Low-dose Prednisolone Research Articles

EP04 Is this scleroderma lung or COVID-19 lung?

Case report - IntroductionThis is a case of Pakistani female with limited systemic sclerosis and associated mild interstitial lung disease. The lung disease was complicated by SARS-COV-2 related pneumonitis in April 2020 and that led to treatment challenges.She was previously seen in multiple private hospitals and labelled as Rheumatoid arthritis. She was being treated with long term steroids and Methotrexate. After her initial presentation to our Rheumatology services, her diagnosis was correctly revised to Systemic Sclerosis with phenotype of CREST. Her treatment was adjusted to Vasodilators and Mycophenolate due to skin and Lung involvement. Case report - Case descriptionThis is a case of 40-year-old Pakistani female who had been having multiple joint pains since 2010. She also experienced severe Raynaud’s.She presented to our Rheumatology clinic in December 2018. Her symptoms included recurrent digital ulcers, tight and tough skin at fingers and Raynaud’s worse during winter months. Her examination confirmed peripheral cyanosis with multiple digital ulcers with superimposed infection, marked sclerodactyly and calcinosis. She was started on Vasodilator therapy including calcium channel blocker and PDE5 inhibitor due to severity of ulceration. Infection was managed with prolonged course of antimicrobial therapy. Her immunology showed positive anti nRNP/Sm. Anti-centromere and anti Scl 70 were negative. Her condition fit description of CREST (Calcinosis, RP, Oesophageal dysmotility, telangiectasia). Her management included weaning off Methotrexate and reduction in the dose of corticosteroids. In February 2019, Respiratory work up showed normal Chest radiograph, High resolution CT chest showing no significant abnormality and FEV1 82%, FVC 86%, and DLCO 77%. Her PASP was 25mmHg. Overall, her condition remained stable over the course of next year. Her medication included Cellcept, low dose prednisolone, hydroxychloroquine, and Sildenafil. More importantly, Digital ulcers have been well controlled with combined vasodilator therapy. In April 2020, she developed SARS-CoV-2 with mild respiratory symptoms and was admitted to a different hospital. Fortunately, she responded well to ward based supportive and symptomatic treatment with no need for respiratory support. Subsequently, she has seen a different respiratory physician and had repeat imaging of chest which has led to dilemma whether the ground glass opacities in both lungs is due to scleroderma lung or COVID-19 related lung disease. She was given high dose prednisolone by the respiratory physician which has been reduced in rheumatology clinic. The new findings on chest imaging are sequelae of SARS-COV-2.Case report - DiscussionThis case highlights few important points as below: Systemic sclerosis diagnosis was not made for many years even though she has had severe digital ulcers for a long time. She was being managed as Rheumatoid arthritis. Systemic sclerosis remains a difficult disease to diagnose and is still under recognised. SARS-COV-2 related illness has not affected this patient adversely despite the fact of being on long term maintenance prednisolone of 7.5mg daily dose and Cellcept 2gm. Her cellcept was temporarily stopped during acute illness. We know that viral pneumonitis can present with typical ground glass opacities in bilateral areas of lungs and differential diagnosis does include connective tissue related lung disease but this lady had no significant respiratory involvement prior to COVID-19 illness and follow up scan will help to decide if this is disease progression or related to viral cause.Case report - Key learning pointsThere are multiple learning points in this case: Continuity of care under same primary team can avoid confusion related to diagnosis and diagnosis related complications. This lady had none, or mild subclinical lung involvement related to systemic sclerosis prior to contracting COVID-19 illness. Her CT chest findings after the episode of SARS-COV-2 were attributed to systemic sclerosis as she was seen by different respiratory team. This continuity is not always possible, but MDT collaboration needs to be improved across hospitals and across various departments. Systemic sclerosis remains an under diagnosed and under recognized complex rheumatic disorder and more primary care physicians need to be educated so they can appropriately refer these cases to Rheumatology services.Multi-disciplinary collaboration between Rheumatology, Respiratory and other specialties is the key point to manage these complex cases. This case also highlights an interesting observation that presence of significant immune disorder and immunosuppressant medication does not always equate to worse outcome if patient contracts SARS-COV-2. Supportive care, appropriate observation, and temporary suspension of DMARD in such cases can avoid any further complications.

