Steroid-sparing Drugs Research Articles

Severe myelosuppression causing pancytopenia in a patient with Crohn’s disease: an uncommon complication of azathioprine

Azathioprine, is widely used to treat many diseases as a steroid sparing drug, including inflammatory bowel disease. Whilst it can commonly result in leucopenia, in rare instances, it can cause severe myelosuppression and pancytopenia. We present a patient with Crohn’s disease, who developed severe myelosuppression resulting in pancytopenia and neutropenic sepsis secondary to azathioprine use.

Adult-onset Still’s disease masquerading as acute coronary syndrome: a case report and review of the literature

IntroductionAdult-onset Still’s disease is a rare systemic autoinflammatory disease. We present a case of a young man with a constellation of symptoms and myopericarditis as a complication of this disease.CaseA 36-year-old Hispanic man with no significant past medical history developed a quotidian fever pattern following an upper respiratory tract infection. He initially presented with chest pain concerning for myocardial infarction and underwent cardiac catheterization, which revealed non-obstructive coronary artery disease. He was found to have myopericarditis, significant neutrophilic leukocytosis, and hyperferritinemia. He improved on high-dose corticosteroids but developed steroid-induced psychosis, and 4 months from symptom onset, he finally received tocilizumab, which eventually induced remission without adverse reactions.DiscussionAdult-onset Still’s disease should be considered in a patient with fevers of undetermined origin. Due to its multisystemic involvement, adult-onset Still’s disease is often a diagnosis arrived at after an extensive cardiac, hematologic, malignant, and infectious workup. Imaging, laboratory testing, and bone marrow biopsy were necessary to rule out alternative etiologies of this patient’s presentation. Steroids are the mainstay of treatment because they are easily affordable, although the high risk of adverse effects makes them less desirable. Interleukin-1 inhibitors (anakinra or canakinumab) and interleukin-6 inhibitor tocilizumab are the steroid-sparing biologic agents of choice but are cost-prohibitive.ConclusionAdult-onset Still’s disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

Faster steroid-free remission with tocilizumab compared to methotrexate in giant cell arteritis: a real-life experience in two reference centres.

Glucocorticoids (GCs) are still the mainstay of treatment of giant cell arteritis (GCA). Although GCs are highly effective in GCA, the high burden of toxicity of GCs as well as the disease relapse during GC tapering is well documented. To compare the efficacy and rapidity of TCZ and MTX as steroid-sparing agents in a real-life cohort of GCA patients. A retrospective analysis was conducted including patients with newly diagnosed GCA from the Rheumatology Units of Udine and Rome. The inclusion criterion was the treatment with TCZ or MTX as first steroid-sparing drug. 112 GCA patients (81 females) with a median age of 70 (IQ 65-75) years were collected. Thirty-one out of 112 (27.7%) patients were treated with TCZ (162mg/week), while 81/112 (72.3%) patients received MTX (up to 20mg/week) as a GC-sparing agent. At month 6 after GCA onset, 5/31 (16.1%) patients in TCZ group and none in MTX group were in GC-free sustained remission (p value = 0.001). Similarly, at month 12, 64.5% (20/31) and 11.1% (9/81) of patients were in sustained GC-free remission in TCZ and MTX group, respectively (p value <0.001). At month 24 of follow-up, at least one relapse of the disease occurred in 7/31 (22.6%) in TCZ-treated and 28/81 (34.6%) in MTX-treated patients, respectively (p value = 0.22). TCZ allowed a faster discontinuation of steroid therapy than MTX in GCA patients, without increasing the risk of relapse.

