Rheumatology 2001; 40: 216-220
© 2001 British Society for Rheumatology
Paediatric Rheumatology |
Pulmonary involvement in juvenile dermatomyositis: a two-year longitudinal study
Paediatric Rheumatology/Series Editor: P. Woo
Department of Paediatrics, Rheumatology Unit and
1 Department of Critical Care, Respiratory Unit, University of Florence, Italy
Abstract
Objective. To investigate the prevalence and features of asymptomatic pulmonary involvement in juvenile dermatomyositis (JDM).
Methods. Twelve JDM patients underwent pulmonary function tests at baseline, 12 and 24 months. Disease activity, duration, serum lactate dehydrogenase (LDH) values and antinuclear antibody (ANA) titres were also evaluated.
Results. Five patients showed lung impairment at baseline and four at 12 and 24 months. Forced expiratory volume in 1s, forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and alveolar volume were the most frequently altered variables, indicating a restrictive pattern and impairment of diffusion. The prevalence and features of pulmonary alterations did not change during follow-up. FVC values were significantly lower in active JDM patients and were inversely related to LDH. DLCO values were significantly lower in ANA-positive patients. About half of the patients of this small case series of JDM had asymptomatic lung disease.
Conclusions. We suggest that lung function should be evaluated at disease onset and regularly during follow-up, as pulmonary function tests can detect otherwise unpredictable pulmonary involvement.
KEY WORDS: Juvenile dermatomyositis, Pulmonary function tests.
Dermatomyositis (DM) is a multisystem disease that is characterized by acute or chronic non-suppurative inflammation of the striated muscles and skin. Its clinical features include deep proximal muscle weakness and upper eyelid and malar rash. As DM is a systemic vasculitis, inflammatory vascular changes may be found in other organs. The joints, heart, gastrointestinal tract and lungs may be affected, either directly or as a complication of severe muscle weakness [1–3]. Almost 50% of adult patients develop acute or chronic, subclinical lung involvement during the first few years of the disease. Lung involvement may contribute to death in about 10% of patients [3]. Diffuse interstitial fibrosis, presenting with fever, dyspnoea, cough and rales [4, 5], and aspiration pneumonia, due to pharyngeal dysmotility, have been reported [6]. Dyspnoea on exertion is a non-specific but serious symptom in DM, and is due either to lung impairment (interstitial fibrosis, aspiration or bacterial pneumonia) or to extrapulmonary involvement (congestive heart failure or cardiac arrhythmia) [3]. Non-productive cough is frequent, especially as a result of interstitial lung involvement. Functional or radiographic findings of interstitial lung involvement may also be found in asymptomatic patients [7].
Most of the available information on lung impairment in DM has been obtained in adults, and few studies have been carried out in children. Juvenile DM (JDM) has been studied in a wide group of connective tissue diseases [8–10] or reported as unusual pulmonary involvement [11, 12]. A reduction in ventilatory capacity in the absence of respiratory complaints was found in 78% of JDM patients by Pachman et al. [13]. Decreased diffusion capacity may be an early sign of interstitial lung disease, and occurs more frequently in those few children who develop antibodies to Jo-1 (histidyl tRNA synthetase) [14] and antisynthetase syndrome. This syndrome is rare in children and is characterized by a high frequency of non-erosive arthritis, Raynaud's phenomenon, fever and interstitial lung disease with severe dyspnoea on exertion, and early radiographic evidence of fibrosis. It has a poor prognosis, with a 5-yr survival rate of 70%; most patients die from pulmonary complications.
The aim of this work was: (i) to assess the prevalence and features of respiratory function abnormalities in patients with JDM in the absence of clinical or radiological signs of lung involvement; (ii) to follow up the changes in pulmonary function prospectively over 2 yr; and (iii) to investigate the relationship between respiratory abnormalities and disease activity and duration.
