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Pneumocystis carinii Infection of the Conjunctiva in a Patient with Acquired Immune Deficiency Syndrome
Pneumocystis carinii Infection of the Conjunctiva in a Patient with Acquired Immune Deficiency Syndrome Gian Marco Ruggli, MD/ Rainer Weber, MD, 2 Elmar Peter Messmer, MD/ Ramon L. Font, MD/ Carl Moll, MD, 4 Wolfgang Bernauer, MD 1 Background: Ocular disease, especially the development of choroidal lesions, is a known extrapulmonary manifestation of Pneumocystis carinii infection in the acquired immune deficiency syndrome (AIDS). To our knowledge, conjunctival involvement due to P. carinii has not been described previously. Methods: The authors describe a 33-year-old homosexual male with AIDS in whom a large placoid, white lesion developed involving the tarsal conjunctiva of the right upper lid. Conjunctival malignancy was suspected and biopsies and swabs were taken. At this time, the patient had been receiving monthly aerosolized pentamidine prophylaxis for 18 months, and there was neither a history of pneumonia nor any clinical signs of disseminated infection due to P. carinii. Results: Histopathologic examination results of the conjunctival biopsy specimen showed a necrotic, frothy tissue surrounded by activated fibroblasts. Within this material, Gomori methenamine silver stains showed numerous round and cup-like cysts of P. carinii, confirming the diagnosis that had already been obtained by an indirect fluorescentantibody stain of a conjunctival smear specimen. Conclusions: The presence of white placoid conjunctival lesions in a patient with AIDS may indicate an infection due to P. carinii. Conjunctival disease due to P. carinii widens the spectrum of AIDS-associated ophthalmic pneumocystosis. Ophthalmology 1997; 104:1853-1856
Originally received: February 20, 1997. Revision accepted: May 19, 1997. 1 Department of Ophthalmology, University Hospital of ZUrich, ZUrich, Switzerland. 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital of ZUrich, ZUrich, Switzerland.
3 Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. 4
Department of Pathology, Division of Cytopathology, University Hospital of ZUrich, ZUrich, Switzerland.
Supported in part by grants from the Retina Research Foundation, Houston, Texas, and Research to Prevent Blindness Inc., New York, New York. The authors have no proprietary interest in the products or techniques described in this article. Reprint requests to Gian Marco Ruggli, MD, University of ZUrich, Department of Ophthalmology, Frauenklinikstrasse 24, CH-8091 ZUrich, Switzerland.
Pneumocystis carinii is an important opportunistic pathogen in patients with congenital or acquired immune deficiencies.1 The taxonomic status of this eukaryotic microorganism has not been clarified fully. The monocellular parasite, which is exclusively present in the extracellular space, shows many morphologic features of protozoa, but is considered by some investigators to be a fungus. 2•3 Pulmonary P. carinii infection is the most common lifethreatening complication in patients with acquired immune deficiency syndrome (AIDS). Extrapulmonary infection or dissemination of the parasite is rare (<1%). 4 Among more than 50 cases of extrapulmonary pneumocystosis that have been reported, the most common sites of involvement are lymph nodes, spleen, liver, bone marrow, gastrointestinal tract, eyes, thyroid gland, adrenal gland, and kidneys. 4 Pneumocystis choroidopathy,5 - 9 retinal manifestations, 10 and orbital involvement11 are the most common ophthalmic manifestations of extrapulmonary AIDS-associated P. carinii infection.
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Volume 104, Number 11, November 1997
To our knowledge, AIDS-associated conjunctivitis due to P. carinii has not yet been reported. We describe the clinical features and histologic findings of a unique case of P. carinii infection with conjunctival involvement.
