Sarcoid Arthritis

SARCOID ARTHRITISMAYLING NGPHARM D CANDIDATE 2016WESTERN NEW ENGLAND UNIVERSITY COLLEGE OF PHARMACYOCTOBER 27,2015

OBJECTIVES

• Identify signs and symptoms associated with sarcoid arthritis• Understand pathophysiology of sarcoidosis• Identify treatment options• Apply treatment options to patient specific cases and form a

therapeutic plan

PATIENT PRESENTATIONCC: 49 y.o female presents with questions about usage of infliximab for sarcoid arthritis and follow up on smoking cessation and endocrine conditions.HPI: At last visit, pt started chloroquine to replace hydroxychloroquine which was causing pruritis. Pt has stopped taking famotine since pruritus has stopped from d/c of hydroxychloroquine. Pt developed blurry vision, reduction in concentration and nausea with chloroquine soon after last visit. PCP thought blurry vision was due to Chantix and d/c Chantix. Pt went to ER X 2 with diagnosis of rare side effects due to chloroquine. Chloroquine was stopped. Pt saw PCP 4 weeks ago with results of ACE levels which were elevated. Pt has lumps on her feet that were exacerbated between therapies. Her mobility is limited when her lumps are exacerbated. During the current visit, her mobility is functional.

PMH• Sarcoid and associated arthritis since 2013• Skin disease (official dx unknown but describes boils on arm and bikini area)• Diabetes since 2002 (on insulin for 4 years)• Acute pancreatitis• Fatty liver• Hypothyroidism• Hypercholesterolemia• Anxiety• Hx of concussion 3 years ago

Medication IndicationRemicade (infliximab) IV at 0, 2, and 6 weeks, then every 8 weeks (dose unknown)Methotrexate 2.5mg 8 tablets po once weeklyPrednisone taper 5mg tid for 10 days, 5mg bid for 10 days, etc., (started 8/17)

Sarcoid/arthritis

Lantus 25 units SC QHSHumalog sliding scale SC prn (using approx. 3 times per week-increased by 1 unit since last seen)Metformin 1000mg po BID

Diabetes

Levothyroxine 125mcg po daily QAM Hypothyroidism

Atorvastatin 80mg po daily QPM Hypercholesterolemia

Aspirin 81mg po daily ASCVD risk prevention

Zolpidem 5-10mg po prn sleep (using 3 times per week)

Insomnia

Medication IndicationFolic acid 1mg 1 tablet po dailyMulti Vit-Min po dailyVitamin D3 2000units po daily

Vitamin Deficiency

CetirizineHydroxyzine 25mg po daily prn (none since last visit)

Pruritus

Amitriptyline 10mg po daily QPM Residual Motion Sickness Post-Concussion

Full spectrum flora po dailyDouble Strength GFSE (grapefruit extract) po daily

Probiotic/GI Upset Prevention

Lavela WS 1265 (lavender oil) po daily Anxiety

D/C Enbrel 50mg SQ weeklyD/C famotidine(dose unknown)

SarcoidosisPruritus

PATIENT PRESENTATION• Allergies: NKDA, allergic to corn and yeast per naturopath• Social History: married with no children• Alcohol: drinks once weekly up to 3 drinks• Smoking: smokes 1.5ppd x 20 years• FH: father with alcoholism, heart disease and esophageal

cancer; mother with diabetes, osteoporosis, and heart disease; brother with diabetes

LABS2/28/2015• Na 137, K 4.2, Cl 106, C02 25, BUN 12, SCr 0.84, eGFR:82• MA/Cr: 4mcg/mg• ALT 21• TSH 5.09 Free T4 1.0• Vitamin D 38• TC 141 HDL 55 LDL 65 TG 106• Glu 113, A1c 7.8%

PROBLEM LIST

1.Sarcoid Arthritis2.Diabetes Mellitus3.Smoking Cessation

WHAT DO YOU KNOW ABOUT SARCOIDOSIS?• HOW PREVALENT IS IT?• IN AMERICANS,WHICH TWO ETHINICITY GROUPS ARE AFFECTED

MOST?• WHICH ORGANS CAN BE AFFECTED?• WHAT ARE COMMON SIGNS AND SYMPTOMS?

…………….LET’S FIND OUT!

