Case report of polymyalgia rheumatica in a male patient with three different neoplasms treated with pembrolizumab.

In this manuscript we aim to describe a particular case of a 63 years-old man who developed three different malignancies (one was a rare case of breast cancer) among nearly five years. In particular, for the diagnosis of melanoma, he was treated with pembrolizumab, a PD-1 inhibitor. After few months of treatment with pembrolizumab, the patient reported the onset of musculoskeletal symptoms such as inflammatory pain at the shoulders and morning stiffness, with raised CRP and ESR and imaging evidence of bursitis and tenosynovitis. A polymyalgia-like syndrome was diagnosed. Understanding if these manifestations are linked to the use of pembrolizumab or to a paraneoplastic syndrome, and how to manage the patient, was the real challenge.

In memory of Dr. Luis Espinoza.

Not available.

Remission, low disease activity and improvement of pain and function in psoriatic arthritis patients treated with IL-12/23 and IL-17 inhibitors. A multicenter prospective study.

The development of new biologic and targeted synthetic DMARDs can lead to good disease control. The aim of the present study was to assess the rate of remission and low disease activity, and the improvement of pain and function, in psoriatic arthritis (PsA) patients treated with new anti-IL-12/23 and anti-IL-17 biologic agents. A prospective 6-month study was performed. Patients fulfilling the CASPAR criteria for PsA that started ustekinumab, secukinumab and ixekizumab were enrolled and prospectively followed in a setting of clinical practice. Patients were considered in minimal disease activity (MDA), when they met at least 5/7 of the criteria previously defined. DAPSA score ≤4 was also evaluated as a remission criterion. Pain on VAS, PtGA and HAQ were also assessed in all patients. Patients achieving MDA were compared to non-MDA to identify outcome predictive factors. Of the 70 patients treated with ustekinumab, secukinumab and ixekizumab, at baseline, no patients were in MDA or had a DAPSA score ≤4. Ten patients (14.2%) were lost during the follow-up. After 6 months, MDA was achieved in 22 (31.4%) patients. DAPSA≤4 was achieved in 17 (24.2%) patients. Significant improvement in pain, PtGA and HAQ was also found. Patients naïve to anti-TNF treatment achieved more frequently MDA compared to anti-TNF-experienced patients. Male sex, high levels of CRP and absence of comorbidities were found to be predictors of MDA. In our prospective observational study, MDA was achieved in 31.4% and DAPSA remission in 24.2% of patients treated with inhibitors of IL-12/23 and IL-17, thus making this target achievable in PsA patients treated with these drugs.

Association between clinical specialty setting and disease management in patients with psoriatic arthritis: results from LOOP, a cross-sectional, multi-country, observational study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic and debilitating disease that can be managed by different clinical specialists. OBJECTIVES: The objective of the LOOP study was to evaluate the impact of clinical specialty setting on the time to diagnosis and treatment of patients with PsA. Clinical disease activity and disease burden were also compared between clinical settings. METHODS: LOOP was a cross-sectional, multicentre, observational study conducted in 17 countries in Western and Eastern Europe, the Middle East, Latin America and Asia. Adult patients (≥18 years) with a suspected or established diagnosis of PsA who were routinely visiting a rheumatologist, dermatologist or non-rheumatology/non-dermatology physician were enrolled. All patients were assessed by both a rheumatologist and a dermatologist. RESULTS: Of 1483 enrolled patients, a total of 1273 had a confirmed diagnosis of PsA. There was no significant difference in the median time from onset of inflammatory musculoskeletal symptoms to PsA diagnosis between patients enrolled by rheumatologists and dermatologists (6.0 vs. 3.9 months). However, the median time from diagnosis to first treatment with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) was significantly shorter in the rheumatology setting compared with the dermatology setting (0 vs. 2.0 months; P < 0.001). In addition, disease activity was significantly higher in the dermatology setting compared with the rheumatology setting. CONCLUSIONS: Differences in the management and clinical status of patients with PsA were observed between the rheumatology and dermatology settings. Importantly, median time from diagnosis to first csDMARD was significantly shorter in the rheumatology setting, and patients in the dermatology setting had higher disease activity. These data show the importance of improved collaboration between rheumatologists and dermatologists.

Occult axial involvement in patients with psoriatic arthritis mutilans: a case report.

We present the case of a patient with psoriatic arthritis (PsA) mutilans and occult axial involvement. The patient had suffered from PsA mutilans for more than a decade, with severe residual articular damage, but had been in clinical remission for years. Clinical axial involvement was never reported; however, magnetic resonance imaging of the sacroiliac joints, performed for other reasons, documented active inflammation and damage even without clinical symptoms. These findings corroborated the hypothesis that axial involvement could be asymptomatic, subclinical and, furthermore, underdiagnosed or even occult in patients with PsA mutilans, in which cases it should be carefully evaluated.

