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.

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.

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.

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.

Older patients with ANCA-associated vasculitis and dialysis dependent renal failure: a retrospective study.

BACKGROUND: ANCA-associated vasculitis (AAV) with renal involvement is not uncommon in older individuals. Unfortunately, this can be catastrophic requiring hemodialysis (HD) and may lead to end stage renal disease (ESRD). However, more than 50 % of patients with AAV who require HD initially have renal recovery and discontinue HD. The aim of this study was to describe a retrospective cohort of older patients with AAV and severe renal involvement which required hemodialysis. METHODS: Between 1995 and 2013 a total of 30 patients with histologic evidence of pauci-immune glomerulonephritis who required HD were evaluated at a single university center. The association of demographic and clinical parameters with age was assessed. Older age of disease onset was defined as age ≥ 60 years. The risk of developing ESRD at 3 months was examined using univariate logistic regression analysis. RESULTS: Among 30 patients with AAV who required HD, the mean age of disease onset was 59 ± 17 years (range 22-88 years). Twelve patients were in the older age group, and 18 were in the younger group. Three months after diagnosis, 43 % of the cohort had ESRD with a statistically similar proportion of older (n = 9, 50 %) versus younger (n = 4, 33 %) patients (p = 0.367). Most patients (93 %) received immunosuppressive therapy. There was not a statistically significant association between age and ESRD. CONCLUSIONS: These data suggest that age alone does not predict renal recovery among individuals on HD due to AAV. Renal recovery is a realistic expectation and outcome, if patients are treated, even among older patients with AAV who require HD initially.

Hematuria duration does not predict kidney function at 1 year in ANCA-associated glomerulonephritis.

OBJECTIVES: Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year. METHODS: We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥ 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria. RESULTS: Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥ 90 days) was not predictive of eGFR at 1 year (p = 0.93). CONCLUSIONS: In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression.

Validation of the new classification of pauci-immune glomerulonephritis in a United States cohort and its correlation with renal outcome.

BACKGROUND: Renal biopsies provide important diagnostic and prognostic information in ANCA associated glomerulonephritis. A new classification for prognostication of pauci-immune glomerulonephritis (GN) based on four categories (Mixed, Crescentic, Sclerotic and Focal) was proposed by an international working group of renal pathologists (IWGRP). The goal of our study was to apply the proposed classification system to a United States cohort of vasculitis patients and determine the association of IWGRP class with estimated glomerular filtration rate (eGFR) at one year. METHODS: Seventy-six cases of pauci-immune glomerulonephritis diagnosed from 1995 to 2011 from a single center were identified for this retrospective study. Clinical data were collected by abstraction from medical records. Histology was reviewed by a pathologist and classified according to the new classification. MDRD formula was used to calculate eGFR. We correlated IWGRP class to renal function at presentation and at one year. ×2, ANOVA, and linear regression analysis were performed as appropriate. RESULTS: Renal biopsies were categorized as focal: n = 20, crescentic: n = 18, mixed: n = 27, sclerotic: n = 11. The baseline e-GFR was lowest in the crescentic class and highest in the focal class. In linear regression analysis investigating e-GFR at 1 year; age and baseline e-GFR were independent predictors of e-GFR at 1 year. CONCLUSIONS: The e-GFR at diagnosis and age were predictors of e-GFR at 1 year. Pathologic class at diagnosis may also be a helpful tool in risk stratification at diagnosis.

Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature.

Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-2.2), renal (OR, 1.6; 95% CI, 1.2-2.1), digital ischemia (OR, 1.5; 95% CI, 1.4-2.2), muscle (OR, 1.7; 95% CI, 1.3-2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1-9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4-2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0-1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.

Bilateral sequential trochleitis as the presenting feature of systemic lupus erythematosus.

