Takeshi Shoda

Pre-Treatment Ferritin Level and Alveolar-Arterial Oxygen Gradient Can Predict Mortality Rate Due to Acute/Subacute Interstitial Pneumonia in Dermatomyositis Treated by Cyclosporine A/Glucocorticosteroid Combination Therapy: A Case Control Study

Background Acute/subacute interstitial pneumonia in dermatomyositis (DM-A/SIP) is a disease associated with a poor prognosis that resists treatment with glucocorticosteroids (GC) and progresses rapidly in a period of weeks to months to death. We retrospectively studied outcomes, prognostic factors, and their relations with survival rate in patients with DM-A/SIP treated with early cyclosporine A (CSA)/GC combination therapy and 2-hour postdose blood concentration monitoring. Methods This study comprised 32 DM-A/SIP patients who were simultaneously treated with CSA and prednisolone. Clinical and laboratory findings were compared between those who died due to DM-A/SIP and those surviving 24 weeks after beginning of therapy. Prognostic factors were extracted, and their relations with the survival rate were evaluated. Results Of the 32 DM-A/SIP patients, 25 survived, 5 died of DM-A/SIP, and 2 died of infections. In those who died due to DM-A/SIP, ferritin level and the alveolar-arterial oxygen gradient were significantly increased compared with the survivors (P<0.001 and P = 0.002, respectively). Multivariate analyses showed that ferritin and alveolar-arterial oxygen gradient were independent prognostic factors of poor outcome. The survival rate 24 weeks after beginning of treatment was significantly lower in those with a ferritin level of ≥600 ng/ml and alveolar-arterial oxygen gradient of ≥45 Torr (P<0.001 and P<0.001, respectively). All patients with both prognostic factors died, and the outcome was significantly poorer in these patients than in those with one or neither of the prognostic factors (P<0.001). Conclusions We identified pre-treatment high serum ferritin level and high alveolar-arterial oxygen gradient as poor prognostic factors in DM-A/SIP patients undergoing early CSA/GC combination therapy and showed that the outcomes were poor in patients with both factors.

Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients.

Abstract Objectives: We retrospectively investigated clinical prognostic factors for interstitial pneumonia (IP) in anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM) patients. Methods: Subjects comprised 18 patients with anti-MDA5 Ab-positive DM-IP (9 survivors; 9 deaths). Results: Initial serum albumin levels, ferritin levels, and ground-glass opacity (GGO) scores in the right middle lobes were significantly higher in the death group than in the survivor group (p = .033, .013, and .005, respectively). Initial alveolar-arterial oxygen gradient (P[A-a]O2) was also higher in the death group than in the survivor group (p = .064). Initial serum ferritin, P[A-a]O2, and right middle lobe GGO score were found to significantly relate to death. Survival rates after 24 weeks were significantly lower among patients with an initial ferritin level of ≥450 ng/mL (25%), P[A-a]O2 of ≥30 mmHg (31%), and a right middle lobe GGO score of ≥2 (11%) than each of the others (p = .006, .020, and .002, respectively). Conclusions: An initial serum ferritin level of ≥450 ng/mL, P[A-a]O2 of ≥30 mmHg, and right middle lobe GGO score of ≥2 (GGO ≥5% of the lobe) were identified as poor prognostic factors for anti-MDA5 Ab-positive DM-IP patients.

