Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study.

INTRODUCTION: Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. METHODS: The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. RESULTS: Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. CONCLUSION: Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.

Spontaneous resolution of focal eosinophilic myositis of the adductor pollicis complicated by lung lesions.

Eosinophilic myositis is characterised by peripheral blood eosinophilia and eosinophilic infiltration in muscles, and is comprised three subtypes: focal eosinophilic myositis (FEM), eosinophilic polymyositis, and eosinophilic perimyositis. Muscle involvement of FEM is usually limited to the lower legs, and pulmonary complications have not been reported. We report a rare case of FEM in the left adductor pollicis complicated by lung lesions. A 37-year-old woman developed swelling of the first web space in the left hand. Magnetic resonance imaging (MRI) of the left hand demonstrated increased signal on fat-suppressed T2-weighted imaging in the left adductor pollicis. A muscle biopsy specimen demonstrated perimysial and endomysial infiltration of mononuclear cells and eosinophils, and necrosis and regeneration of muscle fibres. Chest computed tomography (CT) revealed upper-lobe-dominant ground-glass opacities (GGO). Both focal myositis and pulmonary lesions improved without treatment. This case suggests that FEM could involve adductor pollicis and have pulmonary lesions. In this case, myositis and GGO resolved spontaneously. Some FEM cases treated with glucocorticoids were reported in the past. Further studies are required to determine whether patients with FEM require therapeutic intervention.

Tacrolimus-induced pulmonary injury in rheumatoid arthritis patients.

BACKGROUND: Tacrolimus (TAC) was approved in Japan in 2005 for rheumatoid arthritis (RA) patients having inadequate response to other disease-modifying anti-rheumatic drugs. As of May 2007, spontaneous reports identified twenty-seven cases of exacerbation or new development of interstitial pneumonia among RA patients given TAC in Japan. OBJECTIVE: To describe the clinical and radiological characteristics of TAC-induced pulmonary injury (TIPI). PATIENTS AND METHODS: Eleven RA patients diagnosed with de novo pulmonary injury or exacerbation of IP during treatment with TAC were identified. Clinical, radiological, and laboratory data of ten of these cases were retrospectively analyzed. RESULTS: Baseline data for the ten patients were a mean age of 69.7 years; gender, 70% female; mean RA disease duration, 9.1 years; and pulmonary comorbidities, 90%. Six cases were classified as presumptive TAC-induced pulmonary injury (TIPI) and four as probable TIPI. Among the six presumptive cases, TIPI developed at an average of 84 days after initiation of treatment (n = 5) or four days after reinstitution of TAC (n = 1). Five cases were an exacerbation of pre-existing interstitial pneumonia and one was a de novo pulmonary injury. Radiological patterns of thoracic computed tomography (CT) scans of patients in the presumptive TIPI cases were hypersensitivity pneumonia like-pattern (n = 3), ground-glass opacity (n = 2), and organizing pneumonia-pattern (n = 1). All patients with presumptive TIPI were treated with high dosage glucocorticosteroids and one received concomitant immunosuppressants. Two of the six presumptive TIPI patients died. CONCLUSION: Rheumatologists should be aware of this rare but potentially life-threatening adverse event in RA patients receiving TAC.

Efficacy and safety of intravenous cyclophosphamide pulse therapy with oral prednisolone in the treatment of interstitial lung disease with systemic sclerosis: 4-year follow-up.

