Clin Rheumatol (2011) 30:1251–1256 DOI 10.1007/s10067-011-1781-7

BRIEF REPORT

Laryngeal involvement in juvenile idiopathic patients

Mosaad Abdel-Aziz & Noha A. Azab & Iman H. Bassyouni & Gehan Hamdy

Received: 6 April 2011 /Accepted: 11 May 2011 /Published online: 26 May 2011 # Clinical 2011

Abstract Juvenile idiopathic arthritis (JIA) is an autoim- to be subjected to thorough otolaryngologic examination mune diseases characterized by chronic arthritis and for early diagnosis and prompt management. systemic manifestations. Autoimmune diseases can affect the upper airways including the larynx. The aim of this Keywords Cricoarytenoiditis . Flexible laryngoscopy. study was to investigate laryngeal involvement in JIA Juvenile idiopathic arthritis . Rheumatoid nodule patients and its possible association with JIA disease parameters. Fifty consecutive JIA patients were screened for laryngeal abnormalities using flexible fiberoptic laryn- Introduction goscope and laryngeal computerized tomography. Laryn- geal abnormalities were detected in nine (18%) of our Juvenile idiopathic arthritis (JIA) represents a heteroge- cases, with cricoarytenoiditis in six cases (12%) and a neous group of autoimmune diseases characterized by rheumatoid nodule in the pyriform fossa in only one case chronic arthritis and systemic manifestations [1]. Different (2%). Diffuse congestion and edema of the posterior part of classification criteria have been proposed. The most recent the larynx with normal vocal cord mobility was detected in are those of the International League of Associations for two cases (4%). In our study, laryngeal abnormalities were Rheumatology (ILAR) criteria. The ILAR classification of significantly higher in patients with polyarticular seropos- JIA includes seven subtypes, recognized based on the itive disease subtype and also were significantly higher in clinical features during the first 6 months of disease: patients with longer disease duration, higher disease systemic onset JIA, oligoarticular, polyarticular rheumatoid activity scores, and those with erosive disease. JIA may factor (RF)-positive and RF-negative, enthesitis-related JIA, affect the larynx. Laryngeal involvement in JIA patients is juvenile , and “other arthritides” [2, 3]. more in polyarticular seropositive cases. JIA patients have Laryngeal involvement may occur in autoimmune dis- eases. In (RA), it may involve the cricoarytenoid joint (CAJ), also it may cause rheumatoid M. Abdel-Aziz nodules on the vocal cords and amyloidosis [4]. CAJ is a Department of Otolaryngology, Faculty of Medicine, diarthrodial synovial joint, in the posterior wall of the Cairo University, Cairo, Egypt larynx, and is important for respiration and phonation [5]. : CAJ arthritis is associated with hoarseness, a sense of N. A. Azab (*) I. H. Bassyouni pharyngeal fullness in the throat on speaking and swallow- Department of Rheumatology and Rehabilitation, ing, referred ear pain and dyspnea [6]. In systemic lupus Faculty of Medicine, Cairo University, Cairo, Egypt erythematosus, laryngeal involvement may occur in the e-mail: [email protected] form of epiglottitis, CAJ arthritis, vocal cord paralysis, mucosal ulceration and hemorrhagic bullae, diffuse edema, G. Hamdy chronic hyperplastic laryngitis, and laryngitis sicca [7]. Department of Internal Medicine, Faculty of Medicine, Cairo University, Moreover, cricoarytenoiditis was reported to occur as the Cairo, Egypt sole presentation during the disease flare [8]. 1252 Clin Rheumatol (2011) 30:1251–1256

JIA has been reported to cause CAJ arthritis leading to Statistical method vocal cord fixation either unilaterally resulting in hoarse- ness of voice or bilaterally resulting in stridor with The data were coded and entered using statistical package difficulty of breathing [9, 10]. Affection of the vocal fold SPSS version 15 for windows. Data were summarized itself has been reported as well [11]. Schwemmle and Ptok using mean±SD for quantitative variables and frequency [12] reported nodes histologically resembling rheumatoid and percentage for qualitative variables. Significant differ- nodules called bamboo nodes. It was the aim of this study ences were calculated using Mann–Whitney U test for to investigate laryngeal involvement in patients with JIA continuous variables. For comparing categorical data, chi- and its possible association with JIA disease parameters. square (χ2) test with Yates" correction or Fisher"s exact tests were used. P value<0.05 was considered significant.

