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Gavrilov NS, Ignatyeva NV, Medvedeva EV, Timashev PS. Articular cartilage tissue engineering using genetically modified induced pluripotent stem cell lines. GENES & CELLS 2024; 19:404-424. [DOI: 10.17816/gc633492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2025]
Abstract
Mature hyaline cartilage has a low regenerative potential and its repair remains a complex clinical and research issue. Articular cartilage injuries often contribute to the development of osteoarthritis, resulting in loss of joint function and patient disability. Surgical techniques for repairing articular surfaces, such as mosaic chondroplasty and microfracture, which are designed for small defects, cannot be used for degenerative and dystrophic cartilage lesions. Cell therapy using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising approach to reconstruct articular cartilage tissue. iPSCs have high proliferative activity, which allows the harvesting of autologous cells in quantities necessary to repair a joint defect. CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables the genetic modification of iPSCs to obtain progenitor cells with specific characteristics and properties.
This review describes specific research papers on the combined use of iPSC and CRISPR-Cas technologies for the evaluation of cartilage regenerative medicine. Papers were evaluated for the last twelve years since CRISPR-Cas technology was introduced to the global community. CRISPR-Cas is currently being used to address therapeutic issues in articular cartilage regeneration by increasing the efficiency of chondrogenic differentiation of iPSC lines and harvesting a more homogeneous population of chondroprogenitor cells. Another approach is to remove the pro-inflammatory cytokine receptor sequence to produce inflammation-resistant cartilage. Finally, knocking out genes for components of the major histocompatibility complex allows harvesting chondrocytes that are invisible to the recipient's immune system. This kind of research contributes to personalized healthcare and can improve the quality of life of the world's population in the long term.
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Rivera-Burgos I, Vilá LM. Severe Antiphospholipid Syndrome and Diffuse Glomerulonephritis After Adalimumab Treatment in a Patient With Ulcerative Colitis. Case Rep Rheumatol 2024; 2024:8024757. [PMID: 39529874 PMCID: PMC11554406 DOI: 10.1155/2024/8024757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 07/18/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
Tumor necrosis factor alpha inhibitors (TNFi) are biological drugs used worldwide to treat various autoimmune disorders. Paradoxically, TNF-α antagonists can also induce autoimmune diseases being systemic vasculitis, systemic lupus erythematosus, and psoriasis, the most common. We present a 22-year-old woman with ulcerative colitis (UC) who was started on adalimumab 40 mg subcutaneously every 2 weeks. After two doses of adalimumab, she developed gangrene of all toes and acute kidney injury requiring hemodialysis. Skin biopsy showed thrombi in the small vessels of the dermis. Renal biopsy disclosed diffuse proliferative glomerulonephritis (GN) and acute tubulointerstitial nephritis. Serologic work-up showed positive IgG anticardiolipin (ACL) antibodies and low C3 levels. Antinuclear, anti-dsDNA, anti-Smith, anti-SSA, anti-SSB, anti-RNP, antineutrophil cytoplasmic antibodies, ACL (IgA and IgM), and anti-β2-glycoprotein I (IgG, IgM, and IgA) antibodies were not elevated. Lupus anticoagulant test and cryoglobulins were negative. Adalimumab was discontinued, and she was treated with enoxaparin, intravenous (IV) methylprednisolone pulse, IV cyclophosphamide, and plasmapheresis followed by maintenance therapy with warfarin, prednisone, azathioprine, and hydroxychloroquine. She did not have further thrombotic events, and the acute kidney injury completely resolved. ACL IgG antibodies decreased to normal levels, and repeated tests were negative. After 7 years, anticoagulation and immunosuppressive drugs were discontinued. During a follow-up of 24 months, she remained in complete clinical remission. This report highlights the occurrence of autoimmune disorders induced by TNFi. Thus, careful monitoring of adverse immune reactions to TNFi is highly recommended.
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Affiliation(s)
- Ileana Rivera-Burgos
- Division of Rheumatology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA
| | - Luis M. Vilá
- Division of Rheumatology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA
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Safaei S, Kimiaei A, Kasapoglu M, Coşan F. Clinical Characteristics and Management of Drug-Induced Lupus Caused by Tumor Necrosis Factor Inhibitors: A Comprehensive Review. Cureus 2024; 16:e72522. [PMID: 39606520 PMCID: PMC11600269 DOI: 10.7759/cureus.72522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
Tumor necrosis factor (TNF) inhibitor (TNFi) therapy, commonly used to treat autoimmune conditions, such as ankylosing spondylitis (AS), rheumatoid arthritis, and psoriatic arthritis, has been associated with the development of drug-induced lupus (DIL). While the incidence of TNFi-induced DIL is relatively rare, it typically presents with mild symptoms and can often be managed with continued therapy or medication switches. This review explores the clinical characteristics, management strategies, and outcomes of TNFi-induced DIL through a comprehensive examination of cases reported in the literature. The findings suggest that most patients develop anti-double-stranded DNA (anti-dsDNA) positivity without severe clinical manifestations, and major organ involvement is uncommon. Treatment strategies vary; some patients can maintain TNFi therapy without disease exacerbation, while others require alternative treatments. Further research is needed to refine management protocols and improve patient outcomes.
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Affiliation(s)
| | - Ali Kimiaei
- Internal Medicine, Bahçeşehir University, Istanbul, TUR
| | | | - Fulya Coşan
- Internal Medicine, Bahçeşehir University, Istanbul, TUR
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Kimiaei A, Safaei S, Kasapoglu M, Coşan F. Clinical Characteristics and Management of Drug-Induced Lupus in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy. Cureus 2024; 16:e72388. [PMID: 39583374 PMCID: PMC11586078 DOI: 10.7759/cureus.72388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2024] [Indexed: 11/26/2024] Open
Abstract
Introduction Drug-induced lupus (DIL) is an autoimmune condition triggered by exposure to certain medications, leading to the emergence of clinical features that resemble those of systemic lupus erythematosus (SLE). This study aims to investigate the clinical characteristics, management strategies, and outcomes of patients who develop DIL during tumor necrosis factor inhibitor (TNFi) therapy. Methods We conducted a retrospective case series involving 15 patients who developed positive anti-double-stranded DNA (anti-dsDNA) antibodies while undergoing TNFi therapy between 2015 and 2023. Clinical data were collected and analyzed to assess the relationship between TNFi therapy and the onset of DIL symptoms. Results The case series included 15 patients (13 females and two males) with a mean age of 42.13 years. The primary diagnoses were ankylosing spondylitis (AS) (46.66%), rheumatoid arthritis (RA) (40%), and psoriatic arthritis (PsA) (13.33%). The mean duration from TNFi initiation to the detection of anti-dsDNA positivity was 5.13 years. Two patients (13.33%) exhibited clinical manifestations of DIL; however, no major organ involvement was observed. Sixty percent of patients continued with the same TNFi without disease activation, while 33% switched medications. Conclusion TNFi-induced DIL typically presents with mild symptoms. Both continuation and switching of TNFi therapy can be considered without significant exacerbation of symptoms. Management should be individualized based on clinical and laboratory findings. Further research with larger patient cohorts is warranted to determine optimal management strategies.
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Affiliation(s)
- Ali Kimiaei
- Internal Medicine, Bahçeşehir University, Istanbul, TUR
| | | | | | - Fulya Coşan
- Internal Medicine, Bahçeşehir University, Istanbul, TUR
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Liu R, Liu G, Lu F. VKH-like uveitis during donafenib therapy for hepatocellular carcinoma: a case report and review of the literature. Front Pharmacol 2024; 15:1401017. [PMID: 39092233 PMCID: PMC11291377 DOI: 10.3389/fphar.2024.1401017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/25/2024] [Indexed: 08/04/2024] Open
Abstract
Background The incidence of uveitis has risen with the use of targeted therapies, particularly prevalent in the administration of immune checkpoint inhibitors and MAP-kinase pathway inhibitors. We report the first case of VKH-like uveitis linked to Donafenib employed for the primary hepatocellular carcinoma, highlighting the necessity of ophthalmological follow-up in patients undergoing treatment with Donafenib. Case presentation A 55-year-old man developed VKH-like symptoms, including sporadic white patches, tinnitus, headache, and mild bilateral vision reduction, after 18 months of treatment with Donafenib and Sintilimab for hepatocellular carcinoma. Based on ophthalmological examinations that fundus fluorescein angiography images demonstrating multiple focal areas of pinpoint hyperfluorescence, along with pooling indicative of neurosensory detachment and disc leakage in both eyes, choroid thickening in swept-source optical coherence tomography, and "sunset-glow" fundus appearance, a tentative diagnosis of VKH-like uveitis was made. Initially, his best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/80 in the left eye. Upon discontinuing Donafenib and starting a 3-month course of oral glucocorticoids, his BCVA improved to 20/30 in the right eye and 20/40 in the left eye. Conclusion Targeted drugs have been commonly used for cancer treatment in recent years, but challenges of ocular side effects emerged gradually. To optimize patient outcomes, regular ophthalmological follow-ups are essential for those undergoing treatment with targeted therapies like Donafenib.
