Ann Otol 88 :1979
AUTOIMMUNE SENSORINEURAL HEARING LOSS BRIAN F. McCABE, MD IOWA CITY, IOWA
The author proposes the existence of a new entity, autoimmune sensorineural hearing loss, on the basis of diagnostic study and treatment experience with a series of 18 patients. In each case the clinical pattern did not fit with known entities and thus seemed to merit distinctive categorization. In the one patient in whom tissue was available, a vasculitis was evident, a feature of autoimmune disease. All patients responded to treatment for an autoimmune disease, namely, chronic cortisone and cyclophosphamide therapy. The author suggests that all otolaryngologists should be aware of the possibility of this condition, because it is one of the few forms of sensorineural deafness for which we have a treatment.
There appears to be a form of sensorineural hearing loss which is distinct from other forms of deafness by virtue of its clinical course, laboratory test results, and response to treatment, to a degree sufficient to warrant separate identification. We propose the term autoimmune sensorineural hearing loss on the basis of its laboratory test characteristics and specifics of its response to treatment. We believe it to be important because it is one of the few forms of sensorineural deafness for which we have a treatment. As such all otolaryngologists should be on the lookout for it, be able to recognize it, and be able to treat it. We hazard that most otolaryngologists have seen it at one time but not many have recognized it. The characteristics of the condition will be described in terms of a case report which is a composite of a number of patients seen and treated over a period of ten years, describing the most usual fonn it takes. CASE REPORT The patient is a 25-year-old Caucasian male in excellent health in all respects until two months prior to his initial visit. He awoke one morning with a full feeling in his right ear, tinnitus, and unsteadiness. He received antibiotics for this from his family physician. Two weeks later he was seen by an otolaryngologist who saw no objective abnormality but determined his hearing at
63 dB SRT on the right and 18 dB on the left. One month after development of his ear difficulty he awoke with a complete right facial paralysis. He was started on steroids and noticed some slight improvement of the face. Two months into his illness he was referred because of failure of further improvement of the facial paralysis and steady progression of the hearing loss. A period of progression of the deafness over weeks or months, not hours nor days nor years, is a characteristic of this disease. The physical examination was normal except for a nearly complete right peripheral facial paralysis, total deafness in the right ear, a 30 dB SRT in the left ear with 74% discrimination, and completely absent vestibular responses AU. The ENG showed no activity to a stimulus of 20 cc of ice water in either ear. He was admitted for an exhaustive workup and commencement of therapy. Besides routine tests the following were obtained: SMA/12/60, SMA/6/60, FTA, convalescent viral titres, lipoprotein electrophoresis, cholesterol, triglycerides, quantitative immunoglobulins including IgG, IgA and IgM, antinuclear antibody titre, hepatitis associated antigen, T3, T4 and T7, PT, PTT, CPK. antimitochondrial anti-smooth muscle and antiparietal cell antibody detenninations and complete skin testing. A lum-
From the Department of Otolaryngology and Maxillofacial Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa. Presented at the meeting of the American Neurotology Society, Los Angeles. California. March 30-31, 1979.
585
586
BRIAN F. McCABE
bar puncture was performed. Hypocycloidal tomography of the temporal bones was negative. Other important negatives were no signs of neurofibromatosis in the cornea, iris, or retina, no interstitial keratitis, and no retinitis pigmentosa. The only abnormal responses to tests were a CSF protein of 68 mg/% (normal 11 to 50) and an IgM of 300 (normal 68 to 250). During the nearly two weeks of the workup, no change in the facial paralysis was noted but the SRT dropped to 60 dB and the discrimination to 0% in his only hearing ear. At this point therapy was started consisting of oral dexamethasone, 16 mg daily and intravenous cyclophosphamide in amounts adequate to keep the white cell count between 2,000 and 4,000 per cu mm. At the end of two weeks he no longer had to depend on a pad and pencil for communication. He was discharged and admitted two weeks later for another two-week course of cyclophosphamide. After one month of treatment he had an improved SRT and a measurable discrimination score. He achieved his peak hearing return after two months of treatment with an SRT of 30 dB and a discrimination score of 72%. After three months of treatment his facial paralysis had resolved completely except for moderate loss of corrugator activity of the lips. He was kept under cortisone treatment and was mildly cushingoid for ten months when the cortisone was tapered and discontinued. The only incident of note during this time is that 3Ji months into treatment the cortisone was tapered acording to plan and his hearing "dropped badly." He resumed the prior level of treatment immediately as he had been instructed and in three weeks his hearing was back to its prior level. We now have our eighteenth case of this rare form of ear disease. The picture may be variable. CLINICAL PICTURE
It is usually bilateral. The hearing organs are always involved and usually the balance organs as well. Facial paralysis occurred in five patients. Tissue destruction may occur and may involve the tympanic membrane, the entire mid-
Fig. 1. Granulomatous postauricular mass between auricle and hair of temporal region seen in one patient.
