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ARTICLE
Otorhinolaryngologic Problems in Liver and Kidney Transplant Recipients

Objectives: The aim of this study was to define the otorhinolaryngologic manifestations and clinical characteristics of patients who received kidney or liver transplants at a university hospital.

Materials and Methods: Medical records of patients who received a kidney or liver transplant between 2000 and 2013 and who were referred or applied to the ear, nose, and throat clinic were retrospectively reviewed. Otorhinolaryngologic complaints, signs, examination findings, and diagnoses of patients were noted.

Results: Our analyses included 540 visits to the ear, nose, and throat clinic by 101 liver and 191 kidney transplant recipients. Mean duration between date of transplant and otorhinolaryngologic examination was 747.9 ± 37.1 days. The most common complaint was rhinorrhea (n = 112), whereas the most common diagnosis was acute rhinosinusitis (n = 85). Acute upper respiratory tract infections, including rhinosinusitis, were diag­nosed more frequently during the late postoperative period (ie, > 180 days after transplant). Epistaxis was more frequent during the first 30 days after transplant.

Conclusions: A diverse variety of otorhinolaryngologic conditions, including emergencies and potentially life-threatening infections, were seen in our kidney and liver transplant recipients, both during the early and the late follow-up period. All transplant team members should be familiar with the clinical presentation of frequently seen otorhinolaryngologic diseases.


Key words : Kidney transplantation, Liver transplantation, Otorhinolaryngologic diseases

Introduction

Organ transplant is the most effective modality in the treatment of end-stage kidney or liver disease.1,2 Improvements in surgical techniques and advances in immunosuppressive therapy regimens have led to increased survival rates postoperatively.3,4 However, long-term immunosuppressive therapy is still one of the most important factors affecting mortality and morbidity.

Successful solid-organ transplant requires surgical expertise, meticulous postoperative care, and close and long-term follow-up of patients. During the perioperative and postoperative periods, organ recipients may encounter many additional clinical problems that are seemingly not related to the nonfunctioning organ. Diseases related to those in the field of otorhinolaryngology (ie, ear, nose, throat, head, and neck regions) commonly affect transplant recipients similarly to the general population. However, transplant recipients constitute a special patient group for the field of otorhinolaryngology. Some frequently encountered otorhinolaryngologic problems, such as upper respiratory tract infections, that do not possess a major risk for otherwise healthy individuals may rapidly progress into potentially life-threatening conditions in transplant recipients. Unnecessary laboratory tests, overused imaging modalities, and aggressive interventions, on the other hand, can bring additional risks for the patient and increase health care costs. Symptomatology and frequency of otorhinolaryngologic findings of transplant patients are so far not well documented in the literature.

Our surgical team has performed 2854 kidney transplant procedures since November 3, 1975, and 596 liver transplant procedures since December 8, 1988. Our hospital remains a referral center for solid-organ transplant, with many transplant patients referred to our otorhinolaryngology clinic for evaluation. We aimed to define the type and frequency of otorhinolaryngologic symptoms and the subsequent physical examination findings and diagnoses of patients who underwent kidney or liver transplant at Baskent University Ankara Hospital.

Materials and Methods

This retrospectively designed study was approved by the Baskent University Institutional Review Board (project number KA12/273).

Hospital records were investigated to identify kidney or liver transplant recipients who underwent transplant procedures between January 2000 and December 2012. Among these, patients who were referred to the otorhinolaryngology clinic 1 month before or at any time after transplant were selected. Demographic findings, transplant time, number of visits, symptoms, physical examination findings, and diagnoses of patients were recorded.

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 16.0, IBM Corporation, Armonk, NY, USA). Continuous variables are presented as means ± standard deviation or median values and range, whereas nominal values are given as percentages. Mann-Whitney tests were used to compare means of independent variables, and chi-square tests were used to compare categorical variables.

Results

Between January 2000 and December 2012, there were 1059 patients who had kidney or liver transplant pro­cedures in our hospital. Among them, 558 patients had otorhinolaryngology clinic visits. The hospital records of 292 patients were accessible; therefore, these patients were included in the study. Of these, 96 patients (32.9%) were female (female-to-male ratio of 0.49).

Overall, there were 540 visits to the otorhino­laryngology clinic in our patient group; 181 patients had a single visit, and 111 patients had multiple visits. The distribution of patients according to number of visits is given in Table 1. The kidney transplant group (n = 191; 65.4%) had 360 visits, and the liver transplant group (n = 101; 34.6%) had 180 visits.

