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Cryptococcosis
Pulmonary cryptococcosis is the second most common form of cryptococcosis, after cryptococcal meningitis. Even thought there is evidence that Cryptococcus neoformans virtually always enters the body through the respiratory tract, lung disease is asymptomatic in the majority of cases. The broad range of non-specific clinical and radiologic manifestations related to this infection are determined by the immunocompetence of the host. When the immune system is intact, findings are mostly radiographic and incidental and end-up with the label of pulmonary cryptococcosis when sufficient diagnostic efforts are pursued. On the other hand, immunosuppressed patients commonly have pulmonary involvement as part of disseminated disease and may occasionally have major respiratory symptoms requiring specific therapy.
Relevant ecological and epidemiological characteristics of this fungi have been described elsewhere.
There are no precise data on the incidence of pulmonary cryptococcal disease.First, in contrast to other endemic mycosis like histoplamosis or coccidiodomycosis, there is no skin test to determine the number of people exposed to this fungi. Second, calcification of healed lung lesions in this endemic mycosis is very rare, thus making radiographic surveys impossible. Finally, it is not mandatory to report this entity to the health authorities. In view of that, we will focus the following discussion mostly on data retrieved from case reports.
- Normal hosts
Geraci et. al encountered 13 cases at Mayo Clinic in a 6-year period (1958 to 1964), most of them asymptomatic and all diagnosed through surgical excision when patients with undiagnosed radiologic abnormalities were taken to the operatory room [826]. Perkins reported 9 similar cases, for the period 1953 to 1965 [1762]. According to Gordonson et al., only 26 cases of pulmonary cryptococcosis were diagnosed from 1942 to 1972 at Southern California Medical Center. These cases represented 39% of all cryptococcosis cases seen at that institution [876].Campbell et al. reviewed 101 cases, 97 of them published in the literature prior to this report. Only 10% of them were related to underlying diseases, several of which (tuberculosis, silicosis, pemphigus vulgaris) are probably poorly related but explained why exhaustive diagnostic workups were pursued. Hammerman et. al, from the CDC Cooperative Mycoses Study group, studied 80 cases from 1957 to 1971, half of which were considered to be "colonized" because there was no evidence of tissue invasion or clinical disease [978]. McDonnell et. al reviewed 36 casese diagnosed at autposy from 1936 to 1983 at Johns Hopkins Hospital, of which only two were diagnosed prior to death [1481]. From these series we can conclude that pulmonary cryptococcosis occurs sporadically, affects predominantly previously healthy middle age (30-50 y.o.) white men, and is frequently asymptomatic.
- HIV-positive patients
Before the introduction of highly-active antiretroviral therapy, cryptococcocosis explained 2 to 15% of pneumonia cases in patients with AIDS [1539]. The majority of these patients had concomitant cryptococcal meningitis [366]. From another perspective, cryptococcal pneumonia represents between 30 to 40% of cases of cryptococcosis in the HIV-infected population [366, 441, 1530].
- HIV-negative immunosupressed patients
During the last decade, the majority of non-AIDS immunocompromised hosts with cryptococcal pneumonia belonged to the category of organ transplant recipients [1181, 1733, 2324]. Paterson's series reviewed causes of pulmonary nodules among 11 patients from a cohor of 155 liver transplant recipients [1733]. Pulmonary cryptococcosis was the second most common cause after aspergillosis. A particular situation can occur in lung transplant-recipients--Kanj et. al reported a case in which the recipient developed a pulmonary cryptococcosis after receiving an organ carrying C. neoformans [1149].
Risk factors
Besides the classical risk factors for cryptococcocosis, the only other disease related to pulmonary cryptococcosis is alveolar proteinosis [368, 2198].
