Eosinophilic cystitis refractory to multiple treatments with good response to benralizumab: case report

Case report

Eosinophilic cystitis is a rare condition, first delineated by Brown and Palubinskas in 1960 (1). Its aetiology remains poorly understood, although it has been associated with atopic diseases, bladder tumours, bladder trauma, parasitic infections, and chemotherapeutic agents (2). The disorder is characterised by eosinophilic infiltration of the bladder walls, resulting in inflammation (1). To date, approximately 200 cases have been reported in adults worldwide, with around 30 cases described in children (3, 4).

Clinical presentation often mimics other inflammatory and malignant bladder conditions, presenting symptoms such as urinary frequency, bladder tenesmus, suprapubic pain, dysuria, and haematuria (5). Cystoscopy with biopsy is recommended by international guidelines for diagnosis (3). Yamada et al. (6) proposed a histopathological criterion, specifying that tissue samples should exhibit over 20 eosinophils within five high-power fields, and eosinophils should constitute more than 30% of the round cells in each field.

Eosinophilic cystitis is a heterogeneous condition with a variable clinical course. While some cases are self-limited or respond to conservative management, others can be severely refractory, leading to significant morbidity and requiring escalation of therapy. For instance, a recent report described a case of eosinophilic cystitis associated with membranous nephropathy that achieved complete remission with conservative management at 6 months, without the need for corticosteroids or biologic agents (7). Despite the absence of a well-defined treatment protocol, standard therapeutic options include corticosteroids, anti-inflammatory drugs, antihistamines and antibiotics (1, 3). However, patients who do not respond to these treatments may require more radical interventions, such as partial or total cystectomy (1). Although generally benign, persistent inflammation can lead to recurrent bladder fibrosis and subsequent obstructive uropathy (3).

We present a case of eosinophilic cystitis refractory to multiple treatments that showed a favourable clinical response to benralizumab. The patient provided written informed consent for publication of his clinical data.

We describe a 44-year-old male with allergic rhinoconjunctivitis due to grass pollen and dust mites, referred from the Urology Department after being diagnosed with eosinophilic cystitis. The patient experienced daily, severe macroscopic haematuria (requiring multiple hospital admissions), along with suprapubic pain, urinary urgency and dysuria causing more than ten nightly sleep disruptions.

Cystoscopy revealed diffuse erythematous areas without papillae lesions. Bladder biopsy revealed acute inflammatory changes with abundant eosinophilic infiltration (Figure 1). Further tests excluded other diagnoses: renal ultrasound was normal, and urinary cytology showed no malignant cells, ruling out neoplastic causes of cystitis. Laboratory tests demonstrated elevated total immunoglobulin E levels (169 kUA/L) without peripheral eosinophilia (0,30 × 10³/µL). No new medications, parasitic infections, or bacterial pathogens were identified.

The patient had undergone multiple courses of antibiotics (trimethoprim 160 mg/sulfamethoxazole 800 mg per 24 h), antihistamines (cetirizine 10 mg/24 h) and corticosteroids (dexamethasone 1 mg/24 h). Corticosteroids provided only temporary relief, with rapid symptom recurrence upon discontinuation, significantly affecting his quality of life. Additionally, we would like to highlight that the patient developed adrenal suppression secondary to the oral corticosteroid course, evidenced by a low basal cortisol level and an ACTH of 4 pg/mL, which further supports the complexity of the case.

Given the refractoriness to conventional therapy and to avoid chronic corticosteroids and surgery, off-label treatment with subcutaneous benralizumab (Fasenra®) was proposed. The patient was informed of the off-label use of this treatment. Benralizumab is a monoclonal antibody, approved for severe eosinophilic asthma, that targets the alpha subunit of the interleukin-5 receptor, inhibiting the production and survival of eosinophils. This antibody offers improved efficacy and an excellent safety profile (2).

Treatment was initiated with 30 mg of benralizumab every four weeks, later extending to every eight weeks after the first three months. The severe eosinophilic asthma protocol was applied, since no specific dosing recommendations currently exist for eosinophilic cystitis. Consequently, the optimal dosage and treatment duration warrant further investigation (1). It should be noted that there was a one-month period of overlapping treatment with oral corticosteroids and benralizumab. Although corticosteroids had previously provided only transient symptomatic relief with rapid relapse upon discontinuation in this patient, the possibility of a combined or delayed effect cannot be completely excluded. This represents a limitation inherent to single-case reports.

After over a year of treatment, the patient experienced total remission of haematuria and bladder tenesmus, and nocturnal urgency was reduced to once per night, significantly improving his quality of life. He declined further cystoscopic and biopsy procedures due to past haematuria episodes requiring hospitalization post-biopsy. Although understandable, the absence of post-treatment histological confirmation and laboratory markers of eosinophilic activity limits the ability to objectively demonstrate tissue-level remission. This represents an important limitation of the present case report.

Humanized monoclonal antibodies targeting interleukin-5, such as mepolizumab and reslizumab, and the interleukin-5 alpha subunit receptor, such as benralizumab, have been developed primarily for the management of severe eosinophilic asthma. Mepolizumab is additionally approved for the treatment of eosinophilic granulomatosis with polyangiitis, severe chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome (8). These emerging therapies may offer benefits not only to individuals with eosinophilic cystitis but also to other eosinophilic tissue infiltrative disorders, including cellulitis, fasciitis, cholangitis, pancreatitis, and Kimura's disease (9).

Recent literature has documented cases of eosinophilic cystitis, that have responded favourably to anti interleukin-5 monoclonal antibodies. Trefond et al. reported two cases, both symptomatic and with peripheral eosinophilia, who responded to mepolizumab at a dosage of 100 mg every four weeks (10).

Cooke et al. described a female patient without peripheral eosinophilia refractory to standard therapy who improved significantly with benralizumab 30 mg administered every four weeks (11). Similarly, Shamriz et al. documented positive response to benralizumab 30 mg every eight weeks in a male patient, symptomatic without haematuria or peripheral eosinophilia (9). Furthermore, benralizumab has consistently demonstrated a commendable safety profile, as evidenced not only in our patient but also in analogous cases reported within the literature. This supports its consideration as a potential therapeutic option prior to the undertaking of invasive surgical interventions in select cases of eosinophilic cystitis that do not respond to conventional therapies (2).

In conclusion, this case suggests that off-label use of anti- interleukin-5/ interleukin-5 alpha receptor monoclonal antibodies may represent a promising therapeutic option for selected patients with refractory eosinophilic cystitis, even in idiopathic forms without peripheral eosinophilia. These agents may constitute a valuable alternative to repeated corticosteroid courses or invasive surgical procedures in selected patients.

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Footnotes

Edited by: Ilaria Puxeddu, University of Pisa, Italy

Reviewed by: Federico Spataro, University of Bari Aldo Moro, Italy

Veysel Baran Tomar, Gazi University, Türkiye