Red flags for appropriate referral to the gastroenterologist and the rheumatologist of patients with inflammatory bowel disease and spondyloarthritis.

Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee. Then, a consensus among expert gastroenterologists and rheumatologists (10 in the steering committee and 13 in the expert panel) was obtained using the RAND method to confirm the appropriateness of each red flag as 'major' (one sufficient for patient referral) or 'minor' (at least three needed for patient referral) criteria for specialist referral. The review of the literature confirmed the high prevalence of co-existing IBD-SpA. Positive and negative predictive values of red flags were not calculated, given the lack of available data. A consensus among gastroenterology and rheumatology specialists was used to confirm the appropriateness of each red flag. Major criteria to refer patients with SpA to the gastroenterologist included: rectal bleeding, chronic abdominal pain, perianal fistula or abscess, chronic diarrhoea and nocturnal symptoms. Major criteria to refer patients with IBD to the rheumatologist included: chronic low back pain, dactylitis, enthesitis and pain/swelling of peripheral joints. Several major and minor red flags have been identified for the diagnosis of co-existing IBD-SpA. The use of red flags in routine clinical practice may avoid diagnostic delay and reduce clinic overload.

Consensus on the management of patients with psoriatic arthritis in a dermatology setting.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable. OBJECTIVE: To provide practical recommendations for the management of patients with PsA in the dermatology setting including early diagnosis and treatment. METHODS: A consensus document was written by an expert panel composed by dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant questions were selected and elaborated with answers/statements based on a narrative literature review. The resulting document was discussed in a face-to-face meeting adopting a nominal group technique to reach consensus (i.e. 100% agreement) using the Delphi method. RESULTS: A consensus was achieved in defining the following: the clinical characteristics differentiating inflammatory and non-inflammatory signs and symptoms of joint disease; the most important differential diagnoses of PsA in clinical practice; the most useful screening questionnaires, serum laboratory tests and imaging techniques for the detection of early PsA; the criteria for dermatologist to refer patients with PsO to rheumatologist; the criteria for the diagnosis of PsA; the selection of the indices that the dermatologist could use for measuring the activity and severity of PsA in clinical practice; when systemic steroids and/or intra-articular steroid injections are indicated in the treatment of PsA. Finally, systemic treatments including synthetic and biologic disease-modifying antirheumatic drugs to be considered for the treatment of PsA have been reported. CONCLUSIONS: The implementations of these practical recommendations could be very helpful for the management of patients with PsA in the dermatology setting including early diagnosis and treatment.

Mesenchimal stem cells: a possible role in the pathogenesis and treatment of spondyloarthritis.

Spondyloarthritis (SpAs) are a group of chronic inflammatory diseases that affect joints and enthesis with a possible involvement of other districts such as skin, eye and bowel. In SpAs, the inflammatory process could lead to both erosive damage (as in peripheral joint involvement of psoriatic arthritis), or bone formation (as in ankylosing spondylitis) with a reduction in function and quality of life. Recently, Mesenchimal stem cells (MSCs) transplant was used in different diseases, including autoimmune and inflammatory diseases, with the aim of repairing tissue damage, exploiting their regenerative capacity. However, MSCs also proved to have an immune-modulatory capacity due to their interaction with the cells of the immune system. The aim of this brief paper was to review the possible pathogenic role and the new perspective of MSCs use in SpAs.

[Not Available]. / New approved drugs for psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that possibly leads to structural damage and to a reduction of joint function and poor quality of life. Treatment of PsA has changed since its introduction of anti- TNF drugs, which have shown to reduce the symptoms and signs of the disease and slow the radiographic progression. However, recently, the discovery of new pathogenic mechanisms have made possible the development of new molecules that target pro-inflammatory cytokines involved in skin, joint and entheseal inflammation. New drugs like ustekinumab, secukinumab and apremilast inhibit interleukin axis and intracellular pathways and showed their efficacy and safety in randomized clinical trials. These drugs have been recently approved for the treatment of PsA and included in the new EULAR and GRAPPA treatment recommendations. The aim of this paper is to briefly review the clinical trials that led to their approval for PsA.

Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs.

