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Pulmonary cryptococcosis in non-AIDS patients.

Introduction

Pulmonary cryptococcosis refers to acute or chronic infections of the lungs caused by cryptococcus. Cryptococcal infection can occur in individuals with normal immunity, but is more common in immunocompromised hosts, especially in human immunodeficiency virus (HIV) carriers and recipients of organ transplants. The clinical presentations, radiographic features, and laboratory investigations of pulmonary cryptococcosis are generally non-specific, so it may easily be misdiagnosed or underdiagnosed. The aim of this study was to identify the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients by retrospective analysis of 24 patients admitted to this hospital from November 1999 to November 2011.

The study was approved by the institutional review board. The requirement for a signed informed consent form was waived by the institutional review board due to the retrospective nature of the study.

Material and methods

Study patients

This study included 15 male patients and nine female patients, who were both admitted and diagnosed in the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The diagnoses were confirmed by positive pathology.

Data collection

All the clinical features, treatments, and prognoses of these patients were retrospectively analysed based upon their medical records. Patients without complete, detailed medical records were excluded from this study.

Results

Gender and age

Among these 24 patients, there were 15 male and nine female. Their ages ranged from 24 to 65 years, and the mean ([+ or -] SD) age at the time of diagnosis was 44.2 ([+ or -] 11.3) years.

Occupation and epidemiological histories

Five patients were exposed to poultry (including pigeons, turtle doves, and their feces). Four had close contact with soil (three patients were peasants and one was a geologist), and two worked in a hospital (No. 8 was a nurse while her son No. 22 worked in the clinical microbiology laboratory of the hospital). The remaining 13 patients had no specific epidemiological exposures.

Pre-existing conditions and immune competence

Patients' pre-existing conditions are summarized in Table 1. Of the 24 patients, 13 (54.2%) had comorbidities as follows: chronic viral hepatitis B (four patients, 16.7%), chronic kidney disease (four patients, 16.7%), pulmonary tuberculosis (two patients, 8.3%), diabetes mellitus (two patients, 8.3%), hypertension (one patient, 4.2%), coronary heart disease (one patient, 4.2%), hyperthyroidism (two patients, 8.3%), thyroid carcinoma (one patient, 4.2%), or myasthenia gravis with thymoma (one patient, 4.2%); three patients had two or more comorbidities. All patients were HIV-negative by serologic tests, and none was organ transplant recipient. However, five (20.8%) of these patients were immunocompromised; four had taken corticosteroids for over six months, and one had received chemotherapy for malignancy.

Symptoms and signs

None of these patients had concurrent cryptococcal meningitis based on the absence of meningeal irritation signs and symptoms of intracranial hypertension. 15 patients (62.5%) were symptomatic, including cough (nine patients, 37.5%), chest tightness (eight patients, 33.3%), expectoration (six patients, 25.0%), and fever (six patients, 25.0%, body temperature ranged from 37.7[degrees]C to 39.4[degrees]C). Nine patients (37.5%) were totally asymptomatic. Among them, six had abnormalities on chest X-ray during routine check-ups, and the remaining three had some noted changes on their chest X-rays during the treatment of other diseases. All asymptomatic patients were immunocompetent. Ten of the 19 individuals with immunocompetent were symptomatic (52.6%), and all five (100%) immunocompromised patients were symptomatic. Physical examinations revealed diminished respiratory sounds in only three patients. All patients had pulmonary cryptococcosis without any extrapulmonary involvement, and no progressive dissemination occurred during the follow-up period.

Laboratory investigations

Elevations of the peripheral white blood cell count (WBC) (10.22 x [10.sup.9]/L-12.69 x [10.sup.9]/L) were detected in four patients (16.7%), while WBC counts of the other 20 patients were within normal range. Sputum culture was performed in ten cases, and two were positive for Cryptococcus neoformans. The serum latex agglutination (LA) test, which detects cryptococcal capsule polyglycan antigens, was performed in 12 cases; 11 of them had positive results. The serum fungal (1 [right arrow] 3) 0-D-glucan test (G test) was performed in 12 cases, and weakly positive results were reported in two of them.

