We report a rare case of progressive hearing loss after acquired CMV infection in a child with Langerhans cell histiocytosis (LCH). A 5-month-old female was diagnosed as having LCH. When she was 14 months old, she received an unrelated donor umbilical cord blood transfusion for the treatment of intractable LCH. CMV infection was confirmed after the blood transfusion. Because her own umbilical cord had no CMV, the CMV infection was not congenital. When she was 7 years old, mixed hearing loss was noted with bilateral otitis media with effusion. After that time, the sensorineural hearing loss progressed to bilateral profound hearing loss over 3 years. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging with gadolinium contrast enhancement revealed a high intensity area in the inner ear that suggested bilateral labyrinthitis. This case demonstrates the possibility that, under the immunodeficiency, the acquired CMV infection causes progressive sensorineural hearing loss.
Cytomegalovirus (CMV) is a DNA-containing herpes virus. Its scientific name is human herpes virus 5 and it causes a range of symptoms after the first infection or after reactivation. CMV is well known as the cause of congenital sensorineural hearing loss or the opportunistic pathogen. Congenital CMV infection, which is caused by transplacental infection, also has various symptoms including low birth weight, microcephaly, hepatosplenomegaly, meningitis, and sensorineural hearing loss. Congenital CMV infection is the most widespread cause of sensorineural hearing loss other than inherited disease . However, few reports have described sensorineural hearing loss caused by acquired CMV infection. We report progressive sensorineural hearing loss caused by acquired CMV infection in an immunocompromised child.
A 5-month-old female was referred to the Department of Pediatrics at Nagoya University Hospital because of fever, lymphadenopathy and purpura. Based on histological examination of neck lymph nodes, she was diagnosed with disseminate Langerhans cell histiocytosis (LCH). Then she received chemotherapy. First, one course of DAL-HX 83 study group protocol (etoposide (VP-16) + vinblastine (VBL) + prednisolone (PDN)) as initial chemotherapy and secondly, one course of next chemotherapy (VP-16 + VBL + cyclophosphamide (CPA)) were performed. But the LCH did not response completely. When she was 9 months old, her splenomegaly became worse and caused C-reactive protein (CRP) elevation and anemia had progressed. Although she was given blood transfusions many times, her anemia did not improve. Finally, splenectomy was performed. After the operation, two courses of CHOP therapy (CPA + VP-16 + vincristine (VCR) + PDN) and then, one course of next chemotherapy (CPA + VP-16 + VCR) were performed but her symptom such as fever elevation, anemia, thrombocytopenia, and liver dysfunction became worse.
When she was 14 months old, finally, a cord stem cell transplant from an unrelated donor was performed and her LCH improved. However, CMV infection that was recognized before the cord stem cell transplantation was continuing. Because CMV antigen was not detected in her own cord blood, it was considered that the CMV infection was not congenital infection but acquired during treatment of the LCH. Due to her immunodeficiency with few CD4 + T cells (< 100/μl–400/μl), CMV infection continued including retinitis. CMV retinitis started when she was 18 months old. She was administered the antiviral drugs ganciclovir and foscarnet. During treatment, CMV antigen became negative, but when the antiviral drugs were discontinued, it became positive again, and she underwent repeated hospitalization and discharge. The retinitis did not become worse during this period. Fig. 1 shows changes of CMV-DNA amount that was investigated from the age of seven. When she was 7 years old, CMV DNA increased to 3913 copies/ml, and then decreased to zero or hundreds of copies/ml. When she was 9 years old, CMV DNA increased to 8705 copies/ml, but again decreased to zero or hundreds of copies/ml. Together with antiviral drug therapy, she was transfused with activated CD4 + T cells. Her blood CD4 + T cells increased to within the range of 500–900/μl, but her immunodeficiency did not improve. Her CMV antigen periodically became positive, at which times it was necessary to administer foscarnet.
When she was 6 years old, she consulted the Department of Otorhinolaryngology in our hospital because of suspicion of otitis media. At that time her mother did not notice her hearing impairment. However, three months after her first visit to the Department of Otorhinolaryngology, mixed hearing impairment with otitis media (OME) with effusion was recognized bilaterally (first audiogram in Fig. 2 ). A half year later, bilateral tympanostomy and ventilation tube insertion were performed because OME did not improve. Her bone-conduction hearing levels deteriorated to profound hearing loss ( Fig. 2 ). When she was 8 years old, she complained of dizziness transiently. Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI before and after enhancement showed a high intensity lesion in the internal auditory canal and in the cochlea without inner ear malformation. When she was 11 years old, 3D-FLAIR MRI after enhancement was performed again. The signal intensity of internal auditory canal was much stronger than that taken when she was 8 years old ( Fig. 3 ). These findings suggested the exacerbation of meningitis close to the inner ear. When she was 11 years old, she had inflammation of the ventricles of the brain and a large amount of CMV-DNA was detected from her cerebrospinal fluid.