CTLA-4 haploinsufficiency may present with variable clinical phenotypes including increased risk of EBV viremia and malignancies. To our knowledge, this is the first case of OLP reported in a patient with CTLA-4 haploinsufficiency. Due to persistent psoriasis, methotrexate was initiated without worsening in her tongue lesion. Her tongue lesions waxed and waned over the following months. Two weeks of topical dexamethasone lead to temporary improvement. Epstein-Barr encoding region in situ hybridization was negative. Periodic acid-Schiff diastase stain and Grocott stain were negative. Incisional tongue biopsy revealed ulceration with underlying granulation tissue with lymphocyte and plasma cell infiltration consistent with OLP (Figure). Two months later, she developed painful white patches along her tongue and subsequent 4 kilogram weight loss recalcitrant to viscous lidocaine, antacids, and 14 days of fluconazole. Tongue scraping revealed Candida dubliniensis and she responded to 5 days of fluconazole. Immunologic evaluation revealed low IgA and pan-low lymphocyte subsets (Table). Absolute lymphocyte count ranged from 1.0- 1.7 x10^9 cells/L. Her WBC ranged from 3-4 x10^9 cells/L and hemoglobin 9.4-12.7 g/dL. She denied recent dental procedures, appliances, or tongue biting. Physical exam revealed glossitis with a gel-like coating and ulceration on her tongue, xerosis along her face and scalp without other abnormalities (Figure). Since her abdominal pain persisted repeat endoscopies after six months of abatacept revealed persistent active lymphocytic esophagitis with some improvement in inflammatory injury in her duodenum and colon.
Abatacept was initiated with re-growth of hair, improvement in cytopenias, improvement in psoriasis, and some reduction of gastrointestinal symptoms. Family history is remarkable: father (splenomegaly and psoriasis) and brother (autoimmune hemolytic anemia) have CTLA4 haploinsufficiency with the same mutation. Whole exome sequencing revealed a heterozygous c.239delA (p.Q80Rfs*2) pathogenic mutation in exon 2 of CTLA-4. Colonoscopy revealed mildly active chronic colitis with eosinophils. Esophagogastroduodenoscopy revealed lymphocytic esophagitis and active duodenal inflammation with increased intraepithelial lymphocytes. She had chronic abdominal pain and diarrhea since age 13. At 13, she was diagnosed with alopecia totalis and Epstein-Barr virus (EBV) with resultant and persistent anemia, thrombocytopenia, lymphopenia and neutropenia. Our patient was healthy until 9 years of age when she developed Hashimoto’s thyroiditis. Here, we present a 15 year-old female with a novel CTLA-4 variant, multiple autoimmune conditions, and unusual tongue lesions.
Oral lichen planus (OLP) is a T-cell mediated chronic inflammatory tissue reaction in which presentation can range from asymptomatic plaques to painful, erosive, bullous, or ulcerative lesions. Unexpected Oral Lesions in a Patient with a Novel Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) Variant - A Case ReportĬhristine Rauscher, MD 1, Miguel Reyes-Mugica, MD 2, Elaine Cassidy, MD 3, Raymond Shupak, DMD, MD, MBE 4, Xiaoyi Zhang, MD, PhD 5, Hey Chong, MD, PhD 6ġFellow, Department of Allergy and Immunology/UPMC Children's Hospital of PittsburghĢChief of Pathology and Director of Laboratories/UPMC Children's Hospital of PittsburghģClinical Director of Rheumatology, Assistant Professor of Pediatrics/UPMC Children's Hospital of PittsburghĤAssistant Professor/UPMC School of Dental MedicineĥFellow, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition/UPMC Children's Hospital of PittsburghĦDivision Director of Allergy and Immunology, Associate Professor of Pediatrics/UPMC Children's Hospital of Pittsburgh
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