JAK inhibitors in refractory juvenile rheumatic diseases: Efficacy, tolerance and type-I interferon profiling, a single center retrospective study

Objectives– Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases.This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment. Methods– We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi. According to physicians’ assessment, treatment effectiveness was classified at 12 months as a complete response in the total absence of disease activity, partial response in case of significant (>50%) but incomplete improvement or no response in the case of non-response or improvement of less than 50% of the clinical and biological parameters. ISG were monitored longitudinally using Nanostring technology. Results- 22 children were retrospectively included in this study, treated either by baricitinib or ruxolitinib. Complete response was achieved at 12 months in 9/22 (41%) patients. 6/22 (27%) patients were non-responders and treatment had been discontinued in five of them. Within the interferon (IFN)-related diseases group, ISG-score was significantly reduced 12 months after JAKi onset (p = 0.0068). At 12 months, daily glucocorticoid doses had been reduced with a median dose of 0.16 mg/kg/day (IQR 0.11; 0.33) (p = 0.0425). 7/22 (32%) patients had experienced side effects, infections being the most common. Increase of the body mass index was also recorded in children in the first 6 months of treatment. Conclusion– JAKi represent a promising treatment of immune-mediated pediatric diseases, enabling to decrease type-I IFN transcriptomic signature in responding patients, especially in the context of juvenile dermatomyositis. JAKi represent steroid-sparing drugs but they induce metabolic changes linked to weight gain, posing a concern in the treatment of young patients and teenagers. More data are required to define the efficacy and safety of JAKi in the management of refractory pediatric rheumatic diseases.

Results of omalizumab treatment in chronic eosinophilic pneumonia: Real-life data.

Recurrences occur when corticosteroid therapy is discontinued or reduced during the treatment of chronic eosinophilic pneumonia (CEP). The probability of recurrence is once in 50% of patients and twice or more in 25%. In such instances, new treatment options are deemed necessary. This study aims to assess the efficacy of omalizumab treatment as a steroid-sparing drug in patients with CEP. The clinical features of patients treated with omalizumab for recurrent CEP were evaluated retrospectively before and after treatment. All data from patients and diagnoses were reviewed. The effects of treatment on recurrence rate, oral corticosteroid (OCS) use and lung functions, peripheral eosinophil values, and symptom scores were evaluated. Radiological regression was also evaluated. In the final analysis, we included ten patients with a median follow-up of 22 months after initiation of omalizumab. During this follow-up period, the results were associated with a significant reduction in the number of asthma attacks per year, the number of CEP relapses, the rate of hospitalization, the amount of corticosteroids consumed daily, and the total corticosteroid dose. In addition, improvement was observed in the symptom scores and lung functions of the patients. Systemic steroids were completely discontinued in two patients receiving omalizumab treatment. In other patients, the mean steroid dose was reduced by 77.2 percent in the first year of omalizumab treatment and 82 percent in the second year, respectively. Nevertheless, there was no elevation in peripheral eosinophil count, and radiological regression was observed. Omalizumab can be an effective treatment for CEP and can be used as a steroid-sparing agent.

First validation of the childhood lupus low disease activity state (cLLDAS) definition in a real-life longitudinal cSLE cohort

ObjectivesTo validate the childhood lupus low disease activity state (cLLDAS) definition in cSLE by describing differences in time to reach first adult LLDAS (aLLDAS) versus cLLDAS. Secondly, to analyse positive and negative predictors for maintaining cLLDAS for at least 50% of follow-up time (cLLDAS-50) and for the occurrence of damage. MethodsProspective longitudinal data from a cSLE cohort were analysed. Used definitions were: aLLDAS according to Franklyn, cLLDAS by cSLE treat-to-target (T2T) Task Force, disease activity score by SLEDAI -2 K and damage by SLICC damage index. ResultsFifty cSLE patients were studied, with a median follow-up of 3.1 years. Each patient reached aLLDAS and cLLDAS at least once. Mean time to reach first aLLDAS/cLLDAS was 8.2/9.0 months, respectively. For 22/42 patients the mean steroid-dose related delay to reach first cLLDAS was 6.2 months. 58% of patients were able to maintain cLLDAS-50. Time to first cLLDAS (OR 0.8, p = 0.013) and higher number of flares (OR 0.374, p = 0.03) were negative predictors to maintain cLLDAS-50. Damage occurred in 34% of patients (23.5% steroid-related), in 64.7% within one year after diagnosis. African/Afro-Caribbean ethnicity, neuropsychiatric involvement and ever use of a biologic were significant predictors for damage. ConclusionTime to reach cLLDAS in cSLE differs from time to (a)LLDAS, which validates the new cLLDAS definition. Attaining cLLDAS-50 was difficult in real-life. This cohort shows the high risk for early damage in cSLE. T2T with earlier focus on steroid-tapering and starting steroid-sparing drugs seems important to prevent (steroid-related) damage in cSLE.

