Presence of subclinical giant cell arteritis in patients with morning stiffness of duration less than 45 minutes at the time of diagnosis of polymyalgia rheumatica.

Introduction: In some patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) is subclinical as underlying inflammation of large vessels (LV) is present without evidence of related clinical manifestations. Different factors have been proposed as predictive of subclinical GCA in PMR patients. To date, the literature reports scant data about the association between subclinical GCA and long-lasting morning stiffness (MS) in patients at the time of diagnosis of PMR. Given this background, the aim of this study was to assess the association between subclinical GCA and MS < 45 min in patients with newly diagnosed PMR. Material and methods: We performed an observational, retrospective, single-centre cohort study of patients consecutively referred to our public out-of-hospital rheumatologic clinic between January 2015 and December 2020, who could be classified as having PMR according to the 2012 EULAR/ACR criteria. Subclinical GCA was investigated through ultrasound examination of a core set of arteries (temporal, axillary, common carotid, and subclavian arteries), in accordance with the EULAR recommendations for the use of imaging in LV vasculitis. Patients who did not have GCA symptoms but showed halo sign in at least one of these arteries were described as having subclinical GCA. Results: We included a total of 143 patients (35 men and 108 women). Their median age was of 71.5 years. Thirty-five had MS duration < 45 min at the time of PMR diagnosis. Subclinical GCA was found in 23 PMR patients (16.1%); 18 had a cranial and 5 an extracranial GCA. A univariate analysis highlighted that MS < 45 min was associated with a lower prevalence of GCA (OR = 0.11, 95% CI: 0.04-0.29; p < 0.0001). This association was retained in a multivariable analysis that accounted for 6 different potential covariates (OR = 0.06, 95% CI: 0.01-0.26; p < 0.0001. Conclusions: In our study MS < 45 min at the time of PMR diagnosis was associated with a significantly lower risk of subclinical GCA, when patients were screened by ultrasound, of approximately 90%. Identification of a more accurate MS cut-off value could improve the accuracy for subclinical GCA in patients with newly diagnosed PMR.

Oral isotretinoin and sacroiliitis: causal link or coincidence? Discussion points emerging from a case-based review.

Isotretinoin is a retinoid derivative drug used in acne vulgaris treatment. Sacroiliitis has been reported as an uncommon adverse effect following isotretinoin treatment. We report a 30-year-old male patient who developed sacroiliitis after isotretinoin use. Stopping treatment with isotretinoin resulted in a complete disappearance of inflammatory back pain. A literature search was performed to assess the relevance of this association in everyday clinical practice, and to discuss whether the link between isotretinoin and sacroiliitis is causal or coincidental.

Polymyalgia rheumatica and polymyalgia-like syndromes as adverse events following COVID-19 vaccines: working notes from a narrative review of published literature.

Since the 1990s, polymyalgia rheumatica (PMR) has been reported as a possible adverse event following immunization (AEFI). The aim of this narrative review is to provide an overview of PMR (and PMR-like syndromes) following the most common types of COVID-19 vaccines, namely mRNA (tozinameran and mRNA-1273) and adenovirus-vectored (ChAdOx1-S) vaccines. To date, published literature reports few cases of PMR as vaccine-linked AEFI. Yet Vigibase, the WHO pharmacovigilance database, reports a few hundred cases. Based on these data, we address the question whether PMR/PMR-like syndromes following COVID-19 vaccines can be a true adverse or a coincidental event, and discuss its possible pathogenetic mechanisms.

Antimitochondrial Antibodies and Primary Biliary Cholangitis in Patients with Polymyalgia Rheumatica/Giant Cell Arteritis.

Background and Objectives: Laboratory liver abnormalities can be observed in patients affected with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA), especially with a cholestatic pattern. The first objective of our review article is to discuss the potential link between antimitochondrial antibodies (AMA) and/or primary biliary cholangitis (PBC) and PMR/GCA, according to the evidences of literature. The second objective is to discuss the association of PMR/GCA with the other rheumatic diseases having PBC as a common manifestation. Materials and Methods: A literature search was performed on PubMed and Medline (OVID interface) using these terms: polymyalgia rheumatica, giant cell arteritis, antimitochondrial antibodies, primary biliary cholangitis, primary Sjogren's syndrome, systemic sclerosis, and systemic lupus erythematosus. The search was restricted to all studies and case reports published in any language. Reviews, conference abstracts, comments, and non-original articles were excluded; however, each review's reference list was scanned for additional publications meeting this study's aim. When papers reported data partially presented in previous articles, we referred to the most recent published data. Results and Conclusions: Our literature search highlighted that cases reporting an association between AMA, PBC and PMR/GCA were very uncommon; AMA antigenic specificity had never been detected and biopsy-proven PBC was reported only in one patient with PMR/GCA. Finally, the association of PMR/GCA with autoimmune rheumatic diseases in which PBC is relatively common was anecdotal.

