IgG4-associated Mikulicz disease case report

IgG4-related disease sision is a chronic inflammatory auto
immunedisease that can affect the organs of thedigestivesystem such as the pancreas and bile ducts, as well as the external secretion glands such as the tear glands and salivary glandsAffected organs or glands showed swelling, serum IgG4 levels significantly increased (1.35g/L), and affected histopathology was characterized by massive immersion of IgG4-positive plasma cellsIgG4-related diseases can also be combined with allergic diseases, such as variable rhinitis and bronchial asthmaMikulicz disease is characterized by painless, symmetrical tear, mumps and swollen glands, which are known as IgG4-associated Mikulicz disease if associated with increased serum IgG4 levels1Cases reported, female, aged 60, was admitted to hospital on 28 September 2015 due to "dry eyes and dry mouth for more than 3 years, swelling of the lower jaw area with both sides"Patients 6 years ago consciously dry eyes and mouth dry, affecting swallowing, 1 month ago inadvertently found that the two-sided jaw area painless swelling, slow growth, accompanied by double-sided mumps after the lower area swellingPatients have a history of chronic diseases such as high blood pressure, coronary heart disease anddiabetesclinical examination: double-sided mumps after the lower extreme swelling, not stoic and obvious swellingThe lower area of the left and right jaws can be swollen and mildly swollen under the jaw glands, tough, no tenderness, activity, the boundary is clear The head and neck lymph nodes in other areas are not swollen and swollen In-mouth inspection: 37 face to see silver mercury filling The mouth of the two-sided mumps and jaw gland catheters is free of redness and swelling, the secretion is clear and the secretion is less laboratory examination: 9.4% of eosinophils (reference value: 0.4% to 8.0%), immunoglobulin G (IgG) is 14.5g/L, all higher than the normal range; 109/L (reference value: 1.8 to 6.3 x 109/L), complement C3 is 0.53g/L (reference value: 0.9 to 1.8g/L), complement C4 is 0.063g/L (reference value: 0.1 to 0.4g/L), both are below normal The remaining immune indicators such as C-reactive protein, IgA, IgM, rheumatoid factor, etc are normal values, and the remaining values of liver and kidney function and blood routine are in the normal value range CT axial flat sweep in the lower jaw area: multiple calcification stove in the lower jaw area on the left side (Figure 1) Figure 1 ct shaft scan show left jaw area calcified stove patients admitted to the hospital complained of eyelid swelling discomfort, please ophthalmology consultation, diagnosis for trachoma, double-sided eyelid yellow melanoma, recommended Lomesard eye drops, Orota dyslech oozeros, eye symptoms reduced after medication Analysis of the patient's condition, the patient's left jaw gland calcified, jaw gland function has been lost, and although the right side swelling, but still did not appear instrumental damage, there is still a certain function, so after the improvement of preoperative preparation, in the whole hemp down the left jaw gland removal Postoperative jaw glandous specimens were sent for routine pathological examination: chronic inflammation of the lower jaw gland associated with lymphatic tissue hyperploration (Figure 2) Figure 2 Preliminary Pathology Picture shows the left jaw gland chronic inflammation with lymphatic tissue hyperplasia HE x 200 patients after surgery conventional anti-inflammatory treatment, after the operation of continuous 6d use of dexamethasone sodium phosphate injection 10mg intravenous drip 1 / d, after surgery 7 to 9d hormone adjusted to injection with methyl nylon poured amber Sodium 40mg intravenous drip 1/d, after surgery 10 to 12d reduction in injection with methyl-sprinklenylon sodium amber acid 20mg intravenous drip 1 /d, after surgery 13 to 14d continue to reduce the amount of injection with methyl-sprinklenylon sodium amber acid 1 time /d After surgery, the patient's 14d left jaw undersurgery area healed well, the swelling of the two-sided mumps area and the right jaw gland smaller than when admitted to the hospital, was discharged from the hospital, and re-diagnosed after 1 month Discharged medicine: oral bailenosphine capsules, 1g, 3 times/d each time; 2 Results follow-up after discharge from hospital, patients were instructed to regularly review the immune indicators and closely observe the function of the lower jaw gland in the right side Patients were referred to the clinic on 13 October 2018, with a review of the immunization indicator: IgG4 is 19.5g/L Re-sending surgical specimens for immunohistization (IgG4 antibody markers), showing a large amount of IgG4 positive plasma cells immersion (Figure 3) Therefore, it is clearly diagnosed as "IgG4-associated Mikulicz disease" The patient is currently in stable condition and is still under follow-up observation Figure 3 Re-diagnosis and delivery tissue IgG4 antibody immuno-grouped staining picture x 200 3 Discussion 3.1 etiology the exact pathogenesis of IgG4-related Mikulicz disease is not yet clear, but the disease and abnormal immune response related to the view is increasingly accepted by the academic community The degree of increase in serum IgG4 is related to the number of organs involved: the greater the degree of disease, the higher the likelihood of an increase in serum IgG4 levels Studies have confirmed that