Topical and systemic antifungal therapy for chronic rhinosinusitis

Background: This review adds to a series of reviews looking at primary medical management options for patients with chronic rhinosinusitis.  Chronic rhinosinusitis is common and characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Antifungals have been suggested as a treatment for chronic rhinosinusitis.  Objectives: To assess the effects of systemic and topical antifungal agents in patients with chronic rhinosinusitis, including those with allergic fungal rhinosinusitis (AFRS) and, if possible, AFRS exclusively.  Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 17 November 2017.  Selection criteria: Randomised controlled trials (RCTs) with at least a two‐week follow‐up period comparing topical or systemic antifungals with (a) placebo, (b) no treatment, (c) other pharmacological interventions or (d) a different antifungal agent. We did not include post‐surgical antifungal use.  Data collection and analysis: We used the standard Cochrane methodological procedures. Our primary outcomes were disease‐specific health‐related quality of life (HRQL), patient‐reported disease severity and the significant adverse effects of hepatic toxicity (systemic antifungals). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse effects of gastrointestinal disturbance (systemic antifungals) and epistaxis, headache or local discomfort (topical antifungals). We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.  Main results: We included eight studies (490 adult participants). The presence of nasal polyps on examination was an inclusion criterion in three studies, an exclusion criterion in one study and the remaining studies included a mixed population. No studies specifically investigated the effect of antifungals in patients with AFRS.  Topical antifungal treatment versus placebo or no intervention  We included seven studies (437 participants) that used amphotericin B (six studies; 383 participants) and one that used fluconazole (54 participants). Different delivery methods, volumes and concentrations were used.  Four studies reported disease‐specific health‐related quality of life using a range of instruments. We did not meta‐analyse the results due to differences in the instruments used, and measurement and reporting methods. At the end of treatment (one to six months) none of the studies reported statistically significant differences between the groups (low‐quality evidence ‐ we are uncertain about the result).  Two studies reported disease severity using patient‐reported symptom scores. Meta‐analysis was not possible. At the end of treatment (8 to 13 weeks) one study showed no difference and the second found that patients in the placebo group had less severe symptoms (very low‐quality evidence ‐ we are very uncertain about the result).  In terms of adverse effects , topical antifungals may lead to more local irritation compared with placebo (risk ratio (RR) 2.29, 95% confidence interval (CI) 0.61 to 8.62; 312 participants; 5 studies; low‐quality evidence) but little or no difference in epistaxis (RR 0.97, 95% CI 0.14 to 6.63; 225 participants; 4 studies, low‐quality evidence) or headache (RR 1.26, 95% CI 0.60 to 2.63; 195 participants; 3 studies; very low‐quality evidence).  None of the studies found a difference in generic health‐related quality of life (one study) or endoscopic score (five studies) between the treatment groups. Three studies investigated CT scan ; two found no difference between the groups and one found a significant decrease in the mean percentage of air space occluded, favouring the antifungal group.  Systemic antifungal treatment versus placebo or no treatment  One study (53 participants) comparing terbinafine tablets against placebo reported that there may be little or no difference between the groups in disease‐specific health‐related quality of life or disease severity score (both low‐quality evidence). Systemic antifungals may lead to more hepatic toxicity events (RR 3.35, 95% CI 0.14 to 78.60) but fewer gastrointestinal disturbances (RR 0.37, 95% CI 0.04 to 3.36), compared to placebo, although the evidence was of low quality.  This study did not find a difference in CT scan score between the groups. Generic health‐related quality of life and endoscopic score were not measured.  Other comparisons: We found no studies that compared antifungal agents against other treatments for chronic rhinosinusitis.  Authors' conclusions: Due to the very low quality of the evidence, it is uncertain whether or not the use of topical or systemic antifungals has an impact on patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment. Studies including specific subgroups (i.e. AFRS) are lacking