Back to the future: identification and classification of polymyalgia rheumatica and polymyalgia rheumatica-like syndromes following cancer immunotherapy with checkpoint inhibitors.

Polymyalgia rheumatica (PMR) and PMR-like syndromes are among the most frequent rheumatologic immuno-related adverse events (IRAEs) induced by cancer immunotherapy with "checkpoint inhibitors" (ICIs). Our short communication addresses two key methodological issues laid bare by published literature : 1) how to diagnose PMR and PMR-like syndromes following ICI therapy, 2) how PMR/PMR-like syndromes following ICI therapy are described as adverse drug reactions (ADRs).

Not just pain and morning stiffness duration in the daily experience of patients with polymyalgia rheumatica. Does the rheumatologist listen to all patient-reported outcomes?

Patient-reported outcomes (PROs) provide a means for patients to communicate with their care teams about their disease. Polymyalgia rheumatica (PMR) is considered to be one of the most common inflammatory rheumatic diseases in older adults. The Visual Analogue Scale (VAS) of pain is the only PRO assessed by the PMR activity score (PMR-AS), which is still the only validated score for monitoring disease activity in patients affected with PMR. Other PROs such as fatigue, sleep disturbances, depressive symptoms, and patient's perspective related to adverse effects of prednisolone are still unmet needs. This short communication suggests the gerontorheumatological outpatient clinic as an answer.

Feasibility and usefulness of a fast-track clinic for patients suspected of polymyalgia rheumatica: notes for a work schedule through a narrative review of published literature.

OBJECTIVES: Fast-track clinics (FTC) have been introduced in different fields and have been reporting significant outcomes in terms of reducing mortality, morbidity, and financial costs. To date, scarce evidence is available for FTC specific for patients suspected of polymyalgia rheumatica (PMR). The primary aim of our paper is to provide an overview of the clinical impact of PMR on patients and the healthcare system by analysing multiple aspects: the median time from onset of symptoms to diagnosis and the burden of the disease both on the healthcare system costs and on patients' quality of life (QoL). Secondarily, based on these data, we aim to discuss the potential advantages and feasibility of a PMR FTC in everyday clinical practice. MATERIAL AND METHODS: We performed a narrative non-systematic review (PRISMA protocol not followed) of PubMed and Medline (OVID interface) with the following MeSH terms: [polymyalgia rheumatica AND diagnosis OR diagnosis, delayed OR patient care OR early diagnosis OR length of stay OR costs OR healthcare system OR quality of life] or [polymyalgia rheumatica AND glucocorticoids AND side effects]. We decided to exclude every paper that did not report raw data in terms of diagnostic time or delay, hospitalization rate, socio-economic costs on the healthcare system, patients' QoL, and glucocorticoids-related events in PMR patients. Papers focused primarily on giant cell arteritis patients with overlapping PMR were also excluded. Abstract archives of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) congresses of the last 10 years were screened and included in the search if raw data were available. Each paper's reference list was scanned for additional publications meeting this study's aims. When papers reported data partially presented in previous articles, we opted to use the most recently published data. RESULTS: According to our literature review, a PMR FTC might lighten the burden of the disease. Nevertheless, its feasibility depends mostly on the resources of the national health system and of the territorial health district, which are heterogeneously limited. The usefulness of PMR FTCs depends on closer collaboration with the general practitioner because he/she is the first clinician to visit patients with PMR. CONCLUSIONS: Polymyalgia rheumatica fast-track clinics might lighten the burden of the disease. However, it has some limits that should carefully assessed in planning health policies.

Subjective sleep disturbances at the time of diagnosis in patients with polymyalgia rheumatica and in patients with seronegative elderly-onset rheumatoid arthritis. A pilot study.

