Allergic bronchopulmonary aspergillosis Presented by Natasorn Lekuthai, MD. September 23, 2022

1. Allergic
Brochopulmonary
Aspergillosis
Natasorn Lekuthai,MD.
Allergy and Immunology Fellowship
year 1
1

2. Overview
• Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction in
response to colonization of the airways with Aspergillus fumigatus.
• occurs almost exclusively in patients with asthma or cystic fibrosis.
• Susceptibility to development of ABPA is mediated by genetically determined inflammatory
responses strongly linked to atopy.
Middleton’s Allergy,Principle and Practice, 10th edition.
2

3. Epidemiology
• Among patients with persistent asthma is estimated at 1 to 2 percent, although rates up to 28
percent have been reported.
• Approximately 2% of Asthmatic patients and 1%-15% of Cystic Fibrosis develops ABPA.
• The prevalence of ABPA in asthmatic patients varies depending on the severity of asthma, presence
of immediate hypersensitivity to Aspergillus spp. and method of detection, and diagnostic criteria.
• Later, Agarwal and associates estimated overall prevalence of ABPA in asthmatic populations at
12.9% (95% confidence interval [CI] 7.9 to 18.9).3 The estimated pooled prevalence of Aspergillus
spp. sensitization in CF patients was 39.1% (95% CI 33.3-45.1), whereas ABPA was found in 8.9%
(95% CI 7.4-10.7) of CF patients.
• no gender predilection.
Middleton’s Allergy,Principle and Practice, 10th edition.
3

4. Epidemiology
• Usually manifesting between third and forth decades of life.
• High levels of outdoor spore counts may be associated with ABPA exacerbations, but a clear
relationship between level of exposure to Aspergillus and occurrence of ABPA has not been
established.
• Pathogenic Aspergillus generally grow easily and relatively quickly on routine bacteriologic
and mycological media in the clinical laboratory. Only pathogenic species are capable of
growth at 35 C–37 C , and A. fumigatus in particular is capable of growth at 50 c.
• Most isolates of A. fumigatus are capable of growth at oxygen tensions as low as 0.1%
oxygen but rarely grow on anaerobic plates.
Middleton’s Allergy,Principle and Practice, 10th edition.
4

5. Immunopathogenesis T helper type 2 cell plays an important roles
Exposure
- A. fumigatus spores are 3–5 μm in size, they can readily
deposit in the lower bronchial airways.
- secrete extracellular proteolytic enzymes of the aspartic,
serine, and metalloprotease classes
- hyphae are produced and can invade between and through
epithelial cells
Colonization
- Susceptible hosts include individuals with cystic fibrosis (CF)
or asthma. These populations have abnormalities in their
airway mucosal defenses, including mucociliary clearance and
epithelial cell function and may include the biofilm present in
the airways of these patients, contributing to impaired spore
removal.
J. Fungi 2016, 2(2), 17
Clin. Exp. Allergy 2015, 45, 1765–1778
Clin. Microbiol. Infect. 2014, 20, 1254–1264
Microbiol. Immunol. 2013, 57, 193–197
Immune response
5

6. Pathophysiology of allergic bronchopulmonary aspergillosis.
Richard B. Moss Eur Respir J 2014;43:1487-1500
PRRs
T cells response not by a single
antigen, but by a variety of
Aspergillus spp. antigens (e.g.,
Asp f 1, Asp f 2, Asp f 3, Asp f
4, Cr f 1, and Catalase 1)
6

7. Clinical features : Signs and symptoms
- In asthmatic patient ; recurrent exacerbations
- Chronic productive cough and wheezing
- pleuritic chest pain
- blood stain mucus ,expectoration of golden-brownish mucus
- Hemoptysis, especially in severe bronchiectasis
- Constitutional symptoms ; low grade fever, myalgia, weight loss
- In severe cases, episodes of bronchial obstruction, fever, malaise, expectoration of brownish mucus
plugs, and, at times, hemoptysis may occur.
- Wheezing is not always evident, and some patients present with asymptomatic pulmonary
consolidation.
Middleton’s Allergy,Principle and Practice, 10th edition.
7

8. Clinical Stages of ABPA
Sunman, B., Ademhan Tural, D., Ozsezen, B., Emiralioglu, N., Yalcin, E., & Özçelik, U. (2020). Current approach in the diagnosis
and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Frontiers in Pediatrics, 8, 582964
8

