Giant cell arteritis associated with PD-1 inhibition

A 50-year-old woman was referred to rheumatology for new onset polyarthralgia and headache. She had a history of metastatic lung adenocarcinoma and was started on treatment with the programmed death 1 receptor (PD-1) antagonist pembrolizumab 2 months prior. Examination revealed left temporal artery tenderness and hand synovitis. Investigations revealed enlarged temporal artery on ultrasound imaging. On steroid treatment, she had resolution of symptoms, but due to significant steroid side effects required methotrexate and her PD-1 antagonist therapy was continued in consultation with her oncologist. Her malignant disease has remained stable, and she has improved functional status.

STEROID SPARING DRUGS IN IMMUNE MEDIATED MUCOCUTANEOUS DISEASES-A REVIEW ON THERAPEUTIC REGIMEN

Corticosteroid remains mainstay of treatment for immune mediated mucocutaneous disorders. The very usefulness of the drug, which has become a double-edged sword, when used for long time. The administration of immunomodulators decrease the dose of steroids, reduces the steroid side effects and improves rejuvenation time. In addition to immunomodulatory drugs there are some drugs that are used to spare corticosteroids in the treatment of immune mediated mucocutaneous diseases. This review attempts to elicit the use of steroid sparing drugs in immune mediated diseases.

Benign intracranial hypertension associated with inhaled corticosteroids in a child with asthma

A 13-year-old male asthmatic presented to the general paediatric clinic with papilloedema identified following a check-up with his optician due to blurred vision. His asthma was well controlled on a moderate dose of inhaled corticosteroid and there had been no recent increase or decrease in the dose. A diagnosis of benign intracranial hypertension (BIH) was made based on a raised cerebrospinal fluid opening pressure, papilloedema, a normal neurological examination and normal neuroimaging. The only associated risk factor was his inhaled corticosteroids. He was commenced on acetazolamide and the inhaled corticosteroid dose was reduced, resulting in resolution of his papilloedema. This case serves to highlight that steroid side effects including BIH may occur at moderate doses of inhaled corticosteroids and that inhaled corticosteroid dose should be regularly reviewed and decreased to the lowest dose that maintains asthma control.

Two case reports of corticosteroid administration-prolonged and pulsed therapy-in treatment of pruritus in cholestatic hepatitis A patients

Cholestasis following hepatitis A affects around 0.8% of hepatitis A patients. It is considered a distressing complication in spite of its good prognosis. Despite being subject to multiple studies, causes of cholestasis are still controversial. Many treatments (discussed later) have shown some improvements of the accompanied pruritus. In the following article, we present two cholestatic hepatitis A patients who suffered from severe pruritus. Prednisolone was administered via two different methods: prolonged and pulsed. Both showed great improvement of the pruritus in a short time frame. To the best of our knowledge, our management using pulsed corticosteroid therapy in treatment of pruritus in cholestatic hepatitis A is considered the first experimental management in medical literature. The importance of this experimental case lies in reducing the doses and the duration of steroid intake, thus reducing steroid side effects as far as possible.

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone

Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.