Treating silver, skin and bones, PsA diagnosis and treatment "Art of War" is here!

*Read only for medical professionals Reference What has been achieved in the field of PsA? What is the significance of clinical diagnosis and treatment? Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis with complex and diverse clinical manifestations, and long-term progression can lead to bone destruction and bone remodeling
.

It not only has a variety of joint phenotypes, but also has a variety of extra-articular manifestations, including skin, nail lesions and dactylitis and enthesitis
.

The clinical manifestations of PsA vary greatly, and the lack of specific laboratory test indicators has brought certain difficulties to its clinical diagnosis and treatment
.

 Guided by the Rheumatology Branch of the Chinese Medical Association and sponsored by the "Medical Community" media, "Riding the Wind and Waves - 2021 Rheumatism Annual Inventory" has been successfully concluded
.

A total of 14 well-known experts from the domestic top rheumatology and immunization departments were invited to the year-end inventory, covering 12 hot diseases in the field of rheumatism and immunization
.

 In this issue, Professor Zhang Zhuoli of Peking University First Hospital brings the annual inventory of PsA
.

What achievements have been made in PsA-related research in the past year? What is the significance of clinical diagnosis and treatment? Let's learn quickly! Knowing ourselves and ourselves: fully understanding the heterogeneity of PsA Prof.
Zhang Zhuoli emphasized that PsA has strong heterogeneity and can be divided into six clinical phenotypes: peripheral arthritis, dactylitis, rash, spondylitis, enthesitis, and nail lesions
.

A cross-sectional study of 300 PsA patients at Peking University First Hospital analyzed the proportion of different clinical phenotypes in Chinese PsA patients.
The results showed that 74% of the patients had psoriatic skin lesions first, followed by bone and joint involvement; Nails were involved in 41.
4% of patients [1]
.

Figure 1 Proportion of different clinical phenotypes of PsA patients in China The data in the Corrona registry database provides a reference for the phenotypic status of PsA patients worldwide
.

Among the 354 PsA patients who used biological agents, only 12.
6% of the patients had one phenotype, and the vast majority of patients had a mixture of multiple phenotypes [2]
.

Figure 2 Proportion of different clinical phenotypes of PsA patients using biological agents in the Corrona registry database Prof.
Zhuoli Zhang pointed out that the use of different assessment tools for different disease phenotypes can help to more accurately determine the extent and severity of disease involvement, and to evaluate therapeutic effect
.

Figure 3 Assessment tools for different clinical phenotypes of PsA PsA is a systemic disease, in addition to skin lesions and joint symptoms, patients often have metabolic syndrome, cardiovascular disease, uveitis, digestive system, fatigue, anxiety/depression This further exacerbates the complexity of PsA
.

 A Chinese study included 162 patients with PsA who met CASPAR criteria, 44 (27.
1%) with metabolic syndrome, 36 (22.
2%) with hypertension, and 28 (17.
2%) with diabetes
.

It was found that PsA patients with metabolic syndrome, hypertension or diabetes were older and had higher disease activity (p < 0.
001) [3]
.

Another systematic review included 18 relevant literatures and a total of 724 patients with PsA.
The results showed that the incidence of metabolic syndrome was 23.
5% to 62.
9%, and the incidence of hypertension was 66.
8% [4]
.

The enemy is the first: Make good use of imaging examinations, early diagnosis The diverse manifestations of diseases have brought huge challenges to clinical diagnosis
.

How to achieve early diagnosis and screening? Professor Zhang Zhuoli pointed out that in the process of development and evolution from psoriasis to PsA, it needs to go through multiple stages of preclinical, subclinical, and prodromal stages, and finally develop into PsA that meets the diagnostic criteria
.

 A study published in Nature Review rheumatology showed that skin lesions in specific areas of psoriasis (eg, scalp psoriasis, reverse psoriasis, and nail psoriasis) are associated with an increased risk of developing PsA
.

Other risk factors that can lead to PsA include first-degree family history of PsA, severe psoriasis, obesity, subclinical muscle and joint inflammation, and serum markers such as type17 cells, CD8+ cells, osteoclast precursor cells, CXCL10,
etc.