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Affiliation(s)
| | | | - Fang Lu
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
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Dönges L, Damle A, Mainardi A, Bock T, Schönenberger M, Martin I, Barbero A. Engineered human osteoarthritic cartilage organoids. Biomaterials 2024; 308:122549. [PMID: 38554643 DOI: 10.1016/j.biomaterials.2024.122549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 03/18/2024] [Accepted: 03/21/2024] [Indexed: 04/02/2024]
Abstract
The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening. To exemplify the utility of the model, we exposed the engineered OA cartilage organoids to factors known to attenuate pathological features, including IL-1Ra, and carried out mass spectrometry-based proteomics. We identified that IL-1Ra strongly reduced production of the transcription factor CCAAT/enhancer-binding protein beta [2] and demonstrated that inhibition of the C/EBPβ-activating kinases could revert the degradative processes. Human OA cartilage organoids thus represent a relevant tool towards the discovery of new molecular drivers of cartilage degeneration and the assessment of therapeutics targeting associated pathways.
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Affiliation(s)
- Laura Dönges
- Department of Biomedicine, University Hospital Basel, University of Basel, 4031, Basel, Switzerland
| | - Atharva Damle
- Department of Biomedicine, University Hospital Basel, University of Basel, 4031, Basel, Switzerland
| | - Andrea Mainardi
- Department of Biomedicine, University Hospital Basel, University of Basel, 4031, Basel, Switzerland
| | - Thomas Bock
- Proteomics Core Facility, Biozentrum University of Basel, 4056, Basel, Switzerland
| | - Monica Schönenberger
- Nano Imaging Lab, Swiss Nanoscience Institute, University of Basel, 4056, Basel, Switzerland
| | - Ivan Martin
- Department of Biomedicine, University Hospital Basel, University of Basel, 4031, Basel, Switzerland.
| | - Andrea Barbero
- Department of Biomedicine, University Hospital Basel, University of Basel, 4031, Basel, Switzerland
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Bernardi M, Spadafora L, Andaloro S, Piscitelli A, Fornaci G, Intonti C, Fratta AE, Hsu CE, Kaziròd-Wolski K, Metsovitis T, Biondi-Zoccai G, Sabouret P, Marzetti E, Cacciatore S. Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults. J Clin Med 2024; 13:3064. [PMID: 38892776 PMCID: PMC11173304 DOI: 10.3390/jcm13113064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-β2-glycoprotein I (β2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.
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Affiliation(s)
- Marco Bernardi
- Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy; (L.S.); (G.F.); (C.I.)
| | - Luigi Spadafora
- Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy; (L.S.); (G.F.); (C.I.)
| | - Silvia Andaloro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
| | - Alessandra Piscitelli
- Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; (A.P.); (A.E.F.); (C.-E.H.); (T.M.)
| | - Giovanni Fornaci
- Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy; (L.S.); (G.F.); (C.I.)
| | - Chiara Intonti
- Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy; (L.S.); (G.F.); (C.I.)
| | - Alberto Emanuele Fratta
- Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; (A.P.); (A.E.F.); (C.-E.H.); (T.M.)
| | - Chieh-En Hsu
- Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; (A.P.); (A.E.F.); (C.-E.H.); (T.M.)
| | - Karol Kaziròd-Wolski
- Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University, Al. IX Wieków Kielc 19A, 25-317 Kielce, Poland;
| | - Theodora Metsovitis
- Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; (A.P.); (A.E.F.); (C.-E.H.); (T.M.)
| | - Giuseppe Biondi-Zoccai
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Via XXIV Maggio 7, 04100 Latina, Italy;
- Cardiology Unit, Santa Maria Goretti Hospital, Via L. Scaravelli, 04100 Latina, Italy
| | - Pierre Sabouret
- Heart Institute, Pitié-Salpétrière Hospital, Sorbonne University, 47-83 Bd. de l’Hôpital, 75013 Paris, France;
- National College of French Cardiologists, 13 Niepce, 75014 Paris, France
| | - Emanuele Marzetti
- Department of Geriatrics, Orthopedics, and Rheumatology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
- Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - Stefano Cacciatore
- Department of Geriatrics, Orthopedics, and Rheumatology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy;
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Kennedy O, Kitson A, Okpara C, Chow LW, Gonzalez-Fernandez T. Immunomodulatory Strategies for Cartilage Regeneration in Osteoarthritis. Tissue Eng Part A 2024; 30:259-271. [PMID: 38126327 DOI: 10.1089/ten.tea.2023.0255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023] Open
Abstract
Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability globally. Although many efforts have been made to treat this condition, current tissue engineering (TE) and regenerative medicine strategies fail to address the inflammatory tissue environment that leads to the rapid progression of the disease and prevents cartilage tissue formation. First, this review addresses in detail the current anti-inflammatory therapies for OA with a special emphasis on pharmacological approaches, gene therapy, and mesenchymal stromal cell (MSC) intra-articular administration, and discusses the reasons behind the limited clinical success of these approaches at enabling cartilage regeneration. Then, we analyze the state-of-the-art TE strategies and how they can be improved by incorporating immunomodulatory capabilities such as the optimization of biomaterial composition, porosity and geometry, and the loading of anti-inflammatory molecules within an engineered structure. Finally, the review discusses the future directions for the new generation of TE strategies for OA treatment, specifically focusing on the spatiotemporal modulation of anti-inflammatory agent presentation to allow for tailored patient-specific therapies. Impact statement Osteoarthritis (OA) is a prevalent and debilitating musculoskeletal disorder affecting millions worldwide. Despite significant advancements in regenerative medicine and tissue engineering (TE), mitigating inflammation while simultaneously promoting cartilage tissue regeneration in OA remains elusive. In this review article, we discuss current anti-inflammatory therapies and explore their potential synergy with cutting-edge cartilage TE strategies, with a special focus on novel spatiotemporal and patient-specific anti-inflammatory strategies.
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Affiliation(s)
- Orlaith Kennedy
- Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, USA
- Department of Biomedical Engineering, College of Science and Engineering, University of Galway, Galway, Ireland
| | - Andrew Kitson
- Department of Materials Science and Engineering, Lehigh University, Bethlehem, Pennsylvania, USA
| | - Chiebuka Okpara
- Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, USA
| | - Lesley W Chow
- Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, USA
- Department of Materials Science and Engineering, Lehigh University, Bethlehem, Pennsylvania, USA
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Mihai IR, Rezus C, Burlui MA, Cardoneanu A, Macovei LA, Richter P, Bratoiu I, Rezus E. Autoimmune Liver Diseases and Rheumatoid Arthritis-Is There an Etiopathogenic Link? Int J Mol Sci 2024; 25:3848. [PMID: 38612658 PMCID: PMC11011907 DOI: 10.3390/ijms25073848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/28/2024] [Accepted: 03/23/2024] [Indexed: 04/14/2024] Open
Abstract
Rheumatoid arthritis (RA) is a systemic immune-mediated disease that, in addition to the articular involvement, can have extra-articular manifestations. Even though liver damage in RA is not very common, associated autoimmune liver diseases (AILDs) may occur. The most common AILD associated with RA is primary biliary cirrhosis (PBC), followed by autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). There are common underlying mechanisms that play a role in the emergence of autoimmunity and inflammation in both rheumatic and autoimmune liver diseases. Genetic studies have revealed the existence of several common disease-associated genes shared between RA and AILDs, and infectious triggers, particularly those associated with recurrent or complicated urinary tract infections, are also speculated to be potential triggers for these conditions. Moreover, these diseases share common serologic patterns characterized by the presence of specific autoantibodies and hyper-gammaglobulinemia. In this study, we focus on reviewing the association between RA and AILDs regarding the prevalence and possible etiopathogenic link.
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Affiliation(s)
- Ioana Ruxandra Mihai
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ciprian Rezus
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- “Sfantul Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Maria Alexandra Burlui
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Anca Cardoneanu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Luana Andreea Macovei
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Patricia Richter
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Ioana Bratoiu
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania (L.A.M.); (E.R.)
- Clinical Rehabilitation Hospital, 700661 Iasi, Romania
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Wery AR, Bruyneel M, Alcan I, Semeu PK. Case report: Golimumab-induced anti-PL7 antisynthetase syndrome. Int J Rheum Dis 2024; 27:e15039. [PMID: 38287549 DOI: 10.1111/1756-185x.15039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 12/03/2023] [Accepted: 12/30/2023] [Indexed: 01/31/2024]
Affiliation(s)
- Alexandre-Raphael Wery
- Department of Internal Medicine, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Marie Bruyneel
- Department of Pneumology, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Ibrahim Alcan
- Department of Radiology, Brugmann University Hospital, Brussels, Belgium
| | - Prochore Kamgang Semeu
- Department of Internal Medicine, Brugmann University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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11
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Reesor E, Bhavsar SV. Overlapping systemic lupus erythematosus, seropositive erosive rheumatoid arthritis, and ANCA-associated vasculitis: A case report and literature review. Mod Rheumatol Case Rep 2023; 8:21-25. [PMID: 37804186 DOI: 10.1093/mrcr/rxad056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 09/09/2023] [Accepted: 09/26/2023] [Indexed: 10/09/2023]
Abstract
The overlap of rheumatoid arthritis and systemic lupus erythematosus is well described, with a syndrome known as 'rhupus'. ANCA-associated vasculitis, however, is uncommonly associated with other autoimmune conditions. Here, we present a case of lupus, rheumatoid arthritis, and ANCA-associated vasculitis, with significant time elapsed between presentations, resulting in an accumulation of the three diagnoses over the course of 35 years. The patient was diagnosed with lupus at age 45, presenting with inflammatory polyarthritis, thrombocytopenia, leukopenia, positive ANA, positive anti-DNA, and hypocomplementemia. She was maintained on hydroxychloroquine therapy with minimal disease activity. Approximately 20 years later, she had a flare of polyarthritis with bilateral wrist erosive arthropathy and a positive rheumatoid factor, diagnosed as rheumatoid arthritis. Anti-TNFα therapy was initiated, and she was stable for a further 10 years. At age 79, she developed ANCA-associated vasculitis AAV with pulmonary and renal manifestations, treated with rituximab induction therapy and steroids. She recovered and her MPO-ANCA titre normalised. One year later, off the anti-TNFα, she again experienced an acute kidney injury with a repeat rise in MPO-ANCA. She was re-induced and maintained on steroids and rituximab. This novel case highlights the range of possible overlap syndromes, as well as how multiple autoimmune diagnoses can evolve over decades in previously stable disease. There is growing work around polyautoimmunity with ANCA-associated vasculitis and other systemic autoimmune diseases, which has potential to identify common aetiologies and pathogenesis. Knowledge of these overlap syndromes can help to recognise and manage these conditions in a timely manner.
