Drug-induced Lupus Research Articles

A Curious Case of Drug-induced Subacute Cutaneous Lupus Erythematosus.

Sir, Drugs causing drug-induced systemic lupus erythematosus (DI-SLE) are different from drugs causing drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) except for tumor necrosis factor antagonists.[1] Isoniazid is known to cause DI-SLE. However, isoniazid causing DI-SCLE has been infrequently described in the literature. A 60-year-old female, a known case of tubercular osteomyelitis, presented with multiple erythematous scaly lesions over the body for the last 2 months. The patient was on antitubercular drugs HRZE (isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for 2 months and isoniazid, rifampicin, and ethambutol (HRE) for 2 months. The lesions developed after nearly 8 weeks of intake of HRZE. The cutaneous examination showed multiple annular erythematous scaly plaques over the face, trunk, and limbs with accentuation in the photo-exposed sites along with multiple targetoid lesions [Figure 1a and b]. The complete hemogram showed eosinophilia of 11%. The liver function test, renal function test, chest X-ray, 24-hour urine protein, and electrocardiogram (ECG) were within normal limits. Antinuclear antibody (ANA) was positive (1:90, homogenous pattern). The anti Ro/La, antihistone, anti dsDNA, antismith antibodies, and rheumatoid factor were negative.Skin biopsy revealed basal cell vacuolization, colloid bodies, pigment incontinence, infiltration of the vessel wall by inflammatory cells, and karyorrhectic debris [Figure 2a]. The patient was diagnosed as a case of SCLE and started on hydroxychloroquine 300 mg daily along with oral prednisolone 30 mg daily for 2 weeks, topical mometasone, and sunscreen; however, the lesions persisted. Because of the refractory nature of lesions, the drug was suspected as a possible trigger. As isoniazid is more commonly incriminated in systemic lupus erythematosus, isoniazid was stopped and replaced by oral levofloxacin. Rifampicin, ethambutol, and levofloxacin were continued along with levocetrizine and topical mometasone, and oral steroids were stopped. After 2 weeks of stopping isoniazid, there was a significant improvement in cutaneous lesions with complete subsidence of lesions at 4 weeks [Figure 2b]. The patient is on follow-up and has not reported any new lesions or systemic symptoms since then.Figure 1: Multiple erythematous annular scaly plaques over the gluteal area (a). Close-up photograph of the thigh showing annular scaly plaques and targetoid lesions (b)Figure 2: (a) Skin biopsy showing hyperkeratosis, parakeratoses, basal layer vacuolization, colloid bodies, and infiltration of the vessel wall by inflammatory cells. (H & E 10×). (b) Subsiding lesions over the thigh after 2 weeks of stopping isoniazidDI-LE has predominantly systemic symptoms such as fever, arthritis, and serositis, whereas LE-specific skin changes are relatively uncommon.[234] However, in DI-SCLE, there are specific cutaneous lesions and systemic features are minimal or absent. Anti-histone antibodies are frequently present in DI-LE,[3] whereas anti Ro/SSA antibodies are more frequently positive in DI-SCLE.[2] It is also important to identify and differentiate this subset of patients from idiopathic SCLE (I-SCLE) as removal of the culprit drug is the mainstay of management in DI-SCLE. DI-SCLE usually has an older age of onset than I-SCLE.[34] Latent period between exposure to the drug and the onset of symptoms is 4 to 8 weeks.[2] The disease is more widespread, and involves areas that are usually spared by I-SCLE. Bullous, erythema multiforme–like lesions, purpura, necrotic-ulcerative lesions, malar rash, and the involvement of lower legs are more common in DI-SCLE.[34] Recently, one case of isoniazid-induced SCLE was described in a HIV-positive female.[5] In our patient, temporal correlation with the intake of drugs, widespread involvement including legs, erythema multiforme–like lesions, and eosinophilia suggested drug as a possible etiology. The patient did not meet the criteria for Rowell syndrome,[6] and SLE was ruled out because of lack of systemic involvement. The mainstay of treatment is the discontinuation of the culprit drug which leads to the resolution of lesions in a period of nearly 6 to 12 weeks.[4] Other treatment modalities are topical steroids, topical tacrolimus, hydroxychloroquine, and oral steroids.[2] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Interleukin 4 deficiency limits the development of a lupus-like disease in mice triggered by phospholipids in a non-bilayer arrangement.

