Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review.

INTRODUCTION: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs. METHODS: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data. RESULTS: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity. CONCLUSIONS: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

Expanding the Treatment Team: What Is the Role for Occupational Therapy, Physical Therapy, Wound Care, and Nutritional Support in Systemic Sclerosis?

The optimal systemic sclerosis (SSc) care plan includes an occupational therapist and physical therapist as well as wound care experts and a registered dietitian if indicated. Screening instruments for functional and work disability, hand and mouth limitations, malnutrition, and dietary intake can identify the need for ancillary support services. Telemedicine can assist in developing effective ancillary treatment plans. Reimbursement for services may limit access for patients with SSc to expand their care team but a focus on prevention rather than management of damage is recognized as an important unmet need in SSc. In this review, the role of a comprehensive care team for SSc is discussed.

Nursing interventions for patients with rheumatic and musculoskeletal diseases on biological therapies: a systematic literature review.

Investigating unmet needs and identifying the necessary interventions for patients affected by rheumatic and musculoskeletal diseases (RMDs) may help significantly to ensure the continuity and quality of the chronic care pathway. To this aim, the contribution of rheumatology nurses requires further evidence. The aim of our systematic literature review (SLR) was to identify the nursing interventions directed towards patients with RMDs undergoing biological therapy. To retrieve data, a search was carried out in the MEDLINE database, the Cumulative Index to Nursing and Allied Health Literature (CINAHL database), the APA PsycINFO database and the Excerpta Medica Database (EMBASE) from 1990 to 2022. The systematic review was carried out in accordance with the relevant PRISMA guidelines. Inclusion criteria were as follows: (I) adult patients with RMDs, (II) undergoing therapy with Biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs), (III) original and quantitative research papers in English with available abstract, (IV) specific to nursing interventions and/or outcomes. Two independent reviewers screened the identified records for eligibility according to their title and abstract, full texts were subsequently assessed and, finally, data was extracted. Critical Appraisal Skills Programme (CASP) tools were used to evaluate the quality of the studies included. Among the 2348 records retrieved, 13 articles met the inclusion criteria. These consisted of six randomised controlled trials (RCTs), one pilot study and six observational studies on RMDs. In a total population of 2004 patients, 43% (862/2004) of the cases concerned rheumatoid arthritis (RA) and 56% (1122/2004) of the cases concerned spondyloarthritis (SpA). Three major nursing interventions were identified, namely education, patient-centred care and data collection/nurse monitoring, which were correlated with high satisfaction rates regarding care, increased self-care capacity and treatment adherence among patients. All interventions followed a protocol defined in collaboration with rheumatologists. The large degree of heterogeneity in the interventions did not allow the performance of a meta-analysis. Rheumatology nurses are part of a multidisciplinary team caring for patients with RMDs. Following an accurate initial nursing evaluation, rheumatology nurses can plan and standardise their interventions focusing primarily on patient education and personalised care based on actual needs, such as psychological well-being and disease control. However, the training for rheumatology nurses should define and standardise, as much as possible, the competencies required for the detection of disease parameters. Key Points • This SLR provides an overview of nursing interventions for patients with RMDs. • This SLR considers the specific population of patients on biological therapies. • Training for rheumatology nurses should standardise, as much as possible, the knowledge and methods required for detecting disease parameters. • This SLR highlights the various competencies of rheumatology nurses.

Systemic Sclerosis Patients Experiencing Mindfulness-Based Stress Reduction Program: The Beneficial Effect on Their Psychological Status and Quality of Life.

Psychological concerns in Systemic Sclerosis (SSc) patients represent an important issue and should be addressed through non-pharmacological treatments. Thus, the aim of the present study was to assess the effects of the Mindfulness-Based Stress Reduction (MBSR) program on psychological variables and the perspectives and experiences of patients with an SSc diagnosis. Notably, 32 SSc patients were enrolled and assigned to either the intervention (MBSR) group or the waitlist group. Inclusion criteria were (i) age ≥ 18 years, SSc diagnosis according to EULAR/ACR diagnostic criteria and informed consent. Exclusion criteria were previous participation in any Mind-Body Therapy or psychiatric diagnosis. Quantitative and qualitative outcomes were investigated through clinometric questionnaires and individual interviews. MBSR did not significantly impact outcomes such as physical functionality, anxiety, hopelessness, depression, physical health status, perceived stress, mindfulness and mental health status. For the anger evaluation, statistically significant differences are found for both controlling and expressing anger, indicating that the MBSR program had a favorable impact. As for qualitative results, more awareness of daily activities, stress reduction in terms of recognizing the causes and implementing self-strategies to prevent them, adherence to therapy, and recognition of the effect of medication on their bodies were reported. In conclusion, it is important to highlight the absence of negative or side effects of the MBSR program and the positive impact on patients' experience and perspective; thus, we suggest this approach should be taken into account for SSc patients.