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Affiliation(s)
- Emma Reesor
- Department of Medicine, Division of Rheumatology, McMaster University, Hamilton, ON, Canada
- Internal Medicine, McMaster University, Waterloo, ON, Canada
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12
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Przygocka A, Berti GM, Campus A, Tondolo F, Vischini G, Fabbrizio B, La Manna G, Baraldi O. Rituximab as possible therapy in TNF inhibitor-induced IgA vasculitis with severe renal involvement. BMC Nephrol 2023; 24:381. [PMID: 38124070 PMCID: PMC10731765 DOI: 10.1186/s12882-023-03439-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND We observe the increasing use of tumor necrosis factor (TNF) inhibitors in patients affected by chronic inflammatory diseases. These drugs provide good control of symptoms, contributing to significant improvement in the quality of life in individuals with high disease burden. On the other hand, along with their wider use and longer follow-up periods the number of reports regarding their adverse effects is also increasing. The reported complications include drug-induced vasculitis with possible kidney involvement. In the literature we can distinguish more frequently described ANCA-associated vasculitis and more rarely occurring immunoglobulin A vasculitis. Although uncommon, such complications may present with potentially life-threatening vital organ dysfunction; therefore, adequate monitoring and effective therapy are necessary. CASE PRESENTATION We report two cases of TNF inhibitor-induced vasculitis with severe acute worsening of renal function and significant proteinuria. The first patient was receiving golimumab therapy for ankylosing spondylitis and the second patient was treated with adalimumab for psoriasis and psoriatic arthritis. In the second case dialysis treatment was necessary and the patient presented recurrence of vasculitis after rechallenge with adalimumab. Both patients underwent renal biopsy which showed findings compatible with drug-induced IgA vasculitis and both were treated successfully with corticosteroids and rituximab. CONCLUSIONS To the best of our knowledge this is the first report of rituximab use in drug-induced IgA vasculitis with renal involvement. Combination of corticosteroids and rituximab can be an effective therapy in case of vasculitis with kidney failure and a preferable option for selected patients with drug-induced IgA vasculitis compared to cyclophosphamide. More studies are necessary to establish suitable short- and long-term treatment. Given the rarity of this disorder, case reports and case series can provide practical guidance until additional studies become available.
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Affiliation(s)
- Agnieszka Przygocka
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Gian Marco Berti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Anita Campus
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Francesco Tondolo
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Gisella Vischini
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Benedetta Fabbrizio
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy
| | - Gaetano La Manna
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy, Via Giuseppe Massarenti 9, Bologna, Italy.
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy.
| | - Olga Baraldi
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy
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13
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Simão Raimundo D, Cordeiro AI, Parente Freixo J, Valente Pinto M, Neves C, Farela Neves J. Case Report: Patient with deficiency of ADA2 presenting leukocytoclastic vasculitis and pericarditis during infliximab treatment. Front Pediatr 2023; 11:1200401. [PMID: 37388286 PMCID: PMC10303984 DOI: 10.3389/fped.2023.1200401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/15/2023] [Indexed: 07/01/2023] Open
Abstract
Deficiency of adenosine deaminase 2 (DADA2), first reported in 2014, is a disease with great phenotypic variability, which has been increasingly reported. Therapeutic response depends on the phenotype. We present a case of an adolescent with recurrent fever, oral aphthous ulcers, and lymphadenopathy from 8 to 12 years of age and subsequently presented with symptomatic neutropenia. After the diagnosis of DADA2, therapy with infliximab was started, but after the second dose, she developed leukocytoclastic vasculitis and showed symptoms of myopericarditis. Infliximab was switched to etanercept, with no relapses. Despite the safety of tumor necrosis factor alpha inhibitors (TNFi), paradoxical adverse effects have been increasingly reported. The differential diagnosis between disease new-onset manifestations of DADA2 and side effects of TNFi can be challenging and warrants further clarification.
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Affiliation(s)
- Diana Simão Raimundo
- Pediatrics Department, Hospital do Divino Espírito Santo, Ponta Delgada, Portugal
| | - Ana Isabel Cordeiro
- Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - João Parente Freixo
- Centro de Genética Preditiva e Preventiva, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde, Porto, Portugal
| | - Marta Valente Pinto
- Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- Egas Moniz Center for Interdisciplinary Research (CiiEM); Egas Moniz School of Health & Science, Caparica, Almada, Portugal
| | - Conceição Neves
- Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - João Farela Neves
- Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal
- CHRC, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal
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14
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Makkawy EA, Alanazi MT, Yehia MF, Almazloum AM. Infliximab-Induced Interstitial Pneumonitis: A Case Report. Cureus 2023; 15:e40812. [PMID: 37485130 PMCID: PMC10362944 DOI: 10.7759/cureus.40812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2023] [Indexed: 07/25/2023] Open
Abstract
Anti-tumor necrosis factor inhibitors are increasingly being recommended to treat and control a wide range of diseases, including Crohn's disease, ulcerative colitis, rheumatoid, and psoriatic arthritis. Serious pulmonary consequences, ranging from infectious disease to pulmonary edema, airway involvement, and even interstitial lung disease, are well-known multisystemic side effects. Interstitial lung disease is a well-known but uncommon condition. This report presents a case of a 49-year-old man with ulcerative colitis who developed interstitial pneumonitis following three infusions of infliximab therapy based on clinical, radiologic, and pathology data that are consistent with drug-induced interstitial pneumonitis. After stopping infliximab and starting steroid therapy, we noticed complete symptom resolution and improvement in respiratory symptoms and imaging.
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Affiliation(s)
- Eyad A Makkawy
- Internal Medicine/Gastroenterology, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, SAU
| | - Manal T Alanazi
- Gastroenterology, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, SAU
| | - Mohamed F Yehia
- Internal Medicine/Gastroenterology, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, SAU
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15
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Yun Z, Duan L, Liu X, Cai Q, Li C. An update on the biologics for the treatment of antiphospholipid syndrome. Front Immunol 2023; 14:1145145. [PMID: 37275894 PMCID: PMC10237350 DOI: 10.3389/fimmu.2023.1145145] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 05/04/2023] [Indexed: 06/07/2023] Open
Abstract
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Although anticoagulation is the primary treatment for APS, it fails in approximately 20-30% of obstetric APS cases and more than 30% of thrombotic APS cases. Therefore, there is a need for new, targeted treatments beyond anticoagulants. Biologics, such as rituximab and eculizumab, have been recommended for refractory catastrophic APS. This review focuses on the recent advancements in the pathogenesis of APS and explores the potential of targeted treatments, including eculizumab, rituximab, belimumab, daratumumab, obinutuzumab, and anti-TNF-α antibodies, for APS management.
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Affiliation(s)
- Zelin Yun
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
- Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People’s Hospital, Beijing, China
| | - Lizhi Duan
- Department of Rheumatology and Immunology, Gangkou Hospital of Hebei Port Group Company Limited, Qinhuangdao, Hebei, China
| | - Xiangjun Liu
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
- Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People’s Hospital, Beijing, China
| | - Qingmeng Cai
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
- Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People’s Hospital, Beijing, China
| | - Chun Li
- Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China
- Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking University People’s Hospital, Beijing, China
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16
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Harty T, O'Shaughnessy M, Harney S. Therapeutics in rheumatology and the kidney. Rheumatology (Oxford) 2023; 62:1009-1020. [PMID: 35951751 DOI: 10.1093/rheumatology/keac460] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 07/08/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
The field of rheumatology has advanced significantly in recent years to provide rheumatologists with an extensive array of medications to combat rheumatic joint conditions. In contrast to an older era, when NSAIDs and other nephrotoxic agents were the mainstay of treatment, modern DMARDs vary considerably in their nephrotoxic potential and their use is not always precluded in populations with pre-existing chronic kidney disease (CKD). This review will explore in detail the safety and efficacy profiles of medications used to treat rheumatologic disease, specifically in the setting of CKD. Specifically, we discuss both traditional agents used, i.e. NSAIDs, CSs and conventional synthetic DMARDs, as well as novel biologic DMARDs and targeted synthetic DMARDs. Anti-gout prescribing in CKD is also reviewed. We aim to provide practical guidance to rheumatologists, nephrologists and general physicians when prescribing these medications in the setting of CKD.
