Sudden sensorineural hearing loss is defined as an acquired hearing deficit of up to 30 dB loss in 3 different frequencies on an audiogram, building up over a few hours to up to 3 days. Five to 20 per 100,000 population are affected, both male and female, typically between 30 and 60 years of age. In the majority of cases, hearing loss is unilateral and associated with vestibular symptoms. The pathophysiology is unclear. Viral, genetic, traumatic, or toxic causes have been discussed. Autoimmune or vascular etiology has been put forward in 10% of cases.
Sudden sensorineural hearing loss is an unusual presenting clinical feature of systemic lupus erythematosus. We report the case of a young woman who presented to our hospital for sudden sensorineural hearing loss that was ultimately attributed to systemic lupus erythematosus. We reviewed the medical literature indexed in the Medline database (accessed on December 28, 2015). Our search key words were: “hearing OR sensorineural OR deafness AND lupus,” in all fields, only English and French language articles.
2 Case report
A 19-year-old woman was referred to our hospital in December 2006 for a fever, a sudden profound bilateral hearing loss and a malar rash that had appeared 10 days before hospitalization. She had no significant past medical history. Besides hearing loss, physical examination revealed a malar rash, ulcerated stomatitis, enlarged cervical lymph nodes, and subungual hemorrhage. The remainder of the physical examination was normal.
An audiogram showed a hearing threshold of 40 dB in the right ear and 60 dB in the left ear, both in air and bone conduction. Laboratory tests revealed neutropenia (540 neutrophils/μL), thrombocytopenia (125,000/μL), elevated liver enzymes (aspartate aminotransferase 247 IU/L, 8-fold the upper limit of normal range; alanine transaminase 116 IU/L, 3-fold the upper limit of normal range; gamma-glutamyl transferase 166 IU/L, 3-fold the upper limit of normal range and alkaline phosphatase 40 IU/L, normal), hyperferritinemia (10,965 μg/L) and an elevated titer of lactate dehydrogenase (989 IU/L, 3-fold the upper limit of normal range), and triglycerides (4.96 g/L, normal range: 0.6–1.9 g/L). Hematuria and leucocyturia were initially detected, with an associated proteinuria (3.13 g/L).
Antinuclear antibodies were positive (titer 1/2560), with antidouble stranded DNA (31 IU) and anti-Sm antibodies. Antinucleosome and anti-SSA antibodies were present as well. Coagulation tests disclosed a lupus anticoagulant. Low levels of anticardiolipin antibodies were detected (IgG: 27 μg/L).
Complement was abnormally low with 0.3 g/L C3 (lower limit 0.7 g/L); 0.1 g/L C4 (lower limit 0.1 g/L) and 50% CH50%. Bone marrow aspiration revealed mild hemophagocytosis.
Renal biopsy revealed World Health Organisation class II lupus nephritis with pure mesangial involvement, with IgG, C3, C1q, and IgM deposits on immunofluorescence. There was no alteration of blood vessels (absence of infiltration, necrosis of the vascular wall, or microscopic thromboangiitis), nor proliferation on light microscopy.
Echocardiographic examination was normal, without any valvular abnormality. Cerebral magnetic resonance imaging was normal and displayed no evidence of ischemia.
The patient met the American College of Rheumatology classification criteria for systemic lupus erythematosus. She was treated with high-dose (500 mg) intravenous methylprednisolone for 3 days, and clinically improved within a few days. The hearing completely recovered, as assessed by repeated audiograms. The hemophagocytic syndrome, proteinuria, and hematuria also improved following corticosteroid therapy.
Long-term treatment with prednisone (1 mg/kg/day with gradual decrease), hydroxychloroquine and aspirin was introduced. Six months later, proteinuria and hematuria rebounded and mycophenolate mofetil treatment was introduced. Overall treatment was well tolerated. One year later, clinical examination was normal with a complete remission of systemic lupus erythematosus; mycophenolate mofetil was stopped.
Secondary antiphospholipid syndrome (antiphospholipid syndrome) was excluded on the basis of an uneventful follow-up and the quick fading of anticardiolipin antibodies and lupus anticoagulant that were never detected again over 9 years of follow-up.
A second flare occurred in 2011, with myalgia, arthralgia, fatigue, and hemophagocytic syndrome. This flare was treated by a temporary increase of prednisone dose; no immunosuppressive therapy was necessary. Evolution was unremarkable ever since. When last seen in February 2016, the patient was doing well on 5 mg prednisone and 400 mg hydroxychloroquine daily.
