Chronic Fatigue Syndrome CASE STUDY Neil Hirschenbein MD, PhD Clinical Management of Inflammation Therapy 2/16/13

5/04 JT • 54 yo with chronic fatigue for 7 years and sleep disturbance • Dx with Sleep Apnea, no improvement with CPAP • Multiple supplements, no change • Awaken tired, and tired all day long • Decreased memory & concentration • Some walking, no better or worse

5/04 • • • • • • •

PMH Surgery- GB - ENT for sleep apnea Hospitalizations – none additional Medical – Depression - Hypothyroid - Hypoadrenal

5/04 • Meds – bupropion • - Armour Throid 1 Grain • - hydrocortisome 5 mg bid • No improvement with above meds • Physical Exam - WNL

5/04 Testing • Organic Acids- Bacterial Dysbiosis • - Yeast Dysbiosis • - Nutrient Deficiencies • Heavy Metals- Elevated Mercury

Disability • Forms for State, Social Security, Company Disability

6/05 • • • • • •

Discussed Infectious Agents Lyme Western Blot through Igenex Inflammatory Protocol Discussed and Initiated Vitamin D- 25 and I,25 Checked Olmesartan started 40mg q8h BP monitoring

7/05 Vitamin D • 25 (OH) Vitamin D – 36 NG/ML (20-100) • 1,25 (OH) Vitamin D – 34 PG/ML (15-60)

7/05 IGENEX WB • IgM - *23-25 IND • - * 31 IND • - * 34 • - *39 IND • - *41 IND •

IgG - *23-25 – - *31 IND - *34 - *39 IND - *41` + - *93 -

Olmesartan • • • •

Angiotensin Blockade No difficulty with pharmacy or insurance Tolerated BP 110-120/60-70 Potential Herxheimer(Immunopathology) Reactions • Tolerated without immunopathology

7/05 • Went on Inflammatory Protocol website and very excited to start • Vitamin D discussed – sunlight, florescent lighting, covering self, food, supplements, NOIR glasses, etc. • Herxheimers reviewed – decreased antibiotic, increased Olmesartan • Started Minocycline 25 mg qod

8/05 • • • •

Herx responses – especially on off day Increased fatigue – occasionally bedbound Increased muscular fatigue But excited about Herx’s and felt he was on the road to recovery • Increased Olmesartan to q 6h • Increased Mino to 50 mg qod • ISAC testing ordered

9/05 • ISAC equivocal (missing reagent) • Tolerated increased Mino & Olmesartan, so he increased Mino to 75 mg qod • Noticed periods of significant improvement (light at the end of the tunnel)

11/05 • Increased Herx, so decreased Mino to 50 mg qod for awhile, then increased Mino to 75 and increased olmesartan to q4h and sx tolerable • Many sx similar to those in the past – brain fog, myalgias, fatigue, weakness, sadness, depression, and flu like sx • New sx of nerve like pain in L upper arm & L hip • Ready to increase Mino to 100 mg qod

12/05 • Tolerated Mino 100 mg qod • Typical month – 0 good days, 20 fair days, and 10 bad days. 0 days where he could complete all ADL’s • On fair days, occasionally leave home to grocery or drug store, and doesn’t have to be in bed all day long.

12/05 Cont’d • On bad days, virtually bedridden all day long. Difficulty making decisions and following instructions because of brain fog • Need for written instructions, especially if different than pharmacy instructions • Added azithromycin 250 mg – 1/8 q 10 days and decreased Mino to 50 mg qod

2/06 • Able to increase Mino back to 100 mg qod • Able to increase azithromycin from 1/8 to ¼ q 10d • Daily Herx, tolerating, didn’t want to increase, and wanted to take antibiotic break

3/06 • • • • • •

DC’d antibiotics – no change, then DC’d Olmesartan – no change, then Restarted Mino 50 mg q12h – no change, then Increased Mino to 25 mg q 6h- some relief Then resumed Olmesartan 40 mg q6h Then started Heparin 5000u SQ bid

4/06 • With Heparin, increased Herx • Difficulty giving injections and switched to SL Compounded Heparin • Added lumbrokinase • Hyperbaric Oxygen discussed • Now tolerating Olmesartan 40 mg q6h, Mino 100 mg qod, and Zith increased to 3/8 q 10 d

6/06 • Azithromycin increased to ½ q 10d • Tolerating SL Heparin and Lumbrokinase • Doing well from neck down, but problem from neck up with brain fog and sedation • Discussed Far InfraRed Sauna and German Biologicals (Homeopathic Detox) • Started Clindamycin 150 mg, ¼ qod, and again decreased Mino to 50 & Zith to ¼