These all help predict which psoriasis patients are more likely to develop PsA [5]
.

 A study conducted by Professor Zhang Zhuoli's team also showed that obesity, trauma, etc.
and the incidence of PsA have a significant correlation
.

This brings important hints for the clinical management of psoriasis: reminding patients to change their life>
.

 As early as 2009, studies have shown that the incidence of PsA in patients with psoriasis increases with the duration of the disease [7]
.

The cohort study conducted by Professor Zhang Zhuoli's team showed that the median time from psoriasis to PsA was about 7 years [1]
.

 In addition, Prof.
Zhuoli Zhang emphasized that the rational application of imaging technology is helpful for the early diagnosis of PsA
.

Imaging techniques can help detect the characteristic changes of early psoriatic joints, such as synovitis
.

A study published in 2012 used ultrasound/MRI to screen psoriasis patients and found that the incidence of subclinical tendonitis/synovitis was significantly higher than that of healthy controls, and psoriasis patients with nail lesions were more likely to develop psoriasis.
Subclinical enthesitis [8]
.

 A joint Chinese-UK study included 66 patients with suspected or early PsA who underwent physical examination and ultrasonography to compare their ability to diagnose PsA early
.

The results of the study, reported at the 2021 European League Against Rheumatism (EULAR) annual meeting [9]: Ultrasound-based CASPAR criteria were more specific than physical examination-based CASPAR criteria (96.
7% vs 53.
3%) , the sensitivity was slightly lower (91.
7% vs 97.
2%)
.

 The earliest 36 patients were diagnosed with PsA
.

Compared with non-PsA patients, Nail changes, X-ray new bone formation, synovitis, tenosynovitis and enthesitis were significantly higher in PsA patients (p < 0.
001)
.

 Logistic regression analysis showed that nail changes, X-ray new bone formation, ultrasound tenosynovitis and ultrasound enthesitis were all risk factors for predicting the diagnosis of PsA
.

 The study confirmed that ultrasonography can improve the specificity of CASPAR criteria compared to physical examination
.

Combined with nail changes, X-ray new bone formation, ultrasound tenosynovitis and ultrasound enthesitis can improve the diagnosis of early PsA [9]
.

 An Italian single-center cross-sectional study, also reported at EULAR 2021, compared A1 trochlear inflammation on Doppler ultrasound in patients with PsA and RA, and analyzed the relationship between A1 trochlear inflammation and the modified disease activity index for psoriatic arthritis (DASPA).
correlation
.

The results showed that compared with RA patients, A1 trochlear inflammation was more common in PsA patients (p=0.
03)
.

 Eighty-eight percent of PsA patients with at least one A1 trochlear inflammation had moderate to high disease activity
.

  Linear regression analysis showed that A1 trochitis was significantly associated with higher DASPA score (β=0.
43, p=0.
03)
.

Studies have shown that A1 trochlear inflammation is more common in PsA, and can be used as a feature of PsA to distinguish it from RA; ultrasound A1 trochlear inflammation and PsA activity are significantly positively correlated, suggesting that we may give more aggressive treatment to patients with A1 trochlear inflammation under ultrasound [ 10]
.

 PsA usually starts with skin symptoms
.

How to help dermatologists identify PsA patients earlier? A research group from Italy designed the HERACLES questionnaire, which covers seven questions related to joint symptoms
.

The questionnaire was used to investigate 759 patients with psoriasis, of which 524 were transferred to the Department of Rheumatology and Immunology, and 73 of them were diagnosed with PsA after examination by a rheumatologist
.

Analysis of the data showed that if 3 points (score range of 0-8 points) was used as the cut-off value, the sensitivity was 66% and the specificity was 75%, suggesting that the questionnaire was helpful for the early diagnosis of PsA
.

 Adapting to Individual Conditions: Personalized Decision-Making Assists Treatment to Standardize Prof.
Zhang Zhuoli pointed out that the concept of standard-achieving treatment has been widely implemented in the treatment of rheumatic immune diseases, and the same is true in the field of PsA
.