dIe ear, or the middle ear and mastoid as well (Fig. 1). All patients responded in a manner similar to this patient. We are aware that there is little in the way of laboratory tests to prove this is an autoimmune disease. The exception is a new test, the lymphocyte inhibition assay using inner ear antigen. The only positive tests except for this were an elevated CSF protein and a moderately elevated IgM and a positive LIA. Only one of five of Witebsky's postulates for an autoimmune disease is met, a positive response to treatment. However, the positive lymphocyte inhibition assay, a post-Witebsky development, is a strong argument in itself for autoimmunity. DIFFERENTIAL DIAGNOSIS
The time course of the hearing loss appears to be the best clue to diagnosis. It differs from the other causes of progressive sensorineural deafness, in that it is either quicker or slower, and can be contrasted with them in certain other features. The differential diagnosis of this disease would include only those conditions of sensorineural deafness unaccompanied by morphologic changes identifiable by inspection, radiography or tissue morphology such as osteopetrosis, glomus jugulare, acoustic neuroma, eosinophilic granuloma, etc. Conditions with which it may be confused are as follows.
AUTOIMMUNE HEARING LOSS
1. Sudden deafness occurs over minutes Or hours; this condition progresses slowly over a period of weeks or months. 2. Cochlear Meniere's disease is both sudden and fluctuating, this condition is insidious and slowly progressive without remission. 3. Cochlear (otosclerotic) deafness is seen with a positive family history, excellent discrimination, flat audiometric curve, and progression over a matter of years, whereas this condition progresses over weeks or (at most) a few months and discrimination scores are poor, audiometric curves are sloping, and family histories are negative. 4. Chronic progressive deafness of adolescence may be seen in patients from 6 to 18 years of age with progression of the hearing loss only in the range of 10-20 dB annuallv. whereas in this disease the age of incidence is 20 to 40, there is no fluctuation, and the time course is considerably quicker. 5. Presenile presbycusis is generally a disease of the 40s and 50s, slowly progressive, and accompanied by other changes such as arcus senilis, loss of elastin fibers with drooping of surface features, etc, whereas this disease occurs earlier and progresses much more rapidly. 6. Noise-induced hearing loss is so readily identifiable it should require no comment here, except to say that it may be present as a substrate to this disease. A patient who is a suspect may have a temporary threshold shift in noise who did not have one before. 7. Recessive progressive hereditary deafness patients should be identifiable by family history. If not, the distinction from this condition is a matter of time-years for this (hereditary deafness) disease, weeks or months for the disease in question. 8. Luetic labyrinthitis is accompanied by a hearing loss over months and years rather than weeks, vertigo, virtually never a facial paralysis, and alwavs a positive FTA. In this disease the deafness is more rapidly progressive, vertiginous crises are absent, and the FTA is negative.
587 DISCUSSION
We have now 18 cases of this uncommon form of inner ear disease. The picture is variable, but there has been a diagnostic pattern. It is a bilateral disease althouzh asymmetric. Hearing is always involved, with all localization tests pointing to the end-organs. Vestibular function is involved as well, but so symmetrically that vertigo is not a complaint. Unsteadiness and ataxia in darkness are common complaints, which are the usual manifestations of slow but bilaterally simultaneous failure of vestibular end-organs. Temporary facial paralysis occurred in five patients, with complete remission in four and satisfactory return in one without surgical intervention. It is of interest that tissues beyond the inner ear may become involved. The facial nerve has been mentioned. Cases of tissue destruction of the tympanic membrane, middle ear, or middle ear and mastoid have also been observed in this group of patients Two are particularly notable.