Radiological characteristics

Computed tomography (CT) was performed in all patients (Fig. 1), and the characteristics of the images are listed in Table 2. Round or oval opacities < 3 cm in diameter were considered as nodules. Masses were defined as opacities [greater than or equal to] 3 cm in diameter. The most common radiographic findings were multiple nodules and/or masses, solitary nodule or mass, and consolidations, which could be seen in 58.3%, 25.0%, and 25.0% of patients, respectively. These nodules and masses were distributed mostly in the periphery of the lung field and adjacent to the pleura. The margins of the lesions were mostly poorly defined, while lobulations and few short spikes could be observed in most of the cases. The interior densities of nodules and masses were regular. Pleural thickening and adhesions were present in most of the cases. Concerning the distribution of the lesions, 15 patients (62.5%) had only lower lobe involvement, eight patients (33.3%) had both upper and lower lobe involvement (most lesions were in lower lobes), and only one patient (4.2%) had only left upper lobe involvement (Table 2). Cavitations (one patient), halo sign (two patients), and enlargement of mediastinal and axillary lymph nodes (one patient) were observed in four of 19 immunocompetent patients, while small bilateral pleural effusions were observed in one of five immunocompromised patients.

[FIGURE 1 OMITTED]

Diagnosis

Prior to pathological examinations, 20 patients (83.3%) were misdiagnosed with other pulmonary conditions, including lung cancer in seven cases, pulmonary tuberculosis in six cases, pneumonia in five cases, and pulmonary metastases in two cases. Diagnosis of pulmonary cryptococcosis in all the 24 patients was finally confirmed by pathological evidence (Fig. 2). Percutaneous lung biopsy specimens were obtained in nine cases (eight guided by CT and one guided by ultrasonography), thoracoscopic biopsies were obtained in seven cases (six medical thoracoscopy biopsies and one surgical thoracoscopy excision), and thoracotomy biopsies in eight cases. Cryptococcal granulomas were present in all nine of the intraoperative frozen section examinations performed, and the possibility of malignancy was ruled out. Round or oval vesicular cryptococci were faintly stained and identifiable in the cytoplasm of polynuclear giant cells. In the paraffin-embedded slides, cryptococcal granulomas were found in 21 out of 24 cases. Moreover, colloid lesions containing cryptococci were revealed in the pathological slides of the three other cases. Granulomas were mainly composed of macrophages, polynuclear giant cells, histiocytes, and fibroblasts, as well as infiltrations of lymphocytes and small amounts of neutrophils. Cells were diffusely located within the lesions, and did not converge into any evident nodules; round or oval vesicular cryptococci were faintly visible in the cytoplasm of polynuclear giant cells and macrophages, stroma of lesions, bronchioles, and alveolar cavities. Colloid lesions mainly arose from piles of cryptococcal spores and mucinous degenerated tissues. Cysts circumscribed by fibrous tissues were present in those colloid tissues, while granulomatous reactions or inflammatory infiltrations were not observed. Regarding histochemistry, periodic acid Schiff (PAS) staining was positive in 21 cases (21/22, 95.5%), while periodic acid-silver methenamine (PASM) staining was positive in all 24 cases (24/24, 100%). Lung tissue culture of cryptococcus was performed for patient No. 21, and a positive result was reported.

Management and follow-up

All patients received treatment including surgery or antifungal drug therapy. Eight of nine patients who underwent surgical therapy received pneumonectomy via thoracotomy. Among them, four took oral fluconazole 150-300 mg per day postoperatively for one to two months, and the other four did not take any antifungal drugs after surgery. The other one patient received intravenous fluconazole 400 mg per day for one month, and subsequent oral fluconazole 300 mg per day for another two months. The 15 cases managed without pneumonectomy were given fluconazole 200-800 mg per day and/or voriconazole 400 mg per day for two to six months (Table 3). Among these 24 patients, five are still on therapy. The other 19 patients underwent chest X-ray or CT scans during regular follow-up visits, which lasted from two to 11 years. In followup examinations, no relapse was observed in the nine cases that received surgical treatment, while all the lesions in the ten cases who completed drug therapy shrunk significantly and did not subsequently enlarge.

