In glucocorticoid-dependent polymyalgia rheumatica, tocilizumab improved a composite clinical outcome at 24 wk.

SOURCE CITATION: Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, et al. Effect of tocilizumab on disease activity in patients with active polymyalgia rheumatica receiving glucocorticoid therapy: a randomized clinical trial. JAMA. 2022;328:1053-62. 36125471.

PolyMyalgia Rheumatica treatment with Methotrexate in Optimal Dose in an Early disease phase (PMR MODE): study protocol for a multicenter double-blind placebo controlled trial.

BACKGROUND: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe. The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5-10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing, and dose of MTX in PMR remain unclear, and therefore, our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients. METHODS: We set up a double-blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15 mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse, prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52. DISCUSSION: No relapsing PMR patients were chosen, since the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exists. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects. TRIAL REGISTRATION: Dutch Trial Registration, NL8366 . Registered on 10 February 2020.

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.

Incidence of giant cell arteritis after bisphosphonate exposure: A retrospective cohort study.

OBJECTIVES: Bisphosphonates may cause autoimmune reactions via a cytokine-mediated acute phase response. A case of giant cell arteritis (GCA) after zoledronate injection was recently reported. We aimed to evaluate this association by reviewing the incidence of GCA after bisphosphonate administration. METHODS: This was a retrospective study using the medical claims data of elderly patients in the 20% Medicare random sample from 2008-2014 who had received zoledronate or ibandronate. Patients who had a diagnosis claim of GCA within the past year before receiving either bisphosphonate were excluded. The development of GCA was assessed in 2 ways: GCA diagnosis claim within 28 days of bisphosphonate injection and another claim within 90 days of initial claim; and temporal artery biopsy claim within 28 days of bisphosphonate injection and GCA diagnosis claim within 90 days of biopsy. Due to the Centers for Medicare & Medicaid Services reporting requirements we excluded numbers less than 11 from analysis. RESULTS: The incidence of GCA was 0.010% and 0.013% after zoledronate and ibandronate injection respectively. In the zoledronate group incidence was highest in patients aged 75-85 years (0.011%), in Whites (0.011%), in the northeast census region (0.013%) and higher in females (0.011% vs 0.009%). All GCA cases noted in the ibandronate group involved White females. We are unable to report incidences by age and region due to the paucity of data. CONCLUSION: The incidence of GCA after bisphosphonate injection was not increased compared to the generally reported incidence in the USA.

Giant Cell Arteritis which Developed after the Administration of Granulocyte-colony Stimulating Factor for Cyclic Neutropenia.

A 78-year-old woman diagnosed with cyclic neutropenia 5 years previously had been treated with recombinant granulocyte-colony stimulating factor (G-CSF). She developed fever, tenderness and distension of temporal arteries after the treatment with G-CSF. Magnetic resonance imaging and ultrasonography revealed wall thickening of the temporal arteries. She was therefore diagnosed with giant cell arteritis (GCA). Small vessel vasculitis has been reported as a complication of G-CSF. However, the development of large vessel vasculitis after G-CSF treatment is quite rare. To our knowledge, the present case is the first report of GCA suspected to be associated with coexisting cyclic neutropenia and G-CSF treatment.

Acute Myeloid Leukemia Complicated by Giant Cell Arteritis.

Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin.

Giant cell arteritis with visual loss following zoledronic acid infusion.

Zoledronic acid is used in the treatment of osteoporosis. Giant cell artertitis may lead to vision loss. We report a case in which vision loss occurred after zoledronic acid infusion.

Corticosteroid-induced clinical adverse events: frequency, risk factors and patient's opinion.

