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Mahmud O, Jahangir A, Waqas SM, Nasir N. Drug-Induced Lupus in an HIV-Positive Patient Treated for Tuberculosis: A Case Report. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2025; 18:11795476251329232. [PMID: 40151547 PMCID: PMC11948544 DOI: 10.1177/11795476251329232] [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: 08/03/2024] [Accepted: 03/06/2025] [Indexed: 03/29/2025]
Abstract
The accurate diagnosis of pathologies with obscure presentations requires comprehensive clinical evaluation, epidemiological context, and consideration of the patient's clinical or hospital course. In this case report, we describe a 30-year-old female receiving antituberculosis therapy who developed multiple signs and symptoms that were unexplained by any single diagnosis, including multiple rashes with different features. The patient was determined to have drug induced lupus with concomitant HIV infection. Physicians should consider the possibility of co-existing disease processes when a single unifying diagnosis that reconciles all aspects of the patient's presentation cannot be identified.
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Affiliation(s)
- Omar Mahmud
- Medical College, Aga Khan University, Karachi, Pakistan
| | | | | | - Noreen Nasir
- Section of Internal Medicine, Department of Medicine, Aga Khan University, Karachi, Pakistan
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2
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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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3
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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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4
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Kaya Akca U, Sener S, Batu ED, Balik Z, Basaran O, Bilginer Y, Ozen S. Drug-induced lupus erythematosus in childhood: Case-based review. Lupus 2024; 33:737-748. [PMID: 38580326 DOI: 10.1177/09612033241245078] [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: 04/07/2024]
Abstract
BACKGROUND Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than adults. METHODS In this study, we present four children with DILE and similar published cases through a systematic literature review. RESULTS We report four children (three girls and one boy) who developed DILE associated with the use of topiramate, doxycycline, etanercept, and ethosuximide. Three of them were positive for anti-histone antibodies. In all patients, the drug was discontinued and symptoms resolved completely. The literature review revealed 48 articles describing 61 children with DILE. In the evaluation of 65 patients (our 4 patients and 61 patients from the literature), the most frequently reported drugs associated with DILE were ethosuximide (n = 13) and minocycline (n = 12). Fever (n = 33), arthralgia (n = 31), rash (n = 30), and arthritis (n = 29) were the most common clinical manifestations. Antinuclear antibody (ANA) was positive in 93.5% of patients and anti-histone antibodies were detected in 72.2% of the patients. As for treatment, the responsible drug was discontinued in all patients, and corticosteroids were initiated in 53.3%. Improvement was achieved in 92.0% of patients. CONCLUSION For children presenting with SLE features, proper drug history is crucial since DILE may be more frequent than anticipated. An association of the relevant drug with the symptoms, and resolution of symptoms on drug withdrawal provides evidence for the diagnosis of DILE.
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Affiliation(s)
- Ummusen Kaya Akca
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Seher Sener
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ezgi Deniz Batu
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Zeynep Balik
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ozge Basaran
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Yelda Bilginer
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Seza Ozen
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
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5
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Echevarria V, Pierre E, Quiros J, Eftekhari P. Hydralazine-Induced Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Cureus 2023; 15:e47656. [PMID: 38021694 PMCID: PMC10667955 DOI: 10.7759/cureus.47656] [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: 10/24/2023] [Indexed: 12/01/2023] Open
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis comprises several conditions involving vascular destruction that extends into tissue necrosis. There are several autoimmune and environmental causes implicated in the disease progression; among these is drug-induced vasculitis caused by hydralazine use. Hydralazine-induced vasculitis is an uncommon potential complication of the medication and can progress to multisystem involvement and eventually advance to end-organ damage and renal failure. Our patient presented with symptoms of lower extremity edema, dyspnea, and a nonproductive cough eventually resulting in the identification of hydralazine-induced ANCA-associated vasculitis with hypocomplementemia and positive anti-histone antibody. Due to the prevalence of hydralazine as a cardiac drug, physicians managing patients on the medication should have a high index of suspicion of the potential for vasculitis in order to promote prompt diagnosis and treatment of the ANCA-vasculitis.
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Affiliation(s)
- Victoria Echevarria
- Internal Medicine, American University of the Caribbean School of Medicine, Sint Maarten, SXM
| | - Ednord Pierre
- Internal Medicine, Broward Health Medical Center, Fort Lauderdale, USA
| | - Jorge Quiros
- Internal Medicine, Broward Health Medical Center, Fort Lauderdale, USA
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6
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Merello de Miguel A, Argentina F, Barcon Marques M, Sendagorta Cudos E, Menéndez Colino R. [Drug-induced lupus diagnosed by teledermatology with nursing home: a case report]. Rev Esp Geriatr Gerontol 2022; 57:284-285. [PMID: 36127202 DOI: 10.1016/j.regg.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 07/18/2022] [Accepted: 08/05/2022] [Indexed: 10/14/2022]
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7
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Foti M, Shrimanker TV, Hasan UN, Hussein KI. Recurrent severe neutropenia following doxycycline use in a young healthy woman. Clin Case Rep 2022; 10:e05524. [PMID: 35251651 PMCID: PMC8886723 DOI: 10.1002/ccr3.5524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 01/28/2022] [Accepted: 02/14/2022] [Indexed: 11/25/2022] Open
Abstract
A 29-year-old woman was hospitalized for fever, pharyngitis, and severe neutropenia after recent use of doxycycline and other antimicrobials. Three years later, she again presented with severe neutropenia after recent doxycycline use. Diagnostic workups were unyielding. This is only the second published case of severe neutropenia associated with doxycycline use.
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Affiliation(s)
- Michael Foti
- Department of Medicine Greenwich Hospital Yale-New Haven Health System Greenwich Connecticut USA
| | - Tushaar V Shrimanker
- Department of Medicine Greenwich Hospital Yale-New Haven Health System Greenwich Connecticut USA
| | - Umar N Hasan
- Department of Medicine Greenwich Hospital Yale-New Haven Health System Greenwich Connecticut USA
| | - Khalil I Hussein
- Department of Medicine Greenwich Hospital Yale-New Haven Health System Greenwich Connecticut USA
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8
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Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs. Ann Dermatol Venereol 2021; 148:211-220. [PMID: 34711400 DOI: 10.1016/j.annder.2021.02.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/24/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023]
Abstract
Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.
