First Aid, Chapter 7 Hypersensitivity Disorders, Allergic Bronchopulmonary Aspergillosis (ABPA) and Allergic Fungal Sinusitis

Question 1

What is ABPA an inflammatory and immune response to?

Answer 1

Aspergillus fumigatus colonization. Other fungi are rarely implicated.

Question 2

What are the pathophysiologic results of ABPA?

Answer 2

Poor mucus clearance and recurrent bronchial obstruction. The chronic mucoid impaction of bronchi leads to the development of bronchiectasis, pulmonary fibrosis, and pulmonary function compromise.

Question 3

What receptor on what cell in the lungs protects against Aspergillus? What binds to that receptor? What cytokines are stimulated?

Answer 3

The dectin-1 receptor on alveolar macrophages plays a critical role in defense against Aspergillus. B-1,3-glucan in fungal cell walls binds dectin-1, which leads to production of various cytokines, including, TNFa, IL-1B, IL-1a, IL-6, IL-10, and IFNg leading to Th1 response critical in host defense against this pathogen.

Question 4

What are the clinical features of ABPA in asthmatics as far as symptoms, CXR, and CT chest?

Answer 4

o Exacerbation of asthma symptoms (shortness of breath, cough, and wheezing), brown/tan sputum production, and systemic symptoms (fever and malaise)
o Pulmonary infiltrates on radiograph of the chest mid/upper lung fields (tram line, parallel lines, hilar adenopathy)
o Central- or upper-lobe bronchiectasis, pulmonary nodules and/or air trapping on CT of the chest.

Question 5

What are the clinical features of ABPA in CF patients as far as symptoms, CXR, and CT chest?

Answer 5

Similar to symptoms and radiographic findings seen in primary disease.

Question 6

Is ABPA due to fungal colonization or invasion?

Answer 6

ABPA is due to fungal colonization not local invasion.

Question 7

What is the goal of treatment of ABPA?

Answer 7

In cases with ABPA, the treatment goal is to prevent the development or progression of bronchiectasis and any worsening of pulmonary function.

Question 8

What is the significance of IgE levels in ABPA? What level indicates a flare?

Answer 8

Rising IgE levels can help predict an ABPA recurrence, with a doubling of the baseline IgE often indicating a flare of ABPA.

Question 9

What are the diagnostic criteria for ABPA in asthmatics? In CF? What are the major differences in the criteria?

Answer 9

Asthma:

• Positive immediate skin test to Aspergillus fumigatus -Total serum IgE >1000 ng/mL (417 IU/mL)
• Elevated A. fumigatus specific IgG and IgE
• Central bronchiectasisa
• Peripheral eosinophilia (>1000/mm3)

CF:

• Clinical deterioration not due to other causes
• Total serum IgE >1200 ng/mL (500 IU/mL)
• Positive immediate skin test to A. fumigatus
• Serum IgE or IgG antibodies to A. fumigatus
• Fixed chest film abnormalities (e.g., infiltrates or mucus plugging)

Differences:

• Total IgE>1000 in asthma, >1200 in CF.
• Central bronchiectasis in asthma, fixed chest film abnormality (infiltrates or mucus plugging) in CF
• peripheral eosinophilia in asthma but not CF
• clinical deterioration not due to other causes in CF

Same:

• positive immediate skin test to Aspergillus fumigatus
• elevated A. Fumigatus specific IgG and IgE

Question 10

What is seropositive ABPA?

Answer 10

Absence of bronchiectasis with presence of other criteria is seropositive ABPA (ABPA-S).

Question 11

A 15-year-old soccer player complains of chest tightness that is worsening despite highdose ICS/LABA combination therapy and frequent albuterol use. What alternative diagnosis should be considered?

Answer 11

VCD

Question 12

In the setting of which two lung diseases does ABPA typically occur?

Answer 12

Asthma and cystic fibrosis

Question 13

What is the treatment of ABPA?

Answer 13

—Treat with long-term corticosteroids. Daily prednisone (0.5–1 mg/kg) for at least 14 days; taper and continue for 3–6 months. Steroid therapy can be combined with itraconazole for at least 16 weeks. Voriconazole can be used as it has better absorption and requires less frequent dosing.