PREVALENCE• Can affect all ages, races, genders equally• Occurs usually before age 50 with peak incidence between 20s and 40s• Highest incidence in northern Europeans of Scandinavian descent(more

common in women) and African Americans• In Americans, more prevalent in African Americans vs Caucasian

Americans

ATS. Am J Respir Crit Care Med.1999;160:736-755.

ETIOLOGY

• Causes are unknown: mainly speculation• Several case reports on possible causes

a. Person to person transmissionb. Environmental/occupational exposurec. Genetic factors


PATHOGENESIS

• Immune response trigger by antigen• Antigen induces local TH1T cell response• Macrophages release inflammatory cytokines • Accumulation of Th1 cells locally and creation of granulomas


SIGNS AND SYMPTOMS• GENERAL: Fatigue, night sweats, weight

loss, low grade fever up to 39-40 degrees celsius• Organ specific manifestations: lungs, eyes,

skin, CNS• Women: erythema nodosum more common• Men: ankle periarticular inflammation or

arthritis w.o erythema nodosumATS. Am J Respir Crit Care Med.1999;160:736-755.Sarcoidosis; dactylitis, hands[Internet]. ACR; Rheumatology Image Library. [cited 2015 Oct 27]. Available from: http://images.rheumatology.org/viewphoto.php?imageId=2862597&albumId=75693.Circulation; 2005:111(11): 158-160.Emergency Medicine Atlas. McGraw-Hill Companies,Inc. 2006[cited 2015 Oct 27]. Available from:http://yxzl.baiduyy.com/chm11/jzyxtp/ch.13.htm.

DIAGNOSIS• Diagnosis of exclusion based on signs and symptoms and

clinical data• Transbronchial Lung Biopsy(indication): everyone except

patients with Lofgren’s syndrome• 60% of pts have elevated ACE levels but serum ACE levels can

not be relied upon for diagnosis


DIAGNOSIS OF SARCOID ARTHRITISAcute sarcoid arthritis/Lofgren’s Syndrome:Symptom triad: a. erythema nodosumb. bilateral hilar lymphadenopathy c. arthritis or arthralgia• Common joints affected: ankle, knee,

wrist, metacarpophalangeal joints• Signs and symptoms: fever, increased

ESRATS. Am J Respir Crit Care Med.1999;160:736-755.

Chronic sarcoid arthritis• Synovial fluid analysis(mild

inflammatory infiltrate)• Synovial biopsy to differentiate

in between RA• Rule out rheumatoid arthritis(RA)

and reactive arthritis• Most sarcoid arthritis cases are

polyarthritic

PROGNOSIS

• 2/3 pts have remission within a decade• ½ pts achieve remission in 3 yrs• 1/3 may have significant organ impairment• Mortality rate:< 5% ,death result of complications• Sarcoid arthritis: symptoms occur for 2-3 mths, remission usually

by 6 mths w NSAIDs or corticosteroids. ATS. Am J Respir Crit Care Med.1999;160:736-755.

GOALS

• Prevent organ damage/complications•Relieve symptoms and/or pain• Improve quality of life

TREATMENT OPTIONSDRUG INDICATION WHEN TO USECorticosteroid Prednisone

RA (Topical)mild sarcoidosis-skin, uveitis, cough(Systemic)To improve pulmonary symptoms, systemic manifestations

Cytotoxic Agents Methotrexate(MTX) Azathioprine(AZA)

RA, SLE(off-label) Refractory disease

Aminoquinolone Hydroxychloroquine Chloroquine

Malaria, RA, SLE Pulmonary and cutaneous sarcosis

TNF Inhibitors Infliximab Adalimumab

RA+ Crohn’s DiseaseRA + other forms of arthritis

Refractory disease, reducing symptoms

NSAIDS Pain/Inflammation Erythema nodosum, musculoskeletal symptoms

Tetracycline Derivatives Minocycline Doxycycline

Infection, malaria Cutaneous sarcoidosisSFR. Sarcoidosis treatment guidelines [Internet].[cited 2015 Oct 27]. Available from: https://www.stopsarcoidosis.org/wp-content/uploads/2013/03/FSR-Physicians-Protocol1.pdf.

SFR. Sarcoidosis treatment guidelines [Internet].[cited 2015 Oct 27]. Available from: https://www.stopsarcoidosis.org/wp-content/uploads/2013/03/FSR-Physicians-Protocol1.pdf.