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9
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Worm M, Zidane M, Eisert L, Fischer-Betz R, Foeldvari I, Günther C, Iking-Konert C, Kreuter A, Müller-Ladner U, Nast A, Ochsendorf F, Schneider M, Sticherling M, Tenbrock K, Wenzel J, Kuhn A. S2k-Leitlinie zur Diagnostik und Therapie des kutanen Lupus erythematodes - Teil 2: Therapie, Risikofaktoren und spezielle Fragestellungen. J Dtsch Dermatol Ges 2021; 19:1371-1395. [PMID: 34541800 DOI: 10.1111/ddg.14491_g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 02/20/2021] [Indexed: 01/03/2023]
Affiliation(s)
- Margitta Worm
- Allergologie und Immunologie, Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin
| | - Miriam Zidane
- Division of Evidence-Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin
| | - Lisa Eisert
- Klinik für Dermatologie und Venerologie, Vivantes Klinikum Neukölln, Berlin
| | - Rebecca Fischer-Betz
- Poliklinik und Funktionsbereich für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf
| | - Ivan Foeldvari
- Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg
| | - Claudia Günther
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Dresden
| | - Christof Iking-Konert
- Zentrum für Innere Medizin der III. Medizinischen Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Alexander Kreuter
- Dermatologie, Venerologie und Allergologie, Helios St. Elisabeth Klinik Oberhausen, Oberhausen
| | - Ulf Müller-Ladner
- Abteilung für Rheumatologie und Klinische Immunologie, Kerckhoff-Klinik GmbH, Bad Nauheim
| | - Alexander Nast
- Division of Evidence-Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin
| | - Falk Ochsendorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Matthias Schneider
- Poliklinik und Funktionsbereich für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf
| | | | - Klaus Tenbrock
- Klinik für Kinder- und Jugendmedizin, Uniklinik RWTH Aachen, Aachen
| | - Jörg Wenzel
- Dermatologische Klinik, Universitätsklinikum Bonn, Bonn
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10
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Worm M, Zidane M, Eisert L, Fischer-Betz R, Foeldvari I, Günther C, Iking-Konert C, Kreuter A, Müller-Ladner U, Nast A, Ochsendorf F, Schneider M, Sticherling M, Tenbrock K, Wenzel J, Kuhn A. S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part 2: Therapy, risk factors and other special topics. J Dtsch Dermatol Ges 2021; 19:1371-1395. [PMID: 34338428 DOI: 10.1111/ddg.14491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 02/20/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Margitta Worm
- Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
| | - Miriam Zidane
- Division of Evidence-Based Medicine (dEBM), Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
| | - Lisa Eisert
- Department of Dermatology and Venereology, Vivantes Klinikum Neukölln, Berlin
| | | | - Ivan Foeldvari
- Hamburg Center for Pediatric and Adolescent Rheumatology, Hamburg
| | - Claudia Günther
- Department and Clinic of Dermatology, University Hospital Carl Gustav Carus, Dresden
| | - Christof Iking-Konert
- Center for Internal Medicine at the IIIrd Medical Department and Clinic, University Hospital Hamburg-Eppendorf
| | - Alexander Kreuter
- Dermatology, Venereology and Allergology, Helios St. Elisabeth Klinik Oberhausen
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Kerckhoff-Klinik GmbH, Bad Nauheim
| | - Alexander Nast
- Division of Evidence-Based Medicine (dEBM), Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
| | - Falk Ochsendorf
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt am Main
| | - Matthias Schneider
- Clinic and Functional Division for Rheumatology, University Hospital Düsseldorf
| | | | - Klaus Tenbrock
- Department of Pediatrics and Adolescent Medicine, University Hospital RWTH Aachen
| | - Jörg Wenzel
- Dermatological Department, University Hospital Bonn
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11
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Santoriello D, Bomback AS, Kudose S, Batal I, Stokes MB, Canetta PA, Radhakrishnan J, Appel GB, D'Agati VD, Markowitz GS. Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine. Kidney Int 2021; 100:440-446. [PMID: 33857570 DOI: 10.1016/j.kint.2021.03.029] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/23/2021] [Accepted: 03/05/2021] [Indexed: 01/23/2023]
Abstract
Hydralazine, a widely used therapy for hypertension and heart failure, can elicit autoimmune disease, including anti-neutrophil cytoplasmic antibody associated glomerulonephritis (ANCA-GN). We identified 80 cases of ANCA-GN complicating treatment with hydralazine, accounting for 4.3% (80/1858 biopsies) of ANCA-GN diagnosed between 2006 and 2019. Over three-fourths of patients were on hydralazine for at least one year, with mean daily dose of approximately 250 mg/day. ANCA testing revealed p-ANCA/myeloperoxidase-ANCA seropositivity in 98%, including 39% with dual p-ANCA/myeloperoxidase-ANCA and cANCA/anti-protinase 3-ANCA positivity, often accompanied by anti-nuclear antibody (89%), anti-histone antibody (98%), and hypocomplementemia (58%). Kidney biopsy revealed necrotizing and crescentic glomerulonephritis, similar to primary ANCA-GN, but significantly less frequently pauci-immune (77 vs. 100%) and more commonly associated with mesangial hypercellularity (30 vs. 5%), electron dense deposits (62 vs. 20%), and endothelial tubuloreticular inclusions (11 vs. 0%); all significant differences. On follow-up, 42 of 51 patients received induction immunosuppression: 19 reached the combined end-points of kidney failure or death and 32 had mean creatinine of 1.49 mg/dL at last follow-up. Thus, hydralazine-associated ANCA-GN often exhibits overlapping clinical and pathologic features of mild immune complex glomerulonephritis resembling lupus nephritis. With discontinuation of hydralazine and immunosuppression, outcomes are similar to primary ANCA-GN.