Materials and methods
Subjects
Twelve out-patients (two males, 10 females; mean age 13±4 yr, range 7–16 yr) fulfilling the Bohan et al. criteria for the diagnosis of JDM [15] were enrolled consecutively in the study. The patients' clinical records were reviewed in order to assess their history, clinical disease findings (duration, symptoms), and previous and current drug schedules (duration and cumulative dose of steroids). All patients were treated with prednisone (1–2 mg/kg per day for 2 months, with slow reduction over 2 yr). Cyclosporin A (5 mg/kg per day) was added when no response was evident after 5 months of prednisone treatment.
Methods
At enrolment and at follow-up, each patient underwent a complete clinical and instrumental examination. The following anthropometric data were recorded: age, gender, height, weight, pubertal stage [16] and muscle strength. The musculoskeletal evaluation included the measurement of muscle strength [17] in the upper limbs, lower limbs, abdomen and anterior neck. Symptoms and signs of pulmonary involvement were investigated by means of a standardized questionnaire and a clinical respiratory examination. The questionnaire was administered to each patient and/or the parents to evaluate the presence of dry or productive cough, fever, dyspnoea, recurrent wheezing, allergopathy and smoking habit [18]; no patient complained of any respiratory symptoms at enrolment. Informed consent was obtained from all patients and/or parents.
Laboratory data included concentrations of antinuclear antibodies (ANA), serum lactate dehydrogenase (LDH), creatine kinase (CK) and aldolase. Disease activity was assessed from the CK and LDH concentrations and muscle strength reduction [19].
Lung function measurements were obtained in all subjects according to standard methods. The best of three measurements, obtained while the patient breathed room air connected to a computerized water-sealed spirometer (Pulmonet Godart, Bilthoven, Netherlands), was used to calculate forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and maximal expiratory flow rates at 50 and 25% of FVC (MEF50 and MEF25, respectively). To calculate total lung capacity (TLC), functional residual capacity (FRC) was determined by the helium dilution method. Single-breath alveolar volume (VA) and carbon monoxide diffusing capacity (DLCO) were measured with an Autobox DL6200 (SensorMedics, Yorba, Linda, CA, USA). The concordance between the absolute values of TLC and VA (less than 5% difference) allowed us either to assess the execution of single-breath manoeuvres or to use VA to detect the presence of lung restriction or overinflation.
DLCO values were corrected for haemoglobin concentration according to the formula proposed by Clark et al. [20]. The predicted values of each subject were calculated by the use of the regression equations proposed by Rosenthal et al. [21, 22].
Pulmonary function data were expressed as S.D. score (actual value-predicted value/population S.D.) and defined as significantly reduced or increased when the value was less or more than ±1.64, corresponding to less or more than the fifth and 95th percentiles. Taking into account the wide age variation of our patients and the relationship between puberty and lung function, the S.D. scores were corrected according to the tables given by Rosenthal et al. [21, 22], which classify pubertal development according to Tanner's stages [16].
Statistical analysis
Two-tailed analysis of variance was used to compare functional data at baseline, 12 months and 24 months; the Bonferroni test was applied when the results were significant. The relationships between pulmonary function parameters and disease duration, laboratory data (LDH, CK) and the clinical measurement (muscle strength) were assessed by univariate linear regression. The unpaired Student's t-test was used to compare functional data in patients with and without ANA and patients with active and inactive disease. A P value of <0.05 was considered significant.
Results
All anthropometric and demographic data are reported in Table 1
. Data for patients with significantly altered pulmonary function tests are reported in Figure 1. Chest X-rays were normal in all patients at enrolment and none complained of respiratory symptoms during follow-up. At baseline, evidence of functional lung impairment was present in five (41%) patients (patients 4, 5, 7, 11 and 12). Patients 4 and 7 had reduced FVC, FEV1, MEF25, DLCO and VA; patient 4 also had reduced MEF50. Patients 5 and 12 showed a slight reduction of VA; patient 11 had reduced DLCO. At 12 and 24 months, statistically significant alterations in pulmonary function test values were detected in four cases (33%) (patients 4, 7, 11 and 12). Patient 5 normalized her slight reduction of VA. At 12 months, patients 4 and 7 still had reduced FVC, FEV1 and DLCO; patient 7 developed reduced MEF50 and MEF25. At 24 months, patient 4 had normal FEV1 and FVC and patient 7 had normal FVC and DLCO.
