Drug-induced Lupus Research Articles

S3210 Systemic Drug-Induced Lupus Erythematous Related to Golimumab: Report of a Rare Case and Review of the Literature

S3210 Systemic Drug-Induced Lupus Erythematous Related to Golimumab: Report of a Rare Case and Review of the Literature

S3172 Recurrence of Drug-Induced Lupus in a Patient With Crohn’s Disease on Vedolizumab

S3172 Recurrence of Drug-Induced Lupus in a Patient With Crohn’s Disease on Vedolizumab

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Elevated Antibody Titers to Epstein-Barr Virus and Cytomegalovirus in Patients with Drug-Induced Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which has been associated with Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection. Drug-induced lupus (DIL) is a lupus-like disease caused by the intake of therapeutic drugs, which has been estimated to cause approximately 10-15% of lupus-like cases. Although SLE and DIL share common clinical symptoms, there are some fundamental differences between DIL and SLE onset. Moreover, it remains to be examined whether environmental factors, such as EBV and CMV infections, may contribute to the development of DIL. This study focused on examining the possible association between DIL and EBV and CMV infections, by examining IgG titers to EBV and CMV antigens in serum samples by enzyme-linked immunosorbent assays. Antibody titers to EBV early antigen-diffuse and CMV pp52 were found to be significantly elevated in both SLE and DIL patients compared to healthy controls, although no correlation was found for antibodies to the two virus antigens in the respective disease groups. Moreover, total IgG titers were reduced in SLE and DIL serum samples, which may reflect a general lymphocytopenia, which commonly is associated with SLE. The current findings support that EBV and CMV infections may contribute to the development of DIL and that onset of both diseases are related.

Cutaneous Adverse Reactions to TNF Alpha Blockers. Case Report and Literature Review

Biological therapy is used in a wide range of medical settings. Adverse reactions to biological therapy can limit their widespread use, so early detection and treatment can adjust attempts to stop these molecules. TNF Alpha blockers may cause the following skin reactions in alpha patients: injection site reactions, infections, immune-mediated reactions (psoriasis, psoriasis, drug-induced lupus, vasculitis, hidradenitis, alopecia), allergic or neoplastic reactions. We present the case of a patient with RA who developed skin lesions during biological therapy and was diagnosed with drug induced lupus based on clinical elements, associated autoimmunity, and dermatological evaluation. The skin lesions were attributed to the interaction of three medications (biosimilar Etanercept, Leflunomide, and Isoniazid), all of which have been implicated in causing these side effects. The solutions that saved the patient were temporarily discontinuing the immunosuppressive medication and replacing it with a local corticoid, followed by the continuation of Etanercept in associated with Methotrexate, and the patient was able to continue the biological medication and obtain a favorable response to the treatment. In conclusion, skin changes caused by TNF Alpha inhibitors are common, but vary in severity, and do not warrant therapy interruption.

A Case of Severe Lupus Myocarditis Preceded by Mesalazine-induced Lupus.

In drug-induced lupus (DIL), symptoms similar to those of systemic lupus erythematosus (SLE) usually resolve after discontinuation of the offending drug. A 41-year-old-woman with a history of ulcerative colitis presented with polyarthritis and myositis and was positive for anti-dsDNA IgG antibody. After discontinuation of mesalazine, the symptoms resolved, and the antibody titer decreased. The patient was diagnosed with DIL. Six months later, lupus myocarditis developed. After treatment with glucocorticoids, cyclophosphamide, intravenous immunoglobulin, and an intra-aortic balloon pump, she showed dramatic improvement. Patients with DIL and an immunological predisposition, such as anti-dsDNA antibodies, may have SLE and should be carefully monitored.