O07 Sarcoidosis: it's bone deep

Case report - IntroductionThis is a report of a Caucasian patient with sarcoidosis presenting as groin pain.Case report - Case descriptionA 58-year-old Caucasian female from South Africa self-referred for physiotherapy following sudden onset right groin pain. Pelvic Xray was normal, but MRI pelvis showed lytic lesions in the acetabulum and proximal femur. The presence of night sweats suggested haematological malignancy leading to haematology referral. PET CT showed widespread metabolically active soft tissue lesions, lymph nodes and skeletal foci. Bone marrow trephine biopsy showed well-formed granulomata. An extensive infection screen was negative. A cervical lymph node biopsy and CT guided biopsy of pelvic and femoral lesions confirmed non-necrotising granulomas suggestive of sarcoidosis. Lung function tests were normal. Treatment with 30mg prednisolone for one month was poorly tolerated and steroids were rapidly weaned. She was unable to tolerate even low dose prednisolone. Severe pelvic pain and night sweats continue despite methotrexate, hydroxychloroquine and IV zoledronate (given for osteoporosis).Case report - DiscussionThis patient presented with groin pain, fatigue and night sweats, no demonstrable extra-osseous organ abnormality and normal plain radiography. Our diagnostic strategy was to first exclude malignancy and infection, particularly TB, but the unusual presentation created significant diagnostic uncertainty. Treatment is challenging due to intrusive side effects of steroids and hydroxychloroquine, and neutropenia induced by methotrexate.Osseous involvement is rare and has been reported in 1-15% of sarcoidosis patients. It is usually accompanied by skin lesions. There were no features on history or examination to suggest sarcoidosis and the diagnosis was based on bone biopsies.In a case series of 20 patients with osseous sarcoidosis, bone lesions were found on imaging during the initial presentation in 60% of cases. Ten patients were symptomatic, and all had multiple joint involvement. Axial involvement, primarily pelvis and lumbar spine was seen in 90% of cases. Lesions were detected on plain radiographs in 2 cases and were identified on MRI in 13 cases, PET-CT in 9 cases, CT in 4 cases and technetium-99m bone scintigraphy in 1 case. 55% of the cases required no treatment and 45% were treated most commonly with prednisolone, methotrexate, or hydroxychloroquine. Two cases required treatment with tumour necrosis factor inhibitors for refractory disease.Case report - Key learning pointsOsseous sarcoidosis can mimic many conditions including multiple myeloma and lymphoma, due to presentation with lytic lesions. Even pulmonary presentations can be atypical with predominant ground glass opacity or cavitating consolidation and parenchymal masses. Histopathological diagnosis is of critical importance, particularly in patients with atypical presentations. Assessment of organ involvement and disease extent is important in monitoring of treatment response. Plain radiographs tend to be normal in these cases and advanced imaging, including MRI, PET-CT, and CT, is often required. Symptomatic osseous disease may respond to steroids and conventional immunosuppression; a minority of refractory cases require TNF inhibition.

Efficiency of azathioprine monotherapy for maintenance treatment of autoimmune hepatitis in children.

Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with low dose prednisolone and azathioprine (AZA). The aim of this study is to evaluate the efficiency of AZA monotherapy for maintenance treatment of children with AIH. This study was a retrospective analysis of the 55 children with AIH. Patients were divided into two groups: combination therapy (CT) and AZA group based on maintenance therapy. Results of these two different maintenance treatments were compared in children with AIH. The mean age of the children was 10.67 ± 4.30 years (61.8% females) with a mean follow-up period of 46.8 ± 33.6 months. For maintenance treatment, 39 (70.9%) patients received AZA and 16 (29.1%) patients received CT. Relapse was observed in nine (19.6%) cases in the follow-up period; two were in the CT group (2/16; 12.5%) and seven (7/39; 17.9%) were in the AZA group (P = 0.620). In AZA group, the duration of remission was 22.2 ± 6.1 months and that was longer than CT group (P = 0.025). Our study suggests that AZA monotherapy is an effective and safe therapy for maintaining remission in children with AIH. AZA monotherapy may be used for maintenance treatment of children with AIH, except in cases of overlap syndrome and also to avoid side effects of long-term used steroids and to improve treatment compliance in proper cases.