Non-bilayer phospholipids arrangements (NPAs) are transient molecular associations different from lipid bilayers. When they become stable, they can trigger a disease in mice resembling human lupus, which is mainly characterized by the production of anti-NPA IgG antibodies. NPAs are stabilized on liposomes or cell bilayers by the drugs procainamide or chlorpromazine, which produce drug-induced lupus in humans. Here, we evaluated the participation of the TH 2 response, through its hallmark cytokine IL-4, on the development of the lupus-like disease in mice. Wild-type or IL-4 knockout BALB/c mice received liposomes bearing drug-induced NPAs, the drugs alone, or an anti-NPA monoclonal antibody (H308) to induce the lupus-like disease (the last two procedures stabilize NPAs on mice cells). IL-4 KO mice showed minor disease manifestations, compared to wild-type mice, with decreased production of anti-NPA IgG antibodies, no anti-cardiolipin, anti-histones and anticoagulant antibodies, and no kidney or skin lesions. In these mice, H308 was the only inducer of anti-NPA IgG antibodies. These findings indicate that IL-4 has a central role in the development of the murine lupus-like disease induced by NPA stabilization.

Antithyroid Drug-Induced Lupus Erythematosus and Immunoglobulin A Deficiency

Patient: Male, 32-year-oldFinal Diagnosis: Drug induced lupus erythematosusSymptoms: Lymphadenopathy • proteinuria • rashMedication: —Clinical Procedure: Renal biopsySpecialty: Endocrinology and Metabolic • Immunology • General and Internal MedicineObjective:Rare co-existance of disease or pathologyBackground:Antithyroid drugs, namely methimazole, are well-known causes of drug-induced lupus erythematosus. This is, however, an infrequent adverse effect. Selective Immunoglobulin A (IgA) deficiency, in contrast, is the most common primary immunodeficiency. Patients with IgA deficiency are at risk of developing infectious diseases, but also autoimmune diseases such as Grave’s disease or systemic lupus erythematosus.Case Report:We report a case of methimazole-induced lupus erythematosus in a 32-year-old man with renal involvement and concomitant selective IgA deficiency. Symptoms promptly resolved after treatment with hydroxychloroquine and corticosteroids after discontinuation of methimazole. Lupus nephritis required treatment with cyclophosphamide followed by maintenance therapy with mycophenolate mofetil.Conclusions:Drug-induced lupus erythematosus usually develops after a few months or years of exposure to the causative agent. No specific symptoms exist. The diagnosis is not based on particular specific tests, but relies on a set of arguments evoking the role of the medication inducing the condition. The first step in treatment is to stop the causative drug. The therapeutic management of the various manifestations does not differ from that of idiopathic systemic lupus erythematosus. We briefly discuss the relationship between drug-induced lupus erythematosus, Grave’s disease, and IgA deficiency, and suggest that IgA deficiency may act as a potential risk factor. Testing for IgA deficiency could be helpful in patients being treated with drugs known to be associated with drug-induced lupus erythematosus.

