Am J Clin Dermatol DOI 10.1007/s40257-015-0117-9
ORIGINAL RESEARCH ARTICLE
Risk of Sudden Sensorineural Hearing Loss in Patients with Psoriasis: A Retrospective Cohort Study Yung-Chang Yen • Yung-Song Lin Shih-Feng Weng • Feng-Jie Lai
•
Ó Springer International Publishing Switzerland 2015
Abstract Significance Psoriasis, a common immune-mediated disease, affects approximately 2 % of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis. Objectives We tested the hypothesis that psoriasis is a risk factor for developing SSNHL. Methods Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n = 28,817) with gender-, age-, and comorbidities-matched controls (n = 28,817). We followed each patient until the end of
2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis. Results The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95 % confidence interval [CI] 1.18–1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95 % CI 1.05–2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different. Conclusions and Relevance Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.
Y.-C. Yen Department of Ophthalmology, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan
S.-F. Weng Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
Y.-C. Yen Department of Nursing, Min Hwei College of Health Care Management, Tainan, Taiwan
S.-F. Weng Department of Hospital and Health Care Administration, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
Y.-S. Lin Center of General Education, South Taiwan University of Science and Technology, Tainan, Taiwan Y.-S. Lin (&) Department of Otolaryngology, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan e-mail: [email protected] Y.-S. Lin Department of Otolaryngology, Chi Mei Medical Center, Tainan, Taiwan
F.-J. Lai Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan
Y.-C. Yen et al.
Key Points A nationwide, population-based cohort study revealed an increased risk of sudden sensorineural hearing loss (SSNHL) in patients with psoriasis. Combining the cohort results, comorbid hypertension was an independent risk factor of SSNHL in this study. Awareness of the elevated risk of developing SSNHL in patients with psoriasis might prompt the early detection and treatment of SSNHL.
1 Introduction Sudden sensorineural hearing loss (SSNHL) is generally defined as a sensorineural hearing loss of 30 dB or more over at least three contiguous audiometric frequencies occurring over less than 3 days. It can be an isolated symptom or the presenting symptom of a systemic disease [1]. Although the diagnosis in the majority of patients with SSNHL is idiopathic, multiple etiologies have been identified, including viral infection, vascular impairment, autoimmune disease, inner ear pathology, and central nervous system anomalies [2]. It is well known that SSNHL might be a manifestation of systemic vascular involvement in autoimmune diseases [3]. Psoriasis, a well known immunemediated disease, affects approximately 2 % of the population worldwide. A few case reports [4, 5] have associated psoriasis and chronic sensorineural hearing impairment. A recent case–control study [6] reported that the incidence of bilateral and symmetrical sensorineural hearing loss (SNHL), predominantly in the high-frequency region, was higher in patients with psoriatic arthritis than in controls. Because psoriasis is a chronic inflammatory skin disease that involves multiple underlying genetic and environmental factors, the association between psoriasis and other diseases has drawn increasing interest in recent years. Many studies have reported that the prevalences of cardiovascular disease [3, 7], diabetes mellitus [7, 8], hypertension [9], and dyslipidemia [1, 3, 4] are higher in patients with psoriasis than in the general population. Systemic inflammatory mediators generated in psoriasis were hypothesized to be the underlying mechanism of the associations between these diseases and psoriasis. These diseases are also assumed to be associated with SSNHL [3, 7, 8]. Hence, whether SSNHL and psoriasis share a mechanism that associates them with these chronic
diseases is worth exploring. Furthermore, autoantibodies have been associated with SSNHL. McCabe (2007) first described a clinical entity characterized by steroid-responsive, rapidly progressive sensorineural hearing loss in 1979 [10]. Subsequently, serological support for the involvement of the immune system in SSNHL was provided by Harris and Sharp [11], who found circulating antibodies against several cochlear antigens in patients with idiopathic, progressive, bilateral SSNHL. Hisashi et al. [12] suggested that these autoantibodies induce thrombosis in the labyrinthine vessels, thereby causing subsequent damage to the inner ear that results in sensorineural hearing loss. Therefore, SSNHL might be a manifestation of systemic vascular involvement in psoriasis and might have an important effect on the health of patients with psoriasis. However, the risk of developing SSNHL in patients with psoriasis has not been systematically examined. We hypothesized that psoriasis is a risk factor for developing SSNHL. Therefore, we retrospectively investigated the incidence of SSNHL in patients with psoriasis. The effects of comorbid stroke, coronary artery disease (CAD), hypertension, diabetes mellitus, chronic renal disease (CRD), and hyperlipidemia on the risk of developing SSNHL in patients with psoriasis were also examined.
