Cystic Fibrosis and Nasal Polyposis.docx

1、Cystic Fibrosis and Nasal PolyposisCystic Fibrosis and Nasal PolyposisFord D. Albritton IV, MD, and Todd T. Kingdom, MD, Emory University, Atlanta, Ga. Medscape General Medicine 2(1), 2000. 2000 MedscapePosted 02/18/2000AbstractNasal polyposis is a sinonasal manifestation of cystic fibrosis (CF)-an

2、autosomal recessive exocrinopathy. Up to 67% of all CF patients will manifest polyps in their lifetime. Symptoms include nasal airway obstruction, anosmia, rhinorrhea, and exacerbation of the rhinosinusitis that affects these patients. The polyps are probably a consequence of chronic inflammation; h

3、owever, their specific etiology is unclear. Treatment includes antibiotics, topical nasal steroids, decongestants, and mucolytics. Surgery is necessary when conservative measures fail. Endoscopic sinus surgery (ESS) has replaced traditional treatments such as intranasal polypectomy and Caldwell-Luc

4、procedure. ESS combined with medical therapy has successfully delayed the time to recurrence, decreased the need for surgery, and improved the underlying pulmonary status in several studied patient groups. This article reviews typical patient symptoms, physical examination, the use of computed tomog

5、raphy (CT), nasal endoscopic findings, patient prognosis, and the latest research and innovations. Case PresentationA 7-year-old white female was admitted to the pediatric unit for recurrent bronchitis. She was referred to the otolaryngology clinic with complaints of chronic nasal stuffiness, usuall

6、y clear with episodes of purulent rhinorrhea, anosmia, and occasional headaches. Antibiotics were used in the past to treat similar symptoms. Past medical history was significant only for recurrent episodes of bronchitis. Review of systems was negative. One of her siblings was found to have similar

7、but milder complaints. Physical exam revealed a young white female in the 40th percentile for weight and height. Cranial nerve, otologic, and oropharyngeal exams were within normal limits. Anterior rhinoscopy revealed green, mucoid crusting bilaterally. After suction and decongestion, endoscopic exa

8、mination was performed (Figure 1). Figure 1. Endoscopic view of left nasal cavity showing polyposis in middle meatus. Notice how the polyps exhibit a glistening, almost translucent mucosa in contrast to the normal nasal mucosa seen in the remainder of the photo. The nasal airway is virtually nonexis

9、tent secondary to obstruction.Sinus computed tomography (CT) was obtained with axial (Figure 2) and coronal (Figure 3) views. Figure 2. Axial CT scan of a young patient with CF. Hypoplastic maxillary sinuses are seen bilaterally. Both maxillary sinuses are completely opacified with bulging medial wa

10、lls. This picture of complete opacification with sinus wall expansion is often described by the radiologist as sinusitis with findings consistent with polyposis or mucocele. Figure 3. Coronal view of same patient. Again, notice the small size of the maxillary sinuses compared with the bone of the ma

11、xilla. Also note opacification of the maxillary and ethmoid sinuses. Cuts through the expected locations of the frontal and sphenoid sinuses revealed these sinuses absent. Absence or hypoplasia of the paranasal sinuses is a much more frequent finding in CF than in the general population.This patient

12、 was diagnosed with cystic fibrosis (CF) at age 3 years after 2 positive sweat chloride tests. Genotype analysis was performed by her CF pulmonologist and this test revealed she was homozygous for the Delta-F508 mutation. After pathology and CT review, and because of her recurrent symptoms, this pat

13、ient underwent endoscopic polypectomy, limited ethmoidectomy, and maxillary antrotomy. She remained in hospital postoperatively; 2 days later she was discharged to the CF center. Postoperatively, her headaches, nasal obstruction, and rhinorrhea had much improved, and rhinologic exams over the next 6

14、 months demonstrated improved sinus drainage, improved sinus access, and no recurrent polyps. IntroductionSinonasal polyps are characterized by smooth, pale, almost translucent mucosa on a pedunculated or sessile base. They can occur anywhere in the sinus cavity, often along the middle meatus. Polyp

15、s are frequently multiple and bilateral, and their symptoms relate to their obstructive nature and include nasal stuffiness, mouth breathing, facial pain/pressure, anosmia, and even rhinorrhea.1 All that resembles a polyp is not a polyp. The differential diagnosis includes other nasal masses, such a

16、s gliomas and encephaloceles, as well as normal variants of nasal anatomy. Workup should include a thorough history and rhinoscopic exam. Sinonasal polyposis may be seen in a myriad of clinical situations including asthma, allergic rhinitis, immotile cilia syndrome, allergic fungal sinusitis, chroni