9. The International Society for Human and
Animal Mycology (ISHAM) Criteria
9

10. Modified Rosenberg-Patternson
criteria
10

11. The new diagnostic criteria (Japan)
Asano, K., Hebisawa, A., Ishiguro, T., Takayanagi, N., Nakamura, Y., Suzuki, J., ... &
Program, J. A. R. (2021). New clinical diagnostic criteria for allergic bronchopulmonary
aspergillosis/mycosis and its validation. Journal of Allergy and Clinical
Immunology, 147(4), 1261-1268.
11

12. The new diagnostic criteria (Japan)
Asano, K., Hebisawa, A., Ishiguro, T., Takayanagi, N., Nakamura, Y., Suzuki, J., ... &
Program, J. A. R. (2021). New clinical diagnostic criteria for allergic bronchopulmonary
aspergillosis/mycosis and its validation. Journal of Allergy and Clinical
Immunology, 147(4), 1261-1268.
12

13. Screening for ABPA in Cystic fibrosis
13

14. Sunman, B., Ademhan Tural, D., Ozsezen, B., Emiralioglu, N., Yalcin, E., & Özçelik, U. (2020). Current approach in the diagnosis
and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Frontiers in Pediatrics, 8, 582964
14

15. Criteria who has cystic fibrosis
15

16. 16

17. Differrences of ABPA in CF and Asthma
Sunman, B., Ademhan Tural, D., Ozsezen, B., Emiralioglu, N., Yalcin, E., & Özçelik, U. (2020). Current approach in the diagnosis
and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Frontiers in Pediatrics, 8, 582964
17

18. Sunman, B., Ademhan Tural, D., Ozsezen, B., Emiralioglu, N., Yalcin, E., & Özçelik, U. (2020). Current approach in the diagnosis
and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Frontiers in Pediatrics, 8, 582964
18

19. Chest radiograph
19

20. Gloved finger shadow
Journal of Thoracic Imaging 21(1):76-90, March
2006.
Ring shadow
20

21. Tram line Parallel line
21

22. High-resolution computed tomography
(HRCT)
22

23. Central bronchiectasis
23

24. Radiologic Staging of Allergic
Bronchopulmonary Aspergillosis
Middleton’s Allergy,Principle and Practice, 10th edition.
24

25. Treatment
• Goal of treatment
1. reduction of symptoms of either asthma or CF
2. reducing pulmonary inflammation
3. treatment of exacerbations of ABPA
4. prevent progression to end-stage fibrotic lung disease.
25

26. Oral glucocorticoid
• The most referenced regimen for initial treatment of ABPA (with new pulmonary infiltrates)
has been with oral prednisone 0.5 mg/kg daily for 1–2 weeks, then on alternate days for
6–8 weeks ( or to 3 months) , then followed by a slow taper by 5–10 mg every two
weeks.
• Acute exacerbations should be treated with prednisone, 0.5 to 1.0 mg/kg/day for 1 to 2
weeks, followed by 0.5 mg/kg/day for 6 to 12 weeks on clinical remission, then tapering of
the dose until the pre-exacerbation dose is reached..
J. Allergy Clin. Immunol. 2002, 110, 685–692.
Ther. Adv. Respir. Dis. 2012, 6, 173–187.
Allergy 2005, 60, 1004–1013. 26

27. Oral glucocorticoid
• Total serum IgE level is another useful marker to guide treatment and should be checked
every 6–8 weeks after start of glucocorticosteroid therapy and every eight weeks for at least
one year .
• While the elevated IgE levels are not expected to return to normal, despite treatment, it is
useful to compare follow up values to each patient’s unique baseline level. In a recent study
increases in the total IgE serum level of >50% accompanied exacerbations in >90% of
patients
• Diagnostic imaging with high resolution CT or chest roentgenogram should be repeated
after 4–8 weeks of treatment to assess persistence or clearance of lung infiltrates
Management of allergic bronchopulmonary aspergillosis: A review and update. Ther. Adv. Respir. Dis. 2012, 6, 173–187.
A. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary
aspergillosis. Mycoses 2016, 59, 1–6.
27