Case Report A 33-year-old white homosexual man was found to be human immunodeficiency virus-antibody positive in February 1990, and AIDS was diagnosed in April 1995. A total helper-cell (CD4) depletion was present since June 1995. His general condition progressively deteriorated. Severe anemia of unknown origin developed as well as a disseminated Mycobacterium avium infection. He was treated with different combinations of antimycobacterial agents. Since January 1994, he was receiving prophylaxis for P. carinii pneumonia using aerosolized pentamidine. A systemic trimethoprim-sulfamethoxazole chemoprophylaxis was not tolerated. There were never signs or symptoms of pulmonary infection due to P. carinii. In January 1996, he noted an irritation of his right eye, and he was referred for examination to the ophthalmology department. Except for a moderate myopia and a history of explosion trauma with superficial corneal involvement 20 years ago, his ocular history was unremarkable. Ophthalmic examination showed a visual acuity of 16/20 in the right eye and 20/20 in the left eye. The tarsal conjunctiva of his right upper lid showed a slightly elevated, placoid, white avascular lesion with well-defined borders. Approximately half of the subtarsal area and the margin of the upper lid were involved (Figs 1, 2). The adjacent conjunctiva was slightly hyperemic but without follicular or papillary reactions. Both corneas showed diffusely distributed punctate subepithelial opacities with inclusions of foreign material. The anterior chambers were quiet and the fundi were normal. Steroid drops were prescribed, and 2 weeks later two punch biopsy specimens were taken from the lesion of the tarsal conjunctiva with the patient under local anesthesia. Because of the difficulties establishing the correct diagnosis histopathologically, additional conjunctival smears were taken from the affected eye. After the diagnosis of extrapulmonary P. carinii infection had been established by examination of the conjunctival specimens, the patient started receiving oral treatment with dapsone and trimethoprim. The efficacy of this regimen, however, could not be established because the moribund patient died, most probably because of a disseminated atypical mycobacterial infection. Unfortunately, postmortem examination was not performed.
Biopsy and Laboratory Findings Microscopic examination of the biopsy specimen showed that the tissue of the affected area was partly covered by normal conjunctival mucosa. The underlying stroma showed confluent lakes of amorphous eosinophilic frothy and vacuolated material with remnants of fibrovascular tissue (Figs 3, 4). The deposits were bordered by areas of reactive fibroblastic proliferation and capillary sprouting. There were no inflammatory infiltrates. Gomori methenamine silver stain showed numerous round-to-oval cysts within the necrotic tissue, some of which resemble pingpong balls, that measure 3 to 7 J..Lm in diameter (Fig 5). No other micro-organisms were identified. Based on these
1854
findings, the diagnosis of P. carinii conjunctivitis was established. Light microscopy of conjunctival smear specimen showed numerous toluidine blue-positive cysts (Fig 6). Furthermore, indirect immunofluorescence using monoclonal mouse anti-P. carinii antibodies (DAKO, Glostrup, DK) showed P. carinii cysts.
Discussion Because of a profound defect in cell-mediated immunity, patients with AIDS are susceptible to many opportunistic infections. Among these, P. carinii pneumonia is one of the most common life-threatening complications. Pneumocystosis in patients with immunologic disorders appears to be the result of reactivation of latent disease because there is serologic documentation of widespread (nearly 100%) acquisition of anti-Pneumocystis antibodies in early childhood. 12'13 Despite the high frequency of lung infections caused by P. carinii in immunosuppressed persons, extrapulmonary dissemination rarely occurs. 4·14 The pathogenesis of extrapulmonary P. carinii infection is not fully understood. It might occur by hematogenous or lymphatic dissemination from the lungs, reactivation of latent infection in extrapulmonary sites, or primary infection of these sites. 15 Cases of extrapulmonary P. carinii infection not associated with the AIDS epidemic have been reported in children with hypogammaglobulinemia 16·17 and in adults with a variety of immunodeficiency states (e.g., leukemia, 16 immunosuppressive therapy, 18 idiopathic hypoproteinemia, 19 and lymphoma20). The first report of extrapulmonary P. carinii manifestation associated with AIDS described retinal involvement in a patient who died of P. carinii pneumonia. 10 Since then, pneumocystosis with extrapulmonary involvement with or without concomitant pneumonia is increasingly recognized in patients with AIDS, especially among those receiving inhaled pentamidine prophylaxis. 