Rhuemo Exam #1 - Clinical

Farrell Stuff

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Regulation

Hypothalamus → CRF → AP → ACTH → Adrenal Cortex → Cortisol (Negative feedback system)

Circadian Rhythm

\-Body’s normal release of cortisol

\-Peaks in the AM (\~6/7 am)

Result of giving extra cortisol

\-Going to slow down negative feedback system for long periods of time and then overtime the gland will atrophy since it is not being used

\-Will take time for the gland to wake up (when endogenous cortisol is taken away)

Mineralocorticoids

\*Fludrocortisone (Florinef)

\-Indications: RT for adrenocortical insufficiency (Addison’s Disease); salt-losing syndrome

\-MOA: Mimics Na+ resorption → Increases BP

\-AE: Fluid imbalance, hypokalemia, edema, increased BP and CHF

Topical Glucocorticoids

\-Indications: Eczema, atopic dermatitis, psoriasis, contact dermatitis, vitiligo, etc.

\-Choosing a potency: Low (thin skin, acute inflammatory lesions), medium or high (chronic, hyperkeratotic, lichenified lesions)

\-Vehicle: Ointment (thick lesions; enhances penetration), creams (acute and subacute dermatoses; moist skin and intertriginous areas), solutions, gels and sprays (scalp, where non-oil based vehicles is needed)

\-Duration of use: Medium-high to very high (<3 weeks; irreversible skin atrophy), medium in areas of thin skin (<2 weeks), Diaper rash (mild for 3-7 days), and chronic (intermittent tx preferred; every other day and weekends only)

\-AE’s: Skin atrophy, acne, abnormal pigment, purpura, delayed skin healing, photosensitivity, infection

Topical Glucocorticoids Agents by Potency

\-Very High: Clobetasol prop, halobetasol prop and betamethasone diprop

\-High: Betamethasone diprop/val, flucinonide, triamcinolone ace

\-Medium: Betamethasone benz/diprop/val, flucinolone acet, fluticasone prop, hydrocortisone, mometasone, triamcinolone

\-Low: Aciometasone diprop, dexamethasone, fluocinolone, hydrocortisone

Short-Acting Oral Glucocorticoids

\-Cortisone and Hydrocortisone

\-GC<MC; less anti-inflammatory effects compared to aldosterone effects (fluid retention, electrolyte disturbances, BP issue)

Intermediate-Acting Oral Glucocorticoids

\-Predisone and Methylprednisone

\-Most common

\-5 mg of pred = 4 mg of methylpred

Long-Acting Oral Glucocorticoids

\-Dexamethasone and Betamethasone

\-Dexa used in Onco

Dosing Regimens of Oral Glucocorticoids

\-Low dose (<7.5mg): maintenance therapy

\-Split Day: Used in the beginning of an acute reaction; dose pack

\-Medium (7.5-30 mg): Primary chronic conditions (RA = no more than 20 mg)

\-High (>30-100 mg): Severe allergic rxns; given for a few days then taper off

\-Very high (>100 mg): Should not be given outpatient; increases risk for infection/CNS effects

\-IV pulse (>250 mg): severe or life threatening dx (saving an organ); 1g methyl x3

General Rule of Oral Glucocorticoids

\-May require taper if patient received therapy for >2 weeks at doses >20mg/day (must hit both)

\-Give around 6-7am or risk insomnia

Discontinuation of Oral Glucocorticoids

\-Short-term (<2 weeks eat low doses): no tapering

\-Long term: Decrease by 2.5-5 mg every 3-7 days is most common

Adverse Effects of Oral Glucocorticoids

\-Early: Insomnia, enhanced appetite, weight gain, emotional liability, leukocytosis, hyperglycemia

\-Sustained: Cushingoid habitus, HPA suppression, infection, osteoporosis, impaired wound healing

\-Delayed: Osteonecrosis, ecchymosis, cataracts, growth retardation, fatty liver, atherosclerosis

