Professor Zhao Futao: From the outside to the inside, let you have a more comprehensive understanding of Sjogren’s syndrome

*It is only for medical professionals to read.
Dryness is not all of it.
.
.
Professor Zhao Futao Chief Physician, Professor, Doctor of Medicine, Postgraduate Tutor, Department of Rheumatology and Immunology, the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine Vice Chairman of the Sjogren's Syndrome Group of the Physician Branch Member of the Standing Committee of the Immunoadsorption Academic Committee of the Chinese Medical Doctor Association Director of the Asia-Pacific Society of Medical Bioimmunology and Member of the Standing Committee of the Rheumatology and Immunology Branch of the Cross-Strait Medical and Health Association Member of the Standing Committee of the Rheumatology Committee of the Cross-Strait Medical and Health Association, member of the Gout Group Shanghai Medicine Member of the Society of Rheumatology, Shanghai Association of Integrative Medicine Rheumatology Committee, Sjogren's Syndrome Group Leader, Shanghai Association of Integrative Medicine Rheumatology Committee, Behcet's Disease Group Deputy Leader, National Science and Technology Progress Award and Invention Award Reviewer Won two municipal science and technology progress third prizes, editor-in-chief and co-editor of 11 core journals and 63 SCI papers.
Research direction: Sjogren’s syndrome, rheumatoid arthritis, gout, Behcet's disease and other rheumatic immune diseases pathogenesis He Biotherapy Sjogren’s Syndrome (SS) is a chronic autoimmune disease involving the exocrine glands throughout the body.

As the name suggests, SS can cause local dryness, and the patient has dry mouth and eyes due to decreased saliva and tear secretion, but is that only the case? No, SS is far more complicated than you think.
.
.
In this issue, we invite Professor Zhao Futao from the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine to share clinical knowledge about SS and reveal its more diversified side.

1 Systemic injury, the "flood beast" that has to be prevented Although dry mouth and dry eyes are the most common symptom of SS patients, it is not the only symptom.

Professor Zhao Futao said, “In clinical practice, the early symptoms of some patients are not dry mouth and dry eyes, but enlarged glands (such as parotid glands and submandibular glands), muscle aches, joint pains, low fever, fatigue, etc.

” SS is one This is a chronic progressive autoimmune disease that can involve multiple organ systems throughout the body as the disease progresses.

Commonly affected areas include lungs, liver, kidneys, blood system, nervous system, etc.
, which will cause functional damage to the corresponding organ systems.
In severe cases, more dangerous situations may occur.
The risk of lymphoma in SS patients is several times higher than that of healthy people.
It is also common to involve the respiratory system, and interstitial lung disease is one of the main causes of death in SS patients [1].

 Figure 1: Various symptoms of SS[2] "The above-mentioned systemic manifestations should arouse the attention and alertness of rheumatologists.
After
these symptoms appear, the patient's condition should be confirmed through diagnosis and testing as soon as possible.

" Professor Zhao Futao emphasized , "Early detection and early treatment are essential for the improvement of SS patients.

" At present, a variety of SS diagnostic criteria have been proposed at home and abroad.

Among them, the widely recognized and recommended is the SS International Classification Standard (AECG Standard) revised in the United States and Europe in 2002, which is comprehensive in content, involving oral symptoms, ocular symptoms, eye features, pathological testing of glands, and autoantibody testing.
And many other projects, strong guidance [3].

In addition, the primary Sjogren’s syndrome (pSS) classification standard developed by the American College of Rheumatology (ACR)/European Union Against Rheumatism (EULAR) in 2016 has high specificity and sensitivity, and has great significance in diagnosis.
Advantages, but the standard uses ocular and oral symptoms as the inclusion criteria instead of the classification criteria, and there may be certain limitations in its application [4].

2 An effective disease assessment system is a weapon for treatment decision-making SS is a very heterogeneous disease, and the corresponding treatment strategies vary from person to person.

Professor Zhao Futao believes that in the diagnosis and treatment of SS, disease evaluation is very important.
Today, when individualized treatment is promoted, effective disease evaluation will help clinical patient hierarchical management and scientific treatment decision-making.

At present, there are no special clinical symptoms or biological indicators that can accurately assess the disease activity or damage degree of each involved organ, and a certain evaluation system is needed for disease evaluation.

The most widely used disease activity evaluation systems in the world include the disease activity index (ESSDAI) and SS patient self-report index (ESSPRI) issued by EULAR: Table 1: Introduction to ESSDAI and ESSPRI [5-6] "In the SS disease evaluation system , ESSDAI and ESSPRI are important evaluation tools.

Their application is conducive to the unification of evaluation standards in clinical research.

