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.

Patient-reported outcomes in RA care improve patient communication, decision-making, satisfaction and confidence: qualitative results.

OBJECTIVE: To evaluate the impact of integrating patient-reported outcomes (PROs) into routine clinics, from the perspective of patients with RA, clinicians and other staff. METHODS: We conducted a prospective cohort study using a mixed methods sequential explanatory design at an academic arthritis clinic. RA patients completed selected Patient-Reported Outcomes Measurement Information System measures on tablets in the waiting room. Results were immediately available to discuss during the visit. Post-visit surveys with patients and physicians evaluated topics discussed and their impact on decision making; patients rated confidence in treatment. Focus groups or interviews with patients, treating rheumatologists and clinic staff were conducted to understand perspectives and experiences. RESULTS: Some 196 patients and 20 rheumatologists completed post-visit surveys at 816 and 806 visits, respectively. Focus groups were conducted with 24 patients, 10 rheumatologists and 4 research/clinic staff. PROs influenced medical decision-making and RA treatment changes (38 and 18% of visits, respectively). Patients reported very high satisfaction and treatment confidence. Impact on clinical workflow was minimal after a period of initial adjustment. PROs were valued by patients and physicians, and provided new insight into how patients felt and functioned over time. Reviewing results together improved communication, and facilitated patient-centred care, shared decision making, and the identification of new symptoms and contributing psychosocial/behavioural factors. CONCLUSION: PRO use at RA visits was feasible, increased understanding of how disease affects how patients feel and function, facilitated shared decision-making, and was associated with high patient satisfaction and treatment confidence.

Sequential Therapy for Remission Induction in Severe Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis.

BACKGROUND: The introduction of combination therapy with glucocorticoids (GC) and cyclophosphamide (CYC) or rituximab (RTX) has resulted in remission rates exceeding 90% in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, early treatment-related mortality remains a major concern and has driven the search for safer induction regimens exploring minimization or avoidance of GC and CYC. Most trials have excluded patients with severe renal disease. We report the outcomes of AAV patients with severe renal disease treated with sequential therapy (ST) starting with (GC) and oral (CYC) followed by transition to (RTX). METHODS: Patients with new or relapsing severe AAV who presented with severe renal disease and/or rapidly progressive glomerulonephritis (RPGN) were identified. RPGN was defined as at least a 20% decrease in estimated glomerular filtration rate (eGFR) over a 2-week period along with hematuria and proteinuria. Induction treatment included pulse (GC) for 3 days followed by oral prednisone tapered to 5 mg by month 6, oral (CYC) adjusted for GFR until improvement in Birmingham Vasculitis Activity Score (BVAS), and serum creatinine at which point (CYC) was stopped and induction dose of (RTX) was given. Use of plasmapheresis (PLEX) was allowed. The primary outcome was complete remission defined as BVAS of zero by 6 months. Descriptive data are presented as median with range and mean with SD. RESULTS: Nine patients met the inclusion criteria. Median age at diagnosis was 63 years. The majority were females, myeloperoxidase ANCA positive, and had a new diagnosis. The mean nadir (SD) eGFR was 12 (5) with 3 requiring dialysis. The median BVAS at the time of diagnosis was 15. All patients received ST and 3 received PLEX. The median exposure to oral CYC was 35 days. The mean (SD) eGFR and median BVAS were 26 (12) and 3, respectively, at the time of switching to RTX. The median prednisone dose at 6M was 5 mg. The median follow-up was 44 months. All patients achieved remission. One patient with relapsing disease reached ESRD. The mean (SD) eGFR in the remaining 8 patients at last FU was 37 (27), and the mean (SD) eGFR rise at 1 year was 26 (25). Adverse events included 2 patients with pneumonia and 3 with bone marrow suppression. There were no deaths. CONCLUSION: ST with GC and CYC followed by RTX is effective for in AAV patients with severe renal disease. Therapy-related adverse events are comparable to other studies, and further modification in ST with decrease in GC dosage should be explored.

