Rheumatology Confusion and Pearls

Educational Objectives

The goal of this program is to improve management of rheumatic diseases. After hearing and assimilating this program, the clinician will be better able to:

1. Compare reduction of autoimmune diseases in use of vitamin D with fish oil.
2. Explain the occurrence of gout in premenopausal and menopausal women.
3. Optimize preconception care in patients with rheumatic disorders.

Summary

Case 1: a woman of 20 yr of age, presents without significant medical history but with a strong familial predisposition to erosive, deforming rheumatoid arthritis in her mother and sister; she expresses fear of developing the disease despite currently being asymptomatic and inquires about preventive measures; smoking cessation is emphasized as the primary modifiable risk factor; vitamin D and fish oil supplementation are proposed for autoimmune disease prevention; literature supports the benefits of fish oil in rheumatoid arthritis, showing improvements in fatigue, strength, pain, and joint swelling, possibly through reduced inflammatory mediators and cytokines, with higher doses being more effective

VITAL trial by Hahn et al (2022): assessing vitamin D and fish oil vs placebo in reducing autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, showed positive results; this trial, originally aimed at broader outcomes (eg, cancer, cardiovascular disease [CVD]), revealed that supplementation led to decreased incidence of autoimmune disease while taken; vitamin D’s effect diminished post-supplementation, unlike fish oil, which maintained a lasting benefit; further analysis demonstrated that the fish oil group exhibited sustained lower rates of autoimmune disease compared to placebo, reinforcing its potential role in prevention

Case 2: a woman of 35 yr of age, with no past medical history presents with a several-week history of left knee pain and swelling, previously experienced in the ankle and responsive to nonsteroidal anti-inflammatory drugs (NSAIDs); examination confirms monoarthritis; while considering gout, it is noted that rheumatic diseases (RD) are generally more prevalent in women, except gout; in women gout occurs most commonly after menopause; although premenopausal women can develop gout, it is less frequent because of estrogen’s role in reducing uric acid levels and enhancing excretion; women with gout often have comorbidities (eg, obesity, osteoarthritis, hypertension, diabetes, renal disease) and may use medications affecting uric acid clearance

Case 3: a woman of 25 yr of age, reports a 1-yr history of progressive low back pain without sciatica, worse at night, with prolonged morning stiffness; examination and radiographs are normal; ankylosing spondylitis is considered but not excluded based on normal imaging; historically thought to primarily affect men, it is now understood to affect both sexes equally; in women, radiographic progression may be limited, with inflammation visible only on magnetic resonance imaging (MRI); diagnosis relies on clinical features including inflammatory back pain, good NSAID response, elevated inflammatory markers, human leukocyte antigen-B27 positivity, peripheral joint involvement, extra-articular manifestations, and family history; early rheumatology referral and MRI are essential to reduce diagnostic delays and initiate effective treatments (eg, biologics)

Case 4: a woman of 30 yr of age with a history of well-controlled lupus on hydroxychloroquine and methotrexate expresses a desire for pregnancy but is concerned because of information suggesting infertility and maternal-fetal risks; infertility rates in patients with RD are generally comparable to those in the general population; pregnancy complications are less frequent when disease activity is stable

PROMISSE study by Buyon et al (2015): on patients with mild to moderate lupus reported that ≈20% experienced adverse pregnancy outcomes (ie, fetal or neonatal death, preterm birth, small-for-gestational-age neonates); among patients without specific risk factors (eg, non-Hispanic White ethnicity, negative lupus anticoagulant, low disease activity, platelet count >100, and absence of antihypertensive use) the adverse outcome rate was ≈8%, nearing the general population’s rate; presence of antiphospholipid antibodies significantly increases the risk of adverse outcomes, from 15.4% without antibodies to 44% with them; these antibodies include β-2 glycoprotein, anticardiolipin, and lupus anticoagulant; screening for these is standard during preconception counseling

Preconception care: involves transitioning from teratogenic medications (eg, methotrexate, leflunomide, mycophenolate) to safer alternatives (eg, azathioprine); disease stability for ≥6 mo is recommended before conception; screening for comorbid autoimmune diseases and antibodies, is also conducted because of associations with neonatal lupus erythematosus and congenital heart block, the latter warranting intensive monitoring and possibly high-dose steroids; hydroxychloroquine and low-dose aspirin are recommended during pregnancy; the American College of Rheumatology offers accessible guidelines on maternal health in rheumatology; management of patients with antiphospholipid antibody-positive depends on history; those without prior syndrome receive aspirin, while those with thrombotic or obstetric history require heparin

Case 5: a woman of 26 yr of age with class IV lupus nephritis, on mycophenolate and steroids, is advised against pregnancy; contraceptive choice depends on antiphospholipid antibody status; if present, estrogen-containing methods are avoided because of thrombotic and flare risks, with preference for intrauterine devices or progestin-only pills; without antibodies and with low disease activity, broader contraceptive options are acceptable; hormone replacement therapy is avoided if antiphospholipid antibodies are present because of thrombosis risk

Case 6: a woman of 30 yr of age presents with 1 yr history of progressively worsening generalized joint and muscle pain accompanied by severe fatigue; she expresses concern regarding a potential undiagnosed autoimmune disorder; on physical examination, there is increased sensitivity to light touch across the body, but no definitive signs of active joint inflammation (eg, synovitis); in evaluating further steps, the decision to check an antinuclear antibody (ANA) test hinges upon the degree of clinical suspicion for an ANA spectrum disorder (eg, systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, scleroderma, myositis)

