| | Diagnostic Criteria for Atrophic Rhinosinusitis published online 19 June 2009. Abstract BackgroundPatients with atrophic rhinosinusitis have intractable upper airway symptoms that result from loss of the normal nasal epithelium. There is no consensus on how to diagnose this condition, and diagnostic criteria are not available to perform multicenter treatment trials. We sought to establish diagnostic criteria for atrophic rhinosinusitis. MethodsTwenty-two patients for whom there was a consensus on the diagnosis of atrophic rhinosinusitis were compared with a control group of 22 randomly selected patients with garden-variety chronic rhinosinusitis. Medical records were reviewed on all patients and clinical data were tabulated. Clinical variables included the presence of nasal obstruction, epistaxis, anosmia, purulence, crusting, chronic inflammatory disease involving the upper airway, and multiple sinus surgeries. ResultsBoth groups had similar degrees of persistent nasal obstruction (82% vs 77%). The other 6 clinical features occurred more frequently in patients with atrophic rhinosinusitis than controls (P <.05). Patients with chronic rhinosinusitis and recurrent nasal purulence had a 25-fold (95% confidence interval [CI], 2.9-221.7) increased probability, those with recurrent epistaxis had a 12-fold increased probability (95% CI, 1.3-106.8), and those with 2 or more sinus surgeries had a 15-fold (95% CI, 3.5-66.7) increased probability of having atrophic rhinosinusitis. As the number of symptoms increased, there was an increasing probability of the predetermined diagnosis of atrophic rhinosinusitis (P <.05). The presence of chronic rhinosinusitis and any 2 of the 6 clinical features for 6 months or longer resulted in a sensitivity of 0.95 and specificity of 0.77 for the diagnosis of atrophic rhinosinusitis. ConclusionThe diagnosis of the common secondary form of atrophic rhinosinusitis may be made with certainty if a patient with chronic rhinosinusitis demonstrates 2 or more clinical features for 6 months and longer. These features are patient-reported recurrent epistaxis or episodic anosmia; or physician-documented nasal purulence, nasal crusting, chronic inflammatory disease of the upper airway, or 2 or more sinus surgeries. We have seen an increasing number of patients with atrophic rhinosinusitis in our clinical practice and have attempted to better characterize this entity. However, there is confusion in the medical literature about diagnosis, etiology, and treatment. This results from the fact that diagnostic criteria for this condition have not been established so that the syndrome may be clearly distinguished from other forms of chronic rhinosinusitis. In this article, we sought to develop diagnostic criteria for atrophic rhinosinusitis so that multicenter studies to improve treatment strategies for this condition will be possible. Clinical Significance•Atrophic rhinitis is a common form of chronic rhinosinusitis. •There are no clinical criteria for the diagnosis of this condition. •The lack of clinical criteria leads to underdiagnosis and undertreatment. Atrophic rhinosinusitis is a chronic disease associated with progressive loss of normal upper airway epithelium that results in intractable nasal and sinus symptoms.1 The condition can be severe enough to cause daily symptoms. In the most severe form, it results in a condition commonly called the “nasal cripple.”2 “Primary” and “secondary” forms of atrophic rhinitis have been described, with the primary form more common in developing countries.1, 3, 4 The primary form occurs in a previously healthy nose with a spontaneous onset, slow progression, and a fetid odor apparent to others, called “ozena.” Nasal bone resorption and mucosal colonization with Klebsiella ozaenae also occurs.2 In contrast, the more common secondary form is seen in the US and other developed countries, and appears to be associated with extensive sinus surgery, nasal trauma, radiation therapy to the sinonasal area, and chronic granulomatous diseases such as tuberculosis, syphilis, leprosy, sarcoidosis, and Wegener's granulomatosis.1, 2 Characteristic findings include nasal obstruction, nasal crusting, purulent postnasal drip, epistaxis, anosmia, and facial pressure. Concurrent sinusitis is common. For the purposes of this article, we will refer to secondary atrophic rhinitis as atrophic rhinosinusitis, the focus of this study. Methods  Literature Search We performed extensive computer-assisted searches using PubMed/Medline databases to identify information on the etiology, diagnosis, and treatment of atrophic rhinitis in individuals of all age groups. We reviewed the articles published in English on human subjects, and identified matches for our search criteria, which included