A 26-year old woman presented with headache and pain in the left superonasal orbit, which worsened with vertical eye movements. She had no relevant medical history, and ophthalmologic evaluation was unremarkable. An orbital ultrasound showed enlargement of soft tissue in the region of the left trochlea consistent with trochleitis. Treatment with prednisone and multiple local injections of corticosteroids and analgesic nerve blocks failed to relieve her symptoms. The patient subsequently experienced right trochleitis, and 2 years after the onset of her initial symptoms, she developed systemic symptoms and signs that led to a diagnosis of systemic lupus erythematosus (SLE). Systemic immunosuppressive therapy was instituted, and the patient experienced marked relief in her ophthalmic symptoms. This case is unique in that not only bilateral sequential trochleitis was the presenting feature of SLE but also the ocular manifestations preceded the systemic manifestations of SLE by over 2 years.

OARSI/OMERACT initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis. An OMERACT 10 Special Interest Group.

OBJECTIVE: To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of "need for joint replacement surgery," for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). METHODS: New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons' indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. RESULTS: In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%-12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0-100) + physical function (0-100) > 80]. CONCLUSION: These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define "nonresponders" to disease-modifying drugs in OA clinical trials.

Late-age onset systemic sclerosis.

OBJECTIVE: Although patients who develop systemic sclerosis (SSc) later in life (≥ 65 yrs) may express the entire clinical spectrum of disease, we hypothesize that patients with late-age onset SSc incur a different risk for specific organ manifestations of disease compared to those with early-age onset SSc. METHODS: In total, 2300 patients with SSc were evaluated between 1990 and 2009 and reviewed from a university-based scleroderma center cohort. Demographic profile, SSc subtype, autoantibody status, Medsger severity scores, pulmonary function tests, echocardiography, and right heart catheterization measures were compared between late-age onset vs younger-age onset patients with SSc. RESULTS: Overall, 2084 patients (91%) developed SSc prior to age 65, while 216 (9%) were ≥ 65 years. Late-age onset patients had a significantly higher proportion of anticentromere antibodies (42% vs 27%; p = 0.001) compared to early-age onset patients. Risk of pulmonary hypertension (OR 1.76, 95% CI 1.00, 3.12), muscle weakness (OR 1.85, 95% CI 1.30, 1.64), renal impairment (OR 2.83, 95% CI 1.98, 4.04), and cardiac disease (OR 2.69, 95% CI 1.92, 3.78) was greater among those with late-age onset SSc; although risk of digital ischemia (OR 0.64, 95% CI 0.47, 0.86) was reduced. The cumulative incidence of pulmonary hypertension at 5 years was greater among those with late-age onset SSc (9%) compared to those with early-age onset SSc (2.7%; log-rank, p < 0.001). CONCLUSION: These findings suggest that older patients with SSc are at greater risk for pulmonary hypertension, renal impairment, cardiac disease, and muscle weakness. Awareness of the distinct risk for specific organ manifestations in SSc, in particular pulmonary hypertension, should guide the care of patients with SSc whose disease begins after age 65.

More than meets the eye.

A 27-year-old woman was hospitalized with fever and visual changes. She had been well until nine months earlier when she developed unilateral blurry vision in the left eye. Ophthalmologic examination revealed bilateral acute anterior uveitis. She was treated with topical steroids and her vision returned to baseline. However, over the next few months, she developed debilitating fatigue and experienced an unintentional fifteen pound weight loss. One month prior to presentation, she noted the onset of daily low grade fevers and chills. On the day of admission, she developed a temperature of 103°F and a severe frontal headache. Here we describe a case where the overlap of clinical features led to an initially broad differential diagnosis of seemingly unrelated diseases. Ultimately, the discovery of a key radiographic finding allowed us to more clearly define the diagnosis.

The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma.

Intravascular B-cell lymphoma is a rare type of non-Hodgkin's lymphoma that is characterized by a clonal proliferation of lymphoblasts within small blood vessels. Patients present with nonspecific symptoms and are often only given a diagnosis at autopsy. We report a case of intravascular B-cell lymphoma, characterized by pyrexia, anemia, thrombocytopenia, and mental status decline, without obvious cutaneous manifestations, that was diagnosed with blind skin biopsy.