Abstract
Behçet disease is a multisystem vasculitis characterized by mucosal aphthosis, primarily in the oral and genital mucosa. Only a few cases of involvement of the nasal mucosa have been reported in the literature, and its true prevalence is not known. We conducted a cross-sectional study of 400 consecutively presenting patients with confirmed Behçet disease (according to classification-tree criteria) to determine the incidence of nasal mucosal involvement, to identify its particular characteristics, and to determine if there are any statistically significant differences in clinical and paraclinical parameters between Behçet disease patients with nasal involvement and those without. To the best of our knowledge, this is the first systematic evaluation of nasal involvement in patients with Behçet disease to be published in the literature. Data analysis was performed with Statistical Package for the Social Sciences software (SPSS), and a confidence interval (CI) at 95% was calculated for each finding. Involvement of the nasal mucosa was seen in 31 of the 400 patients (7.8%; CI: 5.1 to 10.5). Among those 31 patients, the most common nasal symptom was dysosmia, which was seen in 15 patients (3.8% of the total population; CI: 1.9 to 5.7); other nasal symptoms included obstruction in 10 patients (unilateral in 9), ulcers in 2, pain in 2, and a burning sensation and discharge in 1 each. No patient reported a history of epistaxis or nasal itching. Abnormal signs were present in only 16 patients (4.0%; CI: 2.1 to 5.9); they included nasal cartilage deformity in 6, unilateral nasal obstruction in 4, postnasal discharge in 3, nonaphthous ulcer in 3, and crusted ulcer in 2 (2 patients each had 2 abnormal signs). No case of aphthous ulcer, nasal discharge, nasal scar or deformity, septal perforation, or nodular or granulomatous cartilage lesion was found. There were no statistically significant differences in clinical and paraclinical disease manifestations between those patients who had nasal mucosal involvement and those who did not.
Introduction
Behçet disease was first described in 1937 by Turkish dermatologist Hulusi Behçet as a triple-symptom disease characterized by recurrent oral and genital aphthosis and anterior uveitis with hypopyon. 1 Subsequently, dermatologic and other systemic manifestations of the disease were described. Today Behçet disease is classified as a multisystem disease in the vasculitis group of diseases because its main pathologic feature is a leukocytoclastic vasculitis.2,3
Behçet disease has a particular geographic distribution that is not seen with other systemic diseases. 4 It is most common in countries along the ancient Silk Road in the Middle East and Southeast Asia.2–4 It is rare in the Western and Southern Hemispheres.
Among the different manifestations of Behçet disease, the most common is mucosal aphthosis, which is seen in 97% of affected patients 5 and which is included in almost all published diagnosis criteria.6–11 Other mucosal lesions such as nonaphthous ulcers and purpuric or hemorrhagic lesions have also been reported. 12 Involvement of mucous layers other than those of the oral and genital areas (e.g., the conjunctiva) has rarely been reported, 13 and only a few cases of nasal mucosal involvement have been reported. 4 As a result, the prevalence of nasal mucosal involvement in Behçet disease is not known, and its characteristics have not been delineated. In an effort to add to the available data, we conducted a study to determine the prevalence of nasal mucosal involvement in Behçet disease, to identify its characteristics and their clinical significance, and to determine if there are any statistically significant differences in clinical and paraclinical parameters between Behçet disease patients with nasal involvement and those without.
Patients and Methods
Our study was designed as a descriptive-analytic cross-sectional study of all consecutively presenting Behçet disease patients who had been referred to the Behçet's Disease Unit of the Rheumatology Research Center at Shariati Hospital in Tehran. All patients who met the classification-tree criteria described by Davatchi et al 11 were enrolled. All patients were questioned for the presence of nasal symptoms, and those who had a history of nasal surgery, nasal or sinus diseases, drug addiction, or other connective tissue diseases were excluded from our analysis. All eligible patients underwent a complete nasal examination, and further complementary investigations were conducted when indicated. The study was closed after we had enrolled 400 eligible patients.
For each patient, we collected 78 items of clinical and paraclinical data, and these were analyzed with the Statistical Package for the Social Sciences software (SPSS; Chicago). We also calculated 95% confidence intervals (CI), means, and standard deviations. Comparisons were done by the chi-square test and the Fisher exact test.
Results
The 400 patients included 227 men (57%) and 173 women (43%), for a male-to-female ratio of 1.31:1. Their mean ages at disease onset were 25.2 years (±9.7) for the men and 27.5 years (±10.3) for the women. The most common sign at presentation was oral aphthosis, which was seen in 349 patients (87%; CI: 83.7 to 90.7). The prevalence of other initial manifestations of disease was as follows: genital aphthosis, 35 patients (8.8%; CI: 5.9 to 11.5); ocular lesions, 27 patients (6.8%; CI: 4.2 to 9.2); joint involvement, 7 patients (1.8%; CI: 0.3 to 3.1); and other manifestations (mostly skin lesions), 27 patients (6.8%; CI: 4.2 to 9.2).