ozena, and primary and secondary atrophic rhinitis. Candidate Diagnostic Criteria We have observed several signs and symptoms that appear to distinguish atrophic rhinosinusitis from garden-variety chronic rhinosinusitis. These signs and symptoms include the presence of the following for >6 months: •patient reported:∘chronic nasal obstruction ∘recurrent epistaxis ∘episodic anosmia •physician documented:∘nasal purulence ∘nasal crusting ∘chronic inflammatory disease involving the upper airway (for instance, sarcoidosis or Wegener's granulomatosis) ∘2 or more sinus surgeries We hypothesized that a combination of these signs and symptoms could be used as adequate diagnostic criteria for atrophic rhinosinusitis. Study and Control Groups We identified 22 patients in our academic referral practice diagnosed clinically with atrophic rhinosinusitis by a faculty member in our group (RD or SS). The control group was composed of 22 patients similarly diagnosed by a faculty member with chronic rhinosinusitis who were selected at random from a computer-generated billing list under the ICD-9 (International Classification of Diseases, 9th Revision) code 472.0 from 2004-2007. Because this ICD-9 code includes patients with atrophic rhinitis, ozena, granulomatous rhinitis, hypertrophic rhinitis, obstructive rhinitis, purulent rhinitis, ulcerative rhinitis, and “rhinitis NOS,” patients already in the atrophic rhinosinusitis group were excluded from the control group. Care was taken to ascertain demographic and clinical data on the control group in order to compare that group with the study group. Data Collection and Statistical Analysis A spreadsheet was constructed that contained the proposed criteria and other variables of interest. Demographic and clinical data on all patients were obtained retrospectively from chart review and entered into a spreadsheet using appropriate methods for protecting their confidentiality. Skin-prick tests using standard technique were performed by trained personnel for 50 common allergens. Appropriate negative (diluent) and positive (histamine) controls were included. Aeroallergen sensitization was defined as a positive response to at least 1 allergen at 15 minutes. We examined the association between atrophic rhinosinusitis and nasal obstruction, epistaxis, anosmia, nasal purulence, nasal crusting, multiple sinus surgeries, and nasal disease using logistic regression analysis. These results are reported as odds ratios and 95% confidence intervals (CI), and P-values from a chi-squared test. In addition, we explored the number of signs and symptoms needed to satisfy a diagnosis of atrophic rhinosinusitis by logistic regression and a receiver operating characteristic curve. All statistical analyses were performed using a commercial software program (SAS version 9.1; SAS Institute Inc., Cary, NC). In this study, P-values <.05 were deemed statistically significant. The protocol for this study was approved by the University of Mississippi Medical Center Institutional Review Board. Imaging, Rhinoscopy and Histopathology Computed tomography studies of the paranasal sinuses were obtained and reviewed with a faculty radiologist. Rhinoscopy was performed by an otolaryngologist using flexible rhinoscopes and standard technique. When available, surgical histopathology slides were reviewed with a faculty pathologist. Results Literature Review We found 211 articles between 1896 and 2008 on the topic of atrophic rhinosinusitis, a condition that has existed since biblical times.5 As early as 1922, authors suggested that there were 2 types of this condition, the “fetid” type (ozena) and the “nonfetid” type.6 By 1932, there was a strong suggestion that there were histological differences between the 2 forms, with endarteritis present as a distinguishing feature in “primary atrophic rhinitis.”7, 8 By 1961, controversy about histopathological differences between the 2 forms developed.9 The primary form continues to be reported in developing nations.4, 10, 11, 12 The literature on the secondary form—the subject of this article—is difficult, if not impossible, to interpret as there has been no consensus on diagnostic criteria. Therefore, it was not possible to use previous reports in the literature as benchmarks for the diagnosis of atrophic rhinosinusitis. Demographics on Patients and Controls All 22 patients with a diagnosis of atrophic rhinosinusitis in our clinic had been evaluated by both an allergist-immunologist and an otolaryngologist. Both specialists had agreed on the diagnosis of atrophic rhinosinusitis, and all patients had at least one rhinoscopy. The presence or absence of nasal obstruction, epistaxis, anosmia, purulence, crusting, chronic inflammatory disease involving the upper airway, or multiple sinus