Abstract
Background: Zygomycosis is an uncommon, severe, life-threatening fungal infection in the immunocompromised host. The most common clinical presentation is rhinocerebral, primary pulmonary and disseminated disease. Myocardial involvement has been described in several case reports, mostly associated with pulmonary symptoms. Cardiac manifestations may, although, dominate the clinical picture of disseminated mucormycosis. These include myocardial infarction, congestive heart failure, conduction system disease, valvular incompetence and pericarditis. Diagnosis is based on histopathology.
Objectives: we describe a 46-year-old man, (refractory follicular lymphoma), submitted to non-myeloablative SCT. Six months after SCT he developed cough, weight loss and skin lesions. Biopsies confirmed the diagnosis of cGVHD, and prednisone and CsA was started on D+180. Day+206 he developed fever and headache, uveitis, vitreous hemorrhage and rapid deterioration of consciousness. The MRI of the brain showed multifocal rounded white matter abnormalities with no gadolinium enhancement over the temporal, frontal and parietal lobes bilaterally as well as the periventricular region. Some lesions showed restriction on the diffusion sequence. The lesions did not show vascular territories distribution. CSF samples were tested for the presence of viral and fungal infection by polymerase chain reaction (PCR). Herpesvirus infections (CMV, HSV1, HSV2, VZV, EBV, HHV-6, HHV-7 and HHV-8 were investigated by a panherpes PCR with two pairs of primers targeting the DNA polymerase region. Polyomavirus (JC and BK) and picornavirus were also investigated. No virus was identified by PCR. Panfungal 18S rDNA directed PCR tested negative in 2 CSF samples taken with one week interval. Without any confirmed diagnosis we treated him with broad spectrum antibiotics and antifungals (initially with amphotericin and afterwards with Voriconazole). On day 212 he developed a cardiac arrhythmia (ventricular bigeminy and premature ventricular beats) promptly reverted by Amiodarone. Echocardiogram showed no alteration. D+214 he had recovered consciousness, but developed uncontrolled seizures and cardiac arrest. At that time electrocardiogram showed left bundle branch block. At autopsy no macroscopic alterations could be found in the brain but in the heart multiple white lesions were seen (fig 1) and in the kidneys. In myocardium, CNS and kidney large, non septate hyphae could be seen. In the brain thrombi occluding vessels could be found.
Conclusions: Zygomycosis is increasingly reported in immunosuppressed patients. Diagnosis is difficult unless extensive radiologic examinations and invasive procedures (surgery and biopsy) can be performed. Unfortunately we focused our diagnostic approach to the SNC because the predominant manifestation was neurologic. Zygomycosis remains a highly lethal infection especially in imunossupressed patients unable to discontinue immunosuppressant drugs. Early diagnosis and aggressive treatment are the only possibilities to reach a successful outcome.
Figure Figure
Fungal Infection in the Brain: What We Learned from Intravital Imaging