Fungal Sinusitis: A Call for a Better Understanding

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Presentation transcript:

Fungal Sinusitis: A Call for a Better Understanding Hail M. Al-Abdely, MD Consultant, Infectious Diseases

What does it mean? Inflammation of the sinuses due to a fungus. Direct effect of the fungus or indirect.

What are the clinical forms? Allergic Fungal ball Invasive Acute Chronic - Invasive - Granulomatous DeShazo. Arch Otolaryngo Head Nech Surg 1997; 123:1181

FEATURES OF NONINVASIVE AND INVASIVE FUNGAL SINUSITIS SYNDROME COMMON CAUSES GEOGRAPHIC DISTRIBUTION HOST ASSOCIATED CONDITIONS Allergic fungal sinusitis Aspergillus Spp., Dematiaceous Humid areas Immune-competent Atopy, nasal polyps Sinus Mycetoma (fungus ball) Aspergillus Spp., Dematiaceous Humid areas Immune-competent Chronic sinusitis Acute invasive fungal sinusitis Mucorales, Aspergillus Spp Non-specific Diabetes, immune-suppressed Diabetes, cancer, iron chelating Chronic invasive fungal sinusitis Aspergillus fumigatus Non-specific Immune-suppressed Diabetes Granulomatous invasive fungal sinusitis Aspergillus flavus Tropical & subtropical Immune-competent None De Shazo: NEJM 337:257. 1997

Allergic Fungal Sinusitis (AFS)

Allergic Fungal Sinusitis (AFS) Most common form of fungal sinusitis A recently recognized 1976: First described in patients with Allergic broncho-pulmonary aspergillosis (Safirstein. Chest 70: 788) 1983: Few Cases with the histologic triad of necrotic eosinophils, charcot-Leyden crystals and non-invasive fungal hyphae and was named Allergic Aspergillus sinusitis (Katzenstein. J Allergy Clin Immunol 72:89) 1998: English-literature review revealed 263 cases. (Maning. Laryngoscope 108: 1485)

AFS: How common? Chronic rhinosinusitis is the most common chronic disease in the US affecting 37 million (14.13% of population). Vital Health Stat 1995, 10:89 Incidence of AFS in chronic rhinosinusitis is 7%. (Cody DT. Laryngoscope.1996; 4:169) In a recent prospective cohort from the US, fungi were isolated from 94% of patients with chronic rhinosinusitis. (Ponikau JU. Mayo Clin Proc.1999; 74:877) In a recent study from Austria, fungi were isolated from 91.3% from patients with chronic rhinosinusitis. 75.5% of patients had fungal elements on histopathology. (Braun H. Laryngoscope.2003; 113:264)

The Mayo Clinic Cohort (Ponikau JU. Mayo Clin Proc.1999; 74:877) Fungal Culture (Ponikau JU. Mayo Clin Proc.1999; 74:877)

(Ponikau JU. Mayo Clin Proc.1999; 74:877)

Pathogenesis of AFS

Eosinophilic mediators Local Factors -Mucostasis -Anatomic anomaly Enviromental -Fungal exposure Genetic -Atopy -Unknown + Exposure Fungal proliferation Antigen exposure Allergic Mucin Inflammatory trigger IgE mediated T-cell & other Edema Obstruction Stasis Reduced ventilation Inflammation Eosinophilic mediators (MBP, ECP & others) Marple: Laryngoscope 111:1006. 2001

Which fungus causes AFS? Aspergillus species. Phaeohyphomycosis: Bipolaris, Exerohilum, Dreschlera. Alternaria. Curvularia Exophiala. Others (rare) Fusarium, Scedosporium (Pseudallescheria).

