thalidomide has been successful use in patients with refractory crohn disease ( cd ) in recent years .
we collected the data of a postoperative cd patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures .
a 51-year - old female was diagnosed as cd after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine ( aza ) .
fortunately , she achieved mucosal healing ( mh ) at a low dose of thalidomide for 15 months .
crohn disease ( cd ) is a progressive and destructive disease , over 70% cd patients require intestinal resection at some time during their life time .
the rate of endoscopic recurrence in cd patients 1 year after operation ranges from 30% to 70% , increasing to 50% to 100% after 3 years . despite evolving prophylactic treatment algorithms , treatment of postsurgical recurrence is still required for a proportion of patients . here presents a case of postoperative endoscopic cd recurrence that achieves mucosal healing ( mh ) on thalidomide .
in march 2014 , a 51-year old female with a history of 3-year gastrointestinal bleeding , underwent the ileocolonoscopy which revealed some terminal ileal longitudinal ulcers and spontaneous hemorrhage ( fig .
the colon was normal . as the bloody stool was out of control with the decreased level of hemoglobin ( hb ) from 113 to 85 
g / l within 24  hours , she subsequently had an urgent resection of the affected terminal intestine , and the remaining intestine were detected to be normal .
four weeks later , the disease was clinically quiescent with no bloody stools ( hb : 112 
g / l ) , which gave a crohn disease index activity ( cdai ) score of 144 .
and she was prescribed azathioprine ( aza ) 100  mg / d because of the high risk of recurrence .
three months later , however , the patient experienced endoscopic recurrence as the colonoscopy ( fig .
2b ) both revealed the anastomotic ulcers which gave a rutgeerts score of i2 with cdai score of 102 .
considering the high cost of biological agents , she refused to take infliximab ( ifx ) and started on thalidomide at 50  mg / d .
six months after initiation of thalidomide therapy , the patient again developed complaints of abdominal pain and bloody stool ( cdai score : 185 ) and noted no improvement of ulcers ( fig .
the cdai reached 101 and the rutgeerts score declined to i1 after 9-month adjusted therapy ( fig .
a telephone conversation confirmed that until may 2016 the patient insisted on thalidomide 100  mg / d with no adverse effect and had been asymptomatic .
( a ) longitudinal ulcers were observed in the terminal ileum and ( b ) spontaneous hemorrhage before surgery .
( c ) the histopathological examination revealed noncaseating granulomas in the submucosal layer ( arrow ) . before treatment with thalidomide .
( a ) no improvement was noted after 6 months therapy with thalidomide 50  mg / d .
( b ) disappearance of anastomotic ulcers with only a few aphthae was revealed after 9-month therapy with thalidomide 100  mg / d .
surgery is not a cure for cd patients , and postoperative recurrence is frequent . among the risk factors for the postoperative recurrence , smoking , perforating disease , perianal disease , extension , and urgent indication for surgery
thioprine was associated with a significantly reduced risk of clinical and severe endoscopic recurrence when compared to placebo .
there are promising data that targeting tnf- therapy prevents postoperative recurrence . nevertheless , its routine prophylactic use after surgery to prevent recurrence is debatable taking into account its high medical cost and the potential side effects .
postoperative management should be personalized based on the estimated probability of cd recurrence . in our case ,
aza ( 100  mg / d ) was started as early as 4 weeks after the surgery to prevent recurrence taking into account the high risk ( urgent procedure ) .
the consensus on the medical paradigm of postoperative cd recurrence has not yet been achieved .
sorrentino et al conducted a pilot study and prescribed ifx to 13 patients and mesalamine to 11 patients who experienced postoperative recurrence , at week 54 , 0/11 patients treated with mesalamine and 7/13 patients treated with ifx had endoscopic remission ( p = 0.01 ) .
the study showed that anti - tnf agents may be efficient in treating postoperative cd recurrence .
thalidomide as a tnf inhibitor was prescribed to our patient other than ifx secondary to the expenses .
thalidomide was originally prescribed to a pregnant woman as its sedative property , and was withdrawn from the market in 1961 because of its teratogenic side effects , particularly phocomelia . during the last decades , it has been reintroduced as a potent antiinflammatory and immunosuppressive drug and shown to have a role in some diseases such as erythema nodosum leprosum , sarcoidosis , behcet syndrome , and cd .