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Affiliation(s)
| | | | - Sinead Harney
- School of Medicine, University College Cork.,Department of Rheumatology, Cork University Hospital, Cork, Ireland
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17
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Waitayangkoon P, Chen L, Liu JB, Weins A, Barbosa F, Treadwell T. Lupus Cardiomyopathy and Nephritis Associated With Adalimumab and Cytomegalovirus Infection in a Patient With Seronegative Rheumatoid Arthritis: A Case of Rhupus Syndrome. Cureus 2023; 15:e34489. [PMID: 36874321 PMCID: PMC9982757 DOI: 10.7759/cureus.34489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2023] [Indexed: 02/04/2023] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) inhibitors are associated with lupus-like disease, known as anti-TNF-α-induced lupus (ATIL). Cytomegalovirus (CMV) was reported to exacerbate lupus in the literature. To date, systemic lupus erythematosus (SLE) triggered by adalimumab in the setting of CMV infection has never been described. We present an unusual case of a 38-year-old female with a past medical history of seronegative rheumatoid arthritis (SnRA) who developed SLE associated with the use of adalimumab and CMV infection. She had severe SLE features including lupus nephritis and cardiomyopathy. The medication was discontinued. She was initiated on pulse steroid therapy and discharged with an aggressive regimen for SLE, including prednisone, mycophenolate mofetil, and hydroxychloroquine. She remained on the medications until a year later upon follow-up. ATIL from adalimumab usually manifests only mild symptoms of SLE such as arthralgia, myalgia, and pleurisy. Nephritis is very rare, and cardiomyopathy is unprecedented. Concomitant CMV infection might contribute to disease severity. Patients with SnRA may have an increased risk of developing SLE later when exposed to such medications and infection.
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Affiliation(s)
- Palapun Waitayangkoon
- Internal Medicine, MetroWest Medical Center, Tufts University School of Medicine, Framingham, USA
| | - Lucas Chen
- Internal Medicine, MetroWest Medical Center, Tufts University School of Medicine, Framingham, USA
| | - Jessica B Liu
- Internal Medicine, MetroWest Medical Center, Tufts University School of Medicine, Framingham, USA
| | - Astrid Weins
- Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Felipe Barbosa
- Infectious Diseases, MetroWest Medical Center, Tufts University School of Medicine, Framingham, USA
| | - Thomas Treadwell
- Infectious Diseases, MetroWest Medical Center, Tufts University School of Medicine, Framingham, USA
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18
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Cutaneous vasculitis associated with molecular tergeted therapies: systematic review of the literature. Clin Rheumatol 2023; 42:339-357. [PMID: 36369405 DOI: 10.1007/s10067-022-06406-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/13/2022]
Abstract
Cutaneo us vasculitis (CV) has a broad spectrum of etiologies, and drugs are one of the main culprits. With the increasing use of targeted therapies in medicine, especially in rheumatology and oncology, the number of CV cases reported due to these drugs has increased. Therefore, the recognition and treatment of CV associated with targeted agents have become more and more important. In the literature, anti-TNFs (n = 73, 59.5%), secukinumab (n = 7, 6%), rituximab (n = 5, 4%), tocilizumab (n = 1, 0.8%), ustekinumab (n = 8, 6.5%), abatacept (n = 3, 2.4%), Janus kinase inhibitors (n = 3, 2.4%), alemtuzumab (n = 3, 2.4%), and immune checkpoint inhibitors (n = 20, 16%) have been reported as responsible agents. However, our knowledge of the pathogenetic mechanisms is fairly limited, and the standardized management is yet to be established. Furthermore, though it is uncommon, this complication may pose a safety issue. In this manuscript, we reviewed the literature on CV with or without systemic involvement related to targeted agents. We also proposed the pathogenetic mechanisms of these adverse events. Thus, we aimed to make it easier for clinicians to manage similar cases by reviewing the diagnosis and treatment processes.
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19
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Zhang J, Wang SH, Zuo YG. Paradoxical phenomena of bullous pemphigoid induced and treated by identical biologics. Front Immunol 2023; 13:1050373. [PMID: 36685489 PMCID: PMC9849796 DOI: 10.3389/fimmu.2022.1050373] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/07/2022] [Indexed: 01/07/2023] Open
Abstract
Objective This study aimed to investigate the clinical features of biologics-induced bullous pemphigoid (BP) and the therapeutic effects of those agents for BP, exploring the underlying pathophysiological mechanisms. Methods We searched PubMed, Web of Science, and Elsevier for studies involving pemphigoid patients treated with or induced by identical biologics published in English from January 2009 to April 2022. Results Seventeen cases of drug-induced BP associated with anti-tumor necrosis factor (aTNF)-α therapies, one with interleukin (IL)-17 inhibitors, and seven with IL-12/IL-23 or IL-23 inhibitors were enrolled. Time to cutaneous toxicity varied among different types of agents, and the characteristics of clinical examinations were similar to idiopathic BP. Discontinuation of the culprit drugs and initiation of topical or systemic corticosteroids were adequate in most cases. Several monoclonal antibodies above have also been reported for the treatment of refractory or recurrent BP, especially concurrent with psoriasis. Conclusion Biologics for immune-related diseases, including TNF-α, IL-17, and IL-12/IL-23 or IL-23 inhibitors, can both induce and treat BP, which might be associated with a helper T cells Th1/Th2 imbalance, complicated inflammatory networks, and a specific individual microenvironment, suggestive of a new perspective on the therapeutic algorithms of BP. There have been numerous reports about biologics inducing or treating BP. We have taken note of this phenomenon and focused on biologics with both pathogenetic and therapeutic effects on BP. Our review summarized the clinical characteristics of associated cases, trying to figure out the underlying mechanisms of this paradoxical phenomenon and to provide an integrated perspective and new therapeutic alternatives for BP.
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20
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Uehara M, Matsushita S, Aochi S, Yamamoto M. Positive antiphospholipid antibodies and pulmonary embolism in a patient with adalimumab-induced lupus. Mod Rheumatol Case Rep 2023; 7:68-73. [PMID: 36208152 DOI: 10.1093/mrcr/rxac074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/07/2022] [Accepted: 07/21/2022] [Indexed: 11/07/2022]
Abstract
It is known that administration of tumor necrotic factor (TNF) inhibitors induces lupus. The case of a Crohn's disease patient who had been treated with adalimumab (ADA) and showed positive anti-DNA and antiphospholipid antibodies and developed pulmonary embolism is presented. Fortunately, early diagnosis and intervention helped her survive. Although ADA was withdrawn, the Crohn's disease did not recur, and the autoantibodies became negative without any steroid therapy. It is important to recognise that administration of TNF inhibitors may be associated with antiphospholipid syndrome. It is necessary to perform therapeutic interventions such as TNF inhibitor withdrawal and prompt anticoagulant therapy when such pathology is suspected.
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Affiliation(s)
- Masaaki Uehara
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Shinya Matsushita
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satsuki Aochi
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Motohisa Yamamoto
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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21
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Bawany F, Lee G, Nousari Y, Ritchlin C, Singh P, Tausk F. Catastrophic Cutaneous Polyarteritis Nodosa Exacerbated by Emotional Stress. Clin Cosmet Investig Dermatol 2022; 15:2943-2947. [PMID: 36605451 PMCID: PMC9809396 DOI: 10.2147/ccid.s396539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/23/2022] [Indexed: 12/31/2022]
Abstract
We present the first case of a patient with indolent polyarteritis nodosa who suffered severe exacerbations following significant emotional stressors. This report highlights the close relationship between emotions and autoimmune diseases mediated by the deleterious effects of stressors presumptively by skewing immunity from Type 1 to Type 2.
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Affiliation(s)
- Fatima Bawany
- Department of Dermatology, New York University, New York, NY, USA
| | - Gayin Lee
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Yasmine Nousari
- Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Christopher Ritchlin
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Partik Singh
- Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA
| | - Francisco Tausk
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA,Department of Dermatology, University of Rochester Medical Center, Rochester, NY, USA,Correspondence: Francisco Tausk, Department of Dermatology, University of Rochester Medical Center, 601 Elmwood Ave, Box 697, Rochester, NY, 14642, USA, Email
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22
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Folci M, Ramponi G, Solitano V, Brunetta E. Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis. Clin Rev Allergy Immunol 2022; 63:107-123. [PMID: 34460071 DOI: 10.1007/s12016-021-08887-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2021] [Indexed: 01/13/2023]
Abstract
Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.
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Affiliation(s)
- Marco Folci
- Humanitas Clinical and Research Center - IRCCS, Milan, Italy.
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.
| | | | - Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Enrico Brunetta
- Humanitas Clinical and Research Center - IRCCS, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
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Abstract
PURPOSE OF REVIEW Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. RECENT FINDINGS The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, and subspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.
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24
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Myelolipoma After Infliximab Treatment for Crohn's Disease. ACG Case Rep J 2022; 9:e00791. [PMID: 35784510 PMCID: PMC9246070 DOI: 10.14309/crj.0000000000000791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 02/23/2022] [Indexed: 11/17/2022] Open
Abstract
A 20-year-old woman with Crohn's disease receiving infliximab therapy presented to the emergency department with lower extremity swelling secondary to compression of the common iliac vein. On magnetic resonance imaging, an enlarging pelvic mass was identified. The pathology of the mass was consistent with myelolipoma. We believe this is the first case of myelolipoma in a patient on immunosuppression with infliximab.