6·9·11 •21 - 25 This method of aerosolized administration shows only little extrapulmonary distribution and, therefore, is ineffective both in controlling and preventing a disseminated P. carinii infection. In addition, many authors expressed concern that the aerosolized administration even facilitates disseminated infection. 24 ' 25 Still, this association remains unconfirmed and needs further investigations. 15 The diagnosis of pneumocystosis rests on the identification of cysts or trophozoites in secretions or exudates of tissue or both or in biopsy specimens. Visualization of the organism with special stains, the most useful of which are the Gomori methenamine silver nitrate, modified toluidine blue 0 stain, and immunohistochemical techniques with monoclonal antibodies, 26 - 29 confirms the diagnosis. Ultrastructural examination is helpful but usually not required.30 At present, trimethoprim-sulfamethoxazole (orally or intravenously) remains the treatment of choice for P. carinii infection. Other regimens include dapsone/trimethoprim (orally), clindamycinlprimaquine (orally or intravenously), atovaquone (orally), or pentamidine isethionate
Ruggli et al · Infection of the Conjunctiva in a Patient with AIDS
Figure 1. Clinical appearance of the right upper tarsal conjunctiva with a slightly elevated, plaque-like, white avascular lesion, which involves approximately half of the subtarsal area. Figure 2. Detail of the lid, as shown in Figure 1. The lesion is restricted to the mucous membrane and does not involve the skin. Figure 3. Low-power view of the biopsy specimen discloses areas of necrotic tissue in the tarsal conjunctiva (stain, hematoxylin-eosin; original magnification, X40). Figure 4. Higher magnification shows confluent lakes of amorphous, eosinophilic frothy and vacuolated material with remnants of fibrovascular tissue. Note the absence of inflammatory infiltrates (stain, hematoxylin-eosin; original magnification, XlOO). Figure 5. Oomori methenamine silver stain (OMS) shows numerous oval and round cysts, some of which resemble collapsed ping-pong balls. They measure 3 to 7 J.Lm in diameter and are located within the necrotic tissue (stain, 90-minute OMS; original magnification, X322). Figure 6. High-power view of the conjunctival smear specimen shows a few toluidine blue-positive cysts (stain, toluidine blue 0; original magnification, X400).
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(intravenously). 31 •32 In our case, the efficacy of the initiated therapy could not be established because of the patient's demise. Only a small number of case descriptions with ophthalmic pneumocystosis, mainly chorioretinal infections, have appeared in the literature. 5 - 11 ' 21 - 23 •33 •34 This case reported herein of P. carinii conjunctivitis, along with the previous reports of chorioretinal lesions and orbital involvement, broadens the clinical spectrum of AIDSassociated ophthalmic pneumocystosis. The ophthalmologist may be the first to recognize extrapulmonary P. carinii manifestation and thus may play a crucial role in the management of this life-threatening opportunistic infection.
15. 16. 17. 18. 19. 20.
References 1. Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 1984; 100:66371. 2. Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988;334:519-22. 3. Matsumoto Y, Matsuda S, Tegoshi T. Yeast glucan in the cyst wall of Pneumocystis carinii. J Protozool 1989;36:21S-2S. 4. Raviglione MC. Extrapulmonary pneumocystosis: the first 50 cases. Rev Infect Dis 1990; 12:1127-38. 5. Freeman WR, Gross JG, Labelle J, et al. Pneumocystis carinii choroidopathy. A new clinical entity. Arch Ophthalmol 1989; 107:863-7. 6. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic, and electron microscopic study of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989; 107:218-28. 7. Macher AM, Bardenstein DS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection [letter]. N Engl J Med 1987;316:1092. 8. Shami MJ, Freeman W, Friedberg D, et al. A multicenter study of Pneumocystis choroidopathy. Am J Ophthalmol 1991; 112:15-22. 9. Hagopian W A, Huseby JS. Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulmonary prophylaxis. Chest 1989;96:949-51. 10. Kwok S, O'Donnell JJ, Wood IS. Retinal cotton-wool spots in a patient with Pneumocystis carinii infection [letter]. N Engl J Med 1982;307:184-5. 11. Friedberg DN, Warren FA, Lee MH, et al. Pneumocystis carinii of the orbit [letter]. Am J Ophthalmol 1992; 113:595-6. 12. Meuwissen JH, Tauber I, Leeuwenberg AD, et al. Parasitologic and serologic observations of infection with Pneumocystis in humans. J Infect Dis 1977; 136:43-9. 13. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978;61:3541. 14. Pilon VA, Echols RM, Celo JS, Elmendorf SL. Dissemin-
1856
21. 22. 23.
24.
25. 26. 27.
28.
29. 30.
