Project description:Bullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP. To report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature. Case report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors. Throughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3). Our findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.
Project description:Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract (iNKLPD) is a newly recognized entity in the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Initially described as "NK-cell enteropathy" and "lymphomatoid gastropathy" over a decade ago, recent molecular and cytogenetic studies have confirmed its neoplastic nature. Although primarily affecting the gastrointestinal tract, iNKLPD has also been reported in rare extra-intestinal sites, including the gallbladder, lymph nodes, nasopharynx, and vagina. Case presentation We present a unique case involving the nasal cavity, which has not been previously reported as a site of involvement. A 67-year-old female patient presented with recurrent postnasal drip symptoms persisting for one year following an upper respiratory tract infection. Imaging studies revealed a nasal mass on head computed tomography (CT), prompting endoscopic resection. Intraoperatively, a mulberry-like neoplasm was identified in the left nasal septum. Histopathological examination using hematoxylin-eosin (HE) staining revealed diffuse infiltration by medium to large round cells. Immunohistochemical profiling demonstrated positive expression of CD56, CD3, BCL-2, TIA-1, and Granzyme B, with a Ki-67 proliferation index of 50%. CD5, CD20, CD21, CD23, CD10, BCL-6, CD30, PAX-5, and PD-1 were negative. Notably, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was negative, and T-cell receptor (TCR) gene rearrangement was not detected by polymerase chain reaction (PCR) analysis, confirming the diagnosis of indolent NK-cell lymphoproliferative disorder (iNKLPD) of the gastrointestinal tract. After 11 months of follow-up, the patient showed no local recurrence or signs of lymph node enlargement in other anatomical regions. Furthermore, proteomics analysis of the case was conducted in conjunction with Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Conclusion Although iNKLPD is a rare tumor, cases involving the nasal cavity are exceptionally uncommon and have not been reported in the literature. This unique case represents the first documented instance of iNKLPD in the nasal cavity, contributing to the comprehensive understanding of its pathological diagnosis and clinical management. Proteomics analysis of the case has provided valuable insights into the molecular mechanisms underlying this rare disease.
Project description:Extranodal marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) is an indolent lymphoma mostly affecting the gastrointestinal tract. In the stomach, MZBL of MALT initially has small cell morphology (SC-MZBL) and arises in the background of Helicobacter pylori induced gastritis. Clonal malignant progression to large cell morphology (LC-MZBL) is observed. During this progression an intermediate stage consisting of both the small cell and large cell morphology is present, called "composite lymphoma". To gain insight into the DNA methylation changes associated with progression of gastric MZBL of MALT, we performed genome-wide DNA methylation profiling using the Illumina Infinium MethylationEPIC BeadChip array for 30 microdissected samples of gastric MZBL of MALT.
2021-05-21 | GSE150417 | GEO
Project description:Recurrent pneumonia with tuberculosis and candida co-infection diagnosed by NGS: a case report and literature review