25 May 2021: Articles
Unusual clinical course, Unusual or unexpected effect of treatmentAhmad Miri12AE*, Alice I. Sato34EF, Ryan K. Sewell56E, Andrew Huang-Pacheco12AE
Am J Case Rep 2021; 22:e929892
BACKGROUND: Anti-TNF-α therapies were the first class of biologics to be used in treatment of moderate to severe IBD. Immunosuppression status that develops from using anti-TNF-a 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.
CASE REPORT: Our patient was a 14-year-old boy with a history of chronic sinusitis and ulcerative colitis who had been on infliximab therapy for the last 3 years. He presented with facial swelling and worsening constant frontal headache. Imaging showed frontal scalp subgaleal abscess, mild frontal calvarial early osteomyelitis, bilateral preseptal cellulitis, and acute and chronic paranasal sinus disease. He was treated with intravenous antibiotics and underwent sinus surgery with incision and drainage of the forehead abscess. He recovered well and resumed his infliximab infusions 3 weeks after the surgery.
CONCLUSIONS: PPT is a serious complication of untreated sinusitis. IBD patients on biologics can have higher risk of developing such complications because of their decreased ability to fight infections. 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.
Keywords: Inflammatory Bowel Diseases, Pediatrics, Pott Puffy Tumor, Abscess, Adolescent, Drainage, Tumor Necrosis Factor Inhibitors
Anti-TNF-α therapies were the first class of biologics to be used in treatment of moderate to severe inflammatory bowel disease (IBD) . 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 . This case report sheds light on this unusual complicated sinus infection and raises awareness of the need for prompt sinusitis treatment in immunosuppressed patients.
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.
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
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 .
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 .
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 . 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 .
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 . Another systematic review showed no difference in increased risk of serious infection between biologic mono-therapy and combined treatment with biologics and immunomodulators . 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 .
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 .
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 .
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 . 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% .
Methotrexate is also known to increase the risk of serious infection . 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 .
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.
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.
FiguresFigure 1.. (A). Orbit and brain MRI with contrast shows 5×0.8×4 cm of frontal scalp subgaleal rime enhancing fluid collection, showing subgaleal abscess (arrow head) with mild restricted diffusion within the frontal calvarium, compatible with early changes of osteomyelitis. Moderate fluid collection is shown in underlying frontal sinuses (arrows). (B) MRI brain and orbit shows fluid throughout maxillary sinuses, with mild mucosal thickening bilaterally (arrows). Fluid and mucosal thickening within ethmoid air cells is shown (arrow heads). The findings show acute and chronic sinusitis.
1.. Adegbola SO, Sahnan K, Warusavitarne J, Anti-TNF therapy in Crohn’s disease: Int J Mol Sci, 2018; 19(8); 2244
2.. Andersen NN, Jess T, Risk of infections associated with biological treatment in inflammatory bowel disease: World J Gastroenterol, 2014; 20(43); 16014-19
3.. Flamm ES, Percivall Pott: An 18th century neurosurgeon: J Neurosurg, 1992; 76(2); 319-26
4.. Bambakidis NC, Cohen AR, Intracranial complications of frontal sinusitis in children: Pott’s puffy tumor revisited: Pediatr Neurosurg, 2001; 35(2); 82-89
5.. Heale L, Zahanova S, Bismilla Z, Pott puffy tumor in a five-year-old girl: CMAJ, 2015; 187; 433-35
6.. Kombogiorgas D, Solanki GA, The Pott puffy tumor revisited: Neurosurgical implications of this unforgotten entity. Case report and review of the literature: J Neurosurg, 2006; 105(2 Suppl.); 143-49
7.. Salomão JF, Cervante TP, Bellas AR, Neurosurgical implications of Pott’s puffy tumor in children and adolescents: Childs Nerv Syst, 2014; 30(9); 1527-34
8.. Gülhadiye A, Nursen B, Senem CK, Arzu K, Gülnar S, Pott’s puffy tumor in a12-year-old boy: Pediatr Int, 2015; 57(1); 163-65
