Pott’s Puffy Tumor in an Inflammatory Bowel Disease Patient on Anti-TNF Therapy

Background

Anti-TNF-α therapies were the first class of biologics to be used in treatment of moderate to severe inflammatory bowel disease (IBD) [1]. Immunosuppression status that develops from using anti-TNF-α therapies increases the risk of serious and opportunistic infections. We present here a rare case of serious infection that developed in an IBD patient while on anti-TNF therapy [2]. This case report sheds light on this unusual complicated sinus infection and raises awareness of the need for prompt sinusitis treatment in immunosuppressed patients.

Case Report

IBD HISTORY:

The patient had been diagnosed with ulcerative colitis 5 years prior to the current presentation. Histology showed pancolitis. He failed mesalamine and 6-Mercaptopurine (6MP). He had 3 flares in less than 1 year after infliximab induction. His flares were under better control after adding methotrexate to infliximab. He remained asymptomatic despite recurrent positive inflammatory markers for the past year, which were attributed to recurrent sinus, nasal, and ear infections. His methotrexate was tapered off 6 months prior to this presentation.

HOSPITAL COURSE:

The patient underwent bilateral maxillary antrostomy, right total ethmoidectomy, left anterior ethmoidectomy, bilateral frontal sinusotomy, and incision and drainage of Pott’s puffy tumor at day 1 of hospital admission. Culture of drainage from the frontal abscess and maxillary sinus showed moderate growth of MRSA and group A Streptococcus. Cefepime was stopped and the patient was discharged after improvement on oral metronidazole and i.v. vancomycin. After discharge, CRP normalized 2 weeks after starting treatment with antibiotics. ESR continued to trend down. He finished a total of 7 weeks of antibiotics, with brain and orbit MRI showing resolution of dural enhancement and abscess. Infliximab was resumed 3 weeks after surgery (10 weeks after the last infliximab infusion). His maintenance infliximab infusion plan prior to infection was scheduled every 7 weeks, so his treatment was delayed by 3 weeks. He developed stomach pain and dark stool color 2 weeks after presentation.

Discussion

ANTI-TNF THERAPY AND INFECTIONS:

Tumor necrosis factor alpha (TNF-α) is part of the innate immune system’s response against infections. It is a potent pro-inflammatory molecule which plays a role in the production of cytokines, recruitment of inflammatory cells, and target cell apoptosis [12].

Anti-TNF-α therapies were the first class of biologics to be used to treat moderate to severe IBD. These therapies are known to increase the risk of serious and opportunistic infections, and up to one-third of IBD patients develop non-serious infections within 1 year of beginning therapy. Other risks related to anti-TNF therapy include infusion reaction, risk of antibody formation, lupus-like syndrome, and malignancies such as lymphoma and melanoma [13].

A metanalysis done in rheumatoid arthritis (RA) patients showed increased risk of serious infection in patients on biologics compared to patients on disease-modifying antirheumatic drugs (DMARDs). Factors found to affect the risk of developing infections include previous treatments used, the dose of anti-TNF administered, and use of combined biologic therapy [14]. Another metanalysis that included 49 randomized controlled trials investigated risk of infection in IBD patients who received biologics, concluding that there is an increase in risk of infections but no significant difference in serious infections. They defined serious infections as those that are life-threatening, need intravenous antibiotics, or require inpatient hospital admission [15].

Various factors have been proposed to increase the risk of infection while on biologic agent therapy. One of these factors is concomitant use of corticosteroids in patients who are on anti-TNF treatment. This was found in another metanalysis of patients with Crohn’s disease treated with adalimumab recruited from 8 clinical trials. They found that the use of corticosteroids while on adalimumab significantly increased the infection risk, especially in the first period of biologic therapy. Also, they found that combining immunomodulators (such as methotrexate) with biologics was associated with a lower risk of serious infection at 1 year. A linear correlation between the incidence of serious infection and the Crohn’s Disease Activity Index (CDAI) measured at follow-up visits was also observed [16]. Another systematic review showed no difference in increased risk of serious infection between biologic mono-therapy and combined treatment with biologics and immunomodulators [17]. A metanalysis and systematic review by Singh et al found that monotherapy with an immunosuppressive agent (methotrexate or thiopurines) is associated with a lower risk of infection compared to anti-TNF monotherapy [18].

Another factor is duration of biologics therapy. After-market registries showed that risk of serious infection is the highest during the first year of anti-TNF therapy, then it decreases with time. The Swedish biologics register ARTIS found that risk of infection is higher with biologics than with DMARDs in the first year of use, but not thereafter. This finding could be influenced by better disease control leading to less use of corticosteroids [19].

In a metanalysis done for several IBD trials of various biologics, including anti-TNF, the most common infection found was upper respiratory tract infection. Other infections were lower respiratory tract infection, urinary tract infection, and gastroenteritis [20].

Dixon et al found that the most common site of serious infection in anti-TNF-treated RA patients was the lower respiratory tract, followed by skin and soft tissue, bone, and uri-nary tract [21]. The incidence of sinusitis with anti-TNF-α was reported in 2 studies as being 7–15% [22,23]. Yoshihara et al suggested that the incidence of refractory sinusitis requiring otolaryngology evaluation and treatment for patients who are on anti-TNF therapy was approximately 2% [24].

Methotrexate is also known to increase the risk of serious infection [25]. Long-term use of methotrexate might be another factor in our patient that could have contributed to developing this serious infection. However, a systematic review showed that methotrexate was associated with increased risk of infection in patients with rheumatoid arthritis but not in other non-rheumatoid arthritis inflammatory disorders, including inflammatory bowel disease [26].

Our literature review found no reports of cases of PPT in patients receiving biologics. Although our patient’s history of recurrent sinusitis put him at risk of developing PTT, the immunosuppression effect of infliximab could be contributory. However, the potential for TNF-α inhibitor therapy to help achieve better control of IBD may outweigh the risk of infections related to TNF-α inhibitors.

Conclusions

PPT is a serious complication of untreated sinusitis. IBD patients on biologics who have sinusitis tend to have higher risk of developing such complications because of their decreased ability to fight infection. Although the risk of serious infections declines significantly after the first year of using biologics, physicians should keep a low threshold for investigating symptomatic patients for serious infections, as they require prompt intervention. Despite the potential complications from using biologics, the benefits of this therapy in IBD patients outweigh the risks.