Faculty Bibliography

Background/Purpose: Thrombocytopenia is a common feature of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and in the former most frequently results from antiplatelet antibodies (i.e., AITP) or aPL antibodies. Patients with AITP paradoxically have an increased risk of thrombosis and it has been speculated that this can result from co-presence of aPL. Primary APS is associated with both thrombosis and thrombocytopenia. We assessed whether there was an association between a history of thrombocytopenia and the prevalence of a thrombotic event in a large, multiethnic cohort of SLE patients. Methods: We analyzed the NYU SLE SAMPLE registry, consisting of patients fulfilling ACR and/or SLICC criteria for SLE. We identified 105 patients whose SLE criteria included the presence of one or more of the following aPL antibodies: lupus anticoagulant, IgG or IgM anti-beta2-glycoprotein-I, and/or IgG or IgM anticardiolipin antibodies; and determined whether these patients had thrombocytopenia (<100,000/muL) recorded among their SLE classification criteria. We reviewed each patient's medical record to identify the prevalence of arterial or venous thrombosis (defined as DVT, PE, stroke, arterial occlusion with gangrene or amputation), and/or obstetric events. We compared the prevalence of thrombotic events in SLE patients with and without history of thrombocytopenia. Results: The NYU SLE SAMPLE currently includes 612 patients (90% female, mean age 43.0+/-0.9 years, and mean age of 41.0+/-0.3 years in the males); 54% of the subjects were Caucasian, 31% African American, 15% Asian, 30% Hispanic White, and 5% Hispanic Black: 17% had aPL antibodies, of whom 89% were female and 11% male (mean age 43.0+/-0.2 years, 56% Caucasian, 33% African American, and 11% Asian, 24% Hispanic white and 4% Hispanic Black). The total numbers of patients with thrombotic events were 45 (43%), with 5/21 (23%) in the SLE patients with aPL and prior history of thrombocytopenia and 40/84 (47%; p=0.042) in the patients without thrombocytopenia. The most common thrombotic event was DVT followed by stroke. Conclusion: The prevalence of aPL in the NYU SLE registry was 17%, and adverse thrombotic events were less common in the patients with prior history of thrombocytopenia (5/21, 23%) as compared to those without (40/84, 47%). This unexpected finding could be explained by protective benefit of anti-platelet antibodies when co-occur with aPL in SLE, or less thrombogenic aPL in SLE when there is concomitant thrombocytopenia. Additionally, our data suggest that there might be different consequences of aPL between primary APS patients and SLE patients with aPL

Background/Purpose: Few studies have analyzed the risk factors for thrombosis in Systemic Lupus Erythematosus (SLE) patients with antiphospholipid antibodies (aPL) and most had small sample sizes and homogenous patient populations. We examined whether a history of nephritis is an additional risk factor for thrombosis on a large multi-ethnic SLE cohort database. Methods: The NYU SLE SAMPLE biorepository and registry was initiated in September 2013 and includes 612 patients fulfilling ACR and/or SLICC criteria for SLE. Within SAMPLE, we identified patients with a positive aPL test (lupus anticoagulant, IgG or IgM anti-beta2- glycoprotein-I antibodies and/or IgG or IgM anticardiolipin antibodies) and determined if these patients had also ever fulfilled nephritis criteria. We reviewed each patient's medical record for presence/absence of venous and arterial thrombosis, and obstetric events as well as the non-criteria manifestations such as thrombocytopenia or valvulitis. We compared the prevalence of antiphospholipid syndrome (APS) manifestations in SLE patients with and without a history of lupus nephritis. Results: Of the initial 612 SLE patients (90% female; mean age 43.0+/-0.9 years), 54% were Caucasian, 31% African American, 15% Asian; 30% Hispanic white, and 5% Hispanic Black. Of the 612 patients, 105 had aPL, including 93 females and 12 males (mean age 43.0+/-0.2 years), 56% Caucasian, 33% African American, 11% Asian, 24% Hispanic white and 4% Hispanic Black. The total number of patients with thrombotic events was 45/105 (43%), including 26/43 (60%) in the nephritis subset and 19/62 (30%) (p=0.04) among patients without prior renal involvement. The most common thrombotic event was deep vein thrombosis (DVT) followed by stroke. Conclusion: The prevalence of APS criteria in the NYU SLE SAMPLE was 17%. Within this group, adverse events were more common among the patients with, versus without, a prior history of renal involvement (60% vs 30%). It remains uncertain if this association can be explained by, for example, by the presence of other accompanying findings that distinguish nephritis from non-nephritis SLE (e.g. anti-dsDNA, complement consumption) or drug treatment. This observation provides further support for the universal use of hydroxychloroquine in SLE, especially in those with current or previous nephritis and suggests that event-free aPL positive patients with a prior history of nephritis may be at increased risk for future thrombosis. Further studies are needed to determine whether such patients could benefit from prophylaxis with low-dose aspirin, statins or even other mild anti-thrombotic agents

