Aural symptoms and hearing loss in patients with lupus

Aural symptoms and hearing loss in patients with lupus NEIL M. SPERLING, MD, FACS, KEVIN TEHRANI, MD, ANNE LIEBLING, MD, and ELLEN GINZLER, MD,

Brooklyn and New York, New York

OBJECTIVE: Systemic lupus erythematosus causes widespread tissue injury from deposition of immune complexes. The prevalence of aural symptoms in this disease was evaluated. METHODS: The presence of tinnitus, hearing loss, and fluctuating hearing was evaluated by a self-directed questionnaire in patients aged 65 or less from a lupus clinic. Patients reporting aural symptoms were compared with those reporting none, by use of demographics and disease duration. Comparison was also made with historic serologic data. Audiometry was offered to all patients with lupus reporting aural symptoms and was completed in 10. RESULTS: Twenty-six (31%) of 84 patients with lupus reported aural symptoms. Patients reported a combination of symptoms: unilateral hearing loss with or without tinnitus in 13 (15%) of 84 and bilateral hearing loss with or without tinnitus in 14 (17%) of 84. No statistical difference was measured between symptomatic and asymptomatic patients when compared by average age, duration of disease, history of noise exposure, head trauma, and infectious ear diseases. Statistically significant differences were detected only when comparing average creatinine and C3 levels. Of those patients tested by audiometry, 7 of 10 had abnormal pure-tone thresholds. Asymmetric findings were present in 6 of these 7 patients tested. CONCLUSION: Aural symptoms are prevalent among patients with lupus. Asymmetric symptoms and hearing loss are most common. The cause may relate to immune-complex disease and/or vasculitis. (Otolaryngol Head Neck Surg 1998;118:762-5.)

Systemic lupus erythematosus (SLE) is a systemic chronic illness of unknown cause. It is characterized by the presence of multiple autoantibodies that participate in immunologically mediated tissue injury. The deposition of antibody-antigen immune complexes leads to diffuse vasculitis and multiorgan dysfunction. Patients with lupus appear to be at increased risk of inner ear injury from immune-complex deposition. Immune-mediated hearing loss (HL) is a disorder with no Ògold standardÓ diagnostic criteria. Its presentation fits into the spectrum of idiopathic HL, but it has clinical features that arouse suspicion for an immunologic pathogenesis. This usually consists of bilateral sensorineural HL (SNHL) progressing for weeks to From the Department of Otolaryngology (Dr. Sperling) and the Division of Rheumatology, Department of Medicine (Drs. Liebling and Ginzler), SUNY-Health Science Center at Brooklyn; and the Department of Surgery (Dr. Tehrani), Beth Israel Medical Center, New York. Presented at the Annual Meeting of the American Academy of OtolaryngologyÐHead and Neck Surgery, Washington, D.C., Sept. 29ÐOct. 2, 1996. Reprint requests: Neil M. Sperling, MD, Department of Otolaryngology, Box 126, SUNY-Health Science Center at Brooklyn, Brooklyn, NY 11203. Copyright © 1998 by the American Academy of OtolaryngologyÐ Head and Neck Surgery Foundation, Inc. 0194-5998/98/$5.00 + 0 23/1/84688

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months that is responsive to antiinflammatory treatment. Suggested immune mechanisms for this presentation have included a humoral-type antibody attack on inner ear antigen,1,2 cell-mediated cytotoxicity to inner ear antigen,3 and immune-complex disease in the microvessels of the inner ear.4 This study was directed at a population of patients with lupus to assess subjective aural symptoms and the prevalence of HL. METHODS AND MATERIAL

The prevalence of aural symptoms and HL was evaluated by a subjective, self-directed patient survey, which was conducted among patients with SLE. All patients were attending the lupus clinic of the University Hospital of Brooklyn, an inner-city tertiarycare facility serving both private and Medicaid patients (Fig. 1). Surveys were designed to elicit ear-specific information regarding HL, tinnitus, and a general otologic history. Additional history was obtained from all patients regarding the duration of their lupus and the medications with which they had been treated. Patients with aural symptoms were compared with those with none by use of demographics and disease duration. The two groups were also compared with respect to age, history of noise exposure, head trauma, family history

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SPERLING et al. 763

Table 1. Unilateral, bilateral, and mixed aural symptoms (N = 84) Symptoms

No. of patients (%)

Unilateral HL only Tinnitus only HL and tinnitus Total Bilateral HL only Tinnitus only HL and tinnitus Total Mixed Unilateral HL, bilateral tinnitus Unilateral tinnitus, bilateral HL Total TOTAL with aural symptoms

1 3 7 11

(1) (4) (8) (13)

1 7 3 11

(1) (8) (4) (13

3 1 4 26

(4) (1) (5) (31)