Discussion

As the clinical descriptions of pulmonary cryptococcosis in non-AIDS individuals are quite limited, this study was performed in order to better characterize this condition. In general, males are more frequently infected than females, (1) and in the present study the disease was also overwhelmingly predominant in males. None of the individuals included in the study was an AIDS patient or a transplant graft recipient. The results indicated that cryptococcosis can occur in immunocompetent patients, and compromised immunity, as well as chronic diseases, are the major risk factors for this condition. Approximately half of the cases studied had infections superimposed on pre-existing conditions, including compromised immunity.

Although pulmonary cryptococcosis is generally an airborne disease, exposures to soil or poultry prior to onset are rather common. It is noteworthy that patients No. 8 and No. 22 were mother and son who lived together, and the son worked in the clinical microbiology laboratory of the hospital. Although the mother had no working experience in the microbiology laboratory, living together may have created an environment in which the mother might have been infected by her son. The reason why the mother was diagnosed four years earlier might be her lower immunity due to age.

Presentations of pulmonary cryptococcosis were nonspecific or even totally silent. In some recent studies, approximately one-third of immunocompetent patients with pulmonary cryptococcosis were asymptomatic. (2,3) The present study revealed an even higher proportion; half (9/19, 47.4%) of immunocompetent patients with pulmonary cryptococcosis were asymptomatic, and their disease was incidentally detected during routine chest X-ray check-ups or follow-up of other diseases, while all immunocompromised patients were symptomatic. Common symptoms included fever, cough, expectoration, chest tightness, chest pain, weight loss, night sweats, and dyspnea. (4-6) These symptoms can also be manifested in other common diseases of the respiratory system, including lung cancer, pneumonia, and pulmonary tuberculosis. Therefore, pulmonary cryptococcosis is likely to be misdiagnosed. However, in comparison to non-AIDS patients, AIDS patients with pulmonary cryptococcosis generally present with more severe symptoms or even global dissemination, and infections may involve the central nervous system, the skin and mucous membranes, or the bones and joints. (7-9) The most common site of dissemination is the central nervous system, which can produce symptoms such as headache, nausea, vomiting, convulsions, or even paralysis and coma. (9,10) These symptoms are not commonly seen in non-AIDS patients.

Routine laboratory investigations, including peripheral white blood cell counts, and erythrocyte sedimentation rate, among others, were generally nonspecific in the present study, which is consistent with a previous study. (10) Regarding microbiology investigations, positive sputum culture result is very important to the diagnosis, but is less sensitive than serum G and LA tests. In this study, 11 of 12 patients had positive LA tests at diagnosis, showing a very high sensitivity. Lin et al. (7) found that LA test positivity rate had no statistical difference between immunocompetent and immunocompromised individuals, but the titers were significantly higher in HIV-infected patients than in those without HIV. LA tests can become negative in response to effective treatment and can remain persistently positive in cases with ineffective treatment or relapse. (3,7,11) However, according to the practice guidelines for the management of cryptococcal disease of the Infectious Disease Society of America (IDSA), (12) the duration of anti-fungal therapy for pulmonary cryptococcosis is not relevant to negative alterations of the cryptococcal antigen tests. Differing from the LA test, the G test targets (1 [right arrow] 3) [beta]-D-glycan, which is a component of the fungal cell wall. In comparison to Candida and Aspergilli, the cell wall of Cryptococcus contains less (1 [right arrow] 3) [beta]-D-glycan and is coated with a thick capsule, which hinders the release of (1 [right arrow] 3) [beta]-D-glycan into the circulation. (7) Therefore, the results of the G test are usually negative or occasionally weakly positive in pulmonary cryptococcosis. However, after antifungal drug therapy, the thick capsule of Cryptococcus is destroyed, and it releases significantly more (1 [right arrow] 3) [beta]-D-glycan into the circulation, which could lead to positive G test results. Then, when the therapy is continued, the growth of Cryptococcus is restrained, so the titer of (1 [right arrow] 3) [beta]-D-glycan decreases or turns negative. In the present study, only two (patients No. 21 and No. 22) out of 12 patients had weakly positive G test results at diagnosis. Four patients (patients No. 20 throught No. 23) who had their G test checked repeatedly demonstrated significant increase in their G test results after antifungal therapy for 1-2 weeks, which turned negative after about one month.