One patient had bilateral middle ear effusions in addition to the inner ear losses which were severe (total AS and 90 dB AD). The left ear had only a moderate loss on outside audiograms before a myringotomy had been performed, after which the patient claimed a total loss of hearing. This was confirmed by our testing. For this reason we would caution against myringotomy in any patient with rapidiy progressive sensorineural deafness with effusion. Our physical examination of the tympanic membranes, however, were of even greater interest: both were thickened and immobile, but the right tympanic membrane was most unusual. A large blood vessel coursed from the annular ligament area posteroinferiorly, up and forward across the umbo, into the opposite quadrant. This vessel was observed periodically. The most astounding feature of all was that after completion of treatment (cyclophosphamide and dexamethasone) over 6 weeks, the vessel had disappeared. There is no blood vessel coursing along this route normally.' This is a clear example of neooascularization, wherein an organ already supplied by vessels is supplied in
588
BRIAN F. McCABE
Fig. 2. A) Frank vasculitis in the granulation tissue from the patient in Figure 1. Chronic inflammatory cells invade all layers of the vessel. B) The ghost of a blood vessel destroyed by inflammatory disease t arrows outline the vessel).
a new way in the absence of prior destruction. This is characteristic of granulomatous diseases, a number of which are autoimmune in nature, the clearest example being lethal midline granuloma. Tissue for pathological examination is very hard to come by in such patients, and would be extremely valuable in search for vasculitis. We have only one such, in a patient whose disease involved the middle ear and mastoid. The tissue from this patient clearly demonstrated not only vasculitis (Fig. 2A) but also the ghosts of blood vessels which are in the end stages of vasculitis, rings of scar tissue in the granulomatous substrate (Fig. 2B). This was one of our first patients and was many months into her illness before we thought to start immunosuppressive therapy, after which she healed and has remained so. LABORATORY TESTS
As in the case report, there are no routine laboratory tests that will identify patients with this disorder. In the last four years of the ten-year period we have been collecting these patients however, new tests for autoimmune diseases have emerged. We have applied one
which has been positive in those patients we have seen in recent years, the lymphocyte inhibition assay. In this test the patient's lymphocytes are challenged by prepared inner ear antigen. The antigen is made from membranous inner ear tissue removed from patients without the disease, ie, during translabyrinthine operations for other disorders. Six patients in the series were tested when this test was available, and all six had positive responses, their lymphocytes responding to inner ear antigen whereas controls did not. In terms of autoimmune diseases however, this is a rather gross test and we are not completely convinced as to its specificity. We need greater experience with it, and it needs verification in other laboratories. SUMMARY
A composite patient representing one of a series of eighteen patients believed to have an autoimmune inner ear disease process is described in detail. An extensive hospital workup was essentially negative except for a positive lymphocyte inhibition assay in recent patients. Evidence of a vasculitis was present in the one patient in whom tissue was available. In each case wherein the hearing loss was not total, a sub-
AUTOIMMUNE HEARING LOSS
stantial improvement of hearing was obtained on cyclophosphamide and dexamethasone therapy. Intensive treatment was required. In each case hearing change paralleled treatment, that is to say, if treatment were diminished or
589
stopped early in the disease, the hearing failed and on recommencement of therapy the hearing improved. The minimum treatment period in the series was eight months and the maximum two years.
REFERENCES 1. Shilling B: Blood Supply
of the External Ear Canal and Tympanic Membrane, thesis.
University of Iowa, Iowa City, Iowa, 1974 REPRINTS - Brian F. McCabe, MD, Department of Otolaryngology and Maxillofacial Surgery, University Hospitals, Iowa City, IA 52242.
XII WORLD CONGRESS OF OTORHINOLARYNGOLOGY The XII World Congress of Otorhinolaryngology will be held June 21-27, 1981 in Budapest, Hungary under the auspices of the International Federation of OtorhinoIaryngological Societies (IFOS). The main topics will be rhinology, oncology, pediatrics, otoneurology, immunology, audiology, traumatology, pathology, pathophysiology and phoniatry. Second World Film Festival, free paper sessions, scientific exhibitions and postgraduate courses will be held. Further information will be available from the Congress Secretariat: 12th World Congress of ORL, c/o Professor L. Surjan, Budapest, Hungary P.O.B. 112 H-1389.