BACKGROUND: More than 50 years after the introduction of corticosteroids, few studies have focused on corticosteroid-induced adverse events after long-term systemic therapy. OBJECTIVES: To assess the frequency, risk factors and patient's opinion regarding clinical adverse events occurring early during prednisone therapy. PATIENTS AND METHODS: We conducted a cohort study in two French centres. All consecutive patients starting long-term (> oir = 3 months), high dosage (> or = 20 mg day(-1)) prednisone therapy were enrolled. The main clinical adverse events attributable to corticosteroids were assessed after 3 months of therapy, by comparison with baseline status. The patient's opinion regarding the disability induced by these adverse events was recorded. Risk factors of frequently observed adverse effects were identified by using logistic regression. RESULTS: Eighty-eight patients were enrolled and 80 were monitored for at least 3 months (women 76%; mean age 59.1 +/- 18.7 years; giant cell arteritis 39%; mean baseline prednisone dosage 54 +/- 17 mg day(-1)). Lipodystrophy was the most frequent adverse event [63.0% (51.0-73.1)], was considered the most distressing by the patients and was most frequent in women and young patients. Neuropsychiatric disorders occurred in 42 patients [52.5% (41.0-63.8)], necessitating hospitalization in five cases. Skin disorders were noted by 37 patients [46.2% (35.0-57.7)] and were more frequent in women. Muscle cramp and proximal muscle weakness were reported by 32.5% (22.5-43.9) and 15% (8.0-24.7) of patients, respectively. Newly developed hypertension occurred in 8.7% (2.9-20.3) of patients. Lastly, 39% (19.7-61.4) of the premenopausal women reported menstrual disorders. CONCLUSIONS: Lipodystrophy and neuropsychiatric disorders are common adverse events of long-term prednisone therapy and are particularly distressing for the patients concerned. The impact of these adverse events on adherence to corticosteroid therapy is not known.

Sildenafil-associated nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To describe the clinical features of five patients who developed nonarteritic anterior ischemic optic neuropathy (NAION) after ingestion of sildenafil citrate (Viagra; Pfizer Pharmaceuticals, New York, NY). DESIGN: Retrospective observational case series. PARTICIPANTS: Five patients with NAION who reported the use of sildenafil citrate before the onset of ocular symptoms. MAIN OUTCOME MEASURES: The symptoms presented, history, ophthalmic examination, and visual field examination of each patient. RESULTS: Nonarteritic anterior ischemic optic neuropathy developed in one eye within minutes to hours after ingestion of sildenafil. Four of the five patients had no vascular risk factors for ischemic optic neuropathy. The patients all developed unilateral blurry vision, altitudinal visual field defects, and optic disc edema. Each of the patients was noted to have a small cup-to-disc ratio in the unaffected optic nerve. CONCLUSIONS: Sildenafil citrate may be associated with NAION. A small cup-to-disc ratio may be a risk factor for development of NAION in association with the use of sildenafil.

Acute reversible cerebral arteritis associated with parenteral ephedrine use.

Cerebrovascular disorders in association with licit or illicit drugs have rarely been reported. We report a first case of stroke associated with the parenteral use of ephedrine. A 44-year-old woman underwent spinal anaesthesia for varicose vein surgery. She was usually treated with propranolol and occasionally with phenoxazoline. During anaesthesia, ephedrine was administered by the venous route because of arterial hypotension. She developed intracranial hypertension and focal cerebral deficits related to multiple haemorrhagic cerebral infarcts associated with a reversible beading appearance on angiography consistent with the diagnosis of acute cerebral arteritis. The role of ephedrine in this case is discussed beside other causes of acute cerebral arteritis.

Enalapril-induced vasculitis resembling rheumatoid arthritis, lupus, sicca syndrome, and giant cell arteritis.

We report a case of vasculitis in a 67-year-old woman who successively developed over a four-month period clinical manifestations suggestive of rheumatoid arthritis, lupus, sicca, syndrome and finally giant cell arteritis. All her symptoms resolved promptly upon discontinuation of enalapril and none recurred over the five-year follow-up period. The only residual manifestation is Jaccoud's arthropathy of the hands.

Tongue necrosis in temporal arteritis provoked by ergotamine.

A case of tongue necrosis in a patient with temporal arteritis who was taking ergotamine is described, and the role of ergotamine tartrate in provoking the tongue necrosis is considered. The literature on this unusual complication is critically reviewed, and the value of a carotid angiography in assessing the tongue ischaemia is exemplified.

Getting to the heart of visual loss: when cardiac medication may be dangerous to the optic nerves.

A 62-year-old lady with hypertension and diabetes developed bilateral, sequential ischemic optic neuropathy, progressive in the right eye. Because of a reported association between amiodarone and optic neuropathy with disc edema, the patient discontinued taking this medication; however, her visual loss continued. The differential diagnoses of bilateral ischemic optic neuropathy--including infiltrative optic neuropathy and temporal arteritis--were exhaustively investigated in this patient.