The mean age at time of transplant was 30.1 ± 0.93 years (median of 28.5 y; range, 0.54-65.42 y). Mean time between transplant and otorhinolaryngology examination was 747.9 ± 37.1 days (median of 412 d; range, 30-5488 d). The mean time between transplant and otorhinolaryngology visit was 490.7 ± 41.9 days (median of 316 d; range, -29 to 2638) in the liver transplant group and 874.8 ± 50.1 days (median of 566 d; range, -32 to 5488) in the kidney transplant group (P < .005).

To assess the relationship between diagnoses and impact of time interval between the otorhino­laryngology visit and transplant, otorhinolar­yngology examination times were classified as pretransplant, acute (0-30 d after transplant), subacute (31-180 d after transplant), and chronic (> 180 d after transplant) (Table 2). Most of the visits (66%, n = 357) were in the chronic period. Kidney transplant recipients were more frequently seen in the chronic period than liver transplant recipients (P = .001). The time of otorhinolaryngology exami­nation according to type of transplant is presented in Table 2.

Otorhinolaryngologic complaints of patients at the time of visit showed great diversity. The most frequent complaint was rhinorrhea (13.6%), followed by sore throat (10.9%), cough (8.3%), and headache (8.3%). Distribution of the chief complaints among the number of visits is presented in Table 3.

The most common physical examination finding was deviated septum (16.8%), followed by discharge and/or crusting in nose (14%) and cerumen in ear (10.5%). The detailed physical examination findings of patients are shown in Table 4.

The most common diagnosis was rhinosinusitis (15.5%). Chronic pharyngitis (13.3%) and epistaxis (12.2%) were also common. Table 5 presents a detailed list and distribution of the diagnoses according to functional regions. The most frequent diagnoses (rhinosinusitis, chronic pharyngitis, and epistaxis) and infectious disorders that have clinical importance for transplant recipients (ie, acute pharyngitis, tonsillitis, laryngitis, and infections affecting multiple regions of head and neck) were analyzed according to time of otorhinolaryngology examination (Table 6). Rhinosinusitis was the diagnosis in 85 visits (15.7%). Time-related analyses revealed that 3 of those visits were made before transplant, whereas 9, 15, and 58 visits were made in the postoperative acute, subacute, and chronic periods, respectively (P = .948). Rhinosinusitis was diagnosed more frequently in kidney transplant recipients (n = 65) than in liver transplant recipients (n = 20) (P = .037).

Presence of acute suppurative otitis media was seen in 12 visits (2.2%), with 9 in kidney and 3 in liver transplant recipients (P = .536). One of those visits was before transplant, whereas 4 were in the postoperative subacute and 7 were in the postoperative chronic time period (P = .529). Chronic pharyngitis was seen in 73 visits (13.5%), with 48 in kidney transplant and 25 in liver transplant recipients. Five patients were diagnosed before transplant, 5 were diagnosed at the postoperative acute, 17 at the postoperative subacute, and 46 at the postoperative chronic time period (P = .150).

Upper respiratory tract infection was the diagnosis in 61 visits (11.3%). Kidney transplant recipients made 49 and liver transplant recipients made 12 of those visits. Upper respiratory tract infection was the diagnosis for 4 visits in the postoperative acute period, for 10 visits in the postoperative subacute period, and for 47 visits in the postoperative chronic period (P = .112).

Allergic rhinitis or nonallergic-noninfectious rhinitis was the diagnosis for 40 visits (7.4%). Kidney transplant recipients made 29 and liver transplant recipients made 11 of those visits. One patient was diagnosed before transplant, whereas 3, 9, and 27 of the visits were made during the postoperative acute, the subacute, and the chronic period, respectively (P = .636).

Epistaxis was diagnosed in 68 visits (12.6%). Forty-seven of those visits were made by kidney transplant recipients, and 21 were made by liver transplant recipients (P = .647). Epistaxis was the diagnosis for 22 visits in the postoperative acute period, for 11 visits in the postoperative subacute period, and for 35 visits in the postoperative chronic period (P > .005). The incidence of epistaxis during the acute period was higher than the incidence at other time periods (P = .003) (Table 7).

Discussion

Organ transplant is inarguably one of the most remarkable therapeutic improvements in modern medicine. Advancements in organ transplant procedures have been closely related with numerous advances and innovations in other fields of medicine, including surgery, immunology, critical care medicine, and infectious diseases.1 Today, the success of an organ transplant depends on collaboration and harmonious work of a team that is composed of members from various medical specialties.

