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Experiences with LDN

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. “Conditions where LDN could be of benefit” 176 diseases, syndromes, and disorders

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Experiences with LDN

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  1. New Use for LDN: SarcoidosisLeonard Weinstock, MDAssociate Professor of Clinical MedicineWashington University School of MedicinePresident, Specialists in Gastroenterology

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

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

  4. Sarcoidosis • Granulomatous disorder with T-cells • & macrophages in multiple organs • CD3+ cells, CD4+ cells w/ HLA-DR antigen, & high CD4/CD8 ratio in bronchus • CD4+ CD29+ memory T-cells increased Iida K et al. Thorax 1997;52:431-7.

  5. Sarcoidosis • Special T-cell interactions in pulmonary and liver sarcoidosis • Activated memory T-cells with CD11a Iida K et al. Thorax 1997;52:431-7.

  6. 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

  7. 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.

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

  9. 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 TH2 to TH1 • Improve GI motility

  10. Sarcoid Case 1 Rash Fatigue Adenopathy Liver/Spleen

  11. 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

  12. Progress 2015 February - LDN 1 mg/day March - less dyspnea, fatigue, able to stop minocycline w/o rash March – LDN increased 12 days to 4.5 mg May – Dec - less DOE, more energy July & Dec – CT’s showed reduction in the size of the splenic lesions and liver lesions

  13. 12/2014 11/2011 Before LDN

  14. 12/12 - 10 mo LDN 7/15 - 5 mo LDN

  15. 12/15 – 10 mo LDN 12/14

  16. Sarcoid Case 2 Pulmonary Fatigue

  17. Case 2: PFB 64 y.o. AAF • 26 yr pulmonary sarcoidosis • 2 yr home O2 (24 hr/d; 2 L) • Dyspnea (rest/activity) and dry cough • 7/15 - Prednisone 20 mg • Last used 16 yr ago • 8/15 - LDN

  18. Case 2: PFB 64 y.o. AAF • 9/15 – 1 mo LDN • No change • 10/15 - 2 mo LDN • Less fatigue • Less dyspnea • O2prn for vigorous activity • Prednisone taper started

  19. Sarcoid Case 3 Pulmonary

  20. 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)

  21. 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

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

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