A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Social Determinants of Health Documentation Among Individuals With Rheumatic and Musculoskeletal Conditions in an Integrated Care Management Program.

OBJECTIVE: Social determinants of health (SDoH), such as poverty, are associated with increased burden and severity of rheumatic and musculoskeletal diseases. This study was undertaken to study the prevalence and documentation of SDoH-related needs in electronic health records (EHRs) of individuals with these conditions. METHODS: We randomly selected individuals with ≥1 International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) code for a rheumatic/musculoskeletal condition enrolled in a multihospital integrated care management program that coordinates care for medically and/or psychosocially complex individuals. We assessed SDoH documentation using terms for financial needs, food insecurity, housing instability, transportation, and medication access according to EHR note review and ICD-10 SDoH billing codes (Z codes). We used multivariable logistic regression to examine associations between demographic factors (age, gender, race, ethnicity, insurance) and ≥1 (versus 0) SDoH need as the odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: Among 558 individuals with rheumatic/musculoskeletal conditions, 249 (45%) had ≥1 SDoH need documented in EHR notes by social workers, care coordinators, nurses, and physicians. A total of 171 individuals (31%) had financial insecurity, 105 (19%) had transportation needs, 94 (17%) had food insecurity; 5% had ≥1 related Z code. In the multivariable model, the odds of having ≥1 SDoH need was 2.45 times higher (95% CI 1.17-5.11) for Black versus White individuals and significantly higher for Medicaid or Medicare beneficiaries versus commercially insured individuals. CONCLUSION: Nearly half of this sample of complex care management patients with rheumatic/musculoskeletal conditions had SDoH documented within EHR notes; financial insecurity was the most prevalent. Only 5% of patients had representative billing codes suggesting that systematic strategies to extract SDoH from notes are needed.

Multiparametric autoantibody analysis: a new paradigm for the diagnosis of connective tissue diseases.

BACKGROUND: In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls. METHODS: Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies. RESULTS: Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies. CONCLUSIONS: This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.

[Pain reduction through physical medicine : Update on the evidence]. / Schmerzreduktion durch physikalische Medizin : Update zur Evidenz.

Epidemiological data from the core documentation of the regional cooperative rheumatism centers in Germany confirm that the symptom of pain is an immense problem in both active inflammatory rheumatic diseases and when in remission. By definition pain is an unpleasant sensory and emotional experience. In the context of inflammatory rheumatic diseases, nociceptive pain is triggered by inflammatory mediators or structurally mechanical distress via activation of the nociceptors. In addition, inflammation is also locally enhanced by the release of proinflammatory substances, such as substance P or calcitonin gene-related peptide (CGRP) from activated nociceptors. The phenomena of inflammation and pain are linked in a self-reinforcing mechanism, which explains why pain can be effectively controlled by inhibiting inflammation and, conversely, why inhibiting pain also has positive effects on the inflammatory response. This review focuses on publications on multimodal rheumatological complex treatment and thermotherapy, which, under evidence-based study criteria, showed a reduction in pain and a partial influencing of molecular markers with a subsequent influence on the development of pain and the inflammatory process. The results are presented in the context of current physiological knowledge on the development of pain.

[Preoperative anemia in patients with rheumatic diseases]. / Präoperative Anämie beim Rheumatiker.

A preoperative anemia is an independent risk factor for the occurrence of complications during and after surgical interventions. It is associated with an increased length of hospital stay, higher mortality and an increased use of blood transfusions. Anemia affects some 30-70% of patients suffering from inflammatory rheumatic diseases, mostly caused by iron deficiency and/or chronic inflammation. The possibilities to treat anemia in rheumatic patients were extremely limited for a long period of time as older studies showed life-threatening side effects, the need of high doses of iron supplements or the occurrence of many nonresponders. Further development of the supplements, new dosage schemes and the combination of supplements increased the efficacy and reduced the occurrence of side effects to a minimum. In addition to orthopedic surgical interventions for rheumatism that despite new therapeutic options in some cases still represent the only way to alleviate the complaints, more and more patients with inflammatory rheumatic diseases also need surgical interventions due to comorbidities. Therefore, anemia should be clarified and preoperatively treated in accordance with the new study situation, to minimize additional complications due to anemia and to increase patient safety.

Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence.

Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40-60 ng/mL (100-150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Exploring the Preferences of Women Regarding Sexual and Reproductive Health Care in the Context of Rheumatology: A Qualitative Study.