28. Intravenous glucocorticoid
• Pulse steroid therapy consists of Intravenous methylprednisolone (10–20 mg/kg/day)
infused daily for three consecutive days every four weeks. In the literature, there are no
controlled trials comparing oral steroids to intravenous steroids.
• However, these reports had few patients and were not controlled studies. There is no long-
term follow up data to further explore the effect this treatment plan had on clinical
outcomes.
Singh Sehgal I., Agarwal R. Pulse methylprednisolone in allergic bronchopulmonary
aspergillosis exacerbations. Eur. Respir. Rev. 2014;23:149–152
28

29. Inhaled corticosteroid
• There is no role for inhaled corticosteroid monotherapy in the treatment of serologic ABPA.
• A double-blind placebo controlled trial of beclomethasone did not show any clinically
significant improvement . A small case series suggested that inhaled corticosteroids may be a
useful adjunct in treatment of ABPA.
• However, for decades, researchers have failed to define a role of inhaled corticosteroids in
the treatment of ABPA and their precise place remains elusive. A double-blind placebo
controlled trial of beclomethasone did not show any clinically significant improvement
Inhaled beclomethasone dipropionate in allergic bronchopulmonary aspergillosis. Report to the Research Committee of the British Thoracic Association. Br. J. Dis. Chest1979, 73, 349–356.
Usefulness of inhaled high-dose corticosteroids in allergic bronchopulmonary aspergillosis. Chest 1993, 103, 1614–1617. 29

30. Antifungal agents
• Steroid-sparing effect.
• Used to reduce the antigen burden arising from fungal colonization of the airway. It is then
expected that the reduction in antigenic stimulation would result in decreased inflammation
and reduced disease severity and progression.
Moreira A.S., Silva D., Ferreira A.R., Delgado L. Antifungal treatment in allergic bronchopulmonary
aspergillosis with and without cystic fibrosis: A systematic review. Clin. Exp. Allergy. 2014;44:1210–1227.
30

31. Itraconazole
• Itraconazole is an orally-administered triazole that has fewer side effects and a wider spectrum of activity
compared to ketoconazole.
• Dosage : 200 mg twice daily for 6 months for corticosteroid-dependent ABPA.
• There are two randomized controlled trials using itraconazole in ABPA. Stevens et al. in 2000 published findings
from their randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo
for 16 weeks in patients.
• The study demonstrated that in patients with corticosteroid-dependent ABPA adding itraconazole can lead to
clinical improvement without significant risk of toxicity. Additionally, the lower dose used in the open label trial
showed benefit as well.
• A response was defined as at least a 50% reduction in steroid dose, a 25% reduction in serum IgE concentration
and either an improvement of 25% in exercise tolerance testing or pulmonary function testing or a resolution of
pulmonary infiltrates on imaging. There was also a follow-on open-label arm of the trial where all patients
received itraconazole 200 mg daily (a lower dose than in the placebo-controlled trial) for 16 weeks.
A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N. Engl. J. Med. 2000, 342, 756–762 31

32. Ketoconazole
• ketoconazole is not typically used for long-term therapy given the increased incidence of
toxicity compared to other azoles.
32

33. Voriconazole and posaconazole
• Better bioavailibilty and have been better tolerated in some patients.
• This small study suggests that both voriconazole and posaconazole can be alternative
antifungal therapy in patients with ABPA; however, it is limited as a retrospective study in an
asthmatic population.
Chishimba L., Niven R.M., Cooley J., Denning D.W. Voriconazole and posaconazole improve asthma severity in allergic
bronchopulmonary aspergillosis and severe asthma with fungal sensitization. J. Asthma. 2012;49:423–433
33

34. Immunotherapy
• A humanized monoclonal antibody to IgE that binds to free serum IgE, interfering with IgE
binding to its high-affinity receptor on mast cells and basophils, and also downregulating IgE
receptors on lymphoid cells.
• The dosing recommendations for omalizumab are currently based on treatment of asthma
with the goal of decreasing the total free IgE to less than 50 ng/mL (20.8 IU/mL). The
drug is delivered either once every two or four weeks by subcutaneous injection.
• There have been many reports and open-label trials in >100 published cases that report
benefits of usual or only modestly increased omalizumab doses in patients with ABPA,
suggesting that it may be an effective steroid-sparing treatment that reduces exacerbations of
ABPA in patients with asthma or cystic fibrosis.
34