2 Materials and Methods 2.1 Data Sources The data used in this analysis were obtained from Taiwan’s National Health Insurance Research Database (NHIRD), which contains all of the claims data from 1996 through 2011 of the 23 million beneficiaries covered by the National Health Insurance Program. There were no significant differences in age, gender, geographic distribution, or healthcare costs between the sample group and all enrollees. The database contains encrypted patient identification numbers, ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes for clinical diagnoses and procedures, details of prescribed drugs, dates of admission and discharge, and basic sociodemographic information like gender and date of birth. 2.2 Design A retrospective cohort study was conducted with two study groups: patients with psoriasis (psoriasis cohort) and matched controls without psoriasis (control cohort). The psoriasis cohort included patients with an initial diagnosis of psoriasis or psoriasis arthritis (ICD-9 codes 690 [Erythematosquamous dermatosis], 696.0, 696.1). Information that identified patients with psoriasis and SSNHL (ICD-9 code
Psoriasis and Sudden Sensorineural Hearing Loss
388.2) was based on a minimum of three visits and a corresponding diagnosis provided by referral teaching hospitals and tertiary referral medical centers. Patients without medical claims for psoriasis that matched the patients in the psoriasis cohort in terms of gender, age (±30 days), baseline comorbidities, geographic distribution, monthly income, and index date were selected for the control group. The index date for the patients with psoriasis was the date between 2001 and 2006 on which they were first registered as having psoriasis. The index dates for the patients without psoriasis were matched based on the index dates of the patients in the psoriasis cohort. Other comorbidities that may have presented before the index date were defined as follows: stroke (ICD-9 codes 430–438), CAD (ICD-9 codes 410–414, A270, A279), migraine (ICD-9 codes 346.0, 346.1, 346.9), hypertension (ICD-9 codes 401–405), diabetes (ICD-9 code 250), CRD (ICD-9 codes 582, 583, 585, 586, 588), and hyperlipidemia (ICD-9 code 272). Propensity-score matching, which can bundle many confounding covariates that may be present in an observational study with this number of variables, was used to reduce any selection bias in our hypothesis [13]. Score matching identified the predicted probability of obtaining one psoriasis cohort patient versus one control cohort patient from the logistic regression model using the baseline covariates of age, gender, and the comorbidities of stroke, CAD, migraine, hypertension, diabetes, CRD, and hyperlipidemia by choosing an 8-digit match. The comorbidities were identified only through a diagnosis made during admission or by a specialist during each of three hospital visits. Diagnoses of psoriasis were provided by referral teaching hospitals and tertiary referral medical centers. Drug histories of the psoriasis cohort patients were examined in the database. Patients who subsequently developed SSNHL were excluded from the psoriasis cohort if they were treated with acitretin or topical salicylate acid within 30 days of the diagnosis of SSNHL. Routine peer reviews have been conducted within Taiwan’s NHI Bureau to maintain the consistency of the diagnoses between every referral teaching hospital and every tertiary referral medical center. To investigate the association between the occurrence of SSNHL and the disease progress of psoriasis, only patients with psoriasis newly diagnosed between 2001 and 2006 were included. The claims data from 1996 to 2000 were used to confirm that no enrolled patients had ever contracted psoriasis before 2001. Patients were followed up for a minimum of 5 years (2006–2011) to determine the incidence of SSNHL (ICD-9 code 388.2) until the end of 2011 or until they were censored due to death. The identification numbers of all of the patients in the NHIRD were encrypted to protect their privacy. The Institutional Review Boards of Chi Mei Medical Center and Taipei Medical University approved this study.
2.3 Statistical Analysis Descriptive statistical analyses using Pearson’s v2 test were done to compare the differences in sociodemographic characteristics and comorbidities between the psoriasis cohort and the control cohort. The incidence rate was calculated as the number of SSNHL cases identified during follow-up divided by the total personyears for each group sub-grouped by gender, age, and comorbidities. The risk of developing SSNHL was compared by estimating the incidence ratio using a Poisson regression. The risks of developing SSNHL associated with the comorbidities of stroke, CAD, migraine, hypertension, diabetes, CRD, and hyperlipidemia were estimated using Cox proportional hazard models. A Cox proportional hazard regression analysis and a Table 1 Demographic characteristics and comorbidities for the psoriasis and control cohorts Psoriasis cohort, n (%) [n = 28,817]
Control cohort, n (%) [n = 28,817]
p value
1.00
Age (years) 0–35
14,059 (48.79)
14,059 (48.79)
35–49
6995 (24.27)
6995 (24.27)
50–64
4072 (14.13)
4072 (14.13)
C65
3691 (12.81)
3691 (12.81)
Gender Female
14,840 (51.50)
14,840 (51.50)
Male
13,977 (48.50)
13,977 (48.50)
1.00
Baseline comorbidity Stroke
512 (1.78)
512 (1.78)
1.00
CAD
801 (2.78)
801 (2.78)
1.00
Hypertension
2875 (9.98)
2875 (9.98)
1.00
Diabetes
1139 (3.95)
1139 (3.95)
1.00
136 (0.47) 661 (2.29)
136 (0.47) 661 (2.29)
1.00 1.00
26 (0.09)
26 (0.09)
CRD Hyperlipidemia Migraine Geographic distribution North
13,853 (48.07)
13,853 (48.07)
Central
5517 (19.14)
5517 (19.14)
South
8710 (30.23)
8710 (30.23)
737 (2.56)
737 (2.56)
East
1.00
Monthly income \NT$15,840
11,343 (39.36)
11,343 (39.36)
NT$15,841–NT$25,000
8070 (28.00)
8070 (28.00)
[NT$25,001
9404 (32.63)
9404 (32.63)
1.00
Propensity score matching scheme choosing an 8-digit match yielded a control cohort with exactly the same frequencies of the comorbidities as in the psoriasis cohort CAD coronary artery disease, CRD chronic renal disease, NT$ new Taiwan dollars (US$1 = ca. NT$30)
Y.-C. Yen et al.
Kaplan–Meier analysis were used to calculate the cumulative incidence rates of SSNHL in the two cohorts, and the log-rank test was used to analyze the differences
between the survival curves. All analyses were done using SAS 9.2 (SAS Institute, Cary, NC). Significance was set at p \ 0.05 (two-sided).