Radiological presentations of pulmonary cryptococcosis are variable. Previous studies (4-6) have shown that solitary or multiple subpleural nodules or masses with/without halo sign are common on CT scans in non-AIDS pulmonary cryptococcosis. Consolidations and pleural effusions with occasional mediastinal lymph node enlargement, although not common, are found in some cases. (6,13) Lesions are mainly located in middle and lower fields, or diffusely distributed throughout the entire lung. (13-15) The radiological findings in the present study are consistent with the findings of these previous studies. Some of the lesions appeared as multiple nodules, mainly located in close proximity to the pleura, generating confusion with pulmonary tuberculosis. Others occurred as solitary nodules, most of which had ill-defined boundaries with lobulations and sparse short spikes, misleading physicians to presumptively diagnose lung cancers. (14,16,17) Therefore, if a patient has a relatively slow progression of lesions, as well as a poor response to antibiotics, with an absence of a systemic inflammation response, tuberculosis septicemia, and chronic consumptive manifestations caused by malignant tumors, then pulmonary cryptococcosis should be carefully considered. In contrast, the chest CT scans of AIDS patients with pulmonary cryptococcosis showed diffusely distributed or patchy shadows in the lungs. (11,18) In cases with central nervous system involvement, the cranial CT scans can also reveal diffuse cerebral edema orpatchyshadows of isodensity, slightly elevated density, or low density. (1)

[FIGURE 2 OMITTED]

Lung tissue biopsies and pathological examinations are the main methods to confirm the diagnosis of pulmonary cryptococcosis. In immunocompetent patients, the initial presentations of pulmonary cryptococcosis are fungi-containing colloid lesions, which will gradually develop into granulomas, manifested radiologically as solitary or multiple nodular lesions in more advanced cases. Conversely, when immune functions are impaired, pulmonary cryptococcosis is commonly found as fungi-containing colloid lesions, which tend to disseminate within the lungs instead of becoming granulomas, giving rise to diffuse multiple nodular shadows or patchy consolidations on imaging scans. (1,19,20) PAS and PASM/GMS (Grocott's methenamine silver) staining are commonly used for cryptococcosis due to their high detection rates. (1,19,20) In the present study, the detection rates by PAS and PASM were 95.5% and 100%, respectively.

Management of pulmonary cryptococcosis depends on the immune condition of the host, and on the existence of extrapulmonary infections. (10,12) The IDSA guideline of 201012 differentiates therapeutic protocols for patients of pulmonary cryptococcosis in normal and impaired immune status. The guideline recommends oral fluconazole 400 mg per day for six to 12 months in immunocompetent patients; in patients with persistent positive serum cryptococcal antigen detections, treatment could be withheld after therapy for six to 12 months. If the diagnosis is not confirmed and radiological or clinical presentations remain after regular anti-fungal therapies, surgical resection should be considered. If the lesions are not responsive to regular fluconazole treatment or if administration of fluconazole is contraindicated, oral itraconazole (200 mg twice a day), voriconazole (200 mg twice a day) or posaconazole (400 mg twice a day) can serve as alternatives. In immunocompromised patients, central nervous system disease should be ruled out by lumbar puncture. For immunocompromised patients with mild to moderate symptoms, negative results for dissemination, without diffuse infiltrates in the lung, and without heavy immunosuppression, the antifungal therapies are the same as those for immunocompetent patients. In AIDS patients, for those who underwent HAART (highly active antiretroviral therapy) and had CD4 counts above 100/ul and in whom the titer of cryptococcal antigens stopped increasing or fell below 1:512, fluconazole can be withheld after one year of therapy. Otherwise, lifelong oral fluconazole as maintenance is necessary to prevent relapse.

Among the 24 patients in this study, five are still undergoing treatments. The follow-up period in the remaining 19 patients who had finished their treatments ranged from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. Hence it can be concluded that early vigorous treatments can prevent cryptococcal meningitis caused by dissemination of cryptococci, and therefore can improve prognosis of pulmonary cryptococcosis.