Vitamin D Status and SLE Disease Activity among Dubai Hospital Lupus Patients

Background: Vitamin D deficiency is common worldwide, but is particularly prevalent in the Middle Eastern region, where cultural and religious factors influence its incidence further. As patients with Systemic Lupus Erythematosus (SLE) avoid sun exposure and use medications that could potentially result in vitamin D deficiency, this problem becomes more apparent. Unfortunately, there are no data available on the prevalence of vitamin D deficiency among patients with SLE in our local area. Objective: To assess the prevalence of vitamin D deficiency among patients with a new onset of systemic lupus erythematosus in Dubai, and to determine whether low vitamin D levels are correlated with disease activity. Methodology and Data Collection: a retrospective cohort study of patients with new onset of Systemic Lupus Erythematosus, being diagnosed in less than 1 year and were followed up at Dubai Hospital (UAE) from January 2009 till December 2012. Demographic and clinical data were collected as well as 25(OH) D3 levels. The incidence of vitamin D insufficiency was calculated as a ratio between the numbers of patients with 25(OH) D levels below the specified cut-off values (30ng/ml and 10ng/ml, respectively). SLE was diagnosed according to the American college of rheumatology (ACR SLE) classification criteria of 1997. Patients with drug-induced SLE and vitamin D deficiency were excluded. Results: a total number of 150 patients were included. 87% (n=131) were females and 13% (n=19) were males. The mean vitamin D level at the baseline was 21.6+/- 47 (mean +/- SD), increased to 27.8+/- 16 at 1 year, while the SLEDAI has improved from 8.3+/-5 (mean +/- SD) to 2.4 +/- 2.9 at 1 year respectively. The changes in vitamin D level as well as the SLEDAI were statistically significant with a P value <0.001. Spearman correlation test showed a statistically significant inverse correlation between vitamin D level versus SLEDAI % from baseline to 1-year later. Conclusion: This study showed a direct inverse relationship between lupus activity and a low level of vitamin D. Furthermore, the SLE disease activity score got better with the improvement in vitamin D level, measured at baseline, and after 12 months period.

Лекарственно-индуцированная красная волчанка

This article presents a clinical case in which a patient observed by neurologists with a diagnosis of neuropathy and treated with anticonvulsants and antidepressants developed new clinical manifestations and laboratory changes characteristic of systemic lupus erythematosus. A clinical version emerged that the neurological changes were the disease onset, followed by the development of the remaining clinical and laboratory symptoms (the diagnosis fully met the 2019 EULAR criteria — a score of 16 points, 10 points are sufficient to make a diagnosis). However, after a very short and low-dose therapy with methylprednisolone and hydroxychloroquine and withdrawal of anticonvulsants, there was a rapid recovery of specific antibodies and improvement of clinical symptoms, which allowed assuming drug-induced lupus erythematosus in this patient. Currently, the list of drugs that can cause this problem includes more than 100 drugs.

Current issues of standardization of antinuclear antibodies’ detection by indirect immunofluorescence on HEp-2 cells

Background. Antinuclear antibodies (ANA) are a group of antibodies that target nuclear and cytoplasmic antigens. Testing for ANA using an immunofluorescence assay (IFA) on HЕp-2 cell (IFA-HEp-2) is a screening test for the diagnosis of systemic autoimmune rheumatic diseases, druginduced lupus erythematosus, autoimmune liver diseases, juvenile idiopathic arthritis. In routine ANA testing final report forms bears important, but unstandardized variables (e. g., screening and final titers of ANA, coding of glow types, the procedure for performing confirmatory tests). Aim of the study. Develop a standard report form for IFA-HEp-2 testing results.Material and methods. Survey of 10 immunological and clinical diagnostic laboratories using the ICAP questionnaire adapted by the Working Group on Standardization of the definition of ANA by the IFA-HEp-2 method (Committee on Immunology of the Association ‘Federation of Laboratory Medicine’).Results. According to the results of a survey: most of the participants use a screening dilution of serum 1:160; indicates the maximum end titer of antinuclear factor (ANF), cytoplasmic staining; identifies staining types (including AC encoding); considers it mandatory to make confirmatory tests to detect ANA to individual nuclear antigens in ANF-positive patients, but does not provide a list of this tests in the results form; describes ANF titer for each of the detected glows separately; designates ANF titers using a colon and does not give a clinical interpretation of the results. Based on interlaboratory consensus, ICAP recommendations and the requirements of ISO 15189, the standard report form for IFA-HEp-2 testing results was developed.Conclusions. To achieve high quality of interaction between clinical diagnostic/immunological laboratories and clinical departments of health care facilities, it’s necessary to introduce into practice a standard form for IFA-HEp-2 testing results, developed relying on modern clinical recommendations and interlaboratory consensus.

Comparison of two anti-histones antibodies commercial assays in an immunology laboratory and systemic lupus erythematosus

BackgroundAnti-histones antibodies (AHAs) are antibodies directed against histone proteins – structural proteins that provides scaffolding for DNA to be wrapped around. AHAs, measured in the serum, are diagnostically helpful in cases of systemic lupus erythematosus (SLE) and drug-induced lupus erythematosus (DILE). In the diagnostic laboratory, they may be measured by enzyme-linked immune-sorbent assay (ELISA) or line immunoassays (LIA); however, the performance of these have never been directly compared in the literature. MethodsWe evaluated a commonly used commercial ELISA and LIA to compare the performance in our immunology laboratory. Retrospective and prospective analyses were undertaken over a 5.5-year period. We also examined their performance in the model disease of SLE and compared their performance to disease activity and the main clinical features. ResultsOne hundred and thirty-five patients were evaluated including 65 SLE patients. Based on the quantitative cut-offs, there was only moderate agreement between the two assays (κ = 0.444). Both assays only had modest agreement with the clinical situation of the evaluated patients. When considered within the SLE context, both assays were moderately correlated with disease activity. Positive AHAs by ELISA were associated with SLE cytopaenias, and both ELISA and LIA correlated with positive anti-double stranded DNA. ConclusionsModerate agreement analytically were seen between ELISA and LIA methods in a general laboratory cohort. Both assays were comparable in their diagnostic performance. ELISA detection of AHAs appears to have some clinical use in our cohort of SLE patients. Future studies are required to explore the clinical utility of AHAs in SLE and other disorders.