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Affiliation(s)
- Dominick Santoriello
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA.
| | - Andrew S Bomback
- Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Satoru Kudose
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | - Ibrahim Batal
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | - M Barry Stokes
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | - Pietro A Canetta
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | - Jai Radhakrishnan
- Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Gerald B Appel
- Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Vivette D D'Agati
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
| | - Glen S Markowitz
- Department of Pathology, Columbia University Irving Medical Center, New York, New York, USA
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Strasma A, Coke H, Mamlouk O, Tchakarov A, Mandayam S. Lupus-Like Glomerulonephritis Associated With Regorafenib, a Multikinase Inhibitor. Kidney Med 2021; 3:294-298. [PMID: 33851126 PMCID: PMC8039408 DOI: 10.1016/j.xkme.2020.11.011] [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] [Indexed: 12/02/2022] Open
Abstract
Drug-induced lupus glomerular diseases have historically been associated with hydralazine, but new drugs that modify the growth, metabolism, and immunity of cells are increasingly found to cause glomerular disease. This includes anti–tumor necrotic factor and other antibody agents used in cancer treatment. Multitarget tyrosine kinases such as regorafenib are increasingly used in metastatic malignancies with good outcomes. Currently, they are not known to have kidney complications except for proteinuria, hypertension, and electrolyte disturbances such as hypophosphatemia. We report a patient who presented within months after starting regorafenib therapy for metastatic colon cancer with acute kidney injury, proteinuria, and hematuria. Biopsy revealed endocapillary proliferative glomerulonephritis with full-house staining on immunofluorescence in the absence of any systemic manifestation of systemic lupus erythematosus. The kidney injury improved with corticosteroid treatment and discontinuation of regorafenib therapy. We discuss the possible mechanisms that led to this class IV pattern of lupus nephritis and conclude that it is likely drug-induced lupus nephritis from regorafenib.
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Affiliation(s)
- Anna Strasma
- Division of Nephrology, Department of Internal Medicine, Duke University, Durham, NC
| | - Howard Coke
- Division of Nephrology, Department of Internal Medicine, University of Texas, Houston, TX
| | - Omar Mamlouk
- Section of Nephrology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amanda Tchakarov
- Department of Pathology and Laboratory Medicine, University of Texas, Houston, TX
| | - Sreedhar Mandayam
- Section of Nephrology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
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13
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Xu ZG, Li WL, Wang X, Zhang SY, Zhang YW, Wei X, Li CD, Zeng P, Luan SD. Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report. World J Clin Cases 2021; 9:707-713. [PMID: 33553412 PMCID: PMC7829731 DOI: 10.12998/wjcc.v9.i3.707] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/23/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies. Their overlap constitutes a rare rheumatologic disease. To date, only dozens of such cases with biopsy-proven glomerulonephritis have been reported worldwide typically in women of childbearing age. Here, we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life.
CASE SUMMARY A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years. As his symptoms were not completely relieved, he visited our hospital for further treatment. Laboratory examinations revealed kidney dysfunction, severe anaemia, hypocom-plementemia, glomerular proteinuria, and microscopic haematuria. Antinuclear antibodies, as well as anti-dsDNA antibodies, were positive. Computed tomography of the chest showed right pleural effusion. Renal biopsy was performed, and histology suggested crescentic glomerulonephritis, pauci-immune type. After treatment with plasmapheresis, glucocorticoid, and cyclo-phosphamide, the disease was in remission, and the patient remained in a stable condition for over 3 years post-hospital discharge.
CONCLUSION Due to its complexity and rarity, SLE and AAV overlap syndrome is easily misdiagnosed. An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.
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Affiliation(s)
- Zi-Gan Xu
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Wei-Long Li
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Xi Wang
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Shu-Yuan Zhang
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Ying-Wei Zhang
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Xing Wei
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Chun-Di Li
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Ping Zeng
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
| | - Shao-Dong Luan
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen 518110, Guangdong Province, China
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14
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Wang S, Wang S, Singh S. Development of Systemic Lupus Erythematosus After Infectious Mononucleosis in a 64-Year-Old Woman. J Investig Med High Impact Case Rep 2020; 8:2324709620961613. [PMID: 32964755 PMCID: PMC7517992 DOI: 10.1177/2324709620961613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by heterogeneous symptoms that can manifest in any organ, and often presents at a young age. Infectious mononucleosis (IM) is the acute clinical manifestation of Epstein–Barr virus (EBV). It is characterized by low-grade fever, malaise, lymphadenopathy, splenomegaly, and occasionally symmetrical arthralgias. It has been proposed that EBV is a trigger for new-onset SLE, and patients with autoimmune disorders such as SLE are more likely to have recurrent IM infections. The patient, a 64-year old Caucasian female who’s only past medical history was hypertension, developed several months–long period of vague symptoms, including fatigue, malaise, nausea, and nonbilious vomiting with oral intake. She presented with symmetrical polyarthritis involving the hands and elbows, with no history of arthritis before this episode. At the 5-month follow-up, she presented with worsening arthritis bilaterally in her elbows and in her right knee. For several decades, there has been a theoretical association between EBV and SLE, with EBV thought to be one of the many possible triggers for development of SLE. Based on the disease course, we theorize that the patient’s IM and EBV infection led to development of SLE. A small fraction of SLE cases have been reported in literature to be associated with EBV. This case adds to that literature with EBV triggering development of SLE in a seemingly previously asymptomatic patient.
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Affiliation(s)
| | - Shiyu Wang
- White River Health System, Batesville, AR, USA
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Chinnusamy M, Viswanathan RA, Janakiraman S, Elayidath R. Drug-Induced Lupus Erythematosus Associated with Proton Pump Inhibitor. JOURNAL OF HEALTH AND ALLIED SCIENCES NU 2020. [DOI: 10.1055/s-0040-1716601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
AbstractDrug-induced lupus erythematosus is an autoimmune phenomenon where the drug exposure leads to the development of systemic lupus erythematous like clinical features. Drug-induced lupus erythematosus can be divided into systemic lupus erythematous, subacute cutaneous lupus erythematous, and chronic cutaneous lupus erythematous. Here, we report a case of a 29-year-old female presented with systemic lupus erythematous due to chronic use of proton pump inhibitors, which is considered to be very rare.
