Clinicopathologic analysis of IgG4-related skin disease
TL;DR: In conclusion, patients with IgG4-related skin disease had uniform clinicopathology, and lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG 4-related lymphadenopathy.
About: This article is published in Modern Pathology.The article was published on 2013-04-01 and is currently open access. It has received 81 citations till now. The article focuses on the topics: Subcutaneous nodule & IgG4-related disease.
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TL;DR: Identification of specific antigens and T-cell clones that drive the disease will be the first steps to elucidate the pathogenesis of IgG4-related disease.
717 citations
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TL;DR: The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs and is now being recognized with increasing frequency.
Abstract: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear.
270 citations
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TL;DR: Presenting features of IgG4-RD vary substantially according to the specialty to which patients present first; in addition, the disease can be diagnosed unexpectedly in pathological specimens or identified incidentally on radiology studies.
241 citations
Cites background from "Clinicopathologic analysis of IgG4-..."
...The two main types of cutaneous lesions are erythematous plaques and subcutaneous nodules (64), although other lesions such as brown papules similar to prurigo nodularis and toe nodules have been reported....
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01 Jul 2015
TL;DR: Most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis are provided.
Abstract: IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.
149 citations
Cites background from "Clinicopathologic analysis of IgG4-..."
...In 11 studies in which the mean number of IgG4þ plasma cells per HPF was detailed, a mean value of more than 100 was found in more than half of the cases, ranging from 13 to 229.(20,21,42,47,50-56) Most patients in whom this feature was detailed had more than10 IgG4þ cells per HPF (498 of 538 [93%]) (Table 2)....
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TL;DR: Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.
114 citations
References
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Vikram Deshpande1, Yoh Zen2, John Kc Chan, Eunhee E Yi3, Yasuharu Sato4, Tadashi Yoshino4, Günter Klöppel5, J. Godfrey Heathcote6, Arezou Khosroshahi1, Judith A. Ferry1, Rob C. Aalberse7, Daniel Bloch1, William R. Brugge1, Adrian C Bateman8, Mollie N. Carruthers1, Suresh T. Chari3, Wah Cheuk, Lynn D. Cornell3, Carlos Fernandez-del Castillo1, David G. Forcione1, Daniel L. Hamilos1, Terumi Kamisawa9, Satomi Kasashima, Shigeyuki Kawa10, Mitsuhiro Kawano11, Gregory Y. Lauwers1, Yasufumi Masaki12, Yasuni Nakanuma11, Kenji Notohara, Kazuichi Okazaki13, Ji Kon Ryu14, Takako Saeki, Dushyant V. Sahani1, Thomas C. Smyrk3, James Robert Stone1, Masayuki Takahira11, George Webster15, Motohisa Yamamoto16, Giuseppe Zamboni17, Hisanori Umehara12, John H. Stone1 •
Harvard University1, University of Cambridge2, Mayo Clinic3, Okayama University4, Technische Universität München5, Dalhousie University6, University of Amsterdam7, Southampton General Hospital8, Tokyo Metropolitan Komagome Hospital9, Shinshu University10, Kanazawa University11, Kanazawa Medical University12, Kansai Medical University13, Seoul National University14, University College London15, Sapporo Medical University16, University of Verona17
TL;DR: This statement proposes a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy, and advocates the use of strict criteria for accepting newly proposed entities or sites as components of the IgG 4- related disease spectrum.
