““Tough Cases”Tough Cases”

Doug Wolf and Gil Y. MelmedDoug Wolf and Gil Y. MelmedAdvances in IBD Advances in IBD

Hollywood, FLHollywood, FLDecember, 2013December, 2013

71 yr retired virologist

• Diagnosed Crohn’s Disease at age 24– Initial presentation in 1966– Diarrhea and perianal abscess– Over next 30 years, 5 ileal resections and many

I & D procedures for perianal abscesses

• 1966-1996 – multiple courses prednisone

• On prednisone since 1966 – addisonian-

• 1996 – 6-MP, metronidazole

• Not effective. Now what?

• In 1997, age 55-Diverting ileostomy due to refractory fistulizing CD

• 5/2000 -Colonoscopy – Perianal fistulas, 40 cm of ileal Crohn’s disease, no colonic disease.

• 1/01 - started infliximab 5 mg/kg 0, 2, 6 and q8w

• 5/01 - Fistula healed after 5th infliximab dose

• 6/01 - Ileostomy reversed

71 yr retired virologist

• 8/13/01 – brought to the emergency room by ambulance– Hypotensive, hands cool, confused– Hypoxemic, tachycardic– CXR – widened mediastinum– ECHO – large pericardial effusion

71 yr retired virologist

• What is the cause?– Heart failure from infliximab– Pneumonia from infliximab– Neoplasm from infliximab– Tuberculosis

Timing of TB with Infliximab – typically occurs between 3-5th dose

• Diagnosis: M. tuberculosis

• Treatment: – Rifampin, INH x 6 months– PZA, ethambutol x 2 months

• IFX held during TB therapy

• Symptoms (diarrhea, fistula) recur

71 yr retired virologist

Now What?

• Can he safely receive an anti-TNF agent ever again?

• Decision made to resume IFX after 8m– Any concern for immunogenicity?– Reinduction?

71 yr retired virologist

• Infliximab resumed: 0,2,6 re-induction.

• (low dose steroid coverage)– Initial response but gradual loss of response– Dose escalation– symptom recurrence– No TB recurrence!

71 yr retired virologist

• Which treatment would you try next?– Start 6-MP – Adalimumab (ADA) (off-label)– ADA/6-MP combination– ADA/methotrexate combination

Now What?

• Continues low dose prednisone (5mg/d)• Treated with ADA 160/80 induction and • 40 mg q.o.w./6-MP.

– Developed rash.– 6-MP discontinued– ADA level checked – 3…….

• Switched to ADA/MTX– Excellent response

71 yr retired virologist

• 2006 – Goes to Italy for 2 weeks

• Returns home with 3 days of feeling ill– Fever, SOB, weak– CXR and CT- left upper lobe consolidation

71 yr retired virologist

Differential diagnosis?a) Recurrent tuberculosis

b) Pulmonary malignancy

c) Methotrexate toxicity

d) Legionella pneumophila

e) Bacterial pneumonia

71 yr retired virologist

• Bronchoscopy – negative

• Urinary Legionella antigen positive.

71 yr retired virologist

• Adalimumab and methotrexate held

• Treated for Legionella pneumophia…….

• Levofloxacin 750 mg a day for 21 days

• Adalimumab and methotrexate resumed 1 week after completing Levofloxacin

71 yr retired virologist

• 2y later- new painful, vesicular rash on left flank• Medications:

– Adalimumab– methotrexate 15 mg/wk– prednisone 9 mg/day

• What is this rash?

71 yr retired virologist

• What to do about IBD medications?– Valtrex for Shingles– Hold adalimumab and methotrexate?

• How long?

71 yr retired virologist

Case 2

32 y Lawyer

• 5y ago: diarrhea, pain/blood with defecation– CRS: “proctitis”, “elephant skin tags” “fissure”, “see GI”

• PMHx: ‘Back surgery’

• Meds: Norco (back pain)

• FHx: No IBD or CRC

• Exam: Mild LLQ tenderness

• WBC 11.0, Hgb 11.9, alb 3.5, ESR 14, CRP 1.26

32 y Lawyer

T IleumTr Colon

R ColonL Colon

• Initiate treatment, or does he need further dx tests?– Serology?– Any need for imaging?– EGD? Capsule Endoscopy?

32 y Lawyer

• Serology – – pANCA=45 (<15)– ASCA IgA = 17.5 (<20)– ASCA IgG =

undetectable– OMPC 18.1 (<16.5)– CBir = 42– “UC Predicted”

• CT Enterography– “thickening of wall of L

colon”– “thickening of multiple

mid small bowel loops with enhancement”

• Rheumatologist– “spondyloarthritis”

• What treatment to start with?

32 y Lawyer

• Treated with – 2 weeks metronidazole– Pentasa 8/day and Rowasa enemas– adalimumab monotherapy

• At 6 weeks, no change in symptoms

• At 8 weeks, FS showed no change in mucosal inflammation

• Now what??

32 y Lawyer

• Adalimumab discontinued at 12 weeks due to ‘primary nonresponse’

• Started Prednisone 40mg, 6-MP 1.5mg/kg• Immediate improvement• 4 months later, unable to wean below 15mg

prednisone despite therapeutic 6MP levels

• Now what???

32 y Lawyer

• Patience with 6mp! – 2 months later, still steroid-dependent

• Added infliximab

• Transient response after first 2 doses– Increased to 10mg q6w– Poor response

32 y Lawyer• Admitted for severe disease• Colonoscopy

– Deep ulcers, path with very active CMV– Polyp at 60cm (inflamed area), “tubular adenoma”– Referred for surgery– Dramatic clinical improvement with CMV

treatment, refusing surgery– Infliximab drug levels low at 4w

32 y Lawyer

• Discharged on ganciclovir slow taper

• Refused infliximab

• Went on carbohydrate-restricted diet off all meds

• 6m later in clinical and endoscopic remission

• 6m later (June, 2013) started to have symptoms again…

• Now what???

32y Lawyer

• Started prednisone and off-label ustekinumab July 2013

• Weaned off prednisone Sept 2013

• Continues to do well on 90mg q8w sq ustekinumab…