Lupus pathogenesis and autoimmunity are exacerbated by high fat diet-induced obesity in MRL/lpr mice.

OBJECTIVE: SLE is an autoimmune disease characterised by persistent inflammation and autoantibody production. Genetic predisposition and environmental factors such as a high-fat diet (HFD) may contribute to lupus development. However, the immune cell profile and gender difference in response to HFD in lupus have not been reported. Here we investigated the impact of HFD on lupus pathogenesis and autoimmunity using lupus-prone mice. METHODS: Thirty male and 30 female MRL/lymphoproliferation (lpr) mice were fed with regular diet (RD) or HFD. Body weights were recorded weekly. SLE progression was monitored by skin lesion, urine protein, titres of antidouble-strand DNA (dsDNA) and ANA. At week 14, kidney and skin tissue sections were stained with H&E and periodic acid-Schiff to detect histological kidney index and skin score. Splenocytes were identified by immunofluorescence staining and flow cytometry. RESULTS: HFD significantly increased body weight and lipid levels compared with RD (p<0.01). Skin lesions were observed in 55.6% of the HFD group compared with 11.1% of the RD group, with greater histopathological skin scores in the female HFD group (p<0.01). Although both male and female mice had higher serum IgG in the HFD group than in the RD group, only the male HFD group showed an increased trend in anti-dsDNA Ab and ANA titres. Kidney pathological changes in the HFD group were more severe in male mice than in female mice (p<0.05), detected by proteinuria, kidney index and glomerular cell proliferation. Significant increases of germinal centre B cells and T follicular helper cells were observed in the spleens of HFD mice (p<0.05). CONCLUSION: HFD induced an accelerated and exacerbated lupus development and autoimmunity in MRL/lpr mice. Our results parallel many known clinical lupus phenotypes and sexual dimorphism in which male patients are likelier to have a severe disease (nephritis) than female lupus patients who may have a broader range of lupus symptoms.

Etiologies and management of haemophagocytic lymphohistiocytosis: is it time for an updated protocol and targeted treatments?

OBJECTIVE: The objective of this study was to analyse the features, therapeutic approaches, and outcomes for adult patients with haemophagocytic lymphohistiocytosis (HLH) at a single centre. METHODS: This study was a retrospective chart review of all patients >18 years of age diagnosed with HLH according to HLH-2004 or H-score criteria at Ochsner Medical Center-New Orleans between 2013 and 2019. RESULTS: A total of 29 patients with HLH met inclusion criteria. A total of 7 patients had an underlying malignancy, 12 had an autoimmune disease, 2 were transplant patients, and 2 had a combination of malignancy, autoimmune disease, or immunodeficiency. A total of 6 patients developed HLH precipitated by infection alone. All 29 patients presented with fever. A total of 28 (97%) patients met H-score criteria, and only 20 (67%) met HLH-2004 criteria. Fifteen patients were treated with the HLH-2004 protocol. Of those treated with the HLH-2004 protocol, 73% (11/15) died, 8% (1/15) had recurrence of HLH, and 20% (3/15) had resolution of HLH. A total of 14 patients were treated with targeted therapy. Of those treated with targeted therapy, 93% (13/14) had resolution of HLH and 1 died. Targeted therapy included pulse steroids, tocilizumab, anakinra, IVIG, CSA, rituximab, and/or CYC in addition to antiviral or antibiotic therapy. CONCLUSION: Our findings suggested that the rheumatologic patient population responded well to a targeted therapeutic approach and poorly to the HLH-2004 protocol. Whether the poor outcomes found with the use of the HLH-2004 protocol are secondary to the protocol itself or the aggressive nature of malignancy-associated HLH is unclear. Further studies are needed to develop tailored therapeutic regimens.

Fibromyalgia: can online cognitive behavioral therapy help?

BACKGROUND: Cognitive behavioral therapy (CBT) has proven useful in treating fibromyalgia, depression, and anxiety. Computerized delivery of CBT allows increased access to such therapy. This study assessed the effect of internet-based CBT on Fibromyalgia Impact Questionnaire (FIQ) composite scores and tender point assessments. METHODS: This 12-week randomized controlled trial included patients ≥18 years of age with 1990 American College of Rheumatology criteria for fibromyalgia and mild to moderate depression and anxiety. A total of 56 subjects were randomized into either a 6-week internet-based CBT group (MoodGYM) or a control group (standard care). We evaluated patients in both groups at 1-, 6-, and 12-week follow-up. The primary outcome measure was change in FIQ composite score. A secondary outcome measure was change in tender point assessment. RESULTS: The mean age of study participants was 55 years, and 88% were female. Mean FIQ scores were significantly lower in the MoodGYM group compared to the control group (P<0.05 for group differences at 6 and 12 weeks). Mean tender point scores were also significantly lower in the MoodGYM group (P<0.001 at 6 and 12 weeks). We found no significant difference in the FIQ scores across the 3 timepoints in the MoodGYM group, but tender points showed a significant negative trend from baseline to 12-week follow-up. CONCLUSION: Patients in the internet-based MoodGYM CBT program had lower FIQ and tender point scores at 6- and 12-week follow-up. Internet-based CBT could be beneficial in the treatment of mild to moderate depression and anxiety in patients with fibromyalgia by allowing increased access to CBT.

Follicular helper T cells: new insights into mechanisms of autoimmune diseases.

