New Use for LDN Sarcoidosis Leonard Weinstock MD

New Use for LDN: Sarcoidosis Leonard Weinstock, MD Associate Professor of Clinical Medicine Washington University School of Medicine President, Specialists in Gastroenterology

Experiences with LDN n “Conditions where LDN could be of benefit” n 176 diseases, syndromes, and disorders n Limited number of publications www. ldnresearchtrust. org

My LDN Experience: (N>1200) n n n n n Alopecia areata Chronic fatigue synd. Complex regional pain * Constipation * Crohn’s disease * Dercum’s disease Eczema Fibromyalgia * AIDS * n n n n Interstitial cystitis Irritable bowel syndrome * Multiple sclerosis * Prostatitis (Type III) Restless legs syndrome Sarcoidosis Small intestinal bacterial overgrowth Ulcerative colitis *

Sarcoidosis Granulomatous disorder with T-cells & macrophages in multiple organs § CD 3+ cells, CD 4+ cells w/ HLA-DR antigen, & high CD 4/CD 8 ratio in bronchus § CD 4+ CD 29+ memory T-cells increased Iida K et al. Thorax 1997; 52: 431 -7.

Sarcoidosis § Special T-cell interactions in pulmonary and liver sarcoidosis § Activated memory T-cells with CD 11 a Iida K et al. Thorax 1997; 52: 431 -7.

Sarcoidosis: Pathogenesis • Genetic susceptibility with functional polymorphisms • Exposure to antigens leading to activation of macrophages • Attainment of T-cell immunity against antigens mediated by antigen processing and presentation by macrophage Zissel

Sarcoidosis: Standard Rx • Initial therapy: prednisone (often 2 yr) with variable initial dose, taper, & duration • Steroid-sparing Rx: • Methotrexate • Azathioprine • Leflunomide • Mycophenolate • Infliximab Baughman; Chapelon-Abric.

Sarcoidosis vs. Crohn’s disease § Similar pathology § Unregulated T-cell activity § Non-caseating granulomas

Sarcoidosis Rx: Role for LDN § § § Regulate T-cell growth Regulate B-cell growth Decrease inflammation Decrease permeability Stabilize Toll-like receptors § § Decrease microglia activation Decrease cytokine release Shift from TH 2 to TH 1 Improve GI motility

Sarcoid Case 1 Rash Fatigue Adenopathy Liver/Spleen

Case 1 AH 73 y. o. AAF – supraglotic resection in 2001 d/t sarcoidosis. Sx weak voice, painful rash, fatigue, and parotitis § Rash prevention by minocycline § Hx MTX neuropathy § Referred abnl CT § LDN – prescribed

Progress 2015 February - LDN 1 mg/day n March - less dyspnea, fatigue, able to stop minocycline w/o rash n March – LDN increased 12 days to 4. 5 mg n May – Dec - less DOE, more energy n July & Dec – CT’s showed reduction in the size of the splenic lesions and n

12/2014 11/2011 Before LDN

12/12 - 10 mo LDN 7/15 - 5 mo LDN

12/15 – 10 mo LDN 12/14

Sarcoid Case 2 Pulmonary Fatigue

Case 2: PFB 64 y. o. AAF § § § 26 yr pulmonary sarcoidosis 2 yr home O 2 (24 hr/d; 2 L) Dyspnea (rest/activity) and dry cough § 7/15 - Prednisone 20 mg § Last used 16 yr ago § 8/15 - LDN

Case 2: PFB 64 y. o. AAF § 9/15 – 1 mo LDN § No change § 10/15 - 2 mo LDN § Less fatigue § Less dyspnea § O 2 prn for vigorous activity § Prednisone taper started

Sarcoid Case 3 Pulmonary

Case 3: PLB 63 y. o. WM § Abnl CXR 17 yr ago – Bx: granulomas § Hx osteopenia § 2 yrs dyspnea with activity § 8/20/15 - LDN § 4. 5 mg (titrated up from 1. 5 over 2 wks)

Case 3: PLB 63 y. o. WM § 1 mo after LDN – unchanged § 2 mo after LDN – less short of breath § 3 mo after LDN – asthma from allergens

Sarcoidosis Rx: Role for LDN Experience needed – enroll AA pts ü Pulmonary response w treadmill testing ü Anti-inflammatory markers