31. 32. 33. 34.
ated Pneumocystis carinii infection in AIDS [letter]. N Engl J Med 1987;316:1410-1. Cohen OJ, Stoeckle MY. Extrapulmonary Pneumocystis carinii infections in the acquired immunodeficiency syndrome. Arch Intern Med 1991;151:1205-14. Barnett RN, Hull JG, Vortel V, Schwarz J. Pneumocystis carinii in lymph nodes and spleen. Arch Pathol 1969;88:175-80. Rahimi SA. Disseminated Pneumocystis carinii in thymic alymphoplasia. Arch Pathol 1974;97:162-5. Awen CF, Baltzan MA. Systemic dissemination of Pneumocystis carinii pneumonia. Can Med Assoc J 1971; 104:809-12. Jamum S, Rasmussen EF, Ohlsen AS, Sorensen A W. Generalized Pneumocystis carinii infection with severe idiopathic hypoproteinemia. Ann Intern Med 1968;68:138-45. Rossi IF, Dubois A, Bengler C, et al. Pneumocystis carinii in bone marrow [letter]. Ann Intern Med 1985; 102:868. Sneed SR, Blodi CF, Berger BB, et al. Pneumocystis carinii choroiditis in patients receiving inhaled pentamidine [letter]. N Engl J Med 1990;322:936-7. Dugel PU, Rao NA, Forster DJ, et al. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1990; 110:113-7. Foster RE, Lowder CY, Meisler DM, et al. Presumed Pneumocystis carinii choroiditis. Unifocal presentation, regression with intravenous pentamidine, and choroiditis recurrence. Ophthalmology 1991;98:1360-5. Hardy WD, Northfelt DW, Drake TA. Fatal, disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine. Am J Med 1989;87:329-31. Sparling TG, Dong SR, Hegedus C, Burdge DR. Aerosolized pentamidine and disseminated infection with Pneumocystis carinii [letter]. Ann Intern Med 1989; 111:442-3. Kovacs JA, Gill V, Swan JC, et al. Prospective evaluation of a monoclonal antibody in diagnosis of Pneumocystis carinii pneumonia. Lancet 1986;2:1-3. Gosey LL, Howard RM, Witebsky FG, et al. Advantages of modified toluidine blue 0 stain and bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia. J Clin Microbiol 1985;22:803-7. Ng VL, Yajko DM, McPhaul LW, et al. Evaluations of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens. J Clin Microbiol 1990;28:975-9. Elvin K. Laboratory diagnosis and occurrence of Pneumocystis carinii. Scand J Infect Dis Suppl 1994; 94:1-34. Carter TR, Cooper PH, Petri W A, Jr, et al. Pneumocystis carinii infection of the small intestine in a patient with acquired immunodeficiency syndrome. Am J Clin Pathol 1988;89:679-83. Huang L, Stansell JD. AIDS and the lung. Med Clin North Am 1996;80:775-801. Miller RF, Mitchell DM. Pneumocystis carinii pneumonia. Thorax 1995;50:191-200. Koser MW, Jampol LM, MacDonell K. Treatment of Pneumocystis carinii choroidopathy [letter]. Arch Ophthalmol 1990; 108:1214-5. Sha BE, Benson CA, Deutsch T, et al. Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. J Acquir Immune Defic Syndr 1992;5:1051-8.
Originally received: February 20, 1997. Revision accepted: May 19, 1997. 1 Department of Ophthalmology, University Hospital of ZUrich, ZUrich, Switzerland. 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital of ZUrich, ZUrich, Switzerland.
3 Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. 4
Department of Pathology, Division of Cytopathology, University Hospital of ZUrich, ZUrich, Switzerland.
Supported in part by grants from the Retina Research Foundation, Houston, Texas, and Research to Prevent Blindness Inc., New York, New York. The authors have no proprietary interest in the products or techniques described in this article. Reprint requests to Gian Marco Ruggli, MD, University of ZUrich, Department of Ophthalmology, Frauenklinikstrasse 24, CH-8091 ZUrich, Switzerland.
Pneumocystis carinii is an important opportunistic pathogen in patients with congenital or acquired immune deficiencies.1 The taxonomic status of this eukaryotic microorganism has not been clarified fully. The monocellular parasite, which is exclusively present in the extracellular space, shows many morphologic features of protozoa, but is considered by some investigators to be a fungus. 2•3 Pulmonary P. carinii infection is the most common lifethreatening complication in patients with acquired immune deficiency syndrome (AIDS). Extrapulmonary infection or dissemination of the parasite is rare (<1%). 4 Among more than 50 cases of extrapulmonary pneumocystosis that have been reported, the most common sites of involvement are lymph nodes, spleen, liver, bone marrow, gastrointestinal tract, eyes, thyroid gland, adrenal gland, and kidneys. 4 Pneumocystis choroidopathy,5 - 9 retinal manifestations, 10 and orbital involvement11 are the most common ophthalmic manifestations of extrapulmonary AIDS-associated P. carinii infection.
