Treatment of discoid lupus with lenalidomide and anifrolumab: Case report and review of the literature.

Discoid lupus erythematosus (DLE) is a devastating autoimmune disease with few therapies available. For patients with little to no symptom improvement with initial treatment, the literature surrounding further treatment options and their efficacy remains limited. Here we report a 46-year-old patient with lupus and refractory DLE, who failed numerous medications since her initial diagnosis in 2014. She had a robust response to lenalidomide with further improvement after adding anifrolumab (ANI), in conjunction with the standard of care hydroxychloroquine. Furthermore, she was able to taper off steroids without interval flares. The patient has not experienced any major infections since the initiation of treatment. No previous case reports describing outcomes of lenalidomide and ANI have been reported, yet the combinational approach has potential. Future clinical trials are needed to investigate the safety of the combination of lenalidomide and ANI in lupus patients with refractory DLE.

COVID vaccine-induced lupus nephritis: Case report and review of the literature.

Vaccines offer an effective strategy to prevent infectious diseases with minimal adverse effects. On rare occasions, vaccination can disrupt the immune response leading to induction of autoimmune diseases. We describe a case of new-onset lupus nephritis following COVID-19 vaccination with the first dose of the Pfizer vaccine. Her symptoms and lab values improved with steroids, hydroxychloroquine, and mycophenolate mofetil.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Stress, mindfulness, and systemic lupus erythematosus: An overview and directions for future research.

Although the pathogenesis of autoimmunity is not fully understood, it is thought to involve genetic, hormonal, immunologic, and environmental factors. Stress has been evaluated as a potential trigger for autoimmunity and disease flares in patients with systemic lupus erythematosus (SLE). The physiologic changes that occur with stress involve numerous catecholamines, hormones, and cytokines that communicate intricately with the immune system. There is some evidence that these systems may be dysregulated in patients with autoimmune disease. Mindfulness-based techniques are practices aimed at mitigating stress response and have been shown to improve quality of life in general population. This review will discuss pathophysiology of chronic stress as it relates to SLE, evidence behind mindfulness-based practices in these patients, and directions for future research.

Factors mediating cancer risk in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are at an elevated risk for certain cancers compared to the population at large. Cancers seen at higher rates in the SLE population include hematologic malignancies, such as non-Hodgkin lymphoma, and cancers of the lung and thyroid. SLE patients also have a decreased risk for certain malignancies, such as breast cancer, melanoma, and prostate cancer. We review the literature on risk factors for malignancy in patients with SLE and discuss the exogenous and innate factors that are thought to contribute to the unique pattern of cancer risk observed in this patient population. These risk factors are important for providers of SLE patients to understand in order to maintain high clinical suspicion and detect malignancy as soon as possible. Further research is needed to determine the most effective guidelines on counseling patients on cancer screening and prevention.

New-onset lupus nephritis associated with COVID-19 infection.

A dysregulated immune response plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Environmental factors such as viruses, including coronavirus 2 (COVID-19), have been described to play a role in SLE presentation and exacerbation. These viruses trigger a host's humoral and cellular immunities typically essential in elimination of the viral infection. We present a case of a Hispanic male who developed new-onset lupus nephritis class II after a COVID-19 infection.

Systemic Lupus Erythematosus and Common Variable Immunodeficiency.

ABSTRACT: Systemic lupus erythematosus (SLE) and common variable immunodeficiency (CVID) are both conditions defined by immune system dysfunction: one hyperactive, the other hypoactive. Although uncommon, these diseases can coexist in the same individual. This review aims to assess the state of the literature on the relationship between SLE and CVID, particularly when workup for CVID should be considered in individuals with SLE and how CVID in individuals with SLE should be treated.

The Effect of Mycophenolate Mofetil as First-Line Therapy on the Timing of Urine Protein-to-Creatinine Ratio Reduction in Immunosuppressant-Naive Patients With Lupus Nephritis at a Single Center.

BACKGROUND/OBJECTIVES: Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis (LN). The purpose of this study was to assess the effect of mycophenolate mofetil (MMF) on the timing of urine protein-to-creatinine ratio reaching 200 mg or less after starting MMF as initial therapy for class III, IV, or V in immunosuppressant-naive patients with LN. METHODS: Patients who had a diagnosis of biopsy-proven LN were included in this cohort study. The initial dose of MMF was 1000 mg twice daily. If no improvement, it was increased to 1500 mg twice daily after 1 month. For statistical analysis, exact binomial distribution 95% confidence intervals were calculated. RESULTS: Nine patients were identified. There were 3 patients with class III, 3 with class IV, 1 with class III to V, 1 with class II to V, and 1 with class V lupus nephritis. The majority were African Americans (70%). At baseline, proteinuria ranged between 0.41 and 4 g, and 88% had normal estimated glomerular filtration rate. Forty-four percent of patients reached 0.28 g of proteinuria within 8 weeks of starting MMF (95% confidence interval, 14%-79%), all of which maintained the same level of response and normal estimated glomerular filtration rate at 12 months. Thirty-three percent of patients achieved the American College of Rheumatology complete response at 8 weeks. CONCLUSIONS: This study demonstrates that only a minority of immunosuppressant-naive LN patients achieved the American College of Rheumatology complete response at 8 weeks after initiation of MMF. A rapid decline in the proteinuria to 0.28 g within the first 8 weeks of the treatment correlated strongly with achieving the same level of response at 12 months.