17、c sinusitis, and CF. Most commonly they are associated with allergic rhinitis and CF.2,3 PathophysiologyCF is the most lethal autosomal recessive disease affecting Caucasians, with an estimated carrier rate of 1 in 25.4 The CF gene has been isolated to chromosome 7 and encodes for a transmembrane pr

18、otein termed the CF transmembrane conductance regulator (CFTR). It is thought to be a cyclic adenosine monophosphate (cAMP)-dependent chloride transport pump, and mutations of the CFTR lead to ion pump dysfunction. Over 550 different mutations have been documented thus far.5 The sweat gland epitheli

19、um of CF patients fails to absorb both chloride and sodium from the glandular lumen, resulting in elevated sweat concentrations of these ions. Consequently, extracellular dehydration ensues, leading to a variety of complications. Inspissated secretions in the bronchi, pancreas, and sinonasal tract l

20、ead to dysfunction in each of these systems. The function of the sinonasal tract is humidification, temperature modification, and filtration of inspired air in addition to olfaction. The nose is lined with ciliated pseudostratified columnar epithelium in combination with goblet cells - the so-called

21、 respiratory epithelium. A mucous bilayer lines this epithelium, working primarily to trap inspired foreign particles. Nasal ciliary function moves the mucous layer in well-established routes to help clear the sinuses and nasal cavity of inspired debris. Any condition that alters mucociliary flow wi

22、ll result in stasis and cause microbial colonization and infection. In CF, intracellular water flux increases mucous viscosity, leading to mucociliary dysfunction, stasis, and sinonasal obstruction. It is this sequence of events that predisposes the CF patient to bacterial colonization by Pseudomona

23、s and Staphylococcus species and leads to the development of chronic rhinosinusitis. Chronic infection may be the underlying catalyst behind the formation of the characteristic hyperplastic mucosal changes and development of nasal polyps so commonly seen in this patient group.6 The pathogenesis of n

24、asal polyps in the general population is not well defined. There are a number of theories regarding specific pathogenesis, with some investigators proposing that CF polyps are distinct from non-CF polyps. Comparative histopathologic studies, such as a 1979 study by Oppenheimer, described histologic

25、differences in basement membrane thickness and eosinophil density between CF polyps and atopic polyps.7 However, similar studies by other investigators fail to demonstrate differences.6,8 CF polyps appear to contain higher numbers of neutrophils than non-CF polyps, but eosinophils exist in both vari

26、eties.9 EpidemiologyCF affects over 18,000 people in the United States alone.10 The incidence of polyposis in CF is approximately 67%11-14 and the peak incidence occurs between 4 and 12 years of age.15 Estimates of the incidence of polyposis in CF are more accurate now, due to the larger numbers of

27、patients being studied and the quality of the diagnostic technology available, particularly the endoscope, which has allowed the otolaryngologist a more comprehensive view of the nasal cavity. Mean survival of CF patients is now approaching 30 years16 due to advances in nutrition, drug therapy, and

28、supportive care. This increase in survival has necessitated comprehensive care of these patients. DiagnosisAny patient with a finding of nasal polyposis/chronic sinusitis and recurrent pulmonary or GI complaints should be considered for CF work-up. Other patients at risk are those who present with n

29、asal polyposis alone, those with recurrent sinusitis refractory to standard antibiotic treatment, and some asthmatics. Eighty-five percent of patients with CF are diagnosed by age 5,17 but adolescents and young adults may also carry an unrecognized CF phenotype. Sweat chloride analysis is the most c

30、ommonly used diagnostic test for CF.18 Some laboratories are also performing genotype analysis, which is more sensitive and more likely to identify mild cases. Although 70% of CF patients have the DeltaF508 mutation, genotype analysis can confirm the diagnosis and provide information on disease seve

31、rity. It appears that polyposis may be more common in patients homozygous for the DeltaF508 genotype5 and there is some evidence that a lower incidence of pulmonary and GI manifestations exist in patients with nasal polyposis. It is hoped that the future of genotype analysis will include prenatal di

32、agnosis.18 Medical TherapyMedical therapy emphasizes relieving the obstruction with decongestants and topical nasal steroids, in concert with antistaphylococcal and antipseudomonal antibiotics. Antimicrobials attempt to lower colonization and infection rates. Additional adjunctive measures include mucolytics such as guaifenesen and nasal saline. By loosening and debriding secretions, drainage improves and the probability of stasis/colonization diminishes. Antihistamines should be reserved for the atopic CF patient because they dry secretions, impairing mucociliary transit and exacerbat