OBJECTIVE: To explore the sexual and reproductive health (SRH) care and counseling needs of young women with rheumatic diseases in the context of their rheumatology care. METHODS: Semistructured qualitative telephone interviews were conducted with female patients with rheumatic diseases ages 18-45 years (n = 30). Women were recruited from outpatient rheumatology clinics in western Pennsylvania. Interviews were audiorecorded and transcribed verbatim. A codebook was inductively developed based on the interview transcripts, and the finalized coding was used to conduct a thematic analysis. RESULTS: Four themes emerged from interviews: 1) women want rheumatologists to initiate conversations about SRH and to revisit the conversation over time; 2) women desire clear and complete information regarding fetal, pregnancy, and infertility risks associated with their diseases and disease-modifying antirheumatic drugs (DMARDs); 3) women want to be treated holistically, with SRH addressed in the context of their life circumstances and personal values in addition to their rheumatic diseases; 4) women generally feel that they are intermediaries between their rheumatologists and obstetrician-gynecologists (OB/GYNs), but preferred for providers to communicate directly with one another about their SRH. CONCLUSION: Patients strongly desired rheumatologists to play an active role in their SRH, by initiating family planning conversations, providing SRH education in the context of their diseases and DMARDs, and directly coordinating SRH care with OB/GYNs. To meet patients' SRH needs, further work is needed to clarify the specific role of rheumatologists in providing SRH care and to identify ways to better facilitate communication between rheumatologists and reproductive health care providers.

[Experiences and results from Rheuma-VOR]. / Erfahrungen und Ergebnisse aus Rheuma-VOR.

Rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis are the most common chronic autoimmune rheumatic diseases. For all three diseases an early diagnosis and initiation of treatment is crucial. The proof of concept network study "Rheuma-VOR" is a further developed version of the predecessor project ADAPTHERA and was extended to several federal states. The aim of this prospective study is to improve the early diagnosis of rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis and thus positively impact the quality of care for patients with the help of multidisciplinary coordinating centers. To date 3710 disease-specific questionnaires from patients with the suspected diagnosis of rheumatoid arthritis, psoriatic arthritis or axial spondylarthritis from 1298 different primary care providers were registered in the multidisciplinary coordination centers. A total of 1958 appointments were made with 1 of the 53 participating rheumatology specialists. In 876 patients, 1 of the 3 rheumatic diseases was diagnosed in an early stage. The waiting period was on average 42.5 days depending on the federal state, which is well below the nationwide average. It should also be noted that the coordinated cooperation and risk stratification of the Rheuma-VOR coordination centers relieved the capacity of rheumatology specialists by 1281 appointments (34.5%). In addition, the 2­week Rheuma Bus Tour and the accompanying initiatives in Rhineland-Palatinate (Rheuma-VOR screening app and the triage consultation) are showing first promising positive results.

Position Statement: A Pragmatic Approach for Medical Cannabis and Patients with Rheumatic Diseases.

OBJECTIVE: Pain is one reason some rheumatology patients may consider use of medical cannabis, a product increasingly perceived as a safe and neglected natural treatment option for many conditions. Legalization of recreational cannabis in Canada will promote access to cannabis. Physicians must therefore provide patients with the best evidence-based information regarding the medicinal effects and harm of cannabis. METHODS: The Canadian Rheumatology Association (CRA) mandated the development of a position statement for medical cannabis and the rheumatology patient. The current literature regarding the effects of medical cannabis for rheumatology patients was assessed, and a pragmatic position statement to facilitate patient care was developed by the Therapeutics Committee of the CRA and approved by the CRA board. RESULTS: There are no clinical trials of medical cannabis in rheumatology patients. Evidence is insufficient about the benefit of pharmaceutical cannabinoids in fibromyalgia, osteoarthritis, rheumatoid arthritis, and back pain, but there is evidence of a high risk of harm. Extrapolating from other conditions, medical cannabis may provide some symptom relief for some patients. Short-term risks of psychomotor effects can be anticipated, but longterm risks have not been determined and are of concern. CONCLUSION: Despite lack of evidence for use of medical cannabis in rheumatology patients, we acknowledge the need to provide empathetic and pragmatic guidance for patient care. This position statement aims to facilitate the dialogue between patients and healthcare professionals in a mutually respectful manner to ensure harm reduction for patients and society.

Patient Perspectives on Intravenous Biologics for Rheumatologic Disease.

