International Journal of Pediatric Otorhinolaryngology Extra (2009) 4, 134138

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CASE REPORT

Young child with cystic brosis and sinonasal destructive polyposis which resolved incidentally with oral antifungals
Z.A. Dewji a,*, J.P. Ludemann c, J.A. Gardiner b
a

University of Manitoba, Canada Department of Ophthalmology and Vision Science University of British Columbia, Canada c Division of Otolaryngology, University of British Columbia, Canada
b

Received 29 February 2008; received in revised form 8 October 2008; accepted 10 October 2008 Available online 29 November 2008

KEYWORDS
Sinonasal polyposis; Cystic brosis; Allergic fungal sinusitis; Proptosis

Summary Cystic brosis (CF) affects between 1 in 2000 and 1 in 4500 children of European descent [R.S. Mendelsohn, B.M. Cohen. Otorhinolaryngologic aspects of cystic brosis. Archives of Otolaryngology 79 March (1964) 31217]. There have been few reported cases of fungal sinus infections in patients with CF [S.K. Wise, T.T. Kingdom, L. McKean, J.M. DelGaudio, G. Venkatraman. Presence of fungus in sinus cultures of cystic brosis patients. American Journal of Rhinology 19 January February (1) (2005) 4751]. We report a unique case of a young male with CF presenting with severe destructive sinonasal polyposis, which was refractory to all treatment until he was treated for a concomitant fungal bronchopulmonary infection. # 2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Cystic brosis is an autosomal-recessive disorder with variable penetrance. CF affects the exocrine glands and multiple organ systems, eventually resulting in such complications as chronic respiratory infections, pancreatic insufciency and otolaryngologic manifestations, which include chronic sinusitis and sinonasal polyposis. CF is caused by defects in the gene for cystic brosis transmembrane conductor regulator (CFTR). This gene codes for a transmembrane regulator protein which acts as a chloride channel. The
* Corresponding author. E-mail address: dewj@hotmail.com (Z.A. Dewji).

chromosome 7 mutation leads to thickened mucous and impaired mucociliary clearance. Nasal polyposis has been reported to have an incidence of 848% in children with CF [1,3]. Fungal sinusitis may be invasive (acute or chronic) or non-invasive (allergic or non-allergic). Allergic fungal sinusitis (AFS) has recently been recognized as a common cause of adult chronic sinusitis with polyposis and may be recalcitrant to endoscopic sinus surgery, topical saline and corticosteroids [4]. Interestingly, AFS has rarely been diagnosed in children [5] and more rarely in children with CF [2]. We report here an unusual case of a 4-year-old with cystic brosis who had severe, destructive sino-

1871-4048/$ see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pedex.2008.10.003

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nasal polyposis causing proptosis and hypertelorism. AFS was suspected but laboratory conrmation could not be achieved. Eventually, the patient needed oral antifungal therapy for a pulmonary fungal infection; this incidentally resulted in complete, long-term resolution of his sinusitis and polyposis and stabilization of his ocular ndings.

2. Case report
A 4-year-old, Caucasian male, with cystic brosis diagnosed by sweat chloride and DF508 gene mutation testing, presented to the British Columbia Childrens Hospital for the evaluation of nasal congestion and snoring. Physical examination demonstrated hypertelorism, a widened nasal dorsum and large nasal polyps bilaterally. Despite therapy with Mometasone nasal steroid spray, his symptoms persisted. The patient returned 2 months later with continued nasal obstruction and mild obstructive sleep apnea. His purulent sinusitis and bronchitis improved with oral antibacterial therapy. On examination, he had telecanthus, hypertelorism, 2 mm of relative left proptosis with normal motility and normal vision. CT scan (Figures 13) of the sinuses demonstrated extensive polyposis. The maxillary antra and ethmoid sinuses were almost completely opacied bilaterally, with expansion of the left ethmoid sinuses. In addition, the left lamina papyracea was markedly thin and partial destruction of the left inferior turbinate was noted. Furthermore, non-contrast-enhanced CT soft tissue windows revealed layering of inammatory debris, suggesting AFS [11]. A 5-day course of Prednisone (1 mg/kg daily) was administered pre-operatively and a functional endoscopic sinus surgery (FESS) was performed; specically, bilateral polypectomies, partial anterior ethmoidectomies and maxillary antrostomies. There was no signicant reduction in polyp size preoperatively. However, intra-operatively, copious yellow-green material, the consistency of peanut butter, was removed and sent for gram stain and culture for fungus and bacteria. Laboratory analysis of this material was negative for fungi, but positive for Escherichia coli. Biopsies of nasal bone and mucosa failed to show evidence of fungal infection. The patients pre-operative WBC count, eosinophil count, total IgE count were within normal limits. Subsequent allergy testing was positive for

Figs. 13 Non-contrast CT scan of the sinuses demonstrating extensive polyposis. The maxillary antra and ethmoid sinuses are almost completely opacied bilaterally, with expansion of the left ethmoid sinuses, resulting in hypertelorism and left proptosis. The left lamina papyracea is markedly thin and there is partial destruction of

the left inferior turbinate. Non-contrast-enhanced CT soft tissue windows revealed layering of inammatory debris, suggesting AFS.

