IgG4/IgG Expression And Significance In Serum And Skin Lesions Of Cutaneous Rosar-Dorfman's Disease

Background:Rosai-Dorfman disease(RDD)also known as Sinus histiocytosis with massive lymphadenopathy,is a rare,benign disorder characterized by a nonclonal proliferation of distinctive cells of macrophage/histiocyte lineage,this disease mainly occurs in the lymph nodes,but in 20-40% of patients,external organs such as the skin,upper respiratory tract,eyes,bones and salivary glands are involved,Skin involvement was called cutaneous Rosai-Dorfman disease(CRDD).In extranodal sites,there is usually prominent fibrosis in addition to infiltration of distinctive histiocytes and other inflammatory cells.The histiocytes characteristically exhibit emperipolesis and contain lymphocytes,plasma cells,and occasionally other cells in their cytoplasm?The histopathology of RDD is silimar to that of IgG4-related disease(IgG4-RD).IgG4-RD is a chronic autoimmune inflammatory disease recognized within a decade,and its pathological changes are also manifested by a large number of lymphocytes and plasma cells infiltration,in which IgG4-positive plasma cells are increased,accompanied by stromal fibrosis,and IgG4 titer in serum is increased,so these findings suggested that RDD may belong to part of the spectrum of Ig G4-related disease(Ig G4-RD).but the research on this field is limitted.In previous studies,it was found that the binding of IgG4 subtype antibody to epidermal desmoglein(Dsg)antigen was the trigger of pemphigus,and the ratio of IgG4/IgG in acute stage patients was significantly higher than that of in stable stage patients.Then is there a certain correlation between IgG4/IgG and the occurrence and development of CRDD.Objective: By detecting the serum level of IgG4 in CRDD patients and the expression level of IgG4 positive plasma cells in skin lesions,the relationship between CRDD and IgG4-RD,as well as the significance of IgG4 expression in CRDD diseases were discussed.Methods: Six patients diagnosed as CRDD in the Department of Dermatology of Northern Jiangsu People's Hospital from May 2015 to November 2018 were collected.Among them,there were 3 males and 3 females,with an average age of 45.5 years,The clinical diagnosis and treatment,relevant pathological analysis and hematological examination are analyzed.Immunohistochemical method was used to detect the expression of IgG and IgG4 positive plasma cells in the skin lesions of patients,and samples of the patients' serum were collected and sent to Beijing Haisite Medical Laboratory for the determination of serum immunoglobulin and IgG4 levels.Results: 1.Clinical manifestations: All the skin lesions of the 6 patients showed fuchsia or dark red nodules or plaques without obvious self-conscious symptoms,Among of them,one patient with facial involvement,two patients with facial and trunk simultaneously involvement,and three patients with trunk involvement.One patient had superficial lymph node enlargement,and the remaining five patients had no lymph node involvement.2.Histopathologic manifestations: Histopathologic features of 6 cases were characterized by dense cellular infiltrations involving in the dermis including histiocytes infiltration(light area)and lymphocytes and plasma cells(dark area),Cytoplasm of the histiocytes contain lymphocytes known as emperipolesis was seen in four patients' lesions.The histiocytes expressed CD68,and S100,partly or didn't express CD1 a.All patients met the diagnosis of CRDD.IgG and IgG4 were expressed to varying degrees in the lesions of three patients.Two patients expressed IgG,but didn't express IgG4.IgG4 and IgG were negative in one patient.3.Serum immunoglobulins and IgG4 levels were detected in four of the six patients,and only one patient had rasied serum IgG4 and IgG levels,accompanied by increased IgE.Another two cases had only IgE elevation.In one case,all the immunoglobulins were normal.4.Treatment information : Two patients were treated with oral prednisone and/or thalidomide,but no significant improvement was found,and the treatment was quit.The current follow-up is fine.One patient was treated with intra-dermal injection of glucocorticoid,and the rash was reduced.One patient received laser treatment for partial skin lesions,while the other two patients did not receive any treatment.Conclusion: 1.Serum IgG4 levels were normal in patients with RDD only with skin affected,and but raised in patient with both lymph node and skin affected.2.Whether serum IgE elevation in patients with CRDD is related to the occurrence of this disease needs further investigation,and an association betweenthe elevation of serum IgE and serum IgG4 needs to be investigated furthur using a large sample.3.Serum IgG4 levels were elevated in only one of the four tested patients.IgG4 positive plasma cells were seen in the lesions of three patients,but the expressions were not strong.It is not clear whether IgG4 has pathogenicity,protective or reactive effect at a certain stage of the development of CRDD and it needs further study.4.Intra-dermal injection of glucocorticoid has a good effect on localized lesions of CRDD.5.In this study,three patients had skin lesions in two or more sites.Were the lesions in other sites induced by migration of the RDD cells in original lesion through the blood circulation ? or there is no substantial link between them,These questions need further study and follow-up.