3 Results 3.1 The Incidence of SSNHL Based on Patient Characteristics
Fig. 1 The sudden sensorineural hearing loss (SSNHL) incidence in the psoriasis and the control cohorts in Taiwan (2001–2011). By the end of the follow-up period, the incidence of SSNHL was significantly higher in the psoriasis cohort than in the control cohort (p \ 0.01)
Based on the 2001–2006 claims data, 28,817 patients with psoriasis met the eligibility criteria, and an additional 28,817 patients without medical claims for psoriasis who were also gender-, age- (±30 days), and index-date-matched with the patients in the psoriasis cohort were then randomly selected as controls. More than half (n = 14,840; 51.5 %) of the patients with psoriasis were female (Table 1). By the end of the follow-up period, the incidence of SSNHL was significantly higher in the psoriasis cohort than in the control cohort (p \ 0.01) (Fig. 1). The incidence rates of SSNHL classified by gender and age were compared between the psoriasis cohort and the control cohort. Patients who were 35–49 and C65 years old had a significantly higher incidence of SSNHL in the psoriasis cohort than in the control cohort (p = 0.04 and p = 0.02, respectively) (Table 2). Combining the results from both groups, the incidence of SSNHL increased with age. The risks of SSNHL in
Table 2 Risk of sudden sensorineural hearing loss for the psoriasis and control cohorts Characteristics
All Age (years) 0–35 35–49 50–64 C65 Gender Male Female Comorbidity Stroke CAD Hypertension Diabetes CRD Hyperlipidemia Migraine
Psoriasis cohort
Control cohort
n
SSNHL
PY
28,817
159
223,268.83
14,059 6995 4072 3691
34 39 39 47
13,977 14,840 512 801 2875 1139 136 661 26
Rate
n
SSNHL
PY
7.12
28,817
106
224,020.21
4.73
111,266.80 55,073.96 30,935.35 25,992.75
3.06 7.08 12.61 18.08
14,059 6995 4072 3691
31 23 25 27
111,078.20 55,287.22 30,981.92 26,672.90
2.79 4.16 8.07 10.12
91 68
107,212.71 116,056.11
8.49 5.86
13,977 14,840
63 43
107,702.54 116,317.66
5.85 3.70
4 9 32 10 2 5 1
3266.48 5718.95 20,483.81 7980.31 852.88 4820.59 183.69
12.25 15.74 15.62 12.53 23.45 10.37 54.44
512 801 2875 1139 136 661 26
4 11 31 12 0 7 0
3535.88 5656.83 20,734.07 8042.20 881.94 4793.91 203.94
11.31 19.45 14.95 14.92 0 14.60 0
IRR (95 % CI)
p value
1.51 (1.18–1.92)
\0.01
Rate
1.09 1.70 1.56 1.79
(0.67–1.78) (1.02–2.85) (0.95–2.58) (1.11–2.87)
0.72 0.04 0.08 0.02
1.45 (1.05–2.00) 1.59 (1.08–2.32)
0.02 0.02
1.08 0.81 1.04 0.84
(0.27–4.33) (0.34–1.95) (0.64–1.71) (0.36–1.94)
0.92 0.64 0.86 0.68
0.71 (0.23–2.24)
0.56
Propensity score matching scheme choosing an 8-digit match yielded a control cohort with exactly the same frequencies of the comorbidities as in the psoriasis cohort CAD coronary artery disease, CI confidence interval, CRD chronic renal disease, IRR incidence rate ratio, PY person-years, Rate per 10,000 person-years, SSNHL sensorineural hearing loss * p \ 0.05
Psoriasis and Sudden Sensorineural Hearing Loss
patients 35–49 years old, 50–64 years old, and C65 years old were significantly higher than in patients 0–35 years old (adjusted hazard ratio [AHR] 1.86; 95 % CI 1.31–2.64; AHR 3.08 95 % CI 2.15–4.42; and AHR 3.70; 95 % CI 2.54–5.44, respectively) (Table 3). The incidence rate of SSNHL was higher in females (incidence rate ratio [IRR] 1.59; 95 % CI 1.08–2.32) and males (IRR 1.45; 95 % CI 1.05–2.00) in the psoriasis cohort than in the control cohort (Table 2). Table 3 Crude and adjusted hazard ratios of Cox proportional hazard regressions and 95 % confidence intervals for the development of sudden sensorineural hearing loss for the psoriasis and control cohorts Cohort
Crude hazard ratio (95 % CI)
Adjusted hazard ratio (95 % CI)
Psoriasis cohort
1.51 (1.18–1.93)*
1.51 (1.18–1.93)*
Control cohort
1.000
1.000
Age (years) 0–35
1.000
1.000
35–49
1.92 (1.36–2.72)*
1.86 (1.31–2.64)*
50–64 C65
3.56 (2.52–5.02)* 4.84 (3.47–6.75)*
3.08 (2.15–4.42)* 3.70 (2.51–5.44)*
Female
0.67 (0.52–0.85)*
0.79 (0.62–1.01)
Male
1.000
1.000
Yes
2.03 (1.01–4.11)*
0.77 (0.37–1.60)
No
1.000
1.000
Yes
2.46 (1.59–3.80)*
1.10 (0.69–1.76)
No
1.000
1.000
Yes
3.10 (2.34–4.11)*
1.49 (1.05–2.13)*
No
1.000
1.000
3.2 SSNHL was not Associated with Comorbidities There were no significant differences in the prevalence of comorbid stroke, CAD, migraine, hypertension, diabetes, CRD, or hyperlipidemia between the two groups (Table 1). A multivariate Cox proportional hazard regression analysis, which combined the results from the psoriasis and control cohorts, and which included gender, age, and comorbidities in the model, was run. The analysis showed that the risk of developing SSNHL was higher in the psoriasis cohort than in the control cohort (AHR 1.51; 95 % CI 1.18–1.92), but that there were no significant differences in the risk of developing SSNHL with the comorbidities of stroke, diabetes, migraine, CAD, CRD, or hyperlipidemia (Table 3). However, hypertension was an independent risk factor for developing SSNHL (AHR 1.49; 95 % CI 1.05–2.13). A Cox proportional hazard regression analysis of the incidence of SSNHL between patients with comorbid hypertension in both cohorts showed no significant differences (p = 0.86) (Table 2).
4 Discussion
Gender
Stroke
Diabetes
Hypertension
CRD Yes
1.97 (0.49–7.93)
0.89 (0.22–3.60)
1.000
1.000
Yes
3.15 (2.00–4.97)*
1.24 (0.75–2.04)
No
1.000
1.000
Yes
2.18 (1.22–3.90)*
1.03 (0.56–1.88)
No
1.000
1.000
Yes
4.41 (0.62–31.39)
4.04 (0.57–28.84)
No
1.000
1.000
No CAD
Hyperlipidemia
Migraine
Adjusted for age, gender, comorbidities, income, and geographic distribution. All patients in the control and psoriasis cohorts were analyzed together CRD chronic renal disease, CAD coronary artery disease, SSNHL sudden sensorineural hearing loss * p \ 0.05
Our major finding was that patients with psoriasis had a significantly (1.51 times) higher incidence of SSNHL than did patients without psoriasis from the general population. The incidence of SSNHL increased with the age of the patients: patients C65 years old had the highest incidence of SSNHL. This was compatible with our finding in patients with SSNHL comorbid with systemic lupus erythematosus, a common autoimmune disease [4]. After combining the results from both cohorts, we found that there was no significant difference in the risk of SSNHL between males and females (Table 3). Although the prevalence of autoimmune diseases is higher in females than in males [14, 15], the reason for this is unclear; however, genetic (X-linked) factors and hormonal aspects are likely involved [16–18]. To the best of our knowledge, there are no English reports that discuss the significance of gender in the association between SSNHL and psoriasis. There is growing evidence that patients with psoriasis have a higher prevalence of associated comorbid diseases, such as CAD, diabetes, hypertension, and dyslipidemia [19]. Both the development of psoriatic lesions and the breakdown of atherosclerotic plaques share the common contributing factors of inflammatory cells and proinflammatory cytokines [20]. For example, tumor necrosis factor (TNF)-a, an inflammatory cytokine, is involved in the pathogenesis of both psoriasis and atherosclerosis [2]. It is possible that a shared mechanism for both psoriasis and SSNHL in association with cardiovascular diseases accounts for the higher risk of
Y.-C. Yen et al.
