Disclosures. Goals. Rheumatology Review for Primary Care. No commercial disclosures. We will be discussing non-fda approved uses for some medications.

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Lorena Perkins
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1 Rheumatology Review for Primary Care April 27, 2018 MONA Coming Together in Advanced Practice Disclosures No commercial disclosures. We will be discussing non-fda approved uses for some medications. Goals A general review of some of the most common rheumatic diseases how to identify them, how they are treated. Knowledge of when to refer such patients to rheumatology. 1

2 Objectives Better understanding on what to expect or how to manage the patient on immunosuppressive medications. Gout A crystalline arthropathy caused by overproduction or underexcretion of urate and an increased total body urate pool. Multiple genetic and metabolic factors lead to hyperuricemia top conditions to consider include myeloproliferative disorders, psoriasis, decreased renal function, metabolic syndrome or DMII, diuretic use, alcohol (especially beer) consumption. Gout Gout is a predominantly male disease, at least in younger ages, after women go through menopause, rates approach that of males. Onset is often mid-life, but in men, especially with family history or multiple risk factors, it can be in the 20's. Hyperuricemia is defined as having a uric acid level >7.0 mg/dl, as many as 5% of normal population may have this. 2

3 Gout The most common early presentation is sudden onset severe monoarthritis often 1 st MTP, but tarsal joints common too. Maximal increase in symptoms over 1 day Swelling, redness, heat around joint Resolves in a week with or without treatment This is the acute intermittent phase Gout The typical pattern is to see these attacks happen perhaps a few times a year for a time, then increase in frequency. Treatment for acute flares can include Indomethacin 50mg tid, or oral corticosteroids typically prednisone, given in a 2-3 week taper down from mg (depending on size of joint involved) Colchicine is no longer recommended as treatment for acute gouty flares. Gout To prevent progression of gout to resistant, polyarticular, tophaceous gout, prophylactic treatment is recommended, especially if lifestyle changes (cessation of alcohol abuse, weight reduction, stopping thiazide diuretics) are ineffective or not an option. Conventional purine-restricted diets are only modestly effective in lowering sodium urate. One caveat limiting beer consumption. 3

4 Gout Traditional prophylactic medication is allopurinol typically initiated if the patient has more than 3 gouty attacks per year or is showing signs of developing tophi. Recommended starting dose is 100mg daily, possibly higher if patient is young with good renal function. The dose is increased slowly every couple of weeks as directed by the serum uric acid level. Goal: 6mg/dl or lower. If tophaceous: <5 Gout Allopurinol is approved by FDA at doses up to 800mg/dl! However, most of the time doses are maxed out at 300mg. If one has creatinine clearance >60mg/dl, the increases should be slower, increasing by 50mg as opposed to 100, and newer studies are suggesting that this is well tolerated and improves the numbers of patients able to reach target uric acid levels Gout #1 thing to remember with allopurinol: Do not start or stop without prophylactic med to prevent flare! When initiating allopurinol or increasing dose, patients require 7-10 days of colchicine 0.6mg bid or indomethacin 50mg tid or prednisone 10mg daily. It is felt the change in uric acid levels destabilizes urate crystal deposition in the synovium and this triggers the flare. 4

5 Gout This also means that allopurinol must be dosed daily to prevent flare. It should not be stopped when a flare occurs (worsens severity), and if one misses a dose, might consider prophylaxis for a few days. Uloric (febuxostat) might also be considered, it can lower uric acid considerably, more expensive, only 2 doses. Same prophylaxis with starting and stopping. Gout Probenecid is another medication to lower uric acid, it increases renal excretion. Can only be used in those with >60mg/dl creatinine clearance and who can drink 2L of fluid daily to prevent development of kidney stones. Other measures reducing/stopping diuretic use, losartan, fenofibrate, and atorvastatin all have minor urate reduction properties. Gout When to Refer Recalcitrant flares they don't respond to a 3-4 week prednisone taper or come back as soon as the steroid is stopped. Tophaceous gout development of tophi indicates a more aggressive form of gout has developed. Polyarticular gout instead of a monoarthritis, patients have flares in multiple joints at once. 5