136 mold (Aspergillis fumigatus), dogs, cats and dust mites. The patient returned 10 weeks post-op with recurrent nasal symptoms after initial improvement. On examination, he continued to have hypertelorism, telecanthus and left proptosis. The right nasal cavity was completely obstructed while the left was only partially obstructed. In addition, polyps were growing through the left inferior turbinate. CT scan showed continued extensive opacication of the sinuses similar to previous CT examinations. A second pre-operative 5-day course of Prednisone (1 mg/kg daily) was administered and again no signicant reduction in polyp size was noted. Subsequently, a second FESS was carried out which included bilateral polypectomies, partial left inferior turbinectomy (removing only the polypoid tissue that had eroded through the inferior turbinate) and revision ethmoidectomies. All sinus cavities were irrigated with saline and 10 ml of Ciprooxacin otic drops were instilled into the sinus cavities. Cultures once again returned negative for fungal infection and no organisms were seen on histopathology. Six months post-op, the patient returned again with dramatic worsening of his nasal obstruction despite conscientiously using saline lavage followed by nasal steroid spray. In addition, the patient was now experiencing frontal headaches and subjective widening of his nasal bridge (Figure 4). A third preoperative 5-day course of Prednisone (1 mg/kg daily), which again appeared to have little effect on polyp size, and FESS operation with bilateral polypectomies plus adenoidectomy was performed. The patient again had transient improvement in his nasal symptoms. One year later, he returned with

Z.A. Dewji et al.

Fig. 5 Chest radiograph showing large areas of consolidation/atelectasis involving the right upper lobe (RUL), right lower lobe superior segment and the left lingula.

Fig. 4 Picture of patient following his third FESS operation depicting hypertelorism and telecanthus and left proptosis.

moderate nasal obstruction, post-nasal drip and a new productive cough. Chest radiograph (Figure 5) showed large areas of consolidation/atelectasis involving the right upper lobe (RUL), right lower lobe superior segment and the left lingula. CT chest (Figures. 6 and 7) showed focal RUL bronchiectasis and a left anteromedial linear RUL opacity with bronchial mucus impaction. At this time, the patient was found to have uctuating IgE levels. Sputum culture was positive for Aspergillus. At 27 kg, he was prescribed a 9-month course of 100 mg Itraconozole daily and 5 mg Prednisone every other day for allergic bronchopulmonary aspergillosis. He was also prescribed Amphotericin nebulization through the oral cavity (little, if any, reached his nasal cavity). Following this treatment, he was found to have essentially complete dramatic incidental resolution of his sinonasal polyposis. His proptosis showed subjective improvement and his hypertelorism remained stable. The patient has been asymptomatic for 2 years, while receiving Amphotericin nebulizations and daily Mometasone nasal steroid spray. He has minimal nasal turbinate edema but no visible sinonasal polyps. His hypertelorism, telecanthus and 12 mm of relative proptosis on the left have stabilized. He has 20/20 vision, normal colour vision, 40 s of stereopsis, no ocular muscle imbalance and normal anterior segments and fundi (Figure 8). His quality of life has improved signicantly.

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Figs. 6 and 7 impaction.

CTchest showed focal RUL bronchiectasis and a left anteromedial linear RUL opacity with bronchial mucus

3. Discussion
There is a broad differential for sinonasal polyposis and concomitant fungal disease. This includes: AFS, chronic indolent sinusitis, mycetoma fungal sinusitis, fulminant (invasive) sinusitis and eosinophilic mucin sinusitis. AFS is thought to result from an IgE hypersensitivity to environmental fungi. AFS is non-invasive but causes severe, recalcitrant chronic sinusitis and sinonasal polyposis. AFS is not a well recognized complication of CF; however, it has been hypothesized that the CFTR gene mutation may play an important role in its pathogenesis [6]. For adults, AFS diagnostic criteria have been developed: (1) Type 1 IgE hypersensitivity, (2) hyper-attenuation on CT, (3) nasal polyps, (4) aller-

Fig. 8 Picture of patient as of January 2008 showing stabilization of his hypertelorism, telecanthus and proptosis.