thalidomide may shift the th1 pattern to th2 with the inhibition of tnf- , ifn- , and il-12 , stimulate il-4 and il-5 and block nf-b activation . since the first report of the efficacy of thalidomide treatment in a complicated cd patient , several studies have demonstrated the role of thalidomide in active cd .
two studies both demonstrated the long - term clinical outcome of thalidomide in refractory cd .
simon et al conducted a recent multicenter observational study of 77 patients with active cd , refractory to conventional immunosuppressive therapies , 54% of the patients were in clinical remission after thalidomide treatment within the first year .
of the 7 cd patients complicated with fistulae who had failed anti - tnf biologic treatment and received thalidomide as rescue therapy , 5 had complete fistula closure during the follow - up period .
fifteen intractable cd patients were started on thalidomide ( 100  mg / d ) after they had responded to ifx ( 5  mg / kg infusions ) , remission rates were 92% , 83% , and 83% at 3 , 6 , and 12 months .
thalidomide also appears to be successful use in refractory esophageal cd and patients who developed ifx - induced delayed hypersensitivity action . in recent years
, mh is recommended to be the therapeutic goal associated with a reduced risk of relapse , fewer surgeries , fewer hospitalization , and steroid tapering .
mh in ibd could be achieved by several drugs , such as aza , biological agents , corticosteroids , and thalidomide .
scribano et al reported the efficacy of thalidomide in 3 patients with moderate - to - severe cd who failed to biological anti - tnf agents , all the 3 patients at a low dose of thalidomide ( 50150 
mg / kg ) for 9 to 36 months achieved clinical remission and mh . in our case ,
the recent consensus guidelines from european crohn 's and colitis organization / european society for pediatric gastroenterology hepatology and nutrition ( ecco / espghan ) commended that thalidomide therapy could be alternative for anti - tnf agent responders who do not tolerate or lost response to biological anti - tnf agents .
zheng et al in a retrospective study evaluated the effects of thalidomide in 6 chinese refractory pediatric cd , all patients clinical symptoms improved remarkably during the follow - up time .
a multicenter randomized clinical trial of 56 children and adolescents with refractory cd also has shown that clinical remission was achieved in significantly more children treated with thalidomide ( 1.52.5  mg / kg ) than with placebo at week 8 ( 46.4% vs 11.5% ) .
few studies have focused on the efficacy of thalidomide in the surgical cd . in 2004 , hershfield et al presented a 29-year - old case affected by cd , he was seen for persistent bleeding and anemia after 1 year of the reoperation procedure , and the colonoscopy revealed terminal ileal ulcers .
his problem was persistent with the use of methotrexate , corticosteroids , and aza , then the patient was placed on thalidomide at 50 to 100  mg / d .
twelve months later , the colonoscopy demonstrated remarkable improvement of the appearance of the terminal ileum with only a few small ulcers remained . in our case , the aza therapy failed to prevent postoperative recurrence , and the low dose of thalidomide succeeded in achieving the mh of the anastomotic ulcers .
no clear correlation between neuropathy and cumulative thalidomide dose were established in inflammatory bowel disease ( ibd ) . in a long - term study on thalidomide in cd patients , during the follow - up for a median of 58 months , an adverse event occurred in 68% of the patients , over a third ( 13/37 ) of patients experienced neuropathy with a median cumulative dose of 11.1  g ( range : 0.35225.5  g ) , and all but 3 patients resolved with dose reduction or discontinuation .
lazzerini et al performed a retrospective study of 28 children and adolescents with chronic refractory ibd treated with thalidomide , 7 patients experienced reversible neuropathy with all cumulative doses over 28  g. in our case , the cumulative dose of thalidomide on the patient was over 28  g , until the mh was achieved , she did not experience any adverse events . in conclusion
, thalidomide is effective to induce mh in the postoperative cd endoscopic recurrence in our case . to our knowledge
thalidomide , the anti - tnf agents , may be an alternative therapy regimen for the postoperative cd endoscopic recurrence .
 abstractbackground : thalidomide has been successful use in patients with refractory crohn disease ( cd ) in recent years.methods:we collected the data of a postoperative cd patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures.results:a 51-year - old female was diagnosed as cd after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine ( aza ) . 
 fortunately , she achieved mucosal healing ( mh ) at a low dose of thalidomide for 15 months.conclusion:thalidomide is effective to induce mh in the postoperative cd endoscopic recurrence . 