Uptake and safety of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide observational study.

The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare. Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series (SCCS) analysis investigated the association between pneumococcal vaccination and IMID flare. The SCCS observation period was up-to six-month before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90-days post-vaccination exposed, and the remaining unexposed periods. We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3,804 with axial spondyloarthritis and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years (32%), with IBD (42%), and without additional indication(s) for vaccination (46%). In the vaccine-safety study, data for 1,067, 935, and 451vaccinated patients with primary-care consultations for joint pain, AIRD flare and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, AIRD flare and IBD flare in the exposed period with incidence rate ratios (95% Confidence Interval) 0.95 (0.83-1.09), 1.05 (0.92-1.19), and 0.83 (0.65-1.06) respectively. Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare.

Steroid-responsive dual neuronal antibody-positive paraneoplastic encephalitis

Here, we report the case of an elderly African male with multifocal neuraxial involvement in the form of progressive parkinsonism and ataxia over a year. On evaluation, dual neuronal antibody positivity was detected. A diagnosis of paraneoplastic encephalitis was made without any detection of primary neoplasm. He was successfully managed with pulse steroid therapy followed by oral steroid and steroid-sparing oral immunosuppressive drug without any need for intravenous immunoglobulin or plasma exchange.

Reggio Emilia (Northern Italy) Interdisciplinary Uveitis Clinic: What We Have Learned in the Last 20 Years

ABSTRACT Purpose To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. Methods Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. Results Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. Conclusions The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

Levamisole Modulation of Podocytes' Actin Cytoskeleton in Nephrotic Syndrome.

Podocytes play a central role in glomerular diseases such as (idiopathic) nephrotic syndrome (iNS). Glucocorticoids are the gold standard therapy for iNS. Nevertheless, frequent relapses are common. In children with iNS, steroid-sparing agents are used to avoid prolonged steroid use and reduce steroid toxicity. Levamisole is one of these steroid-sparing drugs and although clinical effectiveness has been demonstrated, the molecular mechanisms of how levamisole exerts its beneficial effects remains poorly studied. Apart from immunomodulatory capacities, nonimmunological effects of levamisole on podocytes have also been suggested. We aimed to elaborate on the effects of levamisole on human podocytes in iNS. RNA sequencing data from a human podocyte cell line treated with levamisole showed that levamisole modulates the expression of various genes involved in actin cytoskeleton stabilization and remodeling. Functional experiments showed that podocytes exposed to puromycin aminonucleoside (PAN), lipopolysaccharides (LPS), and NS patient plasma resulted in significant actin cytoskeleton derangement, reduced cell motility, and impaired cellular adhesion when compared to controls, effects that could be restored by levamisole. Mechanistic studies revealed that levamisole exerts its beneficial effects on podocytes by signaling through the glucocorticoid receptor and by regulating the activity of Rho GTPases. In summary, our data show that levamisole exerts beneficial effects on podocytes by stabilizing the actin cytoskeleton in a glucocorticoid receptor-dependent manner.

Retraction of cystoid macular edema from the fovea after intravitreal anti-VEGF therapy for birdshot chorioretinopathy.

To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Neuromielitis óptica y enfermedad anti-MOG

The classic term neuromyelitis optica (NMO) has been replaced by NMO spectrum disorder (NMOSD) as a result of the identification of the diagnostic marker of the disease (IgG-AQP4) and the inclusion of features such as area postrema syndrome or diencephalic disturbances, among others. The article includes the diagnostic criteria for IgG-AQP4 positive and negative NMOSD and describes the treatments used in the acute phase and to prevent relapses (namely, oral steroid-sparing drugs, rituximab, tocilizumab, and drugs specifically developed for the disease). Some of the patients with seronegative IgG-AQP4 NMOSD will show positivity for the IgG-MOG (myelin oligodendrocyte glycoprotein) marker, which can also manifest as recurrent optic neuritis, acute disseminated encephalomyelitis, or conus medullaris syndrome, among others. The possibility of recurrences in some cases of persistently seropositive anti-MOG associated disease prompts the chronic use of immunomodulators in a similar way to TENMO, with the particularity of the usefulness of immunoglobulins in children. Finally, the epidemiological, clinical, paraclinical and therapeutic differences between multiple sclerosis, TENMO and anti-MOG disease are described.