Chemokine profiles of interstitial pneumonia in patients with dermatomyositis: a case control study

Chemokines play an important role in the pathophysiology of dermatomyositis (DM) with interstitial pneumonia (IP). However, the relation between chemokines and the disease activity or prognosis of DM-IP has not been elucidated. We evaluated the serum C-C motif chemokine ligand (CCL) 2, Th1 chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11), and Th2 chemokine (CCL17) profiles of 30 patients, and examined the relation between these chemokines and the disease activity or prognosis of DM-IP. Initial serum CCL2 level was higher in the death group (P = 0.007). To determine the cut-off points effective as poor prognostic factors of DM-IP, ROC curve analysis was carried out on initial serum CCL2 level. The value that maximized the area under the ROC curve was 894 pg/mL (sensitivity: 100%, specificity: 70.8%). Serum CCL2, CXCL9, CXCL10, and CXCL11 levels were lower at 2 weeks after treatment initiation than before treatment. Serum CCL2, CXCL10, and CXCL11 levels at 2 weeks after treatment initiation were higher in the death group. Serum levels of chemokines such as CCL2, CXCL10, and CXCL11 may be possible biomarkers of disease activity and prognosis in DM-IP, and serum CCL2 level may be useful when deciding initial treatment.

Efficacy and safety of combination therapy with prednisolone and oral tacrolimus for progressive interstitial pneumonia with systemic sclerosis: a retrospective study.

Abstract Objectives: We retrospectively investigated efficacy and safety of combination therapy with prednisolone (PSL) and tacrolimus (TAC) for progressive interstitial pneumonitis with systemic sclerosis (SSc-PIP). Methods: We studied 11 patients with SSc-PIP who received combination therapy with PSL (0.5 mg/kg/d) and TAC (3 mg/d). Results: Baseline Hugh-Jones grades were I, II, III, and IV in 2, 6, 2, and 1 patients, respectively. Krebs von den Lungen-6 (KL-6) values were elevated to 914 (range 300–2614) U/mL. % Diffusing capacity of carbon monoxide (%DLco) remarkably decreased to 47.4 (range 9.7–64.4) %. All patients were alive at 1 year after therapy. In response to treatment, interstitial pneumonia (IP) improved in three patients, stable in seven patients, and deteriorated in one patient. Total ground-glass opacity (GGO) score improved (p = .005). No significant changes occurred in values of KL-6, % forced vital capacity (%FVC), and %DLco. Presently, all seven patients who could be followed up were alive. IP improved in three patients and stable in four patients. Total GGO score improved (p = .016). KL-6, %FVC, and %DLco did not change. Mild cytomegalovirus or herpes zoster infection occurred in two patients. Grade I renal injuries were observed in three and one patient at 1 year and present, respectively. Conclusion: Combination therapy with PSL and TAC appeared to be well tolerated and effective in suppressing the disease activity of SSc-PIP.

Potential of Krebs von den Lungen-6 as a predictor of relapse in interstitial pneumonia with anti-aminoacyl tRNA synthetase antibodies-positive dermatomyositis

To identify a predictor of relapse in interstitial pneumonia (IP) in patients with anti‐aminoacyl tRNA synthetase antibodies‐positive dermatomyositis (ARS‐DMIP).

Chylothorax in dermatomyositis complicated with interstitial pneumonia

Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron’s papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

FRI0490 Clinical Characteristics of Combined Pulmonary Fibrosis and Emphysema in Patients with Connective Tissue Disease

