Robert Quinet

Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. Methods Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. Results The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. Conclusion The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.

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.

Revisiting Jaccoud arthropathy as an ultrasound diagnosed erosive arthropathy in systemic lupus erythematosus.

Jaccoud arthropathy (JA), now most commonly associated with systemic lupus erythematosus (SLE), is widely perceived as a benign joint deformity that is radiographically nonerosive and that confers little if any disability. Advances and accessibility of imaging modalities such as ultrasound (US) are challenging the complacency in perceiving SLE-JA and SLE arthritis as benign processes. Prompted by a patient with SLE-JA in which joint erosion was detectable on US but not evident on radiograph, this review assesses the potential utility of US to guide management and promote understanding of SLE arthritis and its poorly understood pathogenesis.

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 χ2 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.

Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome

INTRODUCTION Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant disease that usually presents in childhood with recurrent sterile arthritis. As the child ages into puberty, cutaneous features develop and arthritis subsides. We report the case of a now 25-year-old male patient with PAPA syndrome with the E250K mutation in PSTPIP1. We also present a systematic literature review of other PAPA cases. METHOD We conducted a literature search of PubMed using the following search terms: E250K mutation, PSTPIP1, and PAPA. RESULTS PAPA syndrome is caused by mutations on chromosome 15q affecting the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene, also known as CD2-binding protein 1 (CD2BP1). The reported cases of PAPA syndrome currently in the literature involve mutations in A230T and E250Q. One case of a novel E250K mutation has been reported, which presented with a different phenotype to previously described cases of PAPA syndrome. CONCLUSION With variation present between disease presentations from case to case, it is possible that the spectrum of PAPA syndrome is wider than currently thought. Further research is needed which may uncover an as-yet undiscovered genetic abnormality linking these interrelated diseases together.

Phrenic nerve paralysis secondary to Lyme neuroborreliosis

Lyme borreliosis, a multisystem illness caused by a tick-borne spirochete Borrelia burgdorferi , can affect the skin, joints, central and peripheral nervous systems, and heart. In 1922 Garcin and Bujadoux reported radiculopathy following a tick bite and a skin lesion called erythema chronicum migrans.1 Some authors estimate that as many as 40% of patients with late Lyme borreliosis present with peripheral nervous system abnormalities.2 A 64-year-old woman from Louisiana presented with severe neck and upper back pain. Three months earlier she had been on an autumn foliage tour in the northeastern United States, visiting Vermont, Connecticut, Maine, and Massachusetts. A week following, she developed severe sinus-like frontal headaches but no fever, chills, cough, or flu-like illness. She was treated for sinusitis with azithromycin, without headache improvement. She then developed a nonpruritic erythematous papular rash on her forearm that gradually enlarged but without any central clearing and without improvement …

An initial presentation of polyarticular gout with spinal involvement

An 85-year-old woman presented with a chief complaint of 2 months of lower back pain that caused her to fall at home, greatly limiting her mobility. Previous to this she had been active and independent. On examination, she was unable to ambulate; she had warmth, pain and swelling of the left ankle, and the third and fourth digits. Serum uric acid at that time was 10.6 mg/dL, the first elevated measurement recorded for her. Her examination was notable for left ankle edema and tenderness and swelling, warmth and pain with dorsiflexion and plantar flexion. Also, her third and fourth left fingers were swollen. She was unable to ambulate. Her erythrocyte sedimentation rate and C-reactive protein was 22 and 12.4 mg/dL, respectively. A clinical diagnosis of gout was made for the swollen left ankle. Magnetic resonance imaging of the lumbar spine showed increased T2 signal within the L3–L4 disc space with a small amount of fluid (Fig. 1). Aspiration under fluoroscopy was preformed and yielded fluid positive for classic monosodium urate crystals (Fig. 2). She was treated with high dose oral prednisone. Her symptoms improved and she was discharged on a prednisone taper and colchicine. Her diuretics were also discontinued. On follow up, she still had pain in her right shoulder and lower back. She was given a short taper of prednisone which resulted in further improvement of her symptoms. She returned 2 weeks later asymptomatic. Allopurinol was started at that time.

Spanning generations-appointment reminder preferences among patients with rheumatic diseases.