\-Rare: Psychosis, glaucoma, pancreatitis, pseudotumor cerebri

\-PJP prophylaxis is Bactrim x3

Contraindications of Oral Glucocorticoids

\-Live vaccines (>2 weeks/>20 mg)

\-Systemic fungal infections (PCP prophylaxis w/high doses; Bactrim)

\-Hypersensitivity

Warnings for Oral Glucocorticoids

\-Active infections, diabetes, osteoporosis, peptic ulcer, electrolyte imbalances, stress, trauma, surgery, HPA suppression

Monitoring Oral Glucocorticoids Therapy

\-Labs: Including glucose, electrolytes, WBC

\-Stool test for occult blood loss

\-DEXA

\-Growth and development

\-Cushingoid symptoms

\-BP

\-Ophthalmologic exams

Patient Counseling for Oral Glucocorticoids

\-Take in AM w/food

\-Never stop therapy abruptly

\-Side effects!!!

\-Missed doses: daily (take as soon as remember; skip if close to next dose) or QOD (take as soon as remember, if not, skip that day and take the next morning)

\-Monitor salt intake, caloric intake, potassium if necessary and supplement with calcium and vitamin D

Glucocorticoid-Induced Osteoporosis

\-Occurs w/in 6-12 months of therapy

\-Decreased bone formation and increased bone resorption

\-Depending on risk, osteoporosis tx may be needed for prednisone doses b/w 5-7.5 mg daily

\-ACR Guidelines: Maximize calcium and vit D; make lifestyle modifications

Rheumatoid Arthritis

\-Autoimmune disease: attacks synovial and other connective tissues (60-70% of patients have detectable RF levels)

\-Chronic inflammation of synovial tissue lining the joint capsule: Proliferation of tissue, invades cartilage and bone surface and leads to destruction of the joint

Factors associated w/ poor prognosis of RA

\-ACR: early age of onset, elevated ESR, high titer of RF, swelling in more than 20 joints, presence of extra-articular manifestations

\-EULAR: high disease activity state, autoantibody positive (RF and/or anti-CCP)

\-Early presence of joint damage

NSAIDs in RA

\-No impact on disease progression

\-Used for symptomatic relief only

\-Used to BRIDGE THERAPY for pain relief until DMARDs take effect

\-Not the best option: side effects, toxicities, and interactions

Prednisone and Methylpredisone in RA

\-Bridging Therapy: Control pain and inflammation while DMARDs are taking effect

\-Continuous low-dose therapy (difficult to control disease); do not exceed 20 mg

\-High-dose bursts: control flare-ups, injections may control local inflammation

\-Major limitations: HPA suppression, Cushing’s Disease, osteoporosis, glaucoma, HTN, hirsutism, electrolyte imbalances, glucose intolerance, increase risk of infection

Conventional DMARDs in RA

\-Agents: MTX, leflunomide, hydroxychloroquine, sulfasalazine

\-Onset of effect can take up to 6 months

\-Two/Three-drug combos may be needed in severe cases

MTX in RA

\-Dosed Weekly! (increase dose in 4-6 weeks not to exceed 25 mg); oral or SubQ

\-1st-line: decreased signs/symptoms and structural damage

\-Lower CV mortality

\-GI intolerance common

\-Folic acid supplementation needed

\-Lab monitoring: required to detect anemia, kidney dysfunction, and hepatotoxicity

\-Abstain from alcohol day before, day of and day after weekly dose to avoid hepatotoxicity

\-Abortive agent at 50 mg women must use contraception); may damage sperm in men

\-Monitor lung function

\-Baseline tests: CBC, serum transaminases, serum creatinine, chest radiography for first 3 mo then every 1-3 mo

MTX + Antibiotic Interactions

\-Bactrim!!

