Histopathology and expression of the chemokines CXCL10, CXCL13, and CXCR3 and the endogenous TLR-4 ligand S100A8/A9 in lymph nodes of patients with adult-onset Still’s disease

Abstract

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.

Severe pyrexia from nivolumab‐resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib

“…Moreover, serum sCD163, CXCL9, CXCL10 and CXCL11 levels increased after the onset of pyrexia in all three cases treated with E + B combined therapy but not in those who did not develop pyrexia. Because CXCL10 had been previously reported as a biomarker of fever spike in patients with AOSD, 12 the mechanisms of pyrexia may be similar between E + B combined therapy and AOSD. Further cases are needed in the future to evaluate the fundamental mechanisms of pyrexia caused by E + B combined therapy.…”

Adult Onset Still's Disease With Multiple Lymphadenopathy: a Case Report and Literature Review

“…Hyoun ah Kim et al [9] performed histological observation of lymphadenopathy in 48 AOSD patients and summarized 6 morphological patterns of lymph nodes. These include: follicular pattern, dominated by extensive hyperplasia of lymphoid follicles; Paracortical areas pattern, with proliferation and expansion of the paracortical areas and only a few small remnants of lymphoid follicles; Diffuse pattern, diffuse hyperplasia of the paracortical areas, no lymphoid follicular structures seen; Necrotic pattern, proliferative expansion of the paracortical areas, focal scattered necrosis and nuclear fragmentation; Mixed patterns of lymphoid follicles and paracortical areas; And a mixed pattern of diffuse and paracortical areas.…”

“…AOSD patients often present with multiple enlarged lymph nodes, and when the diagnosis is still di cult to be established by a combination of clinical manifestations, laboratory tests, and imaging studies, surgical resection with pathological biopsy of lymph nodes is the inevitable choice for the nal de nite diagnosis. Previous articles have shown that most lymph node lesions histomorphometrically exhibit reactive hyperplasia in the paracortical region, characterized by the proliferation of immunoblasts and high endothelial venules [9][10]. The histomorphological features of AOSD lymphadenopathy are complex and diverse, and change dynamically with the course of the disease, which still needs to be differentiated from the following diseases.…”

Roles of Interactions Between Toll-Like Receptors and Their Endogenous Ligands in the Pathogenesis of Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease

“…The level of HMGB1 in serum was elevated in patients with systemic JIA or AOSD, and then downregulated after disease resolution (24,25). The serum levels of S100A8 (calgranulin A or myeloid-related protein 8, MRP8) and S100A9 (calgranulin B or MRP14) were increased in patients with systemic JIA and AOSD, and these factors were deposited in the skin or lymph nodes of the latter patients (21,26,27). Such DAMPs are recognized by members of the PRR family, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain receptors (NOD-like receptors; NLRs), C-type lectin receptors, and retinoic-acid-inducible gene 1-like receptors, in several inflammatory disorders.…”