Gastrointestinal Mucosal Lymphoid Hyperplasia: Mutation in PIK3CD Gene.

Abstract

A 4-year-old boy presented with difficulty defecating, hematochezia, and large rectal prolapse. Upper endoscopy and colonoscopy showed polypoid lesions throughout the colon and nodular mucosa of the esophagus, stomach, and duodenum (Fig. 1). Histology demonstrated mucosal florid lymphoid hyperplasia (Fig. 2). Workup revealed elevated inflammatory markers (erythrocyte sedimentation rate, C-reactive protein (ESR, CRP)), elevated fecal calprotectin, and positive QuantiFERON. Despite negative computed tomography (CT) chest, with negative for tuberculosis (TB) on his gastrointestinal biopsies, he was treated for latent TB with isoniazid. He had negative workup for lymphoma. Immunologic workup revealed decreased CD4 T-cells, CD21-positive cells, and increase in CD1-negative cells. Genetic testing revealed a heterozygous pathogenic mutation in phosphatidylinositol 3-kinase, catalytic, delta PIK3CD. This mutation is associated with activated phosphoinositide 3-kinase δ syndrome resulting in combined immunodeficiency disorder that can present with lymphoid hyperplasia of gastrointestinal and respiratory mucosal surfaces, recurrent infections, immunodeficiency, and/or malignancy (1). Patients with activated phosphoinositide 3-kinase δ syndrome may benefit from mammalian target of rapamycin (mTOR) inhibitors such as sirolimus or other immunosuppressants (2). Our patient was treated with budesonide and hydroxychloroquine as a bridge therapy to sirolimus while he was being treated for latent TB. Although his repeat endoscopy did not show major improvement, he had excellent clinical response, so he was maintained on the current regimen.FIGURE 1: A, Colon: lymphoid hyperplasia presenting as polypoid lesions. B, Duodenum: lymphoid hyperplasia presenting as nodular lesions.FIGURE 2: Lymphoid hyperplasia of the colonic biopsy. B, Lymphoid hyperplasia of the duodenum biopsy.