BackgroundWe previously described an endogamous Pakistani kindred in whom we identified a novel homozygous missense mutation in the PRKCD gene encoding for protein kinase C δ (PKCδ) as a cause of monogenic systemic lupus erythematosus (SLE). PKCδ has a role in the negative regulation of B cells. Given the nature of the disease, a logical targeted therapeutic approach in these patients is B cell depletion. Indeed, the 3 siblings all had a marked clinical response and resolution of symptoms with rituximab, although 2 of the siblings had severe reactions to rituximab thus precluding further treatment with this. We therefore describe the first successful use of ofatumumab for this rare form of monogenic SLE.Case presentationAll three affected siblings presented with SLE before the age of 3-years with lethargy, intermittent fever, thrombocytopenia, cutaneous involvement, alopecia, and hepatosplenomegaly. Tubulointerstitial nephritis was also present in 1 of the siblings. Homozygosity mapping followed by whole exome sequencing identified a homozygous missense mutation in PRKCD (p.Gly432Trp), subsequently confirmed by Sanger sequencing to be present in all 3 siblings. All 3 patients were initially treated with rituximab, however 2 of the siblings developed severe infusion-related reactions. For subsequent disease flare in these individuals we therefore used an alternative B cell depleting agent, ofatumumab (300 mg/1.73m2 on day 1; 700 mg/1.73m2 on day 15). This resulted in marked clinical improvement in both patients. To the best of our knowledge, this is the first report describing the successful use of ofatumumab for PKCδ deficiency.ConclusionsPKCδ deficiency causes a monogenic form of SLE which responds well to B cell depletion. Ofatumumab is also likely to have a therapeutic role for sporadic juvenile SLE (jSLE) patients intolerant of rituximab.
Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) can be associated with inflammatory arthritis, which is underdiagnosed by clinical examination. This study aimed to compare for the first time the ultrasound (US)-detected joint abnormalities in these two diseases, and to define the role of US in patients' management. A cross-sectional, observational study was conducted in patients with SLE (n=18) and SS (n=23) and symptoms of hand joint pain and no previous diagnosis of arthritis. Data related to disease activity, duration, damage scores, inflammatory and serological markers, treatment, and clinical and ultrasound parameters (derived from the assessment of 902 joints) were analysed and correlated using descriptive statistics, correlation tests and regression models. Subclinical synovitis/tenosynovitis was found in 44.4% SLE patients and 21.7% SS patients (p=0.23). There was no significant correlation between either the total Power Doppler (PD) score or the total Grey Scale (GS) score and disease activity scores (British Isles Lupus Assessment Group BILAG index and European League Against Rheumatism Sjögren's syndrome disease activity ESSDAI index). Both damage scores (Systemic Lupus International Collaborating Clinics index-SLICC and Sjögren's syndrome disease damage index-SSDDI) correlated with the GS synovitis score. A significant proportion of patients with SLE and SS had erosions (55.6% and 34.8%, respectively, p=0.184) and osteophytes (61.1 vs. 60.9, p=0.98) in at least one joint. Lack of correlation between disease activity scores and US outcome measures showed their limitations in diagnosing subclinical synovitis in SLE and SS patients. Future research is needed to establish if the development of erosions could be prevented by early diagnosis and prompt treatment of inflammatory arthritis associated with SLE and SS.
Anaphylaxis is an important emergency which forms part of the adult Advanced Life Support guidelines. The guidelines for anaphylaxis have recently undergone a change in the 2021 revision, with steroids and antihistamine no longer advised for acute anaphylaxis and an adrenaline infusion included as part of the new refractory anaphylaxis algorithm [1]. Scenarios for the medical trainees run at our simulation centre identified a lack of awareness of the revised anaphylaxis guidelines among learners. A QIP was completed to improve the level of learners’ awareness and confidence of the revised anaphylaxis guidelines in conjunction with the simulation team. Online surveys were sent out to the medical registrars and internal medicine trainees regarding the revised anaphylaxis guidelines. This was followed by an email sent two weeks later with the revised guidelines highlighting key changes. The same group were subsequently re-surveyed two weeks following the intervention to identify changes in clinical practice. Concurrently, scenarios based on the revised anaphylaxis guidelines were run for the medical trainees with specific emphasis on whether trainees were aware of the need for an adrenaline infusion (managed in a specialist setting) if symptoms were ongoing despite two IM doses of adrenaline. In the post-simulation debriefing, discussion was focused on the change in the anaphylaxis guidelines. In the first cycle, 100% of 23 respondents felt confident managing anaphylaxis but only 50% of respondents were aware (and were confident) that the guidelines had been revised. 2/3 of respondents had not managed a case of anaphylaxis in the last 12 months. In the second cycle, 100% of 4 respondents were aware of the revised guidelines but only 75% of respondents were confident in following the guidelines. 75% of respondents had not managed a case of anaphylaxis in the last 12 months. The significant drop in number of responders is likely to be multifactorial but may reflect a change in focus of educational needs due to the ongoing COVID-19 pandemic leading to a change in the educational landscape. A survey done on the attitude of medical students during the COVID-19 pandemic towards online learning found that only 54.1% of respondents felt that interactive discussion could occur through e-learning [2]. Following the QI results, the cardiac arrest trolleys were checked and the emergency box with adrenaline now includes the revised anaphylaxis algorithm but not hydrocortisone and chlorphenamine. Refractory anaphylaxis is now a standard scenario for the medical trainees in our simulation centre. 1. Resuscitation Council UK. Emergency treatment of anaphylaxis: Guidelines for healthcare providers. 2021. 2. Alsoufi A, Alsuyihili A, Msherghi A, Elhadi A, Atiyah H, Ashini A, Ashwieb A, Ghula M, Ben Hasan H, Abudabuos S, Alameen H, Abokhdhir T, Anaiba M, Nagib T, Shuwayyah A, Benothman R, Arrefae G, Alkhwayildi A, Alhadi A, Zaid A, Elhadi M. Impact of the COVID-19 pandemic on medical education: Medical students’ knowledge, attitudes, and practices regarding electronic learning. PLoS One. 2020;15(11):e0242905.
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Purpose To study the use in real life clinical practise of glucocorticoids (GCs), immunosuppressive and adjuvant therapy in Class III-IV Lupus Nephritis (LN). Methods A multiple choice electronic questionnaire was sent to Latin American rheumatologists. Ten questions addressing the following topics: use of methylprednisolone pulses at the beginning of treatment and additionally during induction, use of oral GCs (maximum dose, tapering schedules, time on prednisone doses>30 mg/day, time until a prednisone dose of 5 mg/day is reached); use of immunosuppressants during induction and maintenance therapies; and use of adjuvant therapies.
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