Eating Gluten Again After Starting Methotrexate
Globe J Gastroenterol. 2008 Dec seven; 14(45): 7009–7011.
Methotrexate induced sprue-like syndrome
Received 2008 Feb 3; Revised 2008 November vii; Accepted 2008 Nov 14.
Abstract
A 52 year-old male patient diagnosed of ankylosing spondylitis presented with an iron deficiency anemia afterwards a 10-month handling of methotrexate. He did non respond to handling with oral atomic number 26 not a proton pump inhibitor and an upper endoscopy was performed. The histological written report of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administrating intramuscular iron and undertaking a gluten-gratuitous nutrition, the histological and belittling alterations progressively resolved.
Keywords: Methotrexate, Villous atrophy, Iron deficiency anemia, Paucisymptomatic, Absence of celiac antibodies
INTRODUCTION
Methotrexate is an immunosuppressive agent usually used in the daily practice of many specialties. Methotrexate, in a weekly dose, tin can be used for years where its use is primarily limited by toxicity. The chief side effects include renal or liver impairment, orointestinal mucositis, os marrow toxicity and gastrointestinal side furnishings, such as nausea or airsickness, many of which can oftentimes be avoided past using low-doses of the drug, or combining it with folic acid supplementation[1].
Several cases of villus atrophy, after the apply of immunosuppressors[2], accept been reported in the medical literature; even so, only one case of abdominal villus atrophy secondary to Methotrexate, has been described[3]. We present a second case of a sprue-like syndrome secondary to methotrexate treatment, this fourth dimension in a paucisymptomatic patient.
Example REPORT
A 52 yr-old male person patient was referred to our Gastroenterology out-patient dispensary from the Rheumatology Section, as he presented with a progressively increasing iron deficiency anemia, that did not respond to proton pump inhibitors and atomic number 26 taken orally.
He had been diagnosed of ankylosing spondylitis, HLA B-27 positive, in 2000, and was initially treated with the nonsteroidal antiinflammatory drugs (NSAIDs), salazopyrine and omeprazol. In April, 2002, treatment with salazopyrine was stopped, but prednisolone and methotrexate were added in October, 2002, considering the patient had severe arthralgias. The arthralgias lessened with the new treatment, only analytical alterations were progresively seen. An analysis during December, 2002, showed normal hemoglobin (Hb 13.4 g/dL, VCM 87 and HCM 30.2) and iron (70 μg/dL), just in January, 2003, the hemoglobin level had decreased to 11.seven g/dL. By May, 2003, the asymptomatic patient presented with iron deficiency anemia (Hb nine.9 g/dL, Hto. 31%, VCM 71, HCM 22.ix, platelets 489000, atomic number 26 22 μg/dL, transferrine 366, IST v% and ferritine 2 ng/dL), for which he received iron, taken orally, and was referred to the Gastroenterology Section.
He had no digestive symptoms, weight loss, or anorexia. The suspected diagnosis included: (1) gastric erosions secondary to NSAIDs, (2) a side-issue of Methotrexate, or (iii) other causes of fe deficiency anemia. Therefore, an endoscopy and celiac sprue antibodies were requested, and treatment with oral atomic number 26 and proton pump inhibitors continued.
The upper endoscopy showed a tummy with patched mucosa, alternating red and white areas, which connected in the first and second portions of the duodenum, in which many longitudinal erosions, covered with fibrin, were observed, macroscopically uniform with an Inflammatory Bowel Illness, or a Lymphoma.
However, the histological study showed intestinal biopsy with testify of atrophy of the wall, with decreased thickness, increased collagenous fibers in the interstitium, mucosal flattening of the villi and pocket-sized repare glands (Effigy 1A). The mucosa shows a loss of glandular structure, with small and round reparing glands, covered by a cubical one-layer epithelium, with nuclei containing reactive atypia, with balmy pleomorphism, larger in size and variable nucleoli. There was a fibrous stroma and a heterogeneous inflammatory infiltrate, with eosinophil leukocytes in moderate quantity (Figure 1B- C).
Biopsy of duodenum. A: Year 2003, (HE, × 40); B-C: Yr 2003, (HE, × 100); D: Yr 2005, (HE, × 40); E-F: Year 2005, (HE, × 100).
In July, since the hemogram was similar (Hb 9.2 thou/dL), despite three months of oral iron, antibodies were negative, and taking into business relationship the results of the upper endoscopy, an intestinal follow-through and a colonoscopy (which were both normal) were requested and methotrexate was discontinued.