INFLIXIMAB (REMICADE)• INDICATION: Psoriatic arthritis, RA,

Crohn’s Dx• DOSE: IV 3mg/kg at 0,2,6 weeks

followed by 3mg/kg every 8 weeks(RA dosing w. MTX)• MOA: Binds to TNF-alpha

decreasing inflammation and activation of neutrophils and eosinophils

• Infliximab. In: Lexi-Drugs[Database on the Internet].Hudson (OH):Lexi-Comp,Inc.2015;[cited 27 Oct 2015].

REMICADE CONT.

•A/E: infusion related reaction•MONITORING: During infusion, monitor VS q 10 min,

LFTs, signs and symptoms of infection, CBC w Diff•ADMINSTRATION: Should pre-medicate w H1

antagonist+/- H2 antagonist, APAP and/or corticosteroid to avoid infusion reaction

Infliximab. In: Lexi-Drugs[Database on the Internet].Hudson (OH):Lexi-Comp,Inc.2015;[cited 27 Oct 2015].

• Multicenter, randomized, double-blind, place-controlled study with 138 pts allotted to placebo, infliximab 3mg/kg or infliximab 5mg/kg at weeks 0,2, 6, 12,18,24 and were followed through week 52

• Primary Endpoint: change from baseline in % predicted FVC• Secondary Endpoints: George's Respiratory Questionnaire (SGRQ) total score , 6-min

walk distance (6-MWD) test , Borg's CR10 dyspnea score (before 6-MWD test) (and the proportion of Lupus Pernio Physician's Global Assessment (LuPGA) responders for the subset of patients with facial skin involvement at baseline

• Safety: A/E • Results:

• A. Primary Endpoint: :Statistically significant improvement in mean 2.5%increase from base line of FVC in treatment groups, no change in placebo infliximab 3mg/kg group (2.8%, P=0.041) vs infliximab 5mg/day (2.2%,P=0.116) vs placebo.

• B. Secondary endpoint: non significant for changes SGRQ, Borg’s DR, 6MWD.C. Safety: A/E not statistically significant between the control and treatment group(87.0%vs93.2%)-cough, URI, dyspnea, bronchitis

a.2 pts diagnosed with malignancies on week 52(BBW for malignancies)Baughman RP, et al. Am J Respir Crit Care Med. 2006;174(7)795-802.

SUCCESSFUL TUMOR NECROSIS FACTOR ALPHA BLOCKADE TREATMENT IN THERAPY-RESISTANT SARCOIDOSIS• Case report 51 y.o female w severe sarcoidosis refractory on azathioprine,

methotrexate, cyclophosphamide, and pentoxifylline(conventional tx).Pt could not decrease to<20mgprednisone daily w.o worsening of symptoms. Pt had multiorgan manifestations: liver, Lofgren’s syndrome • Immediately after first dose of infliximab(3mg/kg at weeks 0,2,6 and every 8

weeks)pt’s arthralgia and joint swelling decreased. In 10mth follow up arthritis was still in remission. Pt was then stable on low dose prednisone(10mg daily) w.o need for any other immunosuppressant agent

Ulbricht KU, et al. Arthritis Rheum. 2003;48(12):3542-3543.

EFFECTIVENESS OF INFLIXIMAB IN TREATING SELECTED PATIENTS WITH SARCOIDOSIS• Objective: To assess the effectiveness of infliximab (Remicade) in the treatment of

patients with sarcoidosis who either do not respond to corticosteroids and other conventional drugs or develop unacceptable side effects to these drugs.• Design:single center, non-randomized,off label study at a teaching hospital• 12 pt btw ages 45-70 w sarcoidosis w multiorgan involvement refractory to

conventional therapy• Infliximab was infused at a dedicated ambulatory infusion center. The initial dose was

3 mg/kg body weight and subsequent doses were given at weeks 2, 4, 6, 10, and 14. All patients received at least six infusions.• Efficacy:All 12 patients improved significantly. • Safety:One patient had a mild allergic drug reaction that responded to antihistamine.Saleh S, et al. Effectiveness of infliximab in treating selected patients with sarcoidosis. Lancet Respir Med. 2006;100(11):2053-2059.