1853
Ophthalmology
Volume 104, Number 11, November 1997
To our knowledge, AIDS-associated conjunctivitis due to P. carinii has not yet been reported. We describe the clinical features and histologic findings of a unique case of P. carinii infection with conjunctival involvement.
Case Report A 33-year-old white homosexual man was found to be human immunodeficiency virus-antibody positive in February 1990, and AIDS was diagnosed in April 1995. A total helper-cell (CD4) depletion was present since June 1995. His general condition progressively deteriorated. Severe anemia of unknown origin developed as well as a disseminated Mycobacterium avium infection. He was treated with different combinations of antimycobacterial agents. Since January 1994, he was receiving prophylaxis for P. carinii pneumonia using aerosolized pentamidine. A systemic trimethoprim-sulfamethoxazole chemoprophylaxis was not tolerated. There were never signs or symptoms of pulmonary infection due to P. carinii. In January 1996, he noted an irritation of his right eye, and he was referred for examination to the ophthalmology department. Except for a moderate myopia and a history of explosion trauma with superficial corneal involvement 20 years ago, his ocular history was unremarkable. Ophthalmic examination showed a visual acuity of 16/20 in the right eye and 20/20 in the left eye. The tarsal conjunctiva of his right upper lid showed a slightly elevated, placoid, white avascular lesion with well-defined borders. Approximately half of the subtarsal area and the margin of the upper lid were involved (Figs 1, 2). The adjacent conjunctiva was slightly hyperemic but without follicular or papillary reactions. Both corneas showed diffusely distributed punctate subepithelial opacities with inclusions of foreign material. The anterior chambers were quiet and the fundi were normal. Steroid drops were prescribed, and 2 weeks later two punch biopsy specimens were taken from the lesion of the tarsal conjunctiva with the patient under local anesthesia. Because of the difficulties establishing the correct diagnosis histopathologically, additional conjunctival smears were taken from the affected eye. After the diagnosis of extrapulmonary P. carinii infection had been established by examination of the conjunctival specimens, the patient started receiving oral treatment with dapsone and trimethoprim. The efficacy of this regimen, however, could not be established because the moribund patient died, most probably because of a disseminated atypical mycobacterial infection. Unfortunately, postmortem examination was not performed.
Biopsy and Laboratory Findings Microscopic examination of the biopsy specimen showed that the tissue of the affected area was partly covered by normal conjunctival mucosa. The underlying stroma showed confluent lakes of amorphous eosinophilic frothy and vacuolated material with remnants of fibrovascular tissue (Figs 3, 4). The deposits were bordered by areas of reactive fibroblastic proliferation and capillary sprouting. There were no inflammatory infiltrates. Gomori methenamine silver stain showed numerous round-to-oval cysts within the necrotic tissue, some of which resemble pingpong balls, that measure 3 to 7 J..Lm in diameter (Fig 5). No other micro-organisms were identified. Based on these
1854
findings, the diagnosis of P. carinii conjunctivitis was established. Light microscopy of conjunctival smear specimen showed numerous toluidine blue-positive cysts (Fig 6). Furthermore, indirect immunofluorescence using monoclonal mouse anti-P. carinii antibodies (DAKO, Glostrup, DK) showed P. carinii cysts.