Three months afterward, the iron deficiency anemia persisted and a gluten-free diet was tested. In January, 2004, later three months of a gluten-free nutrition and six months of not taking methotrexate, there was still a iron deficiency anemia with a hemoglobin of ix.four m/dL, a new endoscopy was performed. The upper endoscopy showed a loss of duodenal folds and the urease test for Helicobacter pylori was negative. The histological study confirmed the existence of an atrophic gastritis and duodenitis. With the event of the endoscopy, the patient returned to our out-patient-clinic in March, 2004. He had an itchy eruption, fabricated upward of clusters of tiny blisters in the elbows and dorsum, which was compatible with a Dermatitis Herpetiformis. He was referred to the Dermatology out-patient clinic, but was not visited until six weeks later on where the peel lesions had spontaneously disappeared.
Treatment with intramuscular fe was initiated after the Dermatologic evaluation in April, 2004, and iii months subsequently the hemogram was almost normal; there was no anemia, (Hb 13.one grand/dL), but there was still a slight hypocromia and microcytosis. The intramuscular iron was stopped in Dec, 2004, when the still asymptomatic patient reached acceptable levels of iron, ferritine and transferrine (Fe 158 μg/dL, Transf. 275 mg/dL and Iron 93 ng/mL) and had a normal hemogram (Hb fourteen.5 k/dL, Hto. 43%, VCM 84, HCM 28.five).
The patient was periodically seen in our out-patient dispensary the post-obit year. Assay remained normal and a control upper endoscopy was carried out on December, 2005. It showed a dramatic change from the first i, which had been performed 2 years earlier, when the patient was undergoing treatment with methotrexate. The endoscopy was macroscopically normal.
The histological report showed an intestinal biopsy with normal wall thickness, normal size and number of villi, as well equally normal gland and stromal density (Figure 1D). Many intestinal glands, covered past a 1-layer cylindrical epithelium with goblet cells, were observed. Between them, the interstitium showed very mild inflammation with a subtract in the gristly weft. Inflammatory cells were heterogeneously composed of lymphocytes and plasmatic cells (Figure 1E- F).
The patient remains asymptomatic, from a gastrointestinal bespeak of view, and without anemia or ferropenia. Nosotros have not rechallenged methotrexate for ethical reasons.
Give-and-take
The involvement of this case is the appearance of a sprue-like syndrome after the apply of methotrexate, and its complete resolution, following the removal of the drug. Although several cases of small-scale-bowel villus atrophy take been described with other immunosuppresive agents, like Azatioprine[two], to our knowledge, merely 1 similar instance has been described regarding methotrexate[3]. The latter presented a case of diarrhea, progressive weight loss and full general malaise after ii years of low-dose methotrexate. Biopsies taken during the treatment showed pocket-size-bowel villus cloudburst and confirmation of mucosal healing was carried out months afterwards removal of methotrexate.
Our patient did not display any symptoms. He only had an iron deficiency anemia. Six months subsequently beginning low-dose methotrexate (15 mg/wk), a iron deficiency anemia developed. He showed no signs or symptoms of mucositis, or symptoms of os marrow toxicity, or of renal or liver damage. No diarrhea, nausea or other gastro-intestinal symptoms were present. We believe he had an iron malabsorption, secondary to duodenal atrophy, which slowly resolved after removing methotrexate, with clinical, analytical, endoscopical and microscopical confirming the healing.
This drug is oftentimes used in patients with rheumatological, gastroenterological and oncological illnesses. At high doses, and without folic acid supplement-ation, mucositis is a side-upshot in which experimental studies have tried to understand[4,five] for prevention[6-7]; however, non many human being cases accept been described. Its presentation is ordinarily symptomatic (weight-loss, diarrhea, nausea, general malaise, etc) and tends to appear with high doses.
The pathogenesis of the sprue-like syndrome is unclear. Two mechanisms might be involved, local antimetabolite toxicity and genetic predisposition[3].
Our case might allow other clinicians to retrieve of an underlying sprue-similar syndrome when a iron deficiency anemia appears when taking methotrexate, even if, like in our case, the patient is taking low doses of the drug and is completely asymptomatic.
This methotrexate-induced sprue-like syndrome is of clinical interest because of its singularity in the clinical presentation (simply iron deficiency anemia), its origin (a duodenal atrophy induced past depression-dose methotrexate, with no myelosuppression), and its complete resolution later on withdrawal of the drug, which has been confirmed both through the periodical analysis and through the endoscopical study.
Footnotes
Peer reviewers: Dr. Wang-Xue Chen, Institute for Biological Sciences, National Research Concil Canada, 100 Sussex Drive, Room 3100, Ottawa, Ontario K1A 0R6, Canada; Hallgrimur Gudjonsson, Md, Gastroenterology, University Hospital, Academy Hospital, Landspitali, Hringbraut, Reykjavik 101, Iceland; Daniel C Baumgart, Medico, PhD, FEBG, Division of Hepatology and Gastroenterology, Department of Medicine, Charité Medical School, Humboldt-Academy of Berlin, Virchow Hospital, Berlin D-13344, Germany.
Southward- Editor Li JL L- Editor Rippe RA E- Editor Lin YP
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773868/
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