Treatment-resistant granulomatosis with polyangiitis: An unusual presentation

Granulomatosis with polyangiitis (GPA) is a rare systemic small-vessel vasculitis. This inflammatory reaction can affect the upper and lower respiratory tract, as well as the kidneys. The expected age of presentation is in the sixth and seventh decades of life, and Caucasians are mostly affected. The cornerstone of treatment is high-dose glucocorticoids in combination with immunosuppressant, steroid-sparing drugs, which leads to remission in almost 80% of patients. We present an unusual case of a 55-year-old Hispanic woman presenting with acute kidney injury secondary to treatment-resistant GPA. The failure of standard treatment is extremely rare. In addition, this patient presented with primarily renal symptoms, even though head and neck and airway symptoms are expected in almost all cases initially.Keywords: Granulomatosis with polyangiitis, renal failure, treatment failure

E057 A systematic review of new rheumatic immune-mediated inflammatory diseases (R-IMID) following SARS-CoV-2 vaccinations

Abstract Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated ‘SARS-CoV-2 vaccination’ (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title-abstract screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76; 55%), followed by Oxford AstraZeneca vaccine (35; 25%). The mean duration between SARS-CoV-2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34; 25%) and small vessel vasculitis (33; 24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118; 86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125; 91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease; One of them died due to fatal myositis and rhabdomyolysis; two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area. Disclosure A. Nune: None. K. Bora: None. K.P. Iyengar: None. B. Barman: None. V. Durkowski: None. S. Venkatachalam: None. S. Bilgrami: None. L. Ottewell: None. C. Manzo: None.

A Very Rare Case of Juvenile Dermatomyositis with Typical Cutaneous Clinical Signs

A Very Rare Case of Juvenile Dermatomyositis with Typical Cutaneous Clinical Signs

Effect of early initiation of steroid-sparing drugs in patients with bullous pemphigoid.

Bullous pemphigoid (BP) can be treated using systemic and topical glucocorticoids and/or other immunomodulatory agents. However, the long-term use of systemic glucocorticoids causes severe adverse side effects. This study was aimed at investigating whether the early initiation of corticosteroid-sparing therapy (CST) in BP patients results in better outcomes than late or no CST. We retrospectively identified all BP patients referred to the tertiary center, of the Department of Dermatology and Venerology, Aarhus University Hospital, Denmark, from 2015 to 2021. Patients' demographics, comorbidities, treatment, remission of BP, length of admission, relapse, and 1-year mortality were recorded. All patients who received CST were dichotomised into two groups: initiated with CST <28 or >28 days. The groups were compared using t-tests. Additionally, all patients who received CST were compared with those who received systemic glucocorticoids alone. Our cohort was compared with that of a previous study (2006-2013) performed in our department. In 2015, we revised our BP treatment guidelines to include the early initiation of CST. On comparing the group of patients initiated with CST <28 versus >28 days, we found no significant differences in the complications or mortality between the groups (p = 0.63 and p=0.79, respectively). The <28 days group had a lower rate of relapse (p < 0.05). On comparing data from this study with those from the previous study, conducted before we revised our treatment guideline, we found a reduced initial dose of prednisolone and reduced admission time in this study. No significant differences were found between patients treated with CST and those treated with systemic glucocorticoids alone. The rate of complications and 1-year mortality did not differ significantly between the two subgroups in this study. The relapse rate was lower in the CST <28 days group than in the CST >28 days group. The initial dose of prednisolone and admission time were reduced in this study compared with those in the previous study performed before the implementation of a local treatment guideline recommending the early initiation of CST.

