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Biologics in allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tara V. Saco, Farnaz Tabatabaian
Auto-inflammatory syndromes such as Schnitzler syndrome and cryopyrin-associated periodic fever syndromes (CAPSs) are often associated with urticaria. These include Muckle-Wells syndrome, neonatal-onset multisystem inflammatory disease, and familial cold autoinflammatory syndrome. They are believed to be mediated by autosomal dominant mutations in the NLRP3 gene with the subsequent production of altered cryopyrin, which induces constitutive production of IL-1b. Anti-IL-1 monoclonal antibodies are utilized in these subjects to control the urticaria and other associated manifestations of these syndromes [39,40]. The FDA-approved monoclonal options for different types of urticaria include omalizumab, canakinumab, anakinra, and rilonacept.
Phagocytic cells and their functions
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
Neonatal-onset multisystem inflammatory disease (NOMID) is a severe form of these diseases characterized by neonatal-onset rash, continuous fevers, inflammation, aseptic meningitis, deforming arthropathy, sensineuronal hearing loss, and visual loss.
Uncommon Conditions Underlying AA Amyloidosis
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
The hereditary periodic fever syndromes form a unique group of diseases with intermittent clinical manifestations sustained by genetic defects (2). Four syndromes characterized by intermittent bouts of inflammatory symptoms have been clinically and genetically defined: familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), and cryopyrin-associated periodic syndromes which include Muckle-Wells syndrome, familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID). These conditions have been of great importance in unraveling the genes and mechanisms involved in the inflammatory response. Although the diagnosis of hereditary periodic fever syndromes has been greatly facilitated by genetic testing, their protean clinical manifestations hinder prompt recognition. With the exception of HIDS, all of them were known to be associated, at various frequencies, with AA amyloidosis. HIDS is characterized by a moderate deficiency of mevalonate kinase caused by mutations in the MVK gene. It has been reported that lack of isoprenoid products (the end product of the mevalonate enzyme pathway) raises ex vivo interleukin-1 secretion in HIDS. However, mechanisms less directly related to reduced isoprenoid output may contribute to IL-1 hypersecretion (2). We report on a 29-year old patient with recurrent fever attacks since the age of six months who recently developed nephrotic syndrome and renal amyloidosis, typed as AA. The fever attacks were associated with clinical manifestations typical of HIDS. Laboratory investigations documented very high values of SAA during attacks as well as in attack-free periods and high concentrations of serum IgD. Genetic analysis identified two missense mutations in the MVK gene thus fulfilling the diagnostic criteria for HIDS. Searches for mutations known to be pathogenic in other periodic fever syndromes were negative. This case highlights the importance of maintaining a high level of suspicion for amyloidosis even in conditions which are traditionally considered to be at no risk of developing AA amyloidosis.
Hematopoietic stem cell transplantation in systemic autoinflammatory diseases - the first one hundred transplanted patients
Published in Expert Review of Clinical Immunology, 2022
Sara Signa, Gianluca Dell’Orso, Marco Gattorno, Maura Faraci
Cryopyrin-associated periodic syndrome (CAPS) is an inherited inflammatory disorder [8], caused by mutations of NLRP3 encoding for protein involved in a multiprotein complex called Inflammasome, that is crucial for the activation and secretion of IL-1β. CAPS is secondary to gain-of function mutations that lead to an over activation of IL-1β and is characterized by skin rash, fever and inflammatory manifestations involving eyes, ears, bones, joints and central nervous system (CNS), with a variable disease spectrum. Treatment for CAPS consists mainly in IL-1β blockers (anakinra, rilonacept or canakinumab). A recent case report [24] describes a patient with CAPS and an intermediate severity phenotype (Muckle-Wells syndrome), who received an HSCT due to acute lymphoblastic leukemia (ALL) occurrence. After HSCT, the patient was completely free of CAPS signs/symptoms, with normal acute phase reactants. Seven years after HSCT, she is alive in a good condition, with a complete remission of both ALL and CAPS. Authors suggest that, since the expression of NLRP3 is non exclusive of the hematopoietic compartment, careful evaluation and larger studies are required to estimate the possible real benefit of HSCT in CAPS patients, especially those suffering from the most severe form, namely, CINCA (chronic infantile neurologic cutaneous articular) syndrome or NOMID (Neonatal-onset multisystem inflammatory disease).
Intravenous anakinra for tisagenlecleucel-related toxicities in children and young adults
Published in Pediatric Hematology and Oncology, 2022
Alexandra Dreyzin, David Jacobsohn, Anne Angiolillo, Birte Wistinghausen, Reuven J. Schore, Evelio Perez, Elizabeth Wells, Joshua Terao, Challice Bonifant, Radha Rohatgi, Hema Dave, Anant Vatsayan
Anakinra has already been shown to be safe and effective for various macrophage-mediated hyperinflammatory states, including those associated with severe COVID-19 infection, sepsis, and rheumatoid arthritis.12,13,22,23 Neonatal onset multisystem inflammatory disease, which has a similar CSF cytokine signature to that of ICANS, has been treated with subcutaneous anakinra, resulting in symptom reduction as well as reduction of IL-6 levels in the CSF.23 Anakinra has an excellent safety profile and relatively short duration of action when compared to tocilizumab.22 The safety profile documented in other patient populations, pre-clinical data, and robust mechanistic evidence for the therapeutic benefits of 1 L-1 inhibition make anakinra a promising agent which merits further study for treatment of ICANS and HLH-like toxicities after CAR-T, which are currently not well controlled with tocilizumab.
Unconventional therapies for hidradenitis suppurativa
Published in Expert Review of Clinical Pharmacology, 2018
Claudio Marasca, Maria Carmela Annunziata, Maddalena Napolitano, Gabriella Fabbrocini
Anakinra, a recombinant IL-1 receptor A (IL-1Ra) antagonist, is approved for moderate-to-severe RA and neonatal onset multisystem inflammatory disease (NOMID) [45]. In an open label, non-randomized study involving six patients with moderate-to-severe HS, treatment with anakinra SQ (100 mg/0.67 ml) daily for 8 weeks lead to a significant reduction in the Sartorius score (34.8 units from baseline, p ¼ .024) [46]. In a double-blind, randomized, placebo-controlled trial involving 20 patients with Hurley stage II or III HS, treatment with anakinra (100 mg/0.67 ml SQ) daily for 12 weeks led to a significant decrease in the disease activity compared to placebo (78% vs. 20%, p ¼ .02) [47,48]. HiSCR was achieved in 78% of patients in the anakinra arm compared to 30% in the placebo arm at 12 weeks (p ¼ .04). The change in HiSCR at 24 weeks trended toward non-significance (10% vs. 33%, p ¼ .28). Changes in other endpoints included a significant decrease in serum levels of interferon-gamma in the anakinra arm at 12 weeks (p ¼ .04), with a concomitant increase in IL-22 in the anakinra arm at 24 weeks (p ¼ .02). Exact values were not presented [47,48].