6 Rheumatoid Arthritis The most common autoimmune arthritis still incidence is 0.5 persons per 1000 per year in the US. 1-2% prevalence overall, up to 5% in females by age 70. Females 2.5x more likely to develop than males most common onset in 4-5 th decades of life. Typical onset is insidious increasing joint stiffness, pain, fatigue, over weeks to months. RA Most commonly affected joints MCP's, PIP's of hands, wrists, MTP's of feet symmetrically changes to include elbows, shoulders, knees, ankles over time. PIP's and lumbar spine almost always spared. Morning stiffness >1 hour. 70% with positive rheumatoid factor or anti cyclic citrullinated peptide (anti-ccp) antibody RA Goals in managing RA include reduction in pain and improvement in function, but long term goals are to prevent joint destruction/disability and reduce cardiovascular risk. Treatments typically include corticosteroids for the initial phases, with escalation to use of Disease Modifying Anti-Rheumatic Drugs (DMARD's) and Biologic therapies. NSAID use has been relegated to only occasional/additional. 6

7 RA Goals in managing RA include reduction in pain and improvement in function, but long term goals are to prevent joint destruction/disability and reduce cardiovascular risk. Treatments typically include corticosteroids for the initial phases, with escalation to use of Disease Modifying Anti-Rheumatic Drugs (DMARD's) and Biologic therapies. NSAID use has been relegated to only occasional/additional. RA Corticosteroids can be needed for first year of therapy until good response to DMARD's, sometimes 5mg or less used long term in addition to other meds. DMARDS Hydroxychloroquine, Methotrexate, Leflunomide, Sulfasalazine, Minocycline. All require lab monitoring at least q 12 weeks (except HCQ, which requires annual eye exam). RA Liver dysfunction, bone marrow suppression are main concerns with long-term use. Minor risk for increased infections safe to give live attenuated vaccines. Yearly flu vax recommended, pneumonia vaccines as per age recommendations. Consider holding MTX x 2 weeks after vaccine for best antibody response, if arthritis is very stable. 7

8 RA Biologic meds increased risk for infections, especially in COPD patients. If an antibiotic is prescribed, biologic should be held for best immune response. Minimal increased risk for cancer make sure screening UTD. Anti-TNF alpha meds should be used with caution in those with CHF, worsening symptoms should be reported to rheumatology. RA Associated conditions to consider: Osteporosis corticosteroid induced, also risk higher in RA overall Lung involvement up to 30% of RA patients will have some form nodules or insterstitial lung disease. Secondary Fibromyalgia RA When to Refer New onset symmetric small joint pain/swelling with MS>1 hour, positive RF or anti-ccp antibody, or recurrent episodes of mono or oligoarthritis. Known RA patient who is having multiple infections, new SOB or rashes Known RA patient with new lab abnormalities transaminitis, neutropenia, thrombocytopenia, anemia 8

Systemic Lupus Erythematosus (SLE) A highly diverse constellation of signs and symptoms classified as one autoimmune entity. Multiple levels of severity, progression, and system involvement.

9 Systemic Lupus Erythematosus (SLE) A highly diverse constellation of signs and symptoms classified as one autoimmune entity. Multiple levels of severity, progression, and system involvement. Predominantly female, young, with strong minority representation (Black and Hispanic). Onset typically after puberty. SLE SLE American College of Rheumatology Diagnostic Criteria-- defines 11 different criteria of which four must be present for diagnosis. Most commonly affected systems include mucocutaneous, musculoskeletal,renal, hematologic and CNS. Despite specifically treating these areas, the most common reason for mortality is accelerated atherosclerosis. 9

10 SLE Symptoms of note photosensitive rash, persistent proteinuria, small joint arthralgias/arthritis, recurrent pleural or pericardial effusions/itis. Treatments: Also variable, but all SLE patients should be on hydroxychloroquine, as it has been shown to reduce progression and flares. Imuran and Methotrexate often used, and Cellcept and IV cytoxan are the meds of choice for renal involvement. SLE Rituximab is being used more and more for severe manifestations. Benlysta newest FDA approved med for SLE can't be used with nephritis or severe manifestations. Infusions takes a long time to onst of benefit. Still not widely used. Corticosteroids. A cornerstone to initiation of treatment, goal is always to reduce/wean off if possible. SLE Recommendations for primary providers of SLE patients please encourage them to take their meds and keep f/u with rheum. Immunosuppression may be more need for frequent antibiotic use don't need to hold HCQ or pred with tx infections, but may temporarily hold imuran or MTX for best immune response. Encourage good photoprotection. 10

