Transcript 71 yr retired virologist - Advances in Inflammatory Bowel Diseases

“Tough Cases”
Doug Wolf and Gil Y. Melmed
Advances in IBD
Hollywood, FL
December, 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 – addisonian1996 – 6-MP, metronidazole
Not effective. Now what?
71 yr retired virologist
• 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
• 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
71 yr retired virologist
• Diagnosis: M. tuberculosis
• Treatment:
– Rifampin, INH x 6 months
– PZA, ethambutol x 2 months
• IFX held during TB therapy
• Symptoms (diarrhea, fistula) recur
Now What?
• Can he safely receive an anti-TNF agent ever
again?
71 yr retired virologist
• 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!
Now What?
• Which treatment would you try next?
– Start 6-MP
– Adalimumab (ADA) (off-label)
– ADA/6-MP combination
– ADA/methotrexate combination
71 yr retired virologist
• 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?
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
L Colon
Tr Colon
R Colon
T Ileum
• 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…