ANA testing: is highly sensitive for lupus, yielding positive results in 95% to 99% of cases; negative ANA results essentially rule out lupus, though ANA sensitivity is lower for conditions (eg, Sjögren syndrome), where only ≈80% test positive; so, a negative ANA does not exclude Sjögren syndrome; ANA lacks specificity, with 15% to 20% of the healthy population displaying positive results, and this percentage appears to be rising; so, a positive ANA does not confirm lupus; ANA patterns generally lack clinical utility except when a centromere pattern is present, which suggests a scleroderma phenotype; the strength of ANA titer does not correlate with disease severity, but higher titers modestly increase the likelihood of an ANA-associated disorder; in a study analyzing referrals for positive ANA, only half of patients with the highest titers were diagnosed with an autoimmune condition; none of the patients tested for widespread pain were found to have a rheumatic condition, aligning with clinical practice suggesting alternative diagnoses (eg, fibromyalgia)

Fibromyalgia: is characterized by widespread pain, heightened sensitivity to multiple stimuli (eg, light, noise), and often coexists with conditions (eg, temporomandibular joint disorder, irritable bowel syndrome, interstitial cystitis, depression); sleep disturbances are commonly associated; patients with RD may concurrently exhibit fibromyalgia, necessitating evaluation for both; a head-to-toe review of systems, including symptoms (eg, patchy hair loss, oral or nasal ulcers, sicca symptoms, atypical rashes, pleurisy, inflammatory arthritis, objective weakness, Raynaud phenomenon), and abnormal lab findings, supports assessment; basic tests (eg, erythrocyte sedimentation rate, C-reactive protein) are useful screening tools; differentials include depression, hepatitis C, vitamin D or iron deficiency, and hypermobility; screening tools and diagnostic worksheets facilitate the evaluation of fibromyalgia and hypermobility, with specific questionnaires and scoring systems available

Other aspects of ANA testing: if ANA is positive, assessing the reason for testing and clinical context is essential; further testing includes urinalysis, inflammatory markers, complement levels, and extractable nuclear antibodies (ENAs) to determine specificity; anti-Smith and anti-dsDNA antibodies are highly specific for lupus, as are antiphospholipid antibodies; the presence of autoantibodies may precede clinical disease, indicating a potential future diagnosis of autoimmune disease

CVD in patients with RD: exhibit an increased prevalence of CVD compared to the general population because of elevated inflammatory markers; inflammatory cytokines contribute to the progression of atherosclerosis; disease control is prioritized to mitigate these effects; this is emphasized to patients who may be hesitant to initiate lifelong medication, highlighting that the concern extends beyond joint discomfort to cardiovascular health, as effective disease management significantly reduces the risk for cardiovascular events; patients with RD should be recognized as high-risk and managed more aggressively in terms of hypertension and cholesterol control, including the use of statins; despite this, such patients are frequently undertreated

Vaccination for patients with RD: immunization against pneumonia and shingles is crucial, especially given the immunosuppressive nature of most rheumatologic medications; the risk is particularly high for patients on Janus kinase inhibitors (eg, tofacitinib [Xeljanz], baricitinib, upadacitinib [Rinvoq]), making shingles vaccination essential, even for younger individuals outside standard guidelines; a strategy to enhance vaccine response in patients on methotrexate involves withholding a single dose following vaccination, as methotrexate reduces immunogenicity; while there is a theoretical risk for disease flare, a one-dose interruption is generally well-tolerated, according to speaker

Depression: is more prevalent among individuals with RD, often exacerbating disease severity; addressing this is crucial for overall management

Readings

Buyon JP, Kim MY, Guerra MM, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med. 2015;163(3):153-163. doi:10.7326/M14-2235; Cronstein BN. The mechanism of action of methotrexate. Rheum Dis Clin North Am. 1997;23(4):739-755. doi:10.1016/s0889-857x(05)70358-6; Devreese KMJ, de Groot PG, de Laat B, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost. 2020;18(11):2828-2839. doi:10.1111/jth.15047; Gemcioglu E, Erten S. Clinical and laboratory features of patients with undifferentiated spondyloarthritis and ankylosing spondylitis. Rev Med Chil. 2021;149(10):1423-1429. doi:10.4067/s0034-98872021001001423; Hahn J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022;376:e066452. doi:10.1136/bmj-2021-066452; McClory J, Said N. Gout in women. Med Health R I. 2009;92(11):363-368.; Pisetsky DS, Lipsky PE. New insights into the role of antinuclear antibodies in systemic lupus erythematosus. Nat Rev Rheumatol. 2020;16(10):565-579. doi:10.1038/s41584-020-0480-7; Siracusa R, Paola RD, Cuzzocrea S, et al. Fibromyalgia: pathogenesis, mechanisms, diagnosis and treatment options update. Int J Mol Sci. 2021;22(8):3891. doi:10.3390/ijms220838915; Yamamoto Y, Aoki S. Systemic lupus erythematosus: strategies to improve pregnancy outcomes. Int J Womens Health. 2016;8:265-272. doi:10.2147/IJWH.S90157.

Disclosures

For this program, members of the faculty and the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Vreede was recorded at the 32nd Annual Primary Health Care of Women Conference 2024, held December 5-6, 2024, in Ann Arbor, MI, and presented by the University of Michigan School of Medicine. For information about upcoming CME activities from this presenter, please visit https://umich.cloud-cme.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

IM722401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.