Drug-induced Lupus Associated With Vedolizumab in a Patient with Crohn’s Disease

Drug-induced Lupus Associated With Vedolizumab in a Patient with Crohn’s Disease

Dermatologic adverse reactions to proton‐pump inhibitors: A synthetized review

Proton-pump inhibitors (PPIs) are one of the most prescribed drugs. Their dermatological adverse reactions are multiple and vary in severity. This review discusses all reported cutaneous side effects of PPIs in order to help physicians understand them and provide appropriate management. A thorough search of PubMed, Embase, and FDAAQ8 drugs websites was conducted. 56 articles including case reports, case series, and review articles of PPI-induced cutaneous adverse reactions were selected. Data were recorded regarding patient age, gender, history, clinical manifestations, diagnostic tests, management, and clinical outcomes. PPI-induced adverse skin reactions are mostly immunological and include both immediate and delayed-type hypersensitivity reactions. These reactions are sometimes life-threatening. All PPIs can induce immediate IgE-mediated reactions. Most of previously published cases of delayed-type hypersensitivity reactions have involved esomeprazole, omeprazole, and lansoprazole. Skin tests are helpful in confirming PPI-induced hypersensitivity reactions and diagnosing potential cross-reactivities. PPIs should also be added to our list of usual suspects when considering possible culprits for a new presentation of drug-induced subacute lupus erythematosus. PPI-related occupational contact dermatitis has also been numerously reported. PPIs should be considered in our list of culprits when considering a patient with a cutaneous drug reaction, taking into account that these drugs can cause severe immunological manifestations.

Tumor necrosis factor inhibitor-induced pleuropericarditis: A retrospective evaluation using data from VigiBase

ObjectiveThe aim of this study was to assess the causality of anti-TNFα agents-associated pleuropericarditis in VigiBase with a focus on its diverse types. MethodsAll variables contained in the pleuropericarditis reports were reviewed. Well-documented reports, vigiGrade completeness score ≥ 0.80 or with an informative narrative, were analyzed and with a focus on the clinical features of the cases. Bradford-Hill criteria were used in the case series assessment of causality. ResultsFrom 1968 up to 18 December 2019, there were 94 unique cases from 18 countries reporting pleuropericarditis with anti-TNFα agents as a suspected or interacting medicine. Among the 94 reports, 42 were identified as well-documented and further assessed for clinical features. Of the 42 cases, 39 were serious, including three fatal and seven life-threatening. In 35 cases, an anti-TNFα agent was the only suspected drug. Positive de- and re-challenge were reported in 95% and 17% of the 42 cases, respectively. The times to onset (TTO) varied greatly among individual cases, ranging from one month to 75 months (mean = 24 months). The most commonly involved anti-TNFα agents were adalimumab, infliximab and etanercept; and the mostly reported pleuropericarditis types were classified as autoimmune-related with (n = 17) or without (n = 15) co-reported drug-induced lupus (DIL), or infection-related (n = 8). While adalimumab was the most reported in the infection-related cases (7/8), infliximab was the most frequent in the autoimmune-related cases, in particular co-reported with DIL (9/17). There were four cases where the reaction occurred one to two months after the anti-TNFα agents (infliximab and adalimumab) were stopped. Based on the review of the case series using Bradford-Hill criteria the anti-TNFα agents associated pleuropericarditis are considered as a class effect. ConclusionsTo clinically recognize and manage these potentially life-threatening serious cardiopulmonary complications, health care professionals should be aware of this possible risk. Meanwhile, attention should be paid to the clinical features of pleuropericarditis cases, since they may cause diagnostic and therapeutic difficulties. Considering the long elimination time, clinicians need to be reminded to remain vigilant for the adverse reactions even after discontinuing anti-TNFα therapy.

Drug-Induced Lupus Erythematosus Associated with Proton Pump Inhibitor

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.