SSNHL in patients with psoriasis. Because of this, the prevalence of CAD was matched in the present study. Hence, the higher risk of SSNHL in patients with psoriasis in the present study cannot be attributed to a shared mechanism. Several studies [5, 21] have reported elevated plasma renin activity and elevated angiotensin-converting enzyme (ACE) activity. Eventually, poor blood-pressure control might induce changes in the renin–angiotensin system. Higher oxidative stress in patients with psoriasis is also thought to impair the vasodilatory mechanism of the endothelium [22]. Hence, an impaired vasodilatory mechanism might be the reason for the higher risk of SSNHL in patients with psoriasis. Therefore, hypertension was matched as another confounder. Psoriasis has been associated with a higher risk for dyslipidemia [23]. Possible underlying contributing factors include the cytokines IL-1, IL-6, and TNFa, all of which mediate psoriasis. Those cytokines might increase the expression of cellular adhesion molecules, promote lipid deposition on arterial walls, and alter the lipoprotein composition. Ultimately, arterial plaques might develop [24]. Cytokines might also increase the expression of matrix metalloproteinases, which degrade the plaque’s fibrous cap. Eventually, the plaque may rupture and thrombi might appear [24, 25]. Inflammation and a higher level of adhesion and of oxidants in endothelial cells in psoriasis imply early atherogenesis [26]. These processes might also contribute to the development of SSNHL, because one of the proposed risk factors of SSNHL is microvascular compromise in the cochlea. However, the association between inherited and acquired prothrombotic factors and SSNHL suggests that the microvascular impairment that causes SSNHL might be a multifactorial mechanism [27, 28]. Although there are contradictory reports on the role of thrombosis in the development of SSNHL [29–31], we also matched the prevalence of hyperlipidemia as a confounder in the present study. Several epidemiological studies have also argued that psoriasis is an independent risk factor for incident type 2 diabetes [8, 32, 33]. Overproduction of T helper 1 (Th1) cytokines in psoriasis is thought to be a possible mechanism underlying the increase of insulin [8, 34, 35]. Evidence from human temporal bone studies has consistently shown the cooccurrence of cochlear microangiopathy and diabetes [36, 37]. Furthermore, diabetes is associated with a higher risk of SSNHL [38]. Hence, microangiopathy may be one of the mechanisms shared between the association of diabetes and SSNHL and of diabetes and psoriasis. In the present study, diabetes was therefore matched as a confounder. The prevalence of migraine was found to be 1.38 times higher in patients with psoriasis than in the general
population [39]. Migraine has recently been associated with an increased incidence of SSNHL [40, 41]. Migraine with aura can be considered a risk factor for ischemic stroke [42], and SSNHL can be associated with an increased risk of stroke [43]. Migraine without aura is associated with a higher prevalence of hypertension, but the association between migraine and cardiovascular risk is still under debate [44]. Some researchers [40, 45] have claimed that migraine comorbid with hypertension is associated with a trend of developing SSNHL. The migraineassociated inflammation or neurovascular dysfunction in response to certain triggers has been assumed to provoke the occurrence of idiopathic SSNHL [40]. Although the exact mechanism linking migraine and SSNHL is unknown, comorbid migraine was matched as a confounder in this study. Most possible comorbid confounders were matched between the psoriasis and control cohorts. Hence, the factors associated with psoriasis and those comorbid chronic diseases can only be part of the factors underlying the association between psoriasis and the subsequent development of SSNHL. The mechanisms underlying the higher risk of SSNHL in patients with psoriasis remain unclear. The underlying mechanisms of the association between psoriasis and SSNHL require more research. Nevertheless, our results may add evidence of the association between autoimmune disease and SSNHL. The present study’s large national population-based sample allows us to determine the risk factors for developing SSNHL with a minimal selection bias. A large sample also increases the statistical power and precision of risk appraisal. This study has some limitations. Information about several suspected risk factors for SSNHL were not available in the insurance database; for example, data about smoking or about chronic exposure to occupational and environmental noise. The inability to assess these factors may have caused a bias. The insurance claims data did not include information on laboratory test results or the severity of the hearing loss. Clinical examinations for skin lesions, systemic manifestations, and imaging results, for example, were not available to evaluate the extent of psoriasis treatment in patients. Awareness of the elevated risk of developing SSNHL in patients with psoriasis might prompt the early detection and treatment of the condition. Medications that control autoimmune activity might benefit patients with psoriasis who are at risk for developing SSNHL.
5 Conclusion Psoriasis was significantly associated with a higher risk of developing SSNHL. The risk tended to increase directly
Psoriasis and Sudden Sensorineural Hearing Loss
with patient age. This finding may add evidence to the association between autoimmune disease and the development of SSNHL. We suggest that physicians counsel patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL. Acknowledgments The study was designed and conducted by Y. S. Lin and Y. C. Yen. Y. C. Yen, F. J. Lai, and Y. S. Lin recorded the clinical data and supervised the writing of the manuscript. S. F. Wang did the epidemiological and statistical analyses. Y. S. Lin wrote the paper and was primarily responsible for its final content. Y. C. Yen, Y. S. Lin, S. F. Weng, and F. J. Lai have nothing to disclose and declare no conflicts of interest. This study was supported by a Grant from the Taipei Medical University–Chi Mei Medical Center Research Fund
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42. Sacco S, Kurth T. Migraine and the risk for stroke and cardiovascular disease. Curr Cardiol Rep. 2014;16(9):524. 43. Lin HC, Chao PZ, Lee HC. Sudden sensorineural hearing loss increases the risk of stroke: a 5-year follow-up study. Stroke. 2008;39(10):2744–8. 44. Harandi SA, Togha M, Sadatnaseri A, Hosseini SH, Jahromi SR. Cardiovascular risk factors and migraine without aura: a case– control study. Iran J Neurol. 2013;12(3):98–101. 45. Mosnier I, Stepanian A, Baron G, Bodenez C, Robier A, Meyer B, et al. Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss: a case–control study. Audiol Neurootol. 2011;16(1):55–66.
