Performance of myositis-specific antibodies detected on myositis line immunoassay to diagnose and sub-classify patients with suspected idiopathic inflammatory myopathy, a retrospective records-based review.

AIM: To evaluate myositis line immunoassay (LIA) for diagnosis and sub-classification of suspected idiopathic inflammatory myopathy (IIM). To investigate if test performance is improved by increasing signal strength cut-off for myositis-specific antibody (MSA) or combining MSA with indirect immunofluorescence (IIF). METHODS: A retrospective, consecutive case series of patients investigated for MSAs from June 2013 to June 2020 for suspected IIM. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals for diagnosis of IIM. Association of IIM diagnosis with increased signal strength and presence of an expected IIF pattern on Hep-2 cells was assessed by Fisher's exact test in MSA-positive patients. RESULTS: A total of 195 patients were evaluated. IIM was diagnosed in 32/195 (16.4%) patients. MSAs were detected in 41/195 (21%) patients, 18/41 (43.9%) patients with an MSA had a diagnosis of IIM. The probability of an IIM diagnosis was increased in MSA-positive patients with high compared with low signal strength (83.3% vs 43.5%; P = 0.01) and an expected compared with unexpected IIF pattern (61.5% vs 23.8%; P = 0.04). Specificity for IIM was not significantly improved by increasing signal strength cut-off (85.9% vs 93.8%). Positive predictive value of myositis LIA was only modest and not significantly improved by either increasing signal strength cut-off or requiring an expected IIF pattern for determination of MSA positivity (43.9% vs 60% vs 61.5%). Sub-classification of IIM correlated closely for respective MSAs (88.9%). CONCLUSION: Increased MSA signal strength on myositis LIA and the presence of an expected IIF pattern were associated with IIM diagnosis. Test performance was non-significantly improved by these methods. Prevalence of IIM in this patient cohort was low; it is not excluded that LIA performance could be improved by these methods in a higher prevalence cohort.

Longitudinal study of intravenous versus subcutaneous immunoglobulin replacement therapy in hematological malignancy.

AIM: To present findings from a longitudinal study on infection risk, mortality, and patient perspective of intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment for patients with hypogammaglobulinemia secondary to hematological malignancy or its treatment (abbreviated as SID). METHODS: Observational study period included final year of IVIg (13 patients) and of the first 3 years of SCIg (17 patients) with SID. Data were collected on clinical outcomes from medical records and patient perception via study specific questionnaire. RESULTS: The median age was 63 years (53-76 years), and for 82.4% of patients their hematological malignancy was in complete remission. The annual mean serum IgG trough levels remained stable over the 4 years and were 7.0 g/L (±2.77 g/L) with IVIg, and 8.0 g/L (±1.75 g/L), 8.7 g/L (±2.75 g/L), and 7.6 g/L (±2.89 g/L) (year 1, 2, and 3, respectively) with SCIg. While the annual infection rate was similar, the rate of hospitalization due to infection fluctuated, with 37%, 9%, 15%, and 32% in year 1, 2, 3, and 4 respectively. There were no systemic adverse events with IVIg or SCIg. Patients reported a strong preference for SCIg. One patient died due to progression of underlying disease and infection within the study period. CONCLUSION: SCIg was the preferred treatment mode over IVIg in our cohort, but both were well tolerated without any systemic adverse events in 4-year follow up. The dosage and serum IgG levels were stable throughout. However, the number of infections requiring hospitalization fluctuated. It is anticipated that these findings encourage more hospitals to offer SCIg for SID patients.

Granulomatous lymphocytic interstitial lung disease: limiting immunosuppressive therapy-a single-centre experience.

Granulomatous lymphocytic interstitial lung disease (GLILD) is characterized by lymphocytic and granulomatous pulmonary infiltration occurring in common variable immunodeficiency (CVID). It is associated with increased mortality compared with CVID patients without GLILD. There are no treatment guidelines due to the low prevalence and the heterogeneity of the condition. A case review of three patients diagnosed with GLILD was performed from a single Australian centre. Patients met the European Society of Immunodeficiency criteria for CVID and a diagnosis of GLILD was confirmed by a multidisciplinary team. Patients were managed with immunoglobulin (Ig) replacement and immunosuppressive agents if required: the decision for immunosuppression was made on the basis of symptoms and declining pulmonary function. All patients clinically improved. One patient had immunosuppressive treatment ceased. GLILD responds to varying immunosuppressive regimes when IgG monotherapy fails. Immunosuppressive therapy can be discontinued following improvement, but patients require close observation. This series helps inform future GLILD treatment guidelines.

Subcutaneous Immunoglobulin Therapy for Hypogammaglobulinemia Secondary to Malignancy or Related Drug Therapy.

Immunoglobulin replacement therapy (IRT) has an important role in minimizing infections and improving the health-related quality of life (HRQoL) in patients with immunodeficiency, who would otherwise experience recurrent infections. These plasma-derived products are available as intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg). The global demand for these products is growing rapidly and has placed pressure on supply. Some malignancies and their treatment (as well as other medical therapies) can lead to secondary hypogammaglobulinemia or secondary immunodeficiency (SID) requiring IRT. Although IVIg use in this cohort has well-established therapeutic benefits, little is known about SCIg use. A literature search in July 2015 found only 7 published articles on SCIg use. These articles found that both IRT modes had equivalent efficacy in regard to reduction of bacterial infections. In addition, SCIg was reported to produce higher serum IgG trough levels compared with IVIg on equivalent dosage with the added benefit of fewer adverse effects. Patient HRQoL reports demonstrate preference for SCIg because of reduced adverse effects and hospital visits. There are no health economic models published on SCIg use in SID, but models on primary immunodeficiency disease and IRT conclude that SCIg provided greater economic benefits than IVIg. The findings of this small number of reports suggest that SCIg therapy for patients with SID is likely to be beneficial for both the patient and health care providers. To substantiate wider use of SCIg in SID, larger and more detailed studies are needed to accurately quantify the effectiveness of SCIg.

Moving from viral suppression to comprehensive patient-centered care: the high prevalence of comorbid conditions and health risk factors in HIV-1-infected patients in Australia.

HIV clinicians today need to move from focusing on viral suppression to a chronic disease model in which comorbid conditions and risk factors are comprehensively identified and addressed to reduce rates of serious non-AIDS-related morbidity and mortality. This study aimed to determine the prevalence of comorbid conditions in an Australian HIV-positive population. Of 180 patients included, there was a median CD4 count of 0.520 cells/mm(3). The majority (88%) of patients were currently receiving highly active antiretroviral therapy (HAART). There were high rates of failure to attend clinical appointments (30%), current smoking (42%), hypertension (16%), and dyslipidemia (17%). Significant rates of dipstick-positive proteinuria (16%) and elevated blood glucose (15%) were recorded. Risk factors were commonly not addressed by the treating clinician. There is an urgent need to systematize detection and management of high-prevalence comorbid conditions to prevent premature mortality associated with serious non-AIDS events.