A short-term oral corticosteroid for refractory lumbar spinal stenosis: a double-blinded randomized placebo-controlled clinical trial.

Although epidural corticosteroids have been evaluated for the lumbar spinal stenosis (LSS) as an alternative treatment, oral corticosteroids have not been considered as a possible option for the patients with constant pain who have resistant against routine treatments. Therefore, this study aimed to investigate the efficacy of the short-term, low-dose oral prednisolone for refractory LSS. In this double-blinded randomized placebo-controlled clinical trial, 100 participants with the refractory LSS were selected from the out-patient clinics; however, 7 of them excluded before randomization. The patients were randomly allocated into two groups with a 1:1 ratio: the intervention group that received 10 mg prednisolone per day for 1 week and the control group that received the exact placebo. The patients' severity of pain in terms of the numerical rating scale, ability to walk in meters, and Oswestry Disability Index (ODI) were assessed and then compared to the baseline after 2 months. The baseline variables were NS between these two groups. At the 2-month follow-up, the ability to walk in meters has increased and the severity of pain and ODI have decreased in both groups. Notably, except for the walking distance, none of the differences were statistically significant. Except for the significant change in walking distance between the groups, no other significant difference was observed in any variables when comparing the delta of each variable (after-before). One-week treatment with daily 10 mg oral prednisolone was not effective on the patients with refractory LSS in the short-term follow-up.

Utility of azathioprine, methotrexate and cyclosporine as steroid-sparing agents in chronic alopecia areata: a retrospective study of continuation rates in 138 patients.

The management of chronic alopecia areata (CAA) is challenging. There is currently no therapy that produces consistent successful hair regrowth. Systemic therapies, including prednisolone and steroid-sparing agents (SSA), are often tried in patients with CAA. As there are no head-to-head clinical trials that compare efficacy of one SSA over another, retrospective studies of treatment in clinical practice may help guide clinical practice. To investigate the utility of SSAs in the treatment of AA. An electronic medical records search identified patients with AA and those prescribed azathioprine, cyclosporine or methotrexate between 2002 and 2019. Type of AA, treatment duration, reason for cessation, use of concurrent prednisolone, dose of prednisolone and duration of prednisolone use were recorded. The primary outcome was SSA continuation rate at 6 and 12months. A total of 852 AA patients were identified, among whom 138 patients had been treated with azathioprine, methotrexate or cyclosporine. Of these 138 patients treated with a SSA, 92 (66.7%) continued treatment for at least 12months: 75.3% (55/73) of azathioprine users, 50% (11/22) of methotrexate users and 60.5% (26/43) of cyclosporine users. At 12months, 67.3% of azathioprine users required concurrent prednisolone at a mean dose of 5.6mg daily, 63.6% of methotrexate users required prednisolone at a mean dose of 5mg daily and 57.7% of cyclosporine users required prednisolone at a mean dose of 8.7mg daily. The SSA was ceased due to an adverse event in 15.9% of patients and a lack of efficacy in 17.4%. The most well-utilized SSA for CAA patients at our clinic was azathioprine. This study highlights that most CAA patients who commence treatment with azathioprine, methotrexate or cyclosporine continue that treatment for at least 12months and most require concurrent low-dose prednisolone to maintain remission or promote continued hair regrowth.

Reappraisal of Oral Steroid Therapy for Myasthenia Gravis.