ORIGINAL RESEARCH ARTICLE
Risk of Sudden Sensorineural Hearing Loss in Patients with Psoriasis: A Retrospective Cohort Study Yung-Chang Yen • Yung-Song Lin Shih-Feng Weng • Feng-Jie Lai
•
Ó Springer International Publishing Switzerland 2015
Abstract Significance Psoriasis, a common immune-mediated disease, affects approximately 2 % of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis. Objectives We tested the hypothesis that psoriasis is a risk factor for developing SSNHL. Methods Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n = 28,817) with gender-, age-, and comorbidities-matched controls (n = 28,817). We followed each patient until the end of
2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis. Results The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95 % confidence interval [CI] 1.18–1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95 % CI 1.05–2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different. Conclusions and Relevance Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.
Y.-C. Yen Department of Ophthalmology, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan
S.-F. Weng Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
Y.-C. Yen Department of Nursing, Min Hwei College of Health Care Management, Tainan, Taiwan
S.-F. Weng Department of Hospital and Health Care Administration, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
Y.-S. Lin Center of General Education, South Taiwan University of Science and Technology, Tainan, Taiwan Y.-S. Lin (&) Department of Otolaryngology, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan e-mail: [email protected] Y.-S. Lin Department of Otolaryngology, Chi Mei Medical Center, Tainan, Taiwan
F.-J. Lai Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan
Y.-C. Yen et al.
Key Points A nationwide, population-based cohort study revealed an increased risk of sudden sensorineural hearing loss (SSNHL) in patients with psoriasis. Combining the cohort results, comorbid hypertension was an independent risk factor of SSNHL in this study. Awareness of the elevated risk of developing SSNHL in patients with psoriasis might prompt the early detection and treatment of SSNHL.
1 Introduction Sudden sensorineural hearing loss (SSNHL) is generally defined as a sensorineural hearing loss of 30 dB or more over at least three contiguous audiometric frequencies occurring over less than 3 days. It can be an isolated symptom or the presenting symptom of a systemic disease [1]. Although the diagnosis in the majority of patients with SSNHL is idiopathic, multiple etiologies have been identified, including viral infection, vascular impairment, autoimmune disease, inner ear pathology, and central nervous system anomalies [2]. It is well known that SSNHL might be a manifestation of systemic vascular involvement in autoimmune diseases [3]. Psoriasis, a well known immunemediated disease, affects approximately 2 % of the population worldwide. A few case reports [4, 5] have associated psoriasis and chronic sensorineural hearing impairment. A recent case–control study [6] reported that the incidence of bilateral and symmetrical sensorineural hearing loss (SNHL), predominantly in the high-frequency region, was higher in patients with psoriatic arthritis than in controls. Because psoriasis is a chronic inflammatory skin disease that involves multiple underlying genetic and environmental factors, the association between psoriasis and other diseases has drawn increasing interest in recent years. Many studies have reported that the prevalences of cardiovascular disease [3, 7], diabetes mellitus [7, 8], hypertension [9], and dyslipidemia [1, 3, 4] are higher in patients with psoriasis than in the general population. Systemic inflammatory mediators generated in psoriasis were hypothesized to be the underlying mechanism of the associations between these diseases and psoriasis. These diseases are also assumed to be associated with SSNHL [3, 7, 8]. Hence, whether SSNHL and psoriasis share a mechanism that associates them with these chronic
diseases is worth exploring. Furthermore, autoantibodies have been associated with SSNHL. McCabe (2007) first described a clinical entity characterized by steroid-responsive, rapidly progressive sensorineural hearing loss in 1979 [10]. Subsequently, serological support for the involvement of the immune system in SSNHL was provided by Harris and Sharp [11], who found circulating antibodies against several cochlear antigens in patients with idiopathic, progressive, bilateral SSNHL. Hisashi et al. [12] suggested that these autoantibodies induce thrombosis in the labyrinthine vessels, thereby causing subsequent damage to the inner ear that results in sensorineural hearing loss. Therefore, SSNHL might be a manifestation of systemic vascular involvement in psoriasis and might have an important effect on the health of patients with psoriasis. However, the risk of developing SSNHL in patients with psoriasis has not been systematically examined. We hypothesized that psoriasis is a risk factor for developing SSNHL. Therefore, we retrospectively investigated the incidence of SSNHL in patients with psoriasis. The effects of comorbid stroke, coronary artery disease (CAD), hypertension, diabetes mellitus, chronic renal disease (CRD), and hyperlipidemia on the risk of developing SSNHL in patients with psoriasis were also examined.
