Acta Otolaryngol (Stockh) 1991: 11 1: 990-998
Laryngeal Involvement in Rheumatoid Arthritis AKE GETERUD.'
BJORN BAKE.? BIRGITTE
BERTHELSEN" ANDERS BJELLE~
and HASSE EJNELL' From the Departmenis of'lOtor/iinolaryn~olo~~, 'Clinical Physiolog?: zDiagnostic Radiology and 'Rlicwmatology. t niiwsity ($Gothenburg. Sahlgren 's Hospital. Gothenburg SiwdiJn
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
Geterud A. Bake B. Berthelsen B. Bjelle A and Ejnell H. Laryngeal involvement in rheumatoid arthritis. Acta Otolaryngol (Stockh) 1991: 11 1: 990-998. Twenty-nine female patients with definite or classical rheumatoid arthritis (RA)and 30 controls were studied in order to assess the prevalence of laryngeal involvement in patients with RA and the occurrence of extrathoracic airway obstruction. Laryngeal involvement was assessed by physical examination including direct fiberoptic laryngoscopy, respiratory function tests and low-voltage radiography. Physical examination revealed laryngeal involvement in 17 RA patients (59%). extrathoracic airway obstruction was indicated by spirometry in 4 (14%) and radiography revealed pathological findings in 3 patients (10%). One or more signs of laryngeal involvement were found in 20 patients (69 %). Symptoms of breathing difficulties were common (75%) among patients with laryngeal involvement. The erythrocyte sedimentation rate and class-specific rheumatoid factors were not correlated to laryngeal involvement. Key uords: rheumatoid arthritis. laryn.x, cricoarytenoidjoint, spirometry. radiography. rheumatoid .factors. e.\-trarhoracic airu-ay obstniction.
INTRODUCTION Laryngeal involvement in rheumatoid arthritis (RA) was first reported late in the 19th century (1). In postmortem studies, the prevalence of arthritis of the cricoarytenoid joint has varied between 45 and 88 % (2, 3.4). Reported findings resulting from indirect laryngoscopy, direct fiberoptic laryngoscopy and radiography have varied from 26 to 75% (2, 5, 6, 7,s). The wide range of reported prevalence figures can partly be explained by the fact that different methods were used. The definition of laryngeal involvement differed and control groups were not used. In addition. comparisons between the studies were difficult because the studied groups differed in terms of age, sex, disease severity and duration. In the present study, we combined indirect mirror and direct fiberoptic laryngoscopy with spirometry and low-voltage radiography of the cricoarytenoid joints to assess the prevalence of laryngeal involvement and the extent of extrathoracic airway obstruction in a homogeneous group of RA patients. We also studied the association between laryngeal involvement and different symptoms, age, duration, severity and laboratory variables.
MATERIAL AND METHODS Subjects Thirty female outpatients with definite or classical RA participated in the study. They were seIected at random from a register of 139 women with a positive rheumatoid factor test who had received parenteral gold treatment at the Department of Rheumatology in 1985. Twentyseven patients were omitted from the register before the randomising procedure because they fulfilled one or more of the following exclusion criteria: (a) another arthritic disease in addition to RA, (b)other systemic rheumatic disease, (c) pulmonary disease not associated with RA. One patient from each year class from 41 to 70 years of age was selected at random. If no patient could be found in a certain year class, a patient was first sought in the older year
Ana Otolaryngol (Stockh) 11 1
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
I
Laryngeal involvement in RA 991
class and then in the younger year class. Of the 30 first called patients, 23 agreed to participate. A second call was made to obtain a total of 30 patients. All the patients except one had radiographic signs of erosive arthritis. The exception never had a positive rheumatoid factor test and she was omitted from the study. The remaining 29 patients were aged from 41 to 69 years (552 1.6 years, mean +SEM) and their mean disease duration was 1 5 2 1.5 years. Thirteen patients had or had previously had nodules on their elbows. According to the American Rheumatism Association’s functional classification, four patients belonged to class I, 14 to class 11, 1 1 to class 111, and no patient betonged to class IV, which is the most disabled group. Twenty-three patients were on non-steroid anti-inflammatory drugs, 12 on gold (11 parenteral and one per os), 10 on glucocorticosteroids, 6 on immunosuppressive drugs and 2 on chloroquine at the time of the examination. Control subjects. Thirty healthy women aged 40-69 years (mean 53 t 1.5) constituted the control group. Most ofthe control subjects worked at the hospital. The same exclusion criteria as for the RA group were used and in addition signs or symptoms ofjoint disease. The control group did not differ significantly from the patient group in terms of age, height or body weight. No control subjects were on anti-inflammatory drugs. The controls were examined in the same way and at the same time as the RA patients, apart from the radiographic investigation. At the radiographic investigation, a second control group of 30 women was used. Their mean age ranged from 39 to 72 years (572 1.7). These women were either working at the hospital or were under examination at the Department of Radiology for other reasons. This control group was called the radiological control group. The exclusion criteria were the same for both control groups. Smoking habits. Among the RA patients as well as in the control group, 15 women were lifelong nonsmokers and 7 ex-smokers (not having smoked during the last 6 months). Seven RA patients and 8 controls were current smokers. No significant differences were found in terms of smoking debut, duration or daily number of cigarettes smoked between patients and controls. However, the ex-smokers of the RA group reported a significantly (pt0.01)longer duration of smoking than the ex-smokers in the control group. Patients and controls gave their informed consent to i n c h i o n in the study. The study was approved by the Ethics Committee of the Medical Faculty, University of Gothenburg.