OBJECTIVES: To investigate subjective sleep disturbances in patients with recent-onset polymyalgia rheumatica (PMR) and in patients with recent-onset seronegative elderly-onset rheumatoid arthritis (SEORA). MATERIAL AND METHODS: The study involved patients consecutively referred to two outpatient clinics from January to June 2018, with a diagnosis of PMR according to 2012 European League Against Rheumatism and American College of Rheumatology provisional criteria, and patients with a diagnosis of SEORA according to 1987 American Rheumatism Association criteria + age + absence of rheumatoid factor and anti-citrullinated peptide antibodies. All patients were naive to glucocorticoid (GC) therapy. After informed consent, we asked the patients to fill out a questionnaire including the Medical Outcomes Study - Sleep Scale (MOS-SS), pain Visual Analogic Scale (VAS), Cumulative Illness Rating Scale (CIRS), Neuropsychiatric Inventory (NPI), and how many minutes their morning stiffness (MS) lasted, at baseline and after 1 (T1) and 12 (T2) months. Differences between groups were calculated with the t-test; all p-values were two-sided and p < 0.05 was used to determine statistical significance. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration. RESULTS: The MOS-SS scores and MS duration were the only variables to show at T0 a significant difference between the two groups. In particular, MOS-SS scores were 47.6 ±8.4 (PMR) and 28.26 ±12.4 (SEORA), with p-values = 0.000. The MS duration was 90 ±9.9 minutes and 45 ±5.5 minutes, with p-value = 0.000. At T1 and T2, MOS-SS scores and MS duration decreased in the two groups, and no significant differences were found. CONCLUSIONS: The study suggests that the assessment of subjective sleep disturbances can be useful in the differential diagnosis between recent-onset PMR and SEORA.

Polymyalgia rheumatica with normal inflammatory indices at the time of diagnosis: can we just move a step forward?

The existence of polymyalgia rheumatica (PMR) with normal inflammatory indices at the time of diagnosis still represents a diagnostic conundrum. According to the literature, some patients with PMR following immune checkpoint inhibitory therapy had normal values of both erythrocyte sedimentation rate and C-reactive protein concentrations at the time of diagnosis. In this short communication we investigated the possibility that in some patients with PMR the main pathogenic mechanism is constituted by inhibition of some checkpoints, such as programmed death receptor-1, programmed death ligand 1, and "cytotoxic" lymphocyte antigen 4. In these patients, the pathogenetic mechanisms underlying PMR can act much more upstream than commonly suggested. Also, we addressed the question of whether these patients should be considered as affected by PMR-like syndromes or by PMR subset.

Depression and depressive symptoms in patients with polymyalgia rheumatica: discussion points, grey areas and unmet needs emerging from a systematic review of published literature.

OBJECTIVES: In 1979, Bird et al. proposed depression as a diagnostic criterion for polymyalgia rheumatica (PMR). More recently, the significance of depression in PMR patients has been re-proposed, , and some researchers have suggested that PMR may increase the risk of depression. The aim of our article is to evaluate the relationship between PMR and depression. MATERIAL AND METHODS: Systematic literature searches were performed on 19th and 20th May 2020 based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The search was restricted to all studies and case reports with English abstract, published in any language, since 1979 (when depression was first proposed as a diagnostic criterion for PMR) describing the association of PMR with depression. Exclusion criteria were as follows: reviews, conference abstracts, comments, non-original articles; and articles discussing giant cell arteritis (GCA) and PMR when data and observations for the two conditions were not clearly subdivided. RESULTS: The initial search yielded 812 papers, of which 115 duplicates were removed. A total of 697 articles had a first screening and 506 were excluded based on title and abstract reviews; 117 articles underwent full-length scrutiny, and 99 full-text articles were excluded because they did not meet the inclusion and exclusion criteria (reviews and comments = 58; articles with outcome of interest not reported = 34; low-quality articles = 7). At least, 18 articles were included in this review. CONCLUSIONS: The review did not find any studies that clarified the prevalence rates of depression in patients with PMR. Furthermore, the studies reviewed did not offer any clarity as to whether patients suffered from just depressive symptoms or clinical depression, and that accepted diagnostic criteria for depression had not been employed, indicating that a robust method for diagnosing depression had not been employed. Collaboration of different professionals should be improved through shared guidelines.

If something looks like an apple, is it necessarily an apple? - reflections on so-called "statin-induced polymyalgia rheumatica".