Association Between Drug Use and Subsequent Diagnosis of Lupus Erythematosus

It has been estimated that up to 30% of all subacute cutaneous lupus erythematosus (CLE) cases and up to 15% of systemic lupus erythematosus (SLE) cases are drug induced. Based on numerous case reports and several epidemiologic studies, more than 100 drugs from more than 10 drug classes are suspected to cause drug-induced lupus erythematosus. To examine the association between drug use and a subsequent diagnosis of CLE or SLE based on a systematic screening process of the drugs in the Anatomical Therapeutic Chemical classification system in a nationwide setting. A matched case-control study was conducted using all incident cases of CLE and SLE registered in the Danish National Patient Register between January 1, 2000, and December 31, 2017. Patients with CLE and patients with SLE were matched (1:10) on age and sex, with individuals from the general population serving as controls. To select which drugs to examine for an association with CLE or SLE, a screening process of all drugs was performed, including drugs filled at pharmacies and drugs administered in hospitals. Odds ratios (ORs) were calculated for the association between exposures to certain drugs and the subsequent diagnosis of CLE or SLE. In all, 3148 patients with CLE (n = 1298; 1022 women [78.7%]; median age at diagnosis, 50.5 years [interquartile range, 39.4-62.2 years]) or SLE (n = 1850; 1537 women [83.1%]; median age at diagnosis, 45.0 years [interquartile range, 33.6-56.4 years]) and 31 480 controls (25 590 women [81.3%]; median age, 47.5 years [interquartile range, 35.9-59.5 years]) were found. Many significant associations between drug use and a subsequent diagnosis of CLE and SLE were observed. Many associations were likely due to protopathic bias. However, new plausible causal associations were observed between CLE or SLE and some drugs, including fexofenadine hydrochloride (SLE: OR, 2.61 [95% CI, 1.80-3.80]; CLE: OR, 5.05 [95% CI, 3.51-7.26]), levothyroxine sodium (SLE: OR, 2.46 [95% CI, 1.97-3.07]; CLE: OR, 1.30 [95% CI, 0.96-1.75]), metoclopramide hydrochloride (SLE: OR, 3.38 [95% CI, 2.47-4.64]; CLE: OR, 1.47 [95% CI, 0.85-2.54]), and metronidazole hydrochloride (SLE: OR, 1.57 [95% CI, 1.09-2.27]; CLE: OR, 1.93 [95% CI, 1.25-2.97]). The study's findings suggest that physicians should be cognizant about whether a new case of CLE or SLE could be drug induced. Furthermore, the results highlight that the reported associations in the published literature may be due to publication or protopathic bias.

Cutaneous drug eruptions including serum sickness-like reaction, symmetrical drug-related intertriginous and flexural exanthema, and drug-induced lupus

Cutaneous manifestations of drug reactions are common yet vary widely in their appearance and degree of internal organ involvement. Serum sickness-–like reactions, symmetrical drug-related intertriginous and flexural exanthem, granulomatous drug eruption, pseudolymphoma, and drug-induced lupus are medication-induced conditions with dermatologic presentations. Many of the conditions discussed are relatively rare but nonetheless demand our attention and understanding. Some of the conditions presented may be more likely encountered in the hospital setting, as is the case with serum sickness–like reactions and drug-induced lupus, whereas others may present to outpatient clinic for diagnosis. Given the similarities in clinical history of patients presenting with these conditions, an understanding of the clinical presentation, pathophysiology, culprit medications, histologic appearance, and serologic characteristics is warranted to correctly diagnose and manage these uncommon adverse reactions. We also discuss how to differentiate some of these conditions from more serious mimickers, as in the case of pseudolymphoma drug reaction mimicking a true lymphoma and drug-induced lupus mimicking acute systemic lupus erythematosus.

Herbal medication triggering lupus nephritis - a case report

BackgroundHerbal medication is widely used in our region as a mode of alternative medicine. Its contents and combinations are often modified to suit the needs of different populations. These products are said to boost the immune system and may serve as a protective measure against many diseases including Systemic Lupus Erythematosus (SLE). Some even lay claims to be able to cure SLE. Although they are not without side effects, these medications are still preferred due to their widespread availability and affordability, compared to modern medications. However, to date, there have been no reported cases in which these traditional medications can trigger a lupus-like reaction, moreover one involving the kidneys.Case presentationWe report a patient who developed overt lupus nephritis after consuming a course of herbal supplement. Her renal status did not improve upon cessation of the offending drug, and she required immunosuppressive therapy. After one cycle of IV cyclophosphamide, we managed to get the patient into remission - she is now on tapering doses of steroids.ConclusionWe wish to highlight the possibility of consumption of herbal medication and the emergence of drug-induced lupus nephritis. A thorough anamnesis and high index of suspicion of drug-induced lupus nephritis is warranted when a patient on supplements presents with urinary abnormalities.