Criteria for Diagnosis of AFS No consensus but several proposals that share: Presence of allergic mucin on histopathology Presence of non-invasive hyphae on histopathology +/- fungal culture Fungal Ig-E mediated hypersensitivity Nasal polyposis High-signal intensity opacification of sinuses on CT scan ? Associated atopy (65%) with asthma (50%) Marple: Laryngoscope 111:1006. 2001

CT and MRI scans in AFS The sinus filled with high signal intensity soft tissue Bone erosions (20% of cases) and extension to surrounding structures can happen BUT due to pressure and not invasion (Nussenbaum B,Otolaryngol Head Neck Surg 001;124:150–154) Remodeling is common MRI: hypointense central T1 signal, central T2 signal and the presence of increased peripheral T1/T2 enhancement .

Treatment Goals for AFS Clear current episode Reduce number of recurrences. Very common (90% of cases) Improve quality of life It’s NOT easy Patient education about the nature of the disease

Eosinophilic mediators Therapeutic Strategies for Allergic Fungal Sinusitis Surgery Irrigation Antifungals Exposure Fungal proliferation Antigen exposure Inflammatory trigger IgE mediated T-cell & other Edema Obstruction Stasis Reduced ventilation Allergic Mucin Steroids Immunotherapy Inflammation Eosinophilic mediators (MBP, ECP & others)

Management of AFS Clear current episode Prevent recurrence Surgery Steroids Desensitization to fungal antigens Antifungal therapy Combination of the above

Steroids Topical Systemic Indicated post-operative Efficacy is not well established But has the advantage of lower complications Systemic success of this strategy in the treatment of ABPA. Few studies indicated efficacy in reducing recurrences (Schubert MS, J Allergy Clin Immunol 1998;102:395–402. Use is limited by serious long-term complications

Immunotherapy Few and small studies Indicate reduction in recurrences up to 50% (Laryngoscope. 1998 Nov;108:1623) Problems: No adequate data Long and tedious process 3-5 years. Disease can worsen

Antifungal Therapy Prior to Azoles short courses of Amphotericin B were tried mainly because of the concern of invasive disease no success in reducing recurrences Recent data indicate significant success of azoles in ABPA Combining itraconazole with systemic steroids.

Steroids + itraconazole Retrospective study 139 patients Average F/U 31.4 months Strategy: Endoscopic surgery Itraconazole orally, continuous Topical steroids Short courses of low-dose systemic steroids Outcome: recurrence of disease in 50% BUT the need for surgery was 21%) Rains BM. Am J Rhinol. 2003 17(1):1-8.

Topical antifungal Ampho B tried as a nasal lavage for 4 weeks reduced nasal polyps by 39% J Laryngol Otol. 2002, 116(4):261-3.

Prognosis of AFS Mortality is rare even with extensive disease and extension to surrounding structures. Morbidity is high due to recurrent surgeries and nasal blockage Visual loss is rare Marple. Otolaryngol Head Neck Surg 2002;127:361-6.

Acute Invasive Sinusitis

Acute Invasive Sinusitis Relatively uncommon Life-threatening Typically in diabetics and the immunocompromised Caused by Mucorales of Zygomycetes (Rizopus, mucor). Aspergillus species. Fusarium. Scedosporium (Pseudallescheria boydii). Phaeohyphomycosis.

Mucormycosis Mucormycosis is unusual fungal infection caused by fungi of the order Mucorales from the class Zygomycetes of the phylum Zygomycota. Rizopus spp. are responsible for about 90% of reported cases. Identified predisposing factors include uncontrolled diabetes with ketoacidosis, cancer, immunosuppressive conditions and dialysis patients on deferoxamine therapy It affects primarily the sinuses with local destruction extending to the orbit and the brain. The lung is the second most common organ. The overall mortality rate is approximately 50% to 70%

Rizopus Spp. Absidia Spp. Cunninghamella Spp. Rizomucor Spp.