the interaction between B-cell line cells and an abnormal CD4-SLAMF7-cytotoxic T-cell cell may be involved in the process that causes tissue inflammation and fibrosis Recent studies show a cloned amplification of CD4 plus cytotoxic T cells in the blood in patients with IgG4-related diseases, which secrete interleukal interleukin-1 beta and conversion growth factor-beta-1 in peripheral blood and inflammatory tissue lesions, which may be the driver of lesionfibrofibroization Studies have also shown that auxiliary follicle T cells (Tfh cells) are involved in the pathogenesis of IgG4-related diseases, which induce B cells to differentiate into plasma cells and play an important role in the pathogenesis of IgG4-related diseases 3.2 Clinical Manifestations Clinical Characteristics of Classic IgG4-Related Mikulicz disease include: (1) symmetric swelling that causes at least 2 pairs of tear, mumps or jaw glands sustained (more than 3 months); ;() ;(3) IgG4 positive plasma cells are significantly immersed (IgG4/IgG-40%), and The mytopathological changes of IgG4 plus plasma cells of 10/high-view (high power field, HPF) ;(4) are associated with typical tissue fibrosis or hardening Clear diagnosis needs to meet all criteria and can be considered as possible when clinical and pathological standards are met usually, the saliva secretion of patients is normal or slightly reduced, 30% of patients appear dry mouth, the frequency is lower than dry syndrome patients Nuclear magnetic resonance imaging (MRI) is generally characterized by diffuse swelling of the lower jaw glands on both sides or side, or as a single-shot nodule or lump However, MRI performance is not a specific manifestation of IgG4-related Mikulicz disease fluorodedery-oxyglucose PET-CT can be used to assess the overall stress of a patient, which may also play an important role in assessing the response to corticosteroid hormone therapy and identifying specific areas of biopsy IgG4 correlation Mikulicz disease and dry syndrome clinical identification as follows: (1) there is a great difference between histology and imaging, IgG4 correlation Mikulicz disease of the gland substance is usually uniform, MRI salivary imaging performance is relatively normal, while dry syndrome gland strophy, MRI salivary imaging shows the expansion of salivary gland slater catheter; (2) IgG4 correlation Mikulicz patients serum IgG4, IgE level is significantly higher than dry syndrome patients; (3) IgG4 correlation Mi-kulicz disease and dry syndrome the most important difference is that the former tired tissue in the IgG4 positive plasma cells are significantly immersed, while in patients with dry syndrome patients tired glands almost never saw IgG4 positive plasma cells IgG4-related Mikulicz disease and salivary gland benign hypertrophy differential diagnosis: (1) salivary gland benign hypertrophy is non-tumor, non-inflammatory salivary gland disease, tired gland swelling generally sustainable for several years and swelling is slow, when large and small, and no obvious Dry mouth symptoms, and IgG4-related Mikulicz disease and gland swelling will not subside, and 30% of patients have mouth dryness; 3.3 treatment
There is no unified plan for the treatment of IgG4-related Mikulicz disease, mainly in the treatment of the disease In cases with high degree of adenular hardening and basic loss of function, surgical removal of the glands affected by the prevents further deterioration of the glands Current scholars have pointed out that glucocorticoids are a first-line drug to relieve IgG4-related diseases Recommended dose: pernison 0.6 mg/kg, lasting 2 to 4 weeks; But Studies such as Himi found that the first dose of glucocorticoids did not significantly worsen the affected glands After gradually reducing the amount of hormones, the salivary gland function has a mild relief, but once the hypocorticoids are discontinued, the serum IgG4 level of the patient increases again, and the salivary glands and other glands re-emerged swelling and other phenomena So this study proves that IgG4-related People with Mikulicz need to maintain long-term sexual use of glucocorticoids , some scholars have suggested that the use of rituximab B cell depletion therapy can reduce serum IgG4 levels, reduce inflammation immersion, while partially reducing fibrosis, clinical response is rapid In patients with recurrent or refractive diseases, two intravenous drops of rituximab (RTX) 1000mg, at intervals of 15d, each infusion of methyl-strong pine dragon (100mg), phenhylamine (25mg) and acetaminophen (650mg) to reduce the occurrence of infusion reactions Patients who re-form the disease after the return of B cells are treated with the same RTX induction regimen other than that, for those with poor traditional hormone therapy, you can choose to add immunosuppressants such as thionine 2.0 to 2.5 mg/kg, moldphenols (750 mg, 2 times/d), cyclophosphamide, methotrexate, miquine, botimmi and other immunosuppressants The disease is prone to recurrent attacks and requires long-term medication , IgG4-related Mikulicz disease is currently difficult to diagnose, treatment is difficult to cure Therefore, for unexplained patients with enlarged jaw facial glands, hardening and even with dry syndrome, the screening IgG4 immune indicators should be in a timely manner to achieve the purpose of accurate diagnosis The pathogenesis of the disease and the best treatment need to be further studied