Eight out of the nine patients in the present study who underwent surgical therapy were immunocompetent. Among them, four accepted antifungal drugs after the surgery, and the other four did not. These eight patients were followed up from three to 11 years, and no relapse was observed. Thus, it can be inferred that antifungal drugs may not be necessary for immunocompetent patients after their surgical therapy. Besides, there were ten patients in the present study who received antifungal therapy for only two to six months and had already finished treatment. Nine of these ten (five immunocompetent and four immunocompromised) were symptomatic and received only one to three months of antifungal drugs after the symptoms were relieved. The remaining patient, who was asymptomatic, underwent chest-X ray or CT scans during follow-up visits, which showed that the lung lesions diminished to some extent after one month of antifungal therapy, but they had not completely disappeared even after a six-month therapy completed, and did not enlarge or diminish in the three years of follow-up examinations. In clinical work, there were a comparable number of patients who accepted antifungal therapy for various periods, and their lung lesions did not fully disappear either. Thus, in order to choose the appropriate time to stop therapy, in combination with the present study's findings, symptom relief should be taken into consideration. For patients whose symptoms were relieved, one to three months therapy after relief was preferred. For asymptomatic patients, after the entire six months therapy, if the lesions diminished or stopped growing and no new lesion was found, antifungal therapy could be withdrawn.

The present study had some limitations. First, due to the rarity of immunocompetent patients with pulmonary cryptococcosis without cryptococcal meningitis, there were a comparatively small number of cases included in the study, which were selected over a long time. Second, all cases were retrospectively studied, so not all patients in this study had the LA test at the time of diagnosis, because the hospital had not yet initiated the LA test, and furthermore, the dosage and duration for each patient was not identical. However, with further research and more knowledge about pulmonary cryptococcosis as well as the publication of new guidelines, the authors believe that diagnosis and management of this disease will be more accurate and effective.

In conclusion, diagnosis and treatment of pulmonary cryptococcosis are still challenging. However, with early diagnosis and appropriate management, most non-AIDS patients with pulmonary cryptococcosis have a good prognosis.

ARTICLE INFO

Article history:

Received 18 June 2012

Accepted 19 July 2012

Available online 13 November 2012

Conflict of interest

All authors declare to have no conflict of interest.

Acknowledgements

The authors would like to thank Dr. Yuan Lin and Dr. Xiuqing Dong for help with photography and with reading the

pathological sections, and Dr. Caiyun Liao for help with the selection of references in the early stage of work.

REFERENCES

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(2.) Kishi K, Homma S, Kurosaki A, Kohno T, Motoi N, Yoshimura K. Clinical features and high-resolution CT findings of pulmonary cryptococcosis in non-AIDS patients. Respir Med. 2006; 100:807-12.

(3.) Goldman JD, Vollmer ME, Luks AM. Cryptococcosis in the immunocompetent patient. Respir Care. 2010; 55:1499-503.

(4.) Hung MS, Tsai YH, Lee CH, Yang CT. Pulmonary cryptococcosis: clinical, radiographical and serological markers of dissemination. Respirology. 2008; 13:247-51.

(5.) Galanis E, Macdougall L. Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999-2007. Emerg Infect Dis. 2010; 16:251-7.

(6.) Nadrous HF, Antonios VS, Terrell CL. Pulmonary cryptococcosis in nonimmunocompromised patients. Chest. 2003; 124:2143-7.

(7.) Lin TY, Yeh KM, Lin JC, Wang NC, Peng MY, Chang FY. Cryptococcal disease in patients with or without human immunodeficiency virus: clinical presentation and monitoring of serum cryptococcal antigen titers. J Microbiol Immunol Infect. 2009; 42:220-6.

(8.) Chang WC, Tzao C, Hsu HH, et al. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients. Chest. 2006; 129:333-40.

(9.) Jarvis JN, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008; 29:141-50.

(10.) Yang CJ, Hwang JJ, Wang TH, et al. Clinical and radiographic presentations of pulmonary cryptococcosis in immunocompetent patients. Scand J Infect Dis. 2006; 38:788-93.

(11.) Shirley RM, Baddley JW. Cryptococcal lung disease. Curr Opin Pulm Med. 2009; 15:254-60.

