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Bilateral sensorineural hearing loss as a first symptom of chronic myelogenous leukemia
Bilateral sensorineural hearing loss as a first symptom of chronic myelogenous leukemia ERIC M. GENDEN, MD, and ROBERT S. BAHADORI, MD, St. Louis, Missouri
A l m o s t one and a half centuries ago leukemia was the term coined by Virchow, 1 who was the first to relate the association between an enlarged spleen and leukocytosis. Retrospectively, we know that his descriptions probably corresponded to a chronic form of the disease. It was not until 1891 that Ehrlich, 2using newly developed staining techniques, was able to distinguish between lymphoid and myeloid forms of the disease. As leukemia became a more commonly reported clinical entity, unique manifestations of this hematologic malignancy appeared in the world's literature. In 1856VidaP was the first to observe a relationship between leukemia and deafness. External and middle ear involvement were the first to be recognized clinically. Inner ear involvement was later definitively demonstrated by Politzer 4 when he sectioned the temporal bone of a patient with chronic myelogenous leukemia who had sustained hearing loss 1 year before death. His findings confirmed that leukemic infiltration of the inner ear was responsible for the rare complication of sensorineural hearing loss associated with the disease. In 1945 Druss 5 published a landmark p a p e r t h a t defined the otologic complications of leukemia. In his publication, Druss concluded that the aural complications of leukemia were more common than previously believed. H e reported a wide range of findings, including acute otitis media, middle ear infiltration, and inner ear hemorrhage, with an overall prevalence of 16.8%. In this article we record what is, to the best of our knowledge, the first patient with chronic myelogenous leukemia with sudden onset of bilateral sen-
sorineural hearing loss. Unfortunately, there was no response or recovery of hearing after the medical treatment. CASE REPORT
A 53-year-old woman with no significant past medical
history came to the otolaryngology-head and neck surgery clinic with a report Of sudden-onset bilateral hearing loss. The hearing loss occurred on awakening 2 days before her initial visit. It was not associated with otalgia, otorrhea, tinnitus, or vertigo. The patient denied any previous noise exposure, otologic trauma, or toxic medications. The patient did relate a history of intermittent fevers for approximately 1 month. On her initial physical examination in the clinic, both external auditory canals were clear. Both tympanic membranes were normal in appearance, and she had no evidence of injection, retraction, or middle ear effusion. The audiogram (Fig. 1) demonstrated bilateral sensorineural hearing loss. For evaluation of the hearing loss, the following blood tests were ordered: complete blood count, sedimentation rate, fluorescent treponemal antibody test, VDRL, and antinuclear antibody. The sedimentation rate, fluorescent treponemal antibody test, VDRL, and antinuclear antibody results were normal. Hematologic workup demonstrated a leukocyte count of 156,000/mm 3, hemoglobin 8.5 gm/dl, and hematocrit 23.8%. A few days later the patient was admitted to the hospital for further evaluation of the abnormal blood count. The examination of the abdomen at that time revealed a soft, distended abdomen with marked hepatosplenomegaly. The cardiopulmonary examination was normal. Peripheral smear, bone marrow biopsy, and cytogenetic studies were consistent with the diagnosis of chronic myelogenous leukemia. The patient was treated with hydroxyurea resulting in a precipitous drop in leukocyte count. At 6 months after initial visit, the patient has had no change in her sensorineural hearing loss. DISCUSSION
From the Department of Otolaryngology, Washington University School of Medicine. Received for publication Nov. 23, 1994; accepted March 3, 1995. Reprint requests: Eric M. Genden, MD, Department of Otolaryngology, Box 8115, Washington University School of Medicine, 517 South Euclid Ave., St. Louis, MO 63110. OTOLARYYGOI.HEADNECKSURG 1995;113:499-501. Copyright © 1995 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/95/$5.00 + 0 23/4/64772
The incidence of acute-onset sensorineural hearing loss as the first sign of leukemia is extremely rare. Sudden sensorineural hearing loss is a condition that, despite a careful history and exhaustive physical and laboratory evaluation, commonly defies diagnosis; consequently, no effective treatment can be offered. Through a heightened index of suspicion and more discriminating diagnostic tools, otolaryn499
500
Otolaryngology Head and Neck Surgery October t995
GENDEN a n d BAHADORI
Pure Tone Audiogram
12s
250
Soo
I000
2000
4000
8000
20
0 20 Decibels
(dB)
40
60
×
I0
80 100
120 Frequency (Hz)
Fig. t. A u d i o g r a m of patient on initial visit.