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25
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Wang CR, Tsai HW. Autoimmune liver diseases in systemic rheumatic diseases. World J Gastroenterol 2022; 28:2527-2545. [PMID: 35949355 PMCID: PMC9254143 DOI: 10.3748/wjg.v28.i23.2527] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/11/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Systemic rheumatic diseases (SRDs) are chronic, inflammatory, autoimmune disorders with the presence of autoantibodies that may affect any organ or system. Liver dysfunction in SRDs can be associated with prescribed drugs, viral hepatitis, alternative hepatic comorbidities and coexisting autoimmune liver diseases (AILDs), requiring an exclusion of secondary conditions before considering liver involvement. The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders. In AILDs, it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis. Commonly co-occurring SRDs in AILDs are Sjögren syndrome (SS), rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in autoimmune hepatitis (AIH), and SS, RA or systemic sclerosis in primary biliary cholangitis. Owing to different disease complications and therapies, it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease. Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases. The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario. In this review, we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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26
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Pferdehirt L, Damato AR, Dudek M, Meng QJ, Herzog ED, Guilak F. Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation. SCIENCE ADVANCES 2022; 8:eabj8892. [PMID: 35613259 PMCID: PMC9132444 DOI: 10.1126/sciadv.abj8892] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 04/07/2022] [Indexed: 05/16/2023]
Abstract
The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1-induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.
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Affiliation(s)
- Lara Pferdehirt
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
- Shriners Hospitals for Children–St. Louis, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
- Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA
| | - Anna R. Damato
- Department of Biology, Washington University, St. Louis, MO 63130, USA
| | - Michal Dudek
- Wellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK
| | - Qing-Jun Meng
- Wellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK
| | - Erik D. Herzog
- Department of Biology, Washington University, St. Louis, MO 63130, USA
| | - Farshid Guilak
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
- Shriners Hospitals for Children–St. Louis, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
- Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA
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Eksin MA, Erden A, Güven SC, Armagan B, Ozdemir B, Karakas O, Omma A, Kucuksahin O. Secukinumab in the treatment of psoriatic arthritis or ankylosing spondyloarthritis with multiple sclerosis: a case series with literature review. Immunotherapy 2022; 14:401-408. [DOI: 10.2217/imt-2021-0128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background/aim: Multiple sclerosis (MS) is a demyelinating central nervous system disorder with few cases reported to have concomitant spondyloarthritis (SpA) spectrum disorders such as ankylosing spondylitis and psoriatic arthritis. The aim of this study is to evaluate the effectiveness of secukinumab in the treatment of MS and accompanying ankylosing spondylitis or psoriatic arthritis. Materials & methods: In addition to four cases of their own, the authors conducted a systematic literature search. Demographics, comorbidities, symptoms of MS and SpA, medical treatments and changes in clinical and laboratory findings with treatment were recorded. Results & conclusions: After secukinumab therapy, all patients were found to have treatment response regarding axial involvement, without any progression of MS observed. For both SpA spectrum diseases and MS, secukinumab may be an appropriate choice.
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Affiliation(s)
- Mehmet Akif Eksin
- Ministry of Health Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Abdulsamet Erden
- Department of Internal Medicine, Yıldırım Beyazıt University Medical School, Division of Rheumatology, Ankara, Turkey
| | - Serdar Can Güven
- Ministry of Health Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Berkan Armagan
- Ministry of Health Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Bahar Ozdemir
- Ministry of Health Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Ozlem Karakas
- Ministry of Health Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Ahmet Omma
- Health Sciences University, Ankara City Hospital, Clinic of Rheumatology, Ankara, Turkey
| | - Orhan Kucuksahin
- Department of Internal Medicine, Yıldırım Beyazıt University Medical School, Division of Rheumatology, Ankara, Turkey
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Kapur S, Oswal J. New onset of Juvenile Dermatomyositis during Tumor Necrosis Factor Inhibitor (Adalimumab) Therapy. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_266_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Armandi A, Actis GC, Ribaldone DG. Autoimmunity of the liver. TRANSLATIONAL AUTOIMMUNITY 2022:309-331. [DOI: 10.1016/b978-0-12-824466-1.00012-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Association Between Tumor Necrosis Factor-α (G-308A) Polymorphism and Chronic Periodontitis, Aggressive Periodontitis, and Peri-implantitis: A Meta-analysis. J Evid Based Dent Pract 2021; 21:101528. [PMID: 34479676 DOI: 10.1016/j.jebdp.2021.101528] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 10/14/2020] [Accepted: 11/22/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Chronic periodontitis (CP), aggressive periodontitis (AP), and peri-implantitis (PI) are chronic inflammatory diseases. Tumor necrosis factor-α (TNF-a) is an effective immune inflammatory mediator. Several studies have been conducted to explore the association between the TNF-α (G-308A) polymorphism and susceptibility to CP, AP, and PI. Our objective was to examine whether the TNF-α (G-308A) polymorphism is related to these diseases. METHODS We conducted a meta-analysis to investigate the association between the TNF-α (G-308A) polymorphism and CP, AP, and PI. The PubMed, Embase, CNKI, and Web of Science electronic databases were searched for studies published from inception to August 11, 2020; the reference lists of included studies were also searched. The included studies were assessed in the following genetic models: dominant model, recessive model, allelic model, heterozygous model, and homozygous model. RESULTS Forty articles (50 comparisons) with 2243 CP, 824 AP, 615 PI, 795 healthy peri-implant, and 3575 healthy controls were considered for the TNF-α (G-308A) polymorphism in this meta-analysis. Variant A of TNF-α (G-308A) was associated with increased AP risk in the general population, especially in Asians, and this polymorphism was significantly associated with elevated risk of CP in Asians and Caucasians. There was no association between the A allele and PI risk. None of the contrasts of the genetic model yielded a significant finding in Latin Americans. Different genotyping methods may affect the association between the TNF-α (G-308A) polymorphism and these diseases. CONCLUSION These findings supported that variant A of the TNF-α (G-308A) polymorphism may contribute to CP and AP susceptibility, particularly in Asians and Caucasians. More efforts and further studies with larger sample sizes will be required to validate the risk of CP, AP, and PI.
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Drosos AA, Pelechas E, Kaltsonoudis E, Markatseli TE, Voulgari PV. Biologic Therapies and Autoimmune Phenomena. Mediterr J Rheumatol 2021; 32:96-103. [PMID: 34447904 PMCID: PMC8369271 DOI: 10.31138/mjr.32.2.96] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 04/20/2021] [Indexed: 11/30/2022] Open
Abstract
The use of biologic medications has represented a great advancement in the treatment of autoimmune rheumatic diseases. Despite their excellent efficacy, during the last years, a growing number of reports of autoimmune phenomena and paradoxical inflammation has emerged. These phenomena may range from the discovery of an isolated autoantibody to full-blown autoimmune diseases, organ-specific and systemic. This review has been carried out in order to underline the multitude of the potential adverse manifestations from the use of biologic medications. Thus, early recognition of specific types of autoimmune phenomena is an imperative for the physicians allowing them to have an accurate diagnosis and treatment.
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Affiliation(s)
- Alexandros A Drosos
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Eleftherios Pelechas
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Evripidis Kaltsonoudis
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Theodora E Markatseli
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Paraskevi V Voulgari
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
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32
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Insights into the biology and therapeutic implications of TNF and regulatory T cells. Nat Rev Rheumatol 2021; 17:487-504. [PMID: 34226727 DOI: 10.1038/s41584-021-00639-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2021] [Indexed: 02/06/2023]
Abstract
Treatments that block tumour necrosis factor (TNF) have major beneficial effects in several autoimmune and rheumatic diseases, including rheumatoid arthritis. However, some patients do not respond to TNF inhibitor treatment and rare occurrences of paradoxical disease exacerbation have been reported. These limitations on the clinical efficacy of TNF inhibitors can be explained by the differences between TNF receptor 1 (TNFR1) and TNFR2 signalling and by the diverse effects of TNF on multiple immune cells, including FOXP3+ regulatory T cells. This basic knowledge sheds light on the consequences of TNF inhibitor therapies on regulatory T cells in treated patients and on the limitations of such treatment in the control of diseases with an autoimmune component. Accordingly, the next generation of drugs targeting TNF is likely to be based on agents that selectively block the binding of TNF to TNFR1 and on TNFR2 agonists. These approaches could improve the treatment of rheumatic diseases in the future.
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Jordan DR, Park JSY, Al-Breiki D. Acute orbital inflammation with loss of vision: a paradoxical adverse event associated with infliximab therapy for Crohn's disease. Orbit 2021; 41:791-796. [PMID: 34120561 DOI: 10.1080/01676830.2021.1939726] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Anti-TNF-α agents (e.g. infliximab, adalimumab, etanercept) are effective management options in various inflammatory and autoimmune diseases (e.g. inflammatory bowel disease). The occurrence during anti-TNF-α agent therapy of a new onset or exacerbation of an inflammatory condition that usually responds to this class of drug has been termed a paradoxical adverse event (PAE). A wide range of ophthalmic PAEs have been reported including uveitis, optic neuritis/neuropathy, scleritis, orbital myositis, retinal vasculitis, and others. The patient reported herein developed a dramatic orbital inflammatory PAE during his infliximab infusions, which manifested as an acute orbital apex syndrome with vision loss. Physicians using this medication should be aware of this serious vision-threatening PAE, and urgent therapy with high dose intravenous corticosteroids may be required.