surgeries were identified by chart review in the 22 individuals who formed the study group and were compared with those 22 individuals who formed the control group. The groups were similar in age, race, and sex (Table 1). They were dissimilar as to allergy skin-prick results. Of patients with atrophic rhinosinusitis, 19 had skin-prick tests and 9 (42%) had one or more positive test. In contrast, 20 of the patients in the control group had skin-prick tests and 14 (70%) had one or more positive test. In the study group, 18 patients had a history of 2 or more sinus surgeries, of which 14 (78%) included a partial or radical turbinectomy. The study population included patients with remote or current tobacco use (32%), asthma (55%), sarcoidosis (18%), nasal polyposis (45%), and allergic fungal sinusitis (18%). | | |  | | AtR (n =22) | Control (n=22) | χ2 (P Value) | OR (95% CI) | |
|---|
| Age (years) | 54.8±12.9 | 58.5±13.6 | 0.85(.3631) | 0.99(0.93-1.03) | | | Race | | | | | | | White | 18(81.8%) | 18(81.8%) | | | | | Black | 4(18.2%) | 4(18.2%) | 0.00(>.9999) | 1.00(0.2-4.6) | | | Sex | | | | | | | Female | 20(90.9%) | 16(72.7%) | 2.44(.1179) | 0.27(0.1-1.5) | | | Male | 2(9.1%) | 6(27.3%) | | | | | Skin-prick test | | | | | | | Positive | 9(47.4%) | 14(70.0%) | 2.06(.1509) | 2.59(0.7-9.6) | | | Negative | 10(52.6%) | 6(30.0%) | | | | | | |
Presence of Hypothesized Diagnostic Criteria among Study and Control Groups Odds Ratios for Single Criteria Logistic regression analyses demonstrated that patients with chronic rhinosinusitis and recurrent nasal purulence for 6 or more months had a 25-fold increased risk of having atrophic rhinosinusitis (95% CI, 2.9-221.7). In patients with chronic rhinosinusitis, those with 2 or more sinus surgeries had a 15-fold increased associated risk of atrophic rhinosinusitis (95% CI, 3.5-66.7), study subjects with recurrent epistaxis for 6 or more months had a 12-fold increased risk (95% CI, 1.3-106.8), and patients with episodic anosmia for 6 or more months had a 7-fold increased risk of atrophic rhinosinusitis as compared with the control group (95% CI, 0.9-72.1). None of the control participants had nasal crusting or an inflammatory disease of the upper airway. Although odds ratios cannot be computed for these latter 2 criteria, they differentiated the study from the control group (P <.05), with 54.6% of the atrophic rhinosinusitis group exhibiting nasal crusting and 18.2% exhibiting chronic inflammatory disease of the upper airway. Over 95% of patients with atrophic rhinosinusitis had 2 or more of the proposed criteria, compared with 22% of the control group (Table 3). | | | | Number of Characteristics | AtR (n=22) | Control (n=22) | |
|---|
| 0 | 0(0.0%) | 11(50.0%) | | | 1 | 1(4.5%) | 6(27.3%) | | | 2 | 7(31.8%) | 4(18.2%) | | | 3 | 7(31.8%) | 1(4.5%) | | | 4 | 3(13.6%) | 0(0.0%) | | | 5 | 3(13.6%) | 0(0.0%) | | | 6 | 1(4.5%) | 0(0.0%) | | | χ2 (P value) | | | | | 10.4 (.0012) | | | | | OR (95% CI) | | | | | 8.9 (2.4-33.5) | | | | | | |
Odds Ratios for Multiple Criteria An increasing number of criteria were associated with an increased risk of the predetermined diagnosis of atrophic rhinosinusitis by logistic regression analysis (odds ratio 8.9; 95% CI, 2.4-33.5; P <.05). In this case, the odds ratio represents a roughly 9-fold increase in atrophic rhinosinusitis for each criterion (8.9x, where x equals number of criteria present). For example, a participant who met 2 of the criteria was 8.92≈80 times more likely to be diagnosed with atrophic rhinosinusitis compared with a participant with no criterion. We also explored the number of criteria required to make the diagnosis of atrophic rhinosinusitis with a high degree of certainty by a receiver operating characteristic curve (Figure 1). Excluding nasal obstruction from the analysis, the presence of any 2 of the proposed criteria for atrophic rhinosinusitis resulted in a sensitivity of 0.9546 and specificity of 0.7727 (Table 4). Computed Tomography Computed tomography (CT) studies of the paranasal sinuses were performed on all patients in the study and control groups. No participant had evidence of bone erosion suggestive of primary atrophic rhinosinusitis.13 The findings were nonspecific and ranged from normal to evidence of pansinusitis. In the study population, 21 (95%) of the participants had abnormal findings on the sinus CT study, defined as evidence of disease in at least 1 sinus. Of the control population, 13 (59%) had abnormal findings, while 9 (41%) had a normal CT study. Rhinoscopy Findings on rhinoscopy in patients with atrophic rhinosinusitis were highly variable and appeared to reflect the length of time the condition had been present, the presence of an active inflammatory process such as sacoidosis, and the presence