Talaromyces marneffei, the only known dimorphic fungus of the genus Penicillium, was first isolated in 1956 in Vietnam from the bamboo rat Rhizomys sinensis [9]. A diagnostic characteristic of T. marneffei is mould-to-yeast conversion or phase transition, which is thermally regulated. Since the first natural T. marneffei infection was reported in 1973 [10], it has been increasingly observed both in AIDS patients and in HIV-negative individuals in recent years. Among non-HIV-infected individuals, pulmonary T. marneffei infection has been reported in patients with a history of pulmonary tuberculosis [6] or chronic obstructive pulmonary disease (COPD) [11]. However, to our knowledge, the infection has not been reported in patients with a history of pulmonary sarcoidosis. In this article, we first present such a case of a confirmed diagnosis of T. marneffei infection in a non-HIV-infected patient with pre-existing pulmonary sarcoidosis.
The main route of transmission of T. marneffei is inhaling the infectious agent; rarely is there direct animal contact. The typical clinical manifestations are fever, weight loss, skin lesions, generalized lymphadenopathy, hepatosplenomegaly, and respiratory signs, but the severity of the disease depends on the patient’s immune status [12, 13]. The patient in this case was a non-HIV-infected patient and was young, but his lung immunity was probably impaired due to long-standing pulmonary sarcoidosis. Early in 1988, Deng, Z. et al. [14] reported that southern China was one of the endemic regions for T. marneffei. Specifically, these clinical features, as indicated by hyperpyrexia, sputum-coughing, persistent elevated IgE and eosinophils in the blood, eosinophil infiltration in the bronchus, positive BAL-G assay (G assay of BAL), and T-spot negativity as well as the failure to reveal acid-fast bacilli, led to possible infection with a pulmonary fungus. As the accuracy of the BAL-G assay is marginal rather than absolutely specific for invasive fungal disease (IFDs), the results should not be interpreted alone but should be used as a part of a full assessment together with clinical features, image findings and other laboratory results for the diagnosis of IFDs [15]. Finally, the T. marneffei infection was confirmed with bronchoalveolar lavage culture. In addition to the BAL, commonly used clinical specimens in the literature include bone marrow aspirate, blood, lymph node biopsies, skin biopsies, skin scrapings, sputum, pleural fluid, liver biopsies, cerebrospinal fluid, pharyngeal ulcer scrapings, palatal papule scrapings, urine, stool samples, and kidney, pericardium, stomach or intestine specimens [16]. Different from previously reported cases of pulmonary T. marneffei infection in non-HIV-infected patients, the pre-existing pulmonary sarcoidosis covered up the clinical futures of T. marneffei and easily misled us about the progression of the original disease or lymphoma.
The T. marneffei presentation upon chest CT is non-specific, as displayed by multiple patchy exudative shadows, pulmonary consolidation, nodular shadows, a ground-glass appearance, miliary lesions, and nodular masses, commonly accompanied by mediastinal and hilum lymphadenopathy and sometimes by cavitary lesions [17]. Compared to the chest CT (Fig. 1a) 2 yrs prior, the chest CT (Fig. 1b and c) showed the progression of pulmonary nodules and the new consolidation lesions. In this respect, we would be more likely to suspect the progression of pulmonary sarcoidosis and to ignore the possibility of fungal infection. The chest CT (Fig. 1d) re-examined after anti-fungal treatment for 3 months showed that the lung lesions as well as some pulmonary nodules were markedly absorbed. However, the mediastinal lymphadenopathy did not improve in all the groups, as shown in Fig. 1. There was a strong likelihood that the lymphadenopathy was due to long-standing pulmonary sarcoidosis.
The non-specific presentation of T. marneffei highlights the importance of the rapid diagnosis and treatment of this potentially life-threatening mycosis. T. marneffei is susceptible to itraconazole and amphotericin B in vitro [18, 19]. A study from China revealed that voriconazole had the lowest MIC (ranged from 0.004 mg/L to 0.25 mg/L) in comparison to other antifungal agents, and the results showed that voriconazole and itraconazole are active against T. marneffei isolated in vitro [20]. However, a documented study reported that a single dose of itraconazole for the treatment of T. marneffei infection in HIV-infected patients was non-effective [21]. A retrospective study evaluating the efficacy and safety of voriconazole to treat patients with T. marneffei infection suggested that voriconazole was an effective, well-tolerated therapeutic option for this disease [22]. Taken together, we preferred voriconazole as the antifungal drug for this case. Indeed, the patient recovered rapidly, and the lung lesions were markedly absorbed after treatment.