COMBINATION USE• Guidelines are unclear as to best approach to optimal therapy• Treatment is based upon severity of disease and organs affected• Steroid sparing therapies are favored • MTX has similar efficacy as AZA• Most therapies ultimately have the same target: inhibition of TNF-alpha• Steroid therapy may be initiated at first to control symptoms• TNF-alpha inhibitors generally reserved for treatment refractory pts• Currently no clinical trials comparing the 3 available: adalimumab, etanercept,

infliximab • Pts generally start on corticosteroid, add steroid sparing agent such as AZA or MTX

then add on MAB when refractory while decreasing the prednisone doseATS. Am J Respir Crit Care Med.1999;160:736-755.

ACE LEVELS

• Used to measure disease progression in sarcoidosis• Granulomas can increase production of ACE levels• Therefore, ACE levels are Elevated when pt’s disease state worsens• No a reliable marker for ruling out sarcoidosis,it is only present in

50-80%of the sarcoidosis pop

ACE: the test[Internet]. AACC. 2015[cited 2015 Oct 27]. Available from: https://labtestsonline.org/understanding/analytes/ace/tab/test/.

BACK TO OUR PATIENT: ASSESSMENT• RISK FACTORS: Pt is a 49 y.o Caucasian female• SIGNS AND SYMPTOMS: lumps on feet that are not

bothersome currently, elevated ACE levels• PMH OF SARCOID + TREATMENT: HX OF LUMPS ON FEET

AND ELEVATED ACE LEVELS• ENBREL-D/C PER MD• CHLOROQUINE-OCULAR TOXICITY(BLURRY VISION)-D/C• HYDROXYCHLOROQUINE-A/E: PRURITUS-D/C• CURRENTLY ONLY MTX+PREDNISONE+STARTED INFLIXIMAB

TREATMENT TIMELINE

GOALS OF THERAPY

•MAINTAIN REMISSION OF SYMPTOMS• PREVENT COMPLICATIONS/ORGAN DAMAGE

SFR. Sarcoidosis treatment guidelines [Internet].[cited 2015 Oct 27]. Available from: https://www.stopsarcoidosis.org/wp-content/uploads/2013/03/FSR-Physicians-Protocol1.pdf.

ASSESSMENT

• Pt was on MTX and Enbrel and still experiencing lumps on feet>>Tx failure• Pt did not tolerate hydroxychloroquine or chloroquine well>>A/E• Pt currently on steroid which is to be avoided in T2DM due to elevation of

BG levels • Pt may not need steroid while on infliximab. MTX can stay on as in case

studies, it does• RA indication recommends usage of MTX while on infliximab.• Pt tx is appropriate

DIABETES MELLITUS

Goals1. Optimize treatment regimen to meet ADA goals for A1c,

FBG and PPG2. Prevent complications of diabetes3. Improve quality of life

Garber AJ, et al. 2015 AACE/ACE Comprehensive diabetes management algorithm. Endocr Pract. 2015;21(4):e1-e10.

OUR PATIENTHPI: Pt A1c was 10.7% at most recent PCP visit • PCP increased Lantus from10 U to 25 U SQ HS and increased Humalog SSI by 1 unit• Pt adds extra Humalog before eating a high carb meal• Pt was started on Prednisone taper on 8/17(approximate course ~1mth) • Pt checks FBG before breakfast and alternates between lunch and dinner but does not

adhere to checking TIDCurrent Therapy:• Lantus 25 units SC QHS• Humalog sliding scale SC prn (using approx. 3 times per week-increased by 1 unit since

last seen)• Metformin 1000mg po BID

ASSESSMENT/RECOMMENDATIONS• Pt’s most recent A1c above ADA goal of <7% and AACE goal of </=6.5%• Pt was on prednisone which could have affected A1c levels• Pt’s noncompliance with checking BG makes it difficult to assess if meal time dosage of insulin

is sufficient• Pt’s SSI not ideal to control BG• According to AACE Guidelines for Diabetes Management Treatment Algorithm, Pts with A1c>9%

should be on dual, triple or insulin + other therapies. • Pt already on max dose of metformin, basal and bolus insulin but basal and bolus can be

titrated to effect• Other options: GLP-1, SGLT-2 or DPP-4 inhibitor

Garber AJ, et al. 2015 AACE/ACE Comprehensive diabetes management algorithm. Endocr Pract. 2015;21(4):e1-e10.

SMOKING CESSATION

Goals:•Complete and sustain abstinence from tobacco

products •Reduce/prevent cardiovascular risk factors• Improve quality of life

OUR PATIENT

• HPI: PCP d/c Chantix attributing A/E of blurry vision to Chantix• ER clarified that chloroquine was cause of blurry vision and pt

contacted MD for new rx for Chantix• Pt set quit date as 11/1/15.