2 Materials and Methods 2.1 Data Sources The data used in this analysis were obtained from Taiwan’s National Health Insurance Research Database (NHIRD), which contains all of the claims data from 1996 through 2011 of the 23 million beneficiaries covered by the National Health Insurance Program. There were no significant differences in age, gender, geographic distribution, or healthcare costs between the sample group and all enrollees. The database contains encrypted patient identification numbers, ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes for clinical diagnoses and procedures, details of prescribed drugs, dates of admission and discharge, and basic sociodemographic information like gender and date of birth. 2.2 Design A retrospective cohort study was conducted with two study groups: patients with psoriasis (psoriasis cohort) and matched controls without psoriasis (control cohort). The psoriasis cohort included patients with an initial diagnosis of psoriasis or psoriasis arthritis (ICD-9 codes 690 [Erythematosquamous dermatosis], 696.0, 696.1). Information that identified patients with psoriasis and SSNHL (ICD-9 code
Psoriasis and Sudden Sensorineural Hearing Loss
388.2) was based on a minimum of three visits and a corresponding diagnosis provided by referral teaching hospitals and tertiary referral medical centers. Patients without medical claims for psoriasis that matched the patients in the psoriasis cohort in terms of gender, age (±30 days), baseline comorbidities, geographic distribution, monthly income, and index date were selected for the control group. The index date for the patients with psoriasis was the date between 2001 and 2006 on which they were first registered as having psoriasis. The index dates for the patients without psoriasis were matched based on the index dates of the patients in the psoriasis cohort. Other comorbidities that may have presented before the index date were defined as follows: stroke (ICD-9 codes 430–438), CAD (ICD-9 codes 410–414, A270, A279), migraine (ICD-9 codes 346.0, 346.1, 346.9), hypertension (ICD-9 codes 401–405), diabetes (ICD-9 code 250), CRD (ICD-9 codes 582, 583, 585, 586, 588), and hyperlipidemia (ICD-9 code 272). Propensity-score matching, which can bundle many confounding covariates that may be present in an observational study with this number of variables, was used to reduce any selection bias in our hypothesis [13]. Score matching identified the predicted probability of obtaining one psoriasis cohort patient versus one control cohort patient from the logistic regression model using the baseline covariates of age, gender, and the comorbidities of stroke, CAD, migraine, hypertension, diabetes, CRD, and hyperlipidemia by choosing an 8-digit match. The comorbidities were identified only through a diagnosis made during admission or by a specialist during each of three hospital visits. Diagnoses of psoriasis were provided by referral teaching hospitals and tertiary referral medical centers. Drug histories of the psoriasis cohort patients were examined in the database. Patients who subsequently developed SSNHL were excluded from the psoriasis cohort if they were treated with acitretin or topical salicylate acid within 30 days of the diagnosis of SSNHL. Routine peer reviews have been conducted within Taiwan’s NHI Bureau to maintain the consistency of the diagnoses between every referral teaching hospital and every tertiary referral medical center. To investigate the association between the occurrence of SSNHL and the disease progress of psoriasis, only patients with psoriasis newly diagnosed between 2001 and 2006 were included. The claims data from 1996 to 2000 were used to confirm that no enrolled patients had ever contracted psoriasis before 2001. Patients were followed up for a minimum of 5 years (2006–2011) to determine the incidence of SSNHL (ICD-9 code 388.2) until the end of 2011 or until they were censored due to death. The identification numbers of all of the patients in the NHIRD were encrypted to protect their privacy. The Institutional Review Boards of Chi Mei Medical Center and Taipei Medical University approved this study.
2.3 Statistical Analysis Descriptive statistical analyses using Pearson’s v2 test were done to compare the differences in sociodemographic characteristics and comorbidities between the psoriasis cohort and the control cohort. The incidence rate was calculated as the number of SSNHL cases identified during follow-up divided by the total personyears for each group sub-grouped by gender, age, and comorbidities. The risk of developing SSNHL was compared by estimating the incidence ratio using a Poisson regression. The risks of developing SSNHL associated with the comorbidities of stroke, CAD, migraine, hypertension, diabetes, CRD, and hyperlipidemia were estimated using Cox proportional hazard models. A Cox proportional hazard regression analysis and a Table 1 Demographic characteristics and comorbidities for the psoriasis and control cohorts Psoriasis cohort, n (%) [n = 28,817]
Control cohort, n (%) [n = 28,817]
p value
1.00
Age (years) 0–35
14,059 (48.79)
14,059 (48.79)
35–49
6995 (24.27)
6995 (24.27)
50–64
4072 (14.13)
4072 (14.13)
C65
3691 (12.81)
3691 (12.81)
Gender Female
14,840 (51.50)
14,840 (51.50)
Male
13,977 (48.50)
13,977 (48.50)
1.00
Baseline comorbidity Stroke
512 (1.78)
512 (1.78)
1.00
CAD
801 (2.78)
801 (2.78)
1.00
Hypertension
2875 (9.98)
2875 (9.98)
1.00
Diabetes
1139 (3.95)
1139 (3.95)
1.00
136 (0.47) 661 (2.29)
136 (0.47) 661 (2.29)
1.00 1.00
26 (0.09)
26 (0.09)
CRD Hyperlipidemia Migraine Geographic distribution North
13,853 (48.07)
13,853 (48.07)
Central
5517 (19.14)
5517 (19.14)
South
8710 (30.23)
8710 (30.23)
737 (2.56)
737 (2.56)
East
1.00
Monthly income \NT$15,840
11,343 (39.36)
11,343 (39.36)
NT$15,841–NT$25,000
8070 (28.00)
8070 (28.00)
[NT$25,001
9404 (32.63)
9404 (32.63)
1.00
Propensity score matching scheme choosing an 8-digit match yielded a control cohort with exactly the same frequencies of the comorbidities as in the psoriasis cohort CAD coronary artery disease, CRD chronic renal disease, NT$ new Taiwan dollars (US$1 = ca. NT$30)
Y.-C. Yen et al.
Kaplan–Meier analysis were used to calculate the cumulative incidence rates of SSNHL in the two cohorts, and the log-rank test was used to analyze the differences
between the survival curves. All analyses were done using SAS 9.2 (SAS Institute, Cary, NC). Significance was set at p \ 0.05 (two-sided).