Treatment with oral corticosteroids at high doses with an escalation and de-escalation schedule is effective against myasthena gravis (MG). In fact, the use of corticosteroids has led to a reduction in mortality to below 10% after the 1960s. However, long-term use of oral steroids above a certain dosage level is known to cause a number of problems. In 2014, the Japanese clinical guidelines for MG proposed that the first goal in MG treatment (treatment target) should be set at minimal manifestations (MM) with oral prednisolone (PSL) 5 mg/day or below, and that treatment strategies should strive to attain this level as rapidly as possible. In 2015, a multicenter, cross-sectional study revealed that higher PSL dose and longer PSL treatment do not ensure better outcome. In the absence of good response, the PSL dose should be decreased by combining with modalities such as plasma exchange/plasmapheresis and intravenous immunoglobulin (fast-acting treatments). In 2018, we conducted a multicenter, cross-sectional study in a large population of Japanese patients with generalized MG, aiming to elucidate the correlation between oral PSL regimens and achievement of treatment goals. The ORs for low vs. high dose to achieve treatment goals at 1, 2, and 3 years were 10.4, 2.75, and 1.86, respectively, whereas the corresponding ORs for low vs. medium dose were 13.4, 3.99, and 4.92. Early combination with fast-acting therapy (OR 2.19 at 2 years, 2.11 at 3 years) or combination with calcineurin inhibitors (OR 2.09 at 2 years, 2.36 at 3 years) were also positively associated with achieving treatment goals. These results indicate that early combination of low-dose PSL regimens with other therapies is the key for early achievement of treatment goals in generalized MG. However, even with this regimen, ~35% of patients did not achieve the treatment target after 3 years. These results suggest the limitation of the current oral corticosteroid therapy. We need to develop new treatment options to increase the rate of satisfactory outcome.

Impact of systemic steroid treatment on talc pleurodesis: a report of six cases

BackgroundInstillation of sterile graded talc in the pleural space is performed to prevent reaccumulation of malignant pleural effusion after drainage. Talc is thought to encourage pleural adhesions as part of the repair process by provoking inflammation, suggesting that adhesions are less likely to form in patients taking corticosteroids or other drugs with anti-inflammatory effects. However, the relationship between steroid therapy and pleurodesis efficacy remains unclear.Case presentationWe report the outcomes of six patients who underwent pleurodesis at Hiroshima University Hospital while being treated with systemic steroid therapy for non-cancer-related illnesses. Talc pleurodesis was successful at the first attempt in five of the six patients. The five successful cases were receiving low-dose oral prednisolone or methyl prednisolone (range, 1–20 mg/day) at the time of pleurodesis and had serum albumin levels ranging from 2.2 to 3.0 g/dL. In contrast, the patient in whom pleurodesis was unsuccessful was receiving a higher dose of prednisolone (40 mg/day) intravenously and had a relatively low serum album level (1.7 g/dL).ConclusionsThe outcome of pleurodesis may be affected by the dose and/or route of systemic steroid therapy. Further analysis with more patients will be necessary to clarify the relationship between steroid dosage and talc pleurodesis success rate.

Initial Treatment Response in Ocular Myasthenia Gravis: A Comparison Between Low and Moderate Doses of Prednisolone.

PurposeTo evaluate the initial treatment response to low doses of prednisolone, compared with moderate doses, in ocular myasthenia gravis (OMG).Patients and MethodsA retrospective chart review of patients with adult-onset (age ≥15 years old) OMG, who were treated with prednisolone, was conducted. Subjects were divided into two groups according to their prednisolone dosing regimen. The low-dose group was defined as those with an average 12-week cumulative dose of prednisolone <0.435 mg/kg/day and the moderate-dose group averaged 0.435–1.000 mg/kg/day. The primary outcome of interest was the comparison of clinical response to prednisolone at 12 weeks between the low-dose and moderate-dose groups. The secondary outcome was the difference in adverse events between treatment groups.ResultsOf 34 subjects, 16 subjects (47.1%) were male. The mean age at onset was 44.0±18.1 years. The most common presenting ocular feature was ptosis with ophthalmoplegia (22 subjects, 64.7%), followed by isolated ptosis (nine subjects, 26.5%) and isolated ophthalmoplegia (three subjects, 8.8%). Half of the subjects were treated with low-dose prednisolone and the other half were treated with moderate-dose prednisolone. There were no substantial differences in baseline characteristics between treatment groups. After 12 weeks of treatment, nine of 17 subjects (52.9%) and 13 of 17 subjects (76.5%) in the low- and moderate-dose groups, respectively, were regarded as responsive to the prednisolone treatment (P=0.28). Adverse events were exclusively observed in the moderate-dose group.ConclusionTreatment of OMG with an average 12-week cumulative dose of prednisolone <0.435 mg/kg/day (low dose) shows a comparable responsive outcome to 0.435–1.000 mg/kg/day of prednisolone (moderate dose). Treating OMG with low-dose prednisolone can minimize prednisolone-related adverse events. However, a prospective randomized controlled trial with a larger study population is warranted in order to gain more insight into the proper dosage of prednisolone for OMG.

