The incidence of invasive fungal infections has increased in the hospital setting in recent years. The reason may be the extensive use of immune system-suppressing modalities in patients, including stem cell transplantation, organ transplantation, chemotherapy, and immunosuppressive drug therapy. Such immunosuppressive therapies compromise the host immune system and make them vulnerable to invasive fungal infections [
4]. The most common fungal species causing invasive disease is
Candida, followed by
Aspergillus. Cases due to other species such as
Mucorales and
Fusarium and other molds are less common [
5]. For pulmonary invasive fungal infection,
Aspergillus is the major pathogen.
Cryptococcal infections are usually community-acquired, through inhalation of fungal cells from the environment, and rarely cause pulmonary infection in hospitalized patients. In our presented case, a comparison between the initial chest CT in the emergency department and that performed 3 months after admission (Fig.
1a, b) and the final pathology reports indicated pulmonary cryptococcal infection. This result surprised us, and an investigation was conducted to determine the possible infection source. We reviewed microbiology laboratory records in our hospital and found that there were no reported cryptococcal infection cases in the ICU and the general ward up to 1 month before our case was diagnosed of cryptococcal infection. This result excluded the possibility of a cluster outbreak from patient-to-patient transmission, which has been reported [
6]. Additionally, during the prolonged hospitalization in the ICU and the general ward, the patient always stayed in bed, in an environment under a central air-conditioning system without open windows. This excluded the occurrence of acute primary infection through inhalation of fungal cells from the outdoor environment during hospitalization. Environmental sampling for this case, however, was not performed. Therefore, we could not completely exclude the possibility that our case acquired the infection from the hospital environment as reported before [
7,
8]. Based on her contact history, we speculated that the pulmonary cryptococcal infection may be a result of a reactivated endogenous latent infection acquired before admission, which was precipitated by the recent immunosuppressant therapy. In immunocompetent hosts, primary pulmonary cryptococcal infections are cleared by the immune system or they establish themselves as latent infections within the thoracic lymph nodes or pulmonary granuloma for a prolonged period. On subsequent immunosuppression,
Cryptococcus can reactivate and then disseminate to other tissues, thereby causing a life-threatening invasive disease such as cryptococcal meningoencephalitis [
9,
10]. Our presented case showed only mild respiratory symptoms without neurological symptoms at disease onset, which rapidly improved after fluconazole use. Lumbar puncture, therefore, was not performed. Hospital-acquired (48 h or more after admission) pulmonary cryptococcal infections are very rare, with only three cases found in a literature review (Table
1) [
6,
11,
12]. All reported cases had chronic lung disease, which has been reported as a risk factor for cryptococcal infection [
13]. Although our present case had no underlying disease risk for cryptococcal infection, steroid and azathioprine use after admission for the myasthenic crisis may have decreased the immune defense and contributed to subsequent reactivation of latent pulmonary cryptococcal infection. Glucocorticoids can affect the pathogen-clearing function of various phagocytic cells including neutrophils, monocytes, and macrophages, which play important roles in host defense against cryptococcal infection [
14]. Steroid usage, therefore, has been associated with subsequent cryptococcal infection, irrespective of short- or long-term use [
12,
15,
16]. Azathioprine, which inhibits purine synthesis along with B and T lymphocytic cells function, can also compromise the patients’ immune system and make them vulnerable to opportunistic infections [
17].
Table 1
Summary of previous reports of hospital acquired pulmonary cryptococcal neoformans infection cases
1 | 73/female | 41 | Diabetes mellitus and hypertension | Steroid and azathioprine | Lung | Survived | Present case |
2 | 82/male | 4 | Coronary artery disease and emphysema | Steroid | Lung | Death | |
3 | 63/male | 58 | Coronary artery disease and chronic obstructive disease | None | Blood, lung | Death | |
4 | 80/male | 44 | Lung cancer | Unknown | Lung | Death | |
The major limitations of this investigation were the lack of environmental sampling and direct culture of Cryptococcus neoformans. However, based upon pathology findings, clinical history and epidemiologic investigation results, we speculate that our presented case of pulmonary Cryptococcosis may be due to reactivated latent infection. In the evaluation of inpatients receiving immunosuppressive treatments with infection, reactivated latent infection such as pulmonary cryptococcosis should not be missed.