- Asymptomatic
In the normal host, an important number of cases are incidently diagnosed when having a screening chest radiograph [368, 1762]. The large majority of these patients are completely asymptomatic. In the series by Campbell et. al, 32% of cases were in this category [368]. As discussed above, certain diagnostic limitations make particularly difficult the diagnosis of spontaneously healed pulmonary cryptococcosis like the ones occurring in cases of histoplamosis or tuberculosis. However, it is very likely that most cases of cryptococcal lung disease are, indeed, asymptomatic [390].
- Chronically ill patients
When symptomatic, patients will complain for variable periods of time of any of the following symptoms: fever, night sweats, productive cough, shortness of breath, chest pain, weigth loss, general malaise, weakness, and/or hemoptysis. Immunocompromised individuals (patients with cancer, AIDS or under corticosteroid therapy) usually have disseminated disease and therefore may have concurrent CNS manifestations, skin and/or urinary disease [1181, 1539]. Indeed, Kerkering et al. reported 17 cases of pulmonary cryptococcosis that were identified only after the diagnosis of meningeal involvement [1181]. From the same series, 29 out of 34 (85%) patients with cryptococcal pneumonia developed disseminated disease. Only one of the 29 was an immunocompetent host. These patterns also appear valid for patients with AIDS. From a restrospective reviewed of cryptococcal pneumonia in AIDS patients at Duke University, 11 out of 12 had positive CSF cultures [366]. The small series by Miller et al. reported 7 similar cases of cryptococcal pneumonia, all of which had evidence of meningeal involvement [366].
- Acutely ill
Cryptococcal pneumonia can occaisonally present as an acute and severe lower respiratory infection causing acute respiratory failure (ARF) [1027, 1601, 1763, 2110, 2324]. This presentation seems to be particularly frequent in patients with AIDS. Vinegarwala et al. comprehensively studied a cohort of 210 AIDS patients with cryptococcosis and encountered that as high as 14% of them developed life-threatening ARF. This clinical picture impose a major diagnostic challenge in this populations as it looks clinical and radiolagically identical to Pneumocystis carinii pneumonia [2335]. Cryptococcal ARF has been described only once in a normal host [2478].
Another unusual presentation is the development of pneumothorax or pneumomediastinum [53, 2244].
A unique report of a patient presenting clinical picture called "allergic cryptococcal pneumonia" has been published [831]. This patient presented with urticaria, hypotension, and shortness of breath in relation with a cryptococcal infection.
The combination of any of the following patterns have been described in pulmonary cryptococcosis:
- Unilateral or bilateral, solitary or multiple coin or mass lesions [826, 876, 1181].
This presentation seems to be more common among immunecompentent patients [390]. Indeed, none of the AIDS patients of series of cryptococcal pneumonia in this population have had this radiologic finding [366, 1530, 1539].
- Unilateral or bilateral interstitial infiltrates [368, 826, 876].
This presentation has consistenly been described among immunocompromised hosts including patients with AIDS [366, 1530]. Patients with acute respiratory failure and AIDS usually have this radiologic pattern [2335]. As discussed above, the differential diagnosis should include several other common lung infections including Pneumocystis carinii pneumonia [366, 2335]. In some cases, a nodular pattern similar to that of miliary tuberculosis is described [1539].
- Pleural effusions.
Probably explained by the frequent histopathologic reports of frequent subpleural lung nodules, pleural effussions have been described both in normal and immunocompromised hosts [826, 1181, 1539, 2011].
- Massive hilar adenopathy [826, 876]
Salyer et. al described a primary pulmonary-lymph nodal complex, similar to that seen in pulmonary tuberculosis [2011]. These authors postulated that radiologic evidence of these residual granulomas are rare because of lack of calcification. Mitchell and Sorrell report a case of cryptococcal-related Pancoast's syndrome (upper lobe consolidation plus massive enlargement of supraclavicular lymph nodes) [1546]. However, a large autopsy series encountered only 1 out 36 cases of this [1481].
- Cavitary lesions
Cavitation of localized foci of pneumonia account is one of the possible radiologic features of cryptococcal pneumonia. However, when comparing rates of occurance in different series a broad range is seen [826, 876, 1181].