 The EULAR PsA drug treatment recommendation updated in 2019 pointed out that for patients with active PsA who have been diagnosed, the clinical phenotype should be determined first, the corresponding treatment drugs should be selected, and close follow-up should be followed during the treatment process.
Or patients who do not reach the target within 6 months, should upgrade the treatment plan [11]
.

Figure 4 The recommended treatment process for the 2019 EULAR PsA drug treatment Professor Zhang Zhuoli emphasized that the existence of enthesitis is often underestimated
.

In the cohort study conducted by Professor Zhang Zhuoli's team, physical examination showed that only 6% of the patients had enthesitis, while ultrasonography showed that 171 (56.
8%) patients had enthesitis [1]
.

This suggests that ultrasound-assisted examination can help doctors more accurately determine the clinical phenotype of PsA patients and guide clinical decision-making
.

 Professor Zhang Zhuoli introduced that the 2019 EULAR PsA drug treatment recommendations mainly include [11]: 1.
The treatment goal of PsA is to achieve remission, or to reduce disease activity through regular disease activity assessment and appropriate adjustment of the treatment plan
.

2.
Non-steroidal anti-inflammatory drugs (NSAIDs) can be used to relieve symptoms and signs
.

3.
Local hormone injection can be used as adjuvant therapy for PsA
.

Systemic corticosteroids should be used with caution and the lowest effective dose is recommended
.

4.
For patients with polyarthritis, traditional disease-modifying antirheumatic drugs (csDMARD) should be started as soon as possible, and methotrexate (MTX) should be the first choice for patients with skin lesions
.

5.
In patients with mono/oligoarthritis, especially those with poor prognostic factors such as structural damage, elevated ESR/CRP, dactylitis or nail involvement, csDMARD should be considered
.

6.
For patients with peripheral arthritis who are ineffective against ≥1 csDMARDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be started; IL-17 or IL-12/23 inhibitors may be the first choice for skin involvement
.

7.
In patients with peripheral arthritis and insufficient response to ≥1 csDMARD and ≥1 bDMARD, or when bDMARD is not applicable, JAK inhibitors can be considered
.

8.
For patients with mild disease, ≥ 1 csDMARD is ineffective, and bDMARD and JAK inhibitors are not suitable, PDE4 inhibitors can be considered
.

9.
Patients with established enthesitis who are not responding to NSAIDs or topical steroid injections should be considered for bDMARD therapy
.

10.
For patients with axial involvement, if the response to NSAIDs is poor, bDMARD therapy should be considered, and tumor necrosis factor (TNF) inhibitors can be used according to current practice; IL-17 inhibitors may be the first choice for skin involvement
.

11.
For patients with poor efficacy or intolerance to bDMARDs, consideration should be given to switching to another bDMARD or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs)
.

12.
In patients with sustained remission, careful and gradual DMARD reduction may be considered
.

 In recent years, PsA-targeted therapy drugs have emerged in large numbers, bringing a wealth of options for disease treatment
.

A review summarizes the efficacy results of different targeted drugs as follows [12]: Figure 5 Summary of efficacy results of different targeted drugs in the treatment of PsA Innovative drugs also improve the treatment compliance rate of PsA
.

A 15-year prospective study from Spain included 101 patients with PsA to assess the proportion of patients who maintained low disease activity (LDA) after starting their first biologic therapy
.

The results showed that after the patients started biologic therapy, the percentage of reaching the target increased significantly [13]
.

 In order to evaluate whether there is a treatment window period in patients with early PsA, a German retrospective study included 90 patients with PsA who received DMARD/hormonal naïve treatment and were divided into three groups: very early group (duration ≤3 months), early group (3< DAS28, EGA, fatigue and morning stiffness were compared in different groups
.

The results showed that in the three groups of patients, DAS28 and EGA were significantly decreased at 3-year follow-up compared with baseline (P<0.
006)
.

The 3-year end-point follow-up results showed that compared with the early group, DAS28 (P<0.
04) and EGA (P<0.
05) were significantly lower in the very early group
.