\-Additive anti-folate effects

\-Increased bone marrow suppression due to trimethoprim component

\-Sulfonamide can displace MTX from its binding sites and reduce MTX clearance leading to toxicity

Clinical Pearls: Leflunomide

\-PO once daily

\-takes longer for efficacy

\-Hepatotoxicity, peripheral neuropathy, teratogenic

\-Cholestyramine wash-out for toxicity (enterohepatic cycling)

Clinical Pearls: Sulfasalazine

\-PO 2-3x per day (titration required)

\-moderate clinical effect

\-Discoloration of urine/tears/sweat; photo sensitivity

Clinical Pearls: Hydroxychloroquine

\-PO BID; do not exceed 5 mg/kg/day using ABW

\-moderate clinical effect

\-Risk of retinopathy with chronic therapy and worsening psoriasis

\-Annual eye exams (high doses, renal impairment, tamoxifen use, macular disease)

Clinical Pearls: TNFi

\-Entanercept (Enbrel): recombinant DNA-derived protein; QW-BIW dosing; most variable onset

\-Infliximab (Remicade): Chimeric monoclonal antibody (more chance for reaction); IV Q 4-8W; requires MTX on board; infusion reactions most common

\-Adalimumab (Humira): Human monoclonal antibody; SC Q 2W

\-Golimumab (Simponi): Human monoclonal antibody; SC monthly and IV option

\-Certolizumab (Cimzia): Pegylated humanized antibody (safe in pregnancy)

\-Stop all agents if psoriasis develops on hands or feet

\-Does not increase risk of solid tumors

\-Same efficacy across the board; reasonable to switch among class if patient doesn’t respond to one

\-CI: serious infections, Child’s Pugh B or C cirrhosis, lymphoproliferative disorder treated <5years ago, decompensated CHF or any demyelinating disorder

\-BBW: Infections

Clinical Pearls: Non-TNFi

\-Abatacept (Orencia): oral, IV, SC; long time to effect; infection risk clinically lower than other biologics

\-Tocilizumab (Actemra): oral, IV, SC; increased lipids/liver enzymes, GI sx

\-Sarilumab (Kevzara): SC q 2W; anemias, increased lipids/liver enzymes, GI perforations

\-Rituximab (Rituxan): IV q 2W; progressive multifocal leuko

Clinical Pearls: JAKi

\-Tofacitinib (Xeljanz): JAK1,2,3; oral

\-Baricitinib (Oluminant): JAK1,2; oral

\-Upadacitinib (Rinvoq): JAK1; oral

\-AE: similar to other DMARDs; Herpes Zoster

\-Used if inadequate response or intolerance to 1 or more TNF blockers

\-Do not use w/ other JAKs, bDMARDs or other potent immunosuppressants

\-BW: Infections

Clinical Practice Guidelines for Tx of RA

1st line- MTX

2nd- TNFa Antagonist


1. Entanercept (Enbrel) or adalimumab (Humira) or Infliximab (Remicade)
2. Golimumab (Simponi) or Certolizumab pegol (Cimzia)

1\. IL-6 inhibitor

2\. T-cell modulator

3\. Abatacept

4\. JAKi

5\.B-cell modulator

\

NSAIDs in Psoriatic Arthritis

\-Limited data for use

\-May be used initially with mild PsA w/out poor prognostic factors

\-Often first-line for symptomatic relief; structural damage will continue

Glucocorticoids in PsA

\-Intra-articular Injections: 1 or 2 joints dominate symptoms; avoid passing needle through plaque

\-Topical

\-Systemic: use with caution; prednisone 10-20mg w/ taper for acute attacks; NSAIDs & DMARDs for maintenance

* Avoid mono therapy; many clinicians avoid this

Topical: Phototherapy in PsA

\-UVB light; PUVA

\-Can be added to topical and/or systemic therapy

\-MOA: Antiproliferative, anti-inflammatory, immunosuppressive effects

\-ADR’s: Actinic skin damage, dry/wrinkled skin, hyper/hypo-pigmentation, increased skin cancers

