Invasive Esophageal Candidiasis with Chronic Mediastinal Abscess and Fatal Pneumomediastinum

Background

There are more than 20 species of Candida. The species differ considerably in virulence, C. parapsilosis and C. krusei are less virulent than C. albicans, C. tropicalis, C. glabrata, and C. pseudohyphae [1]. Candida species normally live in the gastrointestinal tract and on skin as part of a normal microbiotic flora without causing disease [2]. Invasive candidiasis, on the other hand, is the most common fungal disease among immunosuppressed patients. It comprises both candidemia and deep-seated tissue candidiasis. Mortality among patients with invasive candidiasis, even when receiving antifungal therapy, is as high as 40% [3]. There are a number of risk factors for critical illness, such as treatment in long-term intensive care units, repeat abdominal surgery, acute necrotizing pancreatitis, hematologic malignant disease, solid-organ transplantation, use of broad-spectrum antibiotics, presence of central vascular catheter, total parenteral nutrition, hemodialysis, and glucocorticoid or chemotherapy treatment [4–6]. The methods used for diagnosing invasive candidiasis include direct detection (blood and tissue cultures) and indirect detection (surrogate markers and polymerase chain reaction (PCR) assays) [7–9]. Invasive candidiasis is a potential problem for the majority of immunosuppressive patients. The diagnosis and early treatment are still the basis of the overall approach to the fungal invasive infection after immunosuppressive treatment.

Case Report

The patient was a 68-year-old Norwegian male, diagnosed at the age of 50 with seropositive psoriatic arthritis, treated with long-term medication with prednisolone and nonsteroidal anti-inflammatory drugs (NSAIDS); he had also received methotrexate for 5 years, which was stopped 10 years ago. At the age of 58, he was operated on bilaterally for total knee replacement. He was treated with thyroxin because of hypothyroidism and received salbutamol therapy due to bronchial asthma in recent years. After his first knee surgery, he suffered chest pain and was diagnosed with pneumonia and a transient pericarditis with atrial fibrillation. However, echocardiography showed normal findings without cardiac disease. The year before, he had been admitted to hospital with chest discomfort without findings of coronary ischemia. Repeat radiologic examination over more than 10 years had, however, shown findings interpreted as a ventricular hernia. A gastroscopy performed last year showed a ventricular hernia, with otherwise normal findings. Only 12 days before his last admission to hospital, he underwent right-sided total hip replacement at the Department of Surgery because of coxarthrosis. The operation was performed with spinal anesthesia, without any medical complications. The patient was admitted in the morning at his local hospital with acute dyspnea, with chest and back pain during the night before admission. His systemic blood pressure was low (103/73), heart rate 105, and respiratory rate 30/min. His skin was described as pale, cyanotic, and sweating. He received symptomatic therapy, including oxygen and antibiotics, with suspicion of pulmonary infection. During the day, his condition worsened, with increased respiratory frequency and lowered oxygen saturation, and subcutaneous emphysema occurred. Therefore, on the same evening he was transferred to Førde Central Hospital with a diagnosis of acute respiratory insufficiency. A chest X-ray shortly before showed pneumomediastinum, without signs of pneumothorax. A CT scan after admission showed a large air-containing cystic structure within the mediastinum, and increasing mediastinal emphysema (Figure 1). Blood cultures were negative for bacteria and for Candida species. In spite of treatment at the hospital’s intensive care unit, his respiratory insufficiency worsened and he died the next morning. Laboratory test results are given in Tables 1 and 2.

Autopsy findings are summarized in Table 3. Findings of subcutaneous and mediastinal emphysema were confirmed. Examination of the thoracic cavity revealed a chronic abscess with cystic degeneration (Figure 2), with a diameter of approximately 8 cm in the caudal part of the mediastinum, behind the heart and in front of the esophagus. The abscess was found to be firmly adherent to a large proportion of the oesophagus, with black-colored contents. In spite of the close relationship between the oesophagus and the large abscess, no macroscopic ulcer or perforation of the oesophagus wall were evident. There was no pulmonary emphysema and no signs of rib fractures or lesions of the airways, and significant pneumothorax could not be demonstrated, nor was there any sign of pulmonary embolism. No ventricular hernia was found. On microscopic examination, sections from the mediastinal lesion showed pronounced inflammation, with large amounts of neutrophilic granulocytes and abscess formation. Oesophageal structures formed part of the abscess wall. Within the lesion, PAS-positive organisms with morphology of the fungus Candida was found (Figure 3). Furthermore, necrotic substance within the abscess contained PAS-positive cell walls, consistent with food remnants. A small mediastinal lymph node showed acute lymphadenitis. Specimens for bacterial or fungus cultures were not provided.