(12.) Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2010; 50:291-322.

(13.) Lindell RM, Hartman TE, Nadrous HF, Ryu JH. Pulmonary cryptococcosis: CT findings in immunocompetent patients. Radiology. 2005; 236:326-31.

(14.) Wu B, Liu H, Huang J, Zhang W, Zhang T. Pulmonary cryptococcosis in non-AIDS patients. Clin Invest Med. 2009; 32:E70-7.

(15.) Fox DL, Muller NL. Pulmonary cryptococcosis in immunocompetent patients: CT findings in 12 patients. Am J Roentgenol. 2005; 185:622-6.

(16.) Song KD, Lee KS, Chung MP, et al. Pulmonary cryptococcosis: imaging findings in 23 non-AIDS patients. Korean J Radiol. 2010; 11:407-16.

(17.) Choe YH, Moon H, Park SJ, et al. Pulmonary cryptococcosis in asymptomatic immunocompetent hosts. Scand J Infect Dis. 2009; 41:602-7.

(18.) Piyavisetpat N, Chaowanapanja P. Radiographic manifestations of pulmonary cryptococcosis. J Med Assoc Thai. 2005; 88:1674-9.

(19.) Zinck SE, Leung AN, Frost M, Berry GJ, Muller NL. Pulmonary cryptococcosis: CT and pathologic findings. J Comput Assist Tomogr. 2002; 26:330-4.

(20.) McAdams HP, Rosado-de-Christenson ML, Templeton PA, Lesar M, Moran CA. Thoracic mycoses from opportunistic fungi: radiologic-pathologic correlation. Radiographics. 1995; 15:271-86.

Jin-Quan Yua, Ke-Jing Tang (a), *, Bing-Ling Xu (a), Can-Mao Xie (a), Richard W. Light (b)

(a) Department of Pulmonary Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

(b) Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, USA

* Corresponding author at: The First Affiliated Hospital of Sun Yat-sen University, Department of Pulmonary Medicine, 58 ZhongShan Rd 2, Guangzhou, Guangdong 510080, China.

E-mail address: tangkejing@gmail.com (K.-J. Tang).

http://dx.doi.org/10.1016/j.bjid.2012.07.004
Table 1--Clinical data of patients with pulmonary cryptococcosis.

Patient   Age,    Gender   PCH/SCH   Host status
No.       years

1         63      F        SCH       Pulmonary
                                     tuberculosis

2         34      M        NO        Diabetes mellitus,
                                     diabetic nephropathy,
                                     pulmonary tuberculosis

3         45      F        SCH       Normal

4         31      F        NO        IgA nephropathy Yes

5         40      M        PCH       Normal

6         34      M        NO        Normal

7         42      M        NO        Normal

8         65      F        NO        Hypertension

9         45      M        NO        Nephrotic syndrome,
                                     diabetes mellitus,
                                     chronic viral
                                     hepatitis B
10        50      M        PCH       Normal

11        30      M        NO        Chronic viral
                                     hepatitis B

12        36      F        NO        Normal

13        51      F        SCH       Normal

14        24      F        NO        Hyperthyroidism No

15        45      M        PCH       Normal

16        57      M        SCH       Chronic viral
                                     hepatitis B

17        58      M        NO        Myasthenia gravis
                                     with thymoma

18        61      F        NO        Chronic glomerulonephritis,

                                     thyroid carcinoma

19        37      M        PCH       Normal

20        55      M        NO        Coronary heart
                                     disease

21        45      M        PCH       Normal

22        34      M        NO        Normal

23        36      F        NO        Chronic viral
                                     hepatitis B

24        42      M        NO        Hyperthyroidism No

Patient   Age,    Immunocompromised
No.       years   Symptoms host

1         63      No                  Cough, expectoration,
                                      fever

2         34      Yes                 Cough, expectoration

3         45      No                  Asymptomatic

4         31                          Chest tightness, cough

5         40      No                  Asymptomatic

6         34      No                  Cough, expectoration

7         42      No                  Chest tightness

8         65      No                  Chest tightness

9         45      Yes                 Fever, chest tightness

10        50      No                  Asymptomatic

11        30      No                  Chest tightness, cough

12        36      No                  Asymptomatic

13        51      No                  Asymptomatic

14        24                          Asymptomatic

15        45      No                  Chest tightness

16        57      No                  Asymptomatic

17        58      Yes                 Chest tightness

18        61      Yes                 Fever

19        37      No                  Cough, expectoration,
                                      fever