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Affiliation(s)
- Manokaran Chinnusamy
- Department of General Medicine, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Pondicherry, India
| | - Ram Arvind Viswanathan
- Department of General Medicine, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Pondicherry, India
| | - Sathiyanarayanan Janakiraman
- Department of General Medicine, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Pondicherry, India
| | - Roshna Elayidath
- Department of General Medicine, Sri Manakula Vinayagar Medical College and Hospital, Madagadipet, Pondicherry, India
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16
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Wang L, Chen SY, Ju Q. A case of recombinant human follitropin alfa-induced subacute cutaneous lupus erythematosus presenting with erythema multiforme-like lesion. Lupus 2020; 29:1824-1825. [PMID: 32847460 DOI: 10.1177/0961203320954528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Lanqi Wang
- Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China
| | - Selena Ying Chen
- Department of Dermatology, University of California-San Diego, La Jolla, CA, USA
| | - Qiang Ju
- Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China
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Padala SA, Medepalli VM, Mohammed A, Nahman S. Hydralazine-Induced Dual Antineutrophil Cytoplasmic Antibody Positive Vasculitis and Nephritis. Cureus 2020; 12:e8911. [PMID: 32742877 PMCID: PMC7389885 DOI: 10.7759/cureus.8911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Drug-induced autoimmunity occurs when exposure to a causative agent leads to serologic or clinical autoimmune responses. Syndromes that may be associated with drug-induced autoimmunity include antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) and drug-induced lupus (DIL). When drug-induced autoimmunity involves the kidney, histological patterns of injury include pauci-immune glomerulonephritis (GN), which occurs with AAV, and immune complex-mediated GN, which is associated with DIL. We present a case of hydralazine-induced dual ANCA-positive vasculitis and nephritis.
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Arnaud L, Mertz P, Gavand PE, Martin T, Chasset F, Tebacher-Alt M, Lambert A, Muller C, Sibilia J, Lebrun-Vignes B, Salem JE. Drug-induced systemic lupus: revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database. Ann Rheum Dis 2019; 78:504-508. [PMID: 30793701 DOI: 10.1136/annrheumdis-2018-214598] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 12/05/2018] [Accepted: 12/08/2018] [Indexed: 11/04/2022]
Abstract
OBJECTIVE Drug-induced lupus (DIL) is an idiosyncratic side effect of treatments in which symptoms overlap with those of systemic lupus erythematosus (SLE). The spectrum of DIL constantly evolves with that of the pharmacopoeia. Here, we used VigiBase, the WHO global individual case safety reports (ICSRs) database, to identify the main drugs associated with DIL. METHODS We analysed all ICSRs classified as 'systemic lupus erythematosus' according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase. The drugs considered in the analysis were those not used to treat SLE, with a positive lower end of the 95% credibility interval for the information component (IC025) ≥0, an indicator value for disproportionate Bayesian reporting. RESULTS A total of 12 166 DIL ICSRs were identified using VigiBase. From those, 8163 ICSRs reporting on 118 suspected drugs with IC025 ≥0 were extracted. The median age at DIL onset was 49 years and the female to male sex ratio was 4.3. The median delay between start of suspected treatment and DIL occurrence was 172 days. DIL was reported as serious adverse event in 55.4%. Among the 118 suspected drugs, 42 had not been previously reported in association with DIL. The drugs associated with the highest number of DIL cases were infliximab, adalimumab, etanercept, procainamide and hydralazine. CONCLUSION This study enables the identification of 118 drugs associated with DIL. The list of suspected drugs may prove useful to physicians when confronted with potential DIL cases. TRIAL REGISTRATION NUMBER NCT03480529.
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Affiliation(s)
- Laurent Arnaud
- Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d'Immuno Rhumatologie Moléculaire, INSERM UMR_S1109, Strasbourg, France
- Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, Strasbourg, France
| | - Philippe Mertz
- Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d'Immuno Rhumatologie Moléculaire, INSERM UMR_S1109, Strasbourg, France
- Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, Strasbourg, France
| | - Pierre-Edouard Gavand
- Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, Strasbourg, France
- Service de Médecine Interne et Immunologie Clinique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - Thierry Martin
- Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, Strasbourg, France
- Service de Médecine Interne et Immunologie Clinique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - François Chasset
- Assistance Publique Hôpitaux de Paris (AP-HP), Service de Dermatologie et d'Allergologie, Hôpital Tenon, Paris, France
| | - Martine Tebacher-Alt
- Service de pharmacovigilance, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Aude Lambert
- Service de pharmacovigilance, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Charlotte Muller
- Service de pharmacovigilance, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Jean Sibilia
- Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Laboratoire d'Immuno Rhumatologie Moléculaire, INSERM UMR_S1109, Strasbourg, France
- Centre National de Références des Maladies Systémiques et Autoimmunes Rares Est Sud-Ouest (RESO), Université de Strasbourg, Strasbourg, France
| | - Bénédicte Lebrun-Vignes
- AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, Regional Pharmacovigilance Center, INSERM, Sorbonne Universités, Paris, France
| | - Joe-Elie Salem
- AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, Regional Pharmacovigilance Center, INSERM, Sorbonne Universités, Paris, France
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Álvarez-Lario B, Bártulos-Iglesias M, Colazo-Burlato M, Macarrón-Vicente J. Carbamazepine-induced systemic lupus erythematosus: A case-based review. Eur J Rheumatol 2019; 6:48-54. [PMID: 30388076 PMCID: PMC6459324 DOI: 10.5152/eurjrheum.2018.18046] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 05/07/2018] [Indexed: 01/22/2023] Open
Abstract
A case of carbamazepine-induced systemic lupus erythematosus (CBZ-DILE) is presented, along with a literature review, with the aim to define the clinical and serological characteristics of this group, and compare them with systemic lupus erythematosus (SLE) triggered by other drugs (DILE). A 31-year-old woman presented with a 6-month history of hand arthritis and nasal ulcers. She had been diagnosed with epilepsy at 12 years of age and had continued treatment with carbamazepine (CBZ) for the past 18 years with excellent clinical control. Laboratory data revealed antinuclear antibodies (ANA) positive to a titer of 1/1280, and positive anti-nucleosome antibodies. The patients' clinical symptoms disappeared after the CBZ discontinuation and did not reappear during the 1-year follow-up period. A search was made in the PubMed/Medline database of the (CBZ-DILE) published cases. A total of 26 cases of CBZ-DILE were found in the search. CBZ-DILE cases are characterized by variable latency periods that often last for years and are not related to the dose of CBZ. Most frequent clinical findings of CBZ-DILE in patients are arthralgia/arthritis, mucocutaneous manifestations, constitutional symptoms, and pleuritis or pericarditis. The renal involvement has not been reported in CBZ-DILE. Antihistone antibodies were observed less frequently, and anti-dsDNA antibodies were observed more frequently than in the "classic" DILE. The ANA remained positive in over 60% of cases during the follow-up after withdrawal. The CBZ-DILE has significant clinical and laboratory manifestations that distinguish it from classic DILE or idiopathic SLE.
