A 49-year-old man presented at our hospital complaining of palpitation and shortness of breath upon exertion.
Palpitation and shortness of breath had begun approximately 3 years prior to presentation, but had become exacerbated over the past several weeks. The patient did not experience either palpitation or shortness of breath prior to the onset of CEAS 3 years previously.
Esophagogastroduodenoscopy (EGD) and colonoscopy showed no abnormality, whereas intestinal capsule endoscopy demonstrated scattered round ulcers throughout the entire ileum. He had undergone treatment for the eradication of Helicobacter pylori infection because of a gastric ulcer. No disease-related family history was reported.
Physical examination revealed anemia, tachycardia, functional systolic murmur, and spoon nails.
A blood examination showed severe refractory anemia (hemoglobin: Hb, 2.5 g/dL), hypoproteinemia (total protein: TP, 5.8 g/dL), hypoalbuminemia (albumin: alb, 3.3 g/dL), and normal C-reactive protein (CRP: 0.2 mg/dL) before treatment. The fecal occult blood test was positive. Laboratory parameters improved approximately one month after treatment with iron tablets and mesalazine (Hb, 13.9 g/dL; TP, 7.6 g/dL, alb 4.1 g/dL, CRP, 0.48 mg/dL). Data at the most-effective time point with treatment were Hb, 13.6 g/dL; TP, 7.4 g/dL, alb 4.1 g/dL, CRP, 0.26 mg/dL, and at the time of relapse were Hb, 9.9 g/dL; TP, 6.5 g/dL, alb 3.6 g/dL, CRP, 2.3 mg/dL. The time-course changes of hemoglobin and albumin are demonstrated in Fig. 1.
EGD showed atrophic gastritis, whereas colonoscopy showed no abnormal findings. Video capsule endoscopy (VCE) revealed multiple nonspecific ileal ulcers of various sizes and shapes (Fig. 2). Double balloon enteroscopy (DBE) and VCE showed multiple longitudinal and spiral ulcers in the ileum except in the terminal ileum (Fig. 3a, b). NSAID use was excluded. However, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) or CD could not be excluded based only on the features of ileal ulcers. Although the multiple longitudinal and spiral ulcers in the ileum remained, those ulcers showed improvement, with evidence of granulation, after treatment with mesalazine 3,000 mg/day per oral (p.o.) (Fig. 3c, d). Bone radiography indicated periostosis of the fingers and long bones in the limb (Fig. 4a). Brain-CT revealed skin hypertrophy (Fig. 4b).
A pathological examination of the ileal ulcers showed non-specific inflammation (Fig. 5a, b). Follow-up DBE showed longitudinal or irregular-shaped ulcers and erosions. Immunohistochemistry demonstrated CD68-positive histiocytes of a small granuloma (Fig. 5c). The patient was suspected to have CD. However, the terminal ileum lacked longitudinal ulcers or a cobblestone appearance, which are typical findings in CD. The patient exhibited digital clubbing (Fig. 6a), a deeply wrinkled forehead, and a chiseled face (Fig. 6b). Immunohistochemical studies of SLCO2A1 expression in the vascular endothelial cells of ileal ulcers showed that the patient did not express normal SLCO2A1 protein (Fig. 7). In addition, next-generation sequencing revealed a point mutation of the 1807C>T homo-mutation in the 13 exon allele of SLCO2A1 (Fig. 8).
CD, BD, NSAID-induced ulcers, and tuberculosis should be considered in the differential diagnosis.
The patient was diagnosed with pachydermoperiostosis, which is also known as primary hypertrophic osteoarthropathy (PHO). Since the SLCO2A1 mutation has been reported in pachydermoperiostosis, the present patient was diagnosed with CEAS with ileal ulcers and pachydermoperiostosis.
The patient was treated with an RBC transfusion for severe anemia at hospitalization in 201X/10. The administration of oral Fe tablets (100 mg/day) was commenced a few weeks later, which took 3 months to achieve an improvement in anemia, and he continues to take this medication at the time of writing this report. Additionally, oral mesalazine (3,000 mg/day) has been administered from 201X+1/1 until now. The TP and albumin were improved at 201X+1/2; therefore, improvement in TP and albumin by mesalazine took approximately 4 weeks in the initial phase. However, as shown in Fig. 1, the effect of oral mesalazine for albumin and Hb fluctuated during the time course. The inflammation improved 2 years later after the commencement of mesalazine. The combination of Fe tablets and oral mesalazine was continued without other treatments even in the relapsing periods, because anemia and inflammation were within the acceptable range.
The albumin, Hb as shown in Fig. 1, and inflammation fluctuated during the time course, and the patient occasionally has diarrhea. We continue to follow this patient on an out-patient basis while continuing to administer Fe tablets and mesalazine.