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.

Correction to: Uncommon presentations in ANCA vasculitis: clinical characteristics and outcomes.

The family name of the co-author of the article mentioned above was incorrectly spelled. The correct name should have been "Veena S. Katikineni"instead of "Veena Katikeneni". The original article has been corrected.

Uncommon presentations in ANCA vasculitis: clinical characteristics and outcomes.

ANCA-associated vasculitis (AAV) can present in an atypical manner and obscure the clinical picture. We sought to characterize clinical characteristics and outcomes in these uncommon presentations. We conducted a retrospective study of 171 AAV patients in our vasculitis database to identify patients with atypical presentation of AAV. Patient demographics, serologies, renal indices, and treatment regimens were assessed. Of the 171 patients, eight were identified to have uncommon presentations. These patients were usually extremes of age with three being less than 30 years and four being more than 70 years. Six patients were positive for PR3 antibodies. The mean delay in diagnosis from time of symptom development was 12 months. All patients developed acute kidney injury during their clinical course. Pancreatitis was the most frequent atypical presentation (n = 3), with pulmonary pathologies (cystic lung disease and usual interstitial pneumonia) and splenic infarcts being present in two patients each. The diagnosis of AAV was established by positive ANCA serology and renal or lung biopsy evidence of vasculitis. Six patients received induction therapy with steroids and rituximab, while two received steroids and cyclophosphamide. One patient died of respiratory failure in the first month following diagnosis while the remaining patients achieved disease remission. One patient developed end-stage renal disease. Uncommon presentations of AAV afflict extremes of age with a PR3 ANCA predominance and are associated with subsequent development of AKI. This case series demonstrates that a significant delay in diagnosis can be associated with these presentations. KEY POINTS: • Uncommon manifestations of AAV are seen more often with PR3 ANCA disease and respond to standard induction therapy of AAV. • High index of suspicion is required to avoid delays in diagnosis.

Subcutaneous Immunoglobulin for Antibody Deficiency in Antineutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis.

Objectives Intravenous immunoglobulin G (IVIG) is used to treat antineutrophil cytoplasmic antibody (ANCA) patients with recurrent infections as a result of hypogammaglobulinemia (HG) induced by treatment regimens. We sought to characterize clinical features, treatment, and outcomes for patients treated with the novel subcutaneous IgG (SCIG) for the aforementioned purpose.  Methods We conducted a retrospective study of 136 patients in our ANCA database to identify patients with recurrent infections and HG subsequently treated with SCIG. Patient demographics, serologies, treatment, and immunological parameters were assessed.  Results Of 136 patients, four were treated with SCIG. All were Caucasian, proteinase-3 (PR3)-positive, and the majority (n = 3) were females. All patients had pulmonary involvement, and regimens of cyclophosphamide (CYC) and/or rituximab (RTX) were employed for induction and remission. Three patients each experienced recurrent bouts of respiratory tract infections and shingles. Ig levels (G, M, and A) were reduced in all patients, except for one patient who had normal IgA levels. CD19/20 cells were depleted and CD3/4/8/NK cells were preserved in all patients. Three patients had no discernible antibody response to the pneumococcal vaccine (specific pneumococcal serotypes measured pre- and post-vaccine). The mean duration elapsed between the first rituximab administration and commencement of SCIG was 7.2 years. The IgG level normalized and none of the patients had a recurrence of infection since the initiation of SCIG.  Conclusion This data, albeit preliminary, is the first series that demonstrates SCIG can be a reliable alternative to IVIG in ANCA patients with recurrent infections secondary to HG. Early identification of this subset of patients is likely to mitigate infectious risks, associated morbidity, and hospitalization.

Pauci-immune Glomerulonephritis in Systemic Lupus Erythematosus (SLE).