Compared with the late group, the very early group had more significant differences in DAS28 (P<0.
007), morning stiffness (P<0.
001), EGA (P<0.
05), and fatigue (P<0.
006)
.

 It can be seen that there are significant differences in the 3-year outcomes of the three groups of patients, especially between the early and late groups, suggesting the need for early intervention in PsA
.

 A cross-sectional survey of 2238 patients with PsA in Europe and the United States was conducted to assess the impact of disease recurrence on quality of life and work
.

The results showed that up to one-third of patients had a recurrence of PsA in the current or the past 1 year, which significantly affected patients' quality of life, work efficiency, and could lead to disability and pain
.

Among them, patients with moderate to severe PsA have a higher risk of recurrence, and patients who start biologic therapy after diagnosis have a lower risk of recurrence [14]
.

In 2004, Brinkmann et al.
found that after activation, neutrophils can release a network structure composed of DNA and histones to capture and kill pathogenic microorganisms.
Thus, a new sterilization method for neutrophils—“neutrophil extracellular mesh traps” (NETs) is proposed
.

 This new defense mode is different from necrosis and apoptosis.
It traps and kills pathogenic microorganisms and is accompanied by its own death, which is called NETosis[15]
.

The myeloperoxidase (MPO)-DNA complex is a specific marker of NETosis
.

 It is worth mentioning that Professor Zhang Zhuoli's team explored the role of NETosis in the pathogenesis of psoriasis/PsA
.

The results showed that MPO-DNA levels in psoriasis/PsA patients were significantly higher than those in healthy controls (p < 0.
001), and MPO-DNA levels were positively correlated with DAPSA score and its components (p < 0.
05)
.

 After 12 weeks of treatment, MPO-DNA levels were significantly reduced with disease improvement, and this decrease was significantly correlated with ACR50 and PASI 50 responses
.

The investigators attempted to use baseline MPO-DNA levels to predict ACR70 and PASI 75 responses at 12 weeks of treatment.
The results showed that both baseline MPO-DNA levels and their changes from baseline to 12 weeks could predict efficacy
.

This suggests that NETosis plays an important role in the pathological mechanism of PsA[16]
.

 At the 2021 American College of Rheumatology (ACR) annual meeting, researchers from around the world also reported many basic research results in the field of PsA [17]: Abnormal peripheral lymphocyte subsets can cause Teffs/Tregs imbalance, which may play a role in the pathogenesis of PsA.
important role in the mechanism
.

  Pro-arginine neoepitope fragments (PROM) produced by the novel biomarker matrix metalloproteinases in PsA patients were higher than in healthy controls, and PROM may reflect connective tissue remodeling
.

 Osteopontin (OPN) increases IFNy and IL-12 production, reduces IL-10 production, and promotes the binding of osteoclasts to mineralized bone matrix
.

Antibodies to p66-UreB, p29-UreA and p54-flagelin were more common in PsA patients, suggesting their potential involvement in the pathogenesis of PsA
.

Summary PsA is a highly heterogeneous disease with 6 phenotypes, which seriously affects the quality of life and work efficiency of patients
.

Imaging technology helps to improve the accuracy of early diagnosis of PsA patients
.

The heterogeneity of the disease determines the diversity of assessment methods.
In clinical practice, individual or overall assessment methods should be adopted in a targeted manner to evaluate the disease activity in a single field or as a whole and assist treatment decisions
.

Biologic therapy can bring multiple benefits to patients with PsA
.

The discovery of multiple novel biomarkers helps advance understanding of disease and future treatments
.

Reference: [1] Zhibo Song, et al.
Clinical Characteristics of Psonatic Arthritis in Chinese Patients: A Cross-Sectional Study.
Rheumatol Ther 2021;8:1845-57.
[2]Dr Laura Coates.
To Lump or to split? -PsA outcome assessment in clinical practice and trials.
EULAR Congress 2021.
[3] Li Borui, Deng Xuexiang, Song Zhibo, Li Guangtao, Zhang Zhuoli.
The prevalence of metabolic syndrome in patients with psoriatic arthritis and its components and clinical Association study of characteristics.
Chinese Journal of Rheumatology, 2021.
[