gic mucin, and (5) positive fungal smear [4]. Controversy exists regarding all the above criteria are needed to diagnose AFS, however the patient must be immunocompetent. The presentation of allergic fungal sinusitis in children differs from that of adults. Children with AFS tend to have more facial dysmorphism: proptosis with telecanthus and malar attening is most common, followed by telecanthus alone then malar attening alone. Pediatric patients with AFS also tend to have unilateral or asymmetric disease [7,8]. While our patient presented with clinical characteristics of pediatric AFS, he did not have aspergillis precipitin hypersensitivity or eosinophilia. Although CT characterization of the sinus disease and macroscopic exam of the sinus debris appeared consistent with AFS, his multiple cultures and biopsies did not show any evidence of fungal colonization or infection. However, to emphasize, not all patients diagnosed with AFS have all of the proposed diagnostic criteria [4]. For example, a negative culture does not necessarily exclude a diagnosis of AFS, as fungi may proliferate as saprophytic growth in diseased sinuses [9] and some laboratories are more adept at growing fungi than others. According to deShazo and Swain [10], the diagnosis of AFS should be suspected in patients with sinusitis refractory to antibiotic treatment, especially if multiple surgical interventions have been undertaken. Our patient while having elements of AFS also had macroscopic signs of chronic invasion (polyps eroding through the left inferior turbinate). Therefore, our patients exact diagnosis is quite difcult to pinpoint within the broad spectrum of fungal sinusitis. The fact that oral antifungal and

138 corticosteroid therapy resulted in dramatic, complete, long-term resolution of the sinonasal polyposis conrms that fungi were a cofactor in his sinonasal polypoid disease. Of note, due to the fact that these medications were used in combination, it is difcult for any single therapy to assume responsibility for our patients complete resolution. However, since the pre-operative Prednisone in each of his three FESS did not signicantly reduce polyp size, it can be concluded that perhaps the corticosteroid therapy played a more synergistic and minor role overall. In summary, we reported this case due to its atypical nature and because lessons learned might help direct therapy for future patients. We believe that, for future cases of children with CF and severe sinonasal polyposis refractory to standard treatment but suspicious of AFS, empirical use of systemic antifungals should be considered. Basic science research and larger clinical studies on this topic are needed. However, due to the very limited numbers of these patients, this may be a difcult endeavor.

Z.A. Dewji et al.

[2] S.K. Wise, T.T. Kingdom, L. McKean, J.M. DelGaudio, G. Venkatraman, Presence of fungus in sinus cultures of cystic brosis patients, American Journal of Rhinology 19 (JanuaryFebruary (1)) (2005) 4751. [3] D.E. Tunkel, R.M. Naclerio, F.M. Baroody, B.J. Rosenstein, Bilateral maxillary sinus mucoceles in an infant with cystic brosis, Otolaryngology and Head and Neck Surgery 111 (July (1)) (1994) 116120. [4] F.A. Kuhn, R. Swain Jr., Allergic fungal sinusitis: diagnosis and treatment, Current opinion in otolaryngology & head and neck surgery 11 (February (1)) (2003) 15. [5] J.M. Campbell, M. Graham, H.C. Gray, C. Bower, M.S. Blaiss, S.M. Jones, Allergic Fungal Sinusitis in children, Annals of Allergy, Asthma and Immunology 96 (February (2)) (2006) 286290. [6] D.L. Venarske, R.D. deShazo, Sinobronchial Allergic Mycosis: the SAM syndrome, Chest 121 (May (5)) (2002) 1670 1676. [7] J.E. McClay, B. Marple, L. Kapadia, M.J. Biavati, B. Nussenbaum, M. Newcomer, S. Manning, T. Booth, N. Schwade, Clinical presentation of allergic fungal sinusitis in children, Laryngoscope 112 (March (3)) (2002) 565569. [8] K.D. Carter, S.M. Graham, K.M. Carpenter, Ophthalmic manifestations of allergic fungal sinusitis, American Journal of Ophthalmology 127 (February (2)) (1999) 189195. [9] D.S. Gourley, B.A. Whisman, N.L. Jorgensen, M.E. Martin, M.J. Reid, Allergic Bipolaris sinusitis: clinical and immunopathologic characteristics, The Journal of allergy and clinical immunology 85 (March (3)) (1990) 583591. [10] R.D. deShazo, R.E. Swain, Diagnostic criteria for allergic fungal sinusitis, The Journal of allergy and clinical immunology 96 (July (1)) (1995) 2435. [11] M.F. Mafee, B.H. Tran, A.R. Chapa, Imaging of rhinosinusitis and its complications: plain lm, CT, and MRI, Clinical Reviews in Allergy and Immunology 30 (June (3)) (2006) 165186.

References
[1] R.S. Mendelsohn, B.M. Cohen, Otorhinolaryngologic aspects of cystic brosis, Archives of Otolaryngology 79 (March) (1964) 312317.

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