The Cancer Risk Profile of Systemic Lupus Erythematosus Patients.

ABSTRACT: Systemic lupus erythematosus (SLE) patients have a well-established increased risk for cancer. Research from the past 2 decades has identified the specific malignancies that afflict SLE patients at disproportionate rates. Systemic lupus erythematosus patients are at heightened risk for several hematologic malignancies as well as for certain solid tumors, including lung, thyroid, and hepatobiliary cancers. They are at decreased risk for several cancers as well, including prostate and melanoma. Improved understanding of the unique cancer risk profile of SLE patients has led some professional societies to recommend specialized cancer screening and prevention measures for these patients and has enabled clinicians to better serve the SLE patient population.

A prescription for exercise in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk, and fatigue is a major subjective complaint. Sedentary lifestyle has been shown to have negative health impacts in cardiovascular and rheumatic disease, though exercise has not traditionally been incorporated into routine therapy recommendations. Regular exercise in SLE may improve difficult to treat Type 2 symptoms, such as fatigue, depression, stress, and quality of life. Insufficient counseling on exercise by physicians is a notable barrier for SLE patients to engage in physical activity. Aerobic exercise regimens are more commonly studied, and have been shown to improve cardiovascular health in SLE. Exercise may improve some inflammatory markers, though does not definitively affect SLE clinical disease activity. Physical activity should be recommended to improve quality of life and cardiovascular health in patients with SLE. Developing clearer guidelines for exercise regimens in a patient-centered manner is warranted, especially given diverse phenotypes of SLE patients and varying degrees of physical limitations.

Treatment With Voclosporin and Anifrolumab in a Patient With Lupus Nephritis and Refractory Discoid Lupus Erythematosus: A Case Report and Literature Review.

Systemic lupus erythematosus (SLE) is a complex heterogeneous disease with multiple clinical manifestations. Recently, two medications, anifrolumab and voclosporin, have been approved for the treatment of adults with SLE and lupus nephritis (LN), respectively. We present the case of an elderly woman with LN and refractory discoid lupus erythematosus (DLE), who was treated successfully with a combination of voclosporin and anifrolumab without major infections.

Treatment Using Both Voclosporin and Belimumab in Four Patients With Lupus Nephritis.

Nearly 50% of patients with systemic lupus erythematosus (SLE) will develop lupus nephritis (LN). Current treatment regimens for LN are suboptimal as the majority of patients fail to achieve complete renal response after several months of treatment and there are high rates of relapse. We report outcomes in four LN patients who were treated with both voclosporin and belimumab. These patients had no serious infections, and we were able to taper glucocorticoids and reduce proteinuria.

Adalimumab-Induced Lupus Nephritis: Case Report and Review of the Literature.

Tumor necrosis factor-alpha inhibitors are known causative agents of systemic lupus erythemato- sus but have rarely been implicated in lupus nephritis. A patient with Crohn's disease on long-term adalimumab treatment presented with new-onset Raynaud's phenomenon and was found to have hematuria and proteinuria. Elevated antinuclear, anti-dsDNA, and MPO antibodies were found. A renal biopsy confirmed the diagnosis of lupus nephritis. Adalimumab was discontinued ensuing improvement in urine studies and resolution of dsDNA and MPO antibodies. Adalimumab can induce systemic lupus erythematosus and lupus nephritis.

RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES.

Background: People with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Objective: Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care. Design: Longitudinal registry study. Participants: 4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins. Measurements: Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. Results: A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption. Limitations: Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported. Conclusions: Exposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Anti-Smith Antibody Positivity Without Lupus in the Setting of Lung Cancer.

The interpretation of positive serologic findings in cancer sera remains controversial. Selected antinuclear antibodies (ANAs), such as anti-double-stranded deoxyribonucleic acid (dsDNA) and anti-Smith, are highly specific for the diagnosis of systemic lupus erythematosus (SLE). On the other hand, the ANA titer is sensitive but not specific for SLE and has been reported in healthy individuals, various infections, other autoimmune diseases and cancer. We report for the first time positive anti-Smith antibody in two patients without lupus in the setting of lung cancer.

Lupus intestinal pseudo-obstruction and hydronephrosis: Case report.

