Introduction
Sudden sensorineural hearing loss (SNHL) is defined as hearing loss that develops within 72 hours, characterised by a decrease in hearing greater than 30 dB at 3 or more consecutive frequencies.1 The annual incidence of sudden SNHL has been reported to be approximately 20 cases per 100 000 people.Reference Hughes, Freedman, Haberkamp and Guay2 A diagnosis of sudden SNHL is usually unilateral, warranting magnetic resonance imaging scans of the internal acoustic meati to exclude retro-cochlear pathology.Reference Mijovic, Zeitouni and Colmegna3
It is estimated that up to 90 per cent of cases of sudden SNHL are idiopathic at presentation.Reference Linthicum, Doherty and Berliner4 Potentially treatable causes include autoimmune conditions, vestibular schwannoma, stroke, vasculitis and infection.Reference Linthicum, Doherty and Berliner4 Poor diet and diabetes have been found to increase the incidence of ‘idiopathic’ sudden SNHL.Reference Cadoni, Agostino, Scipione and Galli5 Immune-mediated sudden SNHL tends to be associated with worse prognosis and irreversible hearing loss but can be treated if recognised early, preventing additional damage to the inner ear.Reference Mijovic, Zeitouni and Colmegna3 Bilateral sudden SNHL, fluctuations in hearing, nystagmus, visual disturbance and focal neurology are all signs that indicate an alternative diagnosis to idiopathic sudden SNHL.Reference Mijovic, Zeitouni and Colmegna3 These signs are suggestive of autoimmune inner-ear disease that frequently causes a stepwise decline in hearing.Reference Tayer-Shifman, Ilan, Tovi and Tal6 Pre-existing systemic autoimmune disease is present in 30 per cent of patients with immune-mediated sudden SNHL.Reference Mijovic, Zeitouni and Colmegna3 Haematological investigations can therefore aid in early diagnosis of an underlying disorder.Reference Heman-Ackah, Jabbour and Huang7 Both hyper- and hypothyroidism have been associated with sudden SNHL. Thyroid function tests and thyroid antibody assay can be useful because thyroid disorders can be managed to prevent further inner-ear complications.Reference Rossini, Penido, Munhoz, Bogaz and Curi8 It is widely recommended that autoimmune screening blood tests should also be performed in unexplained sudden SNHL, including tests for antinuclear antibody, antineutrophil cytoplasmic antibody, anti-endothelial cell antibody, antiphospholipid antibody, rheumatoid factor and anti-double stranded DNA.Reference Wiles, Hunt, Callanan and Chevretton9,Reference Boulassel and Deg10
Management of sudden SNHL is similar regardless of whether it is idiopathic or autoimmune,Reference Čvorović, Đeric, Probst and Hegemann11 with steroid therapy recommended within two weeks of presentation.Reference Dayal, Ellman and Sweiss12 This can be in the form of intratympanic or systemic steroid therapy. There is limited evidence for salvage therapy with steroids and hyperbaric oxygen therapy if treatment is not initiated within two weeks.Reference Čvorović, Đeric, Probst and Hegemann11,Reference Dayal, Ellman and Sweiss12
The American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) Foundation recommends follow up six months after presentation, with pure tone audiometry to monitor the progression of hearing loss and outcome of treatment.Reference Chandrasekhar, Tsai Do, Schwartz, Bontempo, Faucett and Finestone13 Follow up is particularly important in idiopathic cases because up to 30 per cent of patients may have an underlying cause diagnosed at follow up.Reference Chandrasekhar, Tsai Do, Schwartz, Bontempo, Faucett and Finestone13 The AAO-HNS Foundation guideline specifically advises against the use of routine laboratory tests in idiopathic sudden SNHL.Reference Chandrasekhar, Tsai Do, Schwartz, Bontempo, Faucett and Finestone13 Recovery of hearing following sudden SNHL varies between patients depending on the severity.Reference Ågrup and Luxon14 Mild to moderate hearing loss resolves spontaneously in up to 65 per cent of patients. Most patients display improvement in hearing, although not necessarily back to their normal baseline. Positive prognosis factors are isolated high or low frequency hearing loss, association with tinnitus and the absence of vertigo.Reference Ågrup and Luxon14 Severe bilateral hearing loss associated with autoimmune causes and vertigo carries the worst prognosis. Hypertension and metabolic syndrome have also been associated with poor prognosis of sudden SNHL because of microangiopathy of brain parenchyma.Reference Magro, Poe, Lubow and Susac15
