Case Report: Sarcoidosis in a Patient with Diabetes

Robby FerrantePharmacy CandidateWestern New England CoP

Objectives

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

Patient Presentation

49 Year old AA male

Initial visit

Pleasant and energetic but disheveled

Newly diagnosed with Type 2 DM

Chief Concern: Help with food choices

Social History

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.

Past Medical History

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

Medication List

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

What is sarcoidosis?

Systemic disease of unknown cause characterized by formation of immune granulomas.

Often affects lungs and lymph system

Epidemiology

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 probandValeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet.

2014 Mar 29;383(9923):1155-67Rybicki 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

Pathophysiology

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 prognosisBaughman 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

Immune Response

APC Helper T cells * Macrophage

cluster Cytokine release

IL-2 IFN gamma IL-10 vs IL-8 + TNF

Diagnosis

Manifestations

Lungs: >90% Skin: 30% Eyes: Vary

>70% in Japan 30% in US (more common in AA

population) Liver: 20-30% Anemia 20%

Chest Manifestations

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

Chest Manifestations

Skin Manifestations

Acute Disease Management

Patient Case

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

Oral Steroids

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

Oral Steroids

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 monthsParamothayan N, Lasserson T, Jones P. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005; Apr 18;(2)

Chronic Treatment

Methotrexate

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)

Methotrexate

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

infectionVorselaars A, Wuyts W, Vorselaars V, et al. Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest. 2013;144(3):805

Hydroxychloroquine

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

Infliximab

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

Patient Review

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

References

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