Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: To evaluate the effector role of cellular ...Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. Methods: Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. Results: The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+cells in SJS/TEN but much fewer in EM. Conclusions: Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.展开更多
The main epiluminescence microscopy (ELM) patterns observed on volar acquired melanocytic naevi are the parallel-furrow, the lattice-like and the fibrillar patterns. Because of the peculiar arrangement and configurati...The main epiluminescence microscopy (ELM) patterns observed on volar acquired melanocytic naevi are the parallel-furrow, the lattice-like and the fibrillar patterns. Because of the peculiar arrangement and configuration of epidermal rete ridges in the glabrous skin, the traditional histological picture does not provide an exact correlation with ELM features. In particular, the fibrillar pattern lacks a histopathological correlate. To clarify the microscopic features of the fibrillar pattern, we used transverse histological sectioning to study an acquired compound melanocytic naevus of the sole, characterized by a mixedparallel-furrow/fibrillar pattern on ELM. Low-magnificati-on images of transverse sections allowed us to highlight the typical anatomical arrangement of the volar skin clearly, while high-magnification images demonstrated that the fibrillar pattern corresponded to parallel striae of intensely pigmented corneocytes arranged obliquely to the cutaneous surface.展开更多
Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To...Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.展开更多
文摘Background: Erythema multiforme (EM) and Stevens-Joh- nson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives: To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. Methods: Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. Results: The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+cells in SJS/TEN but much fewer in EM. Conclusions: Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.
文摘The main epiluminescence microscopy (ELM) patterns observed on volar acquired melanocytic naevi are the parallel-furrow, the lattice-like and the fibrillar patterns. Because of the peculiar arrangement and configuration of epidermal rete ridges in the glabrous skin, the traditional histological picture does not provide an exact correlation with ELM features. In particular, the fibrillar pattern lacks a histopathological correlate. To clarify the microscopic features of the fibrillar pattern, we used transverse histological sectioning to study an acquired compound melanocytic naevus of the sole, characterized by a mixedparallel-furrow/fibrillar pattern on ELM. Low-magnificati-on images of transverse sections allowed us to highlight the typical anatomical arrangement of the volar skin clearly, while high-magnification images demonstrated that the fibrillar pattern corresponded to parallel striae of intensely pigmented corneocytes arranged obliquely to the cutaneous surface.
文摘Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.