or absence of bacterial super-infection. Patients with long histories of disease often complained of intractable nasal dryness, and often had findings of a pale, atrophic nasal mucosa, with adherent dry nasal crusts. We term this the “dry” form (Figure 2). Three of the study patients reported that they had regularly used tweezers to remove dried, bloody crusts that were obstructing nasal airflow. Individuals with active inflammation, either from underlying nasal disease or infection, had thick, viscid seropurulent nasal discharge (Figure 3). We term this the “wet” form. Although it was possible to see pure “wet” or “dry” stages of the disease on rhinoscopy, most patients appeared to have both dryness and seropurulence in some area of their nasal mucosa. The predominance of either form may be a clinical correlate for disease progression, as individuals with longstanding disease tended to have the “dry” form. Histopathology A representative biopsy of a study patient showed histopathological changes in the nasal mucosa like those previously reported in the secondary form of atrophic rhinosinusitis.9 There was progressive loss of pseudostratified columnar epithelium with transition to a squamous epithelium that lacked cilia, goblet cells, and mucus-secreting cells (Figure 4, Figure 5). Discussion Atrophic rhinosinusitis was first characterized by Frankel in 1876 by a triad of symptoms consisting of a foul odor, atrophy, and crust formation.5 The terms atrophic rhinitis, rhinitis sicca, and ozena have been used interchangeably in the literature, making interpretation of the clinical and histopathological findings difficult.1 The prevalence is unknown, although underdiagnosis is likely due to a lack of consensus on diagnostic criteria. Two forms have been reported. The “primary” form occurs primarily in young adults living in developing countries.1, 3, 4 It is characterized by progressive nasal mucosal atrophy, resorption of underlying bones of the turbinates, widened nasal passages with paradoxical nasal congestion, and viscid nasal secretions that dry and form discolored crusts. The distinctive feature is a fetid odor, detectable by others, from secondary infections of the nasal passages. Klebsiella ozenae is the organism most frequently cultured from the nasal discharge. This condition is called ozena, Greek for “the stench.” The more common form is clinically distinct from ozena, and is seen in the US and other developed countries.1, 4 Little is known about this “secondary form” and it remains incompletely characterized. We have noted it in our referral practice to be associated with extensive sinus surgery, often involving radical turbinectomies, nasal or sinus injuries, radiation therapy to the area, or chronic rhinosinusitis in association with chronic granulomatous diseases of the nose. These diseases include tuberculosis, syphilis, leprosy, sarcoidosis, rhinoscleroma, and Wegener's granulomatosis. The symptom complex associated with secondary atrophic rhinosinusitis includes chronic nasal obstruction, purulent postnasal drip, nasal crusting, epistaxis, and episodic anosmia. It is unassociated with resorption of the underlying turbinates and a fetid odor noted by others. When compared with a control group of individuals with typical rhinosinusitis, we found that certain combinations of criteria clearly distinguished patients we previously diagnosed with secondary atrophic rhinosinusitis from controls. Each of the proposed criteria, other than nasal obstruction, occurred more frequently in patients with atrophic rhinosinusitis. Patients with any combination of 2 or more proposed criteria, to include recurrent epistaxis, episodic anosmia, nasal purulence, nasal crusting, chronic inflammatory disease of the upper airway for 6 months, or 2 or more sinus surgeries, had an odds ratio of 8.9 and were over 80 times more likely to have atrophic rhinosinusitis than an individual with none of these criteria. Excluding nasal obstruction, having 2 or more criteria was associated with the sensitivity of 0.95 and a specificity of 0.77 for the condition. Sinus CT findings established that the majority of patients had both rhinitis and sinusitis, supporting our contention that the condition should be best termed atrophic rhinosinusitis. Patients with primary atrophic rhinitis also commonly demonstrate mucosal abnormalities in the paranasal sinuses.13 Almost half of the patients with atrophic rhinosinusitis in our study were atopic, and the majority had multiple sinus surgeries, of which two thirds included a partial or radical turbinectomy. The association of atrophic rhinosinusitis with chronic nasal inflammation or other forms of nasal injury suggests that atrophic rhinosinusitis is a final common pathway following injury