Background/Purpose: Current ACR and EULAR evidence based guidelines provide recommendations for therapeutic choices to induce and maintain remission of lupus nephritis, however, the appropriate duration of maintenance treatment remains unclear. Data from the ALMS, MAINTAIN, and NIH-funded clinical trials in support of duration greater than three years is absent. In an effort to balance drug toxicities with the desire to prevent late disease recurrence some authors recommend maintenance therapy for as long as five years. There is an active NIH sponsored clinical trial for randomization of MMF maintenance withdrawal in SLE patients in remission, however, these results are not yet available. We analyzed the prevalence of renal flare after MMF maintenance therapy withdrawal in NYU's large, multi-ethnic cohort of SLE patients. Methods: We queried the NYU SAMPLE Lupus Registry and biorepository to identify SLE nephritis patients with complete response who experienced renal flare within 12 months of discontinuing maintenance MMF therapy. The NYU SLE SAMPLE registry was initiated in September 2013 and includes 612 patients fulfilling ACR and/or SLICC criteria for SLE of which 42% have clinical nephritis. Results: The NYU SAMPLE registry has 612 SLE patients (90% female; mean age 43.0+/-0.9 years), 54% Caucasian, 31% African American, 15% Asian; 30% Hispanic white, 5% Hispanic Black and 256 patients (42%) have nephritis. Of the 256 SLE nephritis we identified four patients with renal relapse within 12 months of MMF withdrawal summarized in Table 1. Table 1. Characteristics of patients with renal flare after MMF maintenance treatment withdrawal Conclusion: In the two year period between 3/2014 and 3/2016 we identified 4 patients with a renal relapse within 12 months of maintenance therapy withdrawal. All of the patients were on MMF for maintenance and for a duration >4 years of treatment. Based on this experience we recommend that maintenance of SLE GN with MMF absent contraindication should be at least 5 years and in the interval after withdrawal at any juncture careful monitoring and laboratory studies should be performed no less often than every 3 months for at least 2 years from time of maintenance therapy withdrawal. The occurrence of a renal flare during tapering, also highlights the need for guidelines regarding the rate of withdrawal. Determining risk factors for renal flare after maintenance withdrawal is necessary to facilitate clinicians identifying candidates for discontinuations or instances when to exercise caution.(Figure Presented)

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is the most common secondary form of osteoporosis, and glucocorticoid users are at increased risk for fracture compared with nonusers. There is no established relationship between bone mineral density (BMD) and fracture risk in GIO. We used 3 Tesla (T) MRI to investigate how proximal femur microarchitecture is altered in subjects with GIO. METHODS: This study had institutional review board approval. We recruited 6 subjects with long-term (> 1 year) glucocorticoid use (median age = 52.5 (39.2-58.7) years) and 6 controls (median age = 65.5 [62-75.5] years). For the nondominant hip, all subjects underwent dual-energy x-ray absorptiometry (DXA) to assess BMD and 3T magnetic resonance imaging (MRI, 3D FLASH) to assess metrics of bone microarchitecture and strength. RESULTS: Compared with controls, glucocorticoid users demonstrated lower femoral neck trabecular number (-50.3%, 1.12 [0.84-1.54] mm(-1) versus 2.27 [1.88-2.73] mm(-1) , P = 0.02), plate-to-rod ratio (-20.1%, 1.48 [1.39-1.71] versus 1.86 [1.76-2.20], P = 0.03), and elastic modulus (-64.8% to -74.8%, 1.54 [1.22-3.19] GPa to 2.31 [1.87-4.44] GPa versus 6.15 [5.00-7.09] GPa to 6.59 [5.58-7.31] GPa, P < 0.05), and higher femoral neck trabecular separation (+192%, 0.705 [0.462-1.00] mm versus 0.241 [0.194-0.327] mm, P = 0.02). There were no differences in femoral neck trabecular thickness (-2.7%, 0.193 [0.184-0.217] mm versus 0.199 [0.179-0.210] mm, P = 0.94) or femoral neck BMD T-scores (+20.7%, -2.1 [-2.8 to -1.4] versus -2.6 [-3.3 to -2.5], P = 0.24) between groups. CONCLUSION: The 3T MRI can potentially detect detrimental changes in proximal femur microarchitecture and strength in long-term glucocorticoid users. J. MAGN. RESON. IMAGING 2015;42:1489-1496.

