Pancreas swelling before treatment (L), reduced swelling after treatment (R)
An old man suffered obstructive jaundice, and his CT showed pancreas swelling, and especially, the swelling head pressed bile duct and caused jaundice. The doctor highly suspected tumor and suggested immediate surgery. On a female patient, hardened tissues under chins were reported, and CT showed swelling submandibular glands. Again tumor was suspected and a suggestion of surgery was raised. Experts from PUMCH, however, gave different opinions: the two patients may have the same disorder: immunoglobulin G4-related disease (IgG4-RD), which is easily taken as tumor and therefore demands extra attention from doctors.
IgG4-RD is a condition of inflammation with fibrosis newly recognized in recent years, a not so common disease that affects multiple organs and systems. It occurs mostly in middle and old age groups and the male-female ratio is 2.3:1. Clinical manifestations include swelling and hardening organs or tissues, increased IgG4 in serum, and pathologic reports show a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, and a variable degree of fibrosis that has a characteristic “storiform” pattern. Involved organs and tissues usually include lacrimal gland, salivary gland, digestion system, retroperitoneal tissue, kidney and lung. The pathogenesis is still unknown. Presently it is believed that excessively activated Th2 cells caused plasma cells to produce a great amount of IgG4, and the increased secretion of IL-4, IL-13, TGF-β and IL-10 caused the infiltration of inflammatory cells and fibrosis.
IgG4-RD is a newly recognized condition. First reported around 2000, it was only internationally recognized and officially named after 2010. Knowledge about it was very limited in China. PUMCH was the first Chinese hospital to establish comprehensive diagnosis methods using serum IgG subclass test as well as pathologic and imaging techniques. In 2011, led by Professor Zhang Wen from the Department of Immunology and Rheumatology, the hospital carried out China’s largest and earliest prospective clinical cohort study, to which more than 340 cases have been included so far. The Department, in collaboration of departments of dentistry, pathology, gastroenterology, respiratory diseases, nephrology, ophthalmology, radiology, basic surgery, nuclear medicine, general medicine, hematology, neurology, endocrinology, urological surgery and E.N.T, established a research group, a specialty clinic and a green channel to facilitate diagnosis and treatment. In recent years, the research team published, in Chinese and English, dozens of theses on IgG4-RD, with a total impact factor of 60. Professor Zhang was invited by her international colleagues to participate in the compilation of the world’s first expert consensus on the diagnosis and treatment of IgG4-RD, a guide which was published in an authoritative journal of the field in 2015. The IgG4-RD research won first prize of medical achievements of PUMCH in 2015.
The expert consensus gave three comprehensive diagnosis standards: clinical examinations show typical diffuse/localized swelling or forming of bump in one or more organ; blood test show an elevated level of IgG4 (>135mg/dl); histopathologic examination show a large amount of lymphocyte and plasma cell infiltration, accompanied by fibrosis, and the ratio of IgG4+ plasma cells against plasma cells in such issue is >40%, and IgG4+ plasma cells >10 can be found under high power lens. IgG4-RD can be confirmed if all the three standards are fulfilled and can be suspected if two standards are fulfilled.
For early-stage, active IgG4-RD patients, glucocorticosteroid is a first-line drug with an efficacy of more than 80%. After treatment, inflammatory or swelling organs showed apparent improvement and the level of IgG4 was reduced. Some patients need glucocorticosteroid in combination with immunosuppressive drug. IgG4-RD is a chronic disorder, and returns easily if medicine is reduced or stopped. Therefore further research is needed on stable treatment.
PUMCH is verifying the practicality of the diagnosis standards in China, and has carried out prospective observation of different treatment schemes.
According to Professor Zhang, IgG4-RD is easily mis-diagnosed as it shows similar images with tumor and as the disorder starts quietly, often without any clinical manifestations at early stage, and patients usually do not go to see a doctor until feeling inflammation or pressed tissues. This calls for precise knowledge from doctors so as to avoid unnecessary pains due to excessive treatment.