What about coughing and shortness of breath?

*It is only for medical professionals to read for reference.
ILD is an important extraglandular manifestation of SS.
The treatment should not be neglected, and serious organ damage should be avoided
.

 Rheumatic immune diseases are complex and changeable.
Although certain diseases are mainly characterized by damage to an organ, they can also affect multiple organ systems throughout the body.
The patient is constantly sick, which can be described as "moving all over the body"
.

Therefore, the treatment of rheumatic immune diseases is more difficult in the clinic, and the treatment of comorbidities needs to be taken into account
.

Sjogren’s syndrome (SS) is an autoimmune disease characterized by involvement of the exocrine glands, and interstitial lung disease (ILD) is one of its common extraglandular manifestations, which not only damages the patient’s body function, but also affects The quality of life can also increase the risk of death [1]
.

In clinical practice, SS-related ILD diagnosis and treatment should be given extensive attention
.

This time, Professor Qi Xu from the Second Hospital of Hebei Medical University shared a case of Iramod (IGU) in the treatment of SS combined with ILD.
For his diagnosis and treatment experience and ideas, please see below
.

Basic information of case data: female, 68 years old
.

Main complaint: cough and shortness of breath for more than 1 year, worsened by half a month
.

History of present illness: 1 year ago, the patient had cough, shortness of breath, a small amount of white sputum, dyspnea, weakness of limbs, slight dry mouth, no dry eyes, and repeated parotid gland swelling without obvious cause
.

I have been to a local hospital.
The examination results suggested bronchitis, interstitial lung disease, and cough variant asthma.
After treatment with acetylcysteine ​​and budesonide formoterol inhalation powder, my symptoms improved.
The drug was discontinued one month later
.

This time he was admitted to the hospital due to aggravated cough and shortness of breath
.

Physical examination: body temperature (T) 36.
6°C, pulse (P) 112 beats/min, breathing (R) 27 beats/min, blood pressure (BP) 124/82mmHg, clear speech, no skin rash, no superficial lymph nodes all over the body Palpable swelling, cracking sound can be seen at the bottom of both lungs
.

The heart rate is 112 beats/min, the rhythm is uniform, the auscultation area of ​​each valve has no murmur, the abdomen is soft and no tenderness, the liver and spleen are not palpable, the muscle strength of the limbs is normal, and the muscles are not tender
.

Laboratory examination: white blood cell count (WBC) 7.
37×109/L, hemoglobin (HGB) 132g/L, platelet count (PLT) 309×109/L, rheumatoid factor (RF) 21.
9 IU/ml; C-reactive protein (CRP) ) 35.
3 mg/L, erythrocyte sedimentation rate (ESR) 46 mm/h; immunoglobulin IgG 21 g/L, IgA 2.
56 g/L, IgM 3.
64 g/L; antinuclear antibody (ANA) 1:320
.

Stomatology and ophthalmology examination: the saliva flow rate was 0.
1ml under 15 minutes without irritation; corneal fluorescence staining, tear film rupture time measurement, and filter paper experiment were all within the normal range
.

Labial gland biopsy: multifocal lymphocyte and plasma cell infiltration can be seen in the examined gland
.

Meets the Chisholm classification level IV
.

Lung examination: lung CT showed: 1.
The two lungs have uneven density, local thickening, thickened part of the interlobular septum, complicated by multiple patchy ground glass shadows, based on the lower lobe, consider interstitial changes with inflammation; 2.
There are hilar swelling with air sacs; 3.
The second rib on the left does not run naturally; 4.
The trunk of the pulmonary artery is widened (see Figure 1)
.

Lung function: forced vital capacity (FVC) 116.
1%, forced expiratory volume per second (FEV1) 112.
9%, carbon monoxide diffusion volume (DLCO SB) 69.
6%, mild diffuse dysfunction
.

Diagnosis: Sjogren’s syndrome combined with interstitial lung disease was admitted to the hospital for treatment: prednisone acetate 30 mg orally once a day, Iguratimod (IGU) 25 mg orally twice a day
.