This patient presented with bilateral sudden sensorineural hearing loss in the context of a hemophagocytic syndrome, revealing systemic lupus erythematosus, and raising questions about pathophysiology and treatment. Sudden sensorineural hearing loss should be clearly distinguished from other sensorineural hearing loss in patients with systemic lupus erythematosus. Indeed, systematic audiometric tests have shown that 20% to 55% of systemic lupus erythematosus patients have chronic sensorineural hearing impairment, often asymptomatic.[3–8] Thus, the risk of sensorineural hearing loss seems to be much higher in systemic lupus erythematosus patients compared to healthy age-matched controls, with an odds ratio of 20 (95% CI: 2.93–139.6). In contrast, sudden sensorineural hearing loss, which is usually a dramatic condition, has been seldom reported in systemic lupus erythematosus patients (Table 1).
Three pathophysiological hypotheses are proposed for sudden sensorineural hearing loss at the beginning of systemic lupus erythematosus manifestations[9,10]:.
- T-cell autoimmunity: As shown patients with sudden sensorineural hearing loss presented significant proliferation of T lymphocytes specifically responsive to human inner ear antigens, as well as increased interferon-gamma and other inflammatory intracellular cytokines levels in peripheral blood.[11–16]
- Humoral autoimmunity: specific autoantibodies directed against inner-ear antigens have been detected in this context and may be involved in sudden hearing loss.[17–19]
- Antiphospholipid syndrome: case reports have highlighted the possible association of anticardiolipin antibodies with sudden sensorineural hearing loss in systemic lupus erythematosus. Antiphospholipid antibodies (i.e., anticardiolipin antibody, lupus anticoagulant, and anti-β2 GP1) are known to be associated with microcirculation thrombosis and histological proof of microinfarctions has been reported in systemic lupus erythematosus patients with sudden sensorineural hearing loss.[20–22] High concentrations of antiphospholipid antibodies have been reported in case reports of lupus-associated sudden sensorineural hearing loss, with satisfying clinical response to anticoagulant therapy.[20,22–26] Whether the presence of antiphospholipid antibodies in patients presenting sudden sensorineural hearing loss is sufficient to establish a diagnosis of secondary antiphospholipid syndrome in the absence of other symptoms (i.e., thromboembolic or obstetrical complications) remains to be determined.[20,22,24,25]
When reviewing the English and French literature in the Medline database, we found 22 documented cases of sudden sensorineural hearing loss in association with systemic lupus erythematosus (Table 1). Patients were between 20 and 50 years old, mostly women (16/22). Hearing loss was unilateral in 14 out of 22 cases. Hearing loss was the first manifestation of systemic lupus erythematosus in four cases. In 11 cases major systemic involvement of systemic lupus erythematosus such as renal, cardiac, or neurological involvement was also reported.
Besides hearing loss, other reported aural symptoms included: middle ear involvement, otitis, and in 9 cases, vestibular symptoms.
When tested, anticardiolipin antibodies, and/or lupus anticoagulant and/or isolated syphilis reaginic antibody proved positive in 11 out of 15 cases. Half of these patients had a past or present medical history of thrombosis. Ten patients had had a brain CT-scan or MRI: among them, 3 had signs of central nervous system ischemia. However, secondary antiphospholipid syndrome was not explicitly considered in several of those cases. Pathological data were available in three cases, showing middle ear lesions such as vasculitis and nonspecific inflammation.
Twelve patients were treated with steroids (0.5–1 mg/kg equivalent prednisone, 1 was treated with 500 mg methylprednisonolone on 3 consecutive days), 4 patients were prescribed immunosuppressive therapy with azathioprine or cyclophosphamide, 3 were treated with plasmapheresis and 2 with hydroxychloroquine. Anticoagulation or antiplatelet therapy was prescribed to 4 patients. Clinical outcome was reported for 13 patients: recovery from hearing loss was complete in only 4 patients and partial in 2 other cases. None of the patients treated with anticoagulation or antiplatelet therapy recovered.
A recent publication of a retrospective cohort study from the Taiwan National Health Insurance Research Database reported 27 cases of sudden sensorineural hearing loss associated with systemic lupus erythematosus, but no detail on clinical and biological data was available.
We conclude that sudden sensorineural hearing loss can be the presenting clinical feature of systemic lupus erythematosus and may be associated with antiphospholipid antibodies. Although management of such cases remains empirical, the high risk of permanent hearing loss seems to justify emergency treatment with high dose corticosteroids. If the laboratory criteria of antiphospholipid syndrome are present, antiplatelets agents or anticoagulation therapy shall be considered.
Informed oral consent was obtained from the patient.
All data were strictly obtained from the patient's medical file.
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