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Original article
Doxycycline treatment of otosyphilis with hearing loss
  1. Verajit Chotmongkol1,2,
  2. Kittisak Sawanyawisuth1,2,
  3. Kwanchanok Yimtae3,
  4. Thanyaporn Chantarojanasiri1,
  5. Ratchanee Chotmongkol1
  1. 1Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
  2. 2The Research and Diagnostic Centre for Emerging Infectious Disease, Khon Kaen University, Khon Kaen, Thailand
  3. 3Department of Otolaryngology, Khon Kaen University, Khon Kaen, Thailand
  1. Correspondence to Dr Kittisak Sawanyawisuth, Department of Medicine, Faculty of Medicine, 123 Mitraparp Road, Khon Kaen 40002, Thailand; kittisak{at}kku.ac.th

Abstract

Objectives The recommended treatment of otosyphilis is intravenous penicillin therapy. The response rate varied between 23% and 31%. This treatment needs hospitalisation and is costly, inconvenient and time consuming. Oral doxycycline was tested for its efficacy in otosyphilis.

Method The authors reviewed 19 patients diagnosed as having otosyphilis with hearing loss at the outpatient unit between 2004 and 2008 by oral doxycycline 400 mg/day for 21 days.

Results Of those enrolled patients, 12 patients were male and the mean age is 69.4 years. The hearing was improved in nine patients (47.3%) and the audiogram of seven patients (36.8%) showed improvement. There was no serious side effect of doxycycline.

Conclusion The data suggest that doxycycline may be an effective alternate regimen for otosyphilis.

  • Otosyhilis
  • treatment
  • doxycycline
  • clinical trials
  • epidemiology (clinical)
  • infectious diseases

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Syphilis is a systemic disease caused by the spirochete Treponema pallidum. Otosyphilis is well known as a complication of syphilis. The clinical manifestation of otosyphilis include sensorineural hearing loss, tinnitus and vertigo. The presumptive diagnosis of otosyphilis can be made in patients with these symptoms, positive serology for syphilis and no other known aetiology for the inner ear disturbance. The first-line therapy is high-dose intravenous penicillin. However, this treatment needs hospitalisation and inconvenience of intravenous antibiotic.

Oral doxycycline is one of alternative regimens for treatment of syphilis with less expensive and convenience to use. This drug has been found to be effective in early syphilis.1 2 It also have been shown to have good distribution into cerebrospinal fluid (CSF).3 This paper reported the result of doxycycline treatment of otosyphilis with hearing loss that, to our knowledge, has never been reported.

Methods

The study was done at the Out-Patient Department, Srinagarind Hospital, Khon Kaen University. Chart review was done retrospectively in all patients with the diagnosis of otosyphilis and received doxycycline treatment 200 mg orally twice a day for 21 days4 between 2004 and 2009.

Adult patients (aged ≥15 years) who presented with sensorineurol hearing loss (confirmed by audiogram) were studied. Other causes of hearing loss such as Meniere's disease, tumours, trauma, chronic otitis media and toxic substances were excluded. The diagnosis of otosyphilis was confirmed by a positive serum for T pallidum haemagglutination test. We also excluded HIV patients, patients with tinnitus or vertigo, neurological deficit, previous treatment of syphilis, that is, penicillin, or glucocorticoid treatment.

There were two treatment outcomes including clinical outcome and audiogram outcome. Both outcomes were evaluated at approximately 1 year of follow-up and classified as improved, stable or worse. The clinical outcome was the hearing symptom reported by the patient, while the audiogram outcome was the comparison of audiogram reports (initial vs 1 year). The improvement of audiogram was defined if pure tone average threshold at 0.5, 1 or 2 kHz decreased >10 dB or pure tone average threshold decreased >15 dB at any frequency or discrimination score increased >15%.

Data were reported as descriptive statistics. The study protocol was approved by the Khon Kaen University's ethics committee for human research.

