scholarly journals Efficacy of interleukin-1 blockade in Schnitzler’s syndrome without detectable monoclonal gammopathy: a case-based review

2020 ◽  
Author(s):  
Riccardo Bixio ◽  
Maurizio Rossini ◽  
Alessandro Giollo
Keyword(s):  
Complete Remission ◽  
Inflammatory Markers ◽  
Monoclonal Gammopathy ◽  
Interleukin 1 ◽  
Autoinflammatory Disorder ◽  
Urticarial Rash ◽  
Schnitzler’S Syndrome ◽  
Inflammatory Drugs ◽  
Case Based

Abstract Schnitzler’s syndrome (SchS) is a rare autoinflammatory disorder characterized by urticarial rash and monoclonal gammopathy which is currently regarded as IL-1 mediated disease. We present the case of a 21-year-old woman presenting with urticarial rash, arthralgias, and elevated inflammatory markers. She has been suffering these symptoms for 2 years and was treated with antihistamines, omalizumab, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) without success. After an extensive diagnostic workout, we suspected SchS even without monoclonal gammopathy, and started Anakinra 100 mg daily with a dramatic response and achieving complete remission after 48 h of the beginning of the treatment, so we decided to confirm SchS diagnosis. We performed a search of the literature and found seven more cases of patients diagnosed with SchS without monoclonal gammopathy at the presentation. Five were treated with IL-1 blocking therapies and all achieved remission. We, therefore, prompt the possible role of IL-1 blockade therapy remission as support in diagnosing SchS without monoclonal gammopathy.

scholarly journals Increasing the Interval of Canakinumab Administration Effectively Supports the Remission of Schnitzler’s Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Vadim R. Gorodetskiy ◽  
Svetlana O. Salugina ◽  
Evgeny S. Fedorov
Keyword(s):  
Interleukin 1 ◽  
Term Treatment ◽  
Interleukin 1 Beta ◽  
Autoinflammatory Disorder ◽  
Urticarial Rash ◽  
Long Term Treatment ◽  
Schnitzler’S Syndrome ◽  
Injection Interval

Schnitzler’s syndrome (SchS) is a rare, disabling, autoinflammatory disorder characterized by recurrent urticarial rash and monoclonal IgM gammopathy. Interleukin-1 beta (IL-1β) plays an important role in the pathophysiology of SchS. Only anecdotal reports demonstrate the efficiency and safety of human monoclonal anti-human IL-1β antibody (canakinumab) use in SchS therapy. However, there are no generally accepted recommendations concerning the scheme (or frequency) of canakinumab use for this disease. Here, we report the effective long-term treatment of SchS in a 44-year-old male with a standard canakinumab dose (150 mg) but with an increased 4-month injection interval.

scholarly journals FRI0480 SCHNITZLER’S SYNDROME: DESCRIPTION OF AN ITALIAN MULTICENTER COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 837.1-837
Author(s):  
F. Crisafulli ◽  
P. Airò ◽  
F. Franceschini ◽  
A. Tincani ◽  
M. Frassi
Keyword(s):  
Monoclonal Gammopathy ◽  
Interleukin 1 ◽  
Diagnostic Delay ◽  
Injection Site Reaction ◽  
Lymphoproliferative Disease ◽  
Severe Allergic Reaction ◽  
Intermittent Fever ◽  
Multicenter Cohort ◽  
Laboratory Features ◽  
Schnitzler’S Syndrome