Background Granulomatosis with polyangiitis (GPA) relapse can complicate the differential diagnosis of pulmonary lesions. Case Report A 70-year-old male smoker with GPA and emphysema presented with dyspnea, dry cough, and a right upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A trans-bronchial biopsy did not reveal active vasculitis, malignancy, or infection. He was treated for presumed GPA relapse based on pulmonary manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the cystoscopic discovery of a bladder wall lesion, which was diagnosed as micropapillary urothelial carcinoma not involving the muscularis propria. The patient developed an increasing pulmonary infiltrate with a new solid component, satellite lesions, and regional lymphadenopathy. A right upper lobe wedge resection showed metastatic urothelial carcinoma. Conclusions The simultaneous presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The differential diagnosis should include the rare possibility of metastatic urothelial carcinoma, regardless of how the lesion appears radiographically.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a major neurosurgical emergency associated with significant morbidity and mortality. Rapid aneurysm growth is associated with rupture. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder whose complications can include cerebral vasculitis and vasculopathy. Intracranial aneurysms are not known to occur more frequently in SLE patients than the general population; however, aneurysm growth rates have not been studied in SLE. CASE DESCRIPTION: We present a 43-year-old female with SLE on prednisone, hydroxychloroquine, and azathioprine with moderate disease activity who presented with severe, acute-onset headache and was found to have Hunt and Hess grade II SAH due to rupture of an 8 mm saccular anterior communicating artery (ACoA) aneurysm. The patient developed severe vasospasm, re-ruptured, and was taken for angiography and embolization, which was challenging due to a high degree of vasospasm and arterial stenosis. Review of imaging from less than 2 years prior demonstrated a normal ACoA complex without evidence of an aneurysm. CONCLUSION: We review the literature and discuss the risk factors and pathophysiology of rapid aneurysm growth and rupture, as well as the pathologic vascular changes associated with SLE. Although SLE patients do not develop intracranial aneurysm at an increased rate, these changes may predispose them to higher incidence of growth and rupture. This possibility-coupled with increased morbidity and mortality of SAH in SLE-suggests that SAH should be considered in SLE patients presenting with headache, and advocates for more aggressive treatment of SLE patients with unruptured aneurysms.

This 2013 update on the treatment of systemic lupus erythrematosus provides rationale for universal use of antimalarials even absent skin or joint manifestations, but chiefly focuses on the management options for refractory cutaneous, articular, and renal disease and current status of biologics; both FDA approved belimumab and off-label infliximab, rituximab, abatacept, and tociluzimab. A discussion of antiphospholipid syndrome secondary to lupus, specifically use of aspirin for asymptomatic patients, suggestions for catastrophic antibody syndrome, and potential roles for rituximab and eculizumab are provided. This review is a companion to an article published in this journal last year and in combination provides recommendations for standard care in routine cases of lupus as well as for the problematic, intractable patient.

Anal squamous cell carcinoma is a potentially fatal disease. Human papilloma virus (HPV) is the most common sexually transmitted disease worldwide and is responsible for almost all cases of anal cancer. Immunocompromised patients are at increased risk of developing anal dysplasia and malignancies. A lack of awareness of HPV-associated anal malignancies in the immunocompromised may lead to a delay in diagnosis and confer a poor prognosis.