Background Cottin proposed that patients with emphysema of the superior lung field and fibrosis of the inferior lung field on thoracic CT should be regarded as having combined pulmonary fibrosis and emphysema (CPFE). They reported poor prognosis and marked reduction in pulmonary diffusion on a respiratory function test (1). Since then, various reports of CPFE have been published. However, there have been few reports on CPFE in patients with connective tissue disease (CTD). Objectives To investigate the clinical characteristics of CPFE in patients with CTD who consulted our hospital and compare the prognoses. Methods Of patients with interstitial pneumonia (IP) in the presence of rheumatoid arthritis (RA), dermatomyositis (DM), ANCA-associated vasculitis (AAV), or systemic sclerosis (SSc) who were treated in our hospital between August 1988 and October 2014, we identified the patients diagnosed of CPFE on thoracic HRCT findings. We retrospectively examined their clinical characteristics and prognoses. Patients in whom a low attenuation area accounted for 10% or more of the superior lung field on HRCT were regarded as having emphysema (2). Results Overall, 512 patients had IP, and 116 had CPFE. RA-CPFE was detected in 61 (34.1%) of 179 patients with RA-IP. DM-CPFE was detected in 13 (11.6%) of 112 patients with DM-IP. AAV-CPFE was detected in 19 (20.7%) of 64 patients with AAV-IP. SSc-CPFE was detected in 23 (14.6%) of 157 patients with SSc-IP. CPFE was more frequent in RA and AAV patients. The mean age of the CPFE patients was 68.4±9.4 years. They consisted of 78 males and 38 females. There were 99 smokers (85.4%, Brinkman index: 904±514). Before the start of treatment, the LDH, KL-6, A-aDO2, %FVC, FEV1.0/FVC, RV/TLC, %DLco/VA, and eRVSP values were 245±101 U/mL, 841±783 U/mL, 37.1±30.0, 88.1±21.2%, 76.6±15.3%, 51.7±18.1%, 47.5±20.2%, and 32.3±11.9 mmHg, respectively. In the DM-CPFE and SSc-CPFE patients, the FEV1.0/FVC was higher than in the AAV-CPFE and RA-CPFE patients, and the %FVC and %DLco/VA were lower. Eighty-one patients had received PSL therapy, and 79 had received immunosuppressant. In 9, IVCY was combined. During the course, lung cancer was detected in 17 patients. Twenty-three patients died (exacerbation of IP: 12, lung cancer: 4, and others: 7). The mean survival was 12.5±1.1 years. The 3-, 5-, and 10-year survival rates after the start of treatment were 89.9, 75.3, and 66.5%, respectively. The prognosis of the DM-CPFE patients was poorer, and that of the SSc-CPFE patients was favorable. The prognoses of patients with A-aDO2 more than 35 and those with %DLco/VA less than 34 were significantly poor. Conclusions CPFE with CTD was frequent in patients with RA or AAV. Its incidence was higher in males and smokers. Respiratory function tests showed reduction in diffusing capacity. The prognosis of the SSc-CPFE patients was favorable, whereas that of the DM-CPFE patients was poor. Prognostic factors were A-aDO2 and %DLco/VA. References Cottin V et al., Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J. 2005;26(4):586-93. Mejía M et al., Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest. 2009 Jul;136(1):10-5. Disclosure of Interest None declared

Ultrasound evaluation of the effects of leukocytapheresis on rheumatoid arthritis.

Leukocytapheresis (LCAP) is effective in treating rheumatoid arthritis (RA). Ultrasound (US) examination of joints is useful for evaluating disease activity and therapeutic effects in RA, but the clinical assessment of LCAP therapy with US has been little reported. We investigated the usefulness of US for evaluating the effects of LCAP in patients with RA. US examination was performed in six patients (total of seven cases) who underwent LCAP. Twenty‐eight joints (bilateral shoulders, elbows, wrists, 1st to 5th metacarpophalangeal joints, 1st to 5th proximal interphalangeal joints, and knee joints) were evaluated by a systematic multiplanar grey‐scale and power Doppler (PD) examination. Disease activity of RA was evaluated using the 28‐joint Disease Activity Score with erythrocyte sedimentation rate (DAS28‐ESR). Moderate or good responses to LCAP based on the DAS28‐ESR were observed in four of the seven cases although C‐reactive protein (CRP) and ESR did not decrease. LCAP significantly reduced the mean total PD score 17.3 ± 11.6 to 13.0 ± 10.5 (P = 0.0469). The total PD score decreased in six of the seven cases, and the number of joints with PD score ≥2 decreased in five of the seven cases. The rate of decrease in the number of joints with PD score ≥2 correlated strongly with the DAS28‐ESR and its components, especially swollen joint counts and evaluators global assessment, but not with the rate of decrease in CRP and ESR. US imaging of joints may be useful for evaluating the therapeutic effects of LCAP on RA compared to other inflammatory parameters.

