Azathioprine in refractory sprue: results from a prospective, open-label study.
OBJECTIVE
Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue.


METHODS
We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRgamma gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8-12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/ day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial.


RESULTS
After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up.


CONCLUSIONS
The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.
Mauriño
Eduardo
E
Department of Medicine, Dr. Carlos Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina.
Niveloni
Sonia
S
Cherñavsky
Alejandra
A
Pedreira
Silvia
S
Mazure
Roberto
R
Vazquez
Horacio
H
Reyes
Hugo
H
Fiorini
Alcira
A
Smecuol
Edgardo
E
Cabanne
Ana
A
Capucchio
Monica
M
Kogan
Zulema
Z
Bai
Julio C
JC
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001835:Body Weight; D002446:Celiac Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004386:Duodenum / Q000473:pathology; D005260:Female; D005903:Gliadin / Q000276:immunology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012709:Serum Albumin / Q000032:analysis; D000515:alpha 1-Antitrypsin / Q000032:analysis
D001323:Autoantibodies; D006454:Hemoglobins; D007166:Immunosuppressive Agents; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; D005903:Gliadin; D001379:Azathioprine