Single Center Experience with Off-Label Benralizumab in Refractory Hypereosinophilic Syndrome Demonstrates a Satisfactory Safety and Efficacy Profile

Background: Hypereosinophilic syndrome (HES) is characterized by blood and/or tissue eosinophilia resulting in end-organ damage. HES can be primary clonal (in which the eosinophil is part of clonal hematopoiesis), secondary (due to eosinophilic stimulating cytokines) or idiopathic (I-HES). A careful diagnostic work-up for primary causes, as well as vigilant surveillance for end-organ damage should be performed to establish an underlying and treatable diagnosis. Regardless of the cause, treatment of symptomatic HES is mandatory. Treatment may consist of steroids, tyrosine kinase inhibitors, hydroxycarbamide, or interferon, with variable responses. Long-term use of steroids leads to osteoporosis and infections, and treatment with steroid sparing drugs might be hampered by other side-effects. More aggressive treatments such as alemtuzumab is efficacious but severely immunosuppressive. Several antibodies targeting IL-5 or its receptor have been successfully applied for eosinophilic asthma but only mepolizumab is registered by the FDA and EMA for HES. Benralizumab, an anti-IL5R antibody, was efficacious and safe for treatment of HES in a phase-I/II trial. A randomized phase-III trial comparing benralizumab with placebo is currently recruiting. We have treated 15 patients with off-label benralizumab for severe refractory HES or HES with unacceptable steroid dependency. Methods: 15 adults (8 with I-HES, 6 with secondary (lymphocytic variant) HES and one patient with HES secondary to sarcoidosis; age range 19-69 years; 10 male, 5 female) from our institution were treated with benralizumab at a monthly dose of 30 mg after giving consent for off-label use. All had absent HES translocations by FISH, and no evident underlying diagnosis was present after extensive diagnostics including bone marrow examination with cytogenetics and molecular diagnostics. They all were refractory or had contra-indications to conventional treatment, or steroids could not be reduced to an acceptable dose. All had elevated eosinophil counts at diagnosis above 0.6 x 109/L (range 0.32-90 x109/L, median 8.3 x 109/L) except one patient who had a level of 0.32 while on 30 mg prednisolone per day. All patients had at least one organ affected by HES, including 2 patients with myocarditis. Three patients had previously received mepolizumab in a HES dose, 2 of whom were refractory and consequently stopped while one had an allergic reaction necessitating cessation. Median follow-up time after starting benralizumab was 22 months (range, 1-34 months). Results: In terms of efficacy, 13 patients had a reduction of their eosinophil count to below 0.05 x 109/L after one dose, one patient had a reduction from 8.13 to 0.72 x 109/L, with a count that is still decreasing while stopping all other medication. Eosinophil count decreased from 12.38 to 1.45 x 109/L in another patient, but benralizumab was stopped due to the development of MDS, which was most likely the cause of the eosinophilia despite normal cytogenetics and molecular diagnostics at time of diagnosis. All but 2 patients were off steroids completely after 4 months. All but 2 patients experienced a clinically relevant improvement of organ function, mostly to complete resolution of objective symptoms or signs. Interestingly, the 2 patients who did not experience clinically significant reduction of symptoms, despite reduction of peripheral eosinophil counts, both had colitis as one of the cardinal disease symptoms. In one, the diagnosis was revised to inflammatory bowel disease with secondary eosinophilia. In terms of safety, 2 patients experienced mild headache for a few days after the benralizumab dose, and 1 patient had a mild malar rash after the first dose. One patient stopped due to the development of MDS necessitating other treatment and one stopped due to refractoriness. Interestingly, this patient subsequently had an excellent response on mepolizumab, on both clinical symptoms as well as reduction of eosinophil counts. All patients with objective clinical benefit remain on treatment. Conclusions: We report on the largest single center cohort of patients treated with off-label benralizumab for HES. The use of this drug has proven a safe and effective treatment for HES regardless of the underlying cause. It reduces eosinophil counts, reverses organ-damage and use of steroids in most patients. Side effects are infrequent and mild and no severe adverse events were observed.