Topical: Retinoids in PsA

\-Tretinoin: Vitamin A analog

* Increased cell turnover and decreased cell cohesiveness
* Sensitivity to sun exposure, wind, cold
* ADR’s: skin irritation, redness, peeling
* Teratogenicity risk

\-Adapalene (Differin): 3rd gen; less peeling/dryness and skin discoloration then tretinoin

\-Tazarotene (Avage; Tazorac); Prodrug and synthetic acetylenic retinoid; alters gene expression; ADRs: redness, itching, stinging, burning

Oral Small Molecules in PsA

\-Sulfasalazine: PO daily up to BID; urine/skin discoloration and increased LFTs; EC for GI tolerability

\-MTX: oral and SubQ

\-Leflunomide: PO; not recommended in preexisting, teratogenic; reduce to 10 mg if diarrhea occurs

\-Apremilast (Otezla): Day 1-6 dosing; diarrhea, nausea, weight loss, headache, and DEPRESSION; can combo w/biologics

\-Cyclosporine: reserved for refractory disease; PO; Drug interactions!

IL-17 inhibitors in PsA

\-Secukinumab (Cosentyx): SC (titration); infections (yeast)

\-Ixekizumab (Taltz): SC (different dosing plaque and PsA); infections (yeast)

IL-12/23 inhibitors in PsA

\-Ustekinumab (Stelara): SC (different dosing with plaque); infections (TB testing required), injection site rxn

\-Guselkumab (Tremfya): SC may add cDMARDs; infections (TB testing) and injection site reactions

\-Risankizumab (Skyrizi): SC; infections (TB testing) and injection site reactions

Clinical Tx for PsA

\-TNFi > IL-17i > IL-12/23 for biologics

\-OSM for tx naive patients w/out severe disease

\-Combo therapy (i.e. biologic + MTX) generally not recommended (unless partial response to MTX mono therapy)

Special Populations in PsA tx

\-IBD: TNFi (except etanercept) preferred; IL-12/23i preferred among non-TNFi; DO NOT use IL-17i

\-Uveitis: Adalimumab

\-Diabetes: MTX not preferred due to increased risk of fatty liver disease

\-Frequent infections: OSM preferred; Non-TNF-ai preferred over TNF-ai

CVD and RA/PsA

\-TNFi therapy results in 50% reduction in 1st CV event (possibly improve flow-mediated vasodilation and improve carotid intima-media thickness)

\-Tocilizumab increases total cholesterol and LDL-cholesterol

\-Avoids TNFi in pts with NYHA CHD Class III or IV or those with EF <50%

\-JAKi: Tofacitinib (increased risk of all-cause mortality)

Topical Capsaicin (OA)

\-MOA: releases and ultimately depletes substance P from afferent nociceptive nerve nerve fibers; Knee OA only

\-Apply 2-4x day

\-Mono/combo therapy (good add-on therapy)

\-AE’s: Local AE-burning, stinging, erythema

\-Counsel pts to keep away from eyes and mouth, wash hands after use

Topical NSAIDs in OA

\-MOA: COXi in tissues near site of application

\-Use prior to systemic therapy and/or adjunct (NOT for HIP OA)

\-Use for knee OA if pt fails APAP and is preferred over oral NSAIDs for those >75yo

\-Counseling: Wash hands thoroughly after application, watch for localized skin reaction

Tramadol in OA

\-MOA: weak opioid agonist, NE, and 5HT reuptake inhibition

\-Preferred but reserved until after APAP, topical NSAID failure, cannot take oral NSAIDs; alt. 1st line for knee and hip OA