Patients and methods Results Fifty consecutive patients with JIA diagnosed according to the ILAR criteria [2] were included in the present study. All Fifty consecutive JIA patients were included in the present patients had their onset of the disease before the age of study; their clinical and demographic data are shown in 16 years, with arthritis lasting for at least 6 weeks" duration Table 1. Extra-articular involvement was found in five and with other identifiable causes of arthritis excluded [2]. All cases were attending and were recruited from the Table 1 Clinical, demographic, and laboratory features of JIA N Rheumatology and Rehabilitation Department and Internal patients ( =50) Medicine Department, Faculty of Medicine, Cairo Univer- Females N (%) 34 (68) sity in the period from March 2008 to April 2010. The Males N (%) 16 (32) protocol for this research conforms to the provisions of the Age (years) (mean±SD) 13.6±4.64 " World Medical Association s Declaration of Helsinki and Age at onset (years) (mean±SD) 8.12±3.5 informed consent has been obtained from all participants Disease duration (years) (mean±SD) 5.56±3.5 and/or their parents before the study. The study was JIA subtypes performed after institutional board approval. Polyarticular JIA RF+ n (%) 8(16) All patients were subjected to full history taking and Polyarticular JIA RF- n (%) 7(14) thorough clinical examination. Also, routine laboratory Oligoarticular JIA n (%) 26(52) tests were conducted at the day of examination in the form Persistent type n (%) 9 (18) of complete blood picture, erythrocyte sedimentation rate, Extended type n (%) 17(34) C-reactive protein, rheumatoid factor by latex agglutination Systemic onset JIA n (%) 7(14) test, antinuclear antibodies, liver and kidney functions, and Enthesitis-related JIA n (%) 2 (4) complete urine analysis. Psoriatic JIA n (%) 0 (0) All patients underwent clinical evaluation of disease others n (%) 0 (0) activity as assessed by the disease activity score, using a Extra-articular manifestations n (%) 5(10) 28-joint score (DAS-28) [13]. Postero-anterior radiographs Micrognathia n (%) 15(30) of hands, wrists, and forefeet were obtained at inclusion in Medications (in the past 3 months) the study, and joint destruction was classified by compar- n ison with standard reference films according to the Larsen- Methotrexate (%) 36 (72) n Dale index [14]. The patient was considered to have an Antimalarials (%) 24 (48) n erosive disease on finding of at least one definite erosion on Corticosteroids (%) 14 (28) n any of the hands or feet radiographs. Lefulonamide (%) 4 (8) History of coughing, change in voice, breathing diffi- DAS28 (mean±SD) 6.2±1.34 culties, or chronic dysphagia was thoroughly investigated. ESR mm/h (mean±SD) 29.2±25.1 Laryngeal examination was done using flexible laryngos- CRP mg/dl (mean±SD) 6.3±2.4 copy to detect CAJ or ankylosis, mobility of RF (+ve) n (%) 23(46) the vocal cords, or the presence of laryngeal rheumatoid ANA (+ve) n (%) 11 (22) nodules. Also, CT of the larynx was done to all patients to Anti CCP n (%) 6(12) detect CAJ synovial thickening or erosions, arytenoid Erosive arthritis n (%) 18 (36) subluxation, asymmetry of the glottis or aryepiglottic folds, DAS 28 disease activity score, ESR erythrocyte sedimentation rate, or