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Batra J, Kaur S, Kaushal S, Singh A. Lamotrigine-induced Systemic Lupus Erythematosus: A Diagnostic Dilemma. Indian Dermatol Online J 2018; 9:445-447. [PMID: 30505789 PMCID: PMC6232978 DOI: 10.4103/idoj.idoj_24_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Many drugs are known to cause systemic lupus erythematosus (SLE), however there are no well defined criteria for drug induced lupus erythematosus (DILE). We present a rare case of lamotrigine induced lupus presenting as acute syndrome of apoptotic pan epidermolysis (ASAP).
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Affiliation(s)
- Jaskaran Batra
- Department of Dermatology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Sukhjot Kaur
- Department of Dermatology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Sandeep Kaushal
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Aminder Singh
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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Affiliation(s)
- Yi He
- Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, Guangzhou, Guangdong 510630, China
| | - Fang-Yuan Yang
- Southern Medical University, Guangzhou, Guangdong 510630, China
| | - Er-Wei Sun
- Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University; Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, Guangzhou, Guangdong 510630, China
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22
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Kelly AS, De la Harpe Golden P, D'Arcy C, Lally A. Drug-induced lupus erythematosus secondary to pirfenidone. Br J Dermatol 2018; 178:1437-1438. [DOI: 10.1111/bjd.16246] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- A. S. Kelly
- Dermatology Department; St. Vincent's University Hospital; Elm Park, Dublin 4 Dublin Ireland
| | - P. De la Harpe Golden
- Histopathology Department; St. Vincent's University Hospital; Elm Park Dublin 4 Dublin Ireland
| | - C. D'Arcy
- Histopathology Department; St. Vincent's University Hospital; Elm Park Dublin 4 Dublin Ireland
| | - A. Lally
- Dermatology Department; St. Vincent's University Hospital; Elm Park, Dublin 4 Dublin Ireland
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23
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Irizarry-Caro JA, Carmona-Rivera C, Schwartz DM, Khaznadar SS, Kaplan MJ, Grayson PC. Brief Report: Drugs Implicated in Systemic Autoimmunity Modulate Neutrophil Extracellular Trap Formation. Arthritis Rheumatol 2018; 70:468-474. [PMID: 29121457 DOI: 10.1002/art.40372] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 11/02/2017] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug-induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases. RESULTS Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide. CONCLUSION Medications commonly implicated in drug-induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug-induced autoimmunity.
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Affiliation(s)
- Jorge A Irizarry-Caro
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
| | - Carmelo Carmona-Rivera
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
| | - Daniella M Schwartz
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
| | - Sami S Khaznadar
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
| | - Mariana J Kaplan
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
| | - Peter C Grayson
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
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Kumar B, Strouse J, Swee M, Lenert P, Suneja M. Hydralazine-associated vasculitis: Overlapping features of drug-induced lupus and vasculitis. Semin Arthritis Rheum 2018. [PMID: 29519741 DOI: 10.1016/j.semarthrit.2018.01.005] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. METHODS Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record. RESULTS 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography. CONCLUSIONS Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition.
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Affiliation(s)
- Bharat Kumar
- Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242.
| | - Jennifer Strouse
- Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242
| | - Melissa Swee
- Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242
| | - Petar Lenert
- Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242
| | - Manish Suneja
- Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242
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26
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Starobin D, Guller V, Gurevich A, Tal S. Minocycline induced lupus with yellow colored chylous exudative pleural effusion. Respir Med Case Rep 2017; 22:113-116. [PMID: 28761807 PMCID: PMC5524223 DOI: 10.1016/j.rmcr.2017.07.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Revised: 07/08/2017] [Accepted: 07/11/2017] [Indexed: 11/03/2022] Open
Abstract
Ninety years old male was admitted to hospital due to breathlessness. The prominent findings were extensive blue-grey skin pigmentation and large left chylothorax. Drug induced lupus was diagnosed due to either minocycline chronic treatment or no alternative illness to explain his sub-acute disease. Minocycline therapy was stopped with gradual improvement of pleural effusion and skin discoloration. This case is the first presentation of minocycline induced lupus with chylothorax.
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Affiliation(s)
- Daniel Starobin
- Pulmonary Institute, Kaplan Medical Center, Affiliated with The Hebrew University of Jerusalem, Israel, Rehovot, Israel
| | - Vladimir Guller
- Geriatrics Department, Kaplan Medical Center, Affiliated with The Hebrew University of Jerusalem, Israel, Rehovot, Israel
| | - Alexander Gurevich
- Harzfeld Hospital, Kaplan Medical Center, Affiliated with The Hebrew University of Jerusalem, Israel, Rehovot, Israel
| | - Sari Tal
- Geriatrics Department, Kaplan Medical Center, Affiliated with The Hebrew University of Jerusalem, Israel, Rehovot, Israel
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Szczęch J, Samotij D, Werth VP, Reich A. Trigger factors of cutaneous lupus erythematosus: a review of current literature. Lupus 2017; 26:791-807. [PMID: 28173739 DOI: 10.1177/0961203317691369] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
It is currently believed that autoimmune conditions are triggered and aggravated by a variety of environmental factors such as cigarette smoking, infections, ultraviolet light or chemicals, as well as certain medications and vaccines in genetically susceptible individuals. Recent scientific data have suggested a relevant role of these factors not only in systemic lupus erythematosus, but also in cutaneous lupus erythematosus (CLE). A variety of environmental factors have been proposed as initiators and exacerbators of this disease. In this review we focused on those with the most convincing evidence, emphasizing the role of drugs in CLE. Using a combined search strategy of the MEDLINE and CINAHL databases the following trigger factors and/or exacerbators of CLE have been identified and described: drugs, smoking, neoplasms, ultraviolet radiation and radiotherapy. In order to give a practical insight we emphasized the role of drugs from various groups and classes in CLE. We also aimed to present a short clinical profile of patients with lesions induced by various drug classes.