The Role of the Multidisciplinary Health Care Team in the Management of Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterised by immune dysfunction, vascular damage and fibrosis affecting the skin and multiple internal organs. The clinical spectrum of SSc is wide and its manifestations may lead to severe morbidity and mortality, in addition to a great impact on patients' quality of life. Due to the multifaceted clinical manifestations of SSc, its management requires a combined expertise of different medical specialists to guarantee an adequate disease control and prevent organ complications. Multi-disciplinary teams (MDT), which are composed by physicians and other specialized health professionals, represent therefore a key element for the comprehensive management of SSc patients. Moreover, MTD can improve communication and patients' empowerment while the presence of dedicated nurses can help patients to ask questions about their condition. The scope of this narrative review is to analyse the available evidences regarding the role of MDT in the management of SSc patients, and how this holistic approach may improve different disease domains and the overall prognosis. MDT regarding the cardiovascular and lung complication are the more represented in literature, given the great impact in prognosis. Nonetheless, MDT have been shown to be fundamental also in other disease domains as they can intercept early manifestations, thus stratifying patients based on the individual risks in order to personalize patients' follow-up. MDTs may also minimize the treatment delay, enabling fast-track specialist referral. On the other hand, there are few trials specifically studying MDT in SSc and several authors have highlight the lack of standardization.

Information Survey on the Use of Complementary and Alternative Medicine.

Background and Objectives: Complementary and alternative medicines (CAMs) are generally considered non-scientific and poor effective therapies. Nevertheless, CAMs are extensively used in common clinical practice in Western countries. We decided to promote a Delphi consensus to intercept the opinion of Italian physicians on CAM use in clinical practice. Materials and Methods: We run a Delphi-based consensus, interviewing anonymously 97 physicians. Of these, only 78 participate to the questionnaire. Results: Consensus about agreement and disagreement have been reached in several topics, including indication, as well as safety issues concerning CAMs. Conclusions: The use of CAMs in clinical practice still lacks evidence. Experts agree about the possibility to safely use CAMs in combination with conventional medicines to treat non-critical medical conditions.

The Yin-Yang Pharmacomicrobiomics on Treatment Response in Inflammatory Arthritides: A Narrative Review.

(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides.

A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale.

OBJECTIVES: The multi-systemic, heterogenous nature of diffuse cutaneous systemic sclerosis (dcSSc) presents challenges in designing clinical studies that can demonstrate a treatment effect on overall disease burden. We describe the design of the first Phase 3 study in dcSSc patients where the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score was chosen prospectively as the primary outcome. The CRISS measures key clinical disease parameters and patient-reported outcomes (PROs). METHODS: RESOLVE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial of dcSSc patients evaluating the efficacy and safety of lenabasum. Patients ≥18 years of age with dc-SSc and disease duration ≤6 years were eligible. Patients could continue stable background therapy for dcSSc, including stable immunosuppressive therapies. They were randomised to lenabasum 5 or 20 mg twice daily or placebo. The primary efficacy outcome was the mean change from baseline to 52 weeks in the ACR CRISS score. RESULTS: The study enrolled 365 patients over 1.5 years at 77 sites in 13 countries in North America, Europe, Israel, and Asia-Pacific, with the last patient first visit on May 1, 2019. CONCLUSIONS: RESOLVE-1 is the first Phase 3 interventional study to date in dcSSc to prospectively use the ACR CRISS as the primary efficacy outcome. Eligibility criteria allowed background therapy as might occur in clinical practice. This approach also facilitated timely patient enrolment. RESOLVE-1 provides a novel study design that may be used for future Phase 3 dcSSc studies to assess the holistic efficacy of therapy.

The challenge of pet therapy in systemic sclerosis: evidence for an impact on pain, anxiety, neuroticism and social interaction.

