Recurrent rhinosporidiosis: A case report from Malaysia and review of literature

Abstract

Over the decades, rhinosporidiosis has remained an enigma. It is a recalcitrant disease caused by Rhinosporidium seeberi, primarily affecting the nasal cavity, conjunctiva, and less frequently involved sites, including skin, urethra, and others. We report a case of a local from Sabah who has presented with recurring symptoms of nasal obstruction and epistaxis for two decades. He had previously undergone multiple endoscopic excisional surgeries before receiving treatment at our centre. Otorhinolaryngeal examination revealed polypoidal masses occupying bilateral nasal cavities with a perforation of the nasal septum. He underwent surgical resection of the lesions, and the histopathological examination confirmed recurrent rhinosporidiosis. Due to its sporistatic effects, dapsone was chosen as the pharmacological treatment in this case. However, after a year of follow-up, he developed similar symptoms and the endoscopic findings, indicated a recurrence of the disease. The histopathological samples obtained during the repeated surgery for recurrent polypoidal masses, confirmed the diagnosis of rhinosporiodiosis. As the disease poses diagnostic and therapeutic challenges, clinicians should be prudent in establishing the diagnosis in non-endemic areas, such as Malaysia, and evaluating the possibility of recurrence.

Introduction

Rhinosporidiosis is a chronic granulomatous infection caused by Rhinosporidium seeberi, commonly affecting the nose and nasopharynx. ¹ The disease is most common among the low socioeconomic cohorts living in rural areas in the second and third decades of life. ² It occurs worldwide, although it is endemic in southern India and Sri Lanka. Interestingly, sporadic cases have been reported in Turkey, South America, Italy, Iran, and Malaysia. ³ Similarly, males are more predominantly affected than females, owing to occupational exposure. Currently, local data on rhinosporidiosis is scarce, and only three cases of the disease have been previously reported in Malaysia.^2,4,5 Even then, the affected patients were notably immigrants from neighbouring countries. We present a case of recurrent rhinosporidiosis, emphasising the paramount importance of diagnosis and management of recurrence. To the best of our knowledge, this is the first local case of recurrent rhinosporidiosis confirmed in a Malaysian man from Sabah state.

Case description

A 60-year-old Malaysian of Indian ancestry with a background of well-controlled diabetes mellitus presented to the Otorhinolaryngology Department, Kuala Lumpur General Hospital, in 2020, with a 6-month history of nasal obstruction and intermittent epistaxis. He had had similar symptoms since he was 30 years old. In 2009, he underwent his first endoscopic surgery, in which the intraoperative histopathologic examination of the surgical specimen was favourable for rhinosporidiosis. However, the disease recurred, for which he underwent five excisional surgeries at different time points from 2009 to 2019 before receiving treatment at our hospital. Having spent his childhood on Labuan Island, he was frequently involved with water sports. Previously, he did odd jobs around the island before resettling in Kuala Lumpur.

On rhinoscopy examination, there was an erythematous, irregular mass protruding from the right-sided lateral wall of the nasal cavity, the medial turbinate and spreading towards the left-sided posterosuperior margin via the perforated nasal septum. Laboratory evaluation was unremarkable. The nasal mass was excised endoscopically, and the histopathological examination (HPE) of the surgical specimen demonstrated abundant thick-walled sporangia encapsulating endospores, consistent with the diagnosis of recurrent rhinosporidiosis (Figure 1(a)–(c)). After surgery, oral dapsone at a dose of 100 mg/day was administered.

Figure 1.

We describe the nasal endoscopic, radiological, and histopathological findings suggestive of rhinosporidiosis in our case. The histopathology describes the presence of abundant, enormous, thick-walled sporangia containing spores [(a) (H&E staining), (b) (GMS staining), and (c) (PAS staining)] in a background of stratified squamous epithelium surrounded by neutrophils, lymphocytes, plasma cells, macrophages, and multinucleated giant cells. (d) The laryngoscopic examination depicted the medial turbinate and nasal septum with irregular walls and soft tissue mass. The paranasal CT shows an enhancing soft tissue mass in the right naso-ethmoidal region (e), entirely occupying the space of the right maxillary sinus, and encroaching on the right frontal recess, left middle meatus, and sphenopalatine region. The bone window view in (f) depicts erosion of the nasal septum, abutted by soft tissue lesions.

One year later, he was found to have a recurrence of rhinosporidiosis involving bilateral nasal cavities. A polypoidal mass was detected during a diagnostic nasal endoscopy at the right lateral wall, right maxillary sinus, and left middle meatus (Figure 1(d)). The findings were supported by the computed tomography (CT) of the paranasal sinuses (PNS), as shown in Figure 1(e) and (f). He underwent endoscopic excision of bilateral rhinosporidiosis-related masses, followed by dapsone. At follow-up after six months, there was no further recurrence.