Results

We reviewed 20 charts of patients who met the criteria during the study period, and one patient was excluded because of an adverse reaction to doxycycline. Therefore, 19 patients were studied. The clinical presentations are shown in table 1. Of the 19 patients, 12 (63.2%) patients were male with a mean age of 69.4 (range, 54–84 years). Seventeen (89.5%) patients had bilateral sensorineural hearing loss, and nine (47.4%) patients had symptom <1 year. CSF Venereal Disease Research Laboratory Test, CSF India ink and CSF culture were negative in all patients.

Table 1

Characteristics and clinical outcomes after doxycycline treatment in otosyphilis

Regarding the outcomes (table 1), nine (47.4%) patients reported better hearing, while 10 (52.6%) reported no change in hearing. Whereas seven (36.8%) patients had improved audiogram, eight (42.1%) patients had similar results and four (21.1%) patients had worse audiogram. There were nine (47.4%) patients who had concordant results between clinical and audiogram outcomes. For those four patients with worse audiogram, two patients reported better hearing and the other two patients reported no change in hearing. The serum Venereal Disease Research Laboratory Test titer at 1 year after treatment is also shown in table 1. One patient developed minor doxycycline allergy but was able to complete the course of 21 days, while two patients reported mild nausea.

Discussion

Acquired otosyphilis may initially present with intermittent tinnitus. Later, pure tone hearing loss and speech discrimination may develop, respectively, in a few years. Hearing loss rate may depend individually with range from 50 to 120 dB in the first 5 years. The treatment of otosyphilis is the same as the treatment of neurosyphilis. The CDC recommends aqueous penicillin G, 18–24 million units/day administered as 3–4 million units intravenously every 4 h or continuously for 10–14 days. Adjuvant therapy with corticosteroid is previously used; however, there is a lack of controlled study to confirm the efficacy.

Gleich et al5 previously reviewed the efficacy of penicillin in otosyphilis. The combination of intravenous or intramuscular penicillin and corticosteroid improved hearing of 23% with increased discrimination score of 27% and decreased speech reception threshold of 12%. For otosyhilis patients with normal CSF findings, intravenous penicillin 24 million units/day for 10 days and followed by benzathine penicillin 2.4 million units once weekly for 2 weeks along with 500 mg of probenecid twice daily were used. For those with positive CSF findings, intravenous penicillin 24 million units/day for 14 days, benzathine penicillin with probenecid as described earlier for 2 weeks and followed by 3500 mg of amoxicillin orally per day with probenecid for 60 days were prescribed. Prednisone 80 mg every other day for 30 days was also given and then was tapered. The outcome revealed that overall hearing improvement was 31%.5

Comparing with previous results, our study demonstrated that the 21-day treatment of oral doxycycline in otosyphilis provided a similar result with 47.4% improvement of hearing by patient report and 36.8% improvement by audiogram.

The limitations of this study are small sample size and retrospective review. The small sample size may not be adequately powered to show effect. A further study comparing intravenous penicillin and oral doxycycline in otosyphilis is warranted.

Conclusions

Our data suggest that doxycycline may be an effective alternate regimen for otosyphilis. In facilities with limited hospital beds, it is a good alternative choice of therapy for otosyphilis.

Key messages

  • The study aims to evaluate the efficacy of oral doxycycline for the treatment of otosyphilis with hearing loss.

  • Oral doxycycline 200 mg twice a day for 21 days was used in 19 patients.

  • The hearing was improved in nine patients (47.3%), and the audiogram of seven patients (36.8%) showed improvement without serious side effects.

  • The regimen is effective and may be an alternative treatment for otosyphilis.

References

Footnotes

  • Funding This research was supported by the Office of the Higher Education Commission, the National Research Council of Thailand and the National Research Project, Khon Kaen University, Thailand.

  • Competing interests None.

  • Ethics approval The ethics approval was provided by Khon Kaen University.

  • Provenance and peer review Not commissioned; externally peer reviewed.