Anti-Tnf-α Drug-Induced Lupus : A Case Report

Anti-Tnf-α Drug-Induced Lupus : A Case Report

Association of Oxidative Stress with Disease Activity and Damage in Systemic Lupus Erythematosus: A Cross Sectional Study from a Tertiary Care Centre in Southern India.

To study oxidative stress in systemic lupus erythematosus (SLE) by estimating serum oxidised LDL (OxLDL), 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total anti-oxidant status and to correlate with SLE disease activity and disease damage. Eighty SLE patients satisfying the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) 2012 criteria and 80 healthy controls were studied. Exclusion criteria were infections, renal insufficiency, other connective tissue diseases, drug-induced lupus, smoking, alcohol consumption. Disease activity was measured by SLE disease activity index-2K (SLEDAI), disease damage was quantified by SLICC-Damage Index (SDI). Sera was tested for OxLDL, 8-OHdG, and total antioxidant status (TAS) by double-antibody sandwich ELISA; MDA measured by Colorimetric assay. Oxidative stress markers were compared between group1- controls, group 2-mildly active SLE (SLEDAI ≤ 5), group 3- moderate to highly active SLE (SLEDAI ≥ 6). SLE patients had significantly higher MDA, 8-OHdG and lower TAS when compared to healthy controls, while OxLDL was similar in the three groups. MDA, 8-OHdG were significantly higher, TAS lower in group 3 compared to group 2. MDA had positive correlation with SLEDAI, TAS negatively correlated with SLEDAI. SLE with neuropsychiatric manifestations, vasculitis, anti-sdDNA antibodies had higher MDA, MDA/TAS ratio. SLE patients with thrombocytopenia, and vasculitis had higher OxLDL. Only OxLDL was significantly higher in those patients who have SDI > 1. SLE patients have increased oxidative stress measured by increases in MDA, 8-OHdG, and lower total antioxidant status that was associated with disease activity and some disease manifestations. However only OxLDL was associated with damage.

Analysis of clinical characteristics of drug-induced cutaneous lupus erythematosus in men

Analysis of clinical characteristics of drug-induced cutaneous lupus erythematosus in men

P100 REAL-WORLD COMPARISON OF ARTHRALGIAS WITH INFLIXIMAB VS. VEDOLIZUMAB IN THE TREATMENT OF BIO-NAIVE INFLAMMATORY BOWEL DISEASE

Abstract Background Both infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel disease (IBD) in adults. VDZ is gut-specific and thought to be less effective in controlling extraintestinal manifestations than IFX. The purpose of this study was to compare the incidence and timing of arthralgias between IFX and VDZ. Methods We performed a retrospective cohort study of bio-naïve adult patients treated with IFX or VDZ for ulcerative colitis (UC) or Crohn’s disease (CD) at a large multicenter gastroenterology private practice. Patients were case-matched 1:1 based on age, gender, diagnosis, and baseline disease severity using the partial Mayo (pMayo) for UC and the modified Harvey-Bradshaw Index (mHBI) for CD. Arthralgias were captured out to 12 months of therapy and classified as pre-existing or new-onset based on time to occurrence. Those with pre-existing arthralgias were excluded from new-onset arthralgias analyses. Rates of arthralgias and time to new-onset arthralgias were compared between IFX and VDZ patients. Results A total of 77 IFX (58 UC, 19 CD) and 77 VDZ (58 UC, 19 CD) case-matched pairs were generated. Baseline demographics were similar between IFX and VDZ groups: mean age 45±16.9 vs 46±16.2, male gender 60% vs 61%. Rates of pre-existing arthralgias were 13/77 (17%) and 12/77 (16%) in IFX and VDZ cohorts (p=0.83), respectively. Resolution of pre-existing arthralgias was also similar between groups (6/13 vs 7/12, p=0.70). Of the remaining 64 IFX and 65 VDZ patients without arthralgias at baseline, 16 (25%) IFX patients and 17 (26%) VDZ patients experienced new-onset arthralgias (p=1.0). Median time to new-onset arthralgias was 5.0 (IQR 3.4–7.0) months in IFX patients, compared to 3.3 (IQR 1.4–5.3) months in VDZ patients (p=0.15). While VDZ patients appeared to develop new-onset arthralgias earlier, this was not significant (p=0.20) [Figure 1]. Of note, two IFX patients discontinued therapy due to suspected drug-induced lupus with arthralgias; there were no VDZ discontinuations due to arthralgias. Conclusions Our data suggests that resolution of pre-existing arthralgias and new-onset arthralgias are similar, despite the gut selectivity of VDZ compared to IFX. Additionally, there was no difference in overall time to new-onset arthralgias. These data need to be verified in a larger cohort.