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Affiliation(s)
- J Szczęch
- 1 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
| | - D Samotij
- 1 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
| | - V P Werth
- 2 Corporal Michael J. Crescenz (Philadelphia) Veterans Affairs Medical Center and Department of Dermatology University of Pennsylvania School of Medicine Philadelphia, PA, USA
| | - A Reich
- 1 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
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Kuhn A, Aberer E, Bata-Csörgő Z, Caproni M, Dreher A, Frances C, Gläser R, Klötgen HW, Landmann A, Marinovic B, Nyberg F, Olteanu R, Ranki A, Szepietowski JC, Volc-Platzer B. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol 2016; 31:389-404. [PMID: 27859683 DOI: 10.1111/jdv.14053] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 10/26/2016] [Indexed: 12/31/2022]
Abstract
Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used 'off-label'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second- and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell- or interferon α-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.
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Affiliation(s)
- A Kuhn
- Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center Mainz, Mainz, Germany.,Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
| | - E Aberer
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - Z Bata-Csörgő
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
| | - M Caproni
- Department of Medical and Surgical Critical Care Section of Dermatology, University of Florence, Florence, Italy
| | - A Dreher
- Evidence-Based Medicine Frankfurt, Institute for General Practice, Goethe-University Frankfurt, Frankfurt, Germany
| | - C Frances
- Department of Dermatology and Allergology, Hôpital Tenon, Paris, France
| | - R Gläser
- Department of Dermatology, Venerology and Allergology, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - H-W Klötgen
- Department of Dermatology, Inselspital Bern - University Hospital, Bern, Switzerland
| | - A Landmann
- Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
| | - B Marinovic
- Department of Dermatology and Venereology, University Hospital Center Zagreb and School of Medicine University of Zagreb, Zagreb, Croatia
| | - F Nyberg
- Institution for Clinical Sciences, Unit for Dermatology, Karolinska Institutet at Danderyd Hospital (KIDS), Stockholm, Sweden
| | - R Olteanu
- Department of Dermatology, Colentina Clinical Hospital, Bucharest, Romania
| | - A Ranki
- Department of Skin and allergic diseases, Inflammation Center, Helsinki University Central Hospital, Helsinki, Finland
| | - J C Szepietowski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland
| | - B Volc-Platzer
- Department of Dermatology, Donauspital, University affiliated Hospital, Vienna, Austria
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Magno Pereira V, Andrade C, Figueira R, Faria G, Jasmins L. Infliximab-Induced Lupus: A Case Report. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2016; 24:84-88. [PMID: 29255743 DOI: 10.1159/000450877] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 08/09/2016] [Indexed: 12/29/2022]
Abstract
We report the case of a 48-year-old, leukodermic female diagnosed with ulcerative proctitis for 4 years and latent tuberculosis. She was allergic to salicylates and had a minor allergic reaction to infliximab (rash, vertigo, and headache). Thereafter, she started azathioprine (2.5 mg/kg/day). She maintained intravenous infliximab, together with prophylaxis with clemastine and hydrocortisone, due to the steroid-dependent proctitis. The therapy was continued every 8 weeks with anti-tumor necrosis factor for about 3 years. The analytical evaluation when she was diagnosed with ulcerative proctitis (February 2011) showed negative antinuclear antibodies (ANA), double-stranded-DNA antibodies (anti-dsDNA), antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, and a positive outer membrane protein antibody. About 2 years and 6 months after starting infliximab (November 2013), the patient complained of inflammatory symmetrical polyarthralgia (knee, shoulder, elbow, and wrist) without synovitis, which started every week before the administration of infliximab. Resolution of symptoms was observed after each infliximab infusion. In July 2014, the autoantibody re-evaluation showed positive ANA with a homogeneous pattern with a titer of 1:640, weak positive anti-dsDNA (30.2), and positive anti-histone with C3 decreased (80.3). She was then diagnosed with lupus induced by infliximab and initiated hydroxychloroquine 400 mg. Infliximab was suspended. On re-evaluation, the erythrocyte sedimentation rate was 25 mm/h (1st hour), C-reactive protein 0.5 mg/dL (previously erythrocyte sedimentation rate 15 mm/h and C-reactive protein 1.2 mg/dL), and endoscopically, the mucosa was scarred, with some atrophy and scarce mucus in the lower rectum. About 10 months after discontinuation of infliximab, repeated autoantibodies proved all negative, keeping only low C3 (87). The patient also reported complete resolution of the arthralgia.
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Affiliation(s)
| | | | - Ricardo Figueira
- Department of Rheumatology, Hospital Dr. Nélio Mendonça, Funchal, Portugal
| | - Goreti Faria
- Department of Gastroenterology, Funchal, Portugal
| | - Luís Jasmins
- Department of Gastroenterology, Funchal, Portugal
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Lupus eritematoso cutáneo subagudo secundario a tratamiento con diuréticos tiazídicos. Semergen 2016; 42:e174-e176. [DOI: 10.1016/j.semerg.2015.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 10/13/2015] [Accepted: 10/22/2015] [Indexed: 11/21/2022]
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Grau RG. Drug-Induced Vasculitis: New Insights and a Changing Lineup of Suspects. Curr Rheumatol Rep 2015; 17:71. [DOI: 10.1007/s11926-015-0545-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Molina-Ruiz AM, Lasanta B, Barcia A, Pérez-Vega E, Requena L. Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine. Australas J Dermatol 2015; 58:e20-e22. [PMID: 26424435 DOI: 10.1111/ajd.12393] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 08/04/2015] [Indexed: 11/30/2022]
Abstract
Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.