8/06 • After 3 doses of Clindy, increased Herx – involving the head – sedation and sleepy, and decreased appetite and 4# weight loss. • Despite this, increased Clindy from ¼ to ½ and then to 1 (several days before OV) • Stayed on Mino 50 and Zith ¼ • Herx worse, occasionally intolerable. Tried increased Olmesartan and Mino 50 on off day

9/06 • Still problem with 1 Clindy. Noticed similar problems with others on Website, esp going that quickly, so decreased Clindy to ½ and symptoms more tolerable • Later increased back to 1, increased Sx, and went back to ½ • Want to have a “controlled” Herx response

10/3/06 • Continued problem with ½ Clindy qod, so decreased to ½ q 4d, with decrease in fatigue, muscular aching, and emotional sx • Frustrated with length of time on protocol

10/31/06 • Feeling overall 20% better- esp. from neck down • Can walk for ½ hr. at brisk pace with no post exertional fatigue • Above neck sx the same, but increased Clindy from ½ (75mg) q4d to 100mg q2d. Mino & azithromycin unchanged. • Had tapered & DC’d heparin, & no change Sx

11/06 • Again intolerable fatigue and sedation (above head) despite increased Olmesartan and Mino, so DC’d Clindy for several weeks

12/06 • Restarted Clindy at 75mg qod, but had to decrease to 50 mg q4d. Continued Mino at 50 mg q 12h. • Disappointed at lack of progress • Main Sx – fatigue, brain fog, and head sedation

1/07 • Now on Clindy 50mg q4-6d. Zith back to ½ q 10d & Mino 100 qod • Above neck Sx, esp. brain fog improved • Pt. pleased with improvement, despite higher dose • Below neck Sx varariable, but generally the same –occ. Tired or achy • Able to review legal documents for 3 hrs. – previously 5 minutes.

3/07 • 25 (OH) Vitamin D 36 to 9. 1,25 (OH) 34 to 42 (drawn incorrectly) • Now on Mino 100 mg qod, azithromycin ½ q 10d, and Clindy 75 mg q 4d

4/07 • Increased Clindy 75 to 100, with increased above neck Sx • Made list that filled ¾ of page of things he could do, that he couldn’t do 1 year ago, including driving to Palm Springs (2-3 hr) • Wanted to add co-trimoxazole so DC’d azithromycin for 3 weeks (long half life) & started co-trimoxazole DS ¼ qod & decreased Clindy & Mino

5/07 • Co-trimoxazole “knocked him out” – just wanted to sleep • Skipped dose and decreased from ¼ to 1/8 • Had been able to increase Clindy to 1

6/07 • • • •

Dentist q 4 mos. & “pockets” better Eyes unchanged – usually worse annually Able to fly to Northern California & visit father. Multiple people there & able to function properly without brain fog. Had great time. • Disability re-evaluated & extended

8/3/07 • With co-trimoxazole more fatigue (below neck) both with small & large doses • With Clindy most Sx above neck • Mino 100 qod, Clindy 150 q4d, & cotrimoxazole increased from 1/8 to ¼ qod • Mild headaches (had for years) now gone & head clear

8/31/07 • Now Clindy 150 mg qod (taken over 1 year to get there), Mino 100 qod, & increased cotrimoxazole from ¼ to ½ & just to ¾. • Intermittent severe fatigue, but generally more energy • Mental function improved & persisted for 2 mos. Decreased brain fog, able to read, & converse. Not felt this well mentally for 10 yrs.

9/07 • Didn’t tolerate co-trimoxazole ¾ qod, so he increased to 1, & then decreased to ½, both without benefit. • Felt more tired & depressed • Pt. wanted to switch Mino to Demecycline. • Started on ¼ of 150 mg qod (sometimes hard to obtain & expensive) & decreased Clindy to 75 & co-trimoxazole to ½ • LDN discussed

10/07 • • • •

Increased Deme from ¼ to ½ without difficulty Increased Clindy from 75 to 150 qod Continued co-trimoxazole ½ qod Wanted to start LDN 3mg at HS

12/3/07 • Tolerated LDN 3 mg – no effect on sleep • Antibiotics unchanged, although stopped for 8 d because of fatigue (no change) • co-trimoxazole DC’d & restarted azithromycinwith lower doses of Clindy & Deme • LDN increased to 4.5 mg

12/31/07 • Better off co-trimoxazole • Taking Zith ½ q10d, Clindy 150 mg qod, & Deme 150 mg qod – all maximum doses • Able to go to Auto Show – 1st time in 5 years

6/08 • Past month, feeling better than ever • Back to 80% maximum, 70% of the time • Able to cook better, eat better and therefore have more strength & energy • Eye exam stable X 5 years • Gums continue to improve • Took trip to Palm Springs; tolerated heat; improved social interactions