AUTOIMMUNE SENSORINEURAL HEARING LOSS BRIAN F. McCABE, MD IOWA CITY, IOWA
The author proposes the existence of a new entity, autoimmune sensorineural hearing loss, on the basis of diagnostic study and treatment experience with a series of 18 patients. In each case the clinical pattern did not fit with known entities and thus seemed to merit distinctive categorization. In the one patient in whom tissue was available, a vasculitis was evident, a feature of autoimmune disease. All patients responded to treatment for an autoimmune disease, namely, chronic cortisone and cyclophosphamide therapy. The author suggests that all otolaryngologists should be aware of the possibility of this condition, because it is one of the few forms of sensorineural deafness for which we have a treatment.
There appears to be a form of sensorineural hearing loss which is distinct from other forms of deafness by virtue of its clinical course, laboratory test results, and response to treatment, to a degree sufficient to warrant separate identification. We propose the term autoimmune sensorineural hearing loss on the basis of its laboratory test characteristics and specifics of its response to treatment. We believe it to be important because it is one of the few forms of sensorineural deafness for which we have a treatment. As such all otolaryngologists should be on the lookout for it, be able to recognize it, and be able to treat it. We hazard that most otolaryngologists have seen it at one time but not many have recognized it. The characteristics of the condition will be described in terms of a case report which is a composite of a number of patients seen and treated over a period of ten years, describing the most usual fonn it takes. CASE REPORT The patient is a 25-year-old Caucasian male in excellent health in all respects until two months prior to his initial visit. He awoke one morning with a full feeling in his right ear, tinnitus, and unsteadiness. He received antibiotics for this from his family physician. Two weeks later he was seen by an otolaryngologist who saw no objective abnormality but determined his hearing at
63 dB SRT on the right and 18 dB on the left. One month after development of his ear difficulty he awoke with a complete right facial paralysis. He was started on steroids and noticed some slight improvement of the face. Two months into his illness he was referred because of failure of further improvement of the facial paralysis and steady progression of the hearing loss. A period of progression of the deafness over weeks or months, not hours nor days nor years, is a characteristic of this disease. The physical examination was normal except for a nearly complete right peripheral facial paralysis, total deafness in the right ear, a 30 dB SRT in the left ear with 74% discrimination, and completely absent vestibular responses AU. The ENG showed no activity to a stimulus of 20 cc of ice water in either ear. He was admitted for an exhaustive workup and commencement of therapy. Besides routine tests the following were obtained: SMA/12/60, SMA/6/60, FTA, convalescent viral titres, lipoprotein electrophoresis, cholesterol, triglycerides, quantitative immunoglobulins including IgG, IgA and IgM, antinuclear antibody titre, hepatitis associated antigen, T3, T4 and T7, PT, PTT, CPK. antimitochondrial anti-smooth muscle and antiparietal cell antibody detenninations and complete skin testing. A lum-
From the Department of Otolaryngology and Maxillofacial Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa. Presented at the meeting of the American Neurotology Society, Los Angeles. California. March 30-31, 1979.
585
586
BRIAN F. McCABE
bar puncture was performed. Hypocycloidal tomography of the temporal bones was negative. Other important negatives were no signs of neurofibromatosis in the cornea, iris, or retina, no interstitial keratitis, and no retinitis pigmentosa. The only abnormal responses to tests were a CSF protein of 68 mg/% (normal 11 to 50) and an IgM of 300 (normal 68 to 250). During the nearly two weeks of the workup, no change in the facial paralysis was noted but the SRT dropped to 60 dB and the discrimination to 0% in his only hearing ear. At this point therapy was started consisting of oral dexamethasone, 16 mg daily and intravenous cyclophosphamide in amounts adequate to keep the white cell count between 2,000 and 4,000 per cu mm. At the end of two weeks he no longer had to depend on a pad and pencil for communication. He was discharged and admitted two weeks later for another two-week course of cyclophosphamide. After one month of treatment he had an improved SRT and a measurable discrimination score. He achieved his peak hearing return after two months of treatment with an SRT of 30 dB and a discrimination score of 72%. After three months of treatment his facial paralysis had resolved completely except for moderate loss of corrugator activity of the lips. He was kept under cortisone treatment and was mildly cushingoid for ten months when the cortisone was tapered and discontinued. The only incident of note during this time is that 3Ji months into treatment the cortisone was tapered acording to plan and his hearing "dropped badly." He resumed the prior level of treatment immediately as he had been instructed and in three weeks his hearing was back to its prior level. We now have our eighteenth case of this rare form of ear disease. The picture may be variable. CLINICAL PICTURE
It is usually bilateral. The hearing organs are always involved and usually the balance organs as well. Facial paralysis occurred in five patients. Tissue destruction may occur and may involve the tympanic membrane, the entire mid-
Fig. 1. Granulomatous postauricular mass between auricle and hair of temporal region seen in one patient.
