sarcoid arthritis
TRANSCRIPT
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
ATS. Am J Respir Crit Care Med.1999;160:736-755.
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
ATS. Am J Respir Crit Care Med.1999;160:736-755.
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
ATS. Am J Respir Crit Care Med.1999;160:736-755.
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)
PLAN
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!