20        55      No                  Asymptomatic

21        45      No                  Asymptomatic

22        34      No                  Cough, expectoration,
                                      fever

23        36      No                  Chest tightness, cough,
                                      expectoration, fever

24        42                          Cough

Patient   Age,    Original diagnosis   CT scans
No.       years

1         63      Pulmonary            RLL solitary nodule
                  carcinoma

2         34      Pulmonary            Bilateral
                  tuberculosis         consolidations in
                                       lower lobes

3         45      Pulmonary            LLL multiple nodules
                  carcinoma

4         31      Pulmonary            LLL solitary nodule
                  carcinoma

5         40      Pneumonia            Left lung multiple
                                       nodules

6         34      Pulmonary            LLL solitary nodule
                  tuberculosis         with halo sign and
                                       consolidations

7         42      Pulmonary            Right lung
                  tuberculosis         consolidations

8         65      Pulmonary            Bilateral
                  fungal infection     consolidations in
                                       lower lobes

9         45      Pneumonia            LUL solitary nodule
                                       with pleural
                                       effusions

10        50      Pulmonary            Right lung multiple
                  carcinoma            nodules

11        30      Pulmonary            Bilateral
                  fungal infection     consolidations in
                                       lower lobes

12        36      Pulmonary            Bilateral multiple
                  carcinoma            nodules and
                                       cavitations in lower
                                       lobes

13        51      Pulmonary            Bilateral masses
                  carcinoma            with peripheral
                                       small nodules and
                                       consolidations in
                                       lower lobes, with
                                       mediastinal and
                                       bilateral axillary
                                       lymph nodes
                                       enlargement

14        24      Metastatic           Right lung multiple
                  tumors of lungs      nodules

15        45      Pulmonary            Left lung masses
                  fungal infection     with peripheral
                                       small nodules

16        57      Pulmonary            RLL solitary nodule
                  carcinoma

17        58      Metastatic           Bilateral masses
                  tumors of lungs      with peripheral
                                       small nodules in
                                       lower lobes

18        61      Pulmonary            RLL multiple nodules
                  fungal infection

19        37      Pulmonary            Bilateral multiple
                  tuberculosis         nodules

20        55      Pulmonary            RLL mass with halo
                  tuberculosis         sign

21        45      Pneumonia            Bilateral multiple
                                       nodules

22        34      Pneumonia            RLL multiple nodules

23        36      Pneumonia            RLL multiple nodules
                                       and masses

24        42      Pneumonia            Bilateral masses

Patient   Age,    Treatments             Follow-up
No.       years                          period,
                                         years
1         63      Thoracotomy            11
                  pneumonectomy and
                  oral fluconazole 150
                  mg per day for two
                  months after
                  operation

2         34      Fluconazole 200 mg     10
                  IV per day for two
                  months

3         45      Thoracotomy            6
                  pneumonectomy and
                  oral fluconazole 150
                  mg per day for one
                  month after
                  operation

4         31      Thoracotomy            6
                  pneumonectomy and
                  oral fluconazole 150
                  mg per day for two
                  months after
                  operation

5         40      Thoracotomy            6
                  pneumonectomy

6         34      Thoracotomy            5
                  pneumonectomy

7         42      Voriconazole 200 mg    5
                  IV twice a day for
                  four weeks and oral
                  200 mg twice a day
                  for eight weeks

8         65      Voriconazole 200 mg    5
                  IV twice a day for
                  four weeks and oral
                  200 mg twice a day
                  for four weeks

9         45      Oral fluconazole 300   4
                  mg per day for two
                  months

10        50      Thoracotomy            4
                  pneumonectomy

11        30      Fluconazole 400 mg     4
                  IV per day for one
                  month and oral 300
                  mg per day for three
                  months