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Affiliation(s)
- David R Jordan
- Department of Ophthalmology, University of Ottawa and the Ottawa Hospital, Ottawa, Ontario, Canada
| | - John S Y Park
- Department of Ophthalmology, University of Ottawa and the Ottawa Hospital, Ottawa, Ontario, Canada
| | - Danah Al-Breiki
- Department of Ophthalmology, University of Ottawa and the Ottawa Hospital, Ottawa, Ontario, Canada
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Agarwal M, Dutta Majumder P, Babu K, Konana VK, Goyal M, Touhami S, Stanescu-Segall D, Bodaghi B. Drug-induced uveitis: A review. Indian J Ophthalmol 2021; 68:1799-1807. [PMID: 32823396 PMCID: PMC7690475 DOI: 10.4103/ijo.ijo_816_20] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Uveitis maybe induced by the use of various medications known as drug-induced uveitis (DIU), though rare it is an important cause of uveitis which one needs to be aware of. The drugs may be administered through any route including systemic, topical, and intravitreal. Ocular inflammation can be in the form of anterior, intermediate, posterior or pan uveitis, and rarely may present as episcleritis and scleritis. Identification of drug as the offending agent of uveitis is important as many a times stopping the drug may help recover the uveitis or the concomitant use of corticosteroids. An extensive literature review was done using the Pubmed. An overview of DIU is provided as it is important for us to be aware of this clinical entity.
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Affiliation(s)
- Manisha Agarwal
- Vitreoretina and Uveitis Services, Dr. Shroff's Charity Eye Hospital, New Delhi, India
| | | | - Kalpana Babu
- Department of Uveitis and Ocular Inflammation, Vittala International Institute of Ophthalmology, Prabha Eye Clinic and Research Centre, Bangalore, Karnataka, India
| | | | - Mallika Goyal
- Department of Ophthalmology, IHU FOReSIGHT, Pitie-Salpetriere Universtiy Hospital, Paris, France
| | - Sara Touhami
- Department of Ophthalmology, IHU FOReSIGHT, Pitie-Salpetriere Universtiy Hospital, Paris, France
| | - Dinu Stanescu-Segall
- Department of Ophthalmology, IHU FOReSIGHT, Pitie-Salpetriere Universtiy Hospital, Paris, France
| | - Bahram Bodaghi
- Department of Ophthalmology, IHU FOReSIGHT, Pitie-Salpetriere Universtiy Hospital, Paris, France
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35
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Jadhav P, Kulkarni T, Jadhav J, Desai S, Baviskar R. Levetiracetam-induced systemic lupus erythematosus. J R Coll Physicians Edinb 2021; 51:58-60. [PMID: 33877137 DOI: 10.4997/jrcpe.2021.114] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a rare autoimmune disorder in a physician's practice, commonly presenting in young females. It is rare for SLE to present at a late age. Though SLE is idiopathic, sometimes it can present as an adverse reaction to drugs. Quite a few drugs are implicated in this process. However, there are no reports of levetiracetam causing SLE. Here, we present a case of 62-year-old female presenting with SLE after consumption of levetiracetam for 1 year for her epilepsy. Erythematosus rash was her main symptom. This was associated with a strong positivity of antinuclear antibody. The symptoms remitted completely after the discontinuation of levetiracetam, suggesting them to be because of drug-induced lupus (DIL). DIL differs from SLE in being mild, affecting atypical age groups and resolving completely on withdrawal of the drug.
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Affiliation(s)
- Praveen Jadhav
- Omkar Rheumatology Clinic, Gaikwad Mala, Nasik Road, MH 422101, India,
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36
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Bounia CA, Theodoropoulou EN, Liossis SNC. Glomerulonephritis in Two Patients with SpA Treated with TNF-α Blockers and a Review of the Literature. Biologics 2021; 15:61-66. [PMID: 33762816 PMCID: PMC7982436 DOI: 10.2147/btt.s297712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/16/2021] [Indexed: 11/23/2022]
Abstract
Renal failure or acute/chronic kidney damage may present as a clinical manifestation of rheumatic diseases. In addition treatment with DMARDs or biologic drugs may induce nephrotoxicity. In this case-based review, we present two patients with SpA under anti-TNF-α treatment admitted to our hospital because of renal failure and proteinuria. We review previously published yet isolated cases of TNF-α blocker-induced glomerular disease in patients with SpA. Renal manifestations are occasionally seen in patients with ankylosing spondylitis and psoriatic arthritis with IgA nephropathy being the most common of them. Anti-TNF-α agents although reportedly used for the treatment of glomerular nephropathy as a disease manifestation, they have been considered responsible for provoking renal damage in some cases. A diagnostic approach for patients with SpA treated with anti-TNF-α agents presenting with renal manifestations is proposed herein.
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Affiliation(s)
| | | | - Stamatic-Nick C Liossis
- Division of Rheumatology, Patras University Hospital, Patras, Greece.,Department of Internal Medicine, University of Patras Medical School, Patras, Greece
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Systematic review and meta-analysis of dermatological reactions in patients with inflammatory bowel disease treated with anti-tumour necrosis factor therapy. Eur J Gastroenterol Hepatol 2021; 33:346-357. [PMID: 32889976 DOI: 10.1097/meg.0000000000001917] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM The role of anti-tumour necrosis factor (TNF) medications in inflammatory bowel disease (IBD) is now established. Recent studies have reported the incidence of dermatological adverse events with use of anti-TNFs in IBD. The aim of this study was to investigate the incidence of dermatological reactions in patients on anti-TNF therapy for IBD. METHODS We searched MEDLINE, the Cochrane Library and EMBASE to identify studies reporting any dermatological reaction in patients exposed to anti-TNF for treatment of IBD. The incidence of dermatological complications in the entire review population was pooled by meta-analysis of data from individual studies using the random effects model. Pooled estimates in male and female patients and in patients treated with different anti-TNF agents were also calculated. We applied mixed effects (methods of moments) regression models to investigate between-study heterogeneity. RESULTS Forty-eight studies reporting a total of 29 776 patients treated with anti-TNF medications for IBD were identified. Gender distribution was available for 18 960 participants with 45.3% females. Data on type of disease were available for 20 226 patients: 74.9% (n = 15 154) Crohn's disease, 24.2% (n = 4901) ulcerative colitis and 0.9% (n = 171) IBD-unclassified. The type of anti-TNF used was mentioned for 17 085 individuals: 67.5% (n = 11 530) infliximab (IFX), 30.5% (n = 5203) adalimumab (ADA), 1.7% (n = 296) certolizumab and 0.3% (n = 56) golimumab. The pooled incidence of any dermatological reaction from 26 studies was 19.4% [95% confidence interval (CI): 15.2-24.4]. The pooled incidence for IFX and ADA was 23.7% (95% CI: 17.8-30.8) from 12 studies and 33.3% (95% CI 18.8-51.1) from seven studies, respectively. We found a trend of increased event rate with increasing percentage of male population (P = 0.08). The commonest reported event (39 studies) was psoriasis/psoriasiform rash with a pooled incidence of 5.6% (95% CI: 4.2-7.4). The incidence of psoriasis/psoriasiform rashes for IFX and ADA was 6.1% (95% CI 3.4-10.6) from 15 studies and 5.9% (95% CI: 2.5-13.5) from seven studies, respectively. Other reactions reported included eczema with a pooled incidence of 5.5% (95% CI: 3.3-8.9) from 17 studies and skin infections with pooled incidence of 7.9% (95% CI: 5.5-11.2) from 11 studies. CONCLUSION The incidence of dermatological events in patients with IBD treated with anti-TNF medications is high. The most commonly reported reaction is psoriasis/psoriasiform reaction. Clinicians should be vigilant to dermatological side effects following treatment of IBD with anti-TNF.
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Obi ON, Lower EE, Baughman RP. Biologic and advanced immunomodulating therapeutic options for sarcoidosis: a clinical update. Expert Rev Clin Pharmacol 2021; 14:179-210. [PMID: 33487042 DOI: 10.1080/17512433.2021.1878024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Sarcoidosis is a multi-organ disease with a wide range of clinical manifestations and outcomes. A quarter of sarcoidosis patients require long-term treatment for chronic disease. In this group, corticosteroids and cytotoxic agents be insufficient to control diseaseAreas covered: Several biologic agents have been studied for treatment of chronic pulmonary and extra-pulmonary disease. A review of the available literature was performed searching PubMed and an expert opinion regarding specific therapy was developed.Expert opinion: These agents have the potential of treating patients who have progressive disease. Many of these agents have different mechanisms of action, response rates, and toxicity profiles.
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Affiliation(s)
- Ogugua Ndili Obi
- Division of Pulmonary Critical Care and Sleep Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA
| | - Elyse E Lower
- Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Robert P Baughman
- Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
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Roth M, Gray JT, Peterson PG, Clark PA. Dapsone-induced DRESS after infliximab-induced vasculitis: a case of cerebral infarction in the context of multiple drug reactions. BMJ Case Rep 2020; 13:13/12/e237560. [PMID: 33334758 PMCID: PMC7747542 DOI: 10.1136/bcr-2020-237560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening condition characterised by peripheral eosinophilia, rash and multi-organ failure arising several weeks after exposure to the culprit medication. Although rare, DRESS syndrome triggered by specific agents has been associated with specific genetic polymorphisms more prevalent in different ethnic groups, including an association between dapsone-induced DRESS and Human Leukocyte Antigen (HLA)-B:13*01, a single nucleotide polymorphism more prevalent in those of Asian descent. DRESS and drug-related vasculitis may affect any organ system including the central nervous system (CNS), usually manifesting as encephalitis, meningitis or embolic cerebrovascular accidents related to eosinophilic cardiac disease and thrombosis. CNS vasculitis is a much rarer complication of drug reactions that may manifest as multifocal ischemia on neuroimaging. In circumstances of drug-related vasculitides, treatment with high-dose corticosteroids may lead to rapid improvement and, ultimately, resolution of associated focal neurologic deficits.
