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• W1994108683 abstract "To the Editor: Localized granuloma annulare (GA) is a common dermatosis characterized by annular patches and plaques without scale.1Bolognia J. Jorizzo J.L. Rapini R.P. Dermatology. Mosby/Elsevier, St Louis (MO)2008Google Scholar Although GA was initially described more than 100 years ago,2Fox T.C. Ringed eruption of the fingers.Br J Dermatol. 1895; 7: 91Google Scholar it remains poorly understood, with no known origin or pathogenetic mechanism. Since its earliest descriptions, GA has been believed to be a disorder of histiocytes, because dermal palisaded histiocytoid cells surrounding acellular regions with collagen and mucin intermixed are seen on skin biopsy specimen. Microscopically, GA shares some features with necrobiosis lipoidica (characterized by dermal alternating layers of acellular collagen and palisaded histiocytoid inflammatory cells) and rheumatoid nodules (associated with reticular dermal and subcutaneous palisaded histiocytoid inflammation surrounding acellular regions and fibrin).Plasmacytoid dendritic cells (PDCs), sentinels of the immune system recognized by their distinctive expression of CD123, are increasingly being noted for their role in inflammation and tumors.3Reizis B. Bunin A. Ghosh H.S. Lewis K.L. Sisirak V. Plasmacytoid dendritic cells: recent progress and open questions.Annu Rev Immunol. 2011; 29: 163-183Crossref PubMed Scopus (452) Google Scholar We hypothesized that PDCs are involved in GA. In this study, 3 dermatopathologists independently evaluated 10 cases of GA, necrobiosis lipoidica, and rheumatoid nodules. We studied expression of CD123, CD68 (PG-M1 clone; expressed by monocytes, macrophages, and neutrophils), and CD163 (a more specific marker for cells of monocytic/histiocytic lineage). Immunohistochemistry expression was scored as follows: negative (expression of <5% histiocytoid cells), 1+ (5%-25%), 2+ (26%-50%), 3+ (51%-75%), or 4+ (≥76%). Kruskal-Wallis tests were used to evaluate differences among the groups. Statistical significance was defined as P values less than .05.Immunohistochemistry profiles are outlined in Table I. In all 10 GA cases, palisaded histiocytoid cells stained diffusely (4+) with CD123 (Fig 1). Although a subpopulation of CD123+ cells was noted in necrobiosis lipoidica and rheumatoid nodules, CD123+ staining was substantially less diffuse in virtually all cases of necrobiosis lipoidica and rheumatoid nodules tested when compared with that in GA. That is, unlike in GA, CD123+ cells did not appear to be the predominant cell type in necrobiosis lipoidica or rheumatoid nodules. Statistically significant differences were noted among the 3 groups for CD123 (P = .017) and CD68 (P = .004), whereas differences in CD163 showed a trend toward statistical significance (P = .099).Table IImmunostaining profile of granuloma annulare, necrobiosis lipoidica, and rheumatoid noduleDiseaseCD123 No. of cases (cell density)CD68CD163Granuloma annulare10 (4+)9 (4+)6 (4+)1 (2+)4 (2+)Necrobiosis lipoidica4 (4+)3 (4+)1 (4+)3 (3+), 2 (1+), 1 negative7 (2+)9 (2+)Rheumatoid nodule5 (4+)2 (4+)4 (4+)5 (2+)6 (2+), 2 negative5 (2+), 1 negativeP value.017∗P values < .05 are considered statistically significant..004∗P values < .05 are considered statistically significant..099Scale: negative (expression of <5% dermal cells), 1+ (5%-25%), 2+ (26%-50%), 3+ (51%-75%), or 4+ (≥76%). Kruskal-Wallis test was performed to assess for differences among the 3 groups.∗ P values < .05 are considered statistically significant. Open table in a new tab CD123 is relatively specific for PDCs, although low CD123 expression can be observed on myeloid dendritic cells. In normal-appearing skin, only a small number of PDCs are identified,4Ebner S. Ehammer Z. Holzmann S. Schwingshackl P. Forstner M. Stoitzner P. et al.Expression of C-type lectin receptors by subsets of dendritic cells in human skin.Int Immunol. 2004; 16: 877-887Crossref PubMed Scopus (95) Google Scholar unlike what was seen with GA in the current study. The increase of PDCs noted in GA may implicate an infectious cause, as PDCs are the predominant source of interferon alfa, a cytokine central to antiviral immune responses. Alternatively, increased levels of PDCs have also been observed in autoimmune diseases and inflammatory skin disorders and may also play a similar role in patients with GA.Although histiocytes can be identified in GA, necrobiosis lipoidica, and rheumatoid nodules, the PDCs infiltrate is much denser in GA when compared with that of necrobiosis lipoidica and rheumatoid nodules. As we have identified PDCs as a prominent cell type in GA, the results of our preliminary study lay the groundwork to further dissect the cellular infiltrate in GA and its various clinicopathologic subtypes. This preliminary study also raises possibly new avenues to determine whether specifically targeting dendritic cells will be a successful therapeutic strategy in GA. To the Editor: Localized granuloma annulare (GA) is a common dermatosis characterized by annular patches and plaques without scale.1Bolognia J. Jorizzo J.L. Rapini R.P. Dermatology. Mosby/Elsevier, St Louis (MO)2008Google Scholar Although GA was initially described more than 100 years ago,2Fox T.C. Ringed eruption of the fingers.Br J Dermatol. 