rheumatoid nodules. CT scans were done during quite CRP C-reactive protein, RF rheumatoid factor, ANA antinuclear respiration, with 2-mm thickness scan sections. antibodies, anti CCP anti-cyclic citrullinated peptide Clin Rheumatol (2011) 30:1251–1256 1253 cases (10%) mainly in the form of pericardial effusion. Micrognathia was found in 15 cases (30%) which was a potential cause of difficult intubation during laryngoscopy. As regards symptoms of laryngeal involvement, only four cases (8%) complained of change of voice; two of them (4%) gave history of chronic dysphagia, and the other two cases (4%) complained of unilateral throat pain with referred earache. Also, two of our patients (4%) complained of breathing difficulty following severe upper respiratory tract infection and were managed by tracheostomy after failure of conservative measures which included antibiotics and steroids. Fig. 1 The larynx as seen by flexible laryngoscopy, the arrow points Flexible laryngoscopy showed laryngeal abnormalities in to a nodule in the left pyriform fossa nine patients (18%); two cases (4%) showed unilateral vocal cord immobility on the right side with complete compensation of chink by the left cord, two cases(4%) cases (18%). Laryngeal involvement was in the form of showed congestion, and edema of one arytenoid with bilateral vocal cord paramedian location in two cases (4%) sluggish mobility of the related vocal cord (of the right in indicating alteration of cricoarytenoid motion that limited one case and of the left in the other), two cases(4%) showed full lateral rotation; vocal cord thickening in three cases congestion and edema of both arytenoids with sluggish (6%); aryepiglottic fold thickening in four cases (8%) mobility of the related vocal cords, two cases (4%) showed indicating that normal motion of the arytenoids cartilages diffuse congestion and edema of the posterior part of the upon the cricoid was not occurring, thus preventing the larynx (over both arytenoids and in the interarytenoid return of the aryepiglottic folds to their neutral position; region), while one case (2%) showed a nodule in the left anterior displacement of the arytenoid cartilage in three pyriform fossa, as shown in Table 2 and in Fig. 1. The cases (6%) as shown in Table 2 and in Fig. 2. nodule was surgically removed by direct laryngoscopy In general, laryngeal involvement detected in our study under general anesthesia and was sent for histopathological was found in nine (18%) of our cases, in the form of examination that proved the presence of dense fibrous cricoarytenoiditis in six of them (12%) and a rheumatoid tissue with composed of palisading epitheliod nodule in the pyriform fossa in only one case (2%). Diffuse cells surrounding areas of fibrinoid ; special stains congestion and edema of the posterior part of the larynx for tubercle bacilli were negative with no giant cells. The with normal vocal cord mobility was detected in two cases appearance of the lesion was that of a rheumatoid nodule. (4%).CAJ arthritis was found in six cases, with four of Computerized tomography (CT) scanning of the larynx them of polyarticular RF-positive JIA, one case with in our JIA patients revealed laryngeal abnormalities in nine oligoarticular JIA, and one case with systemic onset JIA.

