Jugan MC, Langston C, Plattner BL, Ford AK. Effect of Iron Deficiency on Short-Term Response to Treatment in Cats with Chronic Enteropathies. J Vet Intern Med. 2025 May-Jun;39(3):e70131. doi: 10.1111/jvim.70131. PMID: 40384256.
MT20-002 – an EveryCat-funded research project
Chronic intestinal disease is common in cats, and a major cause of long term morbidity. In humans and dogs, iron deficiency is often seen in cases of chronic intestinal disease; but this has not been documented in cats. This study discusses iron deficiency in cats afflicted with chronic inflammatory enteropathies (CIE) and low-grade alimentary lymphoma (LGAL). It is based on the understanding that chronic gastrointestinal (GI) disease can lead to iron deficiency through both absolute iron deficiency, characterized by decreased iron absorption or loss, and functional iron deficiency, where iron is trapped within cells due despite adequate total body iron.
This project had two primary objectives. First, it sought to compare the prevalence of iron deficiency between cats diagnosed with CIE and those with LGAL at the time of their initial GI disease diagnosis. The second was to assess how iron deficiency influenced the short-term clinical response to standard-of-care treatment in CIE cats, including those with low iron but normal or undefined ferritin levels.
The authors prospectively enrolled 28 client-owned cats with chronic GI disease to veterinary centers at Kansas State University and The Ohio State University between June 2021 and April 2023. These cats underwent a comprehensive work-up and received a definite diagnosis of either CIE (n=14) or LGAL (n=14) through GI endoscopy and histopathology. Owners provided detailed histories and completed questionnaires for standardized clinical disease severity scores (DSS). Anemia was defined by a hematocrit below the laboratory reference interval, and iron deficiency was diagnosed based low serum iron and a transferrin saturation (TSAT) of less than 20%. When ferritin measurements were available, iron deficiency was further categorized as relative or absolute.
Blood samples were collected at enrollment for a complete blood count (CBC), serum iron, total iron binding capacity (TIBC), and in a subset of cats, ferritin. Serum amyloid A (SAA), an inflammatory biomarker, and methylmalonic acid (MMA), a marker for cobalamin deficiency, were also analyzed. All cats underwent upper and lower GI endoscopy, and histopathological evaluations were performed by board-certified pathologists using World Small Animal Veterinary Association (WSAVA) scoring criteria. In cases of diagnostic ambiguity, PCR for antigen receptor rearrangement (PARR) and/or immunohistochemistry for CD3+ lymphocytes were utilized to confirm diagnoses. Following diagnosis, treatments such as diet trials, prednisolone, and cyanocobalamin were initiated based on clinician discretion. CIE cats had rechecks at 14, 30, and 90 days, with therapeutic adjustments allowed for inadequate responses. No cats received iron supplementation during the study period. At rechecks, various parameters were assessed, including physical examination findings, CBC, iron panels, MMA, SAA, clinical DSS, and fecal scores.
The study cohort consisted of 28 cats, predominantly spayed females, with a median age of 10.7 years. The median duration of clinical GI signs was 8 months, with vomiting, weight loss, diarrhea, and hyporexia being the most common presentations. A significant percentage of cats (32%) had lost over 10% of their body weight. Complete iron panels were available for 18 of the 28 cats. Based on TSAT, 21 cats had normal iron status, while 7 cats (25%) were diagnosed with iron deficiency at enrollment. Of these seven, four had ferritin evaluated, allowing for classification of functional iron deficiency in three CIE cats and absolute deficiency in one CIE cat. The relative risk of iron deficiency was not significantly different between CIE and LGAL cats (relative risk 0.4; p=0.39), meaning LGAL cats were not found to be more prone to iron deficiency than CIE cats at diagnosis. While there was no statistical difference in serum iron, ferritin, or TIBC between the two groups, TSAT was significantly lower in LGAL cats (median 22% in LGAL vs. 30% in CIE; p=0.02).
Follow-up was available for 13 of the 14 CIE cats. Among these, nine achieved a complete clinical response to treatment. Importantly, the study found no significant difference in baseline clinical DSS between responders and nonresponders, nor was there a difference in baseline iron, ferritin, or TSAT between CIE cats that achieved a complete response versus those with partial or no response. This indicates that iron deficiency did not affect the short-term clinical response to individualized treatment in CIE cats. While iron deficiency resolved in the initially iron-deficient CIE cats by Day 14, two additional cats developed iron deficiency at that recheck, and six cats were iron deficient at 30 days. By the 90-day recheck, two cats remained iron deficient, both of whom were considered treatment responders. Non-regenerative anemia was present in 32% of cats at enrollment, with no significant difference in hematocrit between CIE and LGAL cats, or between iron-deficient and non-iron-deficient cats. Hematocrit levels also did not change significantly over time in CIE cats and were not associated with any iron indices. Inflammatory markers showed no clear association with iron status or clinical severity. Median SAA concentrations were not different between cats with or without iron deficiency, nor between LGAL and CIE cats. SAA concentrations were also not associated with clinical DSS or iron indices, and did not change significantly over the study period in CIE cats. Intestinal inflammatory WSAVA scores did not differ in any GI region based on the presence or absence of iron deficiency. Regarding cobalamin and MMA, a subset of cats exhibited hypocobalaminemia based on elevated MMA or decreased cobalamin concentrations, but these were not different between CIE and LGAL cats, nor between iron-deficient and non-iron-deficient cats.
Overall, this study provides insights into iron dysregulation in cats with chronic GI disease. While a notable 25% of cats presented with iron deficiency, its prevalence was not significantly different between CIE and LGAL at diagnosis. Iron deficiency did not negatively impact the short-term clinical response to individualized treatment in CIE cats. This suggests that while iron deficiency is a common comorbidity, its presence at diagnosis does not necessarily predict a poorer immediate outcome. ~MK
See Also:
Mahadea D, Adamczewska E, Ratajczak AE, Rychter AM, Zawada A, Eder P, Dobrowolska A, Krela-Kaźmierczak I. Iron Deficiency Anemia in Inflammatory Bowel Diseases—A Narrative Review. Nutrients. 2021; 13(11):4008. doi.org/10.3390/nu13114008