Antineutrophil Cytoplasmic Antibodies Negative Microscopic Polyangiitis With Initial Pulmonary Manifestation

Microscopic polyangiitis (MPA) is a small vessel vasculitides mostly associated with anti-neutrophil cytoplasmic antibodies (ANCA). The kidney is the most commonly affected organ in MPA. We report the case of a 9-year-old girl with ANCA-negative MPA who initially presented with respiratory symptoms, including cough, sputum, and dyspnea. Based on her symptoms, atypical pneumonia was suspected. Also, childhood interstitial lung disease was considered based on findings seen on chest CT. Despite initial improvement of symptoms with oral corticosteroid therapy, dyspnea with initiation of corticosteroid tapering was noted. A final diagnosis of MPA was made after lung biopsy. ANCA was negative in both the initial and repeat blood tests. Oral cyclophosphamide and prednisolone treatments led to full remission. Since then, the patient has been treated with low dose prednisolone and azathioprine for maintenance. A good treatment response was achieved and her clinical symptoms, pulmonary functions, and radiologic findings have since improved. Thus, early and precise diagnosis of MPA is crucial for remission induction and prevention of symptom relapse. (J Rheum Dis 2020;27:203-208)

COVID‐19 in bone marrow transplant recipients: reflecting on a single centre experience

Covid-19 disease is caused by a novel SARS-CoV-2 virus and has been declared a pandemic on the 9th of March by WHO. Hallmark of COVID-19 management is supportive care and there is still no convincing evidence on a treatment which will reduce mortality. Severe COVID-19 associated sepsis characterized by acute respiratory distress syndrome (ARDS), secondary bacterial pneumonias thrombotic complications, myocarditis, and gastrointestinal involvement are more prevalent in those with comorbidities such as hypertension, diabetes, cardiac disease, cancer and age>70 years (Liang et al; 2020, Guan et al; 2019).

P0289MULTI-PARAMETRIC RENAL MAGNETIC RESONANCE IMAGING IN EARLY KIDNEY TRANSPLANTATION

Abstract Background and Aims Existing methods of investigating renal transplant dysfunction do not provide reliable information regarding diagnosis nor prognosis. Multi-parametric magnetic resonance imaging (MRI) may provide novel biomarkers for evaluation of transplant dysfunction. We aim to determine how MRI parameters change over the first year of transplantation, and how these relate to future renal function. Method Patients receiving a kidney transplant attended for study visits at 6, 26 and 52 weeks post operatively, comprising measurement of clinical and biochemical parameters, together with research multi-parametric MRI. Imaging measurements comprised kidney volume, arterial spin labelling (ASL) perfusion, T1 relaxation time, T2*, apparent diffusion coefficient (ADC) and fractional anisotropy (FA). Imaging was performed at 3.0 Tesla using a Siemens MAGNETOM Prisma system. Regions of interest were drawn in whole kidney (WK), cortex (Cx) and medulla (Md) (figure 1). Results 20 patients were included: 16 were male, with age 55.5±12.8 years, baseline eGFR 54.0±23.6 ml/min/1.73m2, and blood pressure 146/80 ± 15/15 mmHg. 14 received deceased, and 6 received live, donor transplants. Patients were all managed with tacrolimus, mycophenolate and low dose prednisolone, following induction therapy with either basiliximab or anti-thymocyte globulin. 6 week ADC was 1.69±0.14 in WK, 1.65±0.08 in Cx, and 1.67±0.10 ×10-3 mm2/s in Md. FA was 0.19±0.04 in WK, 0.14 ± 0.04 in Cx and 0.22 ± 0.10 in Md. T2* was 57.6±9.4 in WK, 63.9±8.7 in Cx and 45.0±8.0 ms in Md. Over the 3 visits there was reduction in FA (p=0.008) and medullary T2* (p&amp;lt;0.001). There was no significant change over 12 months in any other MRI parameter. Over 1 year the median change in eGFR was -2ml/min/1.73m2. There was correlation between baseline eGFR and the following variables: volume (r=0.29, p=0.04), whole kidney ADC (r=0.36, p=0.01), cortical ADC (r=0.46, p=0.001), representative cortex ADC (r=0.48, p&amp;lt;0.001) and medullary ADC (r=0.29, p=0.04). There was no correlation between eGFR and other imaging biomarkers. There was correlation between baseline whole kidney ADC (r=0.54, p=0.02), cortical ADC (r=0.49, p=0.03), and renal function at 12 months. Conclusion Diffusion weighted MRI measurements correlate with eGFR and may allow improved prognostication regarding future renal function. Certain MRI parameters including FA and R2* vary depending on time point of transplantation which may reflect changes in transplant microstructure in the early postoperative period. Multi-parametric MRI provides a novel method of evaluating renal transplants non-invasively and may allow more accurate prediction of future transplant function than existing biochemical measures.