Efficacy observation: After treatment, the patient's condition improved and was discharged
.

Decrease the hormone regularly, and reduce the dose to 5 mg of prednisone acetate once a day for maintenance, and continue to take IGU 25 mg orally twice a day
.

On July 24, 2021, the patient did not complain of obvious chest tightness, shortness of breath, dry mouth improved, and no parotid gland swelling
.

Physical examination: breath sounds clear in both lungs, not as dry or wet as rales; laboratory examinations showed that CRP was 3.
28mg/L, ESR was 3mm/h, both of which had fallen to the normal range; lung function: FVC 130.
6%, FEV1126.
3% , DLCO SB 88.
3%, lung function is roughly normal
.

Lung CT showed uneven perfusion in both lungs, which was reduced compared to the previous one.
There were multiple patchy ground glass density shadows in the two lower lungs.
The density was slightly lower than the previous one, and the range was slightly smaller than the previous one; the rest was basically the same as the original film (Figure 1)
.

Figure 1: Summary of the patient’s lung CT examination: The patient went to the hospital for cough and shortness of breath.
The lung CT and pulmonary function tests revealed ILD, clinical manifestations such as dry mouth, parotid gland enlargement, and salivary gland function, labial gland biopsy and other results suggest SS, so The diagnosis was SS combined with ILD
.

After systemic treatment, the patient's symptoms were relieved, lung inflammation was reduced, lung function was improved, inflammation indicators (CRP, ESR) fell to normal levels, the treatment effect was good, and hormones have been regularly reduced
.

Expert comment ▌ ILD is one of the common extraglandular manifestations of SS, affecting the prognosis of the disease.
SS is a chronic inflammatory autoimmune disease characterized by lymphocyte infiltration of exocrine glands and other organs, leading to keratoconjunctivitis sicca and saliva Hypofunction and various extraglandular manifestations
.

According to statistics, the proportion of SS patients with clinically significant lung involvement is about 9%-24%, of which ILD is more common
.

ILD is the most serious pulmonary comorbidity of SS [2]
.

ILD refers to a group of lung diseases that affect the lung interstitium, which can cause basic pathological changes such as diffuse lung interstitial, alveolar inflammation, and interstitial fibrosis.
Patients often show symptoms such as exertional dyspnea and persistent dry cough.
The patient's quality of life has a significant impact
.

In the diagnosis of clinical ILD, in addition to asking the patient about the history and symptoms, it is also necessary to combine physical examination, serum tests, pulmonary function determination (characterized by reduced DLCO and FVC, and normal FEV1), and chest imaging examinations for comprehensive judgments[ 3]
.

At present, the pathogenesis of SS combined with ILD is unclear, and the reasons may be multi-factorial
.

Studies have shown that during the pathogenesis of SS, the pathogenesis of exocrine glands and extraglandular manifestations are similar, and both involve the autoimmune response of epithelial cells
.

Therefore, some scholars speculate that the immune response starting from the salivary glands may extend to epithelial cells in other parts of the body, such as lung epithelial cells, causing continuous damage and driving the occurrence of lung diseases [4]
.

▌ The treatment and management of SS combined with ILD.
Glucocorticoids and immunosuppressive agents (such as azathioprine, cyclophosphamide, etc.
) Certain curative effect
.

However, there are currently no large-scale clinical trials evaluating the effectiveness of immunosuppressive treatment of SS combined with ILD
.

The use of biological agents with different mechanisms of action also lacks definitive research evidence
.

Therefore, the optimal treatment plan for SS combined with ILD has not been determined [4]
.

Currently in clinical practice, immunosuppressive agents are usually used as first-line treatment or maintenance treatment to help reduce hormone dose
.

When the condition is more serious or in the advanced stage, immunosuppressive agents and hormone therapy can be combined
.

▌ IGU or an effective method for the treatment of SS combined with ILD IGU is a new type of small molecule drug with immunomodulatory effects
.

