The heavy burden and treatment challenges of fungal periprosthetic joint infection: a systematic review of 489 joints.

BACKGROUND: Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. METHODS: A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. RESULTS: A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. CONCLUSIONS: Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients.

Clinical Approach to Dental Root Canal Filler-Induced Maxillary Sinus Fungal Mass Using Transnasal Endoscopy.

Accidentally extruded root canal filler within the sinuses may induce maxillary sinusitis with fungal mass. The authors describe 2 cases of gutta-percha-induced fungal masses in the left maxillary sinus of 2 women. The lesions were evaluated preoperatively using both computed tomography and magnetic resonance imaging, providing comprehensive insights into the condition. In one patient, the lesion was located such that it could be resected through the middle meatal antrostomy alone. However, the second patient presented with an anteroinferiorly situated lesion that necessitated not only a transnasal approach but also an endoscopic modified medial maxillectomy. Both patients recovered uneventfully after surgery. This case series is the first published report of 2 cases of gutta-percha-induced maxillary sinus fungal masses, with their imaging findings, successfully treated through different routes through transnasal endoscopic surgery. These reports highlight the need for a collaborative approach between dental practitioners and otolaryngologists. In addition to the patient's wishes, surgical interventions must consider the unique characteristics of each case and the potential for collaboration across different medical specialties.

The impact of maxillary dimensions on determining surgical approach of fungal ball in the maxillary sinus.

Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior-posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements-anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus-for guiding optimal surgical approaches in MS lesions.

Primary Vitrectomy versus Tap and Inject for Fungal Endophthalmitis: Meta-Analysis and Comparison with Data from a Reference Centre.

PURPOSE: We aimed to compare the visual outcomes after pars plana vitrectomy (PPV) versus tap and inject (T&I) in fungal endophthalmitis (FE) reported in the literature and to compare the findings from the literature with data from a reference centre. METHODS: We performed a systematic review and meta-analysis of studies reporting the use of PPV versus T&I in FE. We also performed a retrospective review of the clinical records of patients with endophthalmitis from a reference centre in Colombia. RESULTS: We included 13 studies with 334 eyes; 53.59% received PPV and 46.4% received T&I. The overall relative risk of improving ≥ 2 lines in PPV versus T&I was 0.98 (95% confidence interval [CI] 0.80-1.22; p = 0.88) with a mean difference of final visual acuity of 0.26 (95% CI 0.12-0.63; p = 0.18). There were no significant differences in subgroup analysis. Data from the reference centre included 32 endophthalmitis cases, 15.6% of which had a fungal aetiology (80% received PPV and 20% T&I). There were no significant differences in the subgroup analysis. CONCLUSIONS: Based on the findings from the literature and the reference centre, T&I is noninferior to PPV. This is the first meta-analysis in the literature evaluating these effects in FE. It is necessary to execute new prospective randomised controlled studies in patients with endophthalmitis.

Factors Impacting Follow-Up Care in Allergic Fungal Rhinosinusitis.

OBJECTIVE: The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS). STUDY DESIGN: Cross-sectional questionnaire-based study with retrospective chart review. SETTING: Tertiary Medical Center. METHODS: Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review. RESULTS: Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs 17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs 5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs 3.1%, P < 0.001) and be lost to follow-up (66.7% vs 9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs 35.1%, P = 0.034), lost to follow-up (77.3% vs 10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs 5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276). CONCLUSION: Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups.

The vanishing nasal septum sign: a case of severe fungal sinusitis.

Acute invasive fungal sinusitis (AIFS) is a fungal infection of the nasal cavity and paranasal sinuses with associated invasion of adjacent vessels and soft/hard tissues. It usually occurs in immunocompromised patients and may follow a rapid course of less than four weeks with high mortality rate. We report a 39-year-old male with relapse of acute myelogenous leukemia (AML) who was under evaluation for neutropenic fever. On his sinus CT, there was loss of calcification of his nasal septum when compared to a prior head CT, a sign indicative of an aggressive infectious process. He was diagnosed with AIFS and underwent emergent surgical debridement and systemic antifungal therapy, leading to a positive outcome. The sign described on CT ("Vanishing Nasal Septum" sign) may provide an additional, reliable tool to prospectively identify locally aggressive cases of invasive fungal infections of the nasal cavity at an earlier stage and improve patient outcomes.

Impact of azole antifungal treatment on outcome in acute invasive fungal rhinosinusitis with orbitocranial involvement: a surgical perspective.

PURPOSE: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI). METHODS: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison. RESULTS: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery. CONCLUSION: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.

Successful management of nasopharyngitis caused by Schizophyllum commune in a captive cheetah (Acinonyx jubatus).