3 Results 3.1 The Incidence of SSNHL Based on Patient Characteristics
Fig. 1 The sudden sensorineural hearing loss (SSNHL) incidence in the psoriasis and the control cohorts in Taiwan (2001–2011). By the end of the follow-up period, the incidence of SSNHL was significantly higher in the psoriasis cohort than in the control cohort (p \ 0.01)
Based on the 2001–2006 claims data, 28,817 patients with psoriasis met the eligibility criteria, and an additional 28,817 patients without medical claims for psoriasis who were also gender-, age- (±30 days), and index-date-matched with the patients in the psoriasis cohort were then randomly selected as controls. More than half (n = 14,840; 51.5 %) of the patients with psoriasis were female (Table 1). By the end of the follow-up period, the incidence of SSNHL was significantly higher in the psoriasis cohort than in the control cohort (p \ 0.01) (Fig. 1). The incidence rates of SSNHL classified by gender and age were compared between the psoriasis cohort and the control cohort. Patients who were 35–49 and C65 years old had a significantly higher incidence of SSNHL in the psoriasis cohort than in the control cohort (p = 0.04 and p = 0.02, respectively) (Table 2). Combining the results from both groups, the incidence of SSNHL increased with age. The risks of SSNHL in
Table 2 Risk of sudden sensorineural hearing loss for the psoriasis and control cohorts Characteristics
All Age (years) 0–35 35–49 50–64 C65 Gender Male Female Comorbidity Stroke CAD Hypertension Diabetes CRD Hyperlipidemia Migraine
Psoriasis cohort
Control cohort
n
SSNHL
PY
28,817
159
223,268.83
14,059 6995 4072 3691
34 39 39 47
13,977 14,840 512 801 2875 1139 136 661 26
Rate
n
SSNHL
PY
7.12
28,817
106
224,020.21
4.73
111,266.80 55,073.96 30,935.35 25,992.75
3.06 7.08 12.61 18.08
14,059 6995 4072 3691
31 23 25 27
111,078.20 55,287.22 30,981.92 26,672.90
2.79 4.16 8.07 10.12
91 68
107,212.71 116,056.11
8.49 5.86
13,977 14,840
63 43
107,702.54 116,317.66
5.85 3.70
4 9 32 10 2 5 1
3266.48 5718.95 20,483.81 7980.31 852.88 4820.59 183.69
12.25 15.74 15.62 12.53 23.45 10.37 54.44
512 801 2875 1139 136 661 26
4 11 31 12 0 7 0
3535.88 5656.83 20,734.07 8042.20 881.94 4793.91 203.94
11.31 19.45 14.95 14.92 0 14.60 0
IRR (95 % CI)
p value
1.51 (1.18–1.92)
\0.01
Rate
1.09 1.70 1.56 1.79
(0.67–1.78) (1.02–2.85) (0.95–2.58) (1.11–2.87)
0.72 0.04 0.08 0.02
1.45 (1.05–2.00) 1.59 (1.08–2.32)
0.02 0.02
1.08 0.81 1.04 0.84
(0.27–4.33) (0.34–1.95) (0.64–1.71) (0.36–1.94)
0.92 0.64 0.86 0.68
0.71 (0.23–2.24)
0.56
Propensity score matching scheme choosing an 8-digit match yielded a control cohort with exactly the same frequencies of the comorbidities as in the psoriasis cohort CAD coronary artery disease, CI confidence interval, CRD chronic renal disease, IRR incidence rate ratio, PY person-years, Rate per 10,000 person-years, SSNHL sensorineural hearing loss * p \ 0.05
Psoriasis and Sudden Sensorineural Hearing Loss
patients 35–49 years old, 50–64 years old, and C65 years old were significantly higher than in patients 0–35 years old (adjusted hazard ratio [AHR] 1.86; 95 % CI 1.31–2.64; AHR 3.08 95 % CI 2.15–4.42; and AHR 3.70; 95 % CI 2.54–5.44, respectively) (Table 3). The incidence rate of SSNHL was higher in females (incidence rate ratio [IRR] 1.59; 95 % CI 1.08–2.32) and males (IRR 1.45; 95 % CI 1.05–2.00) in the psoriasis cohort than in the control cohort (Table 2). Table 3 Crude and adjusted hazard ratios of Cox proportional hazard regressions and 95 % confidence intervals for the development of sudden sensorineural hearing loss for the psoriasis and control cohorts Cohort
Crude hazard ratio (95 % CI)
Adjusted hazard ratio (95 % CI)
Psoriasis cohort
1.51 (1.18–1.93)*
1.51 (1.18–1.93)*
Control cohort
1.000
1.000
Age (years) 0–35
1.000
1.000
35–49
1.92 (1.36–2.72)*
1.86 (1.31–2.64)*
50–64 C65
3.56 (2.52–5.02)* 4.84 (3.47–6.75)*
3.08 (2.15–4.42)* 3.70 (2.51–5.44)*
Female
0.67 (0.52–0.85)*
0.79 (0.62–1.01)
Male
1.000
1.000
Yes
2.03 (1.01–4.11)*
0.77 (0.37–1.60)
No
1.000
1.000
Yes
2.46 (1.59–3.80)*
1.10 (0.69–1.76)
No
1.000
1.000
Yes
3.10 (2.34–4.11)*
1.49 (1.05–2.13)*
No
1.000
1.000
3.2 SSNHL was not Associated with Comorbidities There were no significant differences in the prevalence of comorbid stroke, CAD, migraine, hypertension, diabetes, CRD, or hyperlipidemia between the two groups (Table 1). A multivariate Cox proportional hazard regression analysis, which combined the results from the psoriasis and control cohorts, and which included gender, age, and comorbidities in the model, was run. The analysis showed that the risk of developing SSNHL was higher in the psoriasis cohort than in the control cohort (AHR 1.51; 95 % CI 1.18–1.92), but that there were no significant differences in the risk of developing SSNHL with the comorbidities of stroke, diabetes, migraine, CAD, CRD, or hyperlipidemia (Table 3). However, hypertension was an independent risk factor for developing SSNHL (AHR 1.49; 95 % CI 1.05–2.13). A Cox proportional hazard regression analysis of the incidence of SSNHL between patients with comorbid hypertension in both cohorts showed no significant differences (p = 0.86) (Table 2).
4 Discussion
Gender
Stroke
Diabetes
Hypertension
CRD Yes
1.97 (0.49–7.93)
0.89 (0.22–3.60)
1.000
1.000
Yes
3.15 (2.00–4.97)*
1.24 (0.75–2.04)
No
1.000
1.000
Yes
2.18 (1.22–3.90)*
1.03 (0.56–1.88)
No
1.000
1.000
Yes
4.41 (0.62–31.39)
4.04 (0.57–28.84)
No
1.000
1.000
No CAD
Hyperlipidemia
Migraine
Adjusted for age, gender, comorbidities, income, and geographic distribution. All patients in the control and psoriasis cohorts were analyzed together CRD chronic renal disease, CAD coronary artery disease, SSNHL sudden sensorineural hearing loss * p \ 0.05
Our major finding was that patients with psoriasis had a significantly (1.51 times) higher incidence of SSNHL than did patients without psoriasis from the general population. The incidence of SSNHL increased with the age of the patients: patients C65 years old had the highest incidence of SSNHL. This was compatible with our finding in patients with SSNHL comorbid with systemic lupus erythematosus, a common autoimmune disease [4]. After combining the results from both cohorts, we found that there was no significant difference in the risk of SSNHL between males and females (Table 3). Although the prevalence of autoimmune diseases is higher in females than in males [14, 15], the reason for this is unclear; however, genetic (X-linked) factors and hormonal aspects are likely involved [16–18]. To the best of our knowledge, there are no English reports that discuss the significance of gender in the association between SSNHL and psoriasis. There is growing evidence that patients with psoriasis have a higher prevalence of associated comorbid diseases, such as CAD, diabetes, hypertension, and dyslipidemia [19]. Both the development of psoriatic lesions and the breakdown of atherosclerotic plaques share the common contributing factors of inflammatory cells and proinflammatory cytokines [20]. For example, tumor necrosis factor (TNF)-a, an inflammatory cytokine, is involved in the pathogenesis of both psoriasis and atherosclerosis [2]. It is possible that a shared mechanism for both psoriasis and SSNHL in association with cardiovascular diseases accounts for the higher risk of
Y.-C. Yen et al.
