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A case of penicillium marneffei infection involving the main tracheal structure
- Ye Qiu†1,
- Jianquan Zhang†1Email author,
- Guangnan Liu†1,
- Xiaoning Zhong1,
- Jingmin Deng1,
- Zhiyi He1 and
- Bai Jing1
© Qiu et al.; licensee BioMed Central Ltd. 2014
Received: 18 December 2013
Accepted: 23 April 2014
Published: 7 May 2014
Penicillium marneffei is the only dimorphic member of the genus and is an emerging pathogenic fungus that can cause fatal systemic mycosis. Penicillium marneffei disseminates hematogenously to other locations. Penicillium marneffei infection most commonly involves the skin, lungs, and reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported. Infection involving the trachea has not been previously reported.
We herein report a previously healthy 28-year-old male farmer from Guangxi Province without HIV who became infected with P. marneffei. The infection primarily affected the trachea, resulting in structural damage to the cartilage, tracheal stenosis, and tracheal absence. The infection also involved the lungs and lymph nodes. After antifungal treatment and surgery, his symptoms, signs, and lung imaging findings showed significant improvement. This is the first such case report.
Penicillium marneffei infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. Penicillium marneffei hematogenously disseminates throughout the whole body. This is the first reported case of P. marneffei infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence.
Penicillium marneffei (PM) is a facultative intracellular pathogen that is capable of causing disseminated infection in both humans and wild bamboo rats. PM has been widely described in patients with HIV/AIDS as well as in other hosts, especially those with cellular immune defects . Common clinical manifestations of PM infection are fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs, and skin lesions [1, 2]. PM infection most commonly involves the skin, lungs, and the reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported [1–3]. We herein report a case involving a 28-year-old man without HIV who developed a disseminated PM infection involving the main trachea. The infection resulted in structural damage to the tracheal cartilage, severe tracheostenosis, and up to 2 cm of tracheal absence. This is the first such case reported worldwide.
PM disseminates hematogenously to other locations [1, 2]. The reticuloendothelial system, skin, and lungs are the most commonly involved sites. PM can disseminate into the bone, bone marrow, joints, lymph nodes, pericardium, liver, spleen, mesenteric tissue, and even the central nervous system [1–3]. Healthy hosts infected with PM present with various symptoms. Patients with severe systemic inflammatory response manifests as fever, obvious increases in leukocyte and neutrophil counts, a high erythrocyte sedimentation rate, and a high C-reactive protein level. Moreover, weight loss, anemia, severe hypoproteinemia, and even multiple organ failure have been reported [4–6].
In this paper, we reported a case involving a healthy host without HIV or other underlying diseases who developed disseminated PM infection. Tests for antistreptolysin O, antinuclear antibody, rheumatoid factor, and HIV were negative. We found no possible causes of immunodeficiency. Although rare, PM has been reported in healthy hosts . However, the present patient had risk factors for infection: he was living in an endemic area and had a history of contact with bamboo rats. After 5 months of antifungal treatment, his CD4 T-cell level recovered, indicating that he was not initially immunodeficient. PM grows as yeast bodies inside phagocytes. Immunosuppression after infection is a commonly encountered problem in affected patients. Causes of immune depletion may include prednisolone therapy, initial misdiagnosis, and disease progression.
The patient described herein exhibited symptoms different from those previously reported in the literature. His systemic inflammatory response was mild. The patient was misdiagnosed with tuberculosis as a clinical diagnosis because the lung imaging changes, symptoms, and protrusions on the tracheal wall were very similar to the characteristics of tuberculosis, which is a common disease in China. The long duration of misdiagnosis and mistreatment accelerated the progression of the disease, resulting in structural damage to the tracheal cartilage, tracheostenosis, and a tracheal absence of up to 2 cm. This is the first case of such developments in a patient with PM infection. Humans infected with PM can show three pathological patterns: suppuration, granuloma formation, or anergy with necrosis. The first and second patterns are more commonly seen in healthy hosts . Because of the long duration of misdiagnosis of TB and prednisolone therapy in the present case, the PM infection involved the main trachea and subsequently resulted in severe tracheostenosis and tracheal absence. PM infection can result in the accumulation of massive numbers of neutrophils and the release of proteolytic enzymes in a local inflammatory response, causing tissue dissolution, suppuration, necrosis, and fibroplasia. These changes cause structural damage to the tracheal cartilage and cicatricial reparation, resulting in tracheal collapse, severe tracheostenosis, and tracheal absence.
PM infection is associated with high mortality because it is commonly misdiagnosed in the early stages [8, 9]. PM is identified by culture, pathological examination, and cytological analysis . PM grows as a yeast at 37°C, but as a mold at 25°C on Sabouraud dextrose agar, exhibiting a soluble red pigment that diffuses into the medium [1, 8]. The yeast form of PM has a characteristic morphology, including a transverse septum and sausage-shaped organisms that can be demonstrated by pathological and cytological examination [8, 10].
The differential diagnoses for PM include tuberculosis, histoplasmosis, lymphoma, cryptococcosis, panniculitis, molluscum contagiosum, and various other viral infections [8, 10]. Tuberculosis is the most common misdiagnosis for the following reasons: (i) relevant literature and research on PM are limited; (ii) PM has been strongly emphasized as a common opportunistic infection of patients with AIDS; (iii) the signs, lung imaging findings, and pathological examination results are similar to those of tuberculosis; and (iv) in the early stages, there is a low concentration of viable lesions and a low culture-positive rate.
Penicilliosis is very susceptible to antifungal treatment. PM is susceptible to itraconazole and amphotericin B in vitro[11, 12]. The current recommendation for patients with HIV infection is amphotericin B at a dosage of 0.6 mg/kg daily for 2 weeks, followed by oral itraconazole at a dosage of 200 mg twice daily for 10 weeks . After 24 weeks of regular antifungal therapy and surgery, the symptoms, signs, and lung imaging findings of the present patient showed significant improvements.
PM infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. PM disseminates throughout the whole body via a hematogenous route. This PM infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence is the first such reported case. The patient had a good response to antifungal treatment, but mild tracheostenosis remained after surgery. PM infection is characterized by a high rate of recurrence. Therefore, this patient will require a long follow-up duration to evaluate the long-term effects of the infection. There is no generally recognized treatment that is effective for PM infection in patients without HIV. The recommended treatment for healthy hosts requires further investigation.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Ye Qiu, Jianquan Zhang and Guangnan Liu considered co-first authors.
The authors thank Jiping Su, Professor of Surgery, Department of Head and Neck Surgery and Zhenbo Feng, Professor of Pathology, Department of Pathology, the First Affiliated Hospital of Guangxi Medical University.
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