Discussion

We present a case of lethal, acute mediastinal emphysema in a 68-year-old male, for many years treated with immunosuppression against psoriatic arthritis. From autopsy findings, in conjunction with clinical information, it was suggested that death was due to a massive mediastinal emphysema with respiratory failure and circulatory collapse. The autopsy revealed a hitherto undiagnosed mediastinal abscess that was firmly attached to the oesophageal wall, and with the finding of Candida during microscopic examination. We consider, therefore, invasive candidiasis of the esophagus to be the probable cause of the chronic abscess. Furthermore, we assume that the same process of chronic inflammatory involvement of the oesophageal wall explains the onset of the acute mediastinal emphysema, by microscopic rupture(s) of the oesophagus wall. Importantly, no signs of pulmonary or chest-wall lesions could be demonstrated at autopsy, although a pulmonary/airway source for the soft-tissue emphysema was suspected by the clinicians. Although he had received surgical treatment with hip replacement 12 days before admission, we were not able to find any obvious post-operative complications; it could be assumed however, that the patient in this clinical phase would be more vulnerable to any additional trauma. According to previous clinical reports, an air-containing filling in the mediastinum was demonstrated many years ago, perceived as a ventricular hernia. Follow-up radiologic controls showed persistence of this finding. No hernia was found post-mortem, however, and review of X-ray pictures support that this “hernia” corresponded to the mediastinal abscess demonstrated on autopsy. While the diameter of the abscess at autopsy was estimated to be about 8 cm, photographs taken during the session indicated an even larger lesion; by radiologic assessment of CT pictures taken shortly before death, the lesion was measured as being 11×20×9 cm. Invasive candidiasis is a potential problem for many immunosuppressed patients [10]. Immunosuppression is a treatment option for psoriatic arthritis, despite significant morbidity and mortality due to infectious complications [10]. The Candida species found during microscopy was not further analyzed because tissue culture was not performed. We find it highly probable, however, that the organism was C. albicans, as this is by far the dominant Candida species in our geographic region [11]. General risk factors of invasive candidiasis independent of our case report are critical illness, with particular risk among patients with long-term ICU stay and abdominal surgery. Particular risk also exists among patients who have anastomotic leakage or have had repeat laparotomies, acute necrotizing pancreatitis, hematologic malignant disease, solid-organ transplantation, and solid-organ tumors. Other patients at risk include neonates, particularly those with low birth weight and preterm infants, and patients receiving broad-spectrum antibiotics, presence of central vascular catheter, total parenteral nutrition, hemodialysis, glucocorticoid use or chemotherapy for cancer, and Candida colonization, particularly if multifocal [4–6]. Our patient was initially treated with antibiotics upon suspicion of pneumonia, but without clinical effect, and a bacterial infection was never documented. The diagnosis of Candida infection was made post-mortem, and the patient died before a potential antifungal therapy could have been effective. Early diagnosis and treatment are still the basis of the overall approach to fungal invasive infections in patients treated with immunosuppressive drugs [12,13]. We believe our case illustrates the importance of careful vigilance for infectious diseases, especially fungus infection, in immunocompromised patients. Physicians should also keep this possibility in mind if a patient with systemic infection does not respond to antibacterial treatment.

Conclusions

The autopsy performed in a case of lethal, acute mediastinal emphysema in a 68-year-old man, for many years treated with immunosuppression against psoriatic arthritis, revealed a hitherto undiagnosed mediastinal abscess due to chronic Candida infection. We consider invasive candidiasis of the esophagus to be the probable cause of both the chronic abscess and the acute mediastinal emphysema. This case illustrates the importance of awareness of invasive candidiasis as a possible complication in a patient with long-term immunosuppression.