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Affiliation(s)
| | - Begoña Lasanta
- Department of Dermatology, Hospital San Agustín, Seville, Spain
| | - Ana Barcia
- Department of Paediatrics, Hospital Virgen del Rocío, Seville, Spain
| | - Elisa Pérez-Vega
- Department of Dermatology, Hospital Virgen del Rocío, Seville, Spain
| | - Luis Requena
- Department of Dermatology, Fundación Jiménez Díaz, Madrid, Spain
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Abstract
A 61-year-old man presented with a 1-month history of breathlessness, chest pain and lethargy. He had been taking adalimumab for ankylosing spondylitis for 2 years. Pleural and pericardial effusions were both found. A video-assisted thorascopic (VATS) pleural and lung biopsy were performed. The pleural pathology showed eosinophils, acute inflammatory cells and lymphoid aggregates. The patient was positive for antinuclear, antidouble-stranded and antihistone antibodies consistent with drug-induced lupus due to adalimumab. His serositis resolved on withdrawal of the drug. Drug-induced lupus can occur as a consequence of anti-TNF-α agents from induction of autoimmunity in a predisposed host.
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Affiliation(s)
- Dearbhla Kelly
- Department of Respiratory Medicine, Cork University Hospital and School of Medicine, Cork, Ireland
| | - Oisin O'Connell
- Department of Respiratory Medicine, Cork University Hospital and School of Medicine, Cork, Ireland
| | - Michael Henry
- Department of Respiratory Medicine, Cork University Hospital and School of Medicine, Cork, Ireland
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Tsai WC, Chen CJ, Yen JH, Liu HW. Sulphasalazine-Induced Systemic Lupus Erythematosus in a Patient with Ankylosing Spondylitis. Clin Rheumatol 2014; 21:339-40. [PMID: 12296286 DOI: 10.1007/s100670200089] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Lupus eritematoso inducido por fármacos. ACTAS DERMO-SIFILIOGRAFICAS 2014; 105:18-30. [DOI: 10.1016/j.ad.2012.09.007] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2012] [Revised: 09/13/2012] [Accepted: 09/16/2012] [Indexed: 01/16/2023] Open
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ANA (+) ANCA (+) systemic vasculitis associated with the use of minocycline: case-based review. Clin Rheumatol 2013; 32:1099-106. [PMID: 23604593 DOI: 10.1007/s10067-013-2245-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 03/20/2013] [Indexed: 12/11/2022]
Abstract
Minocycline is a synthetic tetracycline-derived antibiotic with significant anti-inflammatory properties that may benefit patients with rheumatoid arthritis. Surprisingly, chronic exposure to minocycline can also cause a breach in immunologic tolerance resulting in a variety of autoimmune syndromes such as drug-induced lupus or autoimmune hepatitis. Vasculitis, most commonly resembling cutaneous polyarteritis nodosa, has also been seen in patients taking this drug. Herein, we present a case of biopsy-proven systemic vasculitis presenting as an ANA (+) ANCA (+) polyarteritis nodosa-like syndrome in a male patient who was taking minocycline for his acne for approximately 2 years. Patient initially presented with constitutional symptoms such as profound weight loss and fatigue, along with myalgias, oligoarticular arthritis, and livedo reticularis. About 2 months later, he developed a severe left testicular pain. Biopsy showed vasculitis complicated with the infarction of the left testis. Angiography revealed microaneurysms in the renal and splenic circulation. Stopping the offending drug, along with the short course of prednisone and hydroxychloroquine, resulted in prompt resolution of his symptoms. We additionally present a comprehensive review of biopsy-proven cases of vasculitis associated with chronic minocycline treatment focusing on its pathogenesis and clinical manifestations.
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Anyimadu H, Saadia N, Mannheimer S. Drug-induced lupus associated with rifabutin: a literature review. J Int Assoc Provid AIDS Care 2013; 12:166-8. [PMID: 23442494 DOI: 10.1177/2325957412473647] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only rarely been reported as a cause of DIL, and no cases have been reported in blacks. A 55-year-old African American woman with HIV presented with severe generalized arthralgias and recurrent oral ulcers while receiving treatment for tuberculous meningitis. Arthralgias, which began in her knees after 5 weeks of antituberculous therapy, progressed to involve the joints in the ankles, wrists, and hands. She had no associated fever or rash. When she had these symptoms her antinuclear antibody (ANA) was 1:1280 homogenous pattern, antidouble stranded DNA was negative, antihistone antibody was strongly positive, anti-smith and antiribonucleoprotein (anti-RNP) were negative. Her symptoms resolved within 2 months of stopping rifabutin while continuing other antituberculous medications and her ANA titer started to decrease. We review the existing literature on this subject.
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Affiliation(s)
- Henry Anyimadu
- Department of Infectious Disease, Columbia University Medical Center, New York, NY, USA.
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Seo JY, Byun HJ, Cho KH, Lee EB. Methimazole-induced bullous systemic lupus erythematosus: a case report. J Korean Med Sci 2012; 27:818-21. [PMID: 22787382 PMCID: PMC3390735 DOI: 10.3346/jkms.2012.27.7.818] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Accepted: 04/03/2012] [Indexed: 11/20/2022] Open
Abstract
Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.