35. Omalizumab
• Voskamp et al. have now reported the first randomized, blinded, controlled trial with 13
asthmatic ABPA patients who participated in a four-month treatment with omalizumab
(750 mg monthly) or placebo, followed by a three-month washout period in a cross-over
design. The study met its primary endpoint of showing a significant reduction in exacerbations
among patients receiving active treatment with omalizumab. It also met secondary outcomes
of decreased mean fractionated exhaled nitric oxide, a known marker of lower airway
inflammation, and reduced basophil reactivity, a measure of allergic cellular response, during
treatment.
Clinical efficacy and immunologic effects of omalizumab in allergic
bronchopulmonary aspergillosis. J. Allergy Clin. Immunol. Pract. 2015, 3, 192–199.
35

36. Allergic
fungal
rhinosinusitis
36

37. Allergic fungal sinusitis
• Allergic fungal rhinosinusitis (AFRS) is a distinct type of chronic rhinosinusitis (CRS), accounting for
between 5 and 10 percent of all CRS cases.
• Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP)
characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and
characteristic computed tomographic and magnetic resonance imaging findings in paranasal sinuses.
• All forms of CRS are defined as inflammatory conditions involving the paranasal sinuses and linings
of the nasal passages that last 12 weeks or longer AFRS is a distinct subtype of CRS that arises as a
result of a localized allergic reaction to noninvasive fungal growth in areas of compromised mucus
drainage.
• Chronic disorder with significant morbidity and a high recurrence rate needing long-term
follow-up.
37

38. Allergic fungal sinusitis
• Those with AFRS, depending on geographic region, more commonly involved fungal genera
are Aspergillus and dematiaceous (melanin-producing) fungi other than Alternaria species,
such as Bipolaris and Curvularia species.
Dykewicz, Mark S. et al. Allergic fungal rhinosinusitis
Journal of Allergy and Clinical Immunology, Volume 142, Issue 2, 341 - 351
38

39. Pathogenesis
Dykewicz, Mark S. et al. Allergic fungal rhinosinusitis
Journal of Allergy and Clinical Immunology, Volume 142, Issue 2, 341 - 351
39

40. Pathogenesis
• Patients with AFRS have notably higher levels of serum IgE antifungal antibodies, as well as
eosinophil-rich mucus, both type 2 responses that have been attributed traditionally to
exaggerated TH2 adaptive immune responses.
• Group 2 innate lymphoid cells (ILC2s) are the innate immunity analog to TH2 cells in
adaptive immunity in that both cell types produce IL-5, IL-13, and IL-4, the latter in TH2 and
some ILC2 subsets.
• CD8+ T cells did not proliferate or activate in patients with AFRS.
• There were lower percentages of peripheral regulatory T cells (which could result in
increased type 2 responses) but also increased numbers of TH17 cells, suggesting that a
TH17- driven response could promote aggravation of nasal polyposis.
Dykewicz, Mark S. et al. Allergic fungal rhinosinusitis
Journal of Allergy and Clinical Immunology, Volume 142, Issue 2, 341 - 351
40

41. Signs and Symptoms
• The four cardinal symptoms of CRS are:
●Anterior and/or posterior nasal mucopurulent drainage
●Nasal obstruction, nasal blockage, congestion
●Facial pain, pressure, and/or fullness
●Reduction or loss of sense of smell
41

42. Signs and Symptoms
• Severe symptoms : bony expansion or erosion: double or reduced vision, proptosis, dramatic
periorbital edema, ophthalmoplegia, facial dysmorphia, other focal neurologic signs, severe
headache, meningeal signs, or significant or recurrent epistaxis
42

43. Bent and Kuhn criteria for diagnosis
Hoyt, A. E., Borish, L., Gurrola, J., & Payne, S. (2016). Allergic fungal rhinosinusitis. The
Journal of Allergy and Clinical Immunology: In Practice, 4(4), 599-604.
43

44. Diagnostic criteria for AFRS
Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing
definitions for clinical research and patient care. J Allergy Clin Immunol.
2004;114:S155–S212. 44

45. Hoyt, A. E., Borish, L., Gurrola, J., & Payne, S. (2016). Allergic fungal rhinosinusitis. The
Journal of Allergy and Clinical Immunology: In Practice, 4(4), 599-604.
45

46. Lund Mackay score for staging
46

47. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it
used and what does it predict? Otolaryng Head Neck Surg. 2007 Oct;137(4):555-61. 47

48. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it
used and what does it predict? Otolaryng Head Neck Surg. 2007 Oct;137(4):555-61. 48

