ObjectiveTo assess the safety and immunologic impact of inhibiting interferon‐γ (IFNγ) with AMG 811, a human IgG1 monoclonal antibody against IFNγ, in patients with systemic lupus erythematosus (SLE).MethodsTwenty‐six patients with mild‐to‐moderate, stable SLE were administered placebo or a single dose of AMG 811, ranging from 2 mg to 180 mg subcutaneously or 60 mg intravenously.ResultsSimilar to results previously reported following inhibition of type I IFNs, treatment of SLE patients with AMG 811 led to a dose‐dependent modulation of the expression of genes associated with IFN signaling, as assessed by microarray analysis of the whole blood. The list of impacted genes overlapped with that identified by stimulating human whole blood with IFNγ and with those gene sets reported in the literature to be differentially expressed in SLE patients. Serum levels of IFNγ‐induced chemokines, including IFNγ‐inducible protein 10 (IP‐10), were found to be elevated at baseline in SLE patients as compared to healthy volunteers. In contrast to previously reported results from studies using type I IFN–blocking agents, treatment with AMG 811 led to dose‐related reductions in the serum levels of CXCL10 (IP‐10).ConclusionThe scope and nature of the biomarkers impacted by AMG 811 support targeting of IFNγ as a therapeutic strategy for SLE.

The coronavirus disease 2019 (COVID-19) pandemic has created new challenges that necessitate prompt responses in unexpected clinical situations. Multiple extrapulmonary manifestations and complications of COVID-19 have already been described, but only scattered data are present on immunologic manifestations. We present a case of severe refractory thrombocytopenia in a 51-year-old woman with a history of long-standing systemic lupus erythematosus and antiphospholipid syndrome who presented with hemoptysis in the setting of COVID-19 infection. The patient failed to respond to initial treatment with intravenous immunoglobulin, high-dose steroids, and platelet transfusion, but responded to eltrombopag, with prompt improvement of a platelet count. The current case report provides clinical data of relevance to the largely unexplored question of the immunologic complications of COVID-19 in patients with a pre-existing inflammatory state.

Wegener granulomatosis (WG) is a multisystem necrotizing vasculitis that primarily involves the upper and lower respiratory tract and kidneys but can affect almost any organ, including the central nervous system (CNS). We present a patient with WG whose disease was complicated by a massive intracerebral hemorrhage (ICH) despite standard treatment with prednisone and cyclophosphomide. Although CNS involvement is not uncommon in WG, ICH is a rare complication of WG, and although the majority of patients with WG complicated by a cerebrovascular accident have a fatal outcome, our patient survived this event. The disease subsequently progressed with recurrent pulmonary involvement and renal failure. Our patient either did not tolerate or failed to respond to several immunosuppressive agents, including cyclophosphamide, methotrexate, and mycophenolate mofetil, but achieved remission after treatment with rituximab.

Behçet disease is a systemic inflammatory disease of unknown etiology initially described as a triad of recurrent oral ulcers, genital ulcers, and hypopyon uveitis affecting young male adults. Internationally agreed diagnostic criteria have been proposed to assist in the diagnosis. We present the case of a 26-year-old African-American male who presented with right brachial plexopathy due to axillary aneurysm. Further evaluation revealed the presence of a common carotid artery aneurysm, superior vena cava, and left subclavian vein thrombosis. A few months later, he developed severe bilateral panuveitis with hypopyon, retinal vasculitis, and optic nerve inflammation. Although our patient had no recollection of oral or genital ulcers, the constellation of deep vein thrombosis, multiple arterial aneurysms, bilateral panuveitis, positive pathergy skin test, and elevated inflammatory markers led to the working diagnosis of Behçet disease. Arterial involvement occurs in 3%-5% of patients with Behçet disease and may manifest as either true or false aneurysms. Deep vein thrombosis is the most common venous manifestation and involvement of venae cavae and their tributaries is not uncommon. Anterior and posterior uveitis and retinal vasculitis not only have a prognostic value in Behçet disease but in this particular case supported the diagnosis. In conclusion, incomplete forms of Behçet vasculitis exist and clinicians should be alert to atypical presentations of the disease.

A 31-year-old woman with a history of bilateral carpal tunnel surgery complained of worsening hand pains and swelling. Subsequently, she presented for rheumatologic evaluation with generalized arthralgias, symmetric polyarthritis of the hands and feet, shiny skin with tightness and thickening, tender periungual erythema, malar rash, and photosensitivity. The only laboratory abnormality found then was a positive antinuclear antibody. Her joint symptoms were responsive to low-dose prednisone and hydroxychloroquine. However, the skin tightness progressed proximally and centrally and developed around the mouth. At that point, more specific autoimmune work-up showed negative relevant antibodies, and repeat antinuclear antibody tests turned out negative. Later, she reported dysphagia and hoarseness, and ecchymotic rashes appeared on the face and forearm. Biopsy of the forearm lesion showed leukocytoclastic vasculitis. Staining for amyloid was negative. Subsequently, she was found to have hypogammaglobulinemia and Bence-Jones proteinuria; the progression of her skin symptoms provoked a repeat skin biopsy with special stains that demonstrated amyloidosis. Bone marrow biopsy showed >75% plasma cells, skeletal survey revealed multiple lytic lesions, and a diagnosis of multiple myeloma with associated amyloidosis was made. Despite the initial features of connective tissue disease in this young woman, a steadfast workup revealed the source of her problem.