Acta Dermato-Venereologica 98-5CompleteContent | Page 11

506 CLINICAL REPORT Evaluation of IgG4 + Plasma Cell Infiltration in Patients with Systemic Plasmacytosis and Other Plasma Cell-infiltrating Skin Diseases Shintaro TAKEOKA 1 , Masahiro KAMATA 1 , Carren Sy HAU 1 , Mihoko TATEISHI 1 , Saki FUKAYA 1 , Kotaro HAYASHI 1 , Atsuko FUKUYASU 1 , Takamitsu TANAKA 1 , Takeko ISHIKAWA 1 , Takamitsu OHNISHI 1 , Yuko SASAJIMA 2 , Shinichi WATANABE 1 and Yayoi TADA 1 Department of Dermatology, and 2 Department of Histopathology, Teikyo University School of Medicine, Tokyo, Japan 1 Systemic plasmacytosis is a rare skin disorder cha- racterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically charac- terized by lymphoplasmacytic infiltration rich in IgG4 + plasma cells, storiform fibrosis, and obliterative phle- bitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abun- dant infiltration of IgG4 + plasma cells has led to discus­ sion about the relationship between systemic plasma- cytosis and IgG4-related disease. This study examined IgG4 + /IgG + plasma cell ratios in 4 patients with sys- temic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4- related disease (i.e. IgG4 + /IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases. Key words: systemic plasmacytosis; IgG4-related disease; plasma cell; IgG4. Accepted Feb 13, 2018; Epub ahead of print Feb 13, 2018 Acta Derm Venereol 2018; 98: 506–511. Corr: Masahiro Kamata, Department of Dermatology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. E-mail: [email protected] P lasma cells produce various immunoglobulins, which are classified into 5 isotypes: IgG, IgA, IgM, IgD and IgE. There are 4 IgG subclasses (IgG1, 2, 3 and 4), named in order of serum concentration. Thus, IgG4 is the least, and IgG1 the most abundant (1). The mean serum concentration of IgG4 is only 0.35–0.51 mg/ml (2). IgG4 possesses a unique structure and fun- ction (1). Although IgG4 was traditionally considered to play a role only in immune activation, it has been shown that IgG4 does not effectively activate the clas- sical complement pathway. Since the disulphide bonds between heavy chains of IgG4 are unstable, some IgG4 antibodies form intrachain disulphide bonds in the hinge region. These interactions may prevent inflammatory re- sponses by shielding the Fc region from other immune- related molecules. Another unique feature of IgG4 is the half-antibody exchange reaction (3). Through this exchange, IgG4 can bind the Fc region of other IgG doi: 10.2340/00015555-2909 Acta Derm Venereol 2018; 98: 506–511 antibodies, which may result in the anti-inflammatory function of IgG4 (4). IgG4 production is induced by the type 2 helper T (Th2) cytokines, interleukin (IL)-4 and IL-13. Although the production of IgE, as well as IgG4, is induced by those cytokines, IgG4 production is favoured in the presence of IL-10, IL-12 or IL-21 (1). IgG4-related disease (IgG4-RD) is an immune- mediated disease involving multiple organs, such as the pancreas, salivary glands, and lacrimal glands, characterized by a distinctive fibro-inflammatory change. IgG4-RD is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4 + plasma cells, storiform fibrosis, and obliterative phlebitis. Pa- tients with IgG4-RD have elevated serum IgG4 levels (5). Skin lesions have been reported in IgG4-RD, but this is still controversial (6). Systemic plasmacytosis (SP) is a rare disorder that affects various organs and is mainly observed in Japan. Its characteristic skin manifestations are red-brownish eruptions distributed predominantly on the trunk (7). Pathologically SP is characterized by marked, superfi- cial and deep perivascular and periadnexal infiltration of mature plasma cells without atypia. Patients with SP often show generalized lymphadenopathy and polyclo- nal hypergammaglobulinaemia. Its aetiology and patho- genesis remain to be elucidated, although environmental factors, genetic disposition and infectious aetiology have been presumed based on its geographical distribu- tion (8). Recently, since patients with SP show marked plasma cells infiltration of the skin and some cases of SP demonstrate prominent IgG4 + cell infiltration, it has been debated whether SP is a manifestation of IgG4-RD or a disease distinct from IgG4-RD (6, 9–11). Apart from SP, previous studies have shown that prominent IgG4 + plasma cell infiltration and high IgG4 + /IgG + plasma cell ratio also occur under certain inflammatory conditions, such as chronic inflammation of the oral cavity and rheumatoid arthritis (12, 13). These studies indicate that prominent IgG4 + plasma cell infiltration into tissues, resulting in high IgG4 + / IgG + plasma cell ratio alone cannot be used to decisi- vely diagnose IgG4-RD. To date, it is not known how frequently IgG4 + plasma cells are seen among patients with plasma cell-infiltrating skin diseases other than IgG4-RD. Therefore, in this study, we examined the number of infiltrating IgG4 + and IgG + plasma cells per This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.