OUR PATIENT: ASSESSMENT

• Current Therapy: None• Issues: no treatment for major problem• Pt eager to start therapy again• Pt would benefit from other smoking cessation therapies if

Chantix was not effective: NRT(patch and gum/lozenge)

1. SARCOID ARTHRITIS

• Education: MOA of Infliximab and role in therapy for sarcoidosis• Intervention: similar dosage to RA: not labeled for use for sarcoidosis:

(use in combination with methotrexate therapy): IV 3 mg/kg at 0, 2, and 6 weeks, followed by 3 mg/kg every 8 weeks• Monitoring: Infusion site reaction: monitor VS q 2-10 min, LFTs,

worsening HF, CBC w diff• Increased risk of infection, injection site irritation, resolution of bumps• Follow Up: 1 mth: to determine efficacy of infliximab

2. DIABETES• Education: Importance of FBG and PPG, 15/15 rule(treatment of hypoglycemia

with increased insulin dose)• Intervention: Advise pt to alternate meals to differentiate BG after small and

large meals Give pt food log to record amount of Humalog injected per meal and type of food consumed

• Monitoring: Hypoglycemia(dizziness, tachycardia, HA, weakness ,confusion, etc), check BG TID• Follow Up: A1c 3 mths from last A1c, Assess efficacy of new dosage when pt

records food intake and readings for next visit due to new dose change

3. SMOKING CESSATION

• Education: Distracting hobbies to help quit, use stress ball, chew sugar-free gum instead • Intervention: Pt to check w PCP about re-initiating Chantix• A/E-strange dreams, insomnia, HA, depression, suicidal

tendencies• Monitoring: behavioral changes and suicidal thoughts• Follow Up: Next visit after PCP adds Chantix

KNOWLEDGE CHECK!

• PREVALENCE OF SARCOIDOSIS?• ETHNIC GROUPS WITH HIGHEST LIKELIHOOD OF

MANIFESATIONS?• ORGAN INVOLVEMENT?• PRESENTATION OF SARCODOSIS?• TREATMENT OPTIONS FOR SARCOID?

REFERENCES1. ATS. Statement on sarcoidosis. Am J Respir Crit Care Med.1999;160:736-755.2. Sarcoidosis; dactylitis, hands[Internet]. ACR; Rheumatology Image Library. [cited 2015 Oct 27]. Available

from: http://images.rheumatology.org/viewphoto.php?imageId=2862597&albumId=75693. 3. Images in cardiovascular medicine. Circulation; 2005:111(11): 158-160.4. Emergency Medicine Atlas. McGraw-Hill Companies,Inc. 2006[cited 2015 Oct 27]. Available

from:http://yxzl.baiduyy.com/chm11/jzyxtp/ch.13.htm.5. SFR. Sarcoidosis treatment guidelines [Internet].[cited 2015 Oct 27]. Available from:

https://www.stopsarcoidosis.org/wp-content/uploads/2013/03/FSR-Physicians-Protocol1.pdf.6. Infliximab. In: Lexi-Drugs[Database on the Internet].Hudson (OH):Lexi-Comp,Inc.2015;[cited 27 Oct 2015]. 7. Baughman RP, Marjolein D, Kavuru M, et al. Infliximab therapy in patients with chronic sarcoidosis and

pulmonary involvement. Am J Respir Crit Care Med. 2006;174(7)795-802.8. Ulbricht KU, Stoll M, Bierwirth J, et al. Successful tumor necrosis alpha blockade treatment in therapy-

resistant sarcoidosis. Arthritis Rheum. 2003;48(12):3542-3543. 9. Saleh S, Ghodsan S, Yakimova V, et al. Effectiveness of infliximab in treating selected patients with

sarcoidosis. Lancet Respir Med. 2006;100(11):2053-2059. 10. ACE: the test[Internet]. AACC. 2015[cited 2015 Oct 27]. Available from:

https://labtestsonline.org/understanding/analytes/ace/tab/test/.11. Garber AJ, Abrahamson MJ, Barzilay JI, et al. 2015 AACE/ACE Comprehensive diabetes management

algorithm. Endocr Pract. 2015;21(4):e1-e10.

THANK YOU FOR YOUR TIME

NAP TIME!

Sarcoid Arthritis

Documents

Transcript of Sarcoid Arthritis