Table 2. Aural symptoms (N = 84) Symptoms

Fig. 1. Hearing questionnaire.

of HL, and infection. Medical records were inspected to identify each patient treated with furosemide (Lasix) for more than 3 months any time during their treatment. Exposure to other ototoxins, such as aminoglycosides, was not quantified. Historic laboratory data of erythrocyte sedimentation rate (ESR), the C3 component of complement, creatinine, presence of anti-double-stranded DNA, and antinuclear antibody were compiled and analyzed. Statistical analysis was performed with the c2 and StudentÕs t test for equality of means. Patients reporting the presence of HL or tinnitus were offered audiometry. RESULTS

In total 100 surveys were completed. Responders were excluded if the survey was not completed adequately or if they were older than 65 years (to control for presbycusis). Four patients responded positively to hearing fluctuation and negatively to tinnitus and HL. These patients were excluded from analysis because they did not clearly represent a positive or a negative response. The final number of analyzed surveys was 84. Ten patients were tested audiometrically. All 84 responders were female. Ages ranged from 16.9 to 61 years, with an average age of 41 years. Patients reporting symptoms had an average age of 42.9, whereas those reporting no aural symptoms had an average age of 39.2 years. This difference was not statistically significant. Patients reporting HL or tinni-

No. of patients (%)

Fluctuation Sudden HL Recurrent “off-balance” Recurrent vertigo

13 3 7 4

(13) (4) (8) (5)

Table 3. Duration of HL in those reporting it (N = 16) Duration

<1 yr 1-3 yr 3-5 yr 5-10 yr >10 yr

No. of patients (%)

6 5 3 1 1

(37) (31) (19) (6) (6)

tus were considered positive responders. All others were considered negative responders. Twenty-six (31%) of 84 patients with lupus reported aural symptoms (Table 1). Symptoms reported included unilateral HL and/or tinnitus in 11 (13%) of 84, bilateral HL and/or tinnitus in 11 (13%) of 84, and some combination of bilateral and unilateral symptoms (unilateral HL with bilateral tinnitus or unilateral tinnitus with bilateral HL) in 4 (5%) of 84. Fluctuating hearing was reported in 13 (15%) of 84 (Table 2). Sudden HL was reported in 3 (4%) of 84. Other symptoms included recurrent difficulties with sense of balance in 7 (8%) of 84 and recurrent vertigo in 4 (5%) of 84. The duration of HL ranged between recent onset and long-term (Table 3). Notably, 6 (37%) of 16 patients reporting HL stated that its duration was less than 1 year.

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Table 4. Otologic history Noise exposure

Patients with aural symptoms (N = 26) No. of patients (%) Patients with no aural symptoms (N = 58) No. of patients (%)

Family history

Head trauma

Infection

9 (35)

4 (15)

1 (4)

3 (11)

10 (17)

6 (10)

5 (9)

7 (12)

Table 5. Laboratory data: Mean values of historic data Aural symptoms

C3 (ref: 80-170)

Creatinine (Ref: 0.5-1.2)

ESR (Ref: 0-25)

ANA

Yes (%) No (%)

80.9* 92.1*

1.18* 1.00*

49.9 52.1

22/23 (96) 54/55 (98)

aDNA

10/23 (43) 29/55 (52)

Numbers in columns for ANA and aDNA represent numbers of patients with positive results/number of test results available for analysis. ANA, Antinuclear antibody; aDNA, anti-double-stranded DNA. *Statistically significant differences.

We compared patients with aural symptoms with those with none using several parameters. The average duration of SLE was 12.8 years in patients with symptoms and 10.4 in patients with no aural symptoms. This difference was not statistically significant. General otologic histories were compared, and no statistical significant difference was noted (Table 4). Historical laboratory data collected over the patients care for SLE was averaged and compared. The intention was to evaluate any correlation of SLE activity and aural symptoms (Table 5). Data were available from 23 patients with aural symptoms and 55 without. Statistical significance was achieved when comparing values for creatinine and C3. Patients with SLE frequently have renal disease. Many patients require treatment with furosemide (Lasix). Six (23%) of 26 symptomatic patients had a history of furosemide treatment, whereas 18 (31%) of 58 asymptomatic patients had a history of furosemide treatment. This difference was not statistically different. Seven of 10 patients tested by audiometry had abnormal pure-tone thresholds (Table 6). Bilateral asymmetric SNHL was noted in three, unilateral SNHL in three, and bilateral symmetric SNHL in one. Among the three with normal pure-tone thresholds, two showed asymmetry of at least 10 dB at one frequency and one had absent reflexes at all frequencies tested (500 Hz, 1 kHz, 2 kHz, and 4 kHz). DISCUSSION

SLE is the prototypical immune-complex disease with known widespread manifestations. Does the systemic deposition of immune complexes typical of SLE act to incite a destructive process in the inner ear? It is