dIe ear, or the middle ear and mastoid as well (Fig. 1). All patients responded in a manner similar to this patient. We are aware that there is little in the way of laboratory tests to prove this is an autoimmune disease. The exception is a new test, the lymphocyte inhibition assay using inner ear antigen. The only positive tests except for this were an elevated CSF protein and a moderately elevated IgM and a positive LIA. Only one of five of Witebsky's postulates for an autoimmune disease is met, a positive response to treatment. However, the positive lymphocyte inhibition assay, a post-Witebsky development, is a strong argument in itself for autoimmunity. DIFFERENTIAL DIAGNOSIS
The time course of the hearing loss appears to be the best clue to diagnosis. It differs from the other causes of progressive sensorineural deafness, in that it is either quicker or slower, and can be contrasted with them in certain other features. The differential diagnosis of this disease would include only those conditions of sensorineural deafness unaccompanied by morphologic changes identifiable by inspection, radiography or tissue morphology such as osteopetrosis, glomus jugulare, acoustic neuroma, eosinophilic granuloma, etc. Conditions with which it may be confused are as follows.
AUTOIMMUNE HEARING LOSS
1. Sudden deafness occurs over minutes Or hours; this condition progresses slowly over a period of weeks or months. 2. Cochlear Meniere's disease is both sudden and fluctuating, this condition is insidious and slowly progressive without remission. 3. Cochlear (otosclerotic) deafness is seen with a positive family history, excellent discrimination, flat audiometric curve, and progression over a matter of years, whereas this condition progresses over weeks or (at most) a few months and discrimination scores are poor, audiometric curves are sloping, and family histories are negative. 4. Chronic progressive deafness of adolescence may be seen in patients from 6 to 18 years of age with progression of the hearing loss only in the range of 10-20 dB annuallv. whereas in this disease the age of incidence is 20 to 40, there is no fluctuation, and the time course is considerably quicker. 5. Presenile presbycusis is generally a disease of the 40s and 50s, slowly progressive, and accompanied by other changes such as arcus senilis, loss of elastin fibers with drooping of surface features, etc, whereas this disease occurs earlier and progresses much more rapidly. 6. Noise-induced hearing loss is so readily identifiable it should require no comment here, except to say that it may be present as a substrate to this disease. A patient who is a suspect may have a temporary threshold shift in noise who did not have one before. 7. Recessive progressive hereditary deafness patients should be identifiable by family history. If not, the distinction from this condition is a matter of time-years for this (hereditary deafness) disease, weeks or months for the disease in question. 8. Luetic labyrinthitis is accompanied by a hearing loss over months and years rather than weeks, vertigo, virtually never a facial paralysis, and alwavs a positive FTA. In this disease the deafness is more rapidly progressive, vertiginous crises are absent, and the FTA is negative.
587 DISCUSSION
We have now 18 cases of this uncommon form of inner ear disease. The picture is variable, but there has been a diagnostic pattern. It is a bilateral disease althouzh asymmetric. Hearing is always involved, with all localization tests pointing to the end-organs. Vestibular function is involved as well, but so symmetrically that vertigo is not a complaint. Unsteadiness and ataxia in darkness are common complaints, which are the usual manifestations of slow but bilaterally simultaneous failure of vestibular end-organs. Temporary facial paralysis occurred in five patients, with complete remission in four and satisfactory return in one without surgical intervention. It is of interest that tissues beyond the inner ear may become involved. The facial nerve has been mentioned. Cases of tissue destruction of the tympanic membrane, middle ear, or middle ear and mastoid have also been observed in this group of patients Two are particularly notable.