12        36      Thoracoscopic          3
                  pneumonectomy and
                  fluconazole 400 mg
                  IV per day for one
                  month, and then oral
                  300 mg per day for
                  two months after
                  operation

13        51      Thoracotomy            3
                  pneumonectomy and
                  oral fluconazole 150
                  mg twice a day for
                  one month after
                  operation

14        24      Fluconazole 200 mg     3
                  IV twice a day for
                  two months, and then
                  oral 150 mg twice a
                  day for four months

15        45      Voriconazole 200 mg    3
                  IV twice a day for
                  two months, and then
                  oral fluconazole 300
                  mg per day for one
                  month

16        57      Thoracotomy            3
                  pneumonectomy

17        58      Voriconazole 200 mg    3
                  IV twice a day for
                  one month, and then
                  oral fluconazole 150
                  mg twice a day for
                  three months

18        61      Oral voriconazole      3
                  200 mg twice a day
                  for eight weeks

19        37      Fluconazole 400 mg     2
                  IV per day for four
                  months

20        55      Fluconazole 400 mg     Ongoing
                  IV per day for one     therapy
                  week, and then oral
                  300 mg per day

21        45      Fluconazole 600 mg     Ongoing
                  IV per day for 14      therapy
                  days, 400 mg IV per
                  day for ten days,
                  and then oral 450 mg
                  per day

22        34      Fluconazole 600 mg     Ongoing
                  IV per day for six     therapy
                  days, 400 mg IV per
                  day for eight days,
                  and then oral 450 mg
                  per day

23        36      Fluconazole 600 mg     Ongoing
                  IV per day for two     therapy
                  weeks, and then oral
                  450 mg per day

24        42      Fluconazole 800 mg     Ongoing
                  IV per day for one     therapy
                  week, and then oral
          300 mg per day

PCH, poultry contact history; SCH, soil contact history; RLL, right
lower lobe; LUL, left upper lobe; LLL, left lower lobe.

Table 2--Radiological characteristics of pulmonary
cryptococcosis.

Radiological characteristics                  No. (%)

Abnormality
  Solitary nodule or mass                      6 (25.0)
  Multiple nodules and masses                 14 (58.3)
  Consolidations                               6 (25.0)
  With cavitations                             1 (4.2)
  With pleural effusions                       1 (4.2)
  With mediastinal and axillary lymph nodes    1 (4.2)
  enlargement
  With halo sign                               2 (8.3)
Location (lung lesions)
  Lower lobes                                 15 (62.5)
    Left lower lobe                            3 (12.5)
    Right lower lobe                           6 (25.0)
    Bilateral lower lobes                      6 (25.0)
  Upper lobes                                  1 (4.2)
    Left upper lobe                            1 (4.2)
  Lower lobes and upper lobes                  8 (33.3)
    Left lung                                  2 (8.3)
    Right lung                                 3 (12.5)
    Bilateral lungs                            2 (8.3)

Table 3--Treatments of patients with pulmonary cryptococcosis.

Treatment                                             No. (%)

Thoracotomy pneumonectomy only                        4(16.7)

Thoracotomy pneumonectomy, followed by fluconazole    4(16.7)
  150-300 mg per day orally for one to two months

Thoracoscopic pneumonectomy, followed by              1(4.2)
  fluconazole 400 mg per day IV for one month, and
  by 300 mg per day orally for two months

Fluconazole 200-400 mg per day IV for one to four     4(16.7)
  months, with (two cases) or without (two cases)
  300 mg per day orally for three to four months

Fluconazole 400-800 mg per day IV for seven to 24     5(20.8)
  days and then 300-450 mg per day orally (still on
  therapy)

Fluconazole 300 mg per day orally for two months      1(4.2)

Voriconazole 400 mg per day IV for one month and      3(12.5)
  then 400 mg per day orally for one to two months

Voriconazole 400 mg per day IV for one to two         2(8.3)
  months, and then oral fluconazole 300 mg per day
  for one to three months
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Title Annotation:Original article
Author:Yu, Jin-Quan; Tang, Ke-Jing; Xu, Bing-Ling; Xie, Can-Mao; Light, Richard W.
Publication:The Brazilian Journal of Infectious Diseases
Date:Nov 1, 2012
Words:5119
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