Only 1 per cent of sudden SNHL has been attributed to autoimmune disease,Reference Cooper, Bynum and Somers16 although they may make up a much greater proportion than this because of non-specific features during initial presentation and the overlap of immune-mediated sudden SNHL symptoms with other conditions, such as multiple sclerosis, Ménière's disease or stroke.Reference Magro, Poe, Lubow and Susac15 Furthermore, the lack of a standardised battery of autoimmune investigations for sudden SNHL can lead to many of these cases being incorrectly categorised as idiopathic.Reference Cooper, Bynum and Somers16
Despite the potential for early identification of immune-mediated sudden SNHL to be amenable to treatment, there is currently no accepted consensus for recommended haematological investigations in sudden SNHL. Improved screening for autoimmune causes of sudden SNHL might allow immune-mediated sudden SNHL to be identified rather than it being labelled idiopathic;Reference Toubi, Halas, Ben-David, Sabo, Kessel and Luntz17 this would facilitate appropriate therapy and, looking to the future, the potential to identify targets for immune therapy.
Our goal was to systematically review the literature, exploring the role of blood tests as biomarkers for the diagnosis and prognosis of sudden SNHL, and if appropriate, to compile an evidence-based protocol of recommended haematological investigations for use in clinical practice.
Materials and methods
The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) guidelines. The review was pre-registered on the Prospero database (identification: CRD42022351478).
The search was conducted in May 2022. The search was performed on PubMed, Embase via Ovid, Cinahl Plus via EBSCOhost and the Cochrane Library. Search terms were ‘sudden onset sensorineural hearing loss’ OR ‘SSNHL’ OR ‘sudden sensorineural hearing loss’ OR ‘autoimmune hearing loss’ AND ‘haematological’ OR ‘blood test’.
Results from the search were recorded on a secure Google sheet that was editable and trackable by both researchers. Two researchers screened abstracts independently for initial inclusion. Reference lists of all included studies were screened. Full text manuscripts were screened independently by both researchers. Case reports, irrelevant results and research that included paediatric patients were excluded. Systematic reviews, literature reviews and meta-analyses were excluded from the analysis. Only original research was used for the extraction of quantitative data to provide evidence for outcomes.
Data were extracted from included studies and compiled on an Excel® spreadsheet. A pilot search demonstrated that there are very few randomised, controlled trials on this topic. Therefore, studies addressing haematological investigations in adults with sudden SNHL were included regardless of whether there was a control group.
The modality of haematological investigation used was recorded, noting the mean results and major outcomes from each study. Specialty of the journal as well as country of origin was noted. One reviewer conducted the data collection for each report, and this was reviewed independently by the second reviewer. The data collected included average results from blood tests and frequency of each modality used for investigation. Excel software was used to create tables, pie charts and bar graphs displayed in this review.
Results
The literature search returned 201 articles. Following screening using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) guidelines, 43 studies were identified for inclusion (Figs 1). The included studies had a total population of 19 690 patients with sudden SNHL. The majority (31 studies, 72 per cent of total) were published in ENT journals. Four were published in audiology journals. The remainder were in a mixture of general medical and primary care journals. The frequency of study types and country of origin for the included studies are displayed in Figs 2 and 3, respectively. Analysis of the included studies yielded a wide variety of haematological investigations, in differing combinations, that were analysed in the context of diagnosis and/or prognosis of sudden SNHL. Because of the heterogeneous nature of included studies and inconsistent application of investigations and standardised normative values, the results of the review are summarised qualitatively in Table 1. Full systematic review data are available from the first author on request.
