Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.
Published: December 2005
AI Article Synopsis
Article Abstract
Previous studies of acute generalized exanthematous pustulosis, a peculiar drug hypersensitivity reaction, suggested that CXCL8-producing T cells regulate sterile, polymorphonuclear neutrophil-rich skin inflammations. In this study, we test the hypothesis of whether CXCL8-producing T cells are present in autoinflammatory diseases like pustular psoriasis and Behçet's disease. Immunohistochemistry of normal skin revealed few CD4+ and CD8+ T cells, few CXCL8+ cells, and no neutrophilic infiltration, whereas in acute exacerbations of atopic dermatitis, numerous CD4+ T cells but few CD8+ T cells, neutrophils, or CXCL8+ cells were detected. In contrast, a pronounced infiltration of neutrophils and of predominantly CD4+ T cells was observed in skin biopsies from pustular psoriasis, Behçet's disease, and acute generalized exanthematous pustulosis, with infiltrating T cells strongly positive for CXCL8 and the chemokine receptor CCR6. Skin-derived T cell clones from pustular skin reactions were positive for CCR6 but negative for CCR8 and secreted high amounts of CXCL8 and GM-CSF, often together with IFN-gamma and TNF-alpha after in vitro stimulation. Moreover, some skin-derived T cell clones from Behçet's disease and from pustular psoriasis predominantly produced CXCL8 and GM-CSF, but failed to secrete IL-5 and IFN-gamma. These cells might represent a particular subset as they differ from both Th1 as well as Th2 T cells and are associated with a unique, neutrophil-rich sterile inflammation. Our findings suggest that CXCL8/GM-CSF-producing T cells may orchestrate neutrophil-rich pathologies of chronic autoinflammatory diseases like pustular psoriasis and Behçet's disease.
Dr. Irwin M. Braverman is recognized as an expert on many skin diseases including psoriasis, an immune-mediated disorder that presents with scaly erythematous plaques.
Rationale: Takayasu arteritis (TAK) is an autoimmune disease that causes chronic inflammation targeting the aortic wall. Since many patients are resistant to steroid treatment, multiple immunosuppressants or interleukin-6 (IL-6) suppression therapy have served as treatment alternatives. However, there are very few reports on the effectiveness of biologics against inflammatory cytokines upstream of IL-6.
Case Presentation: A female patient with a known history of pustular psoriasis presented with sub-acute development of diffuse erythema and scaling of the skin with areas of exfoliation consistent with erythroderma. She was ill appearing and required admission and aggressive treatment with steroid-impregnated wet dressings, topical emollients, analgesics, and systemic immunosuppressants.
Discussion: Erythroderma is a dermatologic emergency characterized by diffuse erythema and scaling spanning greater than 90% of skin surfaces and is associated with a mortality rate as high as 64%.
Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis.
