1. Robby Ferrante Pharmacy Candidate Western New England CoP

2.  Evaluate patient presenting to the Big Y Health Clinic with history of sarcoidosis  Discuss the pathology of sarcoidosis  Review treatment options  Determine an ideal regimen for the patient

3.  49 Year old AA male  Initial visit  Pleasant and energetic but disheveled  Newly diagnosed with Type 2 DM  Chief Concern: Help with food choices

4.  Recently started a new job  Lost previous job and was evicted due to hospital stay  Living in shelter/housing where he has a bedroom with a roommate and a shared kitchen for the complex  Drinks a couple beers once or twice a week  Denies tobacco use, but smokes marijuana multiple times daily to stimulate appetite.

5.  Recent diagnosis with diabetes  Coronary artery disease  2 stents placed this year following recent MI  Sleep apnea  History of kidney stones  Sarcoidosis  Manifestations in lungs, eyes, and skin

6.  Metformin XR 500 mg every morning  Prasugrel 10 mg daily  Metoprolol tartrate 75 mg twice a day  Atorvastatin 80 mg daily  ASA 81 mg daily  Isosorbide mononitrate 30 mg daily  Hydroxychloroquine 200 mg twice a day  Unknown ointment/cream for sarcoidosis lesions

7.  Systemic disease of unknown cause characterized by formation of immune granulomas.  Often affects lungs and lymph system

8.  70 % of cases reported in ages 25-45  Incidence: 14-24 per 100,000  Prevalence: 8-102 per 100,000  Heritability?  Twin study  61,662 pairs of Danish and Finnish twins  210 pairs had at least 1 proband Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014 Mar 29;383(9923):1155-67 Rybicki B, Ianuzzi M, Frederick M, et al. Familial aggregation of sarcoidosis. A case-control etiology study of sarcoidosis (ACCESS) Am J Respir Crit Care. 2001 Dec 1;164(11):2085-91

9.  Genetic predisposition for exaggerated inflammatory response  Large release of cytokines leads to granuloma formation  Depending upon cytokine release, may be chronic  Chronic in about 20% of patients  Human Leukocyte Antigen dependent  HLA-DRB1*1101 = Higher incidence  HLA-DRB1*03 = better prognosis Baughman R.P., Lower E.E. (2012). Chapter 329. Sarcoidosis. In Longo D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J, Loscalzo J (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved May 06, 2015 from http://0-accesspharmacy.mhmedical.c

10.  APC  Helper T cells *  Macrophage cluster  Cytokine release  IL-2  IFN gamma  IL-10 vs IL-8 + TNF

12.  Lungs: >90%  Skin: 30%  Eyes: Vary  >70% in Japan  30% in US (more common in AA population)  Liver: 20-30%  Anemia 20%

13. http://pixgood.com/sarcoidosis-chest-x-ray.html

17.  What medication is our patient not receiving that we might expect him to be on?

18.  Prednisone 20-40 mg per day then taper down 5 mg/day biweekly to maintenance dose of 5-10 mg/day  Adverse Effects:  Weight gain  Hypertension  Infection  Blood glucose increase (Diabetes)  Cushing’s syndrome  Glaucoma/Cataracts

19.  Cochrane analysis of 3 trials of steroids vs placebo  Chest x –ray showed improvement in 70% of patients with steroids vs. 49% in placebo group  But… No significant difference after 2 years of treatment  Analysis of 2 trials of steroid vs no treatment  Significant improvement at 7 months, but not after 24 months Paramothayan N, Lasserson T, Jones P. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005; Apr 18;(2)

21.  10-20 once a week PO or IM  MOA: Multiple, but in sarcoidosis, inhibition of T cell activation and down regulation of B cells  Toxicities: hepatic, hematologic, renal, pulmonary  Contraindicated:  Liver/Renal Failure  Respiratory Failure  Alcohol abuse  Pregnant/Lactating women  Pregnancy Category X (cytotoxic)

22. SIDE EFFECTS  Hepatic fibrosis  Leukopenia  Pulmonary fibrosis  Non-productive cough  Dyspnea  Fever  Nausea  Alopecia EFFICACY  Have been found to reduce steroid dose  Not significant because of drop out  Retrospective cohort of 200 patient with MXT or AZA  Decrease in prednisone dose ▪ 6 mg/yr  Increase in FEv1 and VC  AZA had high rate of infection Vorselaars A, Wuyts W, Vorselaars V, et al. Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest. 2013;144(3):805

23.  200-400 mg/day  Very limited data, only used when other treatments have failed  More often used for cutaneous sarcoidosis  Major Adverse Effects:  Retinopathy/Blindness  Hepatic failure  Hematologic toxicity  Hearing loss  Angioedema Baughman R, Lower E. Evidence-based therapy for cutaneous sarcoidosis. Clin Dermatol: 2007;25(3):334

24.  Chimeric, humanized monoclonal antibody  Neutralizes TNFa  Dose: 3-5 mg/kg at weeks 0, 2, 6, and 12, then…?  Study performed of 138 patients with sarcoidosis for over a year  FVC increased 2.8% and 2.2% in 3 mg/kg and 5 mg/kg, respectively.  Small study size, relatively small increase, only 24 week study Baughman R, Drent M, Kavuru M. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006: 1;174(7): 795-802

26.  Recently diagnosed with Type 2 DM  Poor diet, inactivity, weight gain, long-term corticosteroid use  History of sarcoidosis (>1 year)  Skin lesions, pulmonary manifestations, visual manifestations, kidney stones  Currently taking hydroxychloroquine 200 mg BID and topical ointment PRN

27.  Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014 Mar 29;383(9923):1155-67  Rybicki B, Ianuzzi M, Frederick M, et al. Familial aggregation of sarcoidosis. A case-control etiology study of sarcoidosis (ACCESS) Am J Respir Crit Care. 2001 Dec 1;164(11):2085-91  Baughman R.P., Lower E.E. (2012). Chapter 329. Sarcoidosis. In Longo D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J, Loscalzo J (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved May 06, 2015 from http://0-accesspharmacy.mhmedical.com  Paramothayan N, Lasserson T, Jones P. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005; Apr 18;(2)  Vorselaars A, Wuyts W, Vorselaars V, et al. Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest. 2013;144(3):805  Baughman R, Lower E. Evidence-based therapy for cutaneous sarcoidosis. Clin Dermatol: 2007;25(3):334  Baughman R, Drent M, Kavuru M. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006: 1;174(7): 795-802