Abstract
The temporal bone may be affected by a variety of systemic pathology because the disease nature, location, and extent determine the symptoms. Middle ear and mastoid infections may be the initial clinical manifestation of autoimmune and acquired immunodeficiency disorders. Rituximab, an anti-CD20 chimeric antibody, has become increasingly popular as a therapeutic agent for patients with a wide range of autoimmune disorders refractory to standard treatments. Normal levels of immunoglobulin levels are usually maintained during and after rituximab therapy, and clinical trials to date have shown no statistically significant increase of serious infections among patients with autoimmune diseases being treated with rituximab (Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al, for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at 24 weeks. Arthritis Rheum . 2006;54:2793-2806. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell–targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med . 2004;350:2572-2581). However, there have been several reports of opportunistic infections associated with rituximab (Kelesidis T, Daikos G, et al. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis 2011;15:e2-e16. Teichmann LL, Woenckhaus M, Vogel C, et al. Fatal Pneumocystis pneumonia following rituximab administration for rheumatoid arthritis. Rheumatology 2008;47:1256-1257), as well as cases of it accelerating the presentation of hypogammaglobulinemia (Diwakar L, Gorrie S, et al. Does rituximab aggravate pre-existing hypogammaglobulinaemia? J Clin Pathol 2010;63:275-277). Humoral immune defects can cause persistent acute and serous otitis media, with the development of chronic suppurative otitis media refractory to medical and surgical therapy (Sasaki CT, Askenase P, Dwyer J, et al. Chronic ear infection in the immunodeficient patient. Arch Otolaryngol 1981;107:82). Here, we describe the first presentation, diagnostic workup, and treatment with intravenous immunoglobulin of chronic bilateral otomastoiditis in the setting of rituximab-induced hypogammaglobulinemia.
1
Case report
A 22-year-old woman being treated by her community otolaryngologist for chronic bilateral otomastoiditis was referred for surgical management of chronic mastoiditis.. The patient was diagnosed with MuSK antibody+ myasthenia gravis 7 years previously, and she had a thymectomy 4 years later. The patient’s symptoms were controlled on pyrostigmine bromide 180 mg daily and prednisone 10 mg every other day. She also had received 4 weekly 375 mg/m 2 doses of rituximab at 6-month intervals over the last year. Her initial presentation to the referring otolaryngologist was with the complaint bilateral aural fullness and pain. The patient had profound left-sided sensorineural hearing loss since childhood but, now, had progressive hearing loss in her right ear. Purulent drainage persisted despite a course of clindamycin 300 mg 3 times daily for 2 weeks and the placement of tympanostomy tubes. Cultures from the left ear grew Moraxella catarrhalis , and because of increasing ear pain, treatment with moxifloxacin 400 mg daily was commenced. An exacerbation of her myasthenia gravis resulted in a discontinuation of the fluoroquinolone and a 2-week course of high-dose steroids (prednisone 60 mg daily 10 days).
A left tympanomastoidectomy was then performed due to worsening symptoms. Operative findings from this procedure were significant for pus and grossly infected granulation tissue that extended from the central mastoid air cells into the middle ear. She was admitted 1 month later with left wound dehiscence and acute right mastoiditis. At this time, she underwent a right tympanomastoidectomy and debridement of the left postauricular wound. Operative findings on the right side showed extensive, dense-granulation tissue with a purulent discharge filling the whole mastoid and extending into the middle ear space. On the left side, the prior postauricular surgical incision had opened throughout, and active granulation tissue and gross bleeding were noted because of infection. Cultures from the right internal ear grew coagulase-negative Staphylococcus , whereas cultures from the left external ear were negative for growth. Over the next 2 months, the patient completed 2 separate courses of linezolid 600 mg twice daily for 2 weeks before being rehospitalized with a weeklong history of right-sided throbbing facial pain and bloody otorrhea from the right external auditory canal and postauricular incision line, along with fevers and chills. A revision right mastoidectomy was completed, and postoperative management included bacitracin irrigations through 2 indwelling Jackson-Pratt drains and intravenous (IV) vancomycin 1500 mg twice daily. In the operating room, pus from the right mastoid region was noted, and biopsies showed only signs of chronic inflammation without granulomas. Immunoglobulin G (IgG) subclass levels were sent at the end of the patient’s admission, and she was discharged after remaining afebrile for 48 hours. However, the patient was again readmitted 2 days later with recurrent fevers, severe and diffuse headaches, neck stiffness, photophobia, and nausea. A magnetic resonance imaging of the brain showed abnormal regional dural enhancement and peripherally enhancing fluid collections within the area of the prior mastoidectomy, concerning for petrous apicitis, abscess, or leptomeningitis ( Fig. 1 ). Lumbar puncture showed lymphocytes in the cerebrospinal fluid with negative cultures. Purulent drainage from the right postauricular incision line was sent for a full series of cultures, including acid-fast bacilli. A review of the immunology studies from the patient’s prior admission showed that she was deficient in IgG subclass 1 and subclass 2 ( Table 1 A). At this point, our immunology colleagues were consulted, and they started the patient on IV immunoglobulin (IVIG) 400 mg/kg. Repeat immunologic studies confirmed the hypogammaglobulinemia and showed a deficiency in immunoglobulin A (IgA) and immunoglobulin M (IgM) ( Table 1 B). Flow cytometry studies revealed almost complete absence of B cells, with normal activated T cells and myeloid maturation. Pneumococcal antibody titers were present, not protective. The result of an antineutrophilic cytoplasmic antibody screen was negative, as well as viral studies, including HIV. Three days after beginning IVIG, the patient became afebrile and her symptoms gradually improved over the next week. She received an additional IVIG infusion 1 week after the initial dose and was discharged home with normalized IgG levels on 1 month of IV vancomycin 1500 mg twice daily, IV ceftazidime 2 g 3 times daily, and oral metronidazole 500 mg 3 times daily. Six months after discharge, the patient is symptom free and her bilateral postauricular fistulas have completely closed.
| A. | ||
|---|---|---|
| IgG subclass | Patient’s values ( μ g/dL) | Reference range ( μ g/dL) |
| 1 | 294 | 382–929 |
| 2 | 121 | 241 |
| 3 | 38 | 22–178 |
| 4 | 14.2 | 4.0 |
| B. | ||
|---|---|---|
| Total immunoglobulin | Patient’s values ( μ g/dL) | Reference range ( μ g/dL) |
| IgG | 399 | 814–1755 |
| IgA | 83 | 105–430 |
| IgM | 36 | 54–267 |
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