Taking into account subsequent signs that developed during the natural course of the disease beyond the initial presentation, the prevalence of various clinical disease manifestations in the entire study population was as follows: oral aphthosis, 396 patients (99%; CI: 98 to 100), genital aphthosis, 244 patients (61%; CI: 56.2 to 65.8); ocular lesions, 249patients (62%; CI: 57.4 to 67); skin lesions, 235 patients (59%; CI: 53.9 to 63.5); joint involvement, 116 patients (29%; CI: 24.6 to 33.4); neurologic involvement (including headache), 41 patients (10%; CI: 7.3 to 13.1); gastrointestinal involvement, 24 patients (6.0%; CI: 3.7 to 8.3); epididymitis, 16 patients (7.0% of men; CI: 3.7 to 10.3); vascular involvement, 15 patients (3.8%; CI: 1.8 to 5.6); and cardiopulmonary involvement, 5 patients (1.3%; CI: 0.3 to 2.3). These findings are similar to the pattern of organ involvement seen in our Behçet disease registry. 5
Although paraclinical evaluation was not done for all patients, the pattern of results was similar to that reported in our previous study on Behçet disease patients in Iran. 5 Seven paraclinical parameters were measured. The pathergy test was positive in 45% of patients (CI: 42 to 48.6), HLA-B5 was positive in 50% (CI: 47.9 to 52.9), HLA-B51 was positive in 42% (CI: 33.6 to 50.2), and HLA-B27 was positive in 6.4% (CI: 3.9 to 8.9). Among tested patients, a high erythrocyte sedimentation rate (≥20 mm in the first hour) was seen in 51% (CI: 48.6 to 53.2), a urine abnormality in 6.2% (CI: 3.8 to 8.6), and a false-positive syphilis test in 1.1% (CI: 0.1 to 2.1).
Of the 400 patients, 67 (17%; CI: 13 to 20.4) had a history of nasal mucosal involvement, although nasal involvement was not present in all of them at the time of the study. This nasal involvement included a history of mucosal ulcers in 51 patients, pain in 49, burning in 32, obstruction in 11 (bilateral in 1), itching in 7, epistaxis in 6, and postnasal discharge in 5.
Current nasal mucosal involvement was present in 31 patients (7.8%; CI: 5 to 10.4). The most common nasal symptom was dysosmia, which was seen in 15 patients (3.8% of the total population; CI: 1.8 to 5,6); other nasal symptoms included obstruction in 10 patients (unilateral in 9), ulcers in 2, pain in 2, and a burning sensation and discharge in 1 each. None of these 31 patients reported a history of epistaxis or nasal itching. Abnormal signs were present in only 16 patients (4.0%; CI: 2.1 to 5.9); they included nasal cartilage deformity in 6, unilateral nasal obstruction in 4, postnasal discharge in 3, nonaphthous ulcer in 3, and crusted ulcer in 2 (2 patients each had 2 abnormal signs). We found no case of aphthous ulcer, nasal discharge, nasal scar or deformity, septal perforation, or nodular or granulomatous cartilage lesion.
Data analysis revealed no statistically significant differences in any of the 10 clinical manifestations between patients with and without nasal mucosal involvement (table 1). Nor were there any significant differences between the two groups with respect to the 7 paraclinical parameters (table 2).
Comparison of Clinical Manifestations in Behcet Disease Patients with and without Nasal Mucosal Involvement
CNS = central nervous system; GI = gastrointestinal.
Comparison of Paraclinical Manifestations in Behcet Disease Patients with and Without Nasal Mucosal Involvement
ESR = erythrocyte sedimentation rate.
Discussion
Nasal (notably mucosal) involvement has been reported in various vasculitic and connective tissue diseases, such as Wegener granulomatosis, 14 Churg-Strauss syndrome, 15 systemic lupus erythematosus,16,17 Sjogren syndrome, 18 systemic sclerosis, 19 and relapsing polychondritis. 20 But until now, there has been no report on the prevalence and characteristics of nasal mucosal involvement in Behçet disease, despite its importance to the diagnosis. 3 To the best of our knowledge, our study represents the first systematic evaluation of nasal involvement in patients with Behçet disease. It revealed that nasal involvement is not common in Behçet disease, and that nasal ulcers are rare (only 2 in our patient population). On the other hand, oral and genital mucosal involvement in Behçet disease is common.3–5 The differences in the rates of mucosal involvement by site may be attributable to the histologic differences between the nasal mucosa and other mucosae; if so, this would suggest that local tissue factors might play a role in the pathogenesis of Behçet disease. Further studies are needed to test this hypothesis.
We did not classify all patients who had a history of “nasal complaints” as having “nasal involvement” because not all of these complaints had been evaluated by a physician and therefore definitive diagnoses were not established. Because most of the clinical manifestations of Behçet disease (including mucosal involvement) are generally transient and self-limiting,2–4 it is quite probable that we underestimated the prevalence of nasal involvement in our patients. If we had included in our study all 81 patients who had a history of nasal complaints as well as a current symptom or sign, the incidence of nasal involvement would have risen to 20% (CI: 16.3 to 24.1).
In conclusion, we found no apparent relationship between nasal mucosal involvement and any clinical or paraclinical findings in Behçet disease, as we could not show any statistically significant difference when comparing these parameters in patients with and without nasal mucosal involvement.