|
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), 5 (
), 7 (
), 11 (*) and 12 (
). The figure shows only significantly altered parameters (S.D. score <-1.64) at baseline (T0), 12 months (T1) and 24 months (T2).No statistically significant difference in FVC, FEV1, MEF50, MEF25, DLCO and VA mean values was found between the baseline, 12- and 24-month recordings in any patient. A significant inverse correlation was detected between the FVC S.D. score and the LDH concentration at baseline (r=-0.78, P=0.02); furthermore, FVC S.D. scores were significantly lower in patients with active disease (P=0.04) while DLCO S.D. scores were significantly lower in patients with ANA (P=0.02).
Discussion
The main result of this study is that about half of the patients in a small case series of JDM had asymptomatic lung disease that was detected by changes in some lung function tests but was otherwise unpredictable. Although they are not specific to this condition, the typical alterations that have been reported both in DM [3–7] and in the few studies carried out in JDM [8–10, 13] are restrictive pulmonary defects. In agreement with these results, in our study the prevalent feature was a restrictive lung disorder, detected in four patients, with a concomitant reduction of FEV1 and FVC in two of them. The reduction in VA was the most frequent alteration in pulmonary function, suggesting that subclinical respiratory muscle weakness may cause a global reduction in static lung volume. Limited involvement of the respiratory muscles has been reported to impair either the cough reflex [23] or the ability to inspire and/or expire maximally [24].
Involvement of the small airways (reduced MEF50 and MEF25) and of the alveolar capillary interface (reduced DLCO), observed in two out of our 12 patients, were additional findings of lung function impairment. These alterations have also been described in a few patients with juvenile rheumatoid arthritis [25] and juvenile systemic lupus erythematosus [26]. Abnormalities of the small airways (leading to bronchiolitis obliterans organizing pneumonia) and pulmonary vascular damage (leading to severe pulmonary hypertension) have been described in DM [27]. Pulmonary vascular damage has been described extensively in DM as a primary fibroproliferative process involving the arterioles and small muscular pulmonary arteries, and it can lead to severe pulmonary hypertension. Recently, unexplained pulmonary hypertension has been observed by Doppler echocardiographic techniques in DM patients [23].
Because of the limited number of observations and the short period of follow-up in the present study, we cannot conclude with confidence that the alterations in small airway flow and gas transfer detected by pulmonary function tests in JDM may predict the development of more severe pathological involvement of the lungs.
During the follow-up we observed neither progressive impairment of respiratory function nor the development of overt clinical or radiological signs of lung involvement. It should be noted, however, that during the study period the disease was stable and under control in all but one of the patients.
There was no apparent relationship between respiratory dysfunction and disease duration, suggesting that pulmonary alterations can develop in both the acute and in the intercritical and chronic phases of the disease.
Although it is difficult to interpret the clinical relevance of the relationship between haematological parameters and changes in pulmonary function of limited prevalence in such a small case series, the inverse correlation between FVC S.D. score and LDH levels and the significant reduction in FVC in patients with active disease may indicate that this functional parameter is more frequently impaired when muscle involvement is prominent and systemic disease is more severe.
The presence of ANA was associated with the reduction in DLCO; this may suggest that lung vascular damage (reduced DLCO) is more prominent in the subgroup of patients with circulating autoantibodies. All these results suggest that the lung may become a target organ of systemic involvement, especially when the disease is active.
The different disease durations in the patients at the time of enrolment and the different cumulative doses of corticosteroids are obvious sources of bias in our investigation. The small number of patients could further reduce the relevance of these results; however, JDM is extremely uncommon and no larger studies on respiratory function in this disease are available. A multicentre study in which a large number of patients are recruited at the time of disease onset could help elucidate the effects of the therapeutic regimen on disease activity and pulmonary dysfunction.
About half of the JDM patients in our study had some impairment of lung function, and we suggest that PFT should be performed at the onset of disease and again during follow-up, especially in patients with persistent disease activity.
Notes
Correspondence to: S. Trapani, Department of Paediatrics, Rheumatology Unit, A. Meyer Hospital, Via Luca Giordano 13, 50132 Florence, Italy 
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