Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor

Publication date: Available online 19 June 2018
Source:Clinical Immunology
Author(s): Yujuan Zhang, Saloni Gupta, Alexandra Ilstad-Minnihan, Sashi Ayyangar, Arielle D. Hay, Virginia Pascual, Norman T. Ilowite, Claudia Macaubas, Elizabeth D. Mellins
Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β, IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.



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A case of ectopic liver tissue adherent to the gallbladder

Abstract

We report a case of a 30-year-old lady who presented to the emergency department with a 1 day history of severe epigastric pain which radiated to the back. Focused history, physical exam findings, haematological and radiological investigations, including ultrasound scanning of the abdomen, supported the diagnosis of acute gallstone pancreatitis. She was managed conservatively and underwent elective laparoscopic cholecystectomy at a later date. Intraoperatively, there was noted to be a small nodule loosely adherent to the gallbladder serosa. Histology from this nodule revealed it to be a portion of anatomically normal liver parenchyma also referred to as ectopic liver tissue (ELT). ELT is a rare developmental abnormality in which normally functioning liver tissue develops at an extra-hepatic site. ELT is known to have an increased risk of neoplastic transformation and so we believe it to be of clinical importance.

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Acute-right-ventricular-failure post-cardiotomy: RVAD as a bridge to a successful recovery

Abstract

This is the case of a 57-year-old woman who underwent coronary-artery-bypass-grafting following a diagnosis of NSTEMI with triple-coronary-vessel-disease. During separation from cardiopulmonary-bypass she developed acute severe-right-ventricular-failure refractory to inotropic support and intra-aortic-balloon-pump-counterpulsation. Therefore VA-ECMO was established in order to separate the patient from cardiopulmonary-bypass. VA-ECMO was then transitioned to RVAD support which allowed complete recovery of RV-function and subsequent explantation. The patient was eventually discharged home.

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Disseminated Mycobacterium abscessus infection with spondylodiscitis of thoracic spine

Abstract

A case is presented of an immunosuppressed 51-year-old man with spondylodiscitis of the thoracic vertebrae from Mycobacterium abscessus infection, in context of disseminated multi-systemic infection with pulmonary and gastrointestinal involvement. Multiple challenges in the diagnosis and management of this confounding case are outlined. The patient underwent aggressive surgical debridement via T8–T10 vertebrectomy plus reconstruction, and right hemicolectomy to obtain source control. This was followed by prolonged combination antibiotic therapy. At time of manuscript patient is 10 months post-surgery and 18 months from initial presentation, with excellent surgical outcome and control of the infection. The unique microbiological and clinical characteristics of M. abscessus are briefly outlined. A synopsis of the relevant literature is given highlighting the relative paucity of evidence to aid management of this unpredictable infection. Current best practice guideline recommends combination of medical therapy and aggressive surgical debridement for infections caused by M. abscessus.

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Analgesic effect of long-acting somatostatin receptor agonist pasireotide in a patient with acromegaly and intractable headaches

A 22-year-old woman presented with worsening vision loss and headaches. A diagnosis of acromegaly was confirmed after detection of an invasive pituitary macroadenoma and biochemical testing. Despite two attempts of surgical debulking of the tumour and administration of long-acting octreotide and cabergoline, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were uncontrolled. The patient experienced persistent headaches despite surgery, gamma knife radiation and ventriculoperitoneal shunt placement; she was then enrolled in the ACCESS trial (ClinicalTrials.gov identifier, NCT01995734). Pasireotide (Signifor; Signifor LAR) was initiated, which led to reduced GH and IGF-1 levels and resolution of her intractable headaches. This highlights the use of monthly pasireotide in resolving headaches and improved biochemical control in a patient with acromegaly. We postulate that the headaches improved due to an analgesic and/or anti-inflammatory effect mediated by somatostatin receptors targeted by pasireotide. This may represent an additional benefit of pasireotide and requires further investigation.

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Cogans syndrome with pyoderma gangrenosum: management of two uncommon disorders with aggressive presentation in a patient

Pyoderma gangrenosum (PG) coexisting with Cogan's syndrome (CS) is uncommon, although cutaneous manifestations are known to develop in CS. A middle-aged white female patient had chronic relapsing PG requiring ciclosporin and prednisolone. Despite receiving optimal doses of ciclosporin and prednisolone, she developed acute vestibulo-auditory symptoms as a result of CS. Ciclosporin was switched to methotrexate and prednisolone was increased. However, she continued to develop acute scleritis, requiring methylprednisolone pulses, and still had further flares of PG. Her methotrexate was held off when she developed severe pneumonia and she then received a trial of intravenous immunoglobulins (IVIG) for her recurrent leg ulcers. Unfortunately, she failed to respond to IVIG. Her ulcers eventually responded to six doses of monthly intravenous cyclophosphamide induction. Although CS is not an antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, we used pulse cyclophosphamide, based on the experience of cyclophosphamide efficacy in severe ANCA-associated vasculitis (AAV). Following induction, both diseases currently remain under control with azathioprine as maintenance treatment.

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Case of severe acute lupus myocarditis and multiple-organ failure

We report a case of severe lupus myocarditis with rapid, acute deterioration to cardiogenic shock and multiorgan failure, highlighting the importance of early identification and treatment of acute presentations in patients with systemic lupus erythematosus. A 31-year-old woman with previously diagnosed subacute cutaneous lupus erythematosus initially presented with abdominal pain and frank per-rectal bleeding. She deteriorated rapidly with type 1 respiratory failure and acute kidney injury requiring dialysis secondary to acute cardiac failure with a prolonged intensive care unit admission, over a month. A significantly elevated troponin, global hypokinesia on echocardiogram and normal coronary artery angiogram and cardiac MRI lead to the diagnosis of acute lupus myocarditis as the cause for the cardiogenic shock. She was treated with high-dose corticosteroids and eventually made a full recovery, with cardiac function returning to normal.

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