BACKGROUND: Autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, etc) are characterized by the production of autoantibodies against one's own cell components, resulting in the dysfunction of normal organs. At present, therapies for autoimmune diseases involve a variety of nonspecific antiinflammatory and immunosuppressive agents with significant side effects. Current studies have suggested that the germinal center (GC) may be the pathogenic hot spot for the production of autoantibodies in autoimmune disease. Events occurring in the GC-such as the selection of high-affinity B cells, proliferation of B cells, and differentiation of B cells into plasma cells-all depend on T cells. Follicular helper T (Tfh) cells are a recently identified T-cell subset, named for their location in GCs. Tfh cells are characterized by their signature transcription factor (B-cell lymphoma 6), surface molecules (CD40 ligand, chemokine [C-X-C] receptor 5, inducible T-cell costimulator, programmed cell death protein-1, etc), and cytokines (interleukin [IL]-21, IL-6, IL-10, etc). Through these signals, Tfh cells help B cells form GCs and drive B cells to differentiate into memory B cells and plasma cells that produce antibodies. However, uncontrolled generation of Tfh cells in the GCs or peripherals could lead to autoimmunity. Recent studies from our group and others have shown that Tfh cells are expanded in the peripheral blood of patients and in the lymphoid tissues of mice with lupus or rheumatoid arthritis and play an important role in promoting pathogenic autoantibody production. METHODS: In this review, we summarize the latest immunologic findings regarding the characteristics and development of Tfh cells, their relation to other CD4(+) T-cell subsets, and the function of Tfh cells in normal immune response and autoimmune diseases. CONCLUSION: A clear understanding of the mechanisms of Tfh cell-mediated immunity and pathology may lead to the development of novel therapeutic targets in autoimmune diseases.

Tumor necrosis factor-alpha antagonist-induced sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.

Implementation of a mandatory rheumatology osteoporosis consultation in patients with low-impact hip fracture.

BACKGROUND: Osteoporosis remains an underdiagnosed and undertreated major health problem. The current treatment rate for patients who have experienced at least 1 osteoporotic fracture is 20%-25%. Therefore, the Rheumatology and Internal Medicine Departments of Ochsner Clinic Foundation New Orleans implemented a mandatory rheumatology osteoporosis consult as part of preprinted admission orders for all patients after hip fracture surgery on the Internal Medicine service. METHODS: We conducted a retrospective study of 78 patients admitted with a low-impact hip fracture between June 2004 and July 2005. These patients were seen by the rheumatology service in the hospital after hip fracture repair (exposed group). Osteoporosis evaluation was performed based on an interview questionnaire. Seventy-eight age-matched patients previously admitted for low-intensity or low-impact hip fracture in 2002-2003 but not exposed to the mandatory rheumatology consult served as our comparison group. Pearson chi2 test was used for statistical analysis. RESULTS: Mean patient age was 80 years. Of the 78 unexposed patients, 17 (22%) were on treatment (calcium, vitamin D, hormones or antiresorptive agents) before the hip fracture, and 18 (23%) were on treatment after fracture repair. Of the 78 patients exposed to the compulsory rheumatology consultation, 34 (44%) patients were receiving osteoporosis treatment before hip fracture and 75 (96%) patients were receiving treatment after fracture repair. Of the patients not treated before hip fracture repair, there was a significant increase in the percent treated for those patients exposed to the rheumatology consult versus those not exposed (97.6% vs. 2.4%, respectively, P < 0.0001). CONCLUSIONS: In our institution, we were successful in identifying and initiating appropriate therapy for osteoporosis patients through an automatic rheumatology osteoporosis consultation after hip fracture. The implementation of a mandatory osteoporosis consult resulted in a statistically significant increase in treatment of the exposed group compared with the unexposed group.

Localized versus systemic vasculitis: diagnosis and management.

Localized vasculitis restricted to a specific anatomic site or organ is often histologically indistinguishable from more severe, systemic forms of vasculitis. By definition, localized vasculitis involves blood vessels within a confined vascular distribution or single organ without clinical evidence of generalized inflammation. Important factors that determine treatment and prognosis, in what appears initially to be a localized process, include histopathologic type, organ site, and the presence of systemic inflammatory markers and symptoms. The major issue is whether single organ vasculitis is actually an isolated form of the disease in which case surgical excision is curative, or whether the single organ involvement is simply a precursor of more threatening systemic vasculitis. The Birmingham Vasculitis Activity Score is a valuable tool to identify those patients with concurrent systemic involvement. The physician's recognition of a localized versus systemic vasculitic process is important in terms of making the correct diagnosis, prescribing treatment, and arranging appropriate clinical follow-up.

Splenic rupture as the presenting manifestation of vasculitis.

BACKGROUND: Although underreported, histologic splenic involvement in Wegener's granulomatosis (WG) is not unusual. Splenic rupture in association with WG, however, is rare. Only 2 cases of nontraumatic splenic rupture have been reported as the initial feature of WG. Isolated cases of splenic rupture also have been noted in rheumatoid arthritis, systemic lupus erythematosus, and polyarteritis nodosa. OBJECTIVE: To report the third case of splenic rupture as the presenting feature of WG and review the literature concerning splenic rupture in other rheumatologic diseases to better delineate a mechanism for this rare occurrence. METHODS: Descriptive case report of 1 patient with WG with antecedent splenic rupture and a review of the relevant literature using a MEDLINE search from 1950 to 2001. RESULTS: Our patient presented with symptoms and signs of WG 2 weeks after nontraumatic splenic rupture. Two similar cases have been reported: one showed splenic vasculitis histologically and the other only a neutrophilic infiltration at the site of the splenic tear and subcapsular zone after surgery. Although splenic capsular and pulp hemorrhage alone without signs of vasculitis were noted in our patient, no other cause (ie, hematologic, infectious, neoplastic, or otherwise) for splenic rupture was found. CONCLUSIONS AND RELEVANCE: As in the 2 reported cases, WG may have been responsible for splenic rupture in our patient. Regardless, early evaluation for connective tissue disease in a patient with spontaneous splenic rupture without apparent cause merits consideration, as it may affect patient follow-up and treatment.