Today, medical disciplines are becoming more and more refined, requiring patients to have a clear direction when seeking medical care. For patients with systemic diseases, finding the right direction is not an easy task, and they often seek medical help but are delayed in receiving effective treatment. Among the systemic diseases, IgG4-related diseases are typical. In 2012, the concept of “IgG4-associated diseases” was officially introduced at the International Symposium on IgG4-associated Diseases, and since then, IgG4-associated diseases have been officially introduced as a new disease group in clinical practice, and more and more patients are diagnosed and receive comprehensive and effective treatment. What are the clinical manifestations of IgG4-associated diseases? IgG4-associated disease is an immune-mediated fibrous inflammatory disease with multi-organ involvement. The main clinical manifestations are swollen tissue changes in the pancreas, salivary glands, lacrimal glands, lymph nodes, kidneys and other organs. Patients with retroperitoneal fibrosis may have pain in the lower abdomen, and fibrous tissue compression of the ureter may also lead to hydronephrosis and abnormal kidney function; patients with bile duct involvement may have yellow skin staining and itching; some patients may have generalized lymph node enlargement as the main manifestation, etc. Before the diagnosis is recognized, patients tend to be seen in various specialties: patients with salivary gland (such as parotid and submandibular glands) involvement may be the first to see a stomatologist; patients with lacrimal gland involvement will be the first to seek help from an ophthalmologist; patients with pancreatic involvement tend to see a gastroenterologist or hepatobiliary physician for “occupancy of the pancreas”. In addition, because of the complex clinical manifestations of the disease and the “mass” as the main feature, many patients are misdiagnosed as malignant tumors, such as pancreatic cancer, bile duct cancer, lymphoma and other diseases, which has a great impact on patients’ psychology. Therefore, it is important that all hospital departments work together so that more patients with “strange” symptoms can be diagnosed and treated early. How is IgG4-related disease diagnosed? Serum IgG4 can be elevated in most patients, and elevated peripheral plasma cells can also aid in the diagnosis, but this program is not currently widely available nationwide. It is important to note that elevated IgG4 alone does not diagnose the disease; it also needs to be combined with the presence or absence of clinical manifestations and pathologic findings common to the disease in patients. In case of abnormal clinical manifestations and laboratory results, pathological biopsy is very important for the diagnosis of the disease. In addition, pathological examination can also help to exclude malignant neoplastic diseases, which plays a very important role in the diagnosis and differential diagnosis of the disease. How to treat IgG4-associated diseases? Currently, there is no recognized optimal treatment for IgG4-associated disease. Glucocorticoids are the first line of treatment for this disease. The vast majority of patients respond well to small to moderate doses of hormones, but reduction or discontinuation may lead to relapse, so treatment regimens will need to be adjusted under medical supervision when the disease is in remission. In addition, some patients may require combination immunosuppressive therapy to better control the disease, but there are few clinical studies in this area. For refractory cases, rituximab has been reported to be more effective overseas, but it has not been widely promoted in China because of the small number of cases studied and the high cost. What is the prognosis of IgG4-associated disease? The prognosis for this disease is good, with most patients seeing improvement in symptoms and laboratory parameters soon after receiving hormone therapy, and the dose of hormone can be gradually reduced as the disease stabilizes. Therefore, IgG4-associated disease, which has a wide variety of manifestations, is not in itself scary. Only by unraveling its “mystery”, early diagnosis and early treatment can we find the right direction on the road to fighting the disease.