Schneider SW, Gaubitz M, Luger TA, Bonsmann G. Prompt response of refractory Schnitzler syndrome to treatment with anakinra

Journal of the American Academy of Dermatology (Impact Factor: 4.45). 06/2007; 56(5 Suppl):S120-2. DOI: 10.1016/j.jaad.2006.05.057
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    • "IL-1RA enters central nervous system within a therapeutic time window J Galea et al C max and tested the validity of our published PPK model. Anakinra has an excellent safety and tolerability profile in the subcutaneous formulation that is currently licensed for use in rheumatoid arthritis and has been used in clinical trials for type 2 diabetes (Larsen et al, 2007), juvenile arthritis (Ilowite et al, 2009), Muckle Wells syndrome (Hawkins et al, 2004), Schnitzler's syndrome (Schneider et al, 2007), and non-ST segment myocardial infarction. Concerns over the potential risk of infection have occasionally arisen given the slight increase (2% in anakinra patients versus < 1% in placebo) in rheumatoid arthritis patients (Nuki et al, 2002). "
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    ABSTRACT: The naturally occurring antagonist of interleukin-1, IL-1RA, is highly neuroprotective experimentally, shows few adverse effects, and inhibits the systemic acute phase response to stroke. A single regime pilot study showed slow penetration into cerebrospinal fluid (CSF) at experimentally therapeutic concentrations. Twenty-five patients with subarachnoid hemorrhage (SAH) and external ventricular drains were sequentially allocated to five administration regimes, using intravenous bolus doses of 100 to 500 mg and 4 hours intravenous infusions of IL-1RA ranging from 1 to 10 mg per kg per hour. Choice of regimes and timing of plasma and CSF sampling was informed by pharmacometric analysis of pilot study data. Data were analyzed using nonlinear mixed effects modeling. Plasma and CSF concentrations of IL-1RA in all regimes were within the predicted intervals. A 500-mg bolus followed by an intravenous infusion of IL-1RA at 10 mg per kg per hour achieved experimentally therapeutic CSF concentrations of IL-1RA within 45 minutes. Experimentally, neuroprotective CSF concentrations in patients with SAH can be safely achieved within a therapeutic time window. Pharmacokinetic analysis suggests that IL-1RA transport across the blood-CSF barrier in SAH is passive. Identification of the practicality of this delivery regime allows further studies of efficacy of IL-1RA in acute cerebrovascular disease.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2011; 31(2):439-47. DOI:10.1038/jcbfm.2010.103 · 5.41 Impact Factor
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    • "Oral steroids have not been beneficial at acceptable doses, and given the chronicity of the disease, are associated with significant cumulative side effects [4]. Despite the significant evidence of inflammation in this condition, there is almost complete failure to respond to a variety of immunosuppressants including azathioprine, ciclosporin, methotrexate, high dose immunoglobulin, hydroxychloroquine, dapsone, colchicine, rituximab, mycophenolate and infliximab [7-10]. Until recently, therefore, treatment of SS has been associated with a very disappointing outcome. "
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    ABSTRACT: Schnitzler Syndrome is an uncommon, inflammatory condition that presents with a constellation of chronic unremitting urticaria, fever, bone pain, arthralgia or arthritis, and a monoclonal IgM gammopathy. There is usually neutrophilia and raised inflammatory markers. Delayed diagnosis is common and treatment often unsuccessful. We report the case of a 43-year-old caucasian man who presented with urticaria unresponsive to conventional therapy. There was considerable delay in recognition of this as Schnitzler Syndrome, and symptoms were unresponsive to conventional immunosuppressive therapy.Commencement of anakinra was associated with a rapid and sustained clinical response. Schnitzler Syndrome is a rare disorder that mimics chronic idiopathic urticaria. This diagnosis should be considered in patients with urticaria unresponsive to antihistamines and conventional immunosuppressive therapy. Anakinra is an effective treatment although further studies are required, to determine long term therapeutic requirements and assess any potential adverse effects.
    Cases Journal 12/2008; 1(1):348. DOI:10.1186/1757-1626-1-348
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    ABSTRACT: We report a case of longstanding multidrug resistant Schnitzler’s syndrome that finally went into clinical remission upon treatment with anakinra and review the literature concerning IL1-RA treatment for Schnitzler’s syndrome. A now 71-year-old patient presenting with recurring episodes of urticaria and fever and secondary weight loss for the past 16years as well as arthralgia, hearing loss. The patient has anemia, leucocytosis with neutrophilia, thrombocytosis, elevated C-reactive protein and erythrocyte sedimentation rate, lymphadenopathy and a monoclonal IgM kappa band that later became oligoclonal with two IgM kappa bands and one IgM lambda band. The patient was treated with moderate effect with combination of prednisolone, azathioprine, and colchicine. In March 2009, anakinra 100mg daily sc was added during a disease flare. Within 24h after the first injection, both the urticaria and the fever disappeared and have not recurred. For the past 6months, the patient has been in clinical and biochemical remission. Colchicine has been stopped while the azathioprine and prednisolone doses are being reduced. Twenty-four patients with Schnitzler’s syndrome, including three patients with a variant of Schnitzler’s syndrome and three patients with a Schnitzler-like syndrome, have been successfully treated with anakinra. Nevertheless, seven out of seven patients, that either interrupted or used anakinra every other day, had relapse of their symptoms within 24-48h; anakinra was restarted in all patients with the same clinical efficiency. The current case history and the literature review already suggest an important role for IL-1 as a mediator in the pathophysiology of Schnitzler’s syndrome. KeywordsAnakinra-Autoinflammatory-Monoclonal gammopathy-Schnitzler syndrome-Urticaria
    Clinical Rheumatology 05/2010; 29(5):567-571. DOI:10.1007/s10067-010-1375-9 · 1.70 Impact Factor
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