Adalimumab (Humira®) Induced Recurrent Peritonsillar Abscess in A Patient Received Three Different Anti-TNF Therapies: A Case Report

Anti-tumor necrosis factor agents are widely used in treating ankylosing spondylitis, but they increase the risk of infection by suppressing the immune response. Therefore, physicians should be careful about recurrent infections in patients under anti-tumor necrosis factor agents.


Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints and spine. Tumor necrosis factor alpha (TNF-α) plays an essential role in the pathogenesis of AS and many other inflammatory diseases, which can be used as a target point during the treatment. If pathology such as lymphoma or infectious mononucleosis was found during the differential diagnostics.
Two and a half months after the discharge, he admitted to our ED again with similar complaints. The vitals and laboratory results were similar to the previous admission. He was diagnosed with PTA for the fourth time in two years. The patient was discharged with an antibiotic prescription after the abscess drainage was performed in the ED and referred to his rheumatologist.

Discussion
The most common bacterium isolated in PTA are Streptococcus and Fusobacterium, but many abscesses have a mixed profile [2,3]. Primary treatment strategies are the initiation of appropriate antibiotic therapy and percutaneous evacuation of the abscess if needed. "Recurrence" term for PTA can be defined as a new episode of PTA in ≥ 30 days from the initial PTA [4]. The frequency of recurrent PTA in the normal population is 5.15-16%, and even much higher in younger populations aged 13-18 [5,6]. As early recurrence can be linked to inadequate treatment, extra-peritonsillar spread of infection, or autoimmune deficiency, late recurrence is more likely related to autoimmune deficiency or prior history of tonsillitis or pharyngitis [6]. Unfortunately, the literature does not answer to the question, "How many times can a PTA recur." Our patient with AS receiving anti-TNF treatment had recurrent PTA attacks (four times), requiring surgical interventions and hospitalizations (two times) in the two-year time period. Although his anti-TNF regimen was the usual suspect, neither the patient himself stated his emergency visits or interventions to his rheumatologist during his follow-up, nor was there any executed rheumatology referral or consultation. Since none of PTAs accompanied by tonsillitis, tonsillectomy was not considered. In addition, the microorganisms causing PTAs were not determined because no culture study was performed. The large-scale studies on the relationship between anti-TNF and infection focused predominantly on tuberculosis activation and opportunistic infections [7,8]. We could not be sure if PTA episodes were related to any opportunistic microorganism since no culture study was conducted.
As we assume that his repetitive medical condition was associated with the anti-TNF agent, we investigated the drug regimens he received. He had used etanercept and infliximab, and he has been treated with adalimumab for the last five years. All three are the most commonly used anti-TNF agents. He had four PTA during active use of adalimumab. However, the findings comparing the risk of infection in patients treated with etanercept, adalimumab, and infliximab showed no significant difference between the three drugs [9]. In a meta-analysis, significant increases were found in anti-TNF drug use by 20% for any infection, 40% for severe infection, and 250% for tuberculosis reactivation [7]. Nevertheless, we did not encounter any reports or studies including or specifically addressing PTA under anti-TNF treatment.

Conclusion
Anti-TNF drugs should also be questioned in specific infection types and repetitive infection patterns that suggest the possibility of immunosuppression in the EDs. Acknowledgements None.
Funding No funding was received for the study.

Conflict of Interest
The authors declare that they have no conflict of interest.

Funding Sources/Disclosures None declared.
Ethical Approval Not applicable.

Informed Consent
Informed consent was obtained from the patient of the case report.

Fig. 1 The examination revealing a left-sided peritonsillar abscess without any tonsillitis findings
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/.