Reminder of important clinical lesson BMJ Case Rep: first published as 10.1136/bcr-2019-230410 on 15 August 2019. Downloaded from Case report Simultaneous candida albicans and herpes simplex virus type 2 esophagitis in a renal transplant recipient Imran Gani, 1 Vatsalya Kosuru,2 Muhammad Saleem,2 Rajan Kapoor1 1Nephrology, Hypertension and SUMMARY episode of biopsy-proven, borderline, acute cellular Transplant Medicine, Augusta Renal transplant recipients are prone to opportunistic rejection in the second month after transplant that University Health, Augusta, infections due to iatrogenic immunosuppression. responded well to pulse steroids with normalisation Georgia, USA Infectious esophagitis can present as an opportunistic of renal function. 2Internal Medicine, Augusta infection in the post-transplant period. Common Nine months after her kidney transplantation she University Health System, Augusta, Georgia, USA pathogens are candida, herpes simplex virus (HSV) presented with sore throat, dysphagia, odynophagia and cytomegalovirus (CMV). Having a dual infection and fever. Her physical examination was significant Correspondence to is uncommon and the diagnoses can be missed at for oropharyngeal thrush, white tonsillar exudates, Dr Imran Gani, initial presentation. Our patient, a 29-year-old African- pharyngeal erythema and enlarged palatine tonsils. igani@ augusta. edu American woman, status post deceased-donor-kidney Blood work showed leukocytosis and acute kidney transplant presented with difficulty and pain in injury (AKI). She was admitted to the hospital for Accepted 22 July 2019 swallowing with clinical features suggestive of candida intravenous fluids and intravenous fluconazole esophagitis, confirmed by fungal culture. She did not therapy for severe oropharyngeal candidiasis and get better with antifungal treatment. On further testing, high suspicion of esophageal candidiasis. After the patient was found to have HSV-2 infection of the 48 hours of intravenous antifungal treatment, the oesophagus as well. She received both fluconazole as patient had improvement of symptoms and was well as acyclovir that lead to complete resolution of her discharged home on oral fluconazole and clinda- symptoms. In the right clinical setting, esophagitis can be mycin. Clindamycin was empirically prescribed for caused by more than one organism present at the same the treatment of any underlying tonsillitis. time and a high level of suspicion is warranted. Three days post discharge, the patient was read- mitted in a septic state, with worse odynophagia, tachycardia, high-grade fever and worsening leuko- BACKGROUND cytosis. The patient appeared ill. Physical exam- http://casereports.bmj.com/ Renal transplant patients are prone to infectious ination again demonstrated white plaques on the esophagitis primarily because of their immunosup- tongue, palate and tonsils with bilateral lingual pressed status. Candida, herpes simplex virus (HSV) and palatine tonsillar swelling (figure 1). The white and cytomegalovirus (CMV) are the usual causative plaques on the tongue were amenable to scraping. A agents in such patients, but having esophagitis due CT scan of the neck was obtained showing swollen to two organisms simultaneously is uncommon and lingual and palatine tonsils with narrowing of the can be missed at the time of initial presentation, pharynx and bilateral level 2A and 2B cervical leading to clinical complications. A dual pathogen lymphadenopathy. It did not show any drainable esophagitis is usually not suspected. Also, clinical abscess. The patient was started on empiric intra- features of one causative agent may dominate over venous antibiotics and intravenous fluconazole on September 30, 2021 by guest. Protected copyright. the other. Missing such diagnoses in immunosup- was restarted. The patient’s fever and tachycardia pressed renal transplant patients can lead to worse improved but she continued to have discomfort and clinical outcomes. pain in her throat while swallowing as well as in her chest. Throat culture was positive for candida CASE PRESENTATION albicans and negative for any bacterial growth. A 29-year-old African-American woman received Blood cultures were negative. Rapid streptococcal a deceased-donor -kidney transplant in September antigen test, Monospot test, Epstein bar virus PCR 2017. She was induced with pulse steroids and and CMV PCR were also negative. thymoglobulin. Her renal graft function was stable An upper gastrointestinal (GI) endoscopy was © BMJ Publishing Group on maintenance immunosuppression with myco- done on day 5 of hospitalisation showing whitish Limited 2019. Re-use phenolic acid 1000 mg two times per day, predni- exudate and plaques at the base of her tongue, a permitted under CC BY-NC. No 