Glomerulonephritis (GN) in lupus is generally an immune complex glomerulonephritis from the deposition of immunoglobulin and complements. Pauci-immune GN is the most common cause of rapidly progressive GN and is frequently associated with an anti-nuclear cytoplasmic antibody (ANCA). We report a patient with a history of systemic lupus erythematosus who presented with worsening proteinuria and was subsequently diagnosed with pauci-immune GN on renal biopsy, in the absence of ANCA.

Ranolazine-induced Elevation of Creatinine Kinase in the Absence of Statin Usage.

Ranolazine received Food and Drug Administration (FDA) approval in 2006 for the treatment of chronic angina. Ranolazine has previously been linked to the development of statin-induced myopathy, because it also inhibits CYP3A4, which increases serum statin levels. In the absence of concomitant statin therapy, elevated creatinine kinase (CK) and myalgias on ranolazine monotherapy has never been reported.

Cerebral Venous Thrombosis Mimicking a Discrete Brain Mass: A Case Report and Literature Review.

The differential diagnosis for a focal brain lesion in a patient with systemic lupus erythematosus (SLE) is broad and includes infection, malignancy, and vascular and inflammatory etiologies. One rarely considered vascular pathology is cerebral venous thrombosis (CVT), which is often associated with a delay in diagnosis because of variable presentation and rare incidence. We present the case of a young woman with a new discrete brain lesion that appeared in the context of highly active SLE and was ultimately diagnosed with a CVT. We provide a literature review for diagnosis and management of cerebral venous thrombosis, a potentially serious complication of untreated systemic lupus erythematosus.

Long-term Clinical Course of Antineutrophil Cytoplasmic Antibody-associated Vasculitis Patients off Maintenance Therapy.

Objectives The optimal duration of maintenance immunosuppressive therapy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is still controversial. The aim of our study is to describe the characteristics and outcomes of patients with AAV who were able to stop maintenance agents completely while remaining on daily prednisone (< 5 mg) for at least 36 months. Materials and methods AAV patients treated at our center from 2000 to 2016 and who were not on maintenance agents while remaining on prednisone < 5 mg daily for at least 36 months were identified by the providers, and their records were retrospectively reviewed. Relapse was defined by the reinitiation of immunosuppressive therapy for biopsy-proven glomerulonephritis or any extra-renal organ involvement. Results Of the 18 patients who fulfilled the study inclusion criteria, 12 were male and 14 were Caucasian. The mean age at AAV diagnosis was 54 years. Seventeen patients had renal involvement and seven had lung involvement. Eleven patients received cyclophosphamide and eight patients received rituximab along with glucocorticoids for remission induction. Twelve patients were weaned completely off prednisone. The median duration of prednisone use was 20 months. Nine patients received maintenance therapy with azathioprine or mycophenolate mofetil. The median duration of maintenance therapy was 24 months. The mean follow-up time after stopping the maintenance agent was 64 months. During this period, three patients had disease relapse. Conclusions Stopping maintenance agents for > 36 months can be achieved in some patients with AAV. Prospective, randomized controlled trials are needed to confirm this finding.

Correction: Fevers in Adult Lupus Patients.

[This corrects the article DOI: 10.7759/cureus.2098.].

Mycophenolate Mofetil in a Lupus Patient with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening complication of several, different connective tissue diseases, including systemic lupus erythematous (SLE), systemic sclerosis, and rheumatoid arthritis. PH can present early in SLE. The severity does not correlate with other organ disease activity or with disease duration. It is still debatable whether immunosuppressive therapy is useful for PH related to SLE or autoimmune connective tissue disease, as there are no large clinical trials. However, several case reports have shown improvement with cyclophosphamide and prednisone with or without vasodilator therapy. We present a case of SLE-related PH in which a dramatic improvement in mean pulmonary artery pressure and exercise capacity was noted after the institution of treatment with mycophenolate mofetil, resulting in a decrease in corticosteroid dose. Our observations support the potential value of mycophenolate mofetil therapy for PH in SLE.