The Effect of Biological Agents on Antinuclear Antibody Status in Patients with Psoriasis: A Single-Center Study.

Background and Aims:Biological agents are being used as treatment of psoriasis for years. However, autoimmunity can develop after the using of these agents. Antinuclear antibody (ANA) status changes during biological therapy can be affected by certain factors including the presence of immunosuppression. We aimed to evaluate the effect of antitumor necrosis factor agents and ustekinumab on ANA status, as well as other factors leading to change in ANA status such as history of phototherapy and methotrexate combination therapy.Methods:In this study, the laboratory findings of thirty-one patients with psoriasis who received biological agents including infliximab, etanercept, adalimumab, and ustekinumab from 2016 to 2018 managed at the department of dermatology were reviewed. The ANA status of the patients was evaluated every 2–3 months.Results:Twelve (38.7%) out of the thirty-one patients developed ANA positivity during treatment. Nine patients receiving infliximab, two patients receiving etanercept, and one patient receiving adalimumab developed ANA positivity. The nuclear homogeneous, nuclear fine speckled, and nuclear large/coarse speckled were the most common patterns of ANA. A patient receiving infliximab also developed anti-dsDNA positivity. None of the patients developed drug-induced lupus erythematosus or any autoimmune diseases. Concomitant methotrexate use and phototherapy history had no effect on ANA status statistically (P = 0.240 and 0.717, respectively).Conclusion:The emergence of ANA positivity during infliximab therapy among all biological agents was more common. ANA positivity during biologic agents does not cause any signs and symptoms of autoimmune diseases in patients with psoriasis; thus, it can be suggested that biological agents are not major risk factors for autoimmunity.

418 A Review of Timelines and Reporters of Adverse Events From Proton Pump Inhibitors (PPIs) That Are Conveyed to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

