By Hayat Al Tabosh, MD
A 14-month-old partially vaccinated male with no significant PMH was brought in by his parents for intermittent periorbital swelling for 3-4 days, associated with intermittent fussiness, decreased appetite, and difficulty sleeping. Periorbital swelling was worse in the mornings and got better throughout the day, although it never went away. There was no swelling in other parts of the body such as the hands, feet, or diaper area. There were no fevers, respiratory symptoms, emesis, diarrhea, rashes, or similar swelling in the past. No history of trauma to the face or eyes and no new exposures (such as new skin products or new foods).
On exam, patient was playful and well-appearing. Mild diffuse facial swelling was noted, slightly more pronounced in the periorbital region. No swelling in other areas of the body was appreciated. Cardiovascular exam revealed no murmurs or gallop, and pulses were strong, equal, and symmetric bilaterally.
During this visit, a urinalysis was obtained which was significant for trace protein, but was otherwise unremarkable. Although the extent of proteinuria was less than would be expected in nephrotic syndrome, lab work-up to measure serum protein and to assess kidney function was discussed with the family and was ultimately deferred.
Patient was discharged home on Zyrtec Qday trial for possible atopy, with strict return precautions with PCP if swelling did not resolve in 2-3 days.
Patient presented to UC 10 days later for persistent periorbital swelling that got worse in the morning, then improved throughout the day. Vitals were significant for tachycardia and hypertension. Weight was stable from most recent visit. Exam was significant for pale skin tone and mild infraorbital swelling. During this visit, CBC, CMP, and urinalysis were performed. CMP was significant for low total protein 3.5 g/dL (Ref: 5.6-7.4 g/dl) and low albumin 2.1 g/dL (Ref: 3.4-5.1 g/dL). The remainder of his electrolytes and liver function test results were within normal limits. Urinalysis was normal with no proteinuria and urine protein: Creatinine ratio was slightly elevated 0.34 mg/mg {creat} (Ref: 0.08-0.28 mg/mg {creat}). CBC clotted twice.
Case was discussed with nephrology who advised this is less likely nephrotic syndrome since there was no protein in the urine. GI was consulted, and patient was initially admitted to rule out protein-losing enteropathy (PLE). On the floor, initial work up included a CBC that was collected revealing severe microcytic anemia with Hemoglobin of 4.2 g/dL, MCV 56.5 fL, and retic count <0.2%. Iron studies showed low iron 14 ug/dL, normal TIBC 313 ug/dL, low iron saturation 4%, and low ferritin of 2 ng/ml.
Upon collecting more history from parents, patient consumed 24 oz of cow’s milk daily, which was a decrease from his earlier consumption. Hematology was consulted who confirmed the diagnosis of severe iron deficiency anemia (IDA) secondary to excessive cow’s milk protein consumption. During this admission, a fecal occult blood test (FOBT) was sent to rule out gastrointestinal bleeding as the source of low iron and came back negative. Fecal calprotectin was normal, ruling out inflammatory bowel disease (IBD). PLE was investigated with fecal alpha 1 antitrypsin (A1AT) which was positive at >1.13 mg/g (Ref: 0.00-0.50 mg/g). Patient received a 25% albumin IV infusion and 15 mg/kg of IV ferric carboxymaltose. His periorbital edema was much improved, and he was deemed stable for discharge on oral supplemental iron and limiting cow’s milk consumption. Hematology follow up was scheduled on outpatient basis.
Discussion
This case of a previously healthy 14-month-old male who presented with worsening periorbital swelling secondary to severe IDA and PLE.
IDA and alpha or beta- thalassemia trait are the most common causes of microcytic anemia in children. Low serum iron level, reticulocyte count, and elevated total iron-binding capacity, as well as an elevated red blood cell distribution width support the diagnosis of IDA. IDA in young children results from inadequate dietary intake, which is the most common cause, or from blood loss, usually gastrointestinal. Particularly, consumption of > 16 oz of cow’s milk per day is a leading cause of iron deficiency for many reasons: cow’s milk iron is poorly absorbed and slows gastric emptying, thus preventing the consumption of heme-containing foods; the calcium content inhibits iron absorption; and its excessive consumption can cause a protein allergy with GI bleeding (1).
Hypoalbuminemia is due to 1. decreased albumin production (poor nutrition or liver dysfunction resulting in decreased synthesis) or 2. an increase in losses (through urine or stool). In this case, the diagnosis of PLE was established by measuring fecal A1AT, a serum protein that is not ingested in the diet. An elevated fecal A1AT level suggests increased enteral protein loss (2).
There are many case reports describing the association between PLE and IDA, although the causal link between the two entities is not clear. However, treating the IDA leads to complete resolution of the PLE in those reports (2-3).
Increasing awareness about this association between IDA and PLE among pediatric urgent care and primary care providers can help improve recognition of IDA and prevent PLE as a complication.
References
- Richardson, M. (2007). Microcytic anemia. Pediatrics In Review, 28(1), 5–14. https://doi.org/10.1542/pir.28.1.5
- Kamzan, A. D., Newcomer, C. A., Wozniak, L. J., Federman, N. C., & Kim, L. S. (2020). A case of a 15-month-old with periorbital edema and severe anemia. Pediatrics, 145(3).
- Shih, M.-Y., Wu, M.-C., Chen, Y.-A., & Wang, J.-D. (2021). Puffy eyes and pale face. The Journal of Pediatrics, 228, 302–303. https://doi.org/10.1016/j.jpeds.2020.08.050
