Arachidonic acid-regulated calcium signaling in T cells from patients with rheumatoid arthritis promotes synovial inflammation.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are two distinct autoimmune diseases that manifest with chronic synovial inflammation. Here, we show that CD4+ T cells from patients with RA and PsA have increased expression of the pore-forming calcium channel component ORAI3, thereby increasing the activity of the arachidonic acid-regulated calcium-selective (ARC) channel and making T cells sensitive to arachidonic acid. A similar increase does not occur in T cells from patients with systemic lupus erythematosus. Increased ORAI3 transcription in RA and PsA T cells is caused by reduced IKAROS expression, a transcriptional repressor of the ORAI3 promoter. Stimulation of the ARC channel with arachidonic acid induces not only a calcium influx, but also the phosphorylation of components of the T cell receptor signaling cascade. In a human synovium chimeric mouse model, silencing ORAI3 expression in adoptively transferred T cells from patients with RA attenuates tissue inflammation, while adoptive transfer of T cells from healthy individuals with reduced expression of IKAROS induces synovitis. We propose that increased ARC activity due to reduced IKAROS expression makes T cells more responsive and contributes to chronic inflammation in RA and PsA.

TNF-alpha inhibition for the treatment of cardiac sarcoidosis.

BACKGROUND: Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking. METHODS: We conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes. RESULTS: We identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-α inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-α inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use. CONCLUSIONS: A large cohort (n = 77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n = 20) received TNF-α inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-α inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

Recurrent carpal tunnel syndrome associated with extension of flexor digitorum muscle bellies into the carpal tunnel: A case series.

While the success or failure of carpal tunnel release ultimately depends on the interplay of a wide array of factors, a broad understanding of the normal anatomy of the carpal tunnel accompanied by awareness of the possible variations of the individual structures that make up its contents is crucial to optimizing surgical outcomes. While anatomic variants such as extension of the flexor digitorum muscle bellies have been described as a cause of primary carpal tunnel syndrome (CTS), there have been no reports depicting its association with recurrent CTS following initially successful carpal tunnel release, a finding with potentially significant prognostic implications that can aid in operative planning. In such cases where muscle extension is identified preoperatively, careful debulking of the muscle belly may be beneficial in improving long-term surgical outcomes.

Cutaneous Vasculitis in a Patient with Antiphospholipid Antibody Syndrome.

Antiphospholipid antibody syndrome (APS) is an acquired thrombophilia, caused by autoantibodies to anticardiolipin (aCL), or antibeta 2 glycoprotein I, or the presence of lupus anticoagulant (LA) in plasma. It is characterized by recurrent venous and/or arterial thrombi and/or pregnancy related morbidities. We present the case of a 52-year-old female with long-standing APS, who developed cutaneous vasculitis following a common cold. Most of the cutaneous manifestations of APS have been found to be thrombotic on histopathology without evidence of perivascular inflammation. Vasculitis is usually seen in APS patients with coexistent Systemic Lupus Erythematosus (SLE). However, our patient had evidence of vasculitis on skin biopsy and did not have SLE. Though rare, this is a disease process which must be considered in patients with primary APS which must be closely monitored for other vasculitic complications of APS, particularly diffuse alveolar hemorrhage.

Adult Onset Henoch-Schönlein Purpura: Case Report and Review of Literature.

Henoch-Schönlein purpura (HSP) is an IgA mediated small-vessel vasculitis, more common in children than adults. We present the case of a 37-year-old male who presented with complaints of nausea, vomiting, abdominal pain, purpuric rash over lower extremities, and migratory polyarthralgia five days after being treated with antibiotics for bronchitis. In addition to the abdominal pain, he developed diarrhea and colonic biopsy findings were suggestive of inflammatory bowel disease (IBD). Skin biopsy revealed leukocytoclastic vasculitis with direct immunofluorescence studies (DIF) staining of IgA deposition confirming the diagnosis of HSP. The clinical features of cutaneous eruption with abdominal complaints can be seen with either HSP or IBD; however the specific skin biopsy findings on DIF can distinguish between the two disease processes. Though HSP is primarily seen in the pediatric population, it is a disease process that must be considered in adults presenting with vasculitic skin rashes and abdominal complaints.