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Affiliation(s)
- Michael Roth
- Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Jeffery T Gray
- Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Paul Gabriel Peterson
- Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Paul A Clark
- Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
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Urushikubo J, Yanai S, Nakamura S, Toya Y, Asakura K, Gonai T, Eizuka M, Uesugi N, Sugai T, Matsumoto T. IgA vasculitis in a patient with ulcerative colitis under infliximab: drug-induced or genetic? Clin J Gastroenterol 2020; 14:198-203. [PMID: 33141395 DOI: 10.1007/s12328-020-01280-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/19/2020] [Indexed: 11/26/2022]
Abstract
We present the case of a 17-year-old male patient with ulcerative colitis (UC) under infliximab therapy and a family history of IgA vasculitis (IgAV). During a maintenance infliximab session, he developed palpable purpura, abdominal pain, and hematochezia. Computed tomography and endoscopy revealed findings compatible with gastrointestinal manifestations of IgAV. He was successfully treated by intravenous prednisolone and did not develop recurrence of IgAV during subsequent infliximab infusions.
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Affiliation(s)
- Jun Urushikubo
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.
| | - Shunichi Yanai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Shotaro Nakamura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Yosuke Toya
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Kensuke Asakura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Takahiro Gonai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Makoto Eizuka
- Division of Molecular Diagnostic Pathology, Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Noriyuki Uesugi
- Division of Molecular Diagnostic Pathology, Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Tamotsu Sugai
- Division of Molecular Diagnostic Pathology, Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
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Yoshikawa N, Matsubara E, Yamamoto M, Yamazaki H, Uehara M, Kamata M, Tanaka H. Drug-induced Bullous Pemphigoid and Lupus Erythematosus Occurring under Anti-TNF-α and IL-6 Therapy in a Patient with Rheumatoid Arthritis. Intern Med 2020; 59:2611-2618. [PMID: 32641647 PMCID: PMC7662041 DOI: 10.2169/internalmedicine.4646-20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
A 65-year-old Japanese woman, who was diagnosed with rheumatoid arthritis and Sjögren's syndrome with various autoantibodies including anti-DNA antibody, developed bullous pemphigoid (BP) and hematological abnormalities like lupus erythematosus after adalimumab therapy. The discontinuation of adalimumab resolved those disorders but polyarthritis thereafter relapsed. The introduction of abatacept was not effective, but tocilizumab was found to be effective for polyarthritis, however, thereafter both bullous disease and severe pancytopenia developed. Discontinuation of tocilizumab was effective, but polyarthritis again developed, and baricitinib resolved it. There is an increasing number of reports of drug-induced BP and lupus erythematosus, and biologics might trigger an alteration in the pathophysiological/clinical course of rheumatic disorder.
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Affiliation(s)
- Noritada Yoshikawa
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
- Division of Rheumatology, Center for Antibody and Vaccine Therap, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Erika Matsubara
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Motohisa Yamamoto
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
- Division of Rheumatology, Center for Antibody and Vaccine Therap, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Hiroki Yamazaki
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Masaaki Uehara
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Masahiro Kamata
- Department of Dermatology, Teikyo University School of Medicine, Japan
| | - Hirotoshi Tanaka
- Department of Rheumatology and Allergy, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
- Division of Rheumatology, Center for Antibody and Vaccine Therap, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
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Liberman P, Burkholder BM. Adalimumab-associated Acquired Hemophilia in a Patient with Scleritis. Ocul Immunol Inflamm 2020; 30:294-296. [PMID: 32966141 DOI: 10.1080/09273948.2020.1808227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Acquired hemophilia A (AHA) is a rare condition that may be drug-induced. In this case report, we describe a patient who presented with extensive subcutaneous bleeding three years after beginning treatment with adalimumab for necrotizing scleritis. His workup was compatible with drug-induced AHA. He was treated with high-dose corticosteroids, cyclophosphamide, and rituximab. Adalimumab was discontinued. We present this case as an example of a rare, but potentially life-threatening, complication of adalimumab.
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Affiliation(s)
- Paulina Liberman
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Departamento de Oftalmología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Bryn M Burkholder
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Moiseev S, Cohen Tervaert JW, Arimura Y, Bogdanos DP, Csernok E, Damoiseaux J, Ferrante M, Flores-Suárez LF, Fritzler MJ, Invernizzi P, Jayne D, Jennette JC, Little MA, McAdoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige JA, Segelmark M, Shoenfeld Y, Sinico RA, Sousa MJ, Specks U, Terrier B, Tzioufas AG, Vermeire S, Zhao MH, Bossuyt X. 2020 international consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 2020; 19:102618. [PMID: 32663621 DOI: 10.1016/j.autrev.2020.102618] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023]
Abstract
This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.
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Affiliation(s)
- Sergey Moiseev
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia.
| | - Jan Willem Cohen Tervaert
- Department of Medicine, Division of Rheumatology, University of Alberta, Edmonton, Canada and Maastricht University, Maastricht, The Netherlands
| | - Yoshihiro Arimura
- Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Dimitrios P Bogdanos
- Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece
| | - Elena Csernok
- Department of Internal Medicine, Rheumatology and Immunology, Vasculitis-Center Tübingen-Kirchheim, Medius Klinik Kirchheim, University of Tübingen, Kirchheim-Teck, Germany
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marc Ferrante
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Luis Felipe Flores-Suárez
- Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
| | - Marvin J Fritzler
- Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Pietro Invernizzi
- Division Gastroenterology and Center for Autoimmune Liver Diseases, University of Milano-Bicocca School of Medicine, Monza, Italy
| | - David Jayne
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - J Charles Jennette
- Division of Nephropathology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Mark A Little
- Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Dublin, Ireland
| | - Stephen P McAdoo
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Pavel Novikov
- Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Charles D Pusey
- Centre for Inflammatory Disease, Department of Medicine, Imperial College London, London, UK
| | - Antonella Radice
- Microbiology and Virology Institute, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milan, Italy
| | - Alan D Salama
- UCL Department of Renal Medicine, Royal Free Hospital, London, UK
| | - Judith A Savige
- Department of Medicine, Melbourne Health, University of Melbourne, Melbourne, Australia
| | - Mårten Segelmark
- Department of Clinical Sciences, Lund University, Department of Nephrology and Rheumatology, Skane University Hospital, Lund, Sweden
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Renato A Sinico
- Department of Medicine and Surgery, Università degli Studi di Milano-Bicocca, Monza, Italy
| | - Maria-José Sousa
- Immunopathology and Autoimmunity Department, Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal
| | - Ulrich Specks
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Benjamin Terrier
- Department of Internal Medicine, National Referral Center for Rare Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France
| | - Athanasios G Tzioufas
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Severine Vermeire
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
| | - Ming-Hui Zhao
- Renal Division, Peking University First Hospital, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Peking-Tsinghua Centre for Life Sciences, Beijing, China
| | - Xavier Bossuyt
- Laboratory Medicine, University Hospitals Leuven, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
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Alrashidi A, Rhodes LE, Sharif JCH, Kreeshan FC, Farrar MD, Ahad T. Systemic drug photosensitivity-Culprits, impact and investigation in 122 patients. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2020; 36:441-451. [PMID: 32564400 DOI: 10.1111/phpp.12583] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 05/19/2020] [Accepted: 06/13/2020] [Indexed: 01/20/2023]
Abstract
BACKGROUND Systemic drugs are a potentially reversible cause of photosensitivity. We explore prevalence, impact, phototest findings and culprit drugs. METHODS Retrospective review of patients was diagnosed with drug-induced photosensitivity in a specialist photoinvestigation centre (2000-2016), using data recorded in standardized pro forma. Patients underwent detailed clinical evaluation. Monochromator phototesting was performed to 300 ± 5 nm, 320 ± 10 nm, 330 ± 10 nm, 350 ± 20 nm, 370 ± 20 nm, 400 ± 20 nm, 500 ± 20nm and 600 ± 20 nm. Broadband UVA and solar-simulated radiation (SSR) testing were performed, and photopatch testing and laboratory tests examined for other causes of photosensitivity. DLQI was evaluated. RESULTS Prevalence of drug-induced photosensitivity was 5.4% (122/2243) patients presenting with photosensitivity. Patients with drug-induced photosensitivity were 52.5% female; median 62 years (range 11-86); phototype I (17.2%), II (39.3%), III (26.2%), IV (6.5%), V (4.1%). Fifty-five (45.1%) patients had reduced erythemal thresholds on monochromator phototesting: 83.6%% to UVA alone, 14.5% to both UVA and UVB, 1.8% to UVA and visible light; 61.4% (n = 75) showed abnormal response to broadband UVR. Drugs implicated: quinine (11.5%), diuretics (10.7%; thiazide 9.8%), antifungals (9.8%), proton-pump-inhibitors (9.8%), angiotensin-converting enzyme inhibitors (7.4%), anti-inflammatory drugs (6.6%), statins (5.7%), selective serotonin reuptake inhibitors (4.9%), calcium channel antagonists (3.3%), anti-epileptics (3.3%), tricyclic antidepressants (3.3%), beta-blockers (2.5%), antibiotics (2.5%), others (≤1.6% cases each). Emerging culprits included azathioprine (2.5%) and biologics (TNF-α inhibitors, denosumab; 2.5%). Median DLQI was 11 (range 2-27) for the past year. CONCLUSION Classically described photosensitizing drugs such as thiazides and quinine remain common offenders, while emerging culprits include biologics such as TNF-a inhibitors and proton-pump-inhibitors. There is very large impact on life quality; identification facilitates measures including drug cessation and implementation of appropriate photoprotection.
