though cryptococcal invasion of the adrenals is demonstrable, it is difficult to ascertain whether this was primarily responsible for adrenal destruction since there was considerable adrenal scarring evident, which might indicate that auto-immune adrenal atrophy was supcrimposcd on her earlier illness. The first detailed account of cryptococcosis in Australia was provided by Cox and Tolhurst4 who documented thirteen cases. Several recent reviews of cryptococcosis are availabkP8 and the infection is now widely recognised as being
FIGURE 2.
Micrograph showing diffuse infiltration of the meninges by cryptococci. PAS
FIGURE 3.
Low-power micrograph of the eye, showing extensive destruction. especially of the retina. PAS x 2 5
X
160
bvorldwide. An antecedent disease is identifiable in up to 5O",, ofcases9; malignancies. especially of the lymphoreticular system'. autoimmune diseases'", l 1 and steroid therapy12 arc important predisposing factors. Ocular involvement is rare: Staib ~f d.13 reported a case and reviewed 20 previously documented instances in the literature and a further single case has since been This patient exhibited many of the classic features of disseminated cryptococcosis, especially with regard to the behaviour of the central nervous system lesions8, although several unusual sites are involved. The striking absence of an inflammatory response is often a feature of disseminated cryptococcosis.2 The ocular infection is noteworthy: chorioretinitis is the usual form of ocular involvement in cryptoc o c c o ~ i s .This ~ case, however, exhibits more florid and widespread ocular lesions.
wish to thank Ihe staff of the Department of Morbid Anatomy. St. Vincent's Hospital, Sydncy. for their assistance with this case. as well as Dr. M. IYipic of the Sydney Eye Hospital for histopathological examination of the eye, and Miss L. Goldacre for photographic assistance.
References !.