P0402TACROLIMUS PLUS LOW DOSE PREDNISOLONE THERAPY IS MORE EFFECTIVE IN PLA2R -VE MEMBRANOUS NEPHROPATHY PATIENTS

Abstract Background and Aims Idiopathic Membranous Nephropathy (IMN); an autoimmune concomitant nephrotic syndrome of the adult is mainly associated with PLA2R antibody expressed on podocytes. The lack of exact mechanisms involved in the pathogenesis of IMN is transmitted to its therapeutic management. There is no standard therapy for patients with frequent relapsing or steroid-dependent IMN. We propose the efficacy of low dose Tacrolimus (Tac) plus prednisolone and associated changes in anti-PLA2R in adult IMN. Method Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients; 15 diabetic; 7 lupus; 1HBV and 1 ankylosing spondylitis patients were excluded. Finally; 77 Patients were followed and evaluated for the anti-PLA2R level at baseline; 3M; 6M; 12M and end of follow-up (17-61 ; median 38 months). CR; PR; relapse; and side-effects were recorded.Of the 77 patients; at 3M 60(77.92%; CR-37; PR-23); at 6M 61(79.22%; CR-53; PR-8); at 12M 53(68.86%; CR-47; PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up; out of 54 responsive patients 37(68.51%; CR-36; PR-1) remained in remission and 17(31.48%) patients relapsed. Results Out of 77 patients; 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M; (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively. There were significant correlations between PLA2R level and 24h proteinuria at baseline; 3M and at 6M. During therapy 4 patients develop cutaneous tenia; 1 osteonecrosis of the femur head; 1 corpus tunnel syndrome; 4 onset diabetes; 3 tremor; and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac; and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note; 4 females had pregnancy and successful delivery in our cohort of patients. Conclusion PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.

Management of immune checkpoint inhibitor–induced bullous pemphigoid

Management of immune checkpoint inhibitor–induced bullous pemphigoid

Pneumocystis jiroveci pneumonia in rheumatoid arthritis patient treated with methotrexate but without prednisolone: A case report

Abstract Background/Purpose Methotrexate (MTX) is an anchor drug for rheumatoid arthritis (RA) if there is no contraindication. However, MTX can increase the risk of opportunistic infections including Pneumocystis jiroveci pneumonia (PCP) if combined with other immunosuppressive drugs such as prednisolone. Herein, we report a case of an RA patient who developed PCP during MTX treatment without prednisolone. Methods A 63-year-old woman with RA was admitted with high fever and shortness of breath. She had demonstrated stable RA activity after taking MTX 12.5 mg/week in addition to leflunomide 10mg daily for RA; however, about five months ago, she stopped taking low dose prednisolone. Computerized tomography (CT) of the chest demonstrated diffuse ground glass opacities in bilateral middle and lower lung fields. Laboratory examinations showed β-D-glucagon 140.2 pg/ml. A polymerase chain reaction (PCR) assay of bronchoalveolar lavage (BAL) fluid showed Pneumocystis carinii (PC). MTX and leflunomide were immediately discontinued. High dose trimethoprim/sulfamethoxazole (TMP-SMX) and methylprednisolone pulse therapy were administered. Following treatment, clinical and radiographic improvement were noted. Results The risk factors for RA-PCP have been reported by several studies. However, in this case, the patient had not taken prednisolone for more than five months before the occurrence of PCP and was considered low risk for PCP. In the RA patient, with or without risk factors, PCP should be considered in the differential diagnosis for respiratory infection and interstitial pneumonitis, including MTX-induced pneumonitis. Conclusion In the RA patient, MTX should be considered an important risk factor of PCP.