- Cavitary lesions and pulmonary cryptococcosis
| |
Series |
| [826] |
[368] |
[2379] |
[1762] |
[876] |
N |
13 |
101 |
17 |
9 |
26 |
| Proportion with cavitary lesions |
23% |
16% |
0 |
0 |
8% |
Microbiology data
- Respiratory samples
Physician meet an important dilemma when dealing with sputum and even a bronchial fluid positive for Cryptococcus neoformans. Warr et. al reviewed the experience of isolating Cryptococcus neoformans at several hospitals in Arkansas, USA over a 7-year period. Seventeen patients had the fungi isolated from sputum, bronchial washing or pleural fluid. Only nine out of 17 cases (53%) were considered to have definitive pulmonary cryptococcosis [2379]. The others have either transitory colonization or spontaneous remission. Colonization seems to be particularly common in patient with other lung diseases like chronic obstructive pulmonary disease [978]. On the contrary, isolations of Cryptococcus neoformans from a patient with AIDS should be taken seriously as this a frequent sign of disseminated infecton [1539]. Indeed, several of the previously discussed cases of ARF were diagnosed by examining bronchioalveolar fluid [2335].
- Cryptococcal antigen
Importantly, both pleural or bronchioalveolar fluids will usually contains polysaccharide antigens, so performing a latex agglutination test is a logic diagnostic step [1595, 2335].
- Pleural fluid studies
In cases of cryptococcal-related pleural effusion, the pleural fluid is expected to be exudative but there is no absolut rule about this. Certain cases have presented with an obvious empyema [1595, 2229].
Histopatological data
As mentioned before, pulmonary cryptococcosis in normal hosts is frequently been diagnosed when pursuing a clear diagnosis in patient with abnormal chest X-rays [826]. McDonnell et. al described specific histologic patterns when assesing the autpsies of 36 cases [1481]. They include:
a) Granulomatous pneumonia. These cases had a bronchoneumonic pattern with variable grades of granulomatous inflammatory response. Proliferating Cryptococcus spp. were seen within alveolar spaces and large aiways often confined within multinucleated giant cells.
b) Granulomas, frequently peripherals or subpleural.
c) Intracapillary/interstitial infection.
d) Massive pulmonary involvement.
Finally, besides the previously mentioned studies, as strees by IDSA guidelines is very important to follow the indication of performing a lumbar puncture in all patients with diagnosis of pulmonary cryptococcosis. Immunocompetent patients with isolated sputum culture positive for C. neoformans, should be closely follow for 3 to 6 months if the CNS infection is not rule out.
Special resource: You may also want to refer to theInfectious Disease Society of America-Mycoses Study Group (IDSA-MSG) Practice Guidelines for this disease. It is available at the IDSA website.
No therapy
Several reports have documented the spontaneous resolution of cases of isolated pulmonary cryptococcosis [978, 1181]. Accordingly, it has been advocated that clinical observation could be enough for asymptomatic healthy hosts. However, current guidelines recommend considering treatment in all patients, regardless of the grade of symptoms [1993].
Antifungal therapy
- Guidelines for the treatment of pulmonary cryptococcosis are essentially based on the studies that have been performed in HIV-positive patients with CNS cryptococcosis. Therefore, the following indications for immunocompetent patients have not been validated with adequate data but are reasonable supported by current knowledge on susceptibility data and pharmacological properties of available antifungals [1993].
When deciding treatment for pulmonary cryptococcosis the most important variables to consider are:
- Grade of dissemination.
If there is evidence of meningeal involvement patient should be treated accordingly.
- Host immune status.
HIV-negative immunocompromised patients should receive the same regimen recommended for meningeal cryptococcosis.
- Symptomatology.
Immunocompentent patients treatement should be based on the severity of pulmonary symptoms.
Normal hosts with mild to moderate symptomatology can be treated with any of the following options:
- Fluconazole 200-400 mg/day for 6 to 12 months.
