Kentaro Isoda

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.

Initial limited three-level thin-section computed tomography scorings predict the prognosis of acute/subacute interstitial pneumonia in patients with dermatomyositis

Abstract Objectives: We investigated the prediction of outcomes of patients with dermatomyositis with acute/subacute interstitial pneumonia (DM-A/SIP) on the basis of chest computed tomography (CT) images. Methods: In 20 patients with DM-A/SIP (13 survivors; seven deaths), the relationships between prognostic outcomes and chest high-resolution CT (HRCT) findings or limited three-level thin-section CT scoring on the first examination were retrospectively investigated. Results: No significant difference was noted in chest HRCT findings between the survivor group and death group. The ground-glass opacity (GGO) scores of the right upper and middle lobes and left upper lobe, and the fibrosis score of the right middle lobe were significantly higher in the death group than in the survivor group (p = 0.01, 0.001, 0.02, and 0.02, respectively). The influence of the GGO score of the right middle lobe on death from IP was the strongest among the items examined, and it was independently significant (p = 0.01). A right middle lobe GGO score of ≥3 (GGO ≥ 25% of the lobe) was determined to be the best cut-off value for a poor prognosis (sensitivity: 85.7%, specificity: 85.7%), and the survival rate after 24 weeks was significantly lower in patients with a right middle lobe GGO score of ≥3 (survival rate: 0.0%) than in those with a score of< 3 (92.9%) (p < 0.0001). Conclusions: The prognosis of patients with DM-A/SIP was poor when the range of right middle lobe GGO was 25% or higher on limited three-level thin-section CT.

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.

Dermatomyositis as a complication of interferon-α therapy: a case report and review of the literature

Autoimmune disorder is one of the important side effects of interferon-α therapy. Some polymyositis cases as complication of interferon-α therapy were reported, but dermatomyositis were rarely. We report a case of dermatomyositis as a complication of interferon-α therapy for hepatitis C. A 52-year-old Japanese man was treated by combination therapy with pegylated interferon-α-2b and ribavirin for hepatitis C. Three months after the initiation of therapy, he showed erythema in the posterior cervical to dorsal and anterior cervical to thoracic regions, weight loss, general malaise, muscle pain, and severe increase in levels of muscle enzymes. We made a diagnosis of dermatomyositis according to these clinical features, proximal muscle-predominant myogenic change on electromyography, and infiltration of monocytes and CD4+-dominant lymphocytes on skin biopsy, although myositis-associated antibodies were absent. He was successfully treated with intravenous immunoglobulin and tacrolimus in addition to glucocorticoid. This is a very rare case of dermatomyositis associated with interferon-α therapy. We reviewed several similar published cases and the association of dermatomyositis and type I interferon.

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.

Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

Background Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness. Methods The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP). Results The median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04). Conclusions The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP.

AB0707 Initial Limited Three-Level Thin-Section Computed Tomography Scorings Predict the Prognosis of Acute/Subacute Interstitial Pneumonia in Patients with Dermatomyositis

Background Interstitial pneumonia (IP) is a common complication of dermatomyositis (DM), causing increased morbidity and mortality. DM with acute/subacute IP (A/SIP) progresses rapidly and the prognosis is poor. Previous studies have reported the following adverse prognostic factors: high initial serum ferritin level, high alveolar arterial oxygen gradient (AaDO2), low vital capacity, negative anti-aminoacyl tRNA synthetase (ARS) antibody, and positive anti-melanoma differentiation associated gene (MDA) 5 antibody. It is crucial to enable early prognosis prediction at the time of DM-A/SIP diagnosis. Objectives We examined to predictable of the prognosis from chest high-resolution computed tomography (HRCT) image of DM/A/SIP. Methods Data were obtained retrospectively from medical records of 20 consecutive DM-A/SIP patients admitted to Osaka Medical College Hospital and Yodogawa Christian Hospital between July 2011 and January 2014. Chest HRCT images were reviewed by 3 independent observers blinded to clinical information, and quantified using the CT score including both ground-glass opacity (GGO) score and fibrosis score as defined by Kazerooni. Each patients lobe was scored by same observers and using the average value. Briefly, limited 3 CT levels were pre-selected: aortic arch, the carina, and 1 cm above the diaphragm. Each lobe (right upper, middle, and lower, and left upper and lower lobes) of the lung was scored at the 3 sites on a scale of 0-5. Results Of the 20 patients, 7 died of IP. No significant differences were observed in patients background excluding anti-ARS antibody positivity and anti-MDA 5 antibody positivity between survivors and those who died. No significant differences were observed in chest HRCT findings between them. GGO scores in both upper lobes and the right middle lobe were significantly higher in the fatalities (P=0.01, 0.001, 0.02), but there was no significant difference in both lower lobes. Fibrosis scores in the right middle lobe was significantly higher in the fatalities (P=0.02), but there was no significantly difference in other lobes. A right middle lobe GGO score of ≥3 was determined as the best cut-off value for a poor prognosis (sensitivity: 85.7%, specificity: 85.7%), and the survival rate after 24 weeks was significantly lower in patients with a right middle lobe GGO score of ≥3 (survival rate: 0.0%) than in those with <3 (92.9%) (P <0.0001). Conclusions Initial limited three-level thin-section CT scorings may be a useful prediction marker of DM-A/SIP. Acknowledgements Takao Kamimori, Hiroshi Fujiwara, Yodogawa Christian Hospital Disclosure of Interest None declared

SAT0479 Increased Serum Light Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis

Background Dermatomyositis (DM) is frequently complicated with interstitial pneumonia (IP), causing increased morbidity and mortality. It is important to identify a useful serum marker associated with the progression, severity, and prognosis of DM-IP patients. Activated CD8+ T cells play an important role in the pathogenesis of DM-IP. LIGHT (the name of which is derived from ‘homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator [HVEM], and expressed by T lymphocytes’) is a member of the TNF superfamily and activates CD4+ and CD8+ T cells, monocytes and macrophages, natural killer cells, immature dendritic cells, and platelets. LIGHT mainly binds to the HVEM receptor on T cells and transmits co-stimulatory signals. HVEM signals stimulated by LIGHT more strongly induce CD8+ T cells than CD4+ T cells. LIGHT has been reported as a biomarker of inflammatory diseases, such as rheumatid arthritis, ankylopoietic spondylarthritis, inflammatory bowel disease, and atopic dermatitis, but its association with the pathology of DM-IP has not been clarified. Objectives Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness. Methods The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP). Results The median serum LIGHT level was 119 (16-335.4) pg/mL, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL-6 level was 14.7 (2.4-154.5) pg/mL (n=13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6-335.4] pg/mL) was significantly higher than that in DM-CIP patients (94.3 [16-164.2] pg/mL) (P =0.02). The serum IL-6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/mL to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R =0.55, P =0.04) and total ground-glass opacity scores (R =0.72, P =0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4-259.3) pg/mL 4 weeks after treatment initiation (P =0.04). Conclusions The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP. Disclosure of Interest None declared