OBJECTIVES: The aim of our study was to evaluate the effect of animal-assisted intervention (AAI), a complementary support to traditional therapies focused on the interaction between animals and human beings, in improving psychological trait, anxiety and pain in a cohort of systemic sclerosis (SSc) patients. METHODS: 42 SSc patients, undergoing iloprost intravenous infusion, were divided in three groups: 1) 14 patients submitted to 20 AAI sessions; 2) 14 patients engaged in alternative social activity (control group 1 - C1); and 3) 14 patients without any alternative activity (control group 2 - C2). All patients underwent Visual Analog Scale (VAS), the State-anxiety (STAI-S) and emotional faces at the beginning (s0) and at the end (s1) of each single session, while General Anxiety State-Trait Anxiety Inventory (STAI-T), Beck Depression Inventory (BDI), Social Interaction Anxiety Scale (SIAS), Eysenck Personality Questionnaire-Revised (EPQ-R), the Social Phobia Scale (SPS), the Toronto Alexythymia Scale (TAS-20), the Thought Control Questionnaire (TCQ) were administered at baseline (t0) and at the end of the project (t1). RESULTS: AAI group showed a significant decrease of the anxiety state level in respect to the two control groups (p<0.001). VAS scale resulted lower both in AAI (p < 0.001) and C1 group (p<0.01). Moreover, STAI-T and TAS scores were significantly reduced in AAI group (p<0.001). TCQ scale showed that patients treated with AAI, compared to control group C2, had greater capacity to avoid unpleasant and unwanted thoughts (p<0.05). In AAI group, the EPQ-R test revealed an enhancement of extroversion trait compared to both control groups (p<0.05). CONCLUSIONS: Our data show that AAI significantly reduces pain perception, anxiety, neuroticism and ameliorates patients' social interaction, therefore it may be a useful to allow a better compliance to traditional therapies.

Determinants of vitamin D levels in children, adolescents, and young adults with juvenile idiopathic arthritis.

OBJECTIVE: Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA. METHODS: We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination. RESULTS: Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001). CONCLUSION: JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.

Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology II. Safety.

Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations, and, to this end, a systematic literature review was performed and the evidence derived from it was discussed and summarized as expert opinions. Levels of evidence and strength of recommendations were reported. The recommendations reported refer to the safety of biologic agents and are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule.

Recommendations for the use of biologic therapy in the treatment of psoriatic arthritis: update from the Italian Society for Rheumatology.

OBJECTIVES: To update the 2006 Italian Society for Rheumatology recommendations for the use of biologic (TNF-α blocking) agents in the treatment of psoriatic arthritis (PsA). METHODS: A panel of experts performed a literature search and identified the items that required updating on the basis of new published data. A draft of the updated recommendations was circulated to a group of Italian Rheumatologists with a specific expertise in PsA and in therapy with biologic agents, and their suggestions were incorporated in the final version. RESULTS: A consensus was achieved regarding the initiation and the monitoring of anti-TNF-α agents in PsA. Inclusion and exclusion criteria were defined and specific recommendations were made for patients with psoriatic peripheral synovitis, spondylitis, enthesitis, and dactylitis, respectively. We also specified criteria for assessment of response to treatment and for withholding and withdrawal of therapy. CONCLUSIONS: These recommendations may be used for guidance in deciding which patients with PsA should receive biologic therapy. Further updates of these recommendations may be published on the basis of the results of new clinical studies and of data from post-marketing surveillance.

Recommendations for the use of biologic therapy from the Italian Society for Rheumatology: off-label use.

The advent of biological agents has provided further opportunities to treat resistant or relapsing rheumatic diseases, with robust data for rheumatoid arthritis and spondyloarthritis coming from randomised controlled trials. However there are data also on other rare inflammatory rheumatic diseases even if the evidence available may be heterogeneous and/or controversial. Another challenging scenario is represented by diseases that are not uncommon, but that may present with multiple manifestations and prove resistant to conventional therapies, thus requiring the use of biological agents. To assist physicians in making correct therapeutic choices in such cases, the Italian Society for Rheumatology (SIR) has developed specific recommendations for the use of biological agents in rare disease or for the off-label use of such agents in refractory inflammatory disorders.

Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology I. Efficacy.

Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations and, to this end, a systematic literature review was carried out and the evidence derived from it was discussed and summarised as expert opinions. Levels of evidence, strength of recommendations and levels of agreement were reported. The recommendations reported are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule.

Neurogenic aspects of inflammation.

The relationship between the inflammatory process and the nervous system is twofold. The nervous system is activated by inflammation which causes inflammatory pain and impaired motor function. Conversely, the nervous system acts back on the peripheral process. This is achieved by output systems at different levels, including primary afferent fibers (neurogenic inflammation), spinal cord (reflexes), and the brain (eg, neuroendocrine functions). This article first addresses the activation of the nociceptive system by inflammation; the second part describes the effects of the nervous system on inflamed tissue.