Physical examination The subjects’ voices were judged to determine whether they were noticeably weak or if phonatory air leakage was present during normal speech in a quiet room. The larynx was externally inspected and paIpated. Aching during pressure on the thyroid cartilage was noted. The larynx was studied indirectly using a mirror and directly using a fiberoptic laryngoscope. Deviation of the larynx from the midline was noted (9).Localised erythema and/or thickening of the mucosa over the arytenoids was noted. The vocal cords and their mobility were inspected. The examinations were performed by the same investigator (AG), who had no knowledge of any other test results at the time of the examinations.
Respiratoryfitnction A volume-displacement, water-sealed spirometer (Bernstein) was used to determine vital capacity (VC) and forced expiratory and inspiratory volume for one second (FEV,, FIV,). At least three acceptable spirograms were obtained for each variable and the best was used in the subsequent analysis. Predicted VC and FEV, values were obtained from Berglund et al. (10). Peak expiratory and inspiratory flow (PEF, PIF) were determined from flow-volume loops obtained with a volume-displacement, rolling, sealed spirometer (Electro Med. 70) connected to a plotter (Hewlett-Packard 7090). The procedure was repeated until acceptable and reproducible recordings were obtained.
992 A. Geterud el al.
Acta Otolaryngol (Sto&h) 11 1
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
The resistance of the respiratory system (RrJwas determined using a 4 Hz forced oscillation technique. The set-up was similar to that described by Aronsson et al. (1 1). The slope of phase 111, i.e. of the alveolar plateau (AN?). was measured using the singlebreath nitrogen test (12). This test has been claimed to be sensitive in terms of detecting structural and functional changes in the small peripheral airways or lung parenchyma. Reference values were predicted according to Sixt et al. ( 1 3). Finally. the lung diffusing capacity for carbon monoxide (DCJ was determined using the single-breath technique (Jaeger Transferscreen I P ) ( I 4) and reference values were obtained according to Salorinne ( 1 4). In line with previous reports, FIV, and PIF were adopted as variables for detecting extrathoracic obstructions (1 5. 16). Radiography Radiography of the larynx was performed on a Siemens Orbix using the low-voltage technique (1 7) on patients as well as on the radiological control group. The arytenoid cartilages were observed. A high-resolution film screen combination (Kodak MRl film and MinR screen) was used. The films were taken while the subjects held their breath. Table I. Thirteen qirestions possibly associated with rheumatic laryngeal inuolvement and the nirrnhers of R4 patients and controls giL1ing positice answers to these questions Groups A. B and C represent patients with two. one or no signs of laryngeal involvement of the RA
I . Do you have a hoarse voice? 2. Do you have an unusually weak voice? 3. Have you had one or more periods of hoarseness during the last year without having a cold? 4. Does your throat sometimes hurt when speaking?
5. Have you experienced difficulties breathing in at any time during the last year? 6. Do you easily get short of breath in connection with moderate physical exercise? 7. Do you experience breathing difficulties when you have a cold? 8. Can a strange or wheezing sound be heard when you breathe? 9. Can a strange or wheezing sound be heard when you speak?
