Mucin-Related Rhinosinusitis YOUSEF ALJATHLANY ORL-HNS RESIDENT
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1 Mucin-Related Rhinosinusitis YOUSEF ALJATHLANY ORL-HNS RESIDENT
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3 Introduction 1965, first attempt to classify FRS, Hora recognized two categories: invasive and noninvasive. McGill et al., in 1980, reported a third type of FRS in immunocompromised patients: a fulminant form.
4 Introduction In 1976, Safirstein noted a combination of nasal polyposis, crust formation, and sinus cultures yielding Aspergillus species He observed the clinical similarity that this constellation of findings shared with allergic bronchopulmonary aspergillosis (ABPA).
5 Introduction In 1981, Miller et al., and in 1983, Katzenstein et al., recognized few cases of CRS associated with a mucosal plug in the sinuses of patients with ABPA, which led to a description of a fourth type of FRS, namely Allergic Aspergillus sinusitis.
6 Introduction Melanized fungi were recognized a etiological agents of this allergic type of sinusitis It led to the renaming of this type of FRS as allergic fungal sinusitis or rhinosinusitis (AFS or AFRS).
7 Introduction AFRS definition has faced a greater challenge with the demonstration of fungi in eosinophilic mucin independently from type I hypersensitivity in most cases of CRS. Ponikau et al. proposed a new term for this condition, namely eosinophilic fungal rhinosinusitis (EFRS), to reflect the striking role of eosinophils
8 Classifications Invasive Acute Invasive Chronic Granulomatous Chronic Invasive Non-Invasive Saprophytic infestation Fungus Ball Eosinophil related FRS (including AFRS)
9 Eosinophilic Mucin Grossly, Eosinophilic mucin is: Thick Tenacious, and highly viscous in consistency Light tan to brown or dark green in color.
10 Eosinophilic Mucin Histologically: Lamellated aggregates of dense inflammatory cells, mostly eosinophils and Charcot-Leyden crystals, the by-products of eosinophils.
11 Eosinophilic Mucin Silver stain: branching fungal hyphae
12 Eosinophilic Mucin Allergic mucin term was based on the historic association of eosinophilia and an IgE mediated allergy. Now, it occurs without any detectable IgE-mediated allergy. The terminology changed to eosinophilic mucin.
13 Eosinophilic Mucin
14 Mucin-Related RS - Categories The diseases with eosinophilic mucin may be broadly divided into nonfungal and fungal categories.
15 Mucin-Related RS - Categories Non-fungal AFRS-like group with fungal specific IgE EMRS (EFRS-like) Aspirin-exacerbated RS (previously known as aspirin-sensitive RS). Fungal AFRS EFRS Limited number of cases of aspirinexacerbated RS, which also have fungal hyphae demonstrable.
16 Mucin-Related RS - Categories
17 Mucin-Related RS - Categories Eosinophilic Mucin Fungal elements Specific IgE AFRS EFRS EMRS AFRS-like + - +
18 Mucin-Related RS - Pathophysiology Fungal allergens elicit IgE +/- type III (immune complex)- in absence of invasion. When sensitized individuals are exposed to an environment of high fungal content, symptoms of upper and/or lower airway hyperresponsiveness increase significantly.
19 Mucin-Related RS - Pathophysiology Generalized sinonasal inflammation with viscid allergic mucin effectively obstructs the normal drainage pathway. Fungi persist locally, stimulating locally destructive immune responses. The process expand to involve adjacent sinuses and may produce sinus expansion and bony erosion.
20 Mucin-Related RS - Pathophysiology Accumulation of eosinophilic mucin leads to elevation of inflammatory mediators, such as: Major basic protein Eosinophil peroxidas Eosinophil-derived neurotoxin Tumor necrosis factor β, and Interleukins (IL)-4, 5, 10, and 13.
21 Mucin-Related RS - Pathophysiology Accumulation of eosinophilic mucin leads to elevation of inflammatory mediators, such as: Major basic protein Eosinophil peroxidas Eosinophil-derived neurotoxin Tumor necrosis factor β, and Interleukins (IL)-4, 5, 10, and 13.
22 Allergic Fungal Rhinosinusitis To diagnose AFRS, Bent and Kuhn criteria is still widely acceptable:
23 Eosinophilic Fungal Rhinosinusitis Ponikau et al. in 1999 demonstrated the presence of fungi in nasal mucus from 96% of patients with CRS and found type I hypersensitivity to be present in <25% of their study group.
24 Eosinophilic Fungal Rhinosinusitis They detected fungi along with eosinophil and eosinophil degraded products in mucus. Often the eosinophils were in clusters along with a few Charcot-Leyden crystals, but sometimes they found the eosinophils in the form of cellular debris and crystals.
