Primary hypertrophic osteoarthropathy related gastrointestinal complication has distinctive clinical and pathological characteristics: two cases report and review of the literature

Abstract

BackgroundPrimary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement.MethodsWe reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without.ResultsThe two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15).ConclusionsDigestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn’s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.

Monoallelic mutations in SLCO2A1 cause autosomal dominant primary hypertrophic osteoarthropathy

“…Because the symptoms and signs of PHOAD were relatively milder and the PGE 2 levels were relatively lower, we should be more mindful about drug therapy for PHOAD patients, taking into account the side effects of etoricoxib on the gastrointestinal system and balancing the benefits and disadvantages. ( 41 )…”

Chronic Enteropathy Associated with SLCO2A1-Associated Primary Hypertrophic Osteoarthropathy in Female Patients: A Case Report and Literature Review

“…That article reviewed and reported the rst symptoms of 138 patients, and only a few patients (3.6%, 5/138) had gastrointestinal disease as their rst symptom, but as the disease progressed, 17.2% (26/151) of patients had gastrointestinal complications. Among PHO patients with gastrointestinal involvement, peptic ulcers and chronic gastritis only occurred in patients with SLCO2A1 gene de ciency [9], and gastrointestinal complications in PHO patients are more closely related to SLCO2A1 [5].…”

“…CEAS mainly occurs in women and it mainly manifests as anaemia and hypoproteinemia, without clubbing, periostosis, or pachydermia [1,2]. PHOAR2 mainly occurs in men, and all reported PHO patients with gastrointestinal involvement are men [5]. All CEAS patients who met the main diagnostic criteria of PHO were male, and no female CEAS patients have developed PHO [1,2].…”

“…CEAS is more likely to occur in women, while PHO is more likely to occur in men [1-3, 5, 9, 10]. All CEAS patients who met the PHO diagnostic criteria so far were male [1,2,5].…”

SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy

“…Wang Q et al. [ 7 ] also reported two male patients with PHO, who presented anaemia and hypoalbuminemia presumably due to small intestinal ulcers. Since CEAS and PHOAR2 share a common causal gene, we presume that patients with PHOAR2 are prone to intestinal ulcerations.…”