"Professor Zhao Futao believes, "If the two scoring systems are used comprehensively, combined with objective and subjective factors, we can have a more comprehensive understanding of patients.
The overall condition.

" Professor Zhao Futao also said that in actual outpatient clinics, due to the large number of consultations and short time, doctors may not be able to fully use the evaluation system to score patients, but most of the evaluation indicators have been covered during the consultation process.
The judgment ideas of the complete evaluation system are basically the same.

At the same time, with the help of auxiliary examination methods such as immunoglobulin and erythrocyte sedimentation rate indicators, it can be judged whether the patient is in the active or stable phase.

Therefore, whether in academic research or actual clinical work, disease assessment tools have important guiding significance.

3 Actively explore new clinical treatment plans for SS, and break through the existing dilemma.
The clinical treatment of SS is quite tricky.

In the early stage of the disease, symptomatic treatment is usually given to relieve symptoms.
For patients with severe disease and organ involvement, most of the existing treatment programs are not very effective and have not achieved the expected results.

In recent years, with the deepening of the knowledge of diseases and the innovation of technical methods, the treatment methods have gradually enriched.

New immunosuppressants, small molecule inhibitors, and biological agents can all be used as reference for clinicians.

However, no drugs have been approved for SS indications, and most of the drugs used at this stage are empirical treatments or refer to the treatment of similar lesions.

"There are huge unmet clinical needs in the field of SS treatment.

For the exploration and optimization of its treatment plan, related research has been actively carried out, and preliminary results have been achieved.

"Professor Zhao Futao pointed out that the new small-molecule anti-rheumatic drug Iguratimod (IGU) is a drug with great therapeutic potential discovered in recent years.
He himself has participated in related research and exploration and has obtained positive curative effects.
Results [7].

IGU is a new class of drugs independently developed by China and an immunomodulator with a comprehensive mechanism.

It can regulate the balance of T cell and B cell subsets, reduce the level of immunoglobulin [8], and inhibit IL-17 And NF-κB signaling pathway [9-11] and IFN-γ and other cytokines [12-13] have been approved for the treatment of rheumatoid arthritis (RA).

"Because of its mechanism of action and the pathological mechanism of SS For many similarities, we guess that IGU may have a certain effect in the treatment of SS.

"Professor Zhao Futao introduced, "Many researchers have explored and verified this, and the results have shown that IGU performs well in the treatment of SS.
Whether it is monotherapy or combined with conventional treatment, IGU can reduce ESSDAI and/or ESSPRI score and alleviate the systemic manifestations of the disease can help patients improve their condition.

"Benefiting from a large number of basic research and clinical research data support (Table 2), the 2020 "Primary Sjogren’s Syndrome Guidelines" will include IGU in the recommended list of immunomodulators, and indicated that SS patients with systemic involvement can use it.
The drug is used for treatment [1].

In addition, in September last year, IGU's new drug clinical trial application for the treatment of pSS has been approved by the National Medical Products Administration, which means that it will prove its efficacy and safety in more extensive clinical studies.
It is expected to be the first drug to be included in the indications.

 Table 2 Brief introduction of published studies in the treatment of pSS by IGU [7, 14-21] In addition to the progress of therapeutic drugs, Professor Futao Zhao also told us how to treat pSS from the perspective of overall clinical management Effectively avoid and reduce the harm caused by SS systemic damage: early consultation, early detection, and early treatment: SS systemic damage usually occurs in the advanced stage of the disease.
If it can be intervened and treated at an early stage, it can be avoided to a large extent hazard.

before treatment, patients should conduct a comprehensive assessment of the condition to guide subsequent treatment.

According to the patient's disease stage, select the appropriate treatment plan to give individualized treatment.

If the patient has shown systemic damage, then local treatment should not stop, but systemic treatment should be chosen to avoid involvement of more organ systems.

Regular review and timely adjustment of the treatment plan: Pay attention to the education and science popularization of patients, improve patient compliance, and maintain a long-term stable treatment strategy.

4 Summary SS is an autoimmune disease with complex manifestations, serious harm, and difficult treatment.

Except the secretory glands, it can also involve multiple organ systems throughout the body.

IGU is a new small-molecule anti-rheumatic drug that has been found to be effective in the treatment of SS in recent years.
It can significantly reduce patients' ESSDAI and ESSPRI scores and alleviate their systemic performance.

We look forward to more clinical evidence to prove its efficacy in the future, and hope that more drugs with therapeutic potential will emerge in the field of SS treatment to help patients overcome the disease.