25 Eosinophilic Fungal Rhinosinusitis They termed this mucin eosinophilic mucin and coined the term eosinophilic fungal rhinosinusitis (EFRS)
26 Eosinophilic Fungal Rhinosinusitis They also demonstrating high levels of toxic major basic protein (MBP) from eosinophils in the mucus of patients with CRS They postulated that MBP damages the nasal epithelium, permitting secondary bacterial infection.
27 AFRS Vs EFRS AFRS EFRS Host Atopy Non-Atopic Demography Geographic distribution Fungi Role of Fungus Urban in USA Villages in Asia Southwest USA, India, Pakistan Dematiaceous hyphae in US A. Flavus in India Allergen Any person Worldwide Dematiaceous hyphae in US A. Flavus in India Not clear
28 AFRS Vs EFRS AFRS EFRS Pathology Eosinophilic mucin, few hyphae Eosinophilic mucin, few hyphae Course of disease Presentation Diagnosis Chronic >12wks Nasal obstruction, facial pain, hyposmia, Orbital symptoms Type I skin test, polyp, eosinophilic mucin, fungi, characteristic CT Chronic >12wks Nasal obstruction, rhinorrhoea, facial pain Non-allergic eosinophilic mucin, fungi
29 AFRS Vs EFRS AFRS EFRS Treatment Surgery, oral/ or local steroid,?immunotherapy Prognosis Recurrence common Not clear Surgery,?steroid,?antifungal therapy
30 Eosinophilic Mucin Rhinosinusitis Proposed by Ferguson, Laryngosocope 2000 Eosinophilic mucin present without fungus A systemic disease with dysregulation of immunological control where eosinophilic mucin could be present without the presence of fungi.
31 Eosinophilic Mucin Rhinosinusitis Significantly associated with asthma, incidence of aspirin sensitivity, incidence of IgG1 deficiency Though systemic steroid could be useful, fungal immunotherapy & antifungal agents would be ineffective
32 AFRS Vs EMRS Ferguson 2000 Laryngoscope AFRS EMRS Age Younger (30.7 yrs) Older (48 yrs) BA 41% 91% ASA sensitivity 13% 54% Total IgE Mean 1941 mg/dl Mean 267 mg/dl Bilateral 55% 100%
33 Eosinophilic Mucin Rhinosinusitis In 2006, Saravanan et al found similar results to Ferguson, but was not statistically significant.
34 Management of Mucin-Related RS All forms treated almost the same at this point in time
35 Therapy of definite benefit Endoscopic sinus surgery 2 objectives Removal of polyps, inflammatory mucin, and fungal debris. Reversal of bony expansion into the orbit and brain. Successful surgical and medical management has been shown to reverse proptosis and orbital remodeling in patients with AFRS
36 Therapy of definite benefit Medical management Medical management consists of systemic and topical glucocorticoids. Other therapies (ie, systemic or topical antifungals, immunotherapy for fungal allergy) are controversial. The use of antifungal therapy is controversial.
37 Medical management Preop Short courses of systemic glucocorticoids. Studies doses are: 1 mg/kg prednisone for 10 days pre-op 40 mg daily for 5 to 10 days 30 mg daily for 5 days improved visualization of the surgical field (whereas 15 mg of prednisolone daily for 10 days preop appeared to have minimal benefit)
38 Medical management Postop Systemic glucocorticoids are the mainstay of postop management A suggested dose of prednisone 0.5 mg/kg daily and tapered over a few weeks to approximately 10 mg daily. The dose is slowly reduced by 1 to 2.5 mg/week to the lowest dose that maintains control of sinus symptoms.
39 Medical management Topical glucocorticoid instillations instillations of topical intranasal steroids, such as budesonide, should be initiated After the mucosa has remained normal for 2 to 3 years, we typically attempt to wean patients from their steroid instillations, as AFRS seems to burn itself out as patients reach the age of 30 to 40 years
40 Therapies of uncertain benefit Therapies that are not supported by high quality evidence include immunotherapy for fungal allergy and systemic and topical antifungal treatments.
41 Therapies of uncertain benefit Immunotherapy for fungal allergy adjunct to surgical and medical therapy No controlled clinical trials have been performed, but shown to be safe, with evidence for reduced rates of disease recurrence in some patients. ubcutaneous immunotherapy (SCIT) instead of oral forms of immunotherapy is suggested.
42 Therapies of uncertain benefit Antifungal agents limited to open-label trials or retrospective case series in adults and children. Taken together, these have not shown convincing benefit, and more rigorous studies are needed. There is also limited studies of the use of topical antifungals for treatment of AFRS. Based on the paucity of supportive data, consensus guidelines do not advocate use of oral or topical antifungal agents in AFRS
43 Therapies of uncertain benefit Investigational therapies include several monoclonal antibodies. Omalizumab was found to be beneficial for AFRS in a case report and in a retrospective chart review of seven AFRS patients who also had moderate or severe asthma There are clinical trials of anti-il-5 and anti-il-4/il-13 monoclonal antibodies for the related condition, CRS with NP. They may prove useful to patients with AFRS.
44 THANK YOU
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