Discussion Because of a profound defect in cell-mediated immunity, patients with AIDS are susceptible to many opportunistic infections. Among these, P. carinii pneumonia is one of the most common life-threatening complications. Pneumocystosis in patients with immunologic disorders appears to be the result of reactivation of latent disease because there is serologic documentation of widespread (nearly 100%) acquisition of anti-Pneumocystis antibodies in early childhood. 12'13 Despite the high frequency of lung infections caused by P. carinii in immunosuppressed persons, extrapulmonary dissemination rarely occurs. 4·14 The pathogenesis of extrapulmonary P. carinii infection is not fully understood. It might occur by hematogenous or lymphatic dissemination from the lungs, reactivation of latent infection in extrapulmonary sites, or primary infection of these sites. 15 Cases of extrapulmonary P. carinii infection not associated with the AIDS epidemic have been reported in children with hypogammaglobulinemia 16·17 and in adults with a variety of immunodeficiency states (e.g., leukemia, 16 immunosuppressive therapy, 18 idiopathic hypoproteinemia, 19 and lymphoma20). The first report of extrapulmonary P. carinii manifestation associated with AIDS described retinal involvement in a patient who died of P. carinii pneumonia. 10 Since then, pneumocystosis with extrapulmonary involvement with or without concomitant pneumonia is increasingly recognized in patients with AIDS, especially among those receiving inhaled pentamidine prophylaxis. 6·9·11 •21 - 25 This method of aerosolized administration shows only little extrapulmonary distribution and, therefore, is ineffective both in controlling and preventing a disseminated P. carinii infection. In addition, many authors expressed concern that the aerosolized administration even facilitates disseminated infection. 24 ' 25 Still, this association remains unconfirmed and needs further investigations. 15 The diagnosis of pneumocystosis rests on the identification of cysts or trophozoites in secretions or exudates of tissue or both or in biopsy specimens. Visualization of the organism with special stains, the most useful of which are the Gomori methenamine silver nitrate, modified toluidine blue 0 stain, and immunohistochemical techniques with monoclonal antibodies, 26 - 29 confirms the diagnosis. Ultrastructural examination is helpful but usually not required.30 At present, trimethoprim-sulfamethoxazole (orally or intravenously) remains the treatment of choice for P. carinii infection. Other regimens include dapsone/trimethoprim (orally), clindamycinlprimaquine (orally or intravenously), atovaquone (orally), or pentamidine isethionate
Ruggli et al · Infection of the Conjunctiva in a Patient with AIDS
Figure 1. Clinical appearance of the right upper tarsal conjunctiva with a slightly elevated, plaque-like, white avascular lesion, which involves approximately half of the subtarsal area. Figure 2. Detail of the lid, as shown in Figure 1. The lesion is restricted to the mucous membrane and does not involve the skin. Figure 3. Low-power view of the biopsy specimen discloses areas of necrotic tissue in the tarsal conjunctiva (stain, hematoxylin-eosin; original magnification, X40). Figure 4. Higher magnification shows confluent lakes of amorphous, eosinophilic frothy and vacuolated material with remnants of fibrovascular tissue. Note the absence of inflammatory infiltrates (stain, hematoxylin-eosin; original magnification, XlOO). Figure 5. Oomori methenamine silver stain (OMS) shows numerous oval and round cysts, some of which resemble collapsed ping-pong balls. They measure 3 to 7 J.Lm in diameter and are located within the necrotic tissue (stain, 90-minute OMS; original magnification, X322). Figure 6. High-power view of the conjunctival smear specimen shows a few toluidine blue-positive cysts (stain, toluidine blue 0; original magnification, X400).
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Volume 104, Number 11, November 1997
(intravenously). 31 •32 In our case, the efficacy of the initiated therapy could not be established because of the patient's demise. Only a small number of case descriptions with ophthalmic pneumocystosis, mainly chorioretinal infections, have appeared in the literature. 5 - 11 ' 21 - 23 •33 •34 This case reported herein of P. carinii conjunctivitis, along with the previous reports of chorioretinal lesions and orbital involvement, broadens the clinical spectrum of AIDSassociated ophthalmic pneumocystosis. The ophthalmologist may be the first to recognize extrapulmonary P. carinii manifestation and thus may play a crucial role in the management of this life-threatening opportunistic infection.
15. 16. 17. 18. 19. 20.
