Volume 4, Issue 3 , Pages 134-138, September 2009
Young child with cystic fibrosis and sinonasal destructive polyposis which resolved incidentally with oral antifungals
Article Outline
Summary
Cystic fibrosis (CF) affects between 1 in 2000 and 1 in 4500 children of European descent [R.S. Mendelsohn, B.M. Cohen. Otorhinolaryngologic aspects of cystic fibrosis. Archives of Otolaryngology 79 March (1964) 312–17]. 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 fibrosis patients. American Journal of Rhinology 19 January–February (1) (2005) 47–51]. 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.
Keywords: Sinonasal polyposis, Cystic fibrosis, Allergic fungal sinusitis, Proptosis
1. Introduction
Cystic fibrosis 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 insufficiency and otolaryngologic manifestations, which include chronic sinusitis and sinonasal polyposis. CF is caused by defects in the gene for cystic fibrosis transmembrane conductor regulator (CFTR). This gene codes for a transmembrane regulator protein which acts as a chloride channel. The chromosome 7 mutation leads to thickened mucous and impaired mucociliary clearance. Nasal polyposis has been reported to have an incidence of 8–48% 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 fibrosis who had severe, destructive sinonasal polyposis causing proptosis and hypertelorism. AFS was suspected but laboratory confirmation 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 findings.
2. Case report
A 4-year-old, Caucasian male, with cystic fibrosis diagnosed by sweat chloride and ΔF508 gene mutation testing, presented to the British Columbia Children's 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 1–3) of the sinuses demonstrated extensive polyposis. The maxillary antra and ethmoid sinuses were almost completely opacified 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 inflammatory debris, suggesting AFS [11].
Figs. 1–3
Non-contrast CT scan of the sinuses demonstrating extensive polyposis. The maxillary antra and ethmoid sinuses are almost completely opacified 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 inflammatory debris, suggesting AFS.
A 5-day course of Prednisone (1mg/kg daily) was administered pre-operatively and a functional endoscopic sinus surgery (FESS) was performed; specifically, bilateral polypectomies, partial anterior ethmoidectomies and maxillary antrostomies. There was no significant reduction in polyp size pre-operatively. 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 patient's pre-operative WBC count, eosinophil count, total IgE count were within normal limits. Subsequent allergy testing was positive for 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 opacification of the sinuses similar to previous CT examinations. A second pre-operative 5-day course of Prednisone (1mg/kg daily) was administered and again no significant 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 10ml of Ciprofloxacin 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 pre-operative 5-day course of Prednisone (1mg/kg daily), which again appeared to have little effect on polyp size, and FESS operation with bilateral polypectomies plus adenoidectomy was performed.
Fig. 4.
Picture of patient following his third FESS operation depicting hypertelorism and telecanthus and left proptosis.
The patient again had transient improvement in his nasal symptoms. One year later, he returned with 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 fluctuating IgE levels. Sputum culture was positive for Aspergillus. At 27kg, he was prescribed a 9-month course of 100mg Itraconozole daily and 5mg 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.
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.
Figs. 6 and 7.
CT chest showed focal RUL bronchiectasis and a left anteromedial linear RUL opacity with bronchial mucus impaction.
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 1–2mm of relative proptosis on the left have stabilized. He has 20/20 vision, normal colour vision, 40s of stereopsis, no ocular muscle imbalance and normal anterior segments and fundi (Figure 8). His quality of life has improved significantly.
Fig. 8.
Picture of patient as of January 2008 showing stabilization of his hypertelorism, telecanthus and proptosis.
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) allergic 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 flattening is most common, followed by telecanthus alone then malar flattening 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 patient's exact diagnosis is quite difficult to pinpoint within the broad spectrum of fungal sinusitis. The fact that oral antifungal and corticosteroid therapy resulted in dramatic, complete, long-term resolution of the sinonasal polyposis confirms 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 difficult for any single therapy to assume responsibility for our patient's complete resolution. However, since the pre-operative Prednisone in each of his three FESS did not significantly 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 difficult endeavor.
References
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PII: S1871-4048(08)00071-3
doi:10.1016/j.pedex.2008.10.003
© 2008 Elsevier Ireland Ltd. All rights reserved.
Volume 4, Issue 3 , Pages 134-138, September 2009