INTRODUCTION: Recent publications have described potential PPI-associated adverse events (AEs) including cardiovascular disease (CVD), cerebrovascular accidents (CVA) and renal disease (acute interstitial nephritis and CKD). There is public interest and potential for lawsuits for these and other PPI-related AEs. The FAERS is a database of voluntarily reported AEs used for post-marketing surveillance of medications. The aim of this study is to analyze reports of all PPI-associated-AEs to FAERS, focusing on reporter sources. This permits an understanding of the effect of published high-profile PPI-associated AEs on FDA drug surveillance. METHODS: A total of 9,144,290 FAERS reports from January 2013 to December 2018 were examined. Analysis of all Primary PPI-related AEs were included (C. difficile, microscopic colitis, atrophic gastritis, hypergastrinemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, vitamin malabsorption, pneumonia, CVD, CVA, renal disease, drug-induced lupus, and dementia). AEs were defined by MedDRA terminology. All reports were categorized according to reporter source (physicians, pharmacists, other health care professionals, consumers, and lawyers). RESULTS: Until 2018, overall reporting of PPI-related AEs generally showed steady changes over time. In 2015 there were 7,024 reports for all PPI-related AEs, in 2016, there were 8,043, and in 2017, there were 7,682. Notably, in 2018, reports for all PPI-related AEs spiked to 14,607. For specific AEs, reports for renal disease and CVD from consumers showed marked increases. In 2015 consumers reported 427 CVD cases and 494 renal cases, while consumers reported 627 CVD cases and 1,155 renal cases in 2018 (Figure 1). Reports for lawyers and physicians for CVD and renal disease both increased between 2015 and 2018. Physicians had an increase from 368 to 503 cases of CVD (36.7% increase) and from 676 cases to 1,112 of renal disease (64.5% increase), while lawyers had an increase of 49 cases of CVD to 99 cases of CVD (102% increase) and increase of 4 cases to 974 of renal disease (24,250% increase). This resulted in a rise in percentage of total reports from lawyers (Figures 2 and 3). CONCLUSION: Consumers are increasing reporting of CVD and renal disease associated with PPI use. The rapid increase in reports of PPI-associated CVD and especially renal disease by lawyers suggests that lawyers are a potential source of interference on pharmacovigilance.

10. Drug-induced lupus as a trigger for macrophage activation syndrome

IntroductionMacrophage activation syndrome (MAS) or haemophagocytic lympohistiocytosis (HLH) is a rare, life threatening cause of fever. It can be due to a primary haematological condition, but can also be triggered by several rheumatological conditions such as Stills disease or systemic lupus erythematosus. It can often be misdiagnosed as infection, leading to a delayed or even missed diagnosis. Given its life threatening course, we need not only recognise the syndrome, but also identify the underlying trigger so that appropriate treatment of the underlying cause can be initiated early. This case is the first reported case of drug-induced lupus causing MAS.Case descriptionThis is a 56-year-old female of Indian origin who initially presented to rheumatology in January 2018 with a seronegative inflammatory arthritis. ANA was negative at this time and she had no other clinical features of a connective tissue disease. She was intolerant of methotrexate, so switched to sulphasalazine in October 2018. Unfortunately, sulphasalazine failed to control her disease, and she was assessed for biologic therapy in March 2019. It was noted she had travelled to India at the start of 2019, but IGRA screening in March returned negative prior to being considered for biologics.She was admitted to Daisy Hill Hospital in Newry, Northern Ireland on 22/3/19 with pyrexia, right sided abdominal pain and leucopenia. She was treated with several courses of broad spectrum antibiotics, but multiple blood and urine cultures came back negative. CT chest, abdomen and pelvis found duodenitis, but failed to identify a source of sepsis or evidence of tuberculosis. Echocardiogram was normal. Investigations from infectious diseases ruled out HIV, Hepatitis B&C, EBV, CMV, stongyloides, leishmaniasis, syphilis and malaria.Daily pyrexia persisted, and she developed a progressive pancytopenia, rash, mucositis and a rising ferritin up to 30000. Skin biopsy was non-specific but showed weak staining for IgM and C3 raising the possibility of vasculitis but was not definitive. Triglycerides were elevated at 3.6 and fibrinogen 1.2. ANA, which had initially been normal before sulphasalazine, was now positive at 1in40 with an anti-chromatin of 3.5 and ds-DNA 18. Complement was normal. CD25 soluble receptor later returned at 5370. Anti histone antibody was negative. Bone marrow biopsy confirmed MAS.She was treated with intravenous immunoglobulins, intravenous methylprednisolone for 3 days followed by prednisolone, and anakinra. Her fevers subsequently settled, ferritin normalised and her blood counts gradually improved. She was commenced on hydroxychloroquine and prednisolone dose weaned.DiscussionOur working diagnosis in this case was that of a drug-induced lupus secondary to sulphasalazine therapy which then was complicated by MAS. This is the first reported case in the literature of a drug-induced lupus-driven MAS. We had considered if this could have represented a systemic lupus erythematosus picture from the onset of the inflammatory arthritis, however, the initial ANA was normal and only became positive after treatment with sulphasalazine. Interestingly, this patient’s ANA profile became negative following treatment with steroid/anakinra and following withdrawal of the drug. It is unusual that complement would be normal if this was a presentation of systemic lupus, and whilst anti histone antibody negativity perhaps points away from drug induced lupus, it can be negative in 5% cases of drug induced lupus.Key learning pointsEarly recognition of MAS is imperative if we are to improve morbidity and mortality from this condition. It is important to be aware of potential triggers of the syndrome, and this case has highlighted a previously unrecorded cause of MAS in drug induced lupus. In this case, treatment with high dose steroid, intravenous immunoglobulin and anakinra, as well as withdrawing the causative drug, proved to be very effective in resolving her MAS.Conflict of interestThe authors declare no conflicts of interest.