Table 6. Audiometric findings in 10 patients with aural symptoms Findings

No. of patients

Audiometry WNL Bilateral asymmetric SNHL Unilateral SNHL Bilateral symmetric SNHL

3 3 3 1

WNL, Within normal limits.

a compelling theory that may explain certain cases of idiopathic audiovestibular dysfunction. A significant number (26 [31%] of 84) of the questioned population in this study reported aural symptoms. Although no cause-and-effect relationship can be established by this type of study, it appears that a relationship exists. Patients with SLE are subject to multiple diseases and exposures that may affect their otologic health. Although most patients with lupus are exposed to potentially ototoxic medications, the asymmetric symptoms (15 [58%] of 26) observed in this study argue against ototoxicity as the cause of aural symptoms. The duration of the HL reported was relatively short (68% less than 3 years and 37% less than 1 year), a pattern consistent with immune-mediated HL. A seemingly high rate of Òsudden-onsetÓ symptoms was reported in three patients in the symptomatic group. A statistically significant difference was noted in the average measured C3 and creatinine levels. Although both averages were within normal limits, they may be a subtle measurement of overall SLE advancement. Higher creatinine and lower C3 levels suggest a higher level of lupus activity in the group with aural symptoms. Our findings rely mostly on the subjective results of

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a questionnaire. This clearly has limitations in formulating direct correlation. Ideally, a longitudinal and prospective study using objective measurements will shed light on this issue. Idiopathic SNHL is clearly a collection of diverse entities yet to be defined. It also appears likely that immune mechanisms are a significant component of at least some of these entities. Recent studies have focused on identifying the provocative antigen that is the target of the antibody artillery. Alternatively, others have focused on the inner ear as an innocent bystander of immune activity subjected to vasculitis from the deposition of immune complexes related to distant cellular events. In 1986 Bowman et al.5 observed HL in 2 (8%) of 30 patients with SLE. This HL was unexplained by the patientsÕ otologic history. These patients were asymptomatic based on an initial interview before audiometry. HL was unilateral in one patient and bilateral in the other. All patients were inpatients for a lupus flare-up and were receiving immunosupppresive therapy, which may have had an impact on HL. Our patients were all outpatients, possibly selecting a more quiescent stage of their disease. The association of immune complexes with inner ear disease has been observed. Brookes6 in 1986 reported the presence of circulating immune complexes in 54% of patients with MeniereÕs disease. Harada et al.7 have measured immune complexes in the endolymphatic sac and in the stria vascularis of animals sensitized to inner ear antigen.8 HL was observed in 3 of 22 patients with elevated immune complexes. One of these patients had audiometric improvement after plasma exchange. Luetje9 also reported good results using plasmapheresis

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in eight patients with immune-mediated HL, with six of eight responding audiometrically. The exact mechanisms active in the individual patient with progressive HL remain elusive. Clinical clues may help establish subgroups of patients who have true autoimmunity to inner ear antigen and those who have a bystander or secondary phenomenon. Measuring circulating immune complexes or complement components such as C3 may become helpful in that effort. Treatment protocols may then be individualized to the likely pathogenesis. REFERENCES 1. Arnold W, Pfaltz R, Altermatt HJ. Evidence of serum antibodies against inner ear tissues in the blood of patients with certain sensorineural hearing disorders. Acta Otolaryngol (Stockh) 1985; 99:437-44. 2. Harris JP, Sharp PA. Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. Laryngoscope 1990;100:516-24. 3. Bernstein JM. The immunobiology of autoimmune disease of the inner ear. In: Bernstein J, Ogra P, editors. Immunology of the ear. New York: Raven Press; 1987. p. 419-26. 4. Veldman JE, Roord JJ, OÕConnor AF, Shea JJ. Autoimmunity and inner ear disorders: an immune-complex mediated sensorineural hearing loss. Laryngoscope 1984;94:501-7. 5. Bowman CA, Linthicum FH Jr, Nelson RA, Mikami K, Quismorio F. Sensorineural hearing loss associated with systemic lupus erythematosus. Otolaryngol Head Neck Surg 1986; 94:197-204. 6. Brookes GB. Circulating immune complexes in MeniereÕs disease. Arch Otolaryngol Head Neck Surg 1986;112:536-40. 7. Harada T, Matsunaga T, Hong K, Inoue K. Enolymphatic hydrops and III Type allergic reaction. Acta Otolaryngol (Stockh) 1984, 97:450-9. 8. Harada T, Sano M, Sakagami M, Ogino S, Matsunaga T. Mechanism of immune complex-mediated inner ear diseases. Ann Otol Rhinol Laryngol 1992;101:72-7. 9. Luetje CM. Theoretical and practical implications for plasmapheresis in autoimmune inner ear disease. Laryngoscope 1989; 99:1137-46.