Fevers in Adult Lupus Patients.

Variability in systemic lupus erythematosus (SLE) disease manifestations is well recognized. Lupus disease activity can range from mild to severe. Fever is a common manifestation of SLE and occurs in 36%-86% of patients. In the Modified Systemic Lupus Erythematosus Disease Activity Index (M-SLEDAI), fever is taken into account as disease activity scoring. Assessment of lupus patients with fever is an important diagnostic challenge, since the initial clinical presentation of a patient with lupus is very similar to the acute febrile phase of an infection. The attribution of fever to SLE holds only after other causes are excluded.

Anakinra for Recurrent Fevers in Systemic Lupus Erythematosus.

Fever is a common manifestation in systemic lupus erythematosus (SLE) and may be associated with disease activity, but should be closely evaluated for infection, drug reaction, thromboembolism, malignancy, or other etiology. We present the case of a 44-year-old Peruvian female with SLE with periodic high fevers and elevated high-sensitivity C-reactive protein (hs-CRP) levels, treated with anakinra, an interleukin-1 (IL-1) inhibitor. Following the birth of her first child, she developed frequent episodic fevers followed by multiple hospitalizations, approximately two to three times per year. She was started on anakinra in September 2016 and had improvement of fevers and joint symptoms. On 26-month follow-up, she had one episode of fever with bandemia requiring hospitalization but otherwise remained afebrile with a significant drop in CRP. Anakinra is well-tolerable and safe due to a short half-life. We report that the inhibition of IL-1 may be a safe and effective treatment for recurrent fevers in SLE.

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. METHODS: We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. RESULTS: We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. CONCLUSIONS: As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.

Inflammatory bowel disease mimicking granulomatosis with polyangiitis: a case report.

BACKGROUND: We report a case in which the extraintestinal manifestations of inflammatory bowel disease preceded development of gastrointestinal symptoms by nearly 9 months in the context of an unusual autoantibody panel, mimicking granulomatosis with polyangiitis. This case highlights the intricacies and overlap of autoimmune diseases, and illustrates an interesting clinical phenotype: cytoplasmic anti-neutrophil cytoplasmic antibody positive inflammatory bowel disease with predominantly extraintestinal manifestations. Perinuclear anti-neutrophil cytoplasmic antibody positivity has been frequently reported in association with inflammatory bowel disease, but cytoplasmic anti-neutrophil cytoplasmic antibody positivity is uncommon. CASE PRESENTATION: A 54-year-old African-American man presented to our internal medicine resident clinic at the Johns Hopkins Hospital with several months of systemic inflammatory features: anterior uveitis, auricular chondritis, monoarthritis, fever, and weight loss. He did not have a primary care physician due to lack of health insurance and had been seen in our emergency department several times over the past year. These features fit nicely with a diagnosis of granulomatosis with polyangiitis, especially given positive cytoplasmic anti-neutrophil cytoplasmic antibodies. However, 9 months into his clinical course he developed hematochezia with perirectal abscess and fistula. A colonoscopy with biopsy confirmed a diagnosis of inflammatory bowel disease. CONCLUSIONS: This case highlights the fact that extraintestinal manifestations may precede gastrointestinal symptoms of inflammatory bowel disease for months, which may delay diagnosis if not understood and recognized. It further highlights an interesting disease phenotype that has not been widely reported, but may deserve further study. Lastly, the case stresses the importance of the internist in identifying a unifying diagnosis in a slowly evolving clinical process with the assistance of subspecialists. In this respect, the case is of interest to general internists, as well as rheumatologists and gastroenterologists.

Rituximab for treatment of severe renal disease in ANCA associated vasculitis.

BACKGROUND: Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking. METHODS: We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m(2). We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events. RESULTS: A total 37 patients met the inclusion criteria. The median age was 61 years. (55-73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m(2) (7-16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200-1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m(2). Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed. CONCLUSIONS: This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.