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Affiliation(s)
- Amirah Alrashidi
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
| | - Lesley E Rhodes
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
| | - Jennifer C H Sharif
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
| | - Firas C Kreeshan
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
| | - Mark D Farrar
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
| | - Tashmeeta Ahad
- Faculty of Biology, Medicine and Health, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Centre for Dermatology Research, Manchester Academic Health Science Centre, University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK
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Guzman AK, Balagula Y. Drug-induced cutaneous vasculitis and anticoagulant-related cutaneous adverse reactions: insights in pathogenesis, clinical presentation, and treatment. Clin Dermatol 2020; 38:613-628. [PMID: 33341196 DOI: 10.1016/j.clindermatol.2020.06.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Drug-induced vasculitis and anticoagulant-related skin reactions are commonly encountered in the inpatient and outpatient settings. The spectrum of clinical presentation is broad and ranges from focal, skin-limited disease, to more extensive cutaneous and soft tissue necrosis, to potentially fatal systemic involvement. The prompt recognition of these adverse events can have a significant impact on patient morbidity and mortality. We highlight the key features of the clinical presentation with an emphasis on primary lesion morphology, distribution, and epidemiology of purpuric drug reactions. The proposed pathophysiology, histologic findings, and therapeutic interventions of these potentially life-threatening diseases are discussed.
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Affiliation(s)
- Anthony K Guzman
- Division of Dermatology, Department of Internal Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
| | - Yevgeniy Balagula
- Division of Dermatology, Department of Internal Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
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Nicolela Susanna F, Pavesio C. A review of ocular adverse events of biological anti-TNF drugs. J Ophthalmic Inflamm Infect 2020; 10:11. [PMID: 32337619 PMCID: PMC7184065 DOI: 10.1186/s12348-020-00202-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 03/23/2020] [Indexed: 12/13/2022] Open
Abstract
The recent introduction of biological agents has revolutionized the treatment of chronic immune-inflammatory diseases; however, this new therapy did not come without significant side effects.Through large controlled studies indicating decrease in the number of uveitis flares, the role of TNF inhibitors therapy for non-infectious uveitis gained more ground. Paradoxically to its therapeutic effect, there are reports associating these drugs with the onset or recurrence of inflammatory eye disease.A number of studies have suggested possible roles for anti-TNF-α agents in precipitating or worsening an underlying inflammatory process, including the hypothesis of a disequilibrium in cytokine balance, but to date the mechanisms responsible for these adverse events are not fully understood.A PubMed literature search was performed using the following terms: ophthalmic complication, uveitis, inflammatory eye disease, optic neuritis, neuropathy, adverse events, anti-TNF, TNF alpha inhibitor, infliximab, etanercept, adalimumab, golimumab, certolizumab, and biologics. The data presented in this study was mainly derived from the use of TNF inhibitors in rheumatology, essentially because these drugs have been used for a longer period in this medical field.Many of the ocular adverse events reported on this review may be considered a paradoxical effect of anti-TNF therapy. We found a variety of data associating new onset of uveitis with anti-TNF therapy for rheumatic conditions, predominantly under etanercept.In conclusion, although there is increasing data on ocular adverse events, it remains to be seen whether the suggested link between TNF inhibitors and the onset of ocular inflammation is substantiated by more quality data. Nevertheless, the awareness of potential treatment side effects with anti-TNF should be highlighted.
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Affiliation(s)
| | - Carlos Pavesio
- Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
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47
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Turk D, Vellaichamy G, Lyons AB, Parks‐Miller A, Nelson T, Meysami A, Hamzavi IH. Anti‐tumor necrosis factor (TNF)‐induced lupus in a patient with hidradenitis suppurativa. Int J Dermatol 2020; 59:e73-e74. [DOI: 10.1111/ijd.14674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/27/2019] [Accepted: 09/08/2019] [Indexed: 01/21/2023]
Affiliation(s)
- Dilara Turk
- Wayne State School of Medicine Detroit MI USA
| | | | - Alexis B. Lyons
- Department of Dermatology Henry Ford Hospital Systems Detroit MI USA
| | | | - Tamara Nelson
- Department of Rheumatology Indiana University Health Indianapolis IN USA
| | - Alireza Meysami
- Department of Rheumatology Henry Ford Hospital Detroit MI USA
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Chang C, Tanaka A, Bowlus C, Gershwin ME. The use of biologics in the treatment of autoimmune liver disease. Expert Opin Investig Drugs 2020; 29:385-398. [PMID: 32102572 DOI: 10.1080/13543784.2020.1733527] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and juvenile autoimmune hepatitis (JAIH). The pathophysiologic features of each disease vary, but generally include presence of autoantibodies, cytokine abnormalities, and/or T and B cell autoreactivity.Areas covered: This article compares conventional therapy with newer biologics available for treatment of autoimmune liver diseases. Conventional therapy involves the use of immunosuppressive agents, or other treatment modalities for specific autoimmune liver diseases such as ursodeoxycholic acid and fibrates for PBC. Biologics were developed to target the production of autoantibodies by B cells, the presence of proinflammatory cytokines, adhesion molecules or T and B cell activation.Expert opinion: Despite the promise of biologics being able to target specific cellular and humoral pathways, results have been generally poor, and safety has not been as expected. Cases of autoimmune hepatitis have also developed with the use of these biologicals. Reasons for the lack of success of biologics in treating autoimmune liver disease has led to a reevaluation of our understanding of underlying pathogenesis, demonstrating that while our knowledge of the immunity has improved over the past two decades, it is far from complete.
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Affiliation(s)
- Christopher Chang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.,Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, USA
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Christopher Bowlus
- Division of Gastroenterology, University of California at Davis, Davis, CA, USA
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA
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Cheemalavagu S, McCoy SS, Knight JS. Digital ischaemia secondary to adalimumab-induced antiphospholipid syndrome. BMJ Case Rep 2020; 13:13/2/e232907. [PMID: 32041760 DOI: 10.1136/bcr-2019-232907] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
A 50-year-old woman with a history of Crohn's disease treated with adalimumab presented with left hand pain and duskiness. Angiogram showed non-filling of the radial and digital arteries of the hand. Antiphospholipid antibody testing was positive, leading to a diagnosis of antitumour necrosis factor-induced antiphospholipid syndrome. Adalimumab was discontinued, and she was treated with the vitamin K antagonist warfarin and low-dose aspirin. Upon resolution of the antiphospholipid antibodies, she was transitioned to aspirin alone without recurrence of thrombosis.
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Affiliation(s)
| | - Sara S McCoy
- Division of Rheumatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Jason S Knight
- Internal Medicine-Rheumatology, University of Michigan Hospital, Ann Arbor, Michigan, USA
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50
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Pferdehirt L, Ross AK, Brunger JM, Guilak F. A Synthetic Gene Circuit for Self-Regulating Delivery of Biologic Drugs in Engineered Tissues. Tissue Eng Part A 2019; 25:809-820. [PMID: 30968743 DOI: 10.1089/ten.tea.2019.0027] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
IMPACT STATEMENT We engineered a synthetic transcription system based on nuclear factor kappa-light-chain-enhancer of activated B cells signaling that can attenuate the effects of the inflammatory cytokine interleukin (IL)-1α in a self-regulating manner. This system responds in a time- and dose-dependent manner to rapidly produce therapeutic levels of IL-1 receptor antagonist (IL-1Ra). The use of lentiviral gene therapy allows this system to be utilized through different transduction methods and in different cell types for a variety of applications. Broadly, this approach may be applicable in developing autoregulated biologic systems for tissue engineering and drug delivery in a range of disease applications.
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Affiliation(s)
- Lara Pferdehirt
- 1 Department of Orthopedic Surgery, Washington University in Saint Louis, Saint Louis, Missouri.,2 Shriners Hospitals for Children-St. Louis, St. Louis, Missouri.,3 Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, Missouri.,4 Center of Regenerative Medicine, Washington University in Saint Louis, Saint Louis, Missouri
| | - Alison K Ross
- 1 Department of Orthopedic Surgery, Washington University in Saint Louis, Saint Louis, Missouri.,2 Shriners Hospitals for Children-St. Louis, St. Louis, Missouri.,3 Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, Missouri.,4 Center of Regenerative Medicine, Washington University in Saint Louis, Saint Louis, Missouri
| | - Jonathan M Brunger
- 5 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California
| | - Farshid Guilak
- 1 Department of Orthopedic Surgery, Washington University in Saint Louis, Saint Louis, Missouri.,2 Shriners Hospitals for Children-St. Louis, St. Louis, Missouri.,3 Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, Missouri.,4 Center of Regenerative Medicine, Washington University in Saint Louis, Saint Louis, Missouri
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