Type B insulin resistance syndrome in a patient with type 1 diabetes.

SummaryType B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. Described here is a patient who within a few months after the onset of autoimmune type 1 diabetes increased her insulin requirements more than 20-fold; despite this she had considerable difficulty maintaining a plasma glucose value of <40–60 mmol/L (720–1100 mg/dL). On suspicion of TBIRS, the patient was started on tapering dose of glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect. Within days, insulin requirements decreased by 80–90% and plasma glucose stabilized around 7–8 mmol/L (126–144 mg/dL). The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses and immune column treatments with temporarily remarkable effect. Mixed and transient results were seen with rituximab, mycophenolic acid and bortezomib, but the glycemic status remained suboptimal. Lack of compliance and recurrent infections may have contributed to this.Learning points:Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with acquired polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia.We describe here a young patient in whom, a few months after the onset of a regular autoimmune diabetes, insulin requirements in a short time increased more than 20-fold, but despite this, the plasma glucose level could be kept at <40–60 mmol/L only with considerable difficulty. Did this patient have TBIRS?On suspicion of TBIRS, the patient was started on tapering glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect; within days insulin requirements decreased by 80–90% and plasma glucose stabilized around 7–8 mmol/L.The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays.After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses with temporarily remarkable effect.TBIRS should be considered in diabetic patients whose glycemia and/or insulin requirements are inexplicably and dramatically increased.

P188 Tocilizumab for giant cell arteritis: real world experience in a single UK centre

Abstract Background Tocilizumab was approved for the treatment of giant cell arteritis (GCA) by NICE in April 2018. This decision followed the GiACTA (Giant Cell Arteritis Actemra) study, a randomised control trial that demonstrated a beneficial effect of tocilizumab in reducing the frequency of disease flare and overall prednisolone requirements. However, as noted in the NICE appraisal, the extent to which the patient population in the GiACTA study reflects the population it is eventually used for in UK clinical practice is not clear. To address this, we analysed the records of all patients started on tocilizumab treatment for GCA in a single centre since its approval. Methods We performed a retrospective analysis of the clinical records of all patients started on tocilizumab for GCA at the Freeman Hospital in Newcastle. All patients are discussed in a regional connective tissue disease MDT prior to the initiation of therapy to ensure they fulfil NICE guidelines. At each subsequent visit adverse events related to both tocilizumab and corticosteroids and any flares of GCA or ischaemic events are recorded. Results In total 14 patients started tocilizumab since June 2018, with a cumulative exposure of 8 patient-years. The mean age was 74 years, slightly older than the average age in the GiACTA trial (69 years). In contrast to GiACTA where 48% of patients were newly diagnosed, all our patients had established disease. In our cohort 36% of patients had CT PET evidence of large vessel vasculitis, similar to the rate in GiACTA (40%) but higher than the national average of around 5%. Incidence of visual loss in our treated patients was higher at 29% than recorded in the general GCA population in the DC-VAS study (7.9%). In those treated for relapsing disease around half (56%) had recorded previous significant adverse events with steroids, including heart failure, hypertension and mood changes. Five patients had infections requiring antibiotics (cellulitis/ulcer in three, chest infection in one, urinary tract infections in two), with two serious infections requiring hospital admission (both urinary tract infections). No patients had further ischaemic events while on treatment. All patients were on a lower dose of prednisolone following treatment with an average of a 63% reduction in steroid dose. Conclusion The modest number of patients receiving tocilizumab for GCA suggests we are not treating everyone at first relapse. The higher rates of large vessel vasculitis, visual loss and previous steroid-induced complications suggest a preference for saving tocilizumab for a more severely affected subset of patients. In this preliminary data there were reassuringly no recorded ischaemic events following treatment and steroid doses were successfully reduced in all patients. Disclosures G. Reynolds None. B. Griffiths None. K. Houghton None. B. Thompson None. A.R. Lorenzi None. J. Heaney None.

Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence.

BackgroundCancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19.MethodsUsing Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig.Results89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19.ConclusionThe COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

Management of HAM/TSP: Systematic Review and Consensus-based Recommendations 2019.

Purpose of ReviewTo provide an evidence-based approach to the use of therapies that are prescribed to improve the natural history of HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP)—a rare disease.Recent FindingsAll 41 articles on the clinical outcome of disease-modifying therapy for HAM/TSP were included in a systematic review by members of the International Retrovirology Association; we report here the consensus assessment and recommendations. The quality of available evidence is low, based for the most part on observational studies, with only 1 double-masked placebo-controlled randomized trial.SummaryThere is evidence to support the use of both high-dose pulsed methyl prednisolone for induction and low-dose (5 mg) oral prednisolone as maintenance therapy for progressive disease. There is no evidence to support the use of antiretroviral therapy. There is insufficient evidence to support the use of interferon-α as a first-line therapy.

Membranoproliferative glomerulonephritis related to a streptococcal infection in a girl with IgA deficiency: a case report

BackgroundIgA deficiency associated with glomerulonephritis is rare. In particular, there is no prior report regarding the association between IgA deficiency and membranoproliferative glomerulonephritis (MPGN) in children. Herein, we describe the case of a 5-year-old girl with selective IgA deficiency and MPGN.Case presentationThe patient presented with persisting urinary abnormality and hypocomplementemia following a group A treptococcal infection. Renal biopsy revealed the presence of diffuse mesangial hypercellularity, endocapillary proliferation, and focal thickening of the walls of the glomerular capillaries using light microscopy, with IgG and moderate C3 deposits observed using immunofluorescence. Electron microscopy images revealed nodular deposits in the subendothelial areas, with hump-shaped subepithelial deposits. The pathological diagnosis was confirmed as MPGN. Treatment using oral prednisolone (PSL), mizoribine (MZR), and angiotensin-converting enzyme inhibitors reduced the proteinuria. The PSL dose was gradually tapered, with the low dose of PSL and MZR continued for 4 years. Histological findings were improved on repeated renal biopsy, and PSL and MZR administration was discontinued.ConclusionsWe report a rare case of MPGN related to a streptococcal infection in a child. The clinical presentation included selective IgAD, with several pathological findings and a clinical course typical of glomerulopathy. The patient was successfully treated using multidrug therapy.

Dexamethasone and prednisolone treatment in beef cattle: influence on glycogen deposition and gene expression in the liver

The illegal administration of glucocorticoids in livestock is problematic and identification of pathways in which these hormones are involved is critically important, and new direct or indirect biomarkers should be identified. In this work, glucocorticoid transcriptional effects on some genes involved in the glucose metabolism were studied in the bovine liver. This study was conducted on adult Charolais male cattle treated with long-term low dose dexamethasone or prednisolone. Gene expression analysis was conducted in the liver by qPCR, and the geNorm algorithm was applied to select optimal reference genes. In line with the literature, a significant overexpression of genes involved in the gluconeogenic pathway and glycogen synthesis was detected in the liver of dexamethasone-treated animals, but histological and biochemical examination showed hepatocyte glycogen depletion particularly in dexamethasone-treated animals. It possible to hypothesize that glucocorticoids or adrenal insufficiency due to glucocorticoids withdrawal inhibit the enzymatic activity of glycogen synthase and/or induce glycogen autophagy in bovine liver. In fact, markers of glycophagy as starch-binding domain-containing protein 1 and γ-aminobutyric acid receptor-associated protein-like 1 mRNAs were upregulated in the liver by glucocorticoids treatment. Furthermore, glycogen synthase kinase-3 beta gene was significantly overexpressed in dexamethasone-treated animals, and this protein is also implicated in liver autophagy modulation and glycogen synthesis inhibition. These results showed that glucocorticoids likley have dual roles in hepatic glycogen metabolism of cattle, and investigation of these pathways could help find treatment biomarkers.