A n=4
B
2 0
3
C n=9
Controls n=30
1
0 0
2
2
3
0
0
1
3
0
1
2
3
3
1
3
3
2
2
0
0
0
0
2
1
0
5
1
2
4
1
1
3
1
0
2.9
1.3
0.4
10. Does your throat sometimes hurt when you cough or clear your throat? 1 1 . Do you sometimes have earache without having a cold? 12. Do you often have a feeling of fulness in your throat? I3 Does it sometimes hurt when you swallow?
Positive answersln
4.8
n=16
1
Acta Otolaryngol (Stockh) 11 1
LarynReal involvement in RA 993
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
Laryngeal involvement At the physical examination laryngeal involvement was defined as a localised erythema andlor thickening of the mucosa over the arytenoids and/or impaired abduction of a vocal cord. FIV, t2.01 and PIFt2.5 Ils were adopted as signs of impairment ofthe extrathoracic airways and as indirect signs of laryngeal involvement. The level was chosen in such a way that the specificity was above 80% (16). Regarding radiography, remnants of one or both arytenoid cartilages as a sign of cartilage destruction were regarded as laryngeal involvement (6). Questionnaire Both the RA group and the control group completed a comprehensive questionnaire. Those questions possibly associated with rheumatic laryngeal involvement are listed in Table I. Questions 1 4 relate to voice problems, 5-9 relate to breathing problems and 10-13 relate to fulness and pain (sometimes radiating to the ears) in the throat. Laboratory data The erythrocyte sedimentation rate was determined and immunoglobulin class-specific rheumatoid factors were analysed using a diffusion-in-gel, enzyme-linked, immunosorbent assay technique (18). Statistical evaluation Student’s t-test for unpaired observations, the chi-square test with continuity correction, Fisher’s exact test and Mantel-Haenszel’s chi-square test were used. Only two-tailed significances are given.
RESULTS
Physical examination. No patient or control subject was judged to have a noticeably weak or hoarse voice or to have inspiratory stridor during tidal breathing or when speaking. Aching during pressure on the thyroid cartilage was reported by 6 patients (21 Yo), compared with none in the control group (p
Laryngeal Involvement in Rheumatoid Arthritis AKE GETERUD.'
BJORN BAKE.? BIRGITTE
BERTHELSEN" ANDERS BJELLE~
and HASSE EJNELL' From the Departmenis of'lOtor/iinolaryn~olo~~, 'Clinical Physiolog?: zDiagnostic Radiology and 'Rlicwmatology. t niiwsity ($Gothenburg. Sahlgren 's Hospital. Gothenburg SiwdiJn
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
Geterud A. Bake B. Berthelsen B. Bjelle A and Ejnell H. Laryngeal involvement in rheumatoid arthritis. Acta Otolaryngol (Stockh) 1991: 11 1: 990-998. Twenty-nine female patients with definite or classical rheumatoid arthritis (RA)and 30 controls were studied in order to assess the prevalence of laryngeal involvement in patients with RA and the occurrence of extrathoracic airway obstruction. Laryngeal involvement was assessed by physical examination including direct fiberoptic laryngoscopy, respiratory function tests and low-voltage radiography. Physical examination revealed laryngeal involvement in 17 RA patients (59%). extrathoracic airway obstruction was indicated by spirometry in 4 (14%) and radiography revealed pathological findings in 3 patients (10%). One or more signs of laryngeal involvement were found in 20 patients (69 %). Symptoms of breathing difficulties were common (75%) among patients with laryngeal involvement. The erythrocyte sedimentation rate and class-specific rheumatoid factors were not correlated to laryngeal involvement. Key uords: rheumatoid arthritis. laryn.x, cricoarytenoidjoint, spirometry. radiography. rheumatoid .factors. e.\-trarhoracic airu-ay obstniction.
INTRODUCTION Laryngeal involvement in rheumatoid arthritis (RA) was first reported late in the 19th century (1). In postmortem studies, the prevalence of arthritis of the cricoarytenoid joint has varied between 45 and 88 % (2, 3.4). Reported findings resulting from indirect laryngoscopy, direct fiberoptic laryngoscopy and radiography have varied from 26 to 75% (2, 5, 6, 7,s). The wide range of reported prevalence figures can partly be explained by the fact that different methods were used. The definition of laryngeal involvement differed and control groups were not used. In addition. comparisons between the studies were difficult because the studied groups differed in terms of age, sex, disease severity and duration. In the present study, we combined indirect mirror and direct fiberoptic laryngoscopy with spirometry and low-voltage radiography of the cricoarytenoid joints to assess the prevalence of laryngeal involvement and the extent of extrathoracic airway obstruction in a homogeneous group of RA patients. We also studied the association between laryngeal involvement and different symptoms, age, duration, severity and laboratory variables.