Interstitial lung disease (ILD) is a noteworthy condition in the treatment of systemic sclerosis (SSc) because of its associated mortality and morbidity; however, the efficacy of various treatments for ILD has been controversial in previous reports. In this study, we examined the efficacy and safety of intravenous cyclophosphamide (IVCY) pulse therapy with prednisolone (PSL) for the treatment of ILD with SSc. A total of 121 patients with SSc were screened and evaluated for ILD, using high-resolution computed tomography of the chest, pulmonary function testing, and bronchoalveolar lavage. Thirteen patients with active ILD were enrolled in this study. The treatment protocol for ILD was 0.4 g/m(2) of body surface area of IVCY monthly plus 0.8 mg/kg of body weight of PSL daily. Two to six doses of IVCY were administered, depending on the remission of ILD. Initial PSL doses were maintained for a month and then gradually tapered to 10 mg daily. An activity index of ILD showed improvements in all patients in the 12 months after the initial intervention; however, four patients experienced recurrence of ILD after 24 months, and one additional patient had recurrence of ILD after 36 months. Seven patients reached the 48-month point with no recurrence of ILD. This long observational study for 48 months showed the efficacy of IVCY with PSL for active alveolitis in the first year. However, because five patients had recurrence of ILD more than 1 year after the treatment, it would be necessary to consider maintenance therapy for ILD beyond 1 year.

A case of severe acute pancreatitis, in overlap syndrome of systemic sclerosis and systemic lupus erythematosus, successfully treated with plasmapheresis.

Here, we describe a case of severe pancreatitis in overlap syndrome of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in an adult female patient. Treatment with plasmapheresis and high-dose prednisone successfully saved her life and led to remission of the pancreatitis. This is the first case report of severe acute pancreatitis in the setting of overlap syndrome of SLE and SSc. The advantages and disadvantages of the use of corticosteroids are discussed.

A case of systemic lupus erythematosus presenting transverse myelitis after an episode of meningitis.

A 27-year-old woman suffering from systemic lupus erythematosus was admitted because she had motor and sensory palsy of the lower extremities, neck stiffness, and a fever. Cerebrospinal fluid study indicated meningitis, and magnetic resonance imaging revealed cord swelling and high signals at Th9-Th12 levels. Antibiotics treatment led to resolution of the meningeal signs. Intravenous cyclophosphamide and prednisolone resulted in a partial recovery from the transverse myelitis neurological disturbance.

Dermatomyositis associated with autoimmune idiopathic thrombocytopenia and anti-Ku antibody.

We describe a case of dermatomyositis with concurrent clinical and laboratory features of idiopathic thrombocytopenia associated with anti-Ku antibody. A diagnosis of dermatomyositis was established by the characteristic skin changes together with a muscle biopsy. Scintigraphic studies indicated cardiac involvement. Autoimmune idiopathic thrombocytopenia (AITP) has been described in association with both systemic lupus erythematosus (SLE) and scleroderma, but there are few reports describing AITP associated with myositis. To our knowledge, this is the first report of a case of dermatomyositis associated with AITP and anti-Ku antibody.

Efficacy of combination treatment with cyclosporin A and corticosteroids for acute interstitial pneumonitis associated with dermatomyositis.

Abstract Interstitial pneumonitis (IP) associated with polymyositis and dermatomyositis (PM/DM) is a serious complication that affects prognosis. We therefore undertook a retrospective multicenter study to examine the efficacy of a combination treatment with cyclosporin A (CsA) and corticosteroids. Fifty-three IP patients with PM/DM (9 PM, 44 DM) were analyzed. Thirty-two patients treated with CsA plus corticosteroids (9 PM, 23 DM) were included in the study. Four parameters, i.e., subjective symptoms, ausculatory sound, chest radiographs, and respiratory index, were serially evaluated. A general evaluation was performed 4 weeks after the start of the combination treatment. All patients with PM and chronic IP with DM, and 52% of those with acute IP with DM were graded as better than "partially effective" in the general evaluation. In contrast, all patients graded as "progressive" in the general evaluation had acute IP with DM. It is of note that in acute IP with DM, the survival rate of the group primarily treated with CsA and corticosteroids from the early stage of their disease was significantly higher than that of the group initially treated with corticosteroids alone (P = 0.049). In conclusion, a combination treatment of CsA and corticosteroids from the early stage of disease may be advantageous for patients with IP with PM/DM, especially acute IP with DM.