Background:Schnitzler’s syndrome is an autoinflammatory disease characterized by monoclonal gammopathy and recurrent episodes of urticaria accompanied by clinical and laboratory signs of acute inflammation. Although the exact pathogenic mechanisms have not been fully clarified, the role of Interleukin-1 seems to be central.Objectives:To describe clinical features and therapeutic approach in patients with Schnitzler’s Syndrome.Methods:Retrospective analysis of an Italian multicenter cohort. Data are expressed as the median (IQR).Results:The clinical data of 24 patients from 9 centers (median follow-up 6 years [2-10]; median age at diagnosis 56.5 years [51.25-64.25]) were collected. The median diagnostic delay was 2 years (0-10); the diagnosis was made consensually at the onset of symptoms in 4 cases. The main clinical and laboratory features are shown in Table 1. Therapeutic response was evaluable in 20 patients: all received corticosteroids (CS; 25mg/day [25-50]); in one case, a good clinical response was observed. Eight patients were initially treated with colchicine: in 3 cases it was effective in controlling symptoms and reducing the dose of CS; other 8 patients were treated with csDMARDs (n:1 [1-2]): only 1 patient had a good response to cyclosporin.Table 1.Clinical and laboratory featuresChronic Urticarial Rash, n (%)24/24 (100)Pruritus, n (%)17/24 (71)Intermittent fever, n (%)23/24 (96)Arthralgia/Arthritis, n (%)20/24 (83)Bone pain, n (%)8/24 (33)Weight loss, n (%)9/24 (38)Angioedema, n (%)4/24 (17)Lymphoadenopathy, n (%)7/24 (29)Hepatomegaly, n (%)3/24 (12)Splenomegaly, n (%)3/24 (12)Neuropathy, n (%)4/24 (17)Raised ESR or CRP, n (%)24/24 (100)Leukocytosis, n (%)17/24 (71)Anemia, n (%)9/24 (38)Monoclonal GammopathyIgG λ, n (%)5/22 (23)IgG κ, n (%)6/22 (27)IgM λ, n (%)1/22 (5)IgM κ, n (%)12/22 (55)Bence Jones Protein, n (%)6/23 (26)A bDMARD was initiated in 15 patients. In 7 of the 14 patients initially treated with anakinra this therapy was continued with benefit whereas in the other 7 patients the treatment was discontinued for primary inefficacy (1 patient), secondary inefficacy (3 patients) and adverse events (3 patients; 2 injection site reaction, 1 severe allergic reaction). After anakinra discontinuation, 5 patients were treated with canakinumab with a good response in 3 cases and a partial response in 1 case (persistent arthritis); 1 patient died during the treatment. No response was observed in 3 patients treated with TNF inhibitors as a 2ndor 3rdline bDMARDs, as well as in 1 case initially treated with tocilizumab (in which a good response was afterwards obtained with canakinumab). bDMARDs were associated with a csDMARD in 2 patients (methotrexate and methotrexate + cyclosporine).In one case monoclonal gammopathy evolved into Multiple Myeloma and the patient died 15 years after the onset of symptoms. Idiopathic myelofibrosis and myelodysplasia were found in one and in two patients, respectively.Conclusion:In most cases csDMARDs and bDMARDs like anti-IL6 and anti-TNFα were not able to control the disease. In contrast, in some cases, a good response to colchicine was observed; refractory patients may be successfully treated with anti-IL1 agents. Patients should be supervised for possible evolution towards lymphoproliferative disease.Disclosure of Interests:None declared

Persistent urticarial rash in a newborn

2021 ◽  
Author(s):  
Iwona Dziewa ◽  
Timothy Hahn ◽  
Neeti Bhardwaj
Keyword(s):  
Differential Diagnosis ◽  
Inflammatory Markers ◽  
Initial Evaluation ◽  
Response To Treatment ◽  
Therapeutic Trial ◽  
Age Group ◽  
Diagnostic Modality ◽  
Urticarial Rash

We presented the case of a 1-month-old girl with diffuse urticarial-like rash since birth. The initial evaluation showed elevated inflammatory markers. The response to treatment helped to narrow the diagnosis. In this case, we explored the differential diagnosis of rashes in this age group and the role of a therapeutic trial of medication as a diagnostic modality.

scholarly journals A case of Schnitzler’s syndrome without monoclonal gammopathy successfully treated with canakinumab

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Akira Sakai ◽  
Natsumi Norikawa ◽  
Toshiyuki Yamamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Urticaria ◽  
Monoclonal Gammopathy ◽  
Bone Pain ◽  
Periodic Fever ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Magnetic Resonance Imaging Examination ◽  
Amyloid A ◽  
Schnitzler’S Syndrome

Abstract Background Schnitzler’s syndrome (SchS) is a rare autoinflammatory syndrome with diagnostic challenge and be characterized by chronic urticaria, a monoclonal gammopath, periodic fever and bone pain. In addition to the monoclonal gammopathy, bone abnormalities are often found at the site of bone pain in patients with SchS. The remarkable efficacy of interleukin-1 (IL-1) inhibition was also demonstrated in this syndrome. Case presentation We describe a case of refractory chronic urticaria presenting with clinical manifestations consistent with SchS without monoclonal gammopathy. A 43-year-old female patient suffering from recurring of urticaria with periodic fever as well as bone pain for the past 4 years. The patient had leukocytosis and elevated levels of C-reactive protein (CRP) and serum amyloid A (SAA). PET/CT (positron emission tomography/computed tomography) and MRI (magnetic resonance imaging) examination revealed hyper-metabolism areas in both femoral bone marrow. Although bone marrow histology revealed no abnormality, urticarial skin lesions shows neutrophilic infiltrations without evidence of vasculitis. We could not exclude the possibility of SchS. The patient had been treated with antihistamines, steroids, omarizumab, colchicine and cyclosporine A, no therapeutic effect was observed. She was started on canakinumab 150 mg subcutaneous injection with 4 weeks interval. Within 48 h after the first injection, the urticarial rash disappeared, and febrile attack and bone pain had not recurred. Elevated levels of serum CRP and SAA were normalized within a week after the first injection of canakinumab. Conclusions The current case suggests an important role for IL-1 as a mediator in the pathophysiology of SchS-like refractory urticaria with bine pain. It had been presumed that monoclonal gammopathy may not always present in SchS. It is important to avoid delay in diagnosis and initiation of proper treatment in SchS or autoinflammatory conditions resembling SchS.

scholarly journals Schnitzler Syndrome treated with canakinumab

2019 ◽  
pp. 34-37
Author(s):  
Pablo Finucci Curi
Keyword(s):  
Monoclonal Gammopathy ◽  
Bone Pain ◽  
Interleukin 1 ◽  
Rare Disorder ◽  
Intermittent Fever ◽  
Urticarial Rash ◽  
Schnitzler Syndrome

Schnitzler syndrome is a rare disorder characterized by chronic urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis, bone pain and lymphadenopathy, in which interleukin 1 (IL-1) has a preponderant role. The case of a 48-year-old male who meets criteria for Schnitzler syndrome and who after failing too many treatments presents a successful response to canakinumab is presented here.

scholarly journals The role of interleukin-1 beta in the pathophysiology of Schnitzler’s syndrome

2015 ◽  
Vol 17 (1) ◽  
Author(s):  
Heleen D. de Koning ◽  
Joost Schalkwijk ◽  
Monique Stoffels ◽  
Johanna Jongekrijg ◽  
Joannes F. M. Jacobs ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Schnitzler’S Syndrome

scholarly journals AB1057 SCHNITZLER’S SYNDROME IN THE DIFFERENTIAL DIAGNOSIS OF ADULT STILL’S DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1818.2-1819
Author(s):  
S. Salugina ◽  
E. Borzova ◽  
V. Gorodetskiy ◽  
E. Fedorov
Keyword(s):  
Monoclonal Gammopathy ◽  
Age At Onset ◽  
Diagnostic Delay ◽  
Gene Mutations ◽  
Complete Response ◽  
Health Improvement ◽  
Urticarial Rash ◽  
Adult Still's Disease ◽  
Schnitzler’S Syndrome ◽  
Musculoskeletal Manifestations

Background:Schnitzler’s syndrome (SchS) and adult onset Still disease (AOSD) are currently considered as multifactorial autoinflammatory diseases (MAIDs) and are classified as systemic inflammation with urticarial rash. Clinical similarities between SchS and AOSD (fever, urticarial rash, arthralgias), increased ESR and CRP and the efficacy of IL-1 inhibitors may lead to the diagnostic delay in SchS pts. Testing for monoclonal gammopathy helps establish the diagnosis in SchS pts but is not routinely used in AOSD pts.Objectives:to examine demographic, clinical and laboratory characteristics, and the therapy of SchS pts in a single rheumatology center.Methods:5 SchS patients (2 females, 3 males), aged 32 to 68, underwent inpatient and outpatient examinations in the rheumatology center. All pts underwent a standard rheumatology examination, including ESR, CRP and M-gradient. 4 pts underwent genetic testing for mutations inNLRP3, TNFRSF1Agenes to exclude MAIDs, such as CAPS and TRAPS.Results:All pts were initially diagnosed with AOSD. The age at onset ranged between 28 and 66 years. Time to diagnosis varied from 2 to 22 years, being within 4 years in 4 of 5 pts. Patients presented with fever (4), urticarial rash (5) and musculoskeletal manifestations (5) (arthralgia in 3, bone pain in 4). Of 2 pts with serositis one presented with pericarditis and another – with pleuritis. Only 1 demonstrated a sore throat and polyneuropathy of the lower extremities. ESR and CRP were increased in all pts, leukocytosis was noted in 4 (Table 1). The monoclonal IgMk secretion was revealed in 5 pts, IgMκ and IgMλ – in 1 and IgGκ and IgGλ - 1. NoNLRP3, TNFRSF1Agene mutations were identified. Prior to the diagnosis, all pts were treated with glucocorticoids with a transient partial clinical response and a disease relapse after reducing the dose or stopping the treatment. 2 pts failed to respond to methotrexate and 1 – to hydroxychloroquine. 4 pts were prescribed with 150 mg canakinumab, a monoclonal antibody targeting IL-1, subcutaneously once every 8 weeks. The treatment duration varied from 6 months to 5 years. 2 pts, who initially received daily 100 mg anakinra subcutaneously for 2 to 3 months with a positive response, were further treated with canakinumab. During the treatment with canakinumab, all pts rapidly responded with a complete resolution of fever, rash, arthralgias and bone pains, an overall health improvement and a normalization in ESR and CRP levels. The therapy was well tolerated. In 1 patient, the intervals between canakinumab injections were prolonged to 5 months without any evidence of relapse. During this period, the male patient became a parent to a healthy child.Conclusion:In rheumatology practice SchS can be misdiagnosed with AOSD. AOSD patients should be tested for monoclonal gammopathy. IL-1 inhibitors are a highly effective and well-tolerated treatment option for SchS. In SchS patients with a complete response to canakinumab, injection intervals can be individualized.Disclosure of Interests:None declared

scholarly journals Inflammatory process as an etiological and prognostic factor of stroke and the goal of potential treatment strategies

2021 ◽  
Vol 36 (4) ◽  
pp. 297-311
Author(s):  
Agnieszka Kraśniej-Dębkowska ◽  
Maciej Śnieżyński ◽  
Anna Członkowska
Keyword(s):  
Inflammatory Process ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Risk Of Infection ◽  
Defence Mechanism ◽  
The Central Nervous System ◽  
Inflammatory Drugs ◽  
The Subject ◽  
Brain Tissue Damage

Objective. Inflammation is the body’s natural defence mechanism against factors that damage its tissues. However, if it lasts chronically, it may adversely affect the body’s homeostasis. Inflammation is not only a long-known risk factor for the development of atherosclerosis and its complications, but also develops brain tissue damage in the course of ischemic stroke or intracerebral haemorrhage, leading to even greater damage. In addition, the immune system functions are impaired, which increases the risk of infection. Literature review. Drugs that can reduce the risk of stroke by inhibiting vascular damage and modifying the inflammatory process in the central nervous system, including counteracting the risk of infection, have become the subject of many experimental and clinical studies on strokes. Such drugs include canakinumab, human recombinant interleukin-1 receptor antagonist, colchicine, fingolimod, siponimod or natalizumab. Conclusions. Considering all available research results, the therapeutic pathway using anti-inflammatory drugs has a high potential; however, the complications associated with evoked immunosuppression in patients should be kept in mind. The paper presents a review of the literature on the role of the inflammatory process in the pathogenesis of stroke as well as related therapeutic options.

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