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) 2020 flow diagram displaying the systematic search methodology.
Figure 2. Study types included in the final review.
Figure 3. Global origin of research.
Table 1. Haematological investigations used in the 43 included studies
SNHL = sensorineural hearing loss; ESR = erythrocyte sedimentation rate
White blood cells
Undifferentiated white blood cell counts were found to be higher in patients with sudden SNHL than controls in all studies investigating this. There was also an observed association between raised white blood cell counts and poor recovery.Reference Sun, Xia, Wang, Chen, Wu and Chen18 Lymphocyte counts were consistently found to be lower in patients than controls and lower still in the sudden SNHL non-recovery group.Reference Salvago, Rizzo, Bianco and Martines19 Neutrophils were consistently raised in sudden SNHL, with higher values associated with severe hearing loss and poorer prognosis.Reference Durmuş, Terzi, Karataş, Doğan, Uysal and Şencan20 In keeping with these observations, neutrophil-lymphocyte ratio was investigated in 42 per cent of included studies and was found to be significantly higher in sudden SNHL than in controls.Reference Seo, Jeong, Choi and Moon21,Reference Seo, Park, Bong, Park and Park22 There was a linear correlation with hearing recovery, and a lower neutrophil-lymphocyte ratio was observed following treatment.Reference Cao, Li, Xiang, Huang, Gao and Zhan23 Neutrophil-lymphocyte ratio was shown to be significantly higher in bilateral compared with unilateral sudden SNHL in one study.Reference Zhang, Weng, Xu, Xiong, Liang and Zheng24
Platelets
Platelet count was investigated in 12 included studies. In sudden SNHL, both platelet count and platelet-lymphocyte ratio are consistently found to be raised.Reference Bozan, Alpaycı, Aslan, Cankaya, Kıroglu and Turan25 Platelet-lymphocyte ratio is higher in bilateral successive hearing loss compared with unilateral hearing loss.Reference Sancaktar, Ağrı, Çeçen, Akgül and Çelebi26 The Systemic Immune Inflammation Index (platelets × neutrophils/lymphocytes) gives an indication of systemic inflammation and is associated with poor recovery.Reference Ulu, Kınar, Bucak and Özdemir27
Prestin
Blood prestin levels were investigated by two studies in relation to sudden SNHL. Both found prestin levels were significantly higher in sudden SNHL compared with controls. Prestin decreased following the complete recovery of hearing loss.Reference Sun, Xuan, Zhou, Yuan and Xue28,Reference Parker, Parham and Skoe29
Lipid profile
Low-density lipoprotein (LDL) levels were up to 42.8 per cent higher in sudden SNHL, and high-density lipoprotein (HDL) levels were up to 40.6 per cent lower, with higher values observed upon recovery.Reference Sciancalepore, de Robertis, Sardone and Quaranta30,Reference Xie, Ning, She, Jing, Jiang and Zhang31
Fibrinogen
Fibrinogen levels were greater in the non-recovery group compared with the control groupReference Kanzaki, Sakagami, Hosoi, Murakami and Ogawa32 and were higher in successive bilateral hearing loss than unilateral sudden SNHL.Reference Kanzaki, Sakagami, Hosoi, Murakami and Ogawa32 The fibrinogen-HDL ratio was found to be lower in complete recovery; elevated levels indicated poor prognosis.Reference Hira, Yasar, Kaya, Bayram and Ozcan33 High fibrinogen-albumin ratios were correlated with poor prognosis.Reference Cayir, Kayabasi and Hizli34
Autoimmune biomarkers
Anti-endothelial cell antibody was investigated in two studies,Reference Cadoni, Fetoni, Agostino, Santis, Manna and Ottaviani35,Reference Cadoni, Agostino, Manna, de Santis, Fetoni and Vulpiani36 with both observing higher rates of anti-endothelial cell antibody in sudden SNHL. Autoimmune screening tests for antineutrophil cytoplasmic antibodies, ANA, rheumatoid factor, antiphospholipid, anticardiolipin and anticitrullinated protein were all observed to be raised in sudden SNHL.Reference Bertoli, Pappas, Barton and Barton37 Endothelial cell-specific molecule 1 (ESM-1), pentraxin-3 and interferon gamma-induced protein 10, also associated with inflammation, can be raised in sudden SNHL.Reference Gündoğan, Bayram, Kalkan and Özcan38,Reference Lee, Kim, Bok, Kim, Choi and Kim39