One patient had bilateral middle ear effusions in addition to the inner ear losses which were severe (total AS and 90 dB AD). The left ear had only a moderate loss on outside audiograms before a myringotomy had been performed, after which the patient claimed a total loss of hearing. This was confirmed by our testing. For this reason we would caution against myringotomy in any patient with rapidiy progressive sensorineural deafness with effusion. Our physical examination of the tympanic membranes, however, were of even greater interest: both were thickened and immobile, but the right tympanic membrane was most unusual. A large blood vessel coursed from the annular ligament area posteroinferiorly, up and forward across the umbo, into the opposite quadrant. This vessel was observed periodically. The most astounding feature of all was that after completion of treatment (cyclophosphamide and dexamethasone) over 6 weeks, the vessel had disappeared. There is no blood vessel coursing along this route normally.' This is a clear example of neooascularization, wherein an organ already supplied by vessels is supplied in
588
BRIAN F. McCABE
Fig. 2. A) Frank vasculitis in the granulation tissue from the patient in Figure 1. Chronic inflammatory cells invade all layers of the vessel. B) The ghost of a blood vessel destroyed by inflammatory disease t arrows outline the vessel).
a new way in the absence of prior destruction. This is characteristic of granulomatous diseases, a number of which are autoimmune in nature, the clearest example being lethal midline granuloma. Tissue for pathological examination is very hard to come by in such patients, and would be extremely valuable in search for vasculitis. We have only one such, in a patient whose disease involved the middle ear and mastoid. The tissue from this patient clearly demonstrated not only vasculitis (Fig. 2A) but also the ghosts of blood vessels which are in the end stages of vasculitis, rings of scar tissue in the granulomatous substrate (Fig. 2B). This was one of our first patients and was many months into her illness before we thought to start immunosuppressive therapy, after which she healed and has remained so. LABORATORY TESTS
As in the case report, there are no routine laboratory tests that will identify patients with this disorder. In the last four years of the ten-year period we have been collecting these patients however, new tests for autoimmune diseases have emerged. We have applied one
which has been positive in those patients we have seen in recent years, the lymphocyte inhibition assay. In this test the patient's lymphocytes are challenged by prepared inner ear antigen. The antigen is made from membranous inner ear tissue removed from patients without the disease, ie, during translabyrinthine operations for other disorders. Six patients in the series were tested when this test was available, and all six had positive responses, their lymphocytes responding to inner ear antigen whereas controls did not. In terms of autoimmune diseases however, this is a rather gross test and we are not completely convinced as to its specificity. We need greater experience with it, and it needs verification in other laboratories. SUMMARY
A composite patient representing one of a series of eighteen patients believed to have an autoimmune inner ear disease process is described in detail. An extensive hospital workup was essentially negative except for a positive lymphocyte inhibition assay in recent patients. Evidence of a vasculitis was present in the one patient in whom tissue was available. In each case wherein the hearing loss was not total, a sub-
AUTOIMMUNE HEARING LOSS
stantial improvement of hearing was obtained on cyclophosphamide and dexamethasone therapy. Intensive treatment was required. In each case hearing change paralleled treatment, that is to say, if treatment were diminished or
589
stopped early in the disease, the hearing failed and on recommencement of therapy the hearing improved. The minimum treatment period in the series was eight months and the maximum two years.
REFERENCES 1. Shilling B: Blood Supply
of the External Ear Canal and Tympanic Membrane, thesis.
University of Iowa, Iowa City, Iowa, 1974 REPRINTS - Brian F. McCabe, MD, Department of Otolaryngology and Maxillofacial Surgery, University Hospitals, Iowa City, IA 52242.
XII WORLD CONGRESS OF OTORHINOLARYNGOLOGY The XII World Congress of Otorhinolaryngology will be held June 21-27, 1981 in Budapest, Hungary under the auspices of the International Federation of OtorhinoIaryngological Societies (IFOS). The main topics will be rhinology, oncology, pediatrics, otoneurology, immunology, audiology, traumatology, pathology, pathophysiology and phoniatry. Second World Film Festival, free paper sessions, scientific exhibitions and postgraduate courses will be held. Further information will be available from the Congress Secretariat: 12th World Congress of ORL, c/o Professor L. Surjan, Budapest, Hungary P.O.B. 112 H-1389.