10 cm patch of whitish exudates in the oesophagus commercial re-use. See rights sone 5 mg daily and tacrolimus with a goal level of and permissions. Published 6–8 ng/mL. Tacrolimus level remained within the with underlying esophagitis (figures 2, 3). Esoph- by BMJ. therapeutic range. She also received valgancyclovir, ageal brushings were obtained. Cytopatholog- nystatin and Bactrim for 3 months post-transplan- ical examination of esophageal brushings showed To cite: Gani I, Kosuru V, Saleem M, et al. BMJ Case tation as prophylaxis for opportunistic infections. cellular changes consistent with HSV infection. Rep 2019;12:e230410. The patient had a negative HSV-1 and HSV-2 Viral culture and immunofluorescence staining doi:10.1136/bcr-2019- serology prior to the transplant. Donor HSV-1 and from esophageal biopsy came positive for HSV-2 230410 HSV-2 status was not known. The patient had an and negative for HSV-1, CMV and adenovirus. Gani I, et al. BMJ Case Rep 2019;12:e230410. doi:10.1136/bcr-2019-230410 1 Reminder of important clinical lesson BMJ Case Rep: first published as 10.1136/bcr-2019-230410 on 15 August 2019. Downloaded from F igure 3 Patch of whitish exudates in the oesophagus with underlying esophagitis. the first 6 months due to intense immunosuppression and trans- plant centres give prophylaxis against common infections during Figure 1 White plaques on tongue and tonsils with bilateral lingual this period. Infectious esophagitis is among such opportunistic and palatine tonsillar swelling. infections. Infectious esophagitis can present with symptoms including discomfort and difficulty in swallowing, pain while Intravenous acyclovir was started for biopsy-proven HSV-2 swallowing and retrosternal chest pain. Patients may have a esophagitis. Immunosuppression was also lowered by halving the prodrome of fever, malaise and nausea. The symptoms based on dose of mycophenolate mofetil. Adjustments in her tacrolimus a previous reviews include dysphagia for both solids and liquids dose were made due to interaction with fluconazole. During the (37.5%), odynophagia (60.7%), chest pain (46.4%) heartburn, treatment period her trough tacrolimus levels ranged between and/or vomiting.1 5.5–8.4 ng/mL. Candida is the most common cause of fungal infection of oral mucosa and oesophagus in immunosuppressed patients. Candida OUTCOME AND FOLLOW-UP albicans or candida tropicalis are the commonly involved species.2 The patient’s symptoms improved with intravenous acyclovir. She 50%–75% of patients with esophageal candidiasis have oropha- was discharged home after 4 days of intravenous acyclovir, and was ryngeal candidiasis. Oropharyngeal candidiasis most commonly http://casereports.bmj.com/ on oral valacyclovir as well as oral fluconazole until completion presents in a pseudomembranous form with white plaques on of 21 days of therapy. The patient followed up in the outpatient the oropharynx, tongue, palate and buccal mucosa. The pres- clinic 3 weeks later and reported complete resolution of her symp- ence of oral thrush may be helpful in the diagnosis of fungal toms. She had a repeat esophagogastroduodenoscopy (EGD) which esophagitis;3 however, the absence of oral involvement does showed complete resolution of esophagitis (figure 4). not exclude esophageal candidiasis. Diagnosis is usually made using endoscopy. Endoscopic evidence of candida lesions may DISCUSSION include superficial erosions, ulcers and white plaques that can be Opportunistic infections in immunocompromised renal trans- severe, resulting in necrosis and perforation. Histopathological plant patients are a fearful complication. The incidence is high in on September 30, 2021 by guest. Protected copyright. Figure 4 Esophagogastroduodenoscopy 3 weeks later showed Figure 2 Whitish exudate and plaques at the base of the tongue. complete resolution of esophagitis. 2 Gani I, et al. BMJ Case Rep 2019;12:e230410. doi:10.1136/bcr-2019-230410 Reminder of important clinical lesson BMJ Case Rep: first published as 10.1136/bcr-2019-230410 on 15 August 2019. Downloaded from examination of biopsies shows the presence of yeast and pseudo- in the distal oesophagus and at the lower esophageal sphincter hyphae with invasion of mucosal cells and the culture of the are a common finding but diffuse esophagitis can also occur. biopsy specimen grows candida.4 5 The treatment includes Ulcers tend to be longitudinal or linear.5 The tissue sample is a course of oral fluconazole. Itraconazole can also be used; usually sent for histopathological examination, antigen detec- however, it has more drug interactions than fluconazole. Intrave- tion, viral culture and PCR. On histopathological examination, nous antifungal therapy may be required in patients with severe mucosal inflammation, along with