Heat shock protein-70
Heat shock protein-70 was explored by 3 studies including 5312 patients and was found to have 90 per cent specificity and 42 per cent sensitivity with 91 per cent positive predictive value when predicting sudden SNHL response to treatment.Reference Ianuale, Cadoni, de Feo, Liberati, Simo and Paludetti40
Discussion
Although the literature is disparate, there are four themes that consistently emerge. First, there is a trend for cases of sudden SNHL to have raised inflammatory markers, suggesting an almost universal inflammatory process. Second, there is no single test which identifies inflammation more effectively than a full blood count. Third, the identification of underlying aetiologies or predisposing factors requires focused investigation. Fourth, there is an increasing body of evidence in regard to biomarkers for sudden SNHL prognosis.
White blood cells are the most frequently investigated biomarkers for sudden SNHL, consistently higher in sudden SNHL than in controls.Reference Cao, Gao, Huang, Xiang, Zhang and Zheng41 Lymphocytes are consistently lower in sudden SNHL than controls and are lower still in cases of sudden SNHL that do not recover.Reference Ulu, Kınar, Bucak and Özdemir27 Raised neutrophils correlate with severe hearing loss and poor prognosis.Reference Masuda, Kanzaki, Minami, Kikuchi, Kanzaki and Sato42 Across numerous studies, these trends indicate inflammatory or autoimmune aetiology.
A total of 42 per cent of included articles investigated neutrophil-lymphocyte ratio as a biomarker to predict diagnosis and prognosis of sudden SNHL. A meta-analysis of neutrophil-lymphocyte ratio as a biomarker for the diagnosis and prognosis of sudden SNHL published in 2018 concluded that neutrophil-lymphocyte ratio values were significantly higher in non-recovered than recovered sudden SNHL patients.Reference Chen, Zhang, Zhang, Wang, Hu and Wu43 A recent study found that neutrophil-lymphocyte ratio was the only inflammatory marker that differed significantly between patients and controlsReference Guo and Liu44 with comparable results to similar studiesReference Zhang, Weng, Xu, Xiong, Liang and Zheng24 and a consistent finding that neutrophil-lymphocyte ratio levels are higher in unrecovered than recovered groups. There is a linear correlation with hearing recovery, with a lower neutrophil-lymphocyte ratio being linked to better prognosis.Reference Kang, Kim, Kim, Im, Dong and Kim45 High neutrophil-lymphocyte ratio is thought to be a representation of the inflammatory mediator response, which leads to vascular inflammation and endothelial dysfunction.Reference Özler46 Raised neutrophil-lymphocyte ratio may be predictive of contralateral recurrence of sudden SNHL, with bilateral successive disease displaying higher neutrophil-lymphocyte ratio than unilateral sudden SNHL.Reference Cao, Li, Xiang, Huang, Gao and Zhan23 Neutrophil-lymphocyte ratio levels have been shown to be elevated in ankylosing spondylosis compared with controls, demonstrating a comparable biomarker profile between sudden SNHL and other autoimmune conditions.Reference Zhang, Weng, Xu, Xiong, Liang and Zheng24 Several studies assess C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as biomarkers for sudden SNHL; however, these are non-specific and add little beyond identification of inflammation, more effectively measured by neutrophil-lymphocyte ratio.Reference Magro, Poe, Lubow and Susac15,Reference Salvago, Rizzo, Bianco and Martines19