\-Can be used in combo

\-AE’s: N/V, dizziness, constipation, HA, somnolence

\-Lower dose w/ SSRIs

\-Do not stop abruptly due to withdrawal symptoms

APAP in OA

\-MOA: Blocks COX to prevent prostaglandin synthesis

\-ADR’s: hepatotoxicity, overdose

\-Monitoring: LFTs, INR

\-Alternative 1st line

Oral NSAIDs in OA

\-MOA: COXi

\-1st line for hand, knee and hip OA

\-Caution in CHF, dehydration and impaired kidney function

\-Avoid: peptic ulcer disease, active bleeding, known ischemic heart disease, cerebrovascular disease, moderate-severe kidney disease and moderate-severe heart failure

\-GI side effects

GI Risk NSAIDs

\-High (Avoid NSAIDs or use celecoxib + GPA), moderate, low risk also H. Pylori

\-Gastroprotective agent (misoprostol, PPI, H2RA)

NSAIDs interaction with ASA

Ibuprofen should be administered 30-120 minutes after immediate release aspirin, 2 to 4 hours after ER aspirin or at least 8 hours before aspirin

Intra-articular Corticosteroid in OA

\-MOA: Decrease the formation and release of prostaglandins, kinins, liposomal enzymes, and histamine

\-Dose: no earlier than every 3 months due to risk of joint space narrowing/osteonecrosis

\-ADR’s: Systemic and local

\-Alt. 1st line tx for both knee and hip after APAP/NSAIDs

\-Systemic corticosteroids are not recommended

Duloxetine in OA

\-MOA: 5-HT and NE reuptake inhibitors

\-ADR’s: nausea, dry mouth, constipation, and anorexia

\-Adjunctive tx in patients w/ knee OA that have partial response to 1st line agents

\-Preferred 2nd line agent for patient w/ both neuropathic and musculoskeletal OA pain

\-Avoid combo with tramadol given risk for serotonergic syndrome

Low-dose opioids in OA

\-Useful for patients who have failed ALL other therapies

\-Usually in combo with APAP

Caution in elderly

Glucosamine and Chondroitin in OA

\-Components of healthy cartilage

\-Shellfish allergy (Chondroitin)

Turmeric in OA

\-Anti-inflammatory activity

\-Dosed at 500 mg BID w/ Black pepper extract

\-Well-tolerated

Treat to target uric acid

Uric acid < 6 mg/dL (and maybe <5 mg/dL)

Indication for urate lowering therapy (ULT)

\-Tophus/tophi

\-Radiographic damage (any modality) attributable to gout

\- >2 gouty arthritis attacks/year

\-Experiencing first flare and CKD stage 3+, SU >9 mg/dL, or urolithiasis

Diet in Gout

\-Do weight loss

\-Limit red meat and certain seafood

\-Avoid alcohol, esp beer and high fructose corn syrup

Nonpharm for Gout

\-Diet

\-Increased fluid intake

\-Decreased salt consumption

\-Restriction of alcohol

\-Caution use of diuretics and other drugs that can increase serum urate

\-Aspirin use: Dose less than 1g can cause uric acid retention

\-Acute attack: not effective except Ice

Drugs that Raise Serum Urate

\-Diuretics

\-Nicotinic Acid

\-Ethanol

\-Low-dose salicylates

\-Cyclosporine

\-Tacrolimus

Management of Acute Gout Attack

\-Mild/mod pain for few small joints: monotherapy with NSAID

\-Severe pain: Combo therapy warranted

* Colchicine + NSAID
* Colchicine + oral corticosteroid
* Intra-articular corticosteroid + oral agent (colchicine, NSAID, corticosteroid)

NSAIDs in Gout Attacks

\-Initiated at max dosage w/in 24 hour of acute gout attack; continue until complete resolution of attack (usually 5-8 days), then taper

\-ADR’s: GI (gastritis, bleeding), renal dysfunction, HTN, fluid retention, HA, dizziness

\-Caution: peptic ulcer disease, CHF, CAD, uncontrolled HTN, renal insufficiency

Corticosteroids in Gout

\-Equivalent to NSAIDs in the tx of acute gout flare

\-Route of admin determined by number of joints involved: 1 or 2 (injection); polyarthritis (systemic agents)