The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was <20 mm (on a visual analogue scale of 0-100 mm) in each of the following 4 domains: 1) patient global assessment (in the last week); 2) pain (spinal pain); 3) function [measured by the bath ankylosing spondylitis functional index (BASFI)]; 4) inflammation [mean of intensity and duration of morning stiffness, from the bath ankylosing spondylitis disease activity index (BASDAI)]. Two hundred fourteen AS patients (M/F=160/54; median age/range=43.2/19-78 years; median disease duration/ range=96/36-189 months) were treated with ADA (15.8%), ETA (28.9%) and INF (55.1%). At 12 and 24 months, high serum level of C reactive protein (CRP) (≥2 vs ≤0.8 mg/dL) were associated with higher rate of PR in AS patients treated with anti-TNFα drugs. At 24 months, PR was associated with shorter disease duration (≤36 vs ≥189 months) and higher erythrosedimentation rate (ESR) values (≥45 vs ≤17 mm/h). In male patients lower bath ankylosing spondylitis metrology index (BASMI) (≤2 vs ≥6) and absence of psoriasis were associated with higher PR rate only at 12 months. Other parameters assessed before treatment, such as BASDAI, BASFI, peripheral arthritis, inflammatory bowel disease and uveitis were not associated with PR. Our long-term longitudinal study in a setting of clinical practice showed that inflammatory parameters (i.e. CRP, ESR) and disease duration represent the most important predictive variables to achieve PR with an anti-TNFα treatment.

Rehabilitation and surgical management of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease which, if untreated, may progress to severe damage of the spine with functional impairment, disability and poor quality of life. An increased mortality has been reported in AS patients compared to the general population. AS requires combined management (pharmacological and non-pharmacological) and advice by different health professionals. Even the pharmacological treatment in the last decade has dramatically changed the outcome, the severity of the disease might require a surgical approach for the hip involvement with total hip replacement, or the corrective spinal surgery. However, this surgery deserves some careful approaches since the complexity of the disease. Rehabilitation still represents a cornerstone of the global management of AS patients. The present review summarizes the state of art of surgical management of these two diseases.

Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices.

The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS) through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range) 43.5/28-69 years; disease duration (median/range) 9.7/1-36) years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT) of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD) of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy). Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR), ASDAS-C-reactive protein (CRP), bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index) and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03). FMD did not statistically differ between patients and controls (12.5% vs 15%; P>0.05). We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04). No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls.

Rapid effectiveness of certolizumab pegol in non-radiographic axial spondyloarthritis.

In axial spondyloarthritis (SpA), the efficacy of certolizumab pegol (CZP), a novel pegylated anti-tumor necrosis factor alpha drug has not been investigated. We report that CZP showed a rapid effectiveness, assessed clinically and by magnetic resonance imaging, in a patient with a non-radiographic axial SpA, classified according to Assessment in SpondyloArthritis International Society (ASAS) criteria. This case suggests that CZP could be considered an useful treatment in non-radiographic axial SpA, supporting that an earlier therapeutic approach could play a relevant role in the management of the disease.

Psoriatic arthritis: imaging techniques.

Imaging techniques to assess psoriatic arthritis (PsA) include radiography, ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy. The radiographic hallmark of PsA is the combination of destructive changes (joint erosions, tuft resorption, osteolysis) with bone proliferation (including periarticular and shaft periostitis, ankylosis, spur formation and non-marginal syndesmophytes). US has an increasing important role in the evaluation of PsA. In fact, power Doppler US is useful mainly for its ability to assess musculoskeletal (joints, tendons, entheses) and cutaneous (skin and nails) involvement, to monitor efficacy of therapy and to guide steroid injections at the level of inflamed joints, tendon sheaths and entheses. MRI allows direct visualization of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in PsA. MRI has allowed explaining the relationships among enthesitis, synovitis and osteitis in PsA, supporting a SpA pattern of inflammation where enthesitis is the primary target of inflammation. CT has little role in assessment of peripheral joints, but it may be useful in assessing elements of spine disease. CT accuracy is similar to MRI in assessment of erosions in sacroiliac joint involvement, but CT is not as effective in detecting synovial inflammation. Bone scintigraphy lacks specificity and is now supplanted with US and MRI techniques.

Psoriatic arthritis: treatment strategies using anti-inflammatory drugs and classical DMARDs.

Psoriatic Arthritis (PsA) is a chronic inflammatory disease typically characterized by arthritis and psoriasis variably associated with other extra-articular manifestations. PsA has been considered a milder and less disabling disease compared with rheumatoid arthritis (RA), even if some studies showed that PsA had joint erosions and damage. In addition, about 20-40% of PsA patients have axial skeleton involvement that may lead to functional limitation and deformity. The treatment of PsA ranged from initial treatment with non-steroidal anti-inflammatory drugs (NSAIDs) to one or more disease-modifying anti-rheumatic agents (DMARDs) for the suppression of inflammation in patients with recalcitrant peripheral joint disease. In clinical practice, the most widely used DMARDs are methotrexate (level of evidence B), sulfasalazine (level of evidence A), leflunomide (level of evidence A), and ciclosporin (level of evidence B). However, the efficacy of these agents in inhibiting joint erosions has not been assessed in controlled studies. Finally, the effectiveness of DMARDs in treating enthesitis and dactylitis is controversial. The present paper revised the evidence-based results on treatment with "conventional" therapy for PsA. The revision was based on all the subsets of the diseases, namely the various manifestations of the articular involvement (peripheral, axial, enthesitis, dactylitis) as well as the skin and nail involvement.