- Itraconazole 200-400 mg/day for 6 to 12 months.
- Amphotericin B 0.7-1 mg/kg/day (total 1000-2000 mg).
Normal hosts with severe symptomatology should be treated like cases of CNS cryptococcosis
Surgical treatment
Thoracotomy with resection of diseased tissue (partial or complete lobectomies) have proven to be enough to cure patients with isolated pulmonary masses [368, 1762]. However, the main reason why these patients ended up having surgical intervention, was to rule out a malignant pulmonary lesion [1957]. These days, surgery is not recommended except for cases of pseudotumorlike lesions [1546].
Finally, cases of severe exudative pleural effusions may require tube drainage and even decortication [1595, 1762, 2229]
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References
53. Alonso-Villaverde, C., S. Hernandez-Flix, R. Tomas, and L. Masana. 1992. [Occurrence of pneumothorax and pneumomediastinum in a patient with AIDS and pulmonary infection caused by Pneumocystis carinii and Cryptococcus neoformans]. Rev Clin Esp. 191:397-8.
366. Cameron, M. L., J. A. Bartlett, H. A. Gallis, and H. A. Waskin. 1991. Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome. Rev. Infect. Dis. 13:64-67.
368. Campbell, G. D. 1966. Primary pulmonary cryptococcosis. Am. Rev. Respir. Dis. 94:236-243.
390. Casadevall, A., and J. R. Perfect. 1998. Cryptococcus neoformans. ASM Press, Washington, D.C.
441. Chuck, S. L., and M. A. Sande. 1989. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N. Engl. J. Med. 321:794-799.
826. Geraci, J. E., F. E. Donoghue, F. H. Ellis, Jr., D. M. Witten, and L. A. Weed. 1965. Focal pulmonary cryptococcosis: Evaluation of necessity of amphotericin B therapy. Mayo Clin. Proc. 40:552-559.
831. Gerstenhaber, B. J., B. Weiner, R. Morecki, R. Bernstein, and S. Luftschein. 1977. "Allergic" cryptococcal pneumonia. Lung. 154:195-9.
876. Gordonson, J., W. Birnbaum, G. Jacobson, and E. N. Sargent. 1974. Pulmonary cryptococcosis. Radiology. 112:557-561.
978. Hammerman, K. J., K. E. Powell, C. S. Christianson, P. M. Huggin, H. W. Larsh, J. R. Vivas, and F. E. Tosh. 1973. Pulmonary cryptococcosis: Clinical forms and treatment. A Center for Disease Control Coooperative Mycoses Study. Am. Rev. Respir. Dis. 108:1116-1123.
1027. Henson, D. J., and A. R. Hill. 1984. Cryptococcal pneumonia: a fulminant presentation. Am J Med Sci. 288:221-2.
1149. Kanj, S. S., K. Welty-Wolf, J. Madden, V. Tapson, M. A. Baz, R. D. Davis, and J. R. Perfect. 1996. Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature. Medicine (Baltimore). 75:142-56.
1181. Kerkering, T. M., R. J. Duma, and S. Shadomy. 1981. The evolution of pulmonary cryptococcosis. Clinical implications from a study of 41 patients with and without compromising host factors. Ann. Intern. Med. 94:611-616.
1481. McDonnell, J. M., and G. M. Hutchins. 1985. Pulmonary cryptococcosis. Hum. Pathol. 16:121-128.
1530. Meyohas, M.-C., P. Roux, D. Bollens, C. Chouaid, W. Rozenbaum, J.-L. Meynard, J.-L. Poirot, J. Frottier, and C. Mayaud. 1995. Pulmonary cryptococcosis: localized and disseminated infections in 27 patients with AIDS. Clin. Infect. Dis. 21:628-633.
1539. Miller, W. T., Jr., J. M. Edelman, and W. T. Miller. 1990. Cryptococcal pulmonary infection in patients with AIDS: Radiographic appearance. Radiology. 175:725-728.