OBJECTIVE: Two surveys were conducted with patients with rheumatologic diseases to evaluate perceptions of different routes of administration (intravenous [IV] or subcutaneous [SC]) for biologic therapy. METHODS: In Survey I, patient preferences toward biologic treatment were evaluated at a rheumatology practice in Buffalo, New York. In Survey II, Canadian patients enrolled in the BioAdvance patient support program and scheduled to receive IV biologic therapy were asked about their opinions of IV treatment. RESULTS: In Survey I, 243 rheumatology patients participated. Median patient age was 60 years, 76% were female, and 44% were naive to treatment with biologic agents. Among biologic-naive patients, the majority (56%) were open to either SC or IV treatment; biologic-naive women were more likely than men to express a preference for the route of administration. In Survey II, 1,598 patients from the BioAdvance program (including 306 rheumatology patients) completed the full survey. Among the rheumatology patients, the median age was 49 years, 58% were female, and 61% had not previously taken biologics before enrolling in the BioAdvance program. The median rating of IV favorability (on a 10-point scale, with higher numbers indicating increased favorability) recalled by rheumatology patients was 5 prior to their first program infusion, which increased to 9 after multiple treatment infusions. CONCLUSION: These survey results indicate that patients with rheumatoid arthritis are generally open to IV treatment and express high satisfaction with IV therapy. Additional patient and provider education may improve shared decision-making regarding biologic therapy administration options.

Prevalence of musculoskeletal manifestations and related disabilities in a Peruvian urban population living at high altitude. COPCORD Study. Stage I. / Prevalencia de manifestaciones musculoesqueléticas y discapacidad asociada en una población peruana urbana habitante a gran altura. Estudio COPCORD. Estadio I.

OBJECTIVE: Estimate the prevalence of musculoskeletal manifestations and related disabilities of an urban population living at high altitude in Juliaca, Puno, Peru, using the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) questionnaire and Health Assessment Questionnaire (HAQ) disability index. METHODS: A cross-sectional study was performed in a sample of 1095 people. In each interview, the COPCORD methodology and the HAQ were applied. The city was divided into 8 sectors. RESULTS: In all, 614 (56.1%) women were evaluated; 44% were from the Quechua community and 5.1% were Aymara. Before the final 7 days of the study, 132 people (12.05%; 95% CI 9.99-14.11) reported musculoskeletal pain. During the final 7 days of the study, 347 people (31.69%; 95% CI 28.36-35.02) who were predominately women (218; 35.5%; 95% CI 30.8-40.2) reported musculoskeletal pain. The most frequent rheumatic diseases were rheumatoid arthritis (1.27%), gout (0.64%), hand osteoarthritis (OA) (2.83%), knee OA (1.55%), hip OA (0.37%), fibromyalgia (1.09%), and soft tissue rheumatism (8.86%). The HAQ showed an incremental increase proportional to age. The HAQ average for the population was 0.18 (±0.36). Ten people (5.71%) of 175 with rheumatic disease received the services of a shaman. CONCLUSION: It is the first COPCORD study in an urban native population living at high altitude in Peru. The population affected by chronic rheumatic disease preferred professional rather than traditional care; this population had access to limited medical services. Impaired functional capacity measured by HAQ was associated with advanced age.

Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia.

Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside.

National variation in the composition of rheumatology multidisciplinary teams: a cross-sectional study.

The objective of this study is to describe the composition of multidisciplinary teams (MDT) working within rheumatology departments across the UK. All rheumatology departments in the United Kingdom (UK) were invited to participate in a national electronic survey between February 2014 and April 2015 as a part of a national audit for the management of rheumatoid and early inflammatory arthritis commissioned by Healthcare Quality Improvement Partnership. Rheumatology departments were asked to report their MDT composition; defined as a rheumatologist (consultant or specialist trainee), specialist nurse, occupational therapist physiotherapist, and podiatrist. The data were collected as Whole Time Equivalent (WTE) of each professional group at each department adjusted to 100,000 population. The data were grouped according to British Society for Rheumatology regions to study regional variations. The survey was completed by 164/167 departments (98% response rate). All departments reported an MDT comprising a rheumatologist (consultant or specialist trainee) and almost all included a specialist nurse but only 28 (17%) of the departments had MDTs comprising all the professional groups. There was a high degree of regional variation in the provision of Allied Health Professionals (physiotherapists, occupational therapists, and podiatrists) in the UK. MDT care is recommended for the management of inflammatory arthritis, but few UK rheumatology departments have a full complement of healthcare professionals within their MDT. There is a high degree of regional variation in the composition and staffing levels of the rheumatology MDT across the UK; the impact of which warrants further investigation.