Ревматологические синдромы, вызываемые лекарствами

An article reviews occurence, mechanism and treatment of drug induced reactions that resemble certain idiopathic rheumatic diseases and syndromes or are indistinguishable from them, that is, drug-induced lupus erythematosus, hyperuricemia and gout, osteopathy, statin-induced skeletal muscle damage, fluoroquinolone-induced tendinopathy, and autoimmune and inflammatory syndromes induced by checkpoint inhibitors.

CHOOSE YOUR OWN ADVENTURE: AUTOINFLAMMATORY DISEASE, IMMUNODEFICIENCY, AND HIRSCHSPRUNG'S, OH MY!

<h3>Introduction</h3> Overlapping manifestations of immune dysregulation and immunodeficiency can create diagnostic challenges. A rapidly expanding array of genetic testing provides additional information in understanding disease manifestation in medically complex patients. Here we present the case of a pediatric patient with recurrent infections, drug reaction and a <i>CARD11</i> variant of uncertain significance (VUS). <h3>Case Description</h3> The patient is a five-year old male with a history of multiple prior gastrointestinal infections in the setting of Hirschsprung's disease. After receiving cephalexin for enterocolitis, he developed a malar facial rash and fatigue which was concerning for drug-induced lupus. Laboratory evaluation showed normal complete blood count, quantitative immunoglobulins, total complement (CH50), and quantitative lymphocytes. He had positive antinuclear, double stranded DNA, ribonucleoprotein, Smith and antichromatin antibodies. Additionally, work-up revealed <i>CARD11</i> exon duplication of unknown significance. Symptoms of lupus improved with medication discontinuation. Ultimately, the patient's infectious history was attributed to his primary Hirschsprung's diagnosis though the impact of the <i>CARD11</i> VUS is unclear. <h3>Discussion</h3> We present a case in which work-up for immunodeficiency in the setting of Hirschsprung's disease and suspected drug-induced lupus led to identification of a <i>CARD11</i> variant. Mutations in <i>CARD11</i> have been implicated in immunodeficiency, atopy and B cell expansion due to signaling dysregulation. Hypomorphic mutations in <i>CARD11</i> are associated with a variety of clinical phenotypes and clinical symptoms that have not been fully elucidated. Although currently recognized as a VUS, this case highlights the need for a high index of suspicion and genetic testing to help guide clinical practice.

TUBERCULOUS PLEURAL EFFUSION MASQUERADING AS DRUG-INDUCED LUPUS

TUBERCULOUS PLEURAL EFFUSION MASQUERADING AS DRUG-INDUCED LUPUS

EP(ILEPT)IC COMPLICATIONS

EP(ILEPT)IC COMPLICATIONS

Effects of Procainamide on CTLA-4 and CD28 Expression in Drug-Induced Lupus: A Research Protocol

Introduction: Lupus erythematosus is a chronic autoimmune disease affecting over 5 million individuals worldwide, characterized by overactivation of B and T lymphocytes. Of these, 10% of patients are diagnosed with drug- induced lupus (DIL), which is caused by high doses of medications such as procainamide, with 20% of procainamide users developing DIL. CTLA-4 and CD28 receptors on T-cell surfaces bind to B7 proteins on antigen-presenting cells, halting and promoting T-cell activation, respectively. Studies indicate that certain lupus symptoms are linked to abnormal CTLA-4/CD28 expression, resulting in overreactive CD4+ T-cells. However, the exact nature of the relationship between CTLA-4 and lupus remains nonunanimous. Other studies show that procainamide alters DNA methylation7, while altered CTLA-4 methylation has been tied to autoimmune disorders. Thus, we hypothesize that procainamide leads to reduced CTLA-4 expression and/or increased CD28 expression, causing DIL symptoms. Methods: We propose an in vivo experiment involving time-matched mouse models. CITE-seq analyses would be run on isolated T-cells from the splenic samples to obtain transcriptome and epitope data and to examine the expression of CTLA-4, CD28, and other potential genes of interest. To corroborate CITE-seq results, the T-cells would undergo immunohistochemical staining with primary and fluorescent antibodies that bind to CTLA-4/CD28. Expected Results: Results are expected to indicate decreased CTLA-4 gene and protein expression, or increased CD28 gene and protein expression on the surface of procainamide-treated T-cells. Discussion: If our analyses prove successful, potential next steps involve using gene editing technologies to screen, pinpoint, and correct the molecular mechanisms implicated in procainamide-induced DIL. Further analysis may also implicate additional or other genes of interest involved in the etiology of the disease. Conclusion: This study is expected to provide insight into the effect of procainamide on molecular mechanisms involved in DIL. Further applications may involve adjunct therapies aimed at mitigating or preventing the development of DIL symptoms.