Discussion

To date, the aetiology of rhinosporidiosis, first described by Seeber in 1900, ⁶ remains contentious and enigmatic. Previously thought to be a fungus related to Colletotrichum and Synchytrium, ⁷ the causative agent, R. seeberi, has been oscillated between fungi, bacteria, and parasites. With 18S rRNA genome sequencing, it has been revised as a protistan parasite, an aquatic eukaryote in the class Mesomycetozoea. ⁷ It is worth noting that Ahluwalia et al. identified Microcystic aeruginosa, a water-borne cyanobacterium, as the causative agent of rhinosporidiosis, which can cause similar infections in fish and amphibians. ⁸ The disease is presumably transmitted through traumatised epithelia by direct contact with free spores in natural aquatic or marshy environments. ¹ Interestingly, the disease is most prevalent in rural settings, notably among paddy cultivators, sand workers, fishermen, and people bathing in stagnant muddy water or contaminated surface water sources. In our case, he was presumably at a higher ecological risk of acquiring the disease, as he lived on an island.

Rhinosporidiosis primarily affects the mucosa membranes of the nasopharynx in 70–75% of cases (especially the lateral wall of the nasal cavity and nasal septum), conjunctiva and lacrimal sac (15%), and less commonly, other body parts (estimated 10%, including the urethra and skin). ⁹ Disseminated disease with visceral involvement, though rare, has been reported. ³ In general, the nasal lesions are characterised by pruritic papules that gradually transform into a friable, erythematous, and polypoidal mass representing mature sporangia, which may potentially cause mechanical obstruction of the nasal cavity and nasopharynx. At a later stage, thick-walled cysts develop in the submucosa, giving rise to a strawberry-like appearance characterised by white dots on the erythematous mucosa. Of note, up to 48% of cases experienced unilateral nasal congestion caused by the mass-like effect. ¹⁰ Other nasal complaints involve epistaxis and rhinorrhoea. Given the atypical clinical presentation, it is mandatory to differentiate rhinosporidiosis from chronic granulomatous diseases, angiomatous polyp, angiofibroma, inverted papilloma, rhinoscleroma, and even malignancy. ¹¹

In general, the diagnosis of rhinosporidiosis is elusive. Nasal endoscopy and laryngoscopy help determine the degree of disease activity by identifying the number of lesions and sites of invasion. Amidst all the diagnostic tools for rhinosporidiosis, HPE with appropriate identification of the pathogen at various stages of maturation is considered the gold standard test. Of note, the histopathology helps reveal sporangia, varying from 100 to 350 μm in diameter, enveloped within a well-defined, chitinous wall in the submucosal layer of the affected site, which are visible as white dots in the mucosa containing sporangiospores (6–12 μm). Commonly, endospores and sporangia are embedded amidst inflammatory cell infiltrates.

In general, the causative agent is easily visualised by examining the smear of tissue samples with lactophenol cotton blue (LCB) staining. Several fungal stains, notably periodic acid-Schiff (PAS), Gomori methenamine silver (GMS), and Mayer’s mucicarmine stain, better aid in fungal species discrimination. Interestingly, fungal cultures and serological tests have no additional diagnostic value.

To date, the disease remains a therapeutic challenge for clinicians. The mainstay of treatment is surgical resection of the lesions from the base of affected areas. Characteristically, endoscopic and laser excision of the associated lesions achieve a recovery rate of up to 90%, ¹ though complications, including atrophic rhinitis, septic perforation, and bleeding, may arise. ¹² Additionally, electric cauterisation of the nasal base can be considered as a treatment option. However, recurrence is not uncommon after surgery, owing to the spillage of endospores that contaminate the surrounding tissue during the surgical removal of lesions. Recurrence rates ranging from 5% to 67%, are solely attributed to the involvement of the nasal cavity (particularly the nasal septum, middle turbinate, nasopharynx, and posterior pharyngeal wall), delayed presentation for more than twelve months duration before intervention, and aggressive dissemination involving more than two sites. ¹³ Other possible causes include an inadequate host immune response to R. seeberi, potential haematogenous or lymphatic spread, and the inability to surgically remove infective foci from difficult-to-reach mucosal sites (particularly the oropharynx and paranasal sinuses).^1,14

Various pharmacological treatments, notably antimicrobials and antifungal agents, have been attempted with variable success. Evidence on drug sensitivity and resistance in R. seeberi is lacking. ¹² At present, dapsone, also known as diaminodiphenyl sulfone (DDS) or 4,4′-sulfonyldianiline (SDA), is widely chosen to control the disease. With its sporistatic property, dapsone helps halt the process of sporangial maturation and promotes fibrogenesis in the stroma. ¹ Considering the high recurrence rate, a prolonged course of dapsone (100 mg daily for at least one year) is required. A multidrug regime containing dapsone, ketoconazole, and cycloserine was recently found to be effective in treating refractory cases of uncontrolled disseminated disease. ¹

Conclusion

In summary, a high index of suspicion for rhinosporidiosis should be raised in cases with nasal masses leading to obstruction and epistaxis in the endemic regions. Recurrence is not uncommon despite optimal surgical and pharmacological treatment. The high relapse rate of the disease warrants long-term follow-up and regular endoscopic surveillance.