5.5.2.7. Fungus ball In addition to
AIFRS, immunocompromised patients can develop non-invasive
fungus balls that present differently than fungus balls in
immunocompetent patients (1567). In a retrospective review of 24
patients, 11 of 24 had some degree of immunocompromise. These
immunocompromised patients (organ transplant or DM) were more
likely to have aspergillus and non-dilated sinus ostia.
5.6. Allergic fungal rhinosinusitis
5.6.1. Introduction There is much debate regarding the role of fungi in
CRSwNP and whether the diagnostic group of AFRS truly represents
a unique disease. In spite of our limited knowledge regarding
the pathophysiology of CRSwNP, there is a subset of patients as
defined by the classic Bent-Kuhn criteria for AFRS who
demonstrate some phenotypic differences when compared to other
CRSwNP patients. The original Bent-Kuhn diagnostic criteria
(721) consist of the following:
- Nasal polyposis,
- Fungi on staining,
-
Eosinophilic mucin without fungal invasion into sinus
tissue,
- Type I hypersensitivity to fungi and
-
Characteristic radiological findings with soft tissue
differential densities on CT scanning.
Although used widely since their inception, many of these
criteria are not unique to AFRS patients. All CRSwNP patients
have nasal polyposis by definition, with a large proportion of
them also demonstrating eosinophilic mucin without fungal
invasion. Furthermore, as fungal detection techniques improve,
so does the sensitivity to detect them, with some studies
demonstrating fungal presence in almost 100% of patients, both
controls and CRS patients (592, 1568). Consequently it appears
that type I hypersensitivity and characteristic CT findings are
the only unique factors in Bent and Kuhn's criteria for AFRS
that allow it be distinguished from other forms of sinus
disease. Subsequently, a number of authors have found other
factors particular to AFRS. Demographically, AFRS patients are
younger, more likely to be African American and present with
more significant bone erosion/expansion than other CRSwNP
patients (728,1569,1570).
While some have reported
immunologic differences, with AFRS demonstrating increased mean
serum total IgE and IgG antiAlternaria antibodies when compared
to CRSwNP (723), this has not been conclusively demonstrated as
others report no significant differences (727-729, 1571). Many
questions remain unanswered:
Are there any significant
underlying immunologic differences between AFRS and other forms
of CRSwNP? What is the relevance of fungi or fungal specific IgE
to the pathophysiology of AFRS? Do these factors truly play a
role in the immunologic response or are they simply a defining
marker of the disease state?
5.6.2. Medical therapy Most reports on treatment options for AFRS are combined
into larger series addressing CRSwNP patients and this issue is
covered elsewhere in this document. It is therefore difficult to
discern if there are varying effects in the AFRS population as
opposed to the entire CRSwNP population. In general, medical
therapies have been divided into oral and topical steroids, oral
and topical anti-fungals, leukotriene antagonists and
immunotherapy. In all but the mildest cases of AFRS, it is felt
that medical therapy alone without surgical intervention, is not
effective in the long term, thus most efficacy studies examining
medical treatments have been performed post operatively
5.6.2.1. Oral steroids Oral steroid studies specific to AFRS patients have
generally been conducted in the postoperative setting where
benefit has been demonstrated. In a prospective, randomized
doubleblinded, placebo-controlled (DBPC) trial in AFRS patients
examining the effectiveness of postoperative oral steroids, as
well as the side effects of such treatments, patients received
oral prednisolone (50 mg qd x 6 weeks, then additional 6 week
taper) or placebo for two weeks after surgery (1572). All
patients received fluticasone nasal spray and oral itraconazole
for 12 weeks. At 12 week follow up, symptoms and endoscopy were
improved in the oral steroid group. All 12 patients in the
steroid group suffered from weight gain, 5 developed Cushinoid
features, 2 developed acne and 1 developed steroid induced
diabetes mellitus. At 18 months of follow up, patients who
stopped all treatment, including topical steroids, developed
recurrent disease. It is unclear if postoperative oral steroids
for 12 weeks had an impact at 18 months. A number of other
non-placebo controlled case series have been reported with
highly variable dosing protocols and durations, but generally
reporting a positive effect when using postoperative oral
steroids (1573-1578).
5.6.2.2. Topical steroids It does not appear that prospective studies on the
effects of topical steroids alone have been conducted in the
AFRS population. A case controlled study of surgery alone vs.
surgery plus the combination of postoperative oral and topical
steroid spray in AFRS patients demonstrated benefits of the
combined therapy at a minimum of 2 year follow up, as 50% of the
no steroid group recurred, while only 15% of the combined
steroid group recurred (1579).
5.6.2.3. Subcutaneous Immunotherapy (SCIT) SCIT may have efficacy in the short term (3-4 years),
however, its long-term efficacy is unclear. Fortunately, there
are a number of reports of both high dose and low dose
subcutaneous immunotherapy that have all demonstrated safety
(1580). A large retrospective, series reported that compliance
with immunotherapy for all fungal and non-fungal antigens was
beneficial in preventing recurrence of disease. A 3-4 year
course of subcutaneous immunotherapy (SCIT) demonstrated benefit
12-26 months after discontinuation (1581) and prolonged courses
of systemic steroids were not used in these patients (1582).
However a subsequent study by the same group on a smaller subset
of patients with longer term follow up ranging from 46 to 138
months failed to demonstrate any benefit of SCIT with 60% of
SCIT patients having normal mucosa or only mild oedema on
endoscopy, while 100% of non-SCIT patients having normal mucosa
or mild oedema (1583). This study was not randomized and
obviously has the potential for bias in selecting treatment
arms.
5.6.2.4. Anti-fungal therapy It is unclear if such therapies have a differing effect
in the AFRS subset of patients. Limited non-placebo controlled
case series have reported benefits of systemic anti-fungal
therapies in patients with AFRS (28, 1584). This is in contrast
to a Cochrane review of topical and systemic anti-fungal
therapies in all CRS patients, which failed to demonstrate any
benefit (1585).