Guía clínica para la rehabilitación de los pacientes con enfermedades reumáticas / Clinical guideline for the rehabilitation of patients with rheumatic diseases

Se presenta la guía clínica para el manejo de los pacientes con enfermedades reumáticas con recomendaciones de procedimientos terapéuticos aplicables en atención secundaria. Se construyó con base en la búsqueda metódica de literatura respecto al tema, y el consenso entre los especialistas en Medicina Tradicional y Natural y en Medicina Física y Rehabilitación del Centro Especializado Ambulatorio del Hospital Dr. Gustavo Aldereguía Lima de Cienfuegos. Se hace énfasis en el manejo individualizado de estos pacientes con diagnóstico previo de enfermedad reumática y la fase en que se consultan, la evaluación consecuente del mismo, la evolución y el manejo oportuno; se aborda el tratamiento farmacológico, la acupuntura y sus técnicas afines, ozonoterapia, homeopatía así como los agentes físicos artificiales, las medidas de prevención y los ejercicios terapéuticos(AU)

The clinical guideline for the management of patients with rheumatic diseases is presented with recommendations of therapeutic procedures applicable in secondary health care level. It was designed based on a methodical search in the bibliography related to the topic, and on the agreement of Natural and Traditional Medicine and Physical Medicine and Rehabilitation specialists of the Specialized Ambulatory Center of the General University Hospital Dr. Gustavo Aldereguía Lima. Cienfuegos. It emphasizes in the individualized patient management with previous diagnosis of rheumatic disease and the phase in which they are consulted, its consequent evaluation, the evolution and the timely management; it also approaches the pharmacological treatment, acupuncture and similar techniques, ozone therapy, homeopathy so as artificial physical agents, preventive measures and therapeutic exercises(AU)

[The regional network ADAPTHERA : Rheumatology care through coordinated cooperation: comprehensive, trans-sectoral, covering all health insurance. Initial results]. / Das landesweite Netzwerk ADAPTHERA : Erste Ergebnisse einer flächendeckenden, krankenkassenübergreifenden und transsektoralen rheumatologischen Versorgung.

The aim of the rheumatology network ADAPTHERA ("risk-adapted rheumatology therapy") is to achieve a comprehensive improvement in rheumatology care by coordinating treatment in a regional, trans-sectoral network. Accompanying biomedical research projects, training concepts, and the construction of a rheumatology register (gathering data and biomaterials) should furthermore ensure the stable and sustainable optimisation of care. In the pilot phase (2012-2015) the focus of the ADAPTHERA network, required as a "regional key project" within the framework of the Initiative on Health Economy of Rheinland-Palatinate (RL-P), Germany, was placed on the optimisation of the early diagnosis of rheumatoid arthritis, where it is well-known that there is a significant care deficit.Through the intensive, stable, and coordinated cooperation of all health care partners in the field of rheumatology (registered general practitioners and orthopaedic specialists, registered core rheumatologists as well as the Association of Rheumatology of RL-P) a unique regional, comprehensive offer with verifiable care optimisation has been established in RL-P. The network is supported by outstanding collaboration with the Association of Statutory Health Insurance Physicians and the self-help organisation Rheumatology League.The aims that were established at the start of the project will be achieved by the end of the pilot phase:- significant improvement in the early diagnosis of rheumatoid arthritis (an average of 23.7 days until diagnosis by rheumatologists)- access covering all health insurance (regardless of the particular scheme the patients belong to)- comprehensive (verifiable participation of general practitioners from all over RL-P)- data and biomaterials collection, established as a basis for biomarker research, and a rheumatology register for RL-P.

Biosimilar monoclonal antibodies: preclinical and clinical development aspects.

Biological drugs and their originated biosimilars are large, highly complex molecules derived from living cells or organisms. Traditional medicines, by contrast, are usually simple molecules of low molecular weight, synthesised by chemical means. The distinct complexities and methods of manufacture create an important difference between biosimilars and conventional generic drugs: while chemical generics can be fully characterised as identical to the originator product, biosimilars cannot. In addition, biological therapies are inherently variable, creating unavoidable differences between even subsequent batches of the same product. An expiring patent does not necessarily mean that the manufacturing process of the originator product becomes available to the biosimilar developers (for instance, the relevant cell line clone and growth medium). Therefore, it cannot be guaranteed that biosimilar products are identical to their reference product on a molecular level. This difference has important implications for the regulation and licensing of biosimilars. While conventional generic drugs require only a limited comparison and demonstration of identical chemical structure to the reference product, biosimilars require far more rigorous testing. In general, there must be a thorough comparison of structural and functional characteristics between biosimilar and originator drug. Stepwise nonclinical in vitro and in vivo approaches are recommended to evaluate the similarity of both drugs and any identified micro-heterogeneities must then be assessed for their impact on safety and clinical performance. Subsequently, clinical pharmacokinetic (PK) studies need to be performed in order to demonstrate a similar PK profile, prior to conducting clinical efficacy trials.