Considerations in Complications Arising from the Management of Pemphigus Vulgaris: A Case Report

Background: This paper reports a case of pemphigus vulgaris in a middle-aged male with oral lesions and skin eruptions&#x0D; Objective: To highlight the complications of prolonged steroid therapy.&#x0D; Case Report&#x0D; A 48-year old male presented with an eight-month history of recurrent mouth ulcers. There was positive history of cutaneous ulcers on the upper extremities, back and genital areas. Patient had been placed on long term steroid therapy prescribed by general practitioners. General examination showed bilateral pitting pedal oedema, moon face and low blood pressure. Intra-oral examination revealed multiple irregular shaped ulcers and erosions with erythematous floor on the buccal mucosa, labial mucosa, floor of the mouth, soft palate and anterior pillar fauces. The dorsum of the tongue had areas of ulcerations with necrotic slough. An impression of pemphigus vulgaris was made based on high index of clinical suspicion and patient was commenced on azathioprine 50mg and prednisolone 40mg daily for a week. Topical use of clobetasol ointment (0.05%) was also commenced to be applied twice daily. There was improvement with the oral lesions on a one-week review. The dose of prednisolone was then stepped down to 20mg daily for one week and 0.2% chlorhexidine mouth rinse twice daily was introduced.&#x0D; Punch biopsy of an intact labial mucosa was done on a subsequent visit and histopathology examination confirmed the diagnosis of pemphigus vulgaris. Patient was referred to the cardiologist on account of the hypotension and bilateral pedal oedema which was suggestive of complications of long-standing steroid use.&#x0D; Patient was placed on maintenance dose of prednisolone 10mg and azathioprine 50mg daily, and topical steroid oral rinse.&#x0D; Conclusion: This study reports a case of pemphigus vulgaris with oral and skin lesions in a middle-aged male. Patient developed some complications due to the prolonged duration of steroid therapy. Regular patient monitoring, adjustment of steroid therapy combined with adjuncts like steroid-sparing drugs are essential to minimizing the steroid-induced adverse effect&#x0D;

AB1518 CASE REPORT OF A HARD TO TREAT DERMATOMYOSITIS AFTER A COVID-19 INFECTION AND SUBSEQUENT VACCINATION

BackgroundA 50 years old woman, a medical doctor, came to our department with symmetrical proximal muscular weakness, several months after Covid-19 infection and three weeks after a second dose of Covid-19 mRNA vaccine. The patient had no prior or family history of autoimmune diseases and take no medicines. In the past she undergone an operation for double-kidney with frequent urinary infections. Objective findings have shown symmetrical proximal muscular weakness and classic sings of dermatomyositis - Gottron’s papules, shawl and holster signs, periungual vasculitis.ObjectivesWe present a case of a 50 old woman with clinical and laboratory proven dermatomyositis, starting three weeks after a second dose of a Covid1-19 mRNA vaccine without other reasons.MethodsThe laboratory tests showed elevated CPK, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase, high ANA – 1:1280 and myositis specific autoantibodies- anti-NXP2 and anti-Mi-2- beta. The electromyography showed myopathic changes and the muscle MRI – symmetrical edema of mm.obturator and mm.adductor brevis. We exclude diseases that may mimic inflammatory myopathies. We made a cancer screening – whole body MRI, colonoscopy, gastroscopy, mammography and gynecological exam, immunoblot for detection of paraneoplastic syndrome-associated neuronal antibodies, with no detection of cancer. Muscle biopsy of m.vastus lateralis showed attenuating muscle inflammation with advancing muscle atrophy and fibrosis.ResultsThe diagnose dermatomyositis was made according Bohan and Peter criteria and we start a high dose (1mg/kg/day) glucocorticoid therapy with good initial clinical and laboratory effect. Two months after starting a therapy muscle weakness worsened together with difficulty of swallowing. We excluded steroid myopathy after second EMG and lack of improvement when tapering the GS dose. Methotrexate 20 mg/weekly was added as a steroid sparing drug with good response, but was stopped because flare of pyelonephritis. Accordning to the opinion of dermatologist hydroxychloroquine was started for a couple of weeks, because of active skin manifestations. Muscle weakness worsened on the background of treatment, which was stopped. We started a therapy with intravenous immunoglobulins and considered therapy with cyclophosphamide or azathioprine after urinary infection. Because the patient was infected for a second time with covid-19, although vaccine, we continued only with glucocorticoids and antiosteoporotic therapy.ConclusionThe etiology and pathogenesis of inflammatory myopathies are not fully clarified so far. We speculate that the infection with Covid-19 as well as mRNA vaccine trigger inflammatory myopathy and compromise the patient’s immunity for poor treatment response with glucocorticoids and immunosuppressives. On the other hand advanced muscle atrophy and fibrosis within a short period show that suspected triggering factors could be a reason for difficult to treat such type of dermatomyiositis.Disclosure of InterestsNone declared