Objective This study aimed to determine the appointment reminder preferences of patients presenting to rheumatology clinics. Methods An anonymous, self-directed survey was given to all patients attending our rheumatology clinic. Patients indicated age and reminder preferences in modality and timing. Patients were then divided into generational age groups as follows: generation Y (18–28 years), generation X (29–49 years), baby boomers (50–67 years), the silent generation (68–85 years), and the GI generation (≥86 years). Overall preferences, as well as preferences by generational age groups, were determined. Results A total of 1000 survey forms were distributed among the patients; 949 were collected for a response rate of 94.9%. Of these 949 survey forms, we analyzed 637 (67.1%) and excluded 312 (32.9%). Of all patients, 99.5% viewed appointment reminders favorably. Most (72%, n = 461) of the patients surveyed indicated that they would prefer the timing of their reminder to be 4 days or less before their clinic appointment; 16% (n = 100) preferred timing between 5 and 7 days; another 12% (n = 77) of the patients indicated that they would prefer 8 days or longer in advance. Overall, the most preferred reminder modality was a telephone call (52%, n = 333). The least preferred modality overall was short message service (SMS)/text messaging (4%, n = 27). The most popular option selected in generation Y was text/SMS reminders, and patients belonging to that generational age group were more likely than any other group to favor text/SMS reminders (P < 0.0001). Conclusions Improved rheumatology clinic attendance would be beneficial given the need for disease assessment and medication monitoring. Most patients view appointment reminders favorably; however, no studies have assessed the modality and timing preferences of patients in a US rheumatology clinic. Modality, but not timing, preferences vary with generational age. The preference for newer modalities such as text/SMS reminder was predominately observed in the patients of generation Y, a population prone to clinic nonattendance.

New-onset systemic lupus erythematosus during chronic dialysis and after transplantation for idiopathic renal failure.

The onset of end-stage renal disease typically leads to quiescence of systemic lupus erythematosus clinical and serologic activity. We report two cases of systemic lupus erythematosus diagnosed for the first time years after dialysis and transplantation, respectively, for idiopathic end-stage renal disease. The transplant patient developed SLE despite ongoing treatment with prednisone and cyclosporine. New onset SLE can occasionally occur despite dialysis or transplantation.

Adoption Of New Electronic Medical Records May Inhibit Documentation Of Physician Quality Reporting System

SUPPLEMENTSex Bias In Autoimmune Diseases : Increased Risk Of 47,XXX In Systemic Lupus Erythematosus (SLE) and Sjogrens Syndrome (SS) Supports The Gene Dose HypothesisBackground/Purpose: Human FoxP3+ Th-cells are heterogeneous in function and include not only suppressive cells (TRegs) but also nonsuppressive cells that abundantly secrete proinflammatory cytokines. We have previously shown that FoxP3+ Th-cells were increased in GPA-patients during remission as compared to healthy controls (HCs). In this group of patients, however, we observed a defective suppressor function of TRegs, and an increase in the percentage of Th-17 cells. These observations make it tempting to investigate whether increased FoxP3+ Th-cells in GPA-patients are attributed to an increase in the cytokine-secreting non-suppressive FoxP3+Th-cells. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 46 GPA-patients in remission and from 22 age- and sex-matched HCs. Expression of CD4, CD45RO, and FoxP3 were determined by flow cytometric analysis. The expression levels of FoxP3 and CD45RO were used for distinction between activated suppressor TRegs (FoxP3HighCD45RO+; ASTReg), resting suppressor TRegs (FoxP3LowCD45RO-; RSTReg), and cytokine-secreting non-suppressor TRegs (FoxP3LowCD45RO+; NONTReg) cells. Intracellular expression of IFNg, IL-17, and IL-21 were determined in the various FoxP3+ Th-cell subsets after in vitro activation of PBMCs by PMA and Ca-Ionophore. Results: A significant increase in the frequency of NONTReg cells was observed in GPA-patients as compared with HCs, whereas no differences were detected in RSTReg- and ASTReg cells between GPA-patients and HCs. The distribution of RSTReg- and NONTReg cells did not differ between ANCA-negative and ANCA-positive patients, whereas lower percentages of ASTReg cells were observed in ANCA-positive patients as compared to ANCA-negative patients and HCs. Importantly, a significant increase in the percentage of IL-17+ and IL-21+ cells was seen within the NONTRegcells from ANCA-positive patients (n= 9) when compared to ANCA-negative (n= 10) and HCs (n= 12), whereas no differences were found between ANCA-negative and HCs. Conclusion: Increased FoxP3 expression in Th-cells from GPA-patients is related to an increase in a subset of non-suppressive Th-cells. Increased production of IL-17 and IL-21 cytokines, in NONTReg cells from ANCApositive patients points towards FoxP3+ effector cells and decrease in suppressive TReg cells in relation to ANCA production.Complex Functional Effects Within The HLA Contribute To Sjogrens Syndrome Pathogenesis and May Influence Both Transcriptional Regulation and Peptide Binding