Herein, we describe the management of nasopharyngitis caused by Schizophyllum commune infection in a captive cheetah. Computed tomography revealed a nodule in the nasal cavity and pharynx, and an endoscopic biopsy was performed. As a result, the nodule was surgically resected because of a suspected carcinoma. However, the surgical specimen was histologically re-evaluated and a fungal granuloma was diagnosed. Sequence analysis of DNA from formalin-fixed, paraffin-embedded samples revealed S. commune infection. The cheetah was administered fluconazole orally for 73 days. However, the drug was ineffective and itraconazole was administered for 14 days. Symptoms such as nasal discharge and sneezing have completely resolved for 4 years.

What is appropriate management for the contralateral uninvolved side in unilateral allergic fungal rhinosinusitis?

PURPOSE OF REVIEW: The aim of this article is to review the current literature regarding development of new or recurrent inflammation of uninvolved contralateral sinuses in unilateral allergic fungal rhinosinusitis (AFRS) and discuss management strategies. RECENT FINDINGS: AFRS is a subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP) that can manifest as either unilateral or bilateral disease. Particular to AFRS compared with other CRSwNP subtypes is the high propensity for recurrence. Multiple recent studies have evaluated the recurrence rate of uninvolved contralateral sinuses in unilateral AFRS and demonstrated eventual involvement of the nondiseased side. Additionally, postoperative medical therapy of the nondiseased side reduced recurrence rates overall. SUMMARY: Recurrence of AFRS is high in both the ipsilateral and contralateral sinuses. Upfront bilateral medical and/or surgical treatment of patients presenting with unilateral AFRS may be considered to improve long-term inflammatory control.

Differences in clinical and imaging presentation of maxillary sinus fungus ball with and without intralesional hyperdensity.

Maxillary sinus fungal balls (MSFBs) mostly occur in older individuals and demonstrate female predominance. Early diagnosis is important to avoid treatment delays. Intralesional hyperdensity (IH) indicates the presence of heavy metal deposition within fungal hyphae and has been the most specific characteristic of MSFB on computed tomography (CT). For those without IH on CT, the diagnosis of MSFB remains challenging. This study aimed to characterize clinical presentation of MSFB with and without IH and to study factors contributing to MSFB with no IH formation. We retrospectively identified 588 patients with MSFB. The clinical characteristics and CT findings were reviewed. Patients with unilateral MSFB had a mean age of 57.4 years and demonstrated female predominance (64.63%). The female-to-male ratio was highest at 51-60 years (2.02) and rose to 2.60 in MSFB with IH only. Compared to those with IH, MSFB without IH was significantly more common in males (OR = 2.49), in those with diabetes mellitus (DM) (OR = 1.87), adjacent maxillary odontogenic pathology (OR = 1.75). Complete opacification on CT was less common in MSFB without IH (OR = 0.60). Patients with MSFB without IH were more likely to have DM, no female predominance, adjacent maxillary odontogenic pathology, and partial opacification of the sinus, compared to those with IH. These may be helpful in better understanding of the formation of MSFBs without IH, early identification of them and prevention of post-operative recurrence.

A case of ureteral fungal mass removal in a patient taking empagliflozin.

With increased use of sodium-glucose co-transporter 2 (SGLT2) inhibitors as antidiabetic agents, the risk of serious fungal urinary tract infection (UTI) may be increased. We present the case of a 67-year-old Caucasian female who was admitted for emphysematous pyelitis and found to have a fungal ball in the renal pelvis. Candida glabrata was cultured and the patient was managed with percutaneous nephrostomy tube placement and antifungal treatment. The fungal ball persisted and required surgical removal with ureteroscopy and basket extraction. Fungal balls can be a difficult sequelae of UTIs requiring a combination of antifungal and surgical intervention for definitive management.

Treatment of Paranasal Sinus Fungus Ball: A Systematic Review and Meta-Analysis.