49. Imaging
CT scan in patients with AFRS demonstrationg
complete opacification of the left maxillary sinus
(star) with central hyperattenuation (arrow).
- Bilateral, multisinus involvement is most common, although
unilateral multi sinus involvement is also seen.
- Multiple punctate foci of high attenuation, a serpentine pattern,
or more diffuse, ground glass type high attenuation.
- The most commonly involved sinus is the ethmoid sinus. The
presence of mucin and local inflammatory changes may result in
expansion of the sinus(es) and may cause osseous erosion or
remodelling.
- Local bony loss is much more common in AFRS than in other
forms of chronic rhinosinusitis and bone erosion.
- The high protein concentration of allergic mucin causes T1
central low signal and T2 central signal void.
Oscher J.2011 Fall; 11(3): 271–275. 49

50. Oscher J.2011 Fall; 11(3): 271–275.
Computed tomography demonstrating the
heterogenous signal intensity that is
characteristic of allergic fungal rhinosinusitis
Sinus computed tomography scan of a pateint with arrows
showing complete opacification of both anterior ethmoid
(upper st of arrows) and maxillary ( lower set of arrows)
sinuses and hyperdensities within these same areas. 50

51. Arshad FA, Kara A, Mirza S (2019) An Update on the Criteria for Diagnosing Allergic Fungal Rhinosinusitis: A Review of the Literature. J Otol Rhinol 8:2.
51

52. Dykewicz, Mark S. et al. Allergic fungal rhinosinusitis
Journal of Allergy and Clinical Immunology, Volume 142, Issue 2, 341 - 351
52

53. Treatment
• The vast majority of clinical studies in the AFRS literature indicate that medical therapy alone
is usually ineffective in alleviating symptoms and that surgical intervention, alone or in
combination with medical therapy
• Except for the mildest cases, AFRS requires surgical intervention, followed by adjuvant
medical therapy.
53

54. Treatment
Surgical Management
Post operative surgical
Management
Preoperative medication
Surgery technique
Revision surgery for AFRS
- Oral steroids
- Topical steroids
- Oral antifungals
- Topical antifungals
- Advanced Therapies ;
Biologics, Immunotherapy
Medikeri G, Javer A. Optimal Management of Allergic Fungal Rhinosinusitis. J Asthma Allergy. 2020 Sep 11;13:323-332.
54

55. Surgery
• Functional endoscopic sinus surgery is usually the preferred modality of surgical
intervention. Complete debridement of all fungal debris and eosinophilic mucin is vital
because incomplete debridement has been linked to early recurrence of the disease and the
need for revision surgery.
55

56. Oral and topical corticosteroids
Preoperative
• reduce the inflammatory response----> polyp regression and decreased sinomucosal edema.
• decrease symptoms arising from mechanical obstruction and improve intraoperative visualization of sinonasal anatomy during functional endoscopic sinus
surgery.
Postoperative
• decrease disease recurrence.
- In a study by Schubert and Goetz, patients taking postoperative oral corticosteroids for as little as 2 months had significant clinical improvement for 12
months, with 12 months of therapy having the best clinical outcome. Patients receiving postoperative oral corticosteroids can also be maintained in
lower stages of the disease.
- In a study by Rupa et al, all patients receiving postoperative systemic steroids (50 mg/d 6 weeks and then an additional 6-week taper had an
improvement in symptoms and endoscopy at 12-week follow-up. All patients in this study received intranasal fluticasone nasal spray and oral itraconazole.
However, patients in the steroid arm also had side effects from systemic steroids, including weight gain, Cushingoid features, acne, and steroid-induced
diabetes mellitus.
- Based on a systematic review, topical corticosteroid therapy, such as budesonide sinonasal rinses, after completion of oral corticosteroid therapy has
been proposed as a means to prevent disease recurrence, but the recommended duration is uncertain. With at least 2 years of follow-up, patients who
received a variable duration of combined oral and topical corticosteroids postoperatively had a better clinical outcome and decreased disease recurrence
compared with those undergoing surgery alone.
- Prednisone starting at 40mg per day bringing it down by 10 mg over 5-day intervals and then stopping it while at the same time continuing with
topical budesonide treatment.
- Rupa, V., Jacob, M., Mathews, M.S. et al. A prospective, randomised, placebo-controlled trial of postoperative oral steroid in allergic fungal sinusitis.Eur Arch Otorhinolaryngol 267, 233 (2010)
- Ikram, M., Abbas, A., Suhail, A., Onali, M. A., Akhtar, S., & Iqbal, M. (2009). Management of allergic fungal sinusitis with postoperative oral and nasal steroids: a controlled study. ENT: Ear, Nose &
Throat Journal.
Medikeri, G., & Javer, A. (2020). Optimal management of allergic fungal rhinosinusitis. Journal of Asthma and Allergy, 13, 323.
56