SSNHL in patients with psoriasis. Because of this, the prevalence of CAD was matched in the present study. Hence, the higher risk of SSNHL in patients with psoriasis in the present study cannot be attributed to a shared mechanism. Several studies [5, 21] have reported elevated plasma renin activity and elevated angiotensin-converting enzyme (ACE) activity. Eventually, poor blood-pressure control might induce changes in the renin–angiotensin system. Higher oxidative stress in patients with psoriasis is also thought to impair the vasodilatory mechanism of the endothelium [22]. Hence, an impaired vasodilatory mechanism might be the reason for the higher risk of SSNHL in patients with psoriasis. Therefore, hypertension was matched as another confounder. Psoriasis has been associated with a higher risk for dyslipidemia [23]. Possible underlying contributing factors include the cytokines IL-1, IL-6, and TNFa, all of which mediate psoriasis. Those cytokines might increase the expression of cellular adhesion molecules, promote lipid deposition on arterial walls, and alter the lipoprotein composition. Ultimately, arterial plaques might develop [24]. Cytokines might also increase the expression of matrix metalloproteinases, which degrade the plaque’s fibrous cap. Eventually, the plaque may rupture and thrombi might appear [24, 25]. Inflammation and a higher level of adhesion and of oxidants in endothelial cells in psoriasis imply early atherogenesis [26]. These processes might also contribute to the development of SSNHL, because one of the proposed risk factors of SSNHL is microvascular compromise in the cochlea. However, the association between inherited and acquired prothrombotic factors and SSNHL suggests that the microvascular impairment that causes SSNHL might be a multifactorial mechanism [27, 28]. Although there are contradictory reports on the role of thrombosis in the development of SSNHL [29–31], we also matched the prevalence of hyperlipidemia as a confounder in the present study. Several epidemiological studies have also argued that psoriasis is an independent risk factor for incident type 2 diabetes [8, 32, 33]. Overproduction of T helper 1 (Th1) cytokines in psoriasis is thought to be a possible mechanism underlying the increase of insulin [8, 34, 35]. Evidence from human temporal bone studies has consistently shown the cooccurrence of cochlear microangiopathy and diabetes [36, 37]. Furthermore, diabetes is associated with a higher risk of SSNHL [38]. Hence, microangiopathy may be one of the mechanisms shared between the association of diabetes and SSNHL and of diabetes and psoriasis. In the present study, diabetes was therefore matched as a confounder. The prevalence of migraine was found to be 1.38 times higher in patients with psoriasis than in the general
population [39]. Migraine has recently been associated with an increased incidence of SSNHL [40, 41]. Migraine with aura can be considered a risk factor for ischemic stroke [42], and SSNHL can be associated with an increased risk of stroke [43]. Migraine without aura is associated with a higher prevalence of hypertension, but the association between migraine and cardiovascular risk is still under debate [44]. Some researchers [40, 45] have claimed that migraine comorbid with hypertension is associated with a trend of developing SSNHL. The migraineassociated inflammation or neurovascular dysfunction in response to certain triggers has been assumed to provoke the occurrence of idiopathic SSNHL [40]. Although the exact mechanism linking migraine and SSNHL is unknown, comorbid migraine was matched as a confounder in this study. Most possible comorbid confounders were matched between the psoriasis and control cohorts. Hence, the factors associated with psoriasis and those comorbid chronic diseases can only be part of the factors underlying the association between psoriasis and the subsequent development of SSNHL. The mechanisms underlying the higher risk of SSNHL in patients with psoriasis remain unclear. The underlying mechanisms of the association between psoriasis and SSNHL require more research. Nevertheless, our results may add evidence of the association between autoimmune disease and SSNHL. The present study’s large national population-based sample allows us to determine the risk factors for developing SSNHL with a minimal selection bias. A large sample also increases the statistical power and precision of risk appraisal. This study has some limitations. Information about several suspected risk factors for SSNHL were not available in the insurance database; for example, data about smoking or about chronic exposure to occupational and environmental noise. The inability to assess these factors may have caused a bias. The insurance claims data did not include information on laboratory test results or the severity of the hearing loss. Clinical examinations for skin lesions, systemic manifestations, and imaging results, for example, were not available to evaluate the extent of psoriasis treatment in patients. Awareness of the elevated risk of developing SSNHL in patients with psoriasis might prompt the early detection and treatment of the condition. Medications that control autoimmune activity might benefit patients with psoriasis who are at risk for developing SSNHL.
5 Conclusion Psoriasis was significantly associated with a higher risk of developing SSNHL. The risk tended to increase directly
Psoriasis and Sudden Sensorineural Hearing Loss
with patient age. This finding may add evidence to the association between autoimmune disease and the development of SSNHL. We suggest that physicians counsel patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL. Acknowledgments The study was designed and conducted by Y. S. Lin and Y. C. Yen. Y. C. Yen, F. J. Lai, and Y. S. Lin recorded the clinical data and supervised the writing of the manuscript. S. F. Wang did the epidemiological and statistical analyses. Y. S. Lin wrote the paper and was primarily responsible for its final content. Y. C. Yen, Y. S. Lin, S. F. Weng, and F. J. Lai have nothing to disclose and declare no conflicts of interest. This study was supported by a Grant from the Taipei Medical University–Chi Mei Medical Center Research Fund
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