Discussion On The Immunological Pathogenesis Of Facial Disseminated Miliary Lupus

Objective:Lupus miliaris disseminatus faciei(LMDF) is one common skin disease occurring to adult’s face, often dealing with the basic characteristics of dark red nodules. Symmetrical lesions occur in the face, especially the lower eyelid, cheek, nose, etc. on both sides, a few cases can occur even in the neck, shoulders and other parts. Miliary lesions are mostly to be bean-sized nodules, slightly out of leather and slightly domed or flat, reddish or reddish-brown, smooth, soft quality.Nodules occur in batches,and isolated scattered;sometimes clustering occurs, which form a dike-like arrangement in the lower eyelid, besides the number is variable, generally without any symptoms.The course of disease is chronic. exists for several months to several years. Sometimes nodules could disappear gradually, but atrophic scarsis are often left.Histopathology show epithelial nodules in the dermal, sometimes with central caseous necrosis and Langerhans giant cells, lymphocyte infiltrating around. So before,researchers think the disease is connected with tuberculosis infection.However, most researchers have not detected Mycobacterium tube rculosis in the nidus.Some researchers think that granuloma is its cause; also some suggested that the disease is only a distortion of rosacea. It was detected that the foreign Lysozyme disease lesions was significantly higher; And it was found in patients’ serum with LMDF,tumor necrosis factor and interleukin-2 levels were significantly higher than normal. But the relevant of macrophages and other inflammatory cells in the pathogenesis of LMDF has not cause significant domestic and international attention.CD68 is specific markers of M2 macrophages that is calledtumor-associated macrophages.M2 macrophages originally found in tumor tissue, and it is closely related to tumor cells’nutrition metabolism, proliferation and migration.It can induce the expression of VEGF, thereby contributing to the proliferation of blood vessels in the relevant organizations,and besides as inflammatory cells, it can release COX-2, angiopoietin and other inflammatory cytokines, thereby promoting the development of inflammation. And recent studies have pointed out, COX-2 and CD68 in facial disseminated miliary lupus were highly expressed, but did not have to explore the relation with inflammatory cells and related factors. Studies have shown that, the expression of TGF-β increase in the disease, and as macrophage polarization factor, TGF-β can induce macrophages from M1 to M2 polarized macrophages, showing that CD68 positive.Therefore, we consider that in facial disseminated miliary lupus, M2 macrophages may be involved in the disease process, and may be closely related to the development of the disease. Therefore, this study aimed to test the expression of TGF-β, CD68, COX-2 in lesions of patients and compared with the surrounding tissue lesions and normal skin tissue, in order to explore their correlation with the onset of LMDF.It enriches the immunological research of LMDF, and provide a theoretical basis for clinical diagnosis and treatment of LMDF.Materials and methods:39 patients are from January 2010-January 2014 dermatology clinic of Provincial Hospital Affiliated to Shandong University.Patients were confirmed by clinical and pathological diagnosis of LMDF, and no other systemic diseases, and no signs of infection.Take lesional tissue of patients for routine pathologic analysis.Detection the expression levels of CD68, TGF-β,and COX-2 in lesions by immunohistochemistry.Selected 30 cases of general surgery as normal healthy skin, tissue pathology observed using HE staining and immunohistochemical SP method. While extracting tissue protein of three patients of 2015,and detected by Western blot TGF-β, CD68, expression of COX-2, we use IMage to analysis, and use statistical methods for testing.Results:Clinical results:Of 39 patients,24 males and 15 females, aged 15 to 70 years, meaning 27.5±1.2 years; the disease of 1 to 12 months, with an average of 5.33±0.58 months. History of tuberculosis infection were not mentioned.29 patients were to be investigated and chest,and there were no tuberculosis.Routine histopathological examination showed:Infiltration of macrophages which showed immune response can be seen in 39 cases selected with lesions of the superficial dermis. Immunohistochemical staining showed:CD68 strong positive macrophages were seen in 39 cases,which showed statistically significant with peri and normal facial tissue lesions.TGF-β expression in 31 cases prompt positive and statistically significant compared with normal tissue visible. Western blot showed:between three different tissue samples, TGF-β, CD68 expression, COX-2 was statistically significant.Conclusion:Expression of TGF-β increased were seen in pathological of patients,while the molecule can induce macrophage infiltration, immune response, and can induce macrophage polarization.The polarization is changed from the M1-type to M2 type macrophages,which showed CD68 positive, while, M2 macrophages secrete VEGF and COX-2 and other inflammatory cytokines, leading to the subsequent development of disease.These factors might be involved in the occurrence of this disease,and may be closely related to the development of the disease.At the same time the disease are less likely to TB infection related.