P244 The use of anti-malarial therapy in UK Rheumatology practice. A UK-based pilot survey for the BILAG group

Abstract Background/Aims Antimalarials have an important role in the management of autoimmune rheumatic disease, especially lupus (SLE) and other connective tissue diseases (CTD). A large North American study demonstrated a risk of retinopathy with hydroxychloroquine, increasing at doses above 5mg/kg and after 10 years or more of continuous therapy. This has influenced the development of specific monitoring ocular guidance for hydroxychloroquine although there has been less attention to potential side effects in routine use. Our aim was to examine hydroxychloroquine use including the effect of changes in ophthalmology guidance Methods We designed a 21-question internet-based survey. This requested information on antimalarials including hydroxychloroquine brand, dosing, monitoring and concerns about use. We requested information about alternatives to hydroxychloroquine including mepacrine and chloroquine, barriers to and indications for prescribing these alternative antimalarials. Results We received 69 responses, 59 (86%) Consultants, 10 (14%) ST’s from across the United Kingdom of which 51% worked in a district general hospital (DGH) setting. Of the Consultants, 28 (47%) ran dedicated CTD clinics. Regarding hydroxychloroquine, 39 respondents (57%) used a defined local pathway for Hydroxychloroquine retinopathy screening. While 59/69 (86%) did not know which hydroxychloroquine brand their pharmacy dispensed, of the remainder, 14/19 (74%) used Quinoric. Regarding hydroxychloroquine dosing, 83% targeted weight-based maintenance dosing with most of these (77%) maintaining at the currently recommended 5mg/kg body weight or less, while 23% used 6.5mg/Kg. No participants measured hydroxychloroquine drug levels. Potential ocular toxicity, cardiac arrythmias and skin hyperpigmentation were reported as the most significant concerns with hydroxychloroquine usage. Of the alternatives, mepacrine was never used by 39%, (77% for chloroquine) while only 4% used either often or very often. Barriers to prescription of these alternative antimalarials were most commonly GP or local Pharmacy unavailability (39% and 17 retrospectively). However, mepacrine/ hydroxychloroquine combination was used by 32% of respondents, most often for refractory skin disease (21 respondents), refractory joint disease (five respondents) and as a steroid sparing drug (six respondents). Conclusion Our results suggest several aspects in which hydroxychloroquine use could be improved. Although recent evidence demonstrates the potential for significant ocular toxicity with Hydroxychloroquine in those taking &amp;gt; 5mg/kg body weight and for &amp;gt;10 years we found practice still varied with 43% Rheumatologists not using a dedicated ocular screening pathway making monitoring long term potentially hazardous. Alternatives to hydroxychloroquine are not considered by 39% perhaps reflecting paucity of data for mepacrine and chloroquine, especially in circumstances including pregnancy but also cost and lack of availability. Our results suggest a need for standardised hydroxychloroquine monitoring processes including improved ophthalmic screening with Optical Coherence Tomography, a need for more evidence about the potential benefits and hazards of hydroxychloroquine and alternative antimalarials and availability of prescribing guidelines. Disclosure A. Kaul: Consultancies; Dr Kaul has received fees for Advisory Boards for AbbVie, Janssen, Novartis, Lilly. Member of speakers’ bureau; r Kaul has received speaker fees from AbbVie, Novartis, Janssen, Leo, Pfizer. A. Mason: None. C. Edwards: None. E. Vital: None.