Colchicine

\-MOA: Decreased leukocyte motility and decreased phagocytosis in joints

\-Start w/in 36 hours from onset

\-Caution: 3A4, P-gp, renal dose adj

\-ADR’s: Dose-related GI toxicity, myelosuppression, interaction with HMG-CoA reductase inhibitor and renal insufficiency

\-Drug interactions: Clarithromycin and cyclosporine

XOI- Allopurinol

\-MOA: Decreases synthesis of uric acid (dose dependent); need xanthine oxidase for metabolism

\-Start at 100 mg then titrate every 2-5 weeks

\-Drug interactions: Thiopurines (ie 6-MP and azathioprine)

ADR’s: Mild includes skin rash, leukopenia, GI, headache, urticaria and severe includes severe rash, hepatitis, interstitial nephritis, allopurinol hypersensitivity syndrome

\-Renal dosing: Stage 4 or worse start at 50mg/day

Allopurinol Hypersensitivity Syndrome (AHS)

\-Severe rash, hepatitis, interstitial nephritis, and eosinophilia

\-Risk for renal insufficiency, thiazide diuretic, HLA B\*5801 positive

\-Safe to use in decreased CrCl

Febuxostat (Uloric)

\-2nd line compared to Allopurinol

\-MOA: selective xanthine oxidase inhibitor and decreases synthesis of uric acid

\-Less titration required

\-AE’s: Nausea, arthralgia, increased LFTs and rash

\-BW: CV risk

\-Drug interactions: Theophylline, 6-MP, and Azathioprine

XOI Drug Interaction: Thiopurines

At minimum, dose of AZA or 6-MP needs to be reduced by 66-75%

Probenecid

*Rarely used*

\-MOA: Increase uric acid excretion

\-ADR’s: Urolithiasis, GI irritation, rash and hypersensitivity; CI in patients w/ CrCl <50 mL/min

Pegloticase (Krystexxa)

\-Pegylated urate oxidase (allergic reactions)

\-Check uric acid prior to each dose

\-Pre-medicate with oral anti-histamine, APAP, and IV corticosteroid; add MTX to decrease immune response

\-ADR: Gout flares, infusion rxns, nausea, ecchymosis

\-CI: G6PD Deficiency

Misc agents in Gout

\-Fenofibrate: Increased clearance of hypoxanthine and xanthine

\-Losartan: inhibits renal tubular resorption of uric acid and increase excretion (NOT a class effect, unique to losartan)

\-Reserved for refractory disease

FIBRO clinical features

F- Fatigue and/or Fibrofog

I- Insomnia

B-Blues (depression and/or anxiety)

R- Rigidity (stiffness in muscles and/or joints)

O- Ow! (pain and work difficulty)

Central FM Mechanism

*HPA Axis Dysfunction*

Decreased growth hormone + dopamine + serotonin → Decreased tissue repair, abnormal function of limbic systems, decreased delta sleep, sensitization to painful stimuli, dysfunctional descending pain inhibitory pathway → Decreased O2, Mg, ATP, PO4 and HPA Axis alterations → Fuel for the body and decreased cortisol

Peripheral FM Mechanism

\-Chronic sympathetic activation (delta sleep disruptions, muscle blood flow micro constrictions, elevated cytokines (IL-6, TNF), elevated Substance P

\-Mitochondrial damage from toxins (pre-oxidative reactions in build-up of lactic acid)

Non-pharmacologic tx for FM

\-Aerobic exercise (walking, water aerobics, stationary bike)

\-Psychological and behavioral approaches to reduce stress (CBT, relaxation training, visual imagery, distraction)

\-Complemental therapies (heat/cold therapy, massage, acupuncture, myofascial release)

Antidepressants used in FM

\-TCAs: Amitriptyline; historically 1st line/gold standard; limiting SE profile (sedation, constipation, and weight gain)