gologists can identify a subgroup of patients with malignant, infectious, or autoimmune sensorineural hearing loss, who may benefit from a well-directed medical therapy. Certain pathologic conditions can be diagnosed, and it is the otolaryngologist's initial aim to ensure that these are not missed. This is usually achieved by taking a good history, examining the patient and obtaining the appropriate blood tests. Since Politzer's presentation at the Otologic Congress at Basel in 1884, several investigators have explored the cause of sensorineural hearing loss in leukemic patients. Schwabach (1897), Finlaysin (1898), and Alexander (1906), all demonstrated inner ear hemorrhages associated with leukemia. Druss 5 found acute otitis media in sectioned temporal bones, as well as leukemic infiltration of both the middle ear space and inner ear apparatus. Inner ear hemorrhage, infection, and leukemic infiltration have all been demonstrated as causes of sudden deafness in leukemic patients. Paparella et al. 6 concurred with these findings, categorizing the histopathology of sectioned temporal bones into one of the three aforementioned categories. Although Paparella's work was monumental, none of his 25 patients studied was diagnosed with chronic lymphocytic leukemia (CLL). Few studies demonstrate the role of inner ear hemorrhage as a cause of sudden deafness in chronic leukemia, but its role in
acute disease is well documented.7 The role of inner ear hemorrhage in CLL is a likely cause of sudden deafness, but the data supporting this theory are scant. Inner ear hemorrhage is, however, not the only etiologic explanation of sudden deafness. Baer et al.8 reported a case of a 47-year-old man with hyperleukocytic CLL in whom retinal hemorrhages, headaches, diplopia,-dysequilibrium, nystagmus, ataxia, and hearing loss developed. The authors attributed these symptoms to a "hyperviscosity syndrome" that occurred as a result of leukostasis. Their hypothesis was supported by the reversal of symptoms that occurred with leukapheresis. Although there are reports of this well-documented phenomenon in the literature, the syndrome is often dependent on leukocyte counts greater than 500,000/mm 3, which rarely occurs in CLL. The prognosis of patients with sudden-onset deafness is variable. Nageris et al. 9 recently reported on a 35-year-old man with CLL whose sensorineural hearing loss dramatically improved after he began chemotherapy. Baer et al. 8 reported on a similar case. Each patient had return of hearing coupled with a drop in leukocyte count. Reversal of the sensorineural hearing loss in leukemic patients is rare. It may be that patients with reversible deafness have a hyperviscosity syndrome that resolves with chemotherapy and leukapheresis, whereas those with nonreversible hearing loss have had leukemic infiltration of the middle ear and inner ear infarction. A second possibility is that hyperviscosity syndrome is a prelude to infarction. If the latter theory is correct, early diagnosis and treatment would be paramount in lowering the incidence of deafness associated with leukemia. Although neither theory is well supported in the literature, it remains that early diagnosis and treatment are imperative to low morbidity and long-term survival. The case presented is unique in that, to the best of our knowledge, there are no reported cases of bilateral sensorineural hearing loss as an initial symptom of chronic myelogenous leukemia. Helpful discussions and critical review of this manuscript were provided by Drs. Barbara A. Bohne and J. Gail Neely. REFERENCES 1. Virchow R. Weisses Blut and Milztumoren. II. Med Z 1847; 16:9. 2. Ehrlich P. Farbenanalytische Untersuchungen zur Histologie und Klinik des Blutes. Berlin: Hirschwald, 1891.
Otolaryngology H e a d a n d N e c k Surgery
Volume 113
Number 4
3. Vidal E. De la leucocythemie splenique, ou de l'hypertrophie de la rate avec alteration du sang consistant dans une augmentation considerable du nombre blancs. Gaz Hebd Sci Med Bordeaux, Par 1856;3:166, 201, 235. 4. Politzer A. Pathologische Veranderungen im Labyrinthe bei leukamischer Taubheit. Cong Int Otol 1885;3:139. 5. Druss J. Aural manifestations of leukemia. Arch Otolaryngology 1945;42:267. 6. Paparella MM, Berlinge NT, Oda M, El-fiky F. Otological manifestations of leukemia. Laryngoscope 1973;83:1510-26.
GENDEN and BAHADORI 5 0 t
7. Schuknecht HF, Igarashi M, Chasin WD. Inner ear hemorrhage in leukemia. A case report. Laryngoscope 1965;75:662-8. 8. Baer RM, Stein RS, Dessypris EN. Chronic lymphocytic leukemia with hyperleukocytosis. The hyperviscosity syndrome. Cancer 1985;56:2865-9. 9. Nageris B, Or R, Hardan I, Polliack A. Sudden onset deafness as a presenting manifestation of chronic lymphocytic leukemia. Leuk Lymphoma 1993;9:269-71.