Validity, responsiveness and feasibility of an Italian version of the Canadian Occupational Performance Measure for patients with ankylosing spondylitis.

OBJECTIVES: The purpose of the present study was to produce an Italian version of the Canadian Occupational Performance Measure (COPM) in a group of patients with Ankylosing Spondylitis (AS) and examine the psychometric properties of this version, evaluating its internal consistency, external validity and reliability. Responsiveness and feasibility were also taken into account. METHODS: The Italian COPM, the Italian version of the COPM, was administered to 30 Caucasian patients affected by AS (24 males, 6 females, median age 48 yrs, range 32-67, median disease duration 14 yrs, range 1-30 yrs) together with the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity (BASDAI) and the Italian version of the Health Assessment Questionnaire (HAQ). Internal consistency was evaluated with Cronbach's alpha for reliability. Construct validity of the COPM was evaluated by a correlation between the BASFI, BASDAI and HAQ scores. Test-retest reliability was assessed by the Intraclass correlation coefficient. Responsiveness and feasibility were also considered. RESULTS: All patients completed the validation study. The questionnaire was internally consistent (alpha coefficient=0.774). A significant correlation was recorded between the COPM and the BASFI (rho=-0.566, p<0.01), BASDAI (rho=-0.491, p<0.01). Test-retest reliability showed a good correlation coefficient and it was confirmed by Bland-Altman method. CONCLUSIONS: The Italian COPM is a valid and reliable instrument focused to detect change in a client's perception of occupational performance over time, in AS patients. Our results confirm the utility of this questionnaire to measure outcome and in planning treatment intervention for patients with AS.

The radiological assessment of axial involvement in psoriatic arthritis: a validation study of the BASRI total and the modified SASSS scoring methods.

OBJECTIVES: To assess the validity of the BASRI and m-SASSS scores for the radiological axial involvement in psoriatic arthritis (PsA). Secondary end-points were to report on clinical, functional and radiographic characteristics of axial involvement. METHODS: Inclusion criteria were satisfaction of the CASPAR criteria and the presence of clinical, functional and/or radiological axial involvement. Three observers scored the radiographs by BASRI and m-SASSS. The construct validity was assessed by examining the correlation of instruments with patient reported outcomes and anthropometric measures. The reliability and the feasibility of the scores were also considered. RESULTS: Seventy-seven patients were enrolled (58 M, 19 F, mean age 49.4 + or - 10.8 yrs, disease duration 13.9 + or - 7.9 yrs). Both instruments showed some modest but significant correlation with clinical measures. When compared, the BASRI showed a correlation with BASMI (rho=0.47, p<0.001), cervical rotation (rho=-0.49, p<0.001), tragus to wall (rho=0.34, p<0.01) and occiput to wall (rho=0.49, p<0.001), modified Schober test (rho=-0.24, p<0.05) and RLDQ (rho=-0.24, p<0.05). When compared, m-SASSS showed a correlation with BASMI (rho=0.39, p<0.001), cervical rotation (rho=-0.41, p<0.001), tragus to wall (rho=0.31, p<0.01) and occiput to wall (rho=0.42, p<0.001), modified Schober and Schober test (rho=-0.34, p<0.001; rho= -0.32, p<0.01), finger to floor (rho=0.37, p<0.01). No correlation was found with BASFI, BASDAI and HAQ. Test-retest showed a good reliability of the scores. Both were feasible but BASRI was the quickest. CONCLUSION: Our results showed that BASRI and m-SASSS were valid instruments for use in spondylitis associated with psoriatic arthritis. Longitudinal data is required to provide sensitivity to change of the two scores.

Aortic involvement in ankylosing spondylitis.

Patients with ankylosing spondylitis (AS) may develop cardiovascular manifestations ranging from asymptomatic forms to life threatening conditions. The most important cardiovascular manifestation of AS is aortitis, which frequently involves the aortic root and the ascending aorta leading to valvular insufficiency. The extension of the subaortic fibrotic process into the interventricular septum may cause conduction abnormalities that represent the second common cardiovascular manifestations occurring in AS patients. More rarely, an involvement of coronary arteries and of thoracic and abdominal aorta could be present. Rheumatologists managing AS patients should carefully consider, both in late and in early phases of the disease, the occurrence of an aortic involvement in order to promptly administer adequate treatment.