MATERIAL AND METHODS Subjects Thirty female outpatients with definite or classical RA participated in the study. They were seIected at random from a register of 139 women with a positive rheumatoid factor test who had received parenteral gold treatment at the Department of Rheumatology in 1985. Twentyseven patients were omitted from the register before the randomising procedure because they fulfilled one or more of the following exclusion criteria: (a) another arthritic disease in addition to RA, (b)other systemic rheumatic disease, (c) pulmonary disease not associated with RA. One patient from each year class from 41 to 70 years of age was selected at random. If no patient could be found in a certain year class, a patient was first sought in the older year
Ana Otolaryngol (Stockh) 11 1
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
I
Laryngeal involvement in RA 991
class and then in the younger year class. Of the 30 first called patients, 23 agreed to participate. A second call was made to obtain a total of 30 patients. All the patients except one had radiographic signs of erosive arthritis. The exception never had a positive rheumatoid factor test and she was omitted from the study. The remaining 29 patients were aged from 41 to 69 years (552 1.6 years, mean +SEM) and their mean disease duration was 1 5 2 1.5 years. Thirteen patients had or had previously had nodules on their elbows. According to the American Rheumatism Association’s functional classification, four patients belonged to class I, 14 to class 11, 1 1 to class 111, and no patient betonged to class IV, which is the most disabled group. Twenty-three patients were on non-steroid anti-inflammatory drugs, 12 on gold (11 parenteral and one per os), 10 on glucocorticosteroids, 6 on immunosuppressive drugs and 2 on chloroquine at the time of the examination. Control subjects. Thirty healthy women aged 40-69 years (mean 53 t 1.5) constituted the control group. Most ofthe control subjects worked at the hospital. The same exclusion criteria as for the RA group were used and in addition signs or symptoms ofjoint disease. The control group did not differ significantly from the patient group in terms of age, height or body weight. No control subjects were on anti-inflammatory drugs. The controls were examined in the same way and at the same time as the RA patients, apart from the radiographic investigation. At the radiographic investigation, a second control group of 30 women was used. Their mean age ranged from 39 to 72 years (572 1.7). These women were either working at the hospital or were under examination at the Department of Radiology for other reasons. This control group was called the radiological control group. The exclusion criteria were the same for both control groups. Smoking habits. Among the RA patients as well as in the control group, 15 women were lifelong nonsmokers and 7 ex-smokers (not having smoked during the last 6 months). Seven RA patients and 8 controls were current smokers. No significant differences were found in terms of smoking debut, duration or daily number of cigarettes smoked between patients and controls. However, the ex-smokers of the RA group reported a significantly (pt0.01)longer duration of smoking than the ex-smokers in the control group. Patients and controls gave their informed consent to i n c h i o n in the study. The study was approved by the Ethics Committee of the Medical Faculty, University of Gothenburg.
Physical examination The subjects’ voices were judged to determine whether they were noticeably weak or if phonatory air leakage was present during normal speech in a quiet room. The larynx was externally inspected and paIpated. Aching during pressure on the thyroid cartilage was noted. The larynx was studied indirectly using a mirror and directly using a fiberoptic laryngoscope. Deviation of the larynx from the midline was noted (9).Localised erythema and/or thickening of the mucosa over the arytenoids was noted. The vocal cords and their mobility were inspected. The examinations were performed by the same investigator (AG), who had no knowledge of any other test results at the time of the examinations.
Respiratoryfitnction A volume-displacement, water-sealed spirometer (Bernstein) was used to determine vital capacity (VC) and forced expiratory and inspiratory volume for one second (FEV,, FIV,). At least three acceptable spirograms were obtained for each variable and the best was used in the subsequent analysis. Predicted VC and FEV, values were obtained from Berglund et al. (10). Peak expiratory and inspiratory flow (PEF, PIF) were determined from flow-volume loops obtained with a volume-displacement, rolling, sealed spirometer (Electro Med. 70) connected to a plotter (Hewlett-Packard 7090). The procedure was repeated until acceptable and reproducible recordings were obtained.