Unusual manifestation of cystic mycetoma lesions:: A case report

Mycetoma is a chronic and debilitating infectious disease characterized by localized swellings and granulomatous lesions. It primarily affects individuals in tropical and subtropical regions and is caused by certain fungi or bacteria. While mycetoma typically presents with sinuses and discharge, this case report presents a unique cystic presentation without these features. The patient, a 12-year-old female from Sudan, presented with a painless swelling on the dorsum of her right foot. Physical examination revealed a round, non-tender, and fluctuant mass. Histopathological examination confirmed actinomycetoma caused by Streptomyces somaliensis. The patient was successfully treated with a combination of antibiotherapy. This atypical presentation underscores the need for healthcare professionals to consider uncommon variations of mycetoma for accurate diagnosis and management

Development of the Mycetoma Activity and Severity clinical Scale (MASS):an international Delphi study

Mycetoma is a chronic, subcutaneous infection that causes local tissue destruction, leading to deformity, disability, and social stigma. Safe and effective treatments for mycetoma are urgently needed; however, there is no systematic measure that allows objective clinical assessment of disease severity and activity, which makes it difficult to accurately assess the effectiveness of treatments and draw comparisons between studies. A Delphi study was conducted, involving a panel of 23 mycetoma experts from five continents, to establish consensus on the structure, wording, and content of a clinical scoring system for mycetoma. Three rounds of anonymous surveys were conducted between August, 2023 and May, 2024. Consensus was defined as 65-85% agreement and strong consensus if 85% or higher. The final version of the Mycetoma Activity and Severity clinical Scale (MASS) consisted of 20 items, 14 pertaining to disease severity and six to disease activity, grouped into objective clinical features, patient-reported measures, and investigations. Consensus was achieved for 19 of the 20 items, and a strong consensus for 14. The MASS is the first clinical scoring system for mycetoma derived from a consensus approach and will facilitate accurate evaluation of treatment response if adopted into routine clinical practice by health-care workers across mycetoma-endemic regions. The MASS will also serve an important function as a research tool for use in prospective clinical studies and comparative drug trials.</p

Recurrent madura foot without draining sinuses: a case report

Madura foot or mycetoma is a chronic granulomatous disease characterized by localized infection of subcutaneous tissues by actinomycetes or fungi. The recurrence rate for the disease if treated inadequately is very high. Recurrence presents with swelling and multiple discharging sinuses. This is an unusual presentation of the disease without discharging sinuses which is probable the first report of this kind in the literature. A 34 year old, male, presented with the painless, progressive swellings over right foot since 4 years. No sinuses or discharge could be found on skin surface. The postoperative recurrence rate is very high, and this can be local or distant at the regional lymph nodes. This could be due to the disease biology and behavior or inadequate surgical excision. Usually it presents with multiple sinus tracts, and granule. We reported a case with classical absence of sinus tracts in recurrent actinomycosis

Determining the burden of fungal infections in Zimbabwe.

Zimbabwe currently faces several healthcare challenges, most notably HIV and associated infections including tuberculosis (TB), malaria and recently outbreaks of cholera, typhoid fever and COVID-19. Fungal infections, which are also a major public health threat, receive considerably less attention. Consequently, there is dearth of data regarding the burden of fungal diseases in the country. We estimated the burden of fungal diseases in Zimbabwe based on published literature and 'at-risk' populations (HIV/AIDS patients, survivors of pulmonary TB, cancer, chronic obstructive pulmonary disease, asthma and patients receiving critical care) using previously described methods. Where there was no data for Zimbabwe, regional, or international data was used. Our study revealed that approximately 14.9% of Zimbabweans suffer from fungal infections annually, with 80% having tinea capitis. The annual incidence of cryptococcal meningitis and Pneumocystis jirovecii pneumonia in HIV/AIDS were estimated at 41/100,000 and 63/100,000, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) was 2,739/100,000. The estimated burden of fungal diseases in Zimbabwe is high in comparison to other African countries, highlighting the urgent need for increased awareness and surveillance to improve diagnosis and management