References: [1] Sjogren's Syndrome Group of Rheumatology and Immunology Physician Branch of Chinese Medical Doctor Association.
Standards for diagnosis and treatment of primary Sjogren's syndrome[J].
Chinese Journal of Internal Medicine, 2020, 59(4): 269-276.
[2] arthritisCARE.
Sjogren's Syndrome About,Causes,Symptoms, Treatment, Recovery, FAQs [EB/OL].
[3]Vitali C,Bombardieoi S,Jonssin R,et al.
Classification criteria for Sjogren's syndrome: a revised version of European criteria proposed by the American European Consensus Group[J].
Ann Rheum Dis, 2002, 61: 554-558.
[4]Jin Yuebo, He Jing.
2016 American Academy of Rheumatology/European Alliance Against Rheumatism Classification Standard for Primary Sjogren’s Syndrome[ J].
Chinese Journal of Rheumatology, 2017, 21(3): 213-213.
[5]Seror R, Bowman SJ, Brito-Zeron P,et al.
EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide [J].
RMD Open, 2015, 1(1): e000022.
[6]Seror R, Ravaud P, Mariette X, et al.
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome[J].
Ann Rheum Dis, 2011, 70(6):968-72.
[7]Wang Yanling, Zhao Futao,Ai Xiangyan, et al.
Observation on the efficacy and safety of Iramod in the treatment of primary Sjogren’s syndrome in the elderly[J].
Geriatrics and Health Care, 2019, 25(2):209-213.
[8]Ye Y, Liu M, Tang L, et al.
Iguratimod represses B cell terminal differentiation linked with the inhibition of PKC/EGR1 axis[J].
Arthritis Research & Therapy, 2019, 21(1): 92.
[9]M Kohno, Y Aikawa, Y Tsubouchi, et al.
Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells[J].
Journal of Rheumatology, 2001, 28(12):2591-6 .
[10]Luo Q, Sun Y, Liu W, et al.
A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine arthritis by blocking IL-17 signaling, distinct from methotrexate and leflunomide[J].
The Journal of Immunology, 2013, 191(10):4969-4978.
[11]Fei Y, Zhang W, Lin D, et al.
Clinical parameter and Th17 related to lymphocytes infiltrating degree of labial salivary gland in primary Sjögren's syndrome[J].
Clin Rheumatol, 2014, 33(4):523-9.
[12] Wang Mengtao, Ni Danhong, Wang Xiaoyuan, et al.
Study on the regulation of CD3+ T cell IFN-γ and cytokine IL-6 in patients with rheumatoid arthritis[J].
Chinese Journal of Endemic Disease Prevention and Treatment, 2016, (12):310.
[13]Hou Jiaqi, Xue Luan.
Yuan Overview of the pathogenesis of primary Sjogren’s syndrome[J].
Modern Immunology,2019,39(1): 58-63.
[14]Wang Xue, Yuan Xiang, Wang Qikai, et al.
Iramod's effect on primary sjogren Therapeutic effect and mechanism of the syndrome[J].
Chinese Journal of Disease Control, 2018, 22(1):75-78.
[15]Jiang Wei.
Evaluation of the curative effect of Ailamod on Sjogren’s syndrome and its mechanism of action on B cells Research[D].
Sichuan: Luzhou Medical College, 2014.
[16]Jiang Dexun, Bai Yunjing, Zhao Liping, et al.
Clinical effect observation on the treatment of primary Sjogren’s syndrome with Iramod[J].
Clinical Misdiagnosis and Mistreatment, 2016 , 29(8): 90-93.
[17]Xu Dong, Lv Xiaowei, Cui Peng, et al.
Comparison of the efficacy and safety of islamod and hydroxychloroquine in the treatment of patients with Sjogren’s syndrome[J].
Journal of Difficult and Difficult Diseases, 2017,16 (9):915-918.
[18]Luo Qiwen, Guo Dongmei, Yu Yangtao, et al.
Efficacy and safety of islammod and hydroxychloroquine in the treatment of patients with Sjogren’s syndrome[J].
Chinese Journal of Clinical Research, 2018, 10(24 ):94-95.
[19]Li Chuanjing, Li Rui, Liu Hanzhong, et al.
The efficacy of methylprednisolone combined with Ilamold in the treatment of primary Sjogren’s syndrome and its effect on immunoglobulin levels[J].
China Pharmaceuticals, 2018, 27(14): 35-27.
[20]Chen H, Qi X, Li Y, et al.
Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An open-label pilot study[J].
Mod Rheumatol, 2020:1-5.
[21]Jiang W, Zhang L, Zhao Y, et al.
The efficacy and mechanism for action of iguratimod in primary Sjögren's syndrome patients[J].
Int Ophthalmol, 2020, 40(11):3059-3065.