2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

Immune dysregulation.

The understanding of immune dysregulation in many different diseases continues to grow. There is increasing evidence that altered microbiome and gut barrier dysfunction contribute to systemic inflammation in patients with primary immunodeficiency and in patients with rheumatic disease. Recent research provides insight into the process of induction and maturation of pathogenic age-associated B cells and highlights the role of age-associated B cells in creating tissue inflammation. T follicular regulatory cells are shown to help maintain B-cell tolerance, and therapeutic approaches to increase or promote T follicular regulatory cells may help prevent or decrease immune dysregulation. Meanwhile, novel studies of systemic-onset juvenile idiopathic arthritis reveal a strong HLA association with interstitial lung disease and identify key aspects of the pathogenesis of macrophage activation syndrome. Studies of hyperinflammatory syndromes, including the recently described multisystem inflammatory syndrome of children, characterize similarities and differences in cytokine profiles and T-cell activation. This review focuses on recent advances in the understanding of immune dysregulation and describes potential key factors that may function as biomarkers for disease or targets for therapeutic interventions. Future trials are necessary to address the many remaining questions with regards to pathogenesis, diagnosis, and treatment of autoimmune, inflammatory, and immunodeficiency syndromes.

Hydroxychloroquine-induced myopathy.

A 70-year-old woman with a history of undifferentiated connective tissue disease was admitted for work-up of shortness of breath and progressive weakness over the course of 1 year. She had been treated with hydroxychloroquine (HCQ) for last 5 years. Her evaluation revealed diffuse muscle weakness and hyperpigmentation of the skin consistent with HCQ deposition, although this did not entirely explain the patient's dyspnea. The patient underwent cardiac evaluation because of occasional substernal chest pain and persistent elevation in serum troponin I, but her ECG and adenosine thallium study did not show any signs of ischemic heart disease. The diagnosis of HCQ-induced myopathy was made with electromyography and muscle biopsy. HCQ was discontinued, with improvement of the patient's signs and symptoms over the course of the next 18 months.We propose that this patient was experiencing myocardial toxicity as a consequence of HCQ deposition disease with her clinical picture of skeletal muscle myopathy and HCQ deposition in the skin. A Medline search yielded several case reports as well as a case series of patients with antimalarial-induced myopathy. HCQ-induced myopathy may be less recognized because of its presentation with signs, symptoms, and laboratory results which suggest other critical diseases. Moreover, this medication is often prescribed to treat illnesses whose clinical manifestations may include myopathy.

Profound hypogammaglobulinemia 7 years after treatment for indolent lymphoma.

We report a case of a previously healthy 31 year old woman diagnosed with Stage IIIA follicular lymphoma treated with fludarabine in combination with cyclophosphamide and rituximab who presented seven years after the completion of therapy with CD4 count depression, panhypogammaglobulinema and a history of recurrent sinus infections. We performed comprehensive immunophenotypic analysis and found her to have only 1.2% switched (normal 21 +/- 8%) and 4.7% non-switched (11 +/- 4%) memory B cells with 92% of B cells belonging to the naïve compartment. We have previously evaluated reconstitution of the B cell compartment during the 6 to 12 month recovery period after treatment with rituximab and found a similar immunophenotypic pattern. In our patient, this defect was observed seven years after the administration of rituximab in combination with an alkylating agent and purine analog. The patient was started on monthly intravenous immunoglobulin treatments with complete resolution of her symptoms.

Neuromyelitis optica spectrum disorder in a patient with systemic lupus erythematosus and anti-phospholipid antibody syndrome.

Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system characterized by severe episodes of optic nerve and spinal cord inflammation. NMO-IgG (anti-aquaporin-4) has been recently described as a sensitive and specific marker for NMO. As there have been prior published reports of an association between NMO and systemic autoimmune diseases, the prognostic value of the antibody test in these cases is uncertain. We describe a 47-year old woman with recurrent transverse myelitis and a long-standing history of systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLS). While she did not have a history of optic neuritis, serological testing for the NMO-IgG was positive when she was admitted for her second episode of transverse myelitis. Testing for the NMO-IgG in cases of isolated or recurrent transverse myelitis attributed to current SLE and APLS may help clarify the diagnosis of a distinct disease process likely to cause recurrent and severe disability, warranting more aggressive immunotherapy.