References 1. Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med 1984; 100:66371. 2. Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988;334:519-22. 3. Matsumoto Y, Matsuda S, Tegoshi T. Yeast glucan in the cyst wall of Pneumocystis carinii. J Protozool 1989;36:21S-2S. 4. Raviglione MC. Extrapulmonary pneumocystosis: the first 50 cases. Rev Infect Dis 1990; 12:1127-38. 5. Freeman WR, Gross JG, Labelle J, et al. Pneumocystis carinii choroidopathy. A new clinical entity. Arch Ophthalmol 1989; 107:863-7. 6. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic, and electron microscopic study of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989; 107:218-28. 7. Macher AM, Bardenstein DS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection [letter]. N Engl J Med 1987;316:1092. 8. Shami MJ, Freeman W, Friedberg D, et al. A multicenter study of Pneumocystis choroidopathy. Am J Ophthalmol 1991; 112:15-22. 9. Hagopian W A, Huseby JS. Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulmonary prophylaxis. Chest 1989;96:949-51. 10. Kwok S, O'Donnell JJ, Wood IS. Retinal cotton-wool spots in a patient with Pneumocystis carinii infection [letter]. N Engl J Med 1982;307:184-5. 11. Friedberg DN, Warren FA, Lee MH, et al. Pneumocystis carinii of the orbit [letter]. Am J Ophthalmol 1992; 113:595-6. 12. Meuwissen JH, Tauber I, Leeuwenberg AD, et al. Parasitologic and serologic observations of infection with Pneumocystis in humans. J Infect Dis 1977; 136:43-9. 13. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978;61:3541. 14. Pilon VA, Echols RM, Celo JS, Elmendorf SL. Dissemin-
1856
21. 22. 23.
24.
25. 26. 27.
28.
29. 30.
31. 32. 33. 34.
ated Pneumocystis carinii infection in AIDS [letter]. N Engl J Med 1987;316:1410-1. Cohen OJ, Stoeckle MY. Extrapulmonary Pneumocystis carinii infections in the acquired immunodeficiency syndrome. Arch Intern Med 1991;151:1205-14. Barnett RN, Hull JG, Vortel V, Schwarz J. Pneumocystis carinii in lymph nodes and spleen. Arch Pathol 1969;88:175-80. Rahimi SA. Disseminated Pneumocystis carinii in thymic alymphoplasia. Arch Pathol 1974;97:162-5. Awen CF, Baltzan MA. Systemic dissemination of Pneumocystis carinii pneumonia. Can Med Assoc J 1971; 104:809-12. Jamum S, Rasmussen EF, Ohlsen AS, Sorensen A W. Generalized Pneumocystis carinii infection with severe idiopathic hypoproteinemia. Ann Intern Med 1968;68:138-45. Rossi IF, Dubois A, Bengler C, et al. Pneumocystis carinii in bone marrow [letter]. Ann Intern Med 1985; 102:868. Sneed SR, Blodi CF, Berger BB, et al. Pneumocystis carinii choroiditis in patients receiving inhaled pentamidine [letter]. N Engl J Med 1990;322:936-7. Dugel PU, Rao NA, Forster DJ, et al. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1990; 110:113-7. Foster RE, Lowder CY, Meisler DM, et al. Presumed Pneumocystis carinii choroiditis. Unifocal presentation, regression with intravenous pentamidine, and choroiditis recurrence. Ophthalmology 1991;98:1360-5. Hardy WD, Northfelt DW, Drake TA. Fatal, disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine. Am J Med 1989;87:329-31. Sparling TG, Dong SR, Hegedus C, Burdge DR. Aerosolized pentamidine and disseminated infection with Pneumocystis carinii [letter]. Ann Intern Med 1989; 111:442-3. Kovacs JA, Gill V, Swan JC, et al. Prospective evaluation of a monoclonal antibody in diagnosis of Pneumocystis carinii pneumonia. Lancet 1986;2:1-3. Gosey LL, Howard RM, Witebsky FG, et al. Advantages of modified toluidine blue 0 stain and bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia. J Clin Microbiol 1985;22:803-7. Ng VL, Yajko DM, McPhaul LW, et al. Evaluations of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens. J Clin Microbiol 1990;28:975-9. Elvin K. Laboratory diagnosis and occurrence of Pneumocystis carinii. Scand J Infect Dis Suppl 1994; 94:1-34. Carter TR, Cooper PH, Petri W A, Jr, et al. Pneumocystis carinii infection of the small intestine in a patient with acquired immunodeficiency syndrome. Am J Clin Pathol 1988;89:679-83. Huang L, Stansell JD. AIDS and the lung. Med Clin North Am 1996;80:775-801. Miller RF, Mitchell DM. Pneumocystis carinii pneumonia. Thorax 1995;50:191-200. Koser MW, Jampol LM, MacDonell K. Treatment of Pneumocystis carinii choroidopathy [letter]. Arch Ophthalmol 1990; 108:1214-5. Sha BE, Benson CA, Deutsch T, et al. Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. J Acquir Immune Defic Syndr 1992;5:1051-8.