A l m o s t one and a half centuries ago leukemia was the term coined by Virchow, 1 who was the first to relate the association between an enlarged spleen and leukocytosis. Retrospectively, we know that his descriptions probably corresponded to a chronic form of the disease. It was not until 1891 that Ehrlich, 2using newly developed staining techniques, was able to distinguish between lymphoid and myeloid forms of the disease. As leukemia became a more commonly reported clinical entity, unique manifestations of this hematologic malignancy appeared in the world's literature. In 1856VidaP was the first to observe a relationship between leukemia and deafness. External and middle ear involvement were the first to be recognized clinically. Inner ear involvement was later definitively demonstrated by Politzer 4 when he sectioned the temporal bone of a patient with chronic myelogenous leukemia who had sustained hearing loss 1 year before death. His findings confirmed that leukemic infiltration of the inner ear was responsible for the rare complication of sensorineural hearing loss associated with the disease. In 1945 Druss 5 published a landmark p a p e r t h a t defined the otologic complications of leukemia. In his publication, Druss concluded that the aural complications of leukemia were more common than previously believed. H e reported a wide range of findings, including acute otitis media, middle ear infiltration, and inner ear hemorrhage, with an overall prevalence of 16.8%. In this article we record what is, to the best of our knowledge, the first patient with chronic myelogenous leukemia with sudden onset of bilateral sen-
sorineural hearing loss. Unfortunately, there was no response or recovery of hearing after the medical treatment. CASE REPORT
A 53-year-old woman with no significant past medical
history came to the otolaryngology-head and neck surgery clinic with a report Of sudden-onset bilateral hearing loss. The hearing loss occurred on awakening 2 days before her initial visit. It was not associated with otalgia, otorrhea, tinnitus, or vertigo. The patient denied any previous noise exposure, otologic trauma, or toxic medications. The patient did relate a history of intermittent fevers for approximately 1 month. On her initial physical examination in the clinic, both external auditory canals were clear. Both tympanic membranes were normal in appearance, and she had no evidence of injection, retraction, or middle ear effusion. The audiogram (Fig. 1) demonstrated bilateral sensorineural hearing loss. For evaluation of the hearing loss, the following blood tests were ordered: complete blood count, sedimentation rate, fluorescent treponemal antibody test, VDRL, and antinuclear antibody. The sedimentation rate, fluorescent treponemal antibody test, VDRL, and antinuclear antibody results were normal. Hematologic workup demonstrated a leukocyte count of 156,000/mm 3, hemoglobin 8.5 gm/dl, and hematocrit 23.8%. A few days later the patient was admitted to the hospital for further evaluation of the abnormal blood count. The examination of the abdomen at that time revealed a soft, distended abdomen with marked hepatosplenomegaly. The cardiopulmonary examination was normal. Peripheral smear, bone marrow biopsy, and cytogenetic studies were consistent with the diagnosis of chronic myelogenous leukemia. The patient was treated with hydroxyurea resulting in a precipitous drop in leukocyte count. At 6 months after initial visit, the patient has had no change in her sensorineural hearing loss. DISCUSSION
From the Department of Otolaryngology, Washington University School of Medicine. Received for publication Nov. 23, 1994; accepted March 3, 1995. Reprint requests: Eric M. Genden, MD, Department of Otolaryngology, Box 8115, Washington University School of Medicine, 517 South Euclid Ave., St. Louis, MO 63110. OTOLARYYGOI.HEADNECKSURG 1995;113:499-501. Copyright © 1995 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/95/$5.00 + 0 23/4/64772
The incidence of acute-onset sensorineural hearing loss as the first sign of leukemia is extremely rare. Sudden sensorineural hearing loss is a condition that, despite a careful history and exhaustive physical and laboratory evaluation, commonly defies diagnosis; consequently, no effective treatment can be offered. Through a heightened index of suspicion and more discriminating diagnostic tools, otolaryn499
500
Otolaryngology Head and Neck Surgery October t995
GENDEN a n d BAHADORI
Pure Tone Audiogram
12s
250
Soo
I000
2000
4000
8000
20
0 20 Decibels
(dB)
40
60
×
I0
80 100
120 Frequency (Hz)
Fig. t. A u d i o g r a m of patient on initial visit.
