Case Presentation: A 3-year-old male of Asian descent with a history of atopy and failure to thrive presented with a two-month history of oral ulcers and progressive facial and lower extremity swelling. On exam, he was underweight with weight <5%ile. He had periorbital and lower extremity edema, and a distended abdomen. He had several flaccid blisters on his oral mucosa, dry cracked lips, and fissures of the lateral tongue bilaterally. His skin exam was otherwise unremarkable. Imaging revealed small ascites and pleural effusions, and laboratory studies were notable for albumin 2.0, eosinophilia 7%, and coronavirus positivity of nasopharyngeal sample. Initial differential diagnosis included an infectious etiology of oral ulcers such as HSV, HIV, or coxsackie virus, versus a rheumatologic etiology such as Behcet’s disease, with a resultant hypoalbuminemia due to prolonged malnutrition. The patient’s voice became increasingly hoarse and flexible nasopharyngoscopy showed lesions extending throughout the distal oropharynx. Stool studies revealed elevated alpha 1 antitrypsin and calprotectin, supporting a diagnosis of protein losing enteropathy. Thus, an endoscopy was conducted to evaluate for inflammatory bowel disease. Biopsies revealed acantholysis and suprabasilar clefting of esophageal squamous mucosa concerning for Pemphigus vulgaris (PV). Subsequent desmoglein 3 autoantibody testing was positive, and indirect immunofluorescence testing confirmed the diagnosis of PV. Treatment with glucocorticoids and dapsone was initiated (1), as well as nasogastric tube feeds to support inadequate nutrition and failure to thrive. The etiology of protein loss in this patient remains unknown and may represent a concurrent inflammatory bowel disease, which has been seen as a trigger of PV.
Discussion: Pemphigus vulgaris (PV) is a rare autoimmune blistering disease caused by autoantibodies to desmoglein molecules on keratinocytes. Binding of these autoantibodies results in loss of cell-cell adhesion, forming intraepithelial blisters (2). PV is most common in adults, presenting at a mean 40-60 years (3). Much less common is the diagnosis in children, which is illustrated in several case reports (4-6). In children, PV presents at a mean of 12 years old with stomatitis, epistaxis, and/or hoarseness (7). In this young patient with a history of failure to thrive, gastrointestinal etiologies were of greater focus on the differential diagnosis, and oral ulcers were initially attributed to vitamin deficiency and malnutrition. Hypoalbuminemia and protein losing enteropathy as presenting factors led to a delay in the diagnosis of PV in our patient, but have been reported in 5 Japanese children in one case study (6), though the etiology of protein loss is not well understood. Our case adds to this literature and highlights the importance of considering autoimmune blistering diseases on a differential diagnosis of presentations of isolated oral ulcers and protein losing enteropathies in children.
Conclusions: We illustrate here the unusual case of a 3-year-old boy who presented with oral ulcers and edema, was initially diagnosed with protein losing enteropathy of unknown etiology, and ultimately was found to have pemphigus vulgaris. In his case, oral ulcers were considered both as a cause and secondary effect of his malnutrition, broadening the differential diagnosis. Autoimmune blistering diseases, though rare, are an important diagnostic consideration in children with isolated oral ulcers.