New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review.

Emerging data evaluated the possible link between the Coronavirus 19 (COVID-19) vaccine and acute flares of rheumatic autoimmune diseases. However, the association between the COVID-19 vaccine and the development of de-novo rheumatic autoimmune diseases remained unclear. We report the first case series of three male patients who developed new-onset systemic lupus erythematosus following receiving Pfizer BNT162b2 mRNA vaccination. The clinical characteristics share some similarities with drug-induced lupus. More patients with SLE following COVID-19 may be diagnosed in the future. Additional studies will provide more significant insights into the possible immunogenic influence of the COVID-19 vaccine.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-022-05203-3.

Proton Pump Inhibitors Associated With Drug-Induced Lupus Erythematosus

This descriptive case series investigates the potential association between the use of proton pump inhibitors and drug-induced lupus erythematosus in cases reported in 2 large pharmacovigilance databases.

Review of secukinumab-induced adverse events of special interest and its potential pathogenesis.

Although secukinumab has demonstrated high efficacy and favorable safety in moderate-to-severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real-world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab-induced AESI. More than 1077 patients (aged 18-74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug-associated vasculitis (n=8), and drug-induced lupus erythematosus (n=4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T-cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment.

DIFFUSE ALVEOLAR HEMORRHAGE DUE TO HYDRALAZINE-INDUCED LUPUS

TYPE: Case Report TOPIC: Pulmonary Manifestations of Systemic Disease INTRODUCTION: Hydralazine is a known cause of drug-induced lupus and has been associated with ANCA-associated vasculitis (AAV) primarily involving the kidney, with rare pulmonary complications. We report a case of Hydralazine-induced lupus presenting as diffuse alveolar hemorrhage (DAH) in the absence of renal disease or AAV. CASE PRESENTATION: An 86 year-old female presented to the hospital due to one week of dyspnea and hemoptysis. She was started on Hydralazine 100mg BID five months prior. CTA of the chest revealed extensive bilateral central ground-glass opacities with relative sparing of the peripheral lungs. She had an unrevealing infectious and cardiac workup. Urinalysis showed bland sediment. Bronchoscopy revealed blood throughout the tracheobronchial tree and serial lavage aliquots were consistent with DAH. Autoimmune studies noted a positive ANA titer of ≥1:1280, and positive anti-histone IgG of 163AU/mL. The remaining studies were normal, including complement, anti-dsDNA, anti-Smith, anti-GBM, ANCA titers, PR3 and MPO antibodies, rheumatoid factor, anti-CCP, anti-RNP, and anti-SSA/SSB. Hydralazine was discontinued and the patient was started on systemic corticosteroids with complete resolution. DISCUSSION: Few cases of DAH attributed to Hydralazine have been reported in the literature. This case is unique in that there was no nephritis or AAV based on the antibody biomarker distribution. CONCLUSIONS: We report a case of DAH as a result of Hydralazine-induced lupus in the absence of renal involvement or AAV. Discontinuation of the offending agent, early bronchoscopy, autoimmune workup, and systemic corticosteroids are paramount to successful patient outcomes. Further investigation is necessary, as there currently exist no randomized trials to guide therapy. DISCLOSURE: Nothing to declare. KEYWORD: diffuse alveolar hemorrhage

Drug-Induced Lupus: A Forgotten Cause of Prolonged Pyrexia of Unknown Origin

The causes of a pyrexia of unknown origin (PUO) are broadly spread across infectious, malignant, or inflammatory conditions. The authors report a case of a 43-year-old female who initially presented with hypoxia and fevers secondary to a presumed acute viral or bacterial infectious pulmonary insult. However, fevers persisted despite pulmonary imaging remaining normal. The case subsequently evolved into a PUO with multiple lines of investigation proving inconclusive. No definitive diagnosis was made at the time of discharge; however, cessation of hydralazine was noted to coincide with the last of the patient’s fevers. Following the discharge, her anti-histone antibodies returned a positive result, and the diagnosis of drug-induced lupus was made with hydralazine as the presumed trigger.