Its mechanism of action is diverse.
It can not only inhibit B cell differentiation and reduce the secretion of immunoglobulins, but also regulate the immune balance mediated by T cells and related inflammatory factors, and inhibit important signal pathways in the pathological mechanism of SS, such as NF-κB and IL.
-17 signal pathway
.

A number of clinical studies have proved that IGU has a good curative effect in the treatment of SS [5-13]
.

For the treatment of ILD, clinical studies have shown that in patients with rheumatoid arthritis (RA) and ILD, IGU treatment can alleviate the inflammatory response, reduce disease activity and improve lung function [14]
.

In preclinical studies, IGU can relieve lung inflammation and fibrosis by inhibiting the secretion of immunoglobulin by B cells, and play a protective role in the lungs in ILD [15]
.

Therefore, IGU may be an effective method for the treatment of SS combined with ILD, and the specific mechanism and therapeutic effect need to be clarified by further research
.

 Expert profile Professor Qi Xun, Department of Rheumatology and Immunology, the Second Hospital of Hebei Medical University, Deputy Chief Physician, Member of the Rheumatology Committee of Hebei Health Education and Rehabilitation Association Member of the Rheumatology Committee of Hebei Pharmaceutical Association.
The main research direction is the pathogenesis of Sjogren's syndrome He has published more than 10 papers and 3 books in international and domestic journals of its diagnosis and treatment, of which the first author SCI 3 papers presided over 3 provincial and departmental projects.
The first lead researcher completed a reference for the first prize of Hebei Medical Science [1] Luppi F,Sebastiani M,Sverzellati N,et al.
Lung complications of Sjogren syndrome[J].
Eur Respir Rev,2020,29(157):200021.
[2]Flament T,Bigot A,Chaigne B,et al.
Pulmonary manifestations of Sjögren's syndrome[J].
Eur Respir Rev,2016,25(140):110-23.
[3]Luppi F,Sebastiani M,Silva M,et al.
Interstitial lung disease in Sjögren's syndrome: a clinical review.
Clin Exp Rheumatol[J],2020,126(4):291-300.
[4]Gupta S,Ferrada MA,Hasni SA.
Pulmonary Manifestations of Primary Sjögren's Syndrome: Underlying Immunological Mechanisms, Clinical Presentation,and Management[J].
Front Immunol, 2019,10:1327.
[5]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].
Geriatric Medicine and Health Care,2019,25 (2):209-213.
[6]Wang Xue, Yuan Xiang, Wang Qikai, et al.
The therapeutic effect and mechanism of Ilamod on primary Sjogren’s syndrome[J].
Chinese Journal of Disease Control, 2018,22(1):75-78.
[7] Jiang Wei.
Evaluation of the efficacy of Ilamod on Sjogren’s syndrome and its mechanism of action on B cells[D].
Sichuan: Luzhou Medical College, 2014.
[8]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.
[ 9]Xu Dong,Lv Xiaowei,Cui Peng,et al.
Comparison of efficacy and safety of irammod and hydroxychloroquine in the treatment of patients with Sjogren’s syndrome[J].
Journal of Difficult and Difficult Diseases,2017,16(9):915-918.
[10] 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.
[11], Li Rui,Liu Hanzhong, et al.
The efficacy of methylprednisolone combined with Iramud in the treatment of primary Sjogren’s syndrome and its effect on immunoglobulin levels[J].
China Pharmaceuticals,2018,27(14):35-27.
[12]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.
[13]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.
[14]Shu P,Shao SQ, Cai XN, et al.
Iguratimod attenuates general disease activity and improves lung function in rheumatoid arthritis-associated interstitial lung disease patients[J].
Eur Rev Med Pharmacol Sci,2021,25(14):4687-4692.
[15]Han Q,Zheng Z,Liang Q ,et al.
Iguratimod reduces B-cell secretion of immunoglobulin to play a protective role in interstitial lung disease[J].
Int Immunopharmacol,2021,97:107596.
This article is only used to provide scientific information to medical and health professionals and does not represent Platform position
.