OBJECTIVES: Paranasal sinus fungus ball is a common non-invasive mycosis with excellent long-term surgical treatment results. The present systematic review and meta-analysis were undertaken to define current treatment concepts and success rates in paranasal sinus fungus ball treatment. METHODS: Systematic searches were performed in multiple databases with criteria designed to include all studies published until May 2020 focusing on paranasal sinuses fungus ball treatment in humans. We selected studies including at least 10 patients, specifying treatment modalities, providing a minimum 6-month follow-up, and objectivating treatment success. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates. Success rates were pooled in a random effect meta-analysis and compared according to the use of intraoperative sinus lavages and postoperative antibiotics. RESULTS: Among 740 unique citations, 14 studies were deemed eligible. Most (n = 11) were retrospective case series. All studies relied on endoscopic sinus surgery. Intraoperative lavages were proposed in 10 studies and postoperative antibiotics in 7 (for all patients in 5 studies and for selected patients in 2). No significant heterogeneity was observed between results (Cochran's Q P = .639, I2 test = 0). Treatment success rate was 98.4% (95% confidence interval 97.4%-99.3%). Intraoperative sinus toilette and postoperative antibiotics didn't significantly improve the success rate. CONCLUSION: Endoscopic sinus surgery shows excellent results in fungus ball treatment. Further prospective studies might help further reducing antibiotics prescriptions in these patients and improve their management.

A Case of Black Fungal Keratitis Caused by Biatriospora mackinnonii.

PURPOSE: To report a novel case of fungal keratitis caused by Biatriospora mackinnonii (Pyrenochaeta mackinnonii), a dematiaceous fungus (black fungus) that rarely causes dermatological infection, in a patient treated for ocular cicatricial pemphigoid. METHODS: An 81-year-old patient with ocular cicatricial pemphigoid was referred to our hospital because of persistent corneal epithelial defects in his left eye. On examination, a slightly elevated dark lesion in the middle of the erosion and hypopyon was observed in that eye, with smear examination of the obtained specimen revealed a filamentous fungal-like material. Initially, treatment included miconazole and fluconazole ophthalmic solution eye drops, natamycin ophthalmic ointment, and systemic voriconazole, followed surgical scraping of the mass, an anterior chamber lavage, and a subconjunctival injection of miconazole. However, the focus had resistance to the treatment and finally led to corneal perforation; hence, therapeutic penetrating keratoplasty (PKP) was subsequently performed. RESULTS: Mycological testing revealed that the lesions were Candida parapsiliosis and black fungus, with the black fungus classified as B. mackinnonii via DNA sequencing of the internal transcribed spacer and the D1/D2 domains of the 28S rRNA gene. Fungal keratitis caused by B. mackinnonii was resistant to the antifungal drugs, yet was ameliorated by PKP, with no recurrence of fungal keratitis for more than 2 years postoperative. CONCLUSIONS: To the best of our knowledge, this is the first reported case of fungal keratitis caused by B. mackinnonii; however, in this case, PKP surgery resulted in a favorable outcome.

Prosthetic joint infection due to Candida species: Case series and review of literature.

INTRODUCTION: The increase in the number of patients with prosthetic joints will entail a rise in the absolute number of infections associated with these procedures. Although less frequent, infections by Candida species are also expected to increase, and the clinical and surgical management of these cases is based on case reports and opinion of specialists. The objective of the present study was to review the available literature and describe the cases of prosthetic joint infection caused by Candida species in patients of the Institute of Orthopedics and Trauma of the University of São Paulo Faculty of Medicine Clinics Hospital (IOT-HCFMUSP) between 2007 and 2014. PATIENT CONCERNS: Eleven patients were diagnosed with prosthetic joint infection due to Candida with mean age of 65 years. The most frequent comorbidities were heart disease and diabetes mellitus, and the main personal antecedent was previous bacterial infection in the prosthetic joint. At least one risk factor for fungal infection was present in 73% of the patients. There was no difference between the prevalence of infections caused by Candida albicans and non-albicans Candida species, and there was bacterial co-infection in 55% of the cases. DIAGNOSIS: For building up the case series, patients with cultures of bone and joint specimens that were positive for Candida species and had a clinical diagnosis of prosthetic joint infection were included in the case series. INTERVENTIONS: Surgical debridement with removal of the prosthesis was the most frequently used surgical approach (45%). All patients were treated with monotherapy, and the most frequently used antifungal agent was fluconazole. The total duration of antifungal therapy was 6 months in 73% of the cases. OUTCOMES: After the initial management, 73% of the patients achieved clinical remission. CONCLUSION: The most indicated initial management was debridement with removal of the prosthesis, and the most used treatment regimen was fluconazole monotherapy. The most prevalent treatment duration was 6 months. The initial management led to a favorable outcome in 73% of the cases. DESCRIPTORS: Prosthetic joint infection, Candida, treatment, and diagnosis.

Clinicopathologic characteristics of paranasal sinus fungus ball: retrospective, multicenter study in Korea.

