Role of Anifrolumab in Refractory Cutaneous Manifestations of Lupus Erythematosus: A Case Series and Literature Review.

Lupus erythematosus (LE) is an autoimmune disease that presents either as a systemic (SLE) or an isolated skin disease (CLE). Currently, there is no FDA-approved medication specifically for CLE, and is treated with the same approach as SLE. We present two refractory cases of SLE with severe cutaneous manifestations unresponsive to the first-line therapy treated with anifrolumab. First, a 39-year-old Caucasian female with a known history of SLE with severe subacute CLE presented to the clinic for her refractory cutaneous symptoms. Her current regimen was hydroxychloroquine (HCQ), mycophenolate mofetil (MMF), and s/c belimumab with no improvement. Belimumab was discontinued, and she was started on anifrolumab with significant improvement. Another, a 28-year-old female with no known medical history was referred to a rheumatology clinic for elevated anti-nuclear antibody (ANA) and ribonucleoprotein (RNP) titers. She was diagnosed with SLE, and was treated with HCQ, belimumab, and MMF but failed to produce a reasonably good outcome. Hence belimumab was discontinued and anifrolumab was added instead with significant cutaneous improvement. The treatment spectrum for SLE is wide, which includes antimalarial (HCQ), oral corticosteroids (OCS), and immunosuppressants (Methotrexate-MTX, MMF, azathioprine-AZT). Anifrolumab, a type 1 IFNα receptor subunit 1 (IFNAR1) inhibitor, has been recently approved by the FDA for moderate to severe SLE while on standard therapy in August 2021. Early use of anifrolumab in moderate to severe cutaneous manifestations of SLE or CLE may result in significant improvement in patients.

Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study.

OBJECTIVES: This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. METHODS: A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3-18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). RESULTS: After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX (p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% (p = 0.0008), R5 by 20% (p = 0.0011), and R15 by 12% (p = 0.0097). DISCUSSION: Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.

Retrospective observations on the ability to diagnose and manage patients with asthma through the use of impulse oscillometry: comparison with spirometry and overview of the literature.

OBJECTIVE: Impulse oscillometry (IOS) is an evolving technology for the diagnosis and followup of patients with asthma. Our objective is to review the findings on patients who underwent both spirometry and IOS during clinical evaluations of their asthma. The goal was to retrospectively evaluate IOS during the initial diagnosis and followup of patients with asthma in comparison with spirometry. METHODS: We routinely perform IOS and spirometry evaluation in patients with suspected asthma during baseline visits and at followup. We reviewed the data on 39 patients over the age of 13 with asthma at baseline and following treatment with inhaled corticosteroids. IOS and spirometry were both done at baseline, following short acting bronchodilator administration, and at followup after at least three months of inhaled corticosteroid treatment. RESULTS: IOS showed improvement in airway function both initially, following short acting bronchodilator introduction, and later after initiation of long term inhaled corticosteroid treatment, even when the spirometry did not reveal improvement. We noted the IOS improvement in the reactance or AX as well as the resistance in smaller airways or R5. CONCLUSION: IOS may provide a useful measure towards identifying an asthma diagnosis and followup without inducing the extra respiratory effort spirometry requires.

Asthma remission in a patient with rheumatoid arthritis while on antiangiogenesis therapy during a rheumatoid arthritis trial demonstrated by forced oscillation and spirometry.

Asthma is a chronic inflammatory condition. An integral part of the inflammation is angiogenesis (neovascularization). This report describes a patient with rheumatoid arthritis (RA) and moderately severe asthma despite maintenance on inhaled corticosteroids (ics) and intermittent systemic steroids (ss). While enrolled in a clinical trial for RA employing MEDI-522 (Vitaxin), her asthma symptoms remitted substantially, with significant improvement in spirometry and airflow resistance measured by forced oscillation. The patient was able to discontinue ics and required no ss while taking MEDI-522. After termination of the clinical trial, the patient's asthma symptoms again increased and required reinstitution of ics for control.

The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, inflammatory lung disease in which tumor necrosis factor-alpha is overexpressed and has been suggested to play a pathogenic role. OBJECTIVES: To determine if infliximab, an anti-TNF-alpha antibody, results in clinical benefit and has an acceptable safety profile in patients with moderate to severe COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study, subjects with moderate to severe COPD received infliximab (3 mg/kg [n = 78] or 5 mg/kg [n = 79]) or placebo (n = 77) at Weeks 0, 2, 6, 12, 18, and 24. Efficacy, health status, and safety were assessed through Week 44. MEASUREMENTS AND MAIN RESULTS: Infliximab was generally well tolerated, but showed no treatment benefit as measured by the primary endpoint, Chronic Respiratory Questionnaire total score. Similarly, there was no change in secondary measures, including prebronchodilator FEV(1), 6-min walk distance, SF-36 physical score, transition dyspnea index, or moderate-to-severe COPD exacerbations. Post hoc analysis revealed that subjects who were younger or cachectic showed improvement in the 6-min walk distance. Malignancies were diagnosed during the study in 9 of 157 infliximab-treated subjects versus 1 of 77 placebo-treated subjects. No opportunistic infections were observed, and there were no differences in the occurrence of antibiotic-requiring infections, although the incidence of pneumonia was higher in infliximab-treated subjects. No infection-related mortality was observed. Higher proportions of infliximab-treated subjects discontinued the study agent due to adverse events (20-27%) than did placebo-treated subjects (9%). CONCLUSIONS: Subjects with moderate to severe COPD did not benefit from treatment with infliximab. Although not statistically significant, more cases of cancer and pneumonia were observed in the infliximab-treated subjects. The impact of infliximab on malignancy risk in patients with COPD needs to be further elucidated.

Clinical applications of forced oscillation to assess peripheral airway function.

Forced oscillation applies external pressures to the respiratory system to measure respiratory impedance. Impedance of larger central airways may be dissected from that of peripheral airways using multiple oscillation frequencies. Respiratory impedance is calculated by computer-assisted methods that yield separate resistive and reactive components. The reactive component includes respiratory system capacitative and inertive properties, which may be separately visualized for clinical purposes using resonance as a rough dividing line. Low oscillation frequencies comprise those below resonance, and relate most prominently to capacitative properties of peripheral airways. High oscillation frequencies comprise those greater than resonance, which relate most prominently to inertial properties of larger central airways. Measurements of resistance and reactance in patients with peripheral airway disease, before and after therapeutic intervention, manifest characteristic patterns of response in low frequency resistance and reactance measures that appear to be closely correlated with each other. In contrast, changes in large central airways manifest resistance change uniformly over low and high frequencies.

Color Doppler ultrasound of the hand: observations on clinical utility in rheumatoid arthritis.

The use of ultrasound with color Doppler in the evaluation of rheumatoid arthritis was followed in 25 patients with joint complaints. Small joint ultrasound of the metacarpophalangeal joints (MCPs) as well as the wrists was performed with supplementation by color Doppler. In addition, 6 patients were followed for at least 3 months after start of treatment of rheumatoid arthritis using the same technique. In patients with what appeared to be definite rheumatoid arthritis, ultrasound supported this diagnosis as evidenced by the finding of cortical defects, extensor tendon sheath thickening, and synovial proliferation. Increased activity by color Doppler ultrasonography was the most common finding. Significant decrease in color Doppler activity was noted in the 6 patients who were followed up after 3 months of therapy with disease-modifying agents. Therefore, the use of ultrasound with color Doppler could aid in the diagnosis and follow up of patients with rheumatoid arthritis.