9.. Koltsidopoulos P, Papageorgiou E, Skoulakis C, Pott’s puffy tumor in children: A review of the literature: Laryngoscope, 2020; 130(1); 225-31
10.. Verbon A, Husni RN, Gordon SM, Pott’s puffy tumor due to Haemophilus influenzae: Case report and review: Clin Infect Dis, 1996; 23(6); 1305-7
11.. Palabiyik FB, Yazici Z, Cetin B, Pott puffy tumor in children: A rare emergency clinical entity: J Craniofac Surg, 2016; 27(3); e313-e316
12.. Olsen NJ, Stein CM, New drugs for rheumatoid arthritis: N Engl J Med, 2004; 350(21); 2167-79
13.. Quezada SM, McLean LP, Cross RK, Adverse events in IBD therapy: The 2018 update: Expert Rev Gastroenterol Hepatol, 2018; 12(12); 1183-91
14.. Singh JA, Cameron C, Noorbaloochi S, Risk of serious infection in biological treatment of patients with rheumatoid arthritis: A systematic review and meta-analysis: Lancet, 2015; 386(9990); 258-65
15.. Bonovas S, Fiorino G, Allocca M, Biologic therapies and risk of infection and malignancy in patients with inflammatory bowel disease: A systematic review and network meta-analysis: Clin Gastroenterol Hepatol, 2016; 14(10); 1385-97
16.. Osterman MT, Sandborn WJ, Colombel JF, Crohn’s disease activity and concomitant immunosuppressants affect the risk of serious and opportunistic infections in patients treated with adalimumab: Am J Gastroenterol, 2016; 111(12); 1806-15
17.. Wheat CL, Ko CW, Clark-Snustad K, Inflammatory bowel disease (IBD) pharmacotherapy and the risk of serious infection: A systematic review and network meta-analysis: BMC Gastroenterol, 2017; 17(1); 52
18.. Singh S, Facciorusso A, Dulai PS, Comparative risk of serious infections with biologic and/or immunosuppressive therapy in patients with inflammatory bowel diseases: A systematic review and meta-analysis: Clin Gastroenterol Hepatol, 2020; 18(1); 69-81
19.. Askling J, Fored CM, Brandt L, Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists: Ann Rheum Dis, 2007; 66(10); 1339-44
20.. Shah ED, Farida JP, Siegel CA, Risk for overall infection with anti-TNF and anti-integrin agents used in IBD: A systematic review and meta-analysis: Inflamm Bowel Dis, 2017; 23(4); 570-77
21.. Dixon WG, Watson K, Lunt M, Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: Results from the British Society for Rheumatology Biologics Register: Arthritis Rheum, 2006; 54(8); 2368-76
22.. Tynjälä P, Kotaniemi K, Lindahl P, Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis: Rheumatology (Oxford), 2008; 47(3); 339-44
23.. Maini R, St Clair EW, Breedveld F, Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial: ATTRACT Study Group. Lancet, 1999; 354(9194); 1932-39
24.. Yoshihara S, Kondo K, Kanaya K, Tumour necrosis factor inhibitor-associated sinusitis: Rhinology, 2014; 52(3); 246-51
25.. Caporali R, Caprioli M, Bobbio-Pallavicini F, Montecucco C, DMARDS and infections in rheumatoid arthritis: Autoimmun Rev, 2008; 8(2); 139-43
26.. Ibrahim A, Ahmed M, Conway R, Carey JJ, Risk of infection with methotrexate therapy in inflammatory diseases: A systematic review and meta-analysis: J Clin Med, 2018; 8(1); 15
11 August 2022 : Case reportA 32-Year-Old Man with Persistent Olfactory Dysfunction Following COVID-19 Whose Recovery Was Evaluated by ...
Am J Case Rep In Press; DOI: 10.12659/AJCR.936496
09 August 2022 : Case reportA Case of Segmental Arterial Mediolysis of Multiple Visceral Arteries Following Anti-COVID-19 Vaccination: ...
Am J Case Rep In Press; DOI: 10.12659/AJCR.937505
29 July 2022 : Case reportPosterior Myocardial Infarction in a 45-Year-Old Javanese Woman with a 1-Month History of COVID-19-Related ...
Am J Case Rep In Press; DOI: 10.12659/AJCR.937105
12 Aug 2022 : Case reportA 30-Day-Old Infant with Necrotizing Fasciitis of the Perineal Region Involving the Scrotum Due to Methicil...
Am J Case Rep In Press; DOI: 10.12659/AJCR.936915
11 Aug 2022 : Case reportA Challenging Case of Streptococcus pneumoniae Meningitis in a 64-Year-Old Woman Who Presented with Symptom...
Am J Case Rep In Press; DOI: 10.12659/AJCR.937139
11 Aug 2022 : Case reportA 32-Year-Old Man with Persistent Olfactory Dysfunction Following COVID-19 Whose Recovery Was Evaluated by ...
Am J Case Rep In Press; DOI: 10.12659/AJCR.936496
Most Viewed Current Articles
13 Jul 2022 : Case reportWhistling Scrotum: An Unusual Presentation of Pneumomediastinum in the Setting of an Open Scrotal Wound
Am J Case Rep 2022; 23:e936441
23 Feb 2022 : Case reportPenile Necrosis Associated with Local Intravenous Injection of Cocaine
Am J Case Rep 2022; 23:e935250
06 Dec 2021 : Case reportLipedema Can Be Treated Non-Surgically: A Report of 5 Cases
Am J Case Rep 2021; 22:e934406