PURPOSE: Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of this study was to compare the clinical characteristics of Korean adult patients with FB and chronic rhinosinusitis (CRS) without FB. METHODS: We retrospectively analyzed data on 1362 patients (147 FB and 1215 CRS) who underwent endoscopic sinus surgery at nine Korean medical centers in 2005, 2010, and 2016. We evaluated the prevalence of FB and compared the clinical characteristics of FB and CRS. Medical records, computed tomography (CT) findings, atopic status, concomitant diseases, tissue, and blood eosinophil count were assessed. RESULTS: The prevalence of FB was significantly higher in 2016 (15.9%) than in the other years (7.8% in 2005 and 7.5% in 2010). The FB patients were more likely to be female, older, have unilateral disease and less likely to have allergy compared to the CRS patients. The most common main complaint related to CRS and FB was nasal obstruction. CT determined that unilateral disease and maxillary sinus dominancy were common in patients with FB. The incidence of concomitant diseases was much higher in FB, with lower tissue and blood eosinophilia. CONCLUSION: FB is commonly encountered in older women with the increased prevalence. FB had a different clinical presentation, radiological findings, and prognosis than CRS. Further studies are needed to understand the pathophysiologic mechanisms underlying the development of FB.

Complications of Isolated Fungal Sphenoiditis: Patient Clinical Characteristics.

OBJECTIVE: To evaluate the clinical characteristics of patients with complications of isolated fungal sphenoiditis. MATERIALS AND METHODS: The records of patients diagnosed with isolated fungal sphenoiditis at Songklanagarind Hospital from January 2004 to December 2017 were retrospectively reviewed. Data related to demographics, clinical presentation, underlying disease, type of complication, surgical procedure, and clinical outcome were collected. RESULTS: Among the 35 participating patients, complications were found at a rate of 40%. The most common complication was visual loss (71.43%). We also compared the clinical characteristics between patients with and without complications via univariate analysis. The enrolled patients consisted of 12 men and 23 women (1:2). The mean age was older in the complications group 64 (41-84) vs. 57.43 (36-81) years, respectively. Underlying diabetes mellitus and complete opacity of the sphenoid sinus were factors that related significantly to the occurrence of complications. After treatment, 35.72% of the participants made a complete recovery; underlying diabetes mellitus was associated with a poor prognosis. CONCLUSION: This report indicates that practitioners must be careful of complications arising in elderly and female patients with isolated fungal sphenoiditis, who have a complete opacity of the sphenoid sinus and underlying diabetes mellitus.

Prognostic role of blood eosinophil and basophil levels in allergic fungal rhinosinusitis (AFRS).

PURPOSE: Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS. MATERIALS AND METHODS: A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed. RESULTS: Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not. CONCLUSIONS: Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.

Omalizumab versus intranasal steroids in the post-operative management of patients with allergic fungal rhinosinusitis.

PURPOSE: Allergic fungal rhinosinusitis (AFRS) is a common disorder with a high prevalence and a very high incidence of recurrence. Management includes surgery and medical treatment in the form of local and/or systemic steroids. However, some cases are resistant to the action of steroids and further treatment is warranted. Being an immune-mediated disorder, targeting IgE seems a logical step. Immunotherapy drugs acting on the IgE (e.g. omalizumab) can modify the clinical course of the disease. This study aimed at evaluating the effect of omalizumab on the clinical course of patients undergoing surgery for AFRS. MATERIALS AND METHODS: This is a two-arm prospective, randomized, single blind clinical trial among patients with AFRS. Twenty patients were included and randomly divided into two groups: Group A; 10 patients received a single subcutaneous injection of omalizumab (Xolair ' Novartis) (150 mg) 2 weeks postoperatively. Group B: 10 patients received local steroids nasal sprays (budesonide or mometasone furoate, 100 µg twice daily for 6 months, starting 2 weeks postoperatively. All patients underwent history, examination, CT scan and IgE level estimation and were submitted to endoscopic sinus surgery. They were evaluated at 4 weeks interval for 6 months. RESULTS: In both groups there were highly significant differences between pre/post-operative SNOT-20 scores, TNSS scores, total IgE level and Philpott-Javer staging scores. Comparison between the two study groups at 24 weeks showed a highly significant difference (p = 0.001) between post-operative SNOT 20 and TNSS scores in favour of group A. There was no statistically significant difference between the two study groups as regarding postoperative total IgE or Philpott-Javer scores. There were two recurrences in both arms, but no significant side effects. DISCUSSION: We compared a single post operative injection of omalizumab with twice daily intranasal steroid spray for 6 months. Both treatments were effective, but the omalizumab group showed a more significant clinical and endoscopic response. There were no significant side effects in both arms. This novel approach used a single low dose injection of omalizumab increased the compliance of the patients with minimal complications. Longer follow-up of the patients is ongoing to determine the optimal time for re-injection. The only downside was the higher cost of omalizumab compared to that of local steroids.