992 A. Geterud el al.
Acta Otolaryngol (Sto&h) 11 1
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
The resistance of the respiratory system (RrJwas determined using a 4 Hz forced oscillation technique. The set-up was similar to that described by Aronsson et al. (1 1). The slope of phase 111, i.e. of the alveolar plateau (AN?). was measured using the singlebreath nitrogen test (12). This test has been claimed to be sensitive in terms of detecting structural and functional changes in the small peripheral airways or lung parenchyma. Reference values were predicted according to Sixt et al. ( 1 3). Finally. the lung diffusing capacity for carbon monoxide (DCJ was determined using the single-breath technique (Jaeger Transferscreen I P ) ( I 4) and reference values were obtained according to Salorinne ( 1 4). In line with previous reports, FIV, and PIF were adopted as variables for detecting extrathoracic obstructions (1 5. 16). Radiography Radiography of the larynx was performed on a Siemens Orbix using the low-voltage technique (1 7) on patients as well as on the radiological control group. The arytenoid cartilages were observed. A high-resolution film screen combination (Kodak MRl film and MinR screen) was used. The films were taken while the subjects held their breath. Table I. Thirteen qirestions possibly associated with rheumatic laryngeal inuolvement and the nirrnhers of R4 patients and controls giL1ing positice answers to these questions Groups A. B and C represent patients with two. one or no signs of laryngeal involvement of the RA
I . Do you have a hoarse voice? 2. Do you have an unusually weak voice? 3. Have you had one or more periods of hoarseness during the last year without having a cold? 4. Does your throat sometimes hurt when speaking?
5. Have you experienced difficulties breathing in at any time during the last year? 6. Do you easily get short of breath in connection with moderate physical exercise? 7. Do you experience breathing difficulties when you have a cold? 8. Can a strange or wheezing sound be heard when you breathe? 9. Can a strange or wheezing sound be heard when you speak?
A n=4
B
2 0
3
C n=9
Controls n=30
1
0 0
2
2
3
0
0
1
3
0
1
2
3
3
1
3
3
2
2
0
0
0
0
2
1
0
5
1
2
4
1
1
3
1
0
2.9
1.3
0.4
10. Does your throat sometimes hurt when you cough or clear your throat? 1 1 . Do you sometimes have earache without having a cold? 12. Do you often have a feeling of fulness in your throat? I3 Does it sometimes hurt when you swallow?
Positive answersln
4.8
n=16
1
Acta Otolaryngol (Stockh) 11 1
LarynReal involvement in RA 993
Acta Otolaryngol Downloaded from informahealthcare.com by Nyu Medical Center on 06/14/15 For personal use only.
Laryngeal involvement At the physical examination laryngeal involvement was defined as a localised erythema andlor thickening of the mucosa over the arytenoids and/or impaired abduction of a vocal cord. FIV, t2.01 and PIFt2.5 Ils were adopted as signs of impairment ofthe extrathoracic airways and as indirect signs of laryngeal involvement. The level was chosen in such a way that the specificity was above 80% (16). Regarding radiography, remnants of one or both arytenoid cartilages as a sign of cartilage destruction were regarded as laryngeal involvement (6). Questionnaire Both the RA group and the control group completed a comprehensive questionnaire. Those questions possibly associated with rheumatic laryngeal involvement are listed in Table I. Questions 1 4 relate to voice problems, 5-9 relate to breathing problems and 10-13 relate to fulness and pain (sometimes radiating to the ears) in the throat. Laboratory data The erythrocyte sedimentation rate was determined and immunoglobulin class-specific rheumatoid factors were analysed using a diffusion-in-gel, enzyme-linked, immunosorbent assay technique (18). Statistical evaluation Student’s t-test for unpaired observations, the chi-square test with continuity correction, Fisher’s exact test and Mantel-Haenszel’s chi-square test were used. Only two-tailed significances are given.
RESULTS
Physical examination. No patient or control subject was judged to have a noticeably weak or hoarse voice or to have inspiratory stridor during tidal breathing or when speaking. Aching during pressure on the thyroid cartilage was reported by 6 patients (21 Yo), compared with none in the control group (p