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Affiliation(s)
- Ji-Yeon Seo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hee-Jin Byun
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Hyun Cho
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Bong Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Liu CL, Tangsombatvisit S, Rosenberg JM, Mandelbaum G, Gillespie EC, Gozani OP, Alizadeh AA, Utz PJ. Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies. Arthritis Res Ther 2012; 14:R25. [PMID: 22300536 PMCID: PMC3392818 DOI: 10.1186/ar3707] [Citation(s) in RCA: 137] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2011] [Revised: 01/22/2012] [Accepted: 02/02/2012] [Indexed: 02/05/2023] Open
Abstract
Introduction Autoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. Methods We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. Results We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. Conclusions Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
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Affiliation(s)
- Chih Long Liu
- Department of Medicine, Division of Immunology and Rheumatology, Stanford School of Medicine, 269 Campus Drive, Stanford, California 94305, USA
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Marzano AV, Lazzari R, Polloni I, Crosti C, Fabbri P, Cugno M. Drug-induced subacute cutaneous lupus erythematosus: evidence for differences from its idiopathic counterpart. Br J Dermatol 2011; 165:335-41. [PMID: 21564069 DOI: 10.1111/j.1365-2133.2011.10397.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is a lupus variant with predominant skin involvement temporally related to drug exposure and resolving after drug discontinuation. It usually presents with annular polycyclic or papulosquamous eruptions on sun-exposed skin and shows serum anti-Ro/SSA antibodies. OBJECTIVES To address the question whether DI-SCLE differs significantly from idiopathic SCLE by virtue of clinical features. METHODS Ninety patients with SCLE seen in our departments from 2001 to 2010 were reviewed. Eleven of them diagnosed as having DI-SCLE were evaluated for type of skin lesions, systemic involvement, clinical course, and histopathological, direct immunofluorescence and laboratory findings. The cutaneous features were compared with those of the 79 patients with idiopathic SCLE. RESULTS The cutaneous picture was widespread in 82% of patients with DI-SCLE and in 6% of those with idiopathic SCLE [odds ratio (OR) 66·6, 95% confidence interval (CI) 11·2-394·9; P = 0·0001]. Bullous and erythema multiforme (EM)-like lesions were present in 45% of patients with DI-SCLE and in 1% of those with idiopathic SCLE (OR 65·0, 95% CI 6·5-649·6; P = 0·0001). Vasculitic lesions were observed in 45% of patients with DI-SCLE and in 3% of those with idiopathic SCLE (OR 32·1, 95% CI 5·1-201·7; P = 0·0001). Malar rash occurred in 45% of patients with DI-SCLE and in 6% of those with idiopathic SCLE (OR 12·3, 95% CI 2·8-54·9; P = 0·001). Visceral manifestations were excluded in all patients with DI-SCLE. Anti-Ro/SSA antibodies were found in all but one patient with DI-SCLE and disappeared after resolution in 73% of cases. CONCLUSIONS DI-SCLE differs from idiopathic SCLE by virtue of distinctive cutaneous features, particularly the widespread presentation and the frequent occurrence of malar rash and bullous, EM-like and vasculitic manifestations.
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Affiliation(s)
- A V Marzano
- Department of Anaesthesia, Intensive Care and Dermatological Sciences, Università degli Studi di Milano - U.O. Dermatologia, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
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Kim BS, Hong YM, Park SM, Park IW, Lee BH, Jeong JH, Lee CW. A Case of Angiotensin Converting Enzyme Inhibitor-Induced Systemic Lupus Erythematosus. JOURNAL OF RHEUMATIC DISEASES 2011. [DOI: 10.4078/jrd.2011.18.4.288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Byung Seok Kim
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Young Mi Hong
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Seong Min Park
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Il Woo Park
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Byung Hee Lee
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Joon Hoon Jeong
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
| | - Choong Won Lee
- Department of Internal Medicine, Wallace Memorial Baptist Hospital, Busan, Korea
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47
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Propylthiouracil-induced autoimmune syndromes: 11 case report. Rheumatol Int 2010; 32:679-81. [DOI: 10.1007/s00296-010-1675-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Accepted: 11/14/2010] [Indexed: 10/18/2022]
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Dobre M, Wish J, Negrea L. Hydralazine-induced ANCA-positive pauci-immune glomerulonephritis: a case report and literature review. Ren Fail 2010; 31:745-8. [PMID: 19814644 DOI: 10.3109/08860220903118590] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
We report a case of hydralazine-induced alveolar hemorrhage and anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis, with serum anti-histone antibodies present, features not previously described in the literature with this drug. A 50-year-old Caucasian female had hypertension treated with hydralazine 75mg TID for three years, and a lung nodule followed up periodically with chest-computed tomographies. She was admitted to the hospital for hemoptysis and newly discovered diffuse pulmonary ground-glass opacities. Transbronchial lung biopsy showed alveolar hemorrhage. Serum creatinine was 3.5 mg/dL and urinalysis showed 2+blood, 30-50RBC/hpf and red blood cell casts. ANCA against myeloperoxidase were present. Anti-double-stranded DNA, ANA, and anti-histone antibodies were positive. Serum complements were normal. Renal biopsy revealed focal crescentic necrotizing glomerulonephritis with negative immunofluorescence, consistent with pauci-immune ANCA-positive vasculitis. Serum creatinine returned to baseline three days after hydralazine was discontinued, and the hemoptysis resolved after treatment with cyclophosphamide and prednisone was started. We concluded that this case represents a hydralazine-induced small vessel vasculitis rather than an idiopathic one. The possibility of hydralazine-induced vasculitis should be considered when patients treated with hydralazine develop a pulmonary-renal syndrome. Anti-histone antibodies may be present in the absence of full classification criteria of drug-induced lupus.
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Affiliation(s)
- Mirela Dobre
- Huron Hospital, a Cleveland Clinic Hospital, East Cleveland, Ohio, USA.
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Abstract
Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)-α antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF-α antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.
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Affiliation(s)
- AV Marzano
- Department of Anesthesiology, Intensive Care and Dermatological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
| | - P Vezzoli
- Department of Anesthesiology, Intensive Care and Dermatological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
| | - C Crosti
- Department of Anesthesiology, Intensive Care and Dermatological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
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Ahmed F, Kelsey PR, Shariff N. Lupus syndrome with neutropenia following minocycline therapy - a case report. Int J Lab Hematol 2009; 30:543-5. [PMID: 18983308 DOI: 10.1111/j.1751-553x.2007.00967.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
An 18-year-old patient is described who presented with febrile neutropenia and hepatitis caused by minocycline therapy. This rare complication of minocycline-induced lupus syndrome is discussed here.
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Affiliation(s)
- F Ahmed
- Department of Haematology, Blackpool Victoria Hospital, Blackpool, UK.
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