9/08 • Restarted co-trimoxazole - now on azithromycin ½ q 10d, Mino 100 mg qod, & co-trimoxazole ¼ qod • Problems with headache, drowsiness, decreased mental function • Stopped co-trimoxazole – no change • Stopped azithromycin – better • Restarted azithromycin and later cotrimoxazole

11/08 • Taking azithromycin ¼ q10d, Mino 100 mg qod, & co-trimoxazole 1/8 q4d • Tried co-trimoxazole 1/8 qod but had increased symptoms – above neck sx of sedation, depression & tension in head & jaw • When not trying to increase co-trimoxazole felt good

1/09 • Taking Mino 100 mg qod, & Zith ½ q10d • Increased co-trimoxazole from 3/16 q 4d to 1/8 qod for 2 wks & did well • Increased co-trimoxazole to ¼ qod & severe reaction, esp. lack of motivation. Had fatigue, above neck. He could go for a walk & do fine, but the main problem was forcing himself to do it

3/09 • Decreased Mino to 50 mg qod, continued cotrimoxazole 1/8 q 4d, DC’d azithromycin, & started Clindy 50 mg qod • After few doses, increased lack of motivation • Tried Benicar q3h for 36 hr & no Improvement • Stopped all antibiotics for 16d & started feeling better Added lithium orotate 20 mg to decrease neurotoxicity

4/09 • Fantastic response to lithium-got motivation back within 2d; depression resolved • Able to do more, & feel good • Increased Clindy to 75 mg qod & cotrimoxazole to 1/8 qod • Able to walk 1 hr/d

6/09 • • • •

Feeling more tired, weak & sleepy DC’d all antibiotics Went to Palm Springs & had a good time After return, restarted and increased Mino from 50 to 100 mg qod; restarted & increased Clindy from 75 to 150 mg qod; & restarted cotrimoxazole ¼ qod • Minimally worse than on no antibiotics

8/09 • DC’d co-trimoxazole & restarted azithromycin • Worked Mino back to 100 mg qod, decreased Clindy to 100 mg qod, & azithromycin from 1/8 to ¼ q 10 d, & feeling better • 25 OH Vitamin D from 8 to 22 • Stopped Lithium for 1 ½ wks & more depressed & unmotivated. Restarted with benefit

10/09 • Continued on Mino & azithromycin • DC’d Clindy & restarted co-trimoxazole 1/8 qod • Increased co-trimoxazole to ¼ qod & felt more angry & depressed. Improved with olmesartan ½ SL • Despite this, felt good. Hiked Torrey Pines for 1 ½ hrs & walked most days for 1 hr • Able to fly cross country to visit mother & relatives in Pa. – 1st tine in 20 yrs.

12/09 • Taking Mino 100 mg qod; increased azithromycin ½ q 10 d; & increased cotrimoxazole to ½ qod. • Some symptoms, but don’t last long Some heartburn, improved with SL olmesartan

2/10 • Had increased Sx, so decreased co-trimoxazole from ½ to ¼ qod; & decreased azithromycin from ½ to ¼ q 10d. • Sx improved & able to increase co-trimoxazole back to ½ qod

5/10 • Later had increased Sx. Problem with that combination previously, but at lower doses • Decreased azithromycin from q10d to q15d; Increased olmesartan to q 4h; took SL olmesartan; & occasionally skipped other antibiotics • By May taking co-trimoxazole ½ qod, Mino 100 mg qod, & azithromycin ½ qod • Decided to downsize & sell house – washing windows, etc in preparation

7/10 • Continued on Mino 100 mg qod, azithromycin ½ q10d, & increased co-trimoxazole to 1 qod for awhile • Got more symptomatic, so decreased cotrimoxazole back to ½ qod

11/10 • Again became worse & stopped all antibiotics • Visited father in Northern California & had good time • Tried increased Lithium, but no change • Retested Testosterone. Decreased from 650 in 4/07 to 359. Started on Testosterone 25 mg with improved mood & strength

1/11 • Able to sell house, buy & move into new condo • Able to handle all physical & mental activities of selling & buying property; loading & unloading boxes; & moving in without feeling overwhelmed • Mental function continues to do well • Restarted azithromycin ¼ q10d, Mino 100 mg qod, & co-trimoxazole ¼ qod

6/11 • Feeling 80 – 90% of normal, 80 -90 % of time • Vision stable for 3 to 5 yrs. • Eyes better than expected for age per his opthalmologist

11/11 • Went to Cape Cod for July 4th and again for Labor Day & had great time. Considering spending entire next summer there • Taking azithromycin ¼ q10d, Mino 100 mg qod, & co-trimoxazole ¼ qod • Did IMT – Arterial Age 49 compared to Chronological Age of 61