Platelet count and platelet-lymphocyte ratio were investigated in 28 per cent of included articles and demonstrated a possible link to prognosis; although some studies observed a linear correlation between elevated platelet count and hearing impairment,Reference Özcan, Hira, Kaya, Yaşar, Doğan and Mutlu47 others found the correlation to not be significant.Reference Koçak, Elbistanlı, Acıpayam, Alakras, Kıral and Kayhan48 Significantly higher platelet-lymphocyte ratio in sudden SNHL than controlsReference Qiao, Li, Wang, Bai, Zheng and Li49 and significantly higher platelet-lymphocyte ratio in bilateral compared with unilateral sudden SNHLReference Cao, Li, Xiang, Huang, Gao and Zhan23 suggests that platelet-lymphocyte ratio may be a reliable biomarker. The mechanism by which a higher platelet count contributes to sudden SNHL is thought to be because of the interaction between platelets and leukocytes in damaged endothelium, forming thrombi which impede blood flow and lead to inner ear ischaemia.Reference Seo, Jeong, Choi and Moon21 Elevated platelet-lymphocyte ratio can be indicative of severe vascular inflammation and plaque formation, which contributes to a worse prognosis.Reference Qiao, Li, Wang, Bai, Zheng and Li49 Mean platelet volume has also been identified to be significantly higher in sudden SNHL than controls,Reference Sun, Guo, Wang, Chen, Wu and Shi50 although it is not universally considered to be a reliable biomarker.Reference Yildiz and Zer Toros51 Similarly, there are discrepancies regarding platelet distribution width, which has been found to be significantly elevated in sudden SNHL,Reference Yildiz and Zer Toros51 whereas other studies found the difference to not be significant.Reference Mirvakili, Dadgarnia, Baradaranfar, Atighechi, Zand and Ansari52 Platelets with higher volumes are more prone to aggregate, triggering inflammation and thrombus formation, which may explain the higher platelet distribution width and mean platelet volume values observed in some studies.Reference Ni, Song and Jiang53
A recent meta-analysis identified a mean fibrinogen level significantly elevated in sudden SNHL compared with controls.Reference Oya, Takenaka, Imai, Sato, Osaki and Ohta54 One studyReference Xie, Dai, Liu, Liu, Hellström and Duan55 showed that hearing recovery correlated with a drop in fibrinogen levels, and another showed that higher levels of fibrinogen were associated with incomplete hearing recovery.Reference Salvago, Rizzo, Bianco and Martines19 Mean fibrinogen has been observed to be significantly higher in bilateral sudden SNHL compared with unilateral sudden SNHL.Reference Zhang, Weng, Xu, Xiong, Liang and Zheng24 Fibrinogen therefore shows promise as a biomarker for diagnosis and prognosis of sudden SNHL and has also been investigated alongside serum albumin levels, with fibrinogen-albumin ratio found to be significantly higher in patients who did not show hearing recovery and being used to predict poor prognosis.Reference Cayir, Kayabasi and Hizli34 Fibrinogen increases blood viscosity, and high levels can reduce blood supply to the inner ear.Reference Berger, Kaiser, Scholz, Bachmann, Ceglarek and Hesse56 Serum albumin levels alone have been shown to be low in sudden SNHL and increased with recovery (therefore potentially useful in prognosis)Reference Li, Zhang, Wang, Zhang, Ma and Wang57 likely because of correlation with the early stages of inflammation. Coagulation is not a useful biomarker in sudden SNHL.Reference Li, Zhou, Feng, Zhao, Wang and Chen58,Reference Zheng, Liu, Shen, Xia, Xiao and Sun59
A total of 21 per cent of included studies in this review investigated metabolic parameters in the context of sudden SNHL. Although LDL and HDL correlated with sudden SNHL,Reference Sciancalepore, de Robertis, Sardone and Quaranta30,Reference Xie, Ning, She, Jing, Jiang and Zhang31 there was minimal evidence to support cholesterol or triglycerides as biomarkers in isolation.Reference Mohammed60 Fibrinogen-HDL ratio was found to be lower in complete recovery, with elevated levels predicting poor recovery.Reference Hira, Yasar, Kaya, Bayram and Ozcan33 High triglycerides and fasting glucose were associated with poor hearing recovery.Reference Lam, Bao, Hua and Sommer61 Metabolic syndrome is thought to lead to microvascular dysfunction within the cochlea, putting patients with poorly controlled diabetes and elevated lipids at higher risk of sudden SNHL.Reference Chang, Kang, Yueh, Fang, Yeh and Tsai62