Immunosuppressive agents are used after allogeneic solid-organ transplant to lower the risk of organ rejection. Immunosuppressive treatment protocols most often include agents such as mycophenolate mofetil, tacrolimus, sirolimus, and steroids. These mainly interfere with various regulatory molecules such as interleukin 2, which either activate or regulate the functions of T and B cells. In general, higher doses are used in the early postoperative period; depending on the absence of organ rejection findings, the doses are usually lowered after postoperative month 6. Despite the diagnostic and therapeutic advances that have been made in recent decades, nosocomial, opportunistic, and community-acquired infections pose serious risks for patients during the postoperative follow-up period. Transplant recipients are expected to be prone to infections since they receive long-term immunosuppressive therapy.

The risk for respiratory complications after solid-organ transplant continues to be high, and post­operative respiratory complications are more frequent after liver, heart, and lung transplant, with a lower incidence after kidney transplant.5 That was the case in our patient group, since nonspecific acute upper respiratory tract infections (including rhinosinusitis, tonsillopharyngitis, and laryngitis) constituted the most common diagnoses among all otorhino­laryngologic diagnoses. In our patient group, however, infections were more frequently encountered in kidney transplant recipients. In a recent epidemiologic study, Bahrami and associates reported that infections were frequently seen in renal allograft recipients followed-up for 1 year after transplant, with the most common site involving the urinary tract.6 Most infections were encountered within the first 3 months after transplant. In our patient group, we only evaluated the head and neck region as the site of infection and found that the incidence of acute infections was higher during the chronic period (ie, ≥ 6 months posttransplant).

Most patients in our study group were assessed in the outpatient clinic, and microbiologic analyses of pathogens were not conducted. Thus, we may only speculate that most of the acute infections in our patient group were community acquired. A prospective, controlled study with microbiologic analyses would better test the validity of that assumption. Nevertheless, prompt diagnosis and treatment of infection in a transplant recipient are extremely important to prevent morbidity and mortality.

In our patient group, epistaxis was more frequently seen in the early postoperative period (within month 1 posttransplant) than in later time periods. The reason for that finding may be the anticoagulant treatment protocol that is used. Anticoagulant treatment is routinely given to all kidney transplant and liver transplant recipients in our hospital. Heparin/nadroparin (low-molecular-weight heparin) is administered for 7 days after liver transplant. Dipyridamole and acetylsalicylic acid are started afterward and used for 3 and 6 months, respectively. Kidney transplant recipients also use acetylsalicylic acid for 6 months. The relatively increased epistaxis frequency in the early post­operative period may also be related to hyper­splenism-related thrombocytopenia and platelet function disorders due to chronic liver and/or kidney diseases, as those disorders may show slow and gradual improvement after transplant.

This descriptive study had a retrospective design, and only available and accessible data were evaluated. Thus, reliability of the results is directly and inherently interrelated with the reliability of the medical records. Our hospital serves as a tertiary care referral center, and most patients who receive procedures at our hospital live in other cities. Although all of the transplant recipients were followed up closely and were advised to apply directly to our hospital in case of any medical problem, it is highly possible that a considerable number of patients may have sought treatment at health care centers that were closer to their home. Thus, our records may not completely reflect the otorhinolaryngologic outpatient profile of the solid-organ transplant recipients and that should be kept in mind when interpreting the results.

In conclusion, liver or kidney transplant recipients are prone to a diversity of otorhino­laryngologic problems that may increase morbidity and mortality during the perioperative and postoperative periods. Surgeons should be aware of the otorhinolaryngologic symptoms, signs, and diagnoses that potentially have important effects in the management of a liver or kidney transplant recipient.


References:

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DOI : 10.6002/ect.2018.0173


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From the 1Department of Otorhinolaryngology and the 2Division of Transplantation, Department of General Surgery, Baskent University Faculty of Medicine, Ankara, Turkey
Acknowledgements: The authors declare no conflicts of interest. This study was supported by the Baskent University Research Fund. This work was presented at the Baskent University XVth Medical Students’ Symposium, 14 May 2013, Ankara, Turkey. The authors thank medical students Merve Civelek, Esra Karataş, Gözde Gümüş, and Özgür Akman for their valuable contributions to the preparation of this work.
Corresponding author: Evren Hizal, Baskent University Hospital, Department of Otorhinolaryngology, 5 Sokak No. 48 Bahcelievler, 06490 Ankara, Turkey
Phone: +90 312 203 0539
E-mail: drevren@gmail.com