\-SSRIs: Fluoxetine decreases fiber-fog, sleep and fatigue; less efficacious

\-SNRIs: Duloxetine (Cymbalta) is FDA approved; do not start above 30 mg bc nausea (requires tapering of dose)

\-NSRI: Milnacipran (Savella) is FDA approved; titration pack; causes crazy anxiety in some patients (+SE profile)

Cyclobenzaprine (Flexeril) in FM

\-Structurally similar to amitriptyline

\-Decreases pain and improves delta sleep

\-Limited by SE profile (extreme drowsiness)

Neuron-specific CCB in FM

\-Decreases the release of glutamate, NE, and Substance P

\-Pregabalin (Lyrica): 1st approved drug; dose titration required; Decreases pain, fatigue, and improved sleep quality; SE profile (angioedema, weight gain, peripheral edema, vision changes)

\-Gabapentin (Neurontin): dose titration required; Decreases pain, improved sleep quality and vitality; Advantages: more experience, lower cost, less peripheral edema, no risk of angioedema

Dopamine Agonists in FM

*Only for restless leg syndrome*

\-Pramipexole (Mirapex): Decreases pain, fatigue and increases overall function; SE: sleep attacks and orthostatic HoTN + weight gain

\-Ropinirole (Requip): some efficacy seen

Analgesics in FM

\-DO NOT use NSAIDs, Corticosteroids, Opioids

\-Tramadol: Central acting opioid analgesic

\-Lidocaine transdermal patches: may be used to treat specific trigger point areas

Herbal/Dietary Supplements & Alt. therapies

\-Melatonin = monster dreams

\-Magnesium

\-Capsaicin: must use consistently

\-Medical cannabis

Naltrexone in FM

\-Low dose (4.5 mg/day)

\-Exhibits paradoxical properties (including analgesia and anti-inflammatory actions)

\-Two mechanisms: Antagonist effect on mu opioid and non-opioid receptors

Clinical Manifestations of SLE

\-Cutaneous: molar rash (butterfly rash), photosensitivity, alopecia

\-Musculoskeletal: arthralgias, synovitis, inflammatory arthritis

\-Renal: Lupus nephritis

\-CNS: Seizures, psychosis, neuropathy

\-Mucosal: Ulcers

\-Hematologic: Thrombocytopenia, leukopenia, hemolytic anemia

ANA levels in SLE

\-Non-specific! Many patients test positive for this and do not have lupus

\-All auto antibodies can change over the course of the disease

Drug Induced Lupus

\-Very common! Must stop the offending agent (if it gets bad then add-on mild immune modulators)

\-Definitely: Procainamide, hydralazine, quinidine, isoniazid, D-penicillamine, methyldopa and minocycline

Nonpharm tx in SLE

\-Sun protection due to sun sensitivity

\-Exercise: reduce obesity, fatigue, sleep disturbances, improve cardio and bone health

\-Rest: Improves stress on joints and prevents further joint destruction

\-Decreased CV factors: Diet, exercise, BP, cholesterol, smoking cessation

Induction therapy in SLE

1. Glucocorticoids + MMF or cyclophosphamide for Class III, IV, V (mixed)
2. Glucocorticoids + MMF for Class V

Maintenance therapy in SLE

MMF or azathioprine

Corticosteroids in SLE

\-Monotherapy or adjunct to other tx

\-Rapid onset of action

\-High dose burst can be used in severe disease flare

\-Taper to a goal of <7.5 mg/day

\-Topical may be utilized for cutaneous manifestations

\-ADE’s: Hyperglycemia, bone density decrease (long-term use) and psychiatric disturbances

Aspirin in SLE

\-Antiphospholipid antibody postive

\-Low dose (81 mg) used as prevention

\-Should avoid other NSAIDs

Hydroxychloroquine (HCG) in SLE

\-Prevents lupus flares, improves long term survival, protective effect on bone mass as well as against thrombosis and organ damage