A retrospective chart review was conducted from 1985 to 2001. Mucormycosis (Zygomycosis) at King Faisal Specialist Hospital and Research Centre A retrospective chart review was conducted from 1985 to 2001. Source for cases identification was medical Records Cases were reviewed for demographic data risk factors clinical features relevant laboratory and radiological studies fungal cultures and histopathology Management, complications and outcome

Case Definition The diagnosis of mucormycosis was defined as: Definite: if the histopathology was positive for fungal hyphae typical of mucorales and positive culture Probable: if histopathology positive for fungal hyphae typical of mucorales or positive culture and compatible clinical and radiological features Possible: if sampling was not done or was negative on hisopathology and culture but has compatible clinical and radiological features

Results

Distribution of Mucormycosis Cases over the Years

Results # Cases (%) Male 13 (72.2) Female 5 (27.8) Age (median) 45 (range 4-83)

Clinical # Cases (%) Fever 11 Facial pain 7 Proptosis 6 Double vision 4 Headache Blindness 5 Palate necrosis Nasal Blockade 3

Diagnosis of Mucormycosis

Underlying Conditions in Patients with Mucormycosis

Fungal Culture in Patients with Mucormycosis All were Rizopus Spp.

Extent of Sinus Disease # cases % Localized lesion to sinus 2 18.2 Involvements of sinus +orbit 1 9.1 Involvements of sinus +orbit + palate Involvements of sinus +orbit + palate + brain 7 63.6

Site of Infection Related to Underlying Condition

Outcome of Patients with Mucormycosis

Outcome Related to Underlying Condition

Mortality Related to Type of Management 5 13

Conclusion of the study Mucormycosis is a relatively uncommon but aggressive fungal infection associated with high mortality. Sinus was the most common site especially in diabetics All the culture-positive cases were due to Rizopus Spp. Combined medical and surgical therapy provided the best outcome.

Management of Acute Invasive Fungal Sinusitis Life-threatening condition with the time factor as the main determinant of success Emergency surgery with radical debridement. Adjunctive aggressive antifungal therapy Amphotericin B is the only drug for mucormycosis Modify risk factors

Chronic Invasive Fungal Sinusitis

Chronic Invasive Fungal Sinusitis Poorly described entity Indolent course with soft-tissue invasion. Classified into two histological entities (DeShazo. Arch Otolaryngo Head Nech Surg 1997; 123:1181) Chronic invasive Invasion of vessels Immunocompromised and diabetics Caused mainly by Aspergillus fumigatus Chronic granulomatous invasive Immune competent individuals Non-caseating granulomatous inflammation, no vessel invasion Reported mainly in Sudan, India and Pakistan Caused by Aspergillus flavus and dematiaceous fungi

CHRONIC INVASIVE ASPERGILLOSIS OF THE PARANASAL SINUSES IN IMMUNOCOMPETENT HOSTS FROM SAUDI ARABIA Patient selection. Cases (N 23) involving positive isolates of Aspergillus from paranasal sinus material between1991 and 1997 grew Aspergillus and had histopathology showing fungi breaching mucosal barriers and causing tissue necrosis. Alrajhi et al: A J Trop Med Hyg 65:83. 2001

Alrajhi et al: A J Trop Med Hyg 65:83. 2001

Alrajhi et al: A J Trop Med Hyg 65:83. 2001

Alrajhi et al: A J Trop Med Hyg 65:83. 2001

Granulomata were found in 6 of 23 patients Fungal organisms: CHRONIC INVASIVE ASPERGILLOSIS OF THE PARANASAL SINUSES IN IMMUNOCOMPETENT HOSTS FROM SAUDI ARABIA Granulomata were found in 6 of 23 patients Fungal organisms: A. flavus 15 (65%) A. fumigatus 2 (9%) Aspergillus spp. 6 (26%) Two cases of visual loss No mortality Alrajhi et al: A J Trop Med Hyg 65:83. 2001

Management of Chronic Invasive Sinusitis Surgery Prolonged antifungal therapy

Conclusion Fungal sinusitis is a relatively common problem Understanding the nature of the disease determine the approach to therapy Surgery is the mainstay treatment for fungal sinusitis The diagnosis of allergic fungal sinusitis could mean a life-long relationship with the patient. Antifungal therapy is an absolute indication in acute and chronic invasive fungal sinusitis and a relative indication in allergic fungal sinusitis

Thank You