Oct. 31, 2025
Chronic rhinosinusitis can be challenging to treat for a variety of reasons, including physiological, genetic, anatomic and environmental factors. However, patients with chronic rhinosinusitis (CRS) that does not respond to medication or surgery, known as recalcitrant CRS, are often immunocompromised. Treating the underlying immune dysfunction can enable medication therapy and surgical interventions to work more effectively.
"But patients requiring ongoing immunosuppressant treatment due to transplant or autoimmune disease can be particularly challenging to treat," says Angela M. Donaldson, M.D., an otolaryngologist specializing in rhinology and anterior skull base surgery at Mayo Clinic in Jacksonville, Florida. Mayo Clinic researchers and clinicians are addressing challenges associated with recalcitrant CRS by:
- Identifying predictive factors associated with increased recalcitrant CRS risk in transplant patients.
- Uncovering the long-term effects of rituximab on immune function, including an increased risk of recalcitrant CRS.
- Exploring new treatment options for recalcitrant CRS in patients who are immunosuppressed.
"Our research has given us a stronger understanding of the incidence of recalcitrant CRS, especially in transplant patients," says Dr. Donaldson. "If we recognize high-risk patients earlier and treat the underlying issue, we may be able to prevent patients from developing recalcitrant disease. For immunosuppressed patients who already have recalcitrant CRS, we are looking to topical therapies to reduce disease symptoms."
Identifying and managing the risk of recalcitrant CRS in transplant patients
To understand the relationship between transplant and recalcitrant CRS, Dr. Donaldson and her colleagues studied patients with nonsolid and solid transplants They assessed the need for endoscopic sinus surgery (ESS) to treat CRS in this population.
"Immunosuppressant drugs are part of the issue, but the duration of treatment with immunosuppressive medications may also play a role," says Dr. Donaldson. "Taking them for a longer period, which is typical with solid transplants, can cause epithelial dysregulation due to immune system dysfunction."
The study, published in the American Journal of Rhinology and Allergy, found that more than 17% of all transplant patients require ESS following transplant. The risk of recalcitrant CRS was nearly 1.78 times greater after a solid organ transplant than after nonsolid organ transplant.
A second study, published a year later in the same journal, reports a 30.4% CRS incidence post-transplant, which is double the risk of the general population. Dr. Donaldson and her team identified several substantial predictive factors associated with post-transplant CRS, including:
- Allergic fungal rhinosinusitis.
- Allergic rhinitis.
- Asthma.
- Chronic rhinosinusitis with nasal polyps.
- Nasal septal deviation.
- Recurrent acute rhinosinusitis.
- Unilateral ESS history.
Hematologic conditions, including autologous transplantation, primary immunodeficiency, graft-versus-host disease and others, also proved to be predictive factors.
Researchers were able to predict 72.66% of CRS cases post-transplant based on these risk factors. Using this information, Mayo Clinic in Florida has implemented practice changes, including the addition of a sinus CT to the pretransplant screening and assessment process for liver and kidney transplant patients. Several studies, including Mayo Clinic research published in World Journal of Otorhinolaryngology — Head and Neck Surgery, have found that patients who have undergone liver or kidney transplant had a higher rate of CRS. Based on this evidence, Mayo Clinic physicians obtain pretransplant sinus CT imaging in these patients, especially if they have active CRS symptoms or a history of sinonasal conditions.
"Now, patients found to be at high risk of CRS see us for evaluation and possibly surgery before their transplant," says Dr. Donaldson. "We are more aggressive with their medical care before and during immunosuppression."
Care coordination is personalized and requires a multidisciplinary approach involving transplant, ENT and anesthesia specialists. Together, they discern who to treat and when, since timing around a transplant and the addition of elective surgery can be complicated.
Recognizing the relationship between rituximab use and immune deficiency
Mayo Clinic researchers also have been exploring lesser-known causes of immune dysfunction and increased CRS risk, specifically the use of rituximab.
"Rituximab causes hypogammaglobulinemia. But it's generally expected that after ending rituximab use, immunoglobulin levels will return to normal," says Dr. Donaldson. "We are learning that does not always happen."
A recent Mayo Clinic study reports an increased risk of CRS diagnoses after the discontinuation of rituximab, compared with the general population. Unpublished research also suggests that longer courses of rituximab are significantly associated with the need for ESS.
"Some people with autoimmune conditions and recalcitrant CRS can have a prolonged symptomatic course, simply because the recognition of previous rituximab use is not made. This potentially delays the consideration of alternative treatment options," says Dr. Donaldson. "We now know it is critical to do a deep dive into their health and medication history to see if they have ever been on rituximab."
Treating recalcitrant chronic rhinosinusitis in patients requiring immunosuppressants
Patients with recalcitrant CRS often have recurrent infections and persistent inflammation. Dr. Donaldson says repeatedly treating those issues can feel like a vicious cycle. Oral antibiotics, in general, also can cause allergic reactions or gastrointestinal upset.
As an alternative, Mayo Clinic is exploring the use of culture-directed topical antibiotics administered in the form of a medicated saline rinse. The topical antibiotics — compounded in a powder form and placed in a saline solution — are not absorbed the same way as oral antibiotics. Dr. Donaldson says the approach reduces the risk of treatment-related gastrointestinal issues and appears to be safe for people who are mildly allergic to the oral form of the medication. However, not all oral antibiotics can be compounded.
Unpublished Mayo Clinic data finds that nearly 60% of patients with immune dysfunction cleared their infection with the use of topical antibiotics within eight weeks.
"There is so much new information about risk, cause and treatment of recalcitrant CRS," says Dr. Donaldson. "It provides major opportunities to increase our knowledge, change our practices and educate patients."
For more information
Candelo E, et al. Risk factors for recalcitrant chronic rhinosinusitis in non-solid and solid transplant recipients. American Journal of Rhinology & Allergy. 2023;37:550.
Candelo E, et al. Predictors for development of chronic rhinosinusitis in transplant recipients. American Journal of Rhinology & Allergy. 2024;38:373.
Spillinger A, et al. Presentation and outcomes of chronic rhinosinusitis following liver and kidney transplant. World Journal of Otorhinolarygology — Head and Neck Surgery. 2021;7:139.
Refer a patient to Mayo Clinic.