gologists can identify a subgroup of patients with malignant, infectious, or autoimmune sensorineural hearing loss, who may benefit from a well-directed medical therapy. Certain pathologic conditions can be diagnosed, and it is the otolaryngologist's initial aim to ensure that these are not missed. This is usually achieved by taking a good history, examining the patient and obtaining the appropriate blood tests. Since Politzer's presentation at the Otologic Congress at Basel in 1884, several investigators have explored the cause of sensorineural hearing loss in leukemic patients. Schwabach (1897), Finlaysin (1898), and Alexander (1906), all demonstrated inner ear hemorrhages associated with leukemia. Druss 5 found acute otitis media in sectioned temporal bones, as well as leukemic infiltration of both the middle ear space and inner ear apparatus. Inner ear hemorrhage, infection, and leukemic infiltration have all been demonstrated as causes of sudden deafness in leukemic patients. Paparella et al. 6 concurred with these findings, categorizing the histopathology of sectioned temporal bones into one of the three aforementioned categories. Although Paparella's work was monumental, none of his 25 patients studied was diagnosed with chronic lymphocytic leukemia (CLL). Few studies demonstrate the role of inner ear hemorrhage as a cause of sudden deafness in chronic leukemia, but its role in
acute disease is well documented.7 The role of inner ear hemorrhage in CLL is a likely cause of sudden deafness, but the data supporting this theory are scant. Inner ear hemorrhage is, however, not the only etiologic explanation of sudden deafness. Baer et al.8 reported a case of a 47-year-old man with hyperleukocytic CLL in whom retinal hemorrhages, headaches, diplopia,-dysequilibrium, nystagmus, ataxia, and hearing loss developed. The authors attributed these symptoms to a "hyperviscosity syndrome" that occurred as a result of leukostasis. Their hypothesis was supported by the reversal of symptoms that occurred with leukapheresis. Although there are reports of this well-documented phenomenon in the literature, the syndrome is often dependent on leukocyte counts greater than 500,000/mm 3, which rarely occurs in CLL. The prognosis of patients with sudden-onset deafness is variable. Nageris et al. 9 recently reported on a 35-year-old man with CLL whose sensorineural hearing loss dramatically improved after he began chemotherapy. Baer et al. 8 reported on a similar case. Each patient had return of hearing coupled with a drop in leukocyte count. Reversal of the sensorineural hearing loss in leukemic patients is rare. It may be that patients with reversible deafness have a hyperviscosity syndrome that resolves with chemotherapy and leukapheresis, whereas those with nonreversible hearing loss have had leukemic infiltration of the middle ear and inner ear infarction. A second possibility is that hyperviscosity syndrome is a prelude to infarction. If the latter theory is correct, early diagnosis and treatment would be paramount in lowering the incidence of deafness associated with leukemia. Although neither theory is well supported in the literature, it remains that early diagnosis and treatment are imperative to low morbidity and long-term survival. The case presented is unique in that, to the best of our knowledge, there are no reported cases of bilateral sensorineural hearing loss as an initial symptom of chronic myelogenous leukemia. Helpful discussions and critical review of this manuscript were provided by Drs. Barbara A. Bohne and J. Gail Neely. REFERENCES 1. Virchow R. Weisses Blut and Milztumoren. II. Med Z 1847; 16:9. 2. Ehrlich P. Farbenanalytische Untersuchungen zur Histologie und Klinik des Blutes. Berlin: Hirschwald, 1891.
Otolaryngology H e a d a n d N e c k Surgery
Volume 113
Number 4
3. Vidal E. De la leucocythemie splenique, ou de l'hypertrophie de la rate avec alteration du sang consistant dans une augmentation considerable du nombre blancs. Gaz Hebd Sci Med Bordeaux, Par 1856;3:166, 201, 235. 4. Politzer A. Pathologische Veranderungen im Labyrinthe bei leukamischer Taubheit. Cong Int Otol 1885;3:139. 5. Druss J. Aural manifestations of leukemia. Arch Otolaryngology 1945;42:267. 6. Paparella MM, Berlinge NT, Oda M, El-fiky F. Otological manifestations of leukemia. Laryngoscope 1973;83:1510-26.
GENDEN and BAHADORI 5 0 t
7. Schuknecht HF, Igarashi M, Chasin WD. Inner ear hemorrhage in leukemia. A case report. Laryngoscope 1965;75:662-8. 8. Baer RM, Stein RS, Dessypris EN. Chronic lymphocytic leukemia with hyperleukocytosis. The hyperviscosity syndrome. Cancer 1985;56:2865-9. 9. Nageris B, Or R, Hardan I, Polliack A. Sudden onset deafness as a presenting manifestation of chronic lymphocytic leukemia. Leuk Lymphoma 1993;9:269-71.