Efficacy and safety of intravenous and subcutaneous immunoglobulin therapy in idiopathic inflammatory myopathy: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis on the efficacy and safety of intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin (Ig) therapy in the treatment of idiopathic inflammatory myopathy (IIM) and juvenile dermatomyositis (JDM). METHODS: PubMed, Embase and SCOPUS were searched to identify studies on Ig therapy in patients with IIM and/or JDM (2010-2020). Outcome measures were complete response (CR) or partial response (PR) in terms of muscle power and extramuscular disease activity measures on the International Myositis Assessment and Clinical Studies Group (IMACS) core set domains. RESULTS: Twenty-nine studies were included (n = 576, 544 IIM, 32 JDM). Muscle power PR with pooled Ig therapy was 88.5% (95% confidence interval (CI): 80.6-93.5, n = 499) and PR with SCIg treatment was 96.61% (95% CI: 87.43-99.15, n = 59). Pooled PR with first-line use of IVIg was 77.07% (95% CI: 61.25-92.89, n = 80). Overall, mean time to response was 2.9 months (95% CI: 1.9-4.1). Relapse was seen in 22.76% (95% CI: 14.9-33). Studies on cutaneous disease activity and dysphagia showed significant treatment responses. Glucocorticoid and immunosuppressant sparing effect was seen in 40.9% (95% CI: 20-61.7) and 42.2% (95% CI: 20.4-64.1) respectively. Ig therapy was generally safe with low risk of infection (1.37%, 95% CI: 0.1-2.6). CONCLUSIONS: Add-on Ig therapy improves muscle strength in patients with refractory IIM, but evidence on Ig therapy in new-onset disease and extramuscular disease activity is uncertain.

Subcutaneous immunoglobulin in inflammatory myopathies: efficacy in different organ systems.

MGD and CG were responsible for the study's conception and design. VP and DM contributed to data acquisition. VP and DB planned and performed the statistical analyses. All Authors contributed to data interpretation. MGD, CG, VP and DM drafted the manuscript. AG and DB revised the manuscript critically for intellectual content. All authors gave their final approval of the version of the manuscript to be published.

Subcutaneous IgG in the Myositis Spectrum Disorders.

The efficacy of subcutaneous immunoglobulin is reported in several neurological disorders and, more recently, its use has been extended to other inflammatory diseases, such as the idiopathic inflammatory myopathies, including polymyositis and dermatomyositis. Due to the rarity of these disorders, the role of immunoglobulin, administered intravenously or subcutaneously, remains unclear and poorly investigated. We report our experience about the use of subcutaneous immunoglobulin in myositis spectrum disorders, from idiopathic inflammatory myopathies to more complex conditions, such as overlap and cancer-associated myositis or pregnancy.

Subclinical Cardiac Dysfunction in Polymyositis and Dermatomyositis: A Speckle-tracking Case-control Study.

OBJECTIVE: Subclinical heart disease occurs in up to 50% of patients with idiopathic inflammatory myopathies (IIM) and is difficult to detect through conventional imaging. We investigated the usefulness of global longitudinal strain (GLS) measurement to detect a subclinical systolic ventricular dysfunction in patients with IIM. METHODS: We enrolled 28 patients with IIM and 28 matched controls in a 1:1 fashion. Standard variables for the left ventricle (LV) and right ventricle (RV) systolic and diastolic function were measured and compared between cases and controls, along with speckle-tracking GLS of the LV and RV. A possible correlation between GLS and muscle strength, disease activity, cardiovascular risk factors, and other organ systems involvement was searched. RESULTS: Standard variables of systolic and diastolic dysfunction were similar between patients and controls. GLS was significantly lower in patients when compared with controls for both LV (-18.7 ± 4.2% vs -21.2 ± 2.1%, p = 0.006) and RV (-19.3 ± 6.3% vs -22.5 ± 3.8%, p = 0.033). Patients with IIM had a 4.9-fold increased risk for impaired left GLS [relative risk (RR) 4.9, 95% CI 1.5-15.8, p = 0.006], which involved usually basal and mid-segments of the anterior, anterior-septal, and lateral wall. Patients with IIM had a 3.4-fold increased risk for impaired right GLS (RR 3.4, 95% CI 1.1-11.7, p = 0.04) with the basal segment of the free RV wall most frequently involved. Muscle strength, disease activity, damage and duration, other organ system involvement, and previous treatment were not associated with reduced GLS. CONCLUSION: Subclinical systolic impairment is common in patients with IIM without overt LV dysfunction. In this context, GLS is a potentially useful variable.

Second generation sequencing of three STRs D3S1358, D12S391 and D21S11 in Danes and a new nomenclature for sequenced STR alleles.

Second generation sequencing (SGS) may revolutionize the field of forensic STR typing. Two of the essential requirements for implementation of an SGS based approach for forensic investigations are (1) establishment of adequate frequency databases and (2) adoption of a new STR nomenclature. We report the STR sequences and allele frequencies of three STR loci: D3S1358, D12S391 and D21S11 in 197 unrelated Danes. We used a new STR nomenclature that depicts the locus name used in forensic genetics, the length of the repeat region divided by the repeat length (typically 4 nucleotides) and detailed sequence information of possible sub-repeats and SNPs within the amplified fragment.

Subcutaneous IgG in immune-mediate diseases: proposed mechanisms of action and literature review.

Intravenous immunoglobulin (IVIg) constitutes a relevant treatment option in various immune-mediated disorders, such as chronic inflammatory neuropathies and idiopathic inflammatory myopathies (IIM). Several advantages are linked to IVIg immunomodulatory and steroid sparing effects and to the possibility to withdraw the immunosuppressant therapy. However, the use of IVIg is not always easy to manage. It is associated with the need of an intravenous route of administration, high costs, and the risk of serious systemic adverse effects. More recently, the subcutaneous administration of immunoglobulin (SCIg) has been used in immunological practice as an alternative to IVIg, administered at lower dosages and more frequent intervals. This results in higher and more stable IgG serum levels and may prevent end-of-dose reduction and adverse effects caused by sudden IgG serum elevation. Moreover, the use of SCIg is more feasible, patient-friendly and cost-effective compared to the intravenous administration. In this context we compared IVIg and SCIg long term efficacy in the treatment of chronic inflammatory neuropathies and IIM, by reviewing the current literature and reporting the data obtained from our clinical experience about the use of SCIg in patients with myositis. We also described the most recent evidence on the immunomodulatory role of immunoglobulin, the pharmacokinetic properties of SCIg compared to the IVIg treatment, and the consequent clinical, laboratory and immunological implications.

Prognostic significance of immunohistochemical phenotypes in patients treated for high-grade cervical intraepithelial neoplasia.

Strong evidence exists that the host's immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P ≤ 0.0001). These data reinforce the evidence of the relevance of the host's immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates.