scholarly journals Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience

2021 ◽  
Vol 12 ◽  
Author(s):  
Deepti Suri ◽  
Amit Rawat ◽  
Ankur Kumar Jindal ◽  
Pandiarajan Vignesh ◽  
Anju Gupta ◽  
...  
Keyword(s):  
Health Care Professionals ◽  
Periodic Fever ◽  
Interleukin 1 ◽  
Immunosuppressive Agents ◽  
Clinical Manifestations ◽  
Immune Dysregulation ◽  
Mevalonate Kinase Deficiency ◽  
Inherited Disorders ◽  
Molecular Features ◽  
Delays In Diagnosis

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.

scholarly journals IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Hana Malcova ◽  
Zuzana Strizova ◽  
Tomas Milota ◽  
Ilja Striz ◽  
Anna Sediva ◽  
...  
Keyword(s):  
Periodic Fever ◽  
Tumor Necrosis Factor Receptor ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Clinical Manifestations ◽  
Musculoskeletal Symptoms ◽  
Mevalonate Kinase Deficiency ◽  
Periodic Fever Syndromes ◽  
Therapeutic Uses ◽  
Fever Syndromes ◽  
Mediterranean Fever

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

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.

MEVALONATE KINASE DEFICIENCY IN AN INFANT: KEY ASPECTS OF DIAGNOSIS AND TREATMENT

2021 ◽  
Vol 100 (2) ◽  
pp. 276-283
Author(s):  
M.F. Dubko ◽  
◽  
R.K. Raupov ◽  
M.A. Kaneva ◽  
E.N. Suspitsyn ◽  
...  
Keyword(s):  
Late Onset ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Autosomal Recessive Inheritance ◽  
Compound Heterozygous ◽  
Mevalonate Kinase Deficiency ◽  
Mevalonate Kinase ◽  
Pathogenic Variants ◽  
Severe Type

Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disease with an autosomal recessive inheritance. The severity of the disease is correlated with the residual enzyme activity. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria. A little more than 300 cases with MDK have been described worldwide. The rarity of this disease, and polymorphism of clinical manifestations lead to late diagnosis and late onset of specific treatment. We described the 7-month-old infant with pathogenic variants c.118C> T (p.R40W) and c.206_207del (p.S69fs) in the MVK gene in a compound heterozygous state with the successful use of an interleukin-1 blocker.

scholarly journals THE BROAD-RANGING PANORAMA OF SYSTEMIC AUTOINFLAMMATORY DISORDERS WITH SPECIFIC FOCUS ON ACUTE PAINFUL SYMPTOMS AND HEMATOLOGIC MANIFESTATIONS IN CHILDREN

2018 ◽  
Vol 10 ◽  
pp. e2018067 ◽  
Author(s):  
Donato Rigante
Keyword(s):  
Periodic Fever ◽  
Interleukin 1 ◽  
Tumor Necrosis Factor Receptor ◽  
Mevalonate Kinase Deficiency ◽  
Periodic Syndrome ◽  
Chronic Infections ◽  
Autoinflammatory Disorders ◽  
Inflammatory Parameters ◽  
Granulomatous Diseases

Systemic autoinflammatory disorders (SAIDs) are inherited defects of innate immunity characterized by recurrent sterile inflammatory attacks involving skin, joints, serosal membranes, gastrointestinal tube and other tissues, which recur with variable rhythmicity and display reactive amyloidosis as a potential long-term complication. Dysregulated inflammasome activity leading to overproduction of many proinflammatory cytokines, such as interleukin-1 (IL-1), and delayed shutdown of inflammation are considered crucial pathogenic keys in the vast majority of SAIDs. Progresses of cellular biology have partially clarified the mechanisms behind monogenic SAIDs, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, hereditary pyogenic diseases, idiopathic granulomatous diseases and defects of the ubiquitin-proteasome pathway, whereas little is clarified for the polygenic SAIDs, such as periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy (PFAPA) syndrome. The puzzle of symptomatic febrile attacks recurring over time in children requires evaluating the mixture of clinical data, inflammatory parameters in different disease phases, therapeutic efficacy of specific drugs such as colchicine, corticosteroids or IL-1 antagonists, and genotype analysis in selected cases. Long-term history of periodic fevers should also need to rule out chronic infections and malignancies. This review is conceived as a practical template for a proper classification of children with recurring fevers and includes tips useful for the diagnostic approach to SAIDs, focusing on the specific acute painful symptoms and blood manifestations encountered in childhood.

scholarly journals Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mouzarllem B. Reis ◽  
Fernanda L. Rodrigues ◽  
Natalia Lautherbach ◽  
Alexandre Kanashiro ◽  
Carlos A. Sorgi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Acetylcholine Release ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Prostaglandin E ◽  
High Dose ◽  
Scorpion Envenomation ◽  
Risk Of Death ◽  
Include Heart Failure

Abstract Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

Varied Clinical Manifestations of LRBA Deficiency (Immune Dysregulation Disorder)

2021 ◽  
Vol 58 (3) ◽  
pp. 285-286
Author(s):  
Deenadayalan Munirathnam ◽  
Vimal Kumar ◽  
Meena Sivasankaran ◽  
Silky Agrawal
Keyword(s):  
Clinical Manifestations ◽  
Immune Dysregulation ◽  
Lrba Deficiency

scholarly journals Commonest modes of presentation of bone and soft tissue tumors at sarcoma services of A Tertiary Care Hospital of KPK.

2020 ◽  
Vol 27 (12) ◽  
pp. 2744-2748
Author(s):  
Muhammad Ibrahim ◽  
Zeeshan Khan ◽  
Muhammad Saeed ◽  
Israr Ahmad ◽  
Salik Kashif ◽  
...  
Keyword(s):  
Health Care Professionals ◽  
Tertiary Care ◽  
Sampling Technique ◽  
Signs And Symptoms ◽  
Soft Tissue Tumors ◽  
Care Hospital ◽  
Duration Of Symptoms ◽  
Mode Of Presentation ◽  
Number Of Patients ◽  
Delays In Diagnosis

Objectives: The aim of this study is to assess the commonest mode of presentation at our sarcoma unit and the duration from onset of symptoms till presentation. Study Design: Retrospectively study. Setting: Sarcoma Unit of Hayatabad Medical Complex, Peshawar. Period: June 2016 to December 2019. Material & Methods: Two hundred and eighty two patients were included in this study of which 172 patients were male and 110 were female. Sample size was calculated through non-probability consecutive sampling technique. Results: Average age of patients presenting to us was 30.2years (±18.5) ranging from 3years to 83years. Highest numbers of patients fell into the age group category of 11-20years i.e. 94 (33.33%). The average duration of symptoms among our patients was 19.6 months (±26.09) ranging from 0.1months (3 days) to 168 months (14years). Highest number of patients fell into the 7months-12months category i.e. 86 patients (30.5%). The commonest mode of presentation among our patients was painful lump i.e. 128(45.3%) while patients presenting with painless lump were 57(20.2%) and those presenting with only pain were 28(9.9%). Conclusion: The study concluded that there is a need of greater awareness amount general population and health care professionals regarding red flag signs and symptoms in order to avoid the delays in diagnosis which may leads to poor prognosis.

scholarly journals Immunogenetics of the Ocular Anterior Segment: Lessons from Inherited Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Jasmine Y. Serpen ◽  
Stephen T. Armenti ◽  
Lev Prasov
Keyword(s):  
Immune System ◽  
Lupus Erythematosus ◽  
Genetic Disorders ◽  
Anterior Segment ◽  
Adaptive Immune System ◽  
Mendelian Inheritance ◽  
Ocular Involvement ◽  
Inherited Disorders ◽  
Molecular Features ◽  
Organ Systems

Autoimmune and autoinflammatory diseases cause morbidity in multiple organ systems including the ocular anterior segment. Genetic disorders of the innate and adaptive immune system present an avenue to study more common inflammatory disorders and host-pathogen interactions. Many of these Mendelian disorders have ophthalmic manifestations. In this review, we highlight the ophthalmic and molecular features of disorders of the innate immune system. A comprehensive literature review was performed using PubMed and the Online Mendelian Inheritance in Man databases spanning 1973–2020 with a focus on three specific categories of genetic disorders: RIG-I-like receptors and downstream signaling, inflammasomes, and RNA processing disorders. Tissue expression, clinical associations, and animal and functional studies were reviewed for each of these genes. These genes have broad roles in cellular physiology and may be implicated in more common conditions with interferon upregulation including systemic lupus erythematosus and type 1 diabetes. This review contributes to our understanding of rare inherited conditions with ocular involvement and has implications for further characterizing the effect of perturbations in integral molecular pathways.

scholarly journals Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Caroline Vinit ◽  
Sophie Georgin-Lavialle ◽  
Aikaterini Theodoropoulou ◽  
Catherine Barbier ◽  
Alexandre Belot ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Literature Review ◽  
Disease Activity ◽  
Severe Disease ◽  
Interleukin 1 ◽  
Real Life ◽  
Treat To Target ◽  
Mevalonate Kinase Deficiency ◽  
Combining Data

BackgroundInterleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified.ObjectiveIdentify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review.Patients and MethodsData were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases.ResultsComplete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients’ quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature.ConclusionIn the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.

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