The existence of polymyalgia rheumatica (PMR) induced by statins has been hypothesised by some investigators. This review article highlights the fact that there is no evidence it is real. On the contrary, PMR and statin-associated muscle symptoms (SAMS) are two totally different conditions. Shoulder and hip ultrasound (US) examinations can make an important contribution in distinguishing a true case of PMR from a PMR-like illness induced by statins. The possibility that SAMS may worsen the clinical manifestations of a PMR patient should be taken into account in clinical practice, and drug discontinuation should be proposed when deterioration or relapse is not otherwise justifiable.

Polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema following intravesical instillation of bacillus Calmette-Guerin.

Intravesical instillation of bacillus Calmette-Guerin (BCG) after transurethral cancer resection is an approved part of the management of non-muscle invasive bladder cancer (NMIBC). The onset of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) following this immunotherapy is anecdotal. We report the case of a 69-year-old male patient suffering from boxing-glove swelling of the hand associated with bilateral pain, aching and stiffness in the shoulders and pelvic girdles, which occurred after a cycle of six intravesical instillations of BCG. Polymyalgia rheumatica associated with RS3PE was diagnosed, prednisone therapy started and definitively stopped after 13 months. During a 16-year follow-up, no alternative diagnosis was possible. The role of genetic factors and of the senescence of the immune system is discussed. According to our best knowledge, this is the first case report of PMR associated with RS3PE following intravesical instillation of BCG.

Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article.

Little is known about the development of psychosis during hydroxychloroquine (HCQ) treatment, especially in elderly patients affected by rheumatic diseases, with multiple comorbidities and treatments. To summarize the available evidence on HCQ-induced psychosis in elders, we performed a literature review. Additionally, individual case safety reports sent to the European Pharmacovigilance database (EudraVigilance) with HCQ as suspected drug and related to adverse events belonging to the System Organ Class 'Psychiatric disorders' were shown. Over the years, evidence was published about the risk of neuropsychiatric clinical manifestations during HCQ treatment for rheumatic diseases, but few of them were related to elderly patients. These adverse events can include less severe clinical manifestations such as affect lability and nervousness or more severe conditions such as actual psychosis and suicidal tendencies, which frequency are actually unknown. The presence of risk factors in these patients may precipitate HCQ-induced psychosis and their precocious detection could be associated with a risk minimization. Among predisposing risk factors, there are the co-exposure to interacting drugs, alcohol intake, familial history of psychiatric diseases, female gender, and the concomitant use of low-dose glucocorticoids. In some cases it was possible to reverse psychotic behaviour with the antipsychotic treatment or with HCQ suspension.

Diagnosis of polymyalgia rheumatica in primary health care: favoring and confounding factors - a cohort study.

OBJECTIVES: To evaluate in a primary care setting the favoring and confounding factors for the diagnosis of polymyalgia rheumatica (PMR). MATERIAL AND METHODS: Among 303 patients consecutively referred by their general practitioners (GPs) to our rheumatologic outpatient clinic, we identified three groups: group A - patients with confirmed diagnosis of PMR, group B - patients with unconfirmed diagnosis, group C - patients with unrecognized PMR. All the diagnostic confounding and favoring factors were discussed with GPs using an e-mail questionnaire. Participation in rheumatology training courses represented the final question. The collected data were statistically assessed in a blind way. In Fisher's exact test and ANOVA test, a p-value was significant if < 0.05. The study was carried out in compliance with the Helsinki Declaration and approved by the Ethics Committee of Mariano Lauro Hospital. Every patient signed an informed consent form at the time of the first visit. RESULTS: All patients were Caucasian; 24.1% were male; mean age was 72.3 ±8.6 years (min. - 51, max. - 94). There were 41 patients in group A, 93 in group B and 169 in group C. The percentage of misdiagnoses was very high (87.1%): among 134 patients diagnosed with PMR by their GPs (group A + group B) confirmation was made in 41, and in 169 unrecognized PMR was found. Participation in training courses was very significant compared to the diagnostic accuracy (p < 0.0001 in χ2 test) and to the diagnosis timing (24.3 days ±12.5 vs. 42.9 ±15.5 with p-value < 0.05 in the ANOVA test). When the percentages were assessed according to participation, an inadequate evaluation of some clinical manifestations favored over-diagnosis among the trained GPs. CONCLUSIONS: The level of diagnostic accuracy for PMR must be improved in primary care. Participation in rheumatology training courses can be an important step.