INTRODUCTION: Intestinal pseudo-obstruction (IPO) is a rare and life-threatening complication of lupus. PATIENT CONCERNS: A patient with long-standing lupus developed recurrent abdominal pain and distension as well as nausea and emesis. DIAGNOSIS: Imaging showed dilated small bowel loops with air-fluid levels and bowel wall thickening. She also had bilateral hydronephrosis. INTERVENTIONS: She was given high-doses of intravenous steroids and cyclophosphamide. OUTCOMES: Her symptoms resolved within a week of starting immunosuppression. She was eventually transitioned to mycophenolate mofetil. She remained in remission and immunosuppression was successfully stopped after 1 year. CONCLUSIONS: Intestinal pseudo-obstruction is a rare complication of lupus that is often seen in association with ureterohydronephrosis and interstitial cystitis. This clinical syndrome is thought to be because of smooth muscle dysmotility of the gastrointestinal and genitourinary tracts, although the exact mechanism of dysmotility remains unknown. This condition is often responsive to immunosuppression if recognized and treated promptly.

Hyperhomocysteinemia and Lupus Nephritis.

Background  In SLE, both disease-specific and traditional risk factors are important. Increased serum homocysteine levels are seen in approximately 15% of patients with systemic lupus erythematosus and are associated with an increased risk of atherothrombotic events in this population. The serum level of homocysteine in patients with lupus nephritis has not been well described. Methods We performed a retrospective review of patients who had both biopsy-proven lupus nephritis (class II-VI) and measured homocysteine levels during routine evaluation. Clinical and laboratory data were obtained from reviews of medical records. Results Of the 15 patients with lupus nephritis, 10 had elevated homocysteine levels. The ages ranged from 21-68 years and were predominately African-American females. There were three patients with class III, one with class III-V, two with class IV, and two with class V lupus nephritis. Two patients had more than one biopsy each, one with class III, IV-V, and one with III and IV. At the time, when the serum homocysteine level was measured, of the 10 patients with elevated homocysteine levels, five patients had positive anti-dsDNA, and four had hypocomplementemia predominately low C3 (three patients). All patients were on hydroxychloroquine. Conclusions  This study demonstrates that patients with lupus nephritis are at a higher risk (66.6%) for developing elevated homocysteine levels.

Pericarditis in Lupus.

Pericarditis is a common cardiac manifestation in systemic lupus erythematosus (SLE). Serositis is recognized in the ACR, SLICC, and EULAR/ACR classification criteria. We reviewed the prior research regarding the epidemiology, risk factors, presentation, and treatment of pericarditis in SLE.

Clinical Characteristics of Hydralazine-induced Lupus.

Introduction The use of hydralazine has been associated with the development of lupus erythematosus and lupus-like syndromes. We performed this retrospective study to identify clinical characteristics of individuals who developed hydralazine-induced lupus. Material and methods We performed a single-center retrospective review of seven individuals who had a diagnosis of hydralazine-induced lupus by International Classification of Diseases, Ninth Revision (ICD9) code and were on hydralazine prior to their diagnosis. Clinical and laboratory data were obtained from a review of the medical record up to 12-month follow-up. Results Of the seven individuals with hydralazine-induced lupus, five were Caucasian (71%) and two were African-American. The mean age at the time of diagnosis was 62 years. Four (57%) were male. The majority of individuals were exposed to hydralazine for more than 12 months (83%). Four individuals had biopsy-proven lupus nephritis and four individuals had cardiopulmonary and skin involvement. Six patients were positive for antinuclear antibody (ANA) with a homogenous pattern, and five of those were positive for anti-histone antibody. Additionally, positive anti-double-stranded DNA (anti-dsDNA) antibody, anti-cardiolipin antibodies, low complements, positive lupus anticoagulant, and leukopenia were seen in 42% of our cohort. Of the five individuals in whom anti-myeloperoxidase (MPO) antibody was strongly positive, all had renal involvement defined by an elevated creatinine with three having biopsy-proven lupus nephritis. Three other individuals with MPO positivity had concurrent cardiopulmonary and skin involvement. Four individuals were positive for anti-proteinase 3 (PR3) antibody, three of whom were strongly positive with renal involvement defined by an elevated creatinine with two having biopsy-proven lupus nephritis. The level of anti-dsDNA antibody and anti-PR3 antibody normalized at three months while anti-MPO antibody took 12 months to normalize following cessation of hydralazine. When checked, low complement component 3 (C3) and anti-histone antibody persisted past 12 months. In addition to the withdrawal of hydralazine, six individuals were treated with hydroxychloroquine and five with mycophenolate mofetil. Three of four individuals with renal involvement received plasmapheresis and two received cyclophosphamide and hemodialysis. Conclusion Hydralazine can aggravate and unmask incipient lupus. Since the presentation can be varied, early recognition of symptoms is critical. Precautions should be taken before initiating this medication in individuals with certain risk factors. Once diagnosed, potential serological findings such as a positive anti-MPO/anti-PR3 antibody could predict more severe manifestations such as pulmonary-renal complications.

Spontaneous pneumomediastinum in limited cutaneous systemic sclerosis and myositis overlap.

A 58-year-old man with limited cutaneous systemic sclerosis and myositis overlap complicated by interstitial lung disease presented with several months of progressive dyspnoea and weakness. CT chest revealed extensive pneumomediastinum that was not present on imaging 6 months before this study and appeared to be spontaneous, with no preceding trauma, infection or invasive procedures.