1546. Mitchell, D. N., and T. C. Sorrell. 1992. Pancoast's syndrome due to pulmonary infection with Cryptococcus neoformans variety gattii. Clin. Infect. Dis. 14:1142-1144.
1595. Mulanovich, V. E., W. E. Dismukes, and N. Markowitz. 1995. Cryptococcal empyema: Case report and review. Clin. Infect. Dis. 20:1396-1398.
1601. Murray, R. J., P. Becker, P. Furth, and G. J. Criner. 1988. Recovery from cryptococcemia and the adult respiratory distress syndrome in the acquired immunodeficiency syndrome. Chest. 93:1304-6.
1733. Paterson, D. L., N. Singh, T. Gayowski, and I. R. Marino. 1998. Pulmonary nodules in liver transplant recipients. Medicine (Baltimore). 77:50-8.
1762. Perkins, W. 1969. Pulmonary cryptococcosis: Report on the treatment of nine cases. Chest. 56:389-394.
1763. Perla, E. N., S. Maayan, S. N. Miller, G. Ramaswamy, and H. Eisenberg. 1985. Disseminated cryptococcosis presenting as the adult respiratory distress syndrome. N Y State J Med. 85:704-6.
1957. Rolston, K. V. I., S. Rodriguez, N. Dholoaki, E. Whimbey, and I. Raad. 1997. Pulmonary infections mimicking cancer: A retrospective, three-year review. Support Care Cancer. 5:90-93.
1993. Saag, M. S., R. J. Graybill, R. A. Larsen, P. G. Pappas, J. R. Perfect, W. G. Powderly, J. D. Sobel, W. E. Dismukes, and the Mycoses Study Group Cryptococcal Subproject. 2000. Practice guidelines for the management of cryptococcal disease. Clin. Infect. Dis. 30:710-718.
2011. Salyer, W. R., and D. C. Salyer. 1974. Pleural involvement in cryptococcosis. Chest. 66:139-140.
2110. Similowski, T., A. Datry, P. Jais, C. Katlama, M. Rosenheim, and M. Gentilini. 1989. AIDS-associated cryptococcosis causing adult respiratory distress syndrome. Respir Med. 83:513-5.
2198. Sunderland, W. A., R. A. Campbell, and M. J. Edwards. 1972. Pulmonary alveolar proteinosis and pulmonary cryptococcosis in an adolescent boy. J. Pediatr. 80:450-456.
2229. Tenholder, M. F., F. W. Ewald, Jr., N. K. Khankhanian, and J. H. Crosby. 1992. Complex cryptococcal empyema. Chest. 101:586-8.
2244. Torre, D., R. Martegani, F. Speranza, C. Zeroli, and G. P. Fiori. 1995. Pulmonary cryptococcosis presenting as pneumothorax in a patient with AIDS. Clin. Infect. Dis. 21:1524-1525.
2324. Vilchez, R. A., P. Linden, J. Lacomis, P. Costello, J. Fung, and S. Kusne. 2001. Acute respiratory failure associated with pulmonary cryptococcosis in non-AIDS patients. Chest. 119:1865-1869.
2335. Visnegarwala, F., E. A. Graviss, C. E. Lacke, A. T. Dural, P. C. Johnson, R. L. Atmar, and R. J. Hamill. 1998. Acute respiratory failure associated with cryptococcosis in patients with AIDS: Analysis of predictive factors. Clin Infect Dis. 27:1231-1237.
2379. Warr, W., J. H. Bates, and A. Stone. 1968. The spectrum of pulmonary cryptococcosis. Ann. Intern. Med. 69:1109-1116.
2478. Yu, F. C., W. C. Perng, C. P. Wu, C. Y. Shen, and H. S. Lee. 1993. Adult respiratory distress syndrome caused by pulmonary cryptococcosis in an immunocompetent host: a case report. Chung Hua I Hsueh Tsa Chih (Taipei). 52:120-4.
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