SAT0181 Prognosis of MPO-ANCA-Positive Interstitial Pneumonia Patients Following Active Treatment

Background Chest CT scan of patients with MPO-ANCA positive interstitial pneumonia often identifies a UIP pattern. This condition shows UIP-dominant pathological features, accompanied by characteristics differing from idiopathic pulmonary fibrosis such as poor fibroblastic foci. If these pathological differences are taken into account, the prognosis may differ between MPO-ANCA-positive interstitial pneumonia and idiopathic pulmonary fibrosis patients. (1) Objectives The prognosis was investigated in patients with MPO-ANCA-positive interstitial pneumonia having received immunosuppressive therapy beginning soon after disease onset. Methods Of the patients with microscopic polyangiitis admitted to our hospital between 2001 and 2012, MPO-ANCA-positive patients complicated by interstitial pneumonia (MPA-ILD) were enrolled in this study, in accordance with the EMEA Classification (2007). The clinical data, prognosis, and other variables were investigated in these patients. Results There were 32 cases of MPA-ILD (14 males and 18 females), with a mean age of 71.8 years (range: 48-87). The data at the start of treatment were: MPO-ANCA 379±486 EU, KL-6 692±551 U/ml, Aa-DO2 33.6±58, %FVC 80.9±18%, %DLco/VA 61.5±19%, and RV/TLC 42.0±8.4%. Chest CT scan at the start of treatment revealed a UIP pattern in 25 cases and a non-UIP pattern in 7 cases. All patients received treatment with PSL, combined with immunosuppressors in 29 cases (CY in 11 cases) and apheresis in 6 cases. After treatment, the MPO-ANCA level was below the detectable limit in most cases. On analysis of the prognosis, 5 patients died (from exacerbation of interstitial pneumonia in 1 case, infection + alveolar bleeding in 1 case, pulmonary hypertension in 1 case, and sudden death in 2 cases), with the median survival period being 124.6 months and the 5-year- survival rate being 85.5%. Following treatment, the ground glass opacity on chest CT disappeared, and the cyst tended to grow slightly. Conclusions The prognosis of MPA-ILD patients was favorable, suggesting that is better than that of usual idiopathic pulmonary fibrosis patients. When immunosuppressive therapy at sufficiently high dose levels, started soon after disease onset, was continued, MPO-ANCA became negative and remained so thereafter. We suggest that the prognosis of MPA-ILD patients may be improved if immunosuppressive therapy is applied more effectively. References Tanaka T, Otani K, Egashira R, Fukuoka J, et al: Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of nine patients. Respir Med. 2012; 106: 1765-70. Disclosure of Interest None Declared

Cyclosporin-Aにて一旦軽快し，減量にて再燃死亡した皮膚筋炎に伴う間質性肺炎の一例

A 67-year-old female noticed dyspnea on exertion associated with the development of erythema in the eyelids and the bilateral fingers, and was admitted to our hospital on July 21, 2004. Proximal muscle weakness in the limbs, heliotrope rash, and Gottrons sign were observed, but the CK level was normal (194 U/l). All autoantibodies except for rheumatoid factor were negative. Hypoxemia and interstitial pneumonia on chest CT images were observed. Based on these findings, a diagnosis of advanced interstitial pneumonia associated with dermatomyositis was made. Combination immunosuppressive therapy was initiated with corticosteroid pulse therapy and cyclosporin-A (Cy-A), resulting in marked improvement. The Cy-A trough concentration was markedly high (456.4 ng/ml). When cytomegalovirus infection developed, the dose of Cy-A was reduced. Although the blood trough concentration of Cy-A was maintained at an adequately high level, the patient died of recurrence of rapidly progressive interstitial pneumonia. Careful observation is required when the dose of Cy-A is reduced for a patient with interstitial pneumonia associated with dermatomyositis. Furthermore, it is suggested that the trough concentration level of Cy-A is not always a useful parameter.