2,041 citations
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John H. Stone1, Arezou Khosroshahi1, Vikram Deshpande1, John K.C. Chan, J. Godfrey Heathcote2, Rob C. Aalberse3, Atsushi Azumi4, Daniel Bloch1, William R. Brugge1, Mollie N. Carruthers1, Wah Cheuk, Lynn D. Cornell5, Carlos Fernandez-del Castillo1, Judith A. Ferry1, David G. Forcione1, Günter Klöppel6, Daniel L. Hamilos1, Terumi Kamisawa7, Satomi Kasashima, Shigeyuki Kawa8, Mitsuhiro Kawano9, Yasufumi Masaki10, Kenji Notohara, Kazuichi Okazaki11, Ji Kon Ryu12, Takako Saeki, Dushyant V. Sahani1, Yasuharu Sato13, Thomas C. Smyrk5, James R. Stone1, Masayuki Takahira9, Hisanori Umehara10, George Webster14, Motohisa Yamamoto15, Eunhee S. Yi5, Tadashi Yoshino13, Giuseppe Zamboni16, Yoh Zen17, Suresh T. Chari5 •
Harvard University1, Dalhousie University2, University of Amsterdam3, Kobe University4, Mayo Clinic5, Technische Universität München6, Tokyo Metropolitan Komagome Hospital7, Shinshu University8, Kanazawa University9, Kanazawa Medical University10, Kansai Medical University11, Seoul National University12, Okayama University13, University College London14, Sapporo Medical University15, University of Verona16, King's College London17
TL;DR: John H. Stone, Arezou Khosroshahi, Vikram Deshpande, John K.Stone, Masayuki Takahira, Hisanori Umehara, George Webster, Motohisa Yamamoto, Eunhee Yi, Tadashi Yoshino, Giuseppe Zamboni, Yoh Zen, and Suresh Chari.
Abstract: John H. Stone, Arezou Khosroshahi, Vikram Deshpande, John K. C. Chan, J. Godfrey Heathcote, Rob Aalberse, Atsushi Azumi, Donald B. Bloch, William R. Brugge, Mollie N. Carruthers, Wah Cheuk, Lynn Cornell, Carlos Fernandez-Del Castillo, Judith A. Ferry, David Forcione, Gunter Kloppel, Daniel L. Hamilos, Terumi Kamisawa, Satomi Kasashima, Shigeyuki Kawa, Mitsuhiro Kawano, Yasufumi Masaki, Kenji Notohara, Kazuichi Okazaki, Ji Kon Ryu, Takako Saeki, Dushyant Sahani, Yasuharu Sato, Thomas Smyrk, James R. Stone, Masayuki Takahira, Hisanori Umehara, George Webster, Motohisa Yamamoto, Eunhee Yi, Tadashi Yoshino, Giuseppe Zamboni, Yoh Zen, and Suresh Chari
607 citations
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TL;DR: Based on histological and immunohistochemical examination of various organs of patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed as discussed by the authors.
Abstract: Based on histological and immunohistochemical examination of various organs of patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prostate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AIP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4-related sclerosing diseases. This disease includes AIP, sclerosing cholangitis, cholecystitis, sialadenitis, retroperitoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AIP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunostaining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.
416 citations
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TL;DR: The present results show that ocular adnexal IgG4‐related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva, and presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B‐cell lymphoma arising in a background of IgG 4‐related chronic inflammation.
Abstract: IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39-86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation.
265 citations
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TL;DR: Clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data are useful for differentiating the two.
253 citations
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Vikram Deshpande, Yoh Zen, John Kc Chan, Eunhee E Yi, Yasuharu Sato, Tadashi Yoshino, Günter Klöppel, J. Godfrey Heathcote, Arezou Khosroshahi, Judith A. Ferry, Rob C. Aalberse, Daniel Bloch, William R. Brugge, Adrian C Bateman, Mollie N. Carruthers, Suresh T. Chari, Wah Cheuk, Lynn D. Cornell, Carlos Fernandez-del Castillo, David G. Forcione, Daniel L. Hamilos, Terumi Kamisawa, Satomi Kasashima, Shigeyuki Kawa, Mitsuhiro Kawano, Gregory Y. Lauwers, Yasufumi Masaki, Yasuni Nakanuma, Kenji Notohara, Kazuichi Okazaki, Ji Kon Ryu, Takako Saeki, Dushyant V. Sahani, Thomas C. Smyrk, James Robert Stone, Masayuki Takahira, George Webster, Motohisa Yamamoto, Giuseppe Zamboni, Hisanori Umehara, John H. Stone
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