Table 2 Laryngeal abnormali- N ties detected in JIA patients (%)

Flexible laryngoscopy abnormalities 9/50 (18) Functional abnormalities Unilateral vocal cord immobility 2/50(4) Unilateral sluggish vocal cord mobility 2/50(4) Bilateral sluggish vocal cord mobility 2/50(4) Mucosal abnormalities Unilateral arytenoid congestion and edema 2/50(4) Bilateral arytenoid congestion and edema 2/50(4) Diffuse congestion and edema of the posterior part of the larynx 2/50(4) Rheumatoid nodule (in the pyriform fossa) 1/50 (2) Laryngeal computerized tomography findings 9/50 (18) Bilateral paramedian vocal cords 2/50 (4) Bilateral vocal cord thickening 3/50(6) Aryepiglottic fold thickening 4/50(8) Anterior displacement of the arytenoid cartilage 3/50(6) 1254 Clin Rheumatol (2011) 30:1251–1256

with clinical disease parameters in our patients was investigated. In our study, dysphonia was detected in four (8%) of our patients; in whom cricoarytenoidits—presenting with con- gested and edematous arytenoids (unilateral in two cases and bilateral in the other two cases)—was most likely the cause. However, CAJ arthritis was detected in six of our cases (12%) using both flexible laryngoscopy and laryngeal CT scans, with two of them having no laryngeal symptoms (33%). Cricoarytenoiditis has been reported to occur in JIA [9, 16], and sometimes, it may be the first presentation of the disease [17]. Brazeau-Lamontagne et al. [18] evaluated 32 patients with RA using flexible fiberoptic laryngoscopy and high-resolution computerized tomography; they detected abnormalities in 75% of patients at endoscopic Fig. 2 Computerized tomography of the larynx, the arrow points to examination while computerized tomography showed ab- anterior displacement of the left arytenoid cartilage normalities in 72%. However, only two of their patients proved to have JIA and they had cricoarytenoiditis. The only case with a rheumatoid nodule in the pyriform Bilateral cricoarytenoiditis may result in upper airway fossa was a case of polyarticular RF-positive JIA. This obstruction [9, 10, 16], two of our patients (4%) experi- means that cases with polyarticular RF-positive JIA had enced upper airway obstruction and they had bilateral CAJ arthritis in four out of eight cases (50%) and a cricoarytenoiditis by flexible laryngoscopy and laryngeal rheumatoid nodule of the larynx in one out of eight cases CT scans. In an autoimmune disease like JIA, patients are (12.5%). immune compromised, they may develop recurrent and As regards to the association of laryngeal abnormalities severe upper airway infection, which raises the possibility with clinical disease subtypes, it was found that most of the of upper airway obstruction .Recognition of cricoarytenoid abnormalities were in the group of patients with poly- arthritis in such patients may prevent the need for articular seropositive subtype. Nine cases of our JIA tracheostomy. patients (18%) had laryngeal abnormalities, with six of One of our cases (2%) showed a painless nodule in the them (66.7%) being of the seropositive polyarticular JIA, left pyriform fossa, he had as well multiple subcutaneous two cases (22.2%) of oligoarticular extended JIA, and one rheumatoid nodules on the extensor surface of both case with systemic onset JIA (p value<0.001). forearms .The nodule was removed and the diagnosis of a Laryngeal abnormalities detected in the study group were rheumatoid nodule was confirmed by histopathological significantly higher in older patients (p value<0.001), with examination. Friedman [19] reported that there are no longer disease duration (p value=0.007), and higher DAS28 clinical clues that would lead to the diagnosis of rheumatoid scores (p<0.001), also they showed a highly significant nodule of the larynx and that the index of suspicion should association with erosive disease (p=0.023).However, laryn- be high in patients with RA. Raven et al. [20] were the first geal abnormalities showed a non-significant association with to describe small submucous rheumatoid nodule in the gender of the patients (p=0.22) or presence of extra-articular larynx, and their findings were later confirmed by other manifestations (p=0.315). studies [21, 22]. Rheumatoid deposits in the form of bamboo nodes which are white–yellow bands in the middle of the membranous portion of the vocal folds had been Discussion described [11]. Upile et al. [21] reported a rheumatoid nodule of the thyrohyoid membrane in a case of RA. Our The upper airways comprise mucosal, cartilaginous, artic- patient was treated for many years with methotrexate, ular, muscular, and neurologic structures. Given this, which increases the development of rheumatoid nodules patients with autoimmune diseases can develop a number [23]. Repeated microtrauma may also predispose to of upper airway abnormalities [15]. Laryngeal involvement laryngeal rheumatoid nodules [24]. in JIA has been reported before; however, most of the Diffuse congestion and edema of the posterior part of the published data were case reports. In this study, 50 larynx with normal vocal cord mobility was detected in two consecutive JIA patients were screened for laryngeal of our cases (4%), this lesion may be due to steroids and abnormalities using flexible fiberoptic laryngoscope and other anti-inflammatory medications that may result in laryngeal CT, and the possible association of these findings hyperacidity. This explanation is considered, as the con- Clin Rheumatol (2011) 30:1251–1256 1255 gestion was diffuse and not localized over the arytenoids. though it may occur in any clinical subtype, and is more in Both cases reported chronic dysphagia and hoarseness of severe prolonged cases. JIA patients have to be subjected to voice. Gastroesophageal reflux laryngitis causes a globus thorough otolaryngologic examination for early diagnosis feeling and frequent throat clearing. Also, patients may and prompt management. have hoarseness in the morning, persistent sore throat and nocturnal coughing [24]. Cricoarytenoid arthritis is rare in JIA patients, and few Disclosures None. case reports have been reported [10, 16, 17, 25] .This is in contrast to the high prevalence of CAJ affection reported in RA in adults that varies between 32% and 75% by flexible laryngoscopy and between 54% and 72% on CT scans [18, References 26]. 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