Faculty Bibliography

Pseudo-pseudo Meigs' syndrome (PPMS) is a rare manifestation of patients with systemic lupus erythematosus (SLE), defined by the presence of ascites, pleural effusions and an elevated CA-125 level. We describe a patient with longstanding lupus who presented with localized lymphadenopathy and subsequently developed massive chylous ascites with marked hypoalbuminemia. A brief historical overview of Meigs' syndrome and related entities is presented, along with a discussion of the differential diagnosis of hypoalbuminemia and ascites in an SLE patient. In addition, we speculate on the optimal therapeutic intervention in such a patient.

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: 'A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment.' The LFA proposes this definition for lupus flare on the basis of its high face validity

Gelatinous transformation of the bone marrow is a rare disease characterised by a focal marrow hypoplasia, fat atrophy and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid, which is often associated with extreme malnutrition and weight loss. There are only two reports describing its association with systemic lupus erythematosus (SLE). One described underlying diseases in 155 cases of gelatinous transformation of the bone marrow and found one case with clinical diagnosis of SLE, but no clinical details were provided. The other described three SLE patients with gelatinous transformation of the bone marrow; however, two of these were cachectic and one was diagnosed with concomitant tuberculosis. We describe one active SLE patient without other comorbidities whose pancytopaenia was histologically confirmed as gelatinous transformation. The combination of high-dose steroid, intravenous immunoglobulin and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed the bone marrow abnormalities.

After institutional review board approval and informed consent were obtained for this HIPAA-compliant investigation, a three-dimensional electrocardiographically gated variable flip angle (VFA) fast spin-echo magnetic resonance (MR) angiography technique was evaluated as an unenhanced method for imaging hand arteries in 13 subjects (including four patients) at 3.0 T; this included evaluation of vessel visualization with warming and cooling in seven subjects. Examinations were evaluated for image quality and vessel conspicuity. Clear separation of arteries from veins was achieved in all subjects, with excellent vessel conspicuity and depiction of stenoses. Warming improved vessel visualization in healthy volunteers. VFA MR angiography is a high-spatial-resolution technique that enables the assessment of vascular reactivity in response to temperature challenge

OBJECTIVE: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy. METHODS: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year. RESULTS: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices. CONCLUSION: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN

OBJECTIVE: To evaluate responses to mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) in lupus nephritis in a multiethnic population. METHODS: This was a retrospective study of all patients with systemic lupus erythematosus (SLE) that underwent kidney biopsy at New York University Medical Center. Patients with followup of at least 6 months were included. Clinical response was defined as complete (return to +/- 10% of normal) or partial (improvement of 50% in abnormal renal measurements). RESULTS: Ninty-nine patients were included in the study: 86% females, 86% non-Caucasian, age 34.2 +/- 1.1 years, 62% with proliferative nephritis (PN; ISN/RPS-III and IV), and 32% with membranous nephritis (MN; ISN/RPS-V). Of the 70 patients with PN, 37 were treated with CYC and 33 with MMF. The baseline characteristics of the 2 treatment groups were different in the incidence of ISN/RPS-IV, values of serum creatinine and serum albumin, and type of insurance (p < 0.05). The response rate was greater in the MMF than in the CYC group (70% vs 41%). Responses to MMF were different in Asians (11/11), Caucasians (4/5), African Americans (3/5), and Hispanics (5/11). Responses to CYC had a similar distribution (Asians 6/10, Caucasians 4/5, African Americans 4/9, Hispanics 1/11). In the MN group (N = 23) responses were similar to the PN group (73% MMF and 38% CYC). After adjusting for race, serum creatinine, serum albumin, type of insurance, and class of nephritis, in a logistic regression model, response to MMF was superior to CYC: OR 6.2 (95% CI 1.9-20.2). Hispanics had worse outcome than Caucasians (OR 0.17). Longterm followup suggested no difference in maintenance with MMF or CYC. CONCLUSION: After controlling for the fact that less severe nephritis is preferentially treated with MMF, we found overall that response to MMF was superior to CYC. In this US population, ethnicity was observed to have an influence on response

OBJECTIVE: Individualized therapy based on genetic background and monitoring of metabolites can optimize drug safety and efficacy. Such an approach is available for azathioprine (AZA), the thiopurine antimetabolite. AZA exerts therapeutic effects when metabolized to the active thiopurine nucleotide, 6-thioguanine (6-TGN). In inflammatory bowel disease (IBD), 6-TGN levels in the target range of 235-400 pmol/8x10(8) red blood cells (RBC) are associated with a high likelihood of response. Our objective was to evaluate whether drug escalation based on metabolite levels improves efficacy and maintains safety in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a 6-month open-label dose-escalation clinical study of patients with active SLE treated with azathioprine dosed by body weight and metabolite levels. The primary endpoint was >or=50% improvement in any one parameter of disease activity, or 50% decrease in glucocorticoid dose. RESULTS: Of 50 patients enrolled in the study, 21 achieved clinical responses, 13 of whom had 6-TGN<235 pmol/8 x10(8) RBC. Ten patients had no clinical response at 6 months, yet achieved either therapeutic IBD 6-TGN levels (>235, n=4) or received maximum AZA dose>or=3.5 mg/kg (n=6). In 19 patients the drug was discontinued prematurely due to side effects or SLE activity. For those patients in whom either liver function test or white blood cell count abnormalities were encountered, metabolites guided attribution to drug or disease activity. CONCLUSION: Clinical responses in SLE can occur at levels of 6-TGN lower than the target range established for IBD. During followup, measurements of AZA metabolites may provide a rational approach to safety