Question 14

What is the role of antifungal therapy is ABPA?

Answer 14

Antifungal therapy decreases antigenic stimulus for bronchial inflammation and decreases Aspergillus IgG. It may also affect steroid levels, thus allowing decreased doses of steroid with concomitant use.

Question 15

How often should serum IgE be monitored in treatment of ABPA?

Answer 15

Monitor response to steroid therapy with monthly total serum IgE.

Question 16

What are the categories of fungal sinusitis? What is the most common form?

Answer 16

Acute/fulminant (invasive form), chronic/indolent (also invasive), fungus ball, and AFS categories. AFS is the most common form.

Question 17

Where is AFS more prevalent?

Answer 17

Southern US

Question 18

What is AFS?

Answer 18

Allergic fungal sinusitis is a noninvasive hypersensitivity reaction to fungi affecting the nasal cavity and paranasal sinuses, resulting in the formation of thick fungal debris, mucin, and polyposis.

Question 19

What are the causative fungi in AFS?

Answer 19

Causative fungi are from the dematiaceous family (i.e., genera Bipolaris, Curvularia, Alternaria, Rhizopus, Drechslera, Helminthosporium, Fusarium, and Aspergillus).

Question 20

What percentage of CRS patients requiring surgery have AFS?

Answer 20

Approximately 5–10% of patients with chronic rhinosinusitis requiring surgery have AFS.

Question 21

What role does fungal culture have in AFS?

Answer 21

Positive fungal culture does not confirm the diagnosis of AFS, nor does a negative culture exclude it.

Question 22

What are Charcot-Leyden crystals composed of?

Answer 22

Eosinophil-degradation products.

Question 23

What is the pathophysiology of AFS?

Answer 23

AFS is due to an exaggerated immunologic reaction following exposure to a fungus to which the patient is sensitized. This results in the development of chronic edema and obstruction, leading to the obstruction of the sinuses, mucosal stasis, and fungal proliferation. The fungal proliferation further contributes to the hypersensitivity response and worsening of nasal symptoms.

Question 24

What are the signs and symptoms of acute AFS? Chronic AFS?

Answer 24

Acute: fever, nasal congestion, acute facial pain, HA, diplopia, acute loss of smell

Chronic: vision changes/loss due to ophthalmic nerve compression, proptosis, sinus tenderness to palpation/pressure, malaise, fatigue.

Question 25

What are CT sinus findings of AFS?

Answer 25

CT shows hyperattenuation, heterogeneous opacification, and calcification in affected sinus(es).

Question 26

What are the gross and histologic findings in AFS?

Answer 26

Allergic mucin
(gross): thick, tenacious, highly viscous, light tan to brown colored; (histologically) branching noninvasive fungal hyphae, sheets of eosinophils, and Charcot-Leyden crystals.

Question 27

What are the diagnostic criteria for AFS?

Answer 27

• Type I hypersensitivity to fungi confirmed on skin testing or by specific IgE
• Nasal polyposis
• Positive fungal stain of sinus contents
• Characteristic histology: Eosinophil-rich allergic mucin and fungal elements with no invasion of respiratory mucosa

Question 28

What is the treatment of AFS?

Answer 28

• Endoscopic sinus surgery: Surgical debridement of fungal debris and polyps
• Nasal saline irrigations: Provides mild symptomatic relief
• Oral corticosteroids: Usually initiated before surgery and most often continued 3–4 weeks postoperatively delayed the need for repeat surgery
• Topical nasal steroids: Most effective when begun postoperatively and chronically continued for control of inflammation
• Immunotherapy: Effectiveness is controversial, but this is frequently used as an adjuvant treatment
• Antifungals: Have not been shown to significantly modify clinical course

Question 29

What is the prognosis of AFS?

Answer 29

Chronic condition that requires life-long therapy, with recurrence of disease varying from 10–100%.

Question 30

What can predict AFS recurrence?

Answer 30

IgE level increase.