Multidisciplinary approach to connective tissue disease (CTD) related pleural effusions: a four-year retrospective evaluation

BackgroundCTD-related pleural effusions are rare and challenging to diagnose. Our lung inflammation service (with expertise in rheumatology, interstitial lung disease and respiratory failure) works closely with the pleural team. This study aims to review the multidisciplinary approach to CTD-related pleural effusions at a tertiary centre.MethodsAll patients with CTD-related pleural effusions at St Thomas’ Hospital, London were included. Retrospective data were collected from Dec 2013 to 2016.ResultsThe lung inflammation service performed an expert clinical assessment and targeted investigations. 11 patients (ages 23–77) were identified with CTD related pleural disease. 9 (82%) patients were given a new CTD diagnosis, with pleural disease as the first manifestation. The range of conditions were: rheumatoid arthritis [3] ,IgG4-related disease [2] ,adult Still’s disease [2] ,vasculitis [1] ,SLE [1] ,drug-induced lupus [1] ,and Behcet’s [1].The pleural team review took place 1 day (median) after referral. 73% of diagnoses (8 patients) were achieved with local anaesthetic pleural interventions (a combination of: aspiration, drain, or percutaneous biopsy). This included 1 patient who required no pleural intervention. 1 required medical thoracoscopy, and 2 underwent thoracic surgery.Diagnoses were made by integrating all available evidence such as clinical assessment, imaging, and autoimmune serology. No diagnosis was achieved by pleural cytology or histology analysis alone.8 (73%) were commenced on prednisolone acutely (vasculitis, SLE, drug-related lupus, 1 patient with rheumatoid arthritis, Behcet’s, 2 patients with Adult Still’s disease, 1 patient with IgG4-related disease). Of these 8, one patient with rheumatoid arthritis received IV methylprednisolone beforehand, one patient with IgG4-related disease was weaned off prednisolone to methothrexate, two patients with Adult Still’s disease were on colchicine as well, and one patient with Behcet’s was on cyclophosphamide as well. 7 (64%) were managed as outpatients; 4 required admission. The median time from pleural review to diagnosis was 53 days.ConclusionsDiagnosis can be challenging in patients presenting with pleural disease as the first manifestation of a CTD. We recommend a multidisciplinary approach in management.

Valvulitis in a Pediatric Patient with Drug-induced Lupus Secondary to Minocycline

Introduction: Minocycline is a tetracycline derivative with anti-inflammatory properties considered safe and effective for the treatment of acne vulgaris. However, minocycline is known to have a breadth of side effects ranging from mild to severe. Based on the FDA’s data from 1998 to 2003, minocycline adverse reactions occur at a rate of 72 per 1 million prescriptions. Patients commonly experience lightheadedness, GI symptoms, skin hyperpigmentation, and tooth discoloration. This drug is also well known to cause more severe systemic involvement, namely Drug-Induced Lupus (DIL). …

Valvulitis in a Pediatric Patient with Drug-induced Lupus Secondary to Minocycline

Valvulitis in a Pediatric Patient with Drug-induced Lupus Secondary to Minocycline