Polskie Archiwum Medycyny Wewnętrznej
-
Pol. Arch. Med. Wewn. · Jun 2022
ReviewParoxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment.
In recent years, "old" paroxysmal nocturnal hemoglobinuria (PNH) has achieved new advances in terms of the understanding of its pathophysiology, modern approach to diagnostics, optimization of therapy, and dynamic development of new therapeutic agents. This review emphasizes the greater than previously recognized importance of the reduced susceptibility of PNH stem cells to apoptosis in the selection of a defective clone. Some changes in cytokine and chemokine profiles in patients with PNH have been interpreted in the context of autoimmunity and apoptosis. ⋯ Determinants of modern treatment, such as strategies (complement C5 inhibitors vs hematopoietic stem cell allotransplantation), the safety and efficacy of treatment with eculizumab or ravulizumab, policy of initiation and monitoring of treatment, the criteria for response to treatment and final outcomes of treatment are described. Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted.
-
Pol. Arch. Med. Wewn. · Jun 2022
Recent advances in the diagnosis and therapy of large vessel vasculitis.
Large vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), causes granulomatous vascular inflammation mainly in large vessels, and is the most common primary vasculitis in adults. Vascular inflammation may evoke many clinical features including vision impairment, stroke, limb ischemia, and aortic aneurysms. The best way to diagnose LVV is to combine medical history, physical examination, various laboratory tests, and imaging modalities. ⋯ Tumor necrosis factor inhibitors are ineffective in GCA but effective in TAK. On the other hand, tocilizumab may be used to treat both diseases. Promising targeted therapies evaluated in ongoing clinical trials include, for example, anti‑IL‑12/23 (ustekinumab), anti‑IL‑17 (secukinumab), anti‑IL‑1 (anakinra), anti‑IL‑23 (guselkumab), anti‑cytotoxic T‑lymphocyte antigen 4 (abatacept), Janus kinase inhibitors (tofacitinib and upadacitinib), anti‑granulocyte / macrophage colony‑stimulating factor (mavrilimumab), and endothelin receptor (bosentan) therapies.