Autoimmune screening tests for antineutrophil cytoplasmic antibodies, antiphospholipid and anticardiolipin are consistently found to be elevated in sudden SNHL; however, they are no more sensitive than inflammatory markers in indicating a diagnosis.Reference Xie, Ning, She, Jing, Jiang and Zhang31,Reference Jeong, Lim, Lee, Hong and Choi63 Anti-endothelial cell antibody is positive in patients with sudden SNHL, with a statistically significant difference compared with controls,Reference Cadoni, Fetoni, Agostino, Santis, Manna and Ottaviani35,Reference Cadoni, Agostino, Manna, de Santis, Fetoni and Vulpiani36 and 88 per cent of patients with no hearing recovery being anti-endothelial cell antibody positive. Anti-endothelial cell antibody is thought to induce irreversible vascular damage to the inner ear that is refractory to treatment. As such, it is widely used as a biomarker for immune-mediated vasculitis.Reference Zhai64 Several studies found a promising role for heat shock protein-70 in the diagnostic investigations of sudden SNHL,Reference Hirose, Wener and Duckert65 and endothelial cell-specific molecule 1 levels were found to be higher in sudden SNHL compared with the control group,Reference Gündoğan, Bayram, Kalkan and Özcan38 supporting evidence of vascular impairment. Endothelial cell-specific molecule 1 is associated with premature endothelial dysfunction, which can cause reduced inner-ear perfusion. Pentraxin 3 gene, which promotes vascular inflammation, has also been found to be raised in sudden SNHL,Reference Gündoğan, Bayram, Kalkan and Özcan38 and interferon gamma-induced protein 10 inflammatory chemokine, which promotes T-cell adhesion to endothelial cells, is also raised in sudden SNHL.Reference Lee, Kim, Bok, Kim, Choi and Kim39 Although largely non-specific with regard to diagnosis and prognosis, these findings support the role of endothelial dysfunction and inflammation in the pathogenesis of sudden SNHL. Prestin is a protein released into circulation following degradation of the outer hair cells.Reference Parker, Parham and Skoe29 Research using this protein is in its early stages. Early work demonstrates raised prestin levels in sudden SNHL patients, which decreases following treatment but remains significantly raised in patients with no hearing recovery.Reference Sun, Xuan, Zhou, Yuan and Xue28 Prestin may be a promising biomarker for sudden SNHL prognosis and response to treatment.
Limitations
Although conducted thoroughly, the results of this review may have limitations. The majority of included studies originated from Asian authors and populations, which may limit the global applicability of findings because of population-specific factors. A further potential limitation is that research was included regardless of hearing loss severity or underlying disease in the patient population. For example, patients with diabetes and hypertension were included in the sample, but as demonstrated in the review, metabolic syndromes can impact the severity of hearing loss and prognosis.Reference Sancaktar, Ağrı, Çeçen, Akgül and Çelebi26
Throughout the analysed studies, there is variation in the values obtained for biomarkers and the stated normative values. This has rendered accurate data synthesis a challenge. Although this may reflect differences between populations or accepted practices, it presents a barrier to producing a definitive guideline that includes numeric values. A consensus process to define normative values may be a useful future research direction.
Implications for clinical practice
The literature review appraises evidence for the use of haematological tests for the diagnosis and prognosis of sudden SNHL. A patient-specific approach dictated by the timing and type of hearing lossReference Kanzaki, Sakagami, Hosoi, Murakami and Ogawa32 is proposed across the literature, but a consensus regarding blood tests is lacking. Our recommended protocol is detailed in Table 2. The AAO-HNS clinical practice guideline on sudden SNHLReference Chandrasekhar, Tsai Do, Schwartz, Bontempo, Faucett and Finestone13 advises the deployment of guided haematological investigations for the purpose of identifying aetiologies. However, subsequent published evidence offers neutrophil-lymphocyte ratio, neutrophil platelet ratio and fibrinogen as accessible and increasingly useful biomarkers for the prognosis of SNHL.
Table 2. Recommended blood tests for sudden sensorineural hearing loss in adults
Although steroid administration is the universally recommended therapy for sudden SNHL worldwide, greater insight into aetiology and prognosis will serve to guide individualised care and provide a grounding for future innovation and developments.
Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio have value in the diagnosis and prognosis of sudden SNHL in adults; they are also widely accessible as part of a full blood count. Inflammatory markers such as CRP and ESR do not offer additional information. Autoimmune biomarkers add little to treatment decisions or prognostication, except for anti-endothelial cell antibody which demonstrates potential as a biomarker for prognosis. Fibrinogen is an accessible blood test that has been shown to be valuable when considered in isolation and alongside albumin levels; coagulation profiles have not been shown to be of value.
Autoimmune and metabolic disorders may present as sudden SNHL, and clinicians should pursue aetiology guided by individual patient profiles. Underlying conditions may require treatment in addition to management of sudden SNHL.
Several specialised proteins have been investigated in the context of sudden SNHL. Most have yielded little more information than neutrophil-lymphocyte ratio, indicating the presence of inflammation. Heat shock protein-70 shows potential as a biomarker for predicting response to sudden SNHL treatment. Prestin also shows potential as a biomarker for sudden SNHL prognosis and response to treatment.
The future
Several targets require further research before translation into clinical practice. Human leucocyte antigen has been found in 75.4 per cent of patients with sudden SNHL and may offer potential for future research.Reference Psillas, Binos, Dimas, Daniilidis and Constantinidis66 Interleukin-10 deficiency may be linked to sudden SNHL,Reference Zhou, Kermany, Cai, Cai, Zhou and Nair67 and changes in interleukin-1 and interleukin-2 may also be implicated.Reference Chien, Tai, Li, Yang, Chan and Hsi68 Immunoglobulin levels may show promise as a biomarker for sudden SNHL diagnosis and prognosis.Reference Bertoli, Pappas, Barton and Barton37 Beyond confirmation of an inflammatory process, diagnostic tests are minimally informative; therefore, the identification of new targets for treatment, such as single nucleotide polymorphisms,Reference Nelson, Johns, Gu and Hoa69 may also be on the horizon.
Conclusion
The literature is consistent in identifying that cases of sudden SNHL demonstrate raised inflammatory markers, suggesting an almost universal inflammatory or autoimmune process. There is no single test that identifies inflammation more effectively than a full blood count.
Although 90 per cent of sudden SNHL cases are thought to be idiopathic, emerging evidence suggests that there may be a significant proportion of sudden SNHL with an identifiable underlying aetiology or predisposing factor. Focused investigations should therefore be deployed on a case-by-case basis to identify underlying metabolic, infective and autoimmune conditions.
We recommend a full blood count and coagulation screen (fibrinogen) for all cases of sudden SNHL. These are inexpensive, accessible and, alongside patient-specific investigations, they offer as much information on the diagnosis and prognosis of sudden SNHL as any other biomarker.
There is an increasing body of evidence regarding biomarkers for sudden SNHL prognosis, with heat shock protein-70, anti-endothelial cell antibody and prestin demonstrating potential. We recommend the investigation of their validity through prospective research.
Data availability statement
Full systematic review data are available from the first author on request.
Competing interests
None declared.