1895; 7: 91Google Scholar it remains poorly understood, with no known origin or pathogenetic mechanism. Since its earliest descriptions, GA has been believed to be a disorder of histiocytes, because dermal palisaded histiocytoid cells surrounding acellular regions with collagen and mucin intermixed are seen on skin biopsy specimen. Microscopically, GA shares some features with necrobiosis lipoidica (characterized by dermal alternating layers of acellular collagen and palisaded histiocytoid inflammatory cells) and rheumatoid nodules (associated with reticular dermal and subcutaneous palisaded histiocytoid inflammation surrounding acellular regions and fibrin). Plasmacytoid dendritic cells (PDCs), sentinels of the immune system recognized by their distinctive expression of CD123, are increasingly being noted for their role in inflammation and tumors.3Reizis B. Bunin A. Ghosh H.S. Lewis K.L. Sisirak V. Plasmacytoid dendritic cells: recent progress and open questions.Annu Rev Immunol. 2011; 29: 163-183Crossref PubMed Scopus (452) Google Scholar We hypothesized that PDCs are involved in GA. In this study, 3 dermatopathologists independently evaluated 10 cases of GA, necrobiosis lipoidica, and rheumatoid nodules. We studied expression of CD123, CD68 (PG-M1 clone; expressed by monocytes, macrophages, and neutrophils), and CD163 (a more specific marker for cells of monocytic/histiocytic lineage). Immunohistochemistry expression was scored as follows: negative (expression of <5% histiocytoid cells), 1+ (5%-25%), 2+ (26%-50%), 3+ (51%-75%), or 4+ (≥76%). Kruskal-Wallis tests were used to evaluate differences among the groups. Statistical significance was defined as P values less than .05. Immunohistochemistry profiles are outlined in Table I. In all 10 GA cases, palisaded histiocytoid cells stained diffusely (4+) with CD123 (Fig 1). Although a subpopulation of CD123+ cells was noted in necrobiosis lipoidica and rheumatoid nodules, CD123+ staining was substantially less diffuse in virtually all cases of necrobiosis lipoidica and rheumatoid nodules tested when compared with that in GA. That is, unlike in GA, CD123+ cells did not appear to be the predominant cell type in necrobiosis lipoidica or rheumatoid nodules. Statistically significant differences were noted among the 3 groups for CD123 (P = .017) and CD68 (P = .004), whereas differences in CD163 showed a trend toward statistical significance (P = .099). Scale: negative (expression of <5% dermal cells), 1+ (5%-25%), 2+ (26%-50%), 3+ (51%-75%), or 4+ (≥76%). Kruskal-Wallis test was performed to assess for differences among the 3 groups. CD123 is relatively specific for PDCs, although low CD123 expression can be observed on myeloid dendritic cells. In normal-appearing skin, only a small number of PDCs are identified,4Ebner S. Ehammer Z. Holzmann S. Schwingshackl P. Forstner M. Stoitzner P. et al.Expression of C-type lectin receptors by subsets of dendritic cells in human skin.Int Immunol. 2004; 16: 877-887Crossref PubMed Scopus (95) Google Scholar unlike what was seen with GA in the current study. The increase of PDCs noted in GA may implicate an infectious cause, as PDCs are the predominant source of interferon alfa, a cytokine central to antiviral immune responses. Alternatively, increased levels of PDCs have also been observed in autoimmune diseases and inflammatory skin disorders and may also play a similar role in patients with GA. Although histiocytes can be identified in GA, necrobiosis lipoidica, and rheumatoid nodules, the PDCs infiltrate is much denser in GA when compared with that of necrobiosis lipoidica and rheumatoid nodules. As we have identified PDCs as a prominent cell type in GA, the results of our preliminary study lay the groundwork to further dissect the cellular infiltrate in GA and its various clinicopathologic subtypes. This preliminary study also raises possibly new avenues to determine whether specifically targeting dendritic cells will be a successful therapeutic strategy in GA." @default.
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• W1994108683 title "Dendritic cells are prominent in granuloma annulare" @default.
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