57. Antifungal drugs
Preoperative
- In a study by Patro et al, patients with AFRS receiving preoperative itraconazole for 1
month (200 mg BD for 2 days followed by 100 mg BD for 26 days) before surgery had
decreased Sino-Nasal Outcome Test 20 scores, Lund-MacKay scores, Kupferberg nasal
endoscopic grades, polyp size, hyperdensities on CT imaging, and postoperative fungal cultures
compared with control subjects.
- However, a Cochrane review of topical and systemic antifungal therapies in patients
with all phenotypes of CRS did not demonstrate any clinical benefit.
- Oral antifungals do not seem to drastically improve symptom scores or radiological
scores, but could be tried in some recalcitrant cases as adjunctive therapy together with
topical steroids.
Patro SK, Verma RK, Panda NK, Chakrabarti A, Singh P. Efficacy of preoperative itraconazole in allergic fungal rhinosinusitis. Am J Rhinol Allergy 2015;29:299-304.
Sacks, P. L., Harvey, R. J., Rimmer, J., Gallagher, R. M., & Sacks, R. (2011). Topical and systemic antifungal therapy for the symptomatic treatment of chronic
rhinosinusitis. Cochrane database of systematic reviews.
Medikeri, G., & Javer, A. (2020). Optimal management of allergic fungal rhinosinusitis. Journal of Asthma and Allergy, 13, 323. 57

58. Biologic agents : Omalizumab
• In asthmatic patients endotyping (through identification of increased blood and tissue
eosinophilia, IgE levels, and expression of type 2 inflammatory biomarkers, such as IL-4, IL-5,
IL-13, and periostin) has been successfully applied to selection of biologic agents that benefit
asthma. Beyond limited reports of omalizumab use in AFRS cited earlier, there is a good
rationale for use of biologic agents in patients with AFRS, given that it is a type 2–driven
disease and previous evidence of benefit of some agents in patients with CRSwNP. Formal
studies of biologics in patients with AFRS are required.
58

59. Biologic agents : Dupilumab
• Dupilumab is a new drug that has recently been approved for use in patients with CRSwNP. It
has shown some promise in some RCTs which show reduction in polyp size, sinus
opacification and symptom severity.
Medikeri, G., & Javer, A. (2020). Optimal management of allergic fungal rhinosinusitis. Journal of
Asthma and Allergy, 13, 323.
59

60. Allergen immunotherapy
• No firm conclusions about efficacy of allergen immunotherapy (AIT) in AFRS can be made
because of a general lack of placebo-controlled arms in studies. Both subcutaneous
immunotherapy (SCIT) and sublingual AIT have been reported to confer clinical benefit in patients
with AFRS. Even high-dose fungal AIT has been shown to be safe in 8 patients with AFRS, one
treated for up to 43 months, with no increased risk of local reactions or need for dose adjustments.
• In generally uncontrolled studies by Mabry et al, patients with AFRS had improved clinical
outcomes after 1-3 years of SCIT, with a decrease in polyp recurrence, nasal crusting, allergic
mucin, need for systemic steroids, less recurrence and absence of any severe adverse reactions.
• The use of sublingual immunotherapy in patients with AFRS has been associated in an uncontrolled
study with favorable outcomes with decrease in subjective symptoms, physical findings, serum IgE
levels, and Lund-McKay scores, with the absence of any significant side effects.
Medikeri G, Javer A. Optimal Management of Allergic Fungal Rhinosinusitis. J Asthma Allergy. 2020 Sep 11;13:323-332.
60

61. Take Home Messages
• Host and Environmental factors can increase the risk for AFRS
• Fungi most commonly associated with AFRS can differ from those that cause infectious fungal
sinusitis
• AFRS is predominantly driven by type 2 inflammatory responses, both adaptive and innate.
• Sinus surgery is essential for mananagent of most patients.
• Oral corticosteroids have demonstrated benefit in patients with AFRS
• AFRS is often a recurrent and chronic diseases.
61