11 SLE When to Refer You discover significant proteinuria on UA in absence of infection. Classic photosensitive rashes. Systemic symptoms fevers, weight loss, profound fatigue, arthritis/arthralgias Positive DS-DNA antibody, positive Ro/La, RNP or positive Smith antibody on ANA profile. Psoriatic Arthritis (PsA) Inflammatory arthritis associated with psoriasis. Up to one-third of psoriasis patients can develop PsA. Seen equally in men and women, distribution of joints slightly different from RA, also seronegative. Can affect both peripheral joints and axial involvement (sacroilliac joints, spine). Also more patterns of onset with DIP involvement, oligoarticular, polyarticular, spondylarthritic. PsA Dactylitis and enthesitis are specific findings as opposed to RA. Iritis and nonspecific colitis can be seen as well. As in RA, treatment goals are to improve pain and function, but prevent joint destruction and disability. Medications used are the same as for RA initially, with the oral options, but some differences in biologics approved for PsA. 11

12 PsA Same concerns for medication side effects in general as well as labs and f/u. When to Refer: Inflammatory back pain in person with psoriasis alternating buttock pain, back pain at night that improves after 1 hour up in morning, back pain at night that's better with activity. Dactylitis, active joint swelling in patient with psoriasis. Don't forget to check for unusual forms of psoriasis! Osteoporosis Not an inflammatory condition, but exceedingly common in the rheumatic patient. Corticosteroid use is a big risk, but RA in particular linked to increased incidence. Consider checking DEXA's earlier than generally recommended in your rheumatic patient, especially if they are frail, smokers, strong family hx of osteoporosis or have history of what sounds like fragility fractures. Osteoporosis FRAX score tool designed to help decide when to treat ostepenia/osteoporosis. Can find online at Takes into account major risk factors and comorbidities. If a patient is on chronic corticosteroids, especially at doses > 7.5mg/day, consider initiation of bisphosphonate therapy for osteoporosis prevention. 12

13 Osteoporosis Treatments Bisphosphonate are still #1 recommended step Reclast if oral is not an option. Treatment is typically 6 years, then a break to watch for regression. If no response to bisphonsphonates, intolerance, or fractures despite tx, can move on to Prolia or Forteo. Both are injectables, Prolia is quarterly, Forteo is daily selfadministered. Osteoporosis Supplements standard recommendations for calcium and vitamin D intake include mg of calcium in a divided dose, and at least 800IU of vitamin D. Screening for vitamin D deficiency/malabsorption is recommended, as many people require more to keep level at goal. Fibromyalgia Secondary to most autoimmune disorders high levels in SLE, but also seen in RA and PsA. Felt to be due to hyperactive/sensitive nervous system. Functional PET scans and MRI's have demonstrated higher/earlier activation of pain pathways with less stimulation, but no specifics of why/how this happens have been identified. 13

Fibromyalgia For the most part, this is the cause of the generalized pain that many lupus and inflammatory arthritis patients report, as opposed to specific joint pains.

14 Fibromyalgia For the most part, this is the cause of the generalized pain that many lupus and inflammatory arthritis patients report, as opposed to specific joint pains. New ACR diagnostic criteria 2010 There is no recommended blood test to identify FMS, but we do have to r/o autoimmune activity to diagnose it. Micronutrient deficiencies and thyroid disease should also be r/o. Fibromyalgia Standard treatment goals for fibromyalgia management include evaluating and working toward sound sleep so r/o sleep apnea, treating insomnia and RLS, good sleep hygeine. Best treatment for depression/anxiety, PTSD and other psychiatric conditions. Mild daily aerobic exercise, started with a slow onset and increasing as tolerated is highly recommended. 14

15 Fibromyalgia Medication options include Gabapentin, Lyrica, duloxetine, and Savella. You can use a anti-seizure med along with one of the SNRI's to cover both ascending and descending pain pathways. Muscle relaxants and NSAID's of varying benefit. Cognitive Behavioral Therapy Resources Current Rheumatology Diagnosis and Treatment, Imboden, John; Hellmann, David; Stone, John. Primer on the Rheumatic Diseases, Klippel, John; Crofford, Leslie; White, Patience, eds. Stamp, Lisa, Chapman, Peter, et al. A Randomised Controlled Trial of the Efficacy and Safety of Allopurinol Dose Escalation to Achieve Target Serum Urate in People With Gout. Annals of Rheumatic Disease, 2017;0:1-7 Tan EM, Cohen AS, Fries JF, et al. The 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus. Arthritis and Rheumatism 1982;25: Wolfe, et al. Arthritis Care and Research, Oct 1, 2010 Epub ahead of print. 15

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