\-Do not exceed 5 mg/kg/day due to retinal toxicity risk (risk factors: tamoxifen use, renal impairment, low body weight and macular disease)

\-AE’s: retinopathy, HA, dizziness, skin reactions and N/V/D

\-SAFE in pregnancy (use if anti-Ro/SSA and anti-La/SSB antibodies present)

MTX in SLE

\-Mainly for resistant arthritis; doe not have organ involvement

\-Folic acid supplementation

\-GI intolerance

\-Avoid alcohol

\-Women must use contraception and can damage sperm in men

\-Monitor pulmonary function

Mycophenolate mofetil (CellCept) and Mycophenolate sodium (Myfortic) in SLE

\-Indications: Lupus nephritis, subacute cutaneous dx, refractory to other immunosuppressants

\-Titration of dose is required (diarrhea = rate limiting step)

\-SE’s: GI upset (diarrhea), increased risk for infection, headache, elevated liver enzymes, peripheral edema, leukopenia, thrombocytopenia

\-Monitoring: CBC, serum electrolytes, liver enzymes, kidney function

\-Drug interactions: PPI (take 90 mins prior to PPI)

\-REMS program

Azathioprine (Imuran) in SLE

\-Indications: Lupus nephritis- maintenance dosing

\-Drug interactions: Xanthine oxidase inhibitors

\-Screening: TPMPT deficiency

\-SE’s: N/V/D, myalgia, leukopenia, thrombocytopenia, risk of infection, elevated hepatic enzymes and/or elevation of serum alkaline phosphatase and bilirubin

\-Contraindications: Signs of bleeding, sx of jaundice, change in color of stool

\-Used in pregnancy if SEVERE flare

Belimumab (Benlysta) in SLE

\-MOA: IgG1 monoclonal antibody

\-Indication: Active SLE and lupus nephritis

\-ADE’s: N/D, neutropenia, infections, psychiatric disturbances, infusion related reactions, injection site reactions, insomnia

Voclosporin (Lupkynis) in SLE

\-Used in combo w/ immuno therpy for active lupus nephritis

\-MOA: Calcineurin inhibitor - inhibition of lymphocyte proliferation, T-cell cytokine production and expression of T-cell activation surface antigens

\-ADR’s: Decreased GFR, hypertension, diarrhea, headache, anemia, HA, UTI, cough

\-oral admin

\-Avoid use with strong CYP3A4 inhibitor

\-Warnings: Lymphomas/skin malignancies and serious infections

\-Counseling: Small whole on empty stomach, take w/in 4 hours of missed dose, long time to experience benefits, do not become pregnant

Anifrolumab (Saphnelo) in SLE

\-MOA: IgG1-kappa MAB that blocks the biologic activity of type 1 interferon receptors

\-ADE’s: Infection, cough and infusion related reactions

Rituximab în SLE

\-MOA: Binds to CD20 antigen on B-cells to activate complement-dependent B-cell cytotoxicity

\-Tx of severe refractory SLE and lupus nephritis (biggest immunosuppressant agent)

\-ADE’s: PML! infusion reactions, rash, neutropenia, diarrhea, risk of infection

\-May be pe-treated with APAP, diphenhydramine and corticosteroids

Cyclophosphamide

\-MOA: Alkylating agent leading to cell death. Proposed to suppress B-cell and IgG production, and decrease production of adhesion molecules and cytokines

\-Indications: Lupus nephritis, neuropsychiatric lupus, and severe systemic vasculitis

\-ADE: Interstitial cystitis! Infertility, N/V, decreased appetite

\-Mesna can be co-prescibed to decrease risk of cystitis

Pregnancy counseling

\-Should conceive after their disease has been in remission for 6 months or longer

\-If patient needs to remain on immunosuppression: mycophenolate is usually switched to azathioprine at least 6 mo prior to conceiving

\-Mycophenolate mofetil and other drugs are teratogenic (MTX, leflunomide, cyclophosphamide)