of the nasal mucosa. The loss of ciliated nasal epithelium and transformation from a pseudostratified columnar epithelium to one that is squamous results in mucus stagnation and the milieu for chronic super-infection with bacteria.1, 4, 14 Mucus and serous gland atrophy along with loss of mucus-producing cells, appears to result in a spectrum of nasal findings that range from the mucopurulent, or the wet form of the disease, to a drier, crusted form. We were surprised to hear from our patients with the “dry” form how frequently they used tweezers to remove bloody crusts from their nose to relieve nasal obstruction. Conclusion The data reported here demonstrate that combinations of 6 of the 7 candidate diagnostic criteria adequately distinguish patients with atrophic rhinosinusitis. The highest level of sensitivity and specificity occurred when any 2 of the 6 criteria are present for 6 months or longer, including epistaxis, anosmia, nasal purulence, nasal crusting, chronic inflammatory disease of the airway, and 2 or more sinus surgeries. The availability of these diagnostic criteria in future studies of this common condition should prove useful in multicenter trials necessary to develop improved treatment strategies. Acknowledgements We thank Gailen D. Marshall, MD, PhD for his advice and consultation on this study and Leigh Wright, BA for editorial assistance on the manuscript. References 1. 1Moore EJ, Kern EB. Atrophic rhinitis: a review of 242 cases. Am J Rhinol. 2001;15:355–361. MEDLINE 2. 2deShazo RD, Stringer SP. Atrophic rhinitis. http://www.uptodate.com/home/index.html2007;. 3. 3Chand MS, MacArthur CJ. Primary atrophic rhinitis: a summary of four cases and review of the literature. Otolaryngol Head Neck Surg. 1997;116:554–558. Full Text |
Full-Text PDF (1024 KB)
|
CrossRef
4. 4Dutt SN, Kameswaran M. The aetiology and management of atrophic rhinitis. J Laryngol Otol. 2005;119:843–852. MEDLINE 5. 5Wright J. Atrophic rhinitis in its historical, etiological and histological aspects. Laryngoscope. 1913;23:641–666. 6. 6Rundstrom A. The pathologicoanatomic difference between the fetid and the nonfetid ozena. Ann Otol Rhinol Laryngol. 1922;31:950–959. 7. 7Ruskin SL. A differential diagnosis and therapy of atrophic rhinitis and ozena. Arch Otolaryngol. 1932;15:222–257. 8. 8Ruskin SL. Rationale of estrogen therapy of primary atrophic rhinitis (ozena). Arch Otolaryngol. 1942;32:632–649. 9. 9Taylor M, Young A. Histopathological and histochemical studies on atrophic rhinitis. J Laryngol Otol. 1961;75:574–590. MEDLINE 10. 10Talmi YP, Bar-Ziv J, Cohan D, et al. Computed tomography study of sinus involvement in ozena. Am J Rhinol. 1995;9:281–284.
CrossRef
11. 11Shehata MA. Atrophic rhinitis. Am J Otolaryngol. 1996;17:81–86.
Full-Text PDF (1365 KB)
|
CrossRef
12. 12Bunnag C, Jareoncharsri P, Tansuriyawong P, et al. Characteristics of atrophic rhinitis in Thai patients at the Siriraj Hospital. Rhinology. 1999;37:125–130. MEDLINE 13. 13Pace-Balzan A, Shankar L, Hawke M. Computed tomographic findings in atrophic rhinitis. J Otolaryngol. 1991;20:428–432. MEDLINE 14. 14Abdel-Latif SM, Baheeg SS, Aglan YI, et al. Chronic atrophic rhinitis with fetor (ozena): a histophathologic tretise. Rhinology. 1987;25:117–120. MEDLINE a Division of Clinical Immunology and Allergy, Department of Medicine, University of Mississippi Medical Center, Jackson b NSW Injury Risk Management Research Centre, University of New South Wales, Sydney, Australia c School of Mathematics and Statistics, University of New South Wales, Sydney, Australia d Department of Otolaryngology, University of Mississippi Medical Center, Jackson e Department of Pathology, University of Mississippi Medical Center, Jackson f School of Medicine, University of Mississippi Medical Center, Jackson  Requests for reprints should be addressed to Richard D. deShazo, MD, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505
Conflict of Interest: None. Authorship: The authors each had access to the data and a role in writing this manuscript. PII: S0002-9343(09)00334-9 doi:10.1016/j.amjmed.2008.12.025 © 2009 Elsevier Inc. All rights reserved. | |
|
FULL TEXT00334-9/journalimage?img=PIIS0002934309003349.gr1.lrg.gif&fig=fig1&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
00334-9/journalimage?img=PIIS0002934309003349.gr2.lrg.gif&fig=fig2&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
00334-9/journalimage?img=PIIS0002934309003349.gr3.lrg.gif&fig=fig3&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
00334-9/journalimage?img=PIIS0002934309003349.gr4.lrg.gif&fig=fig4&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
00334-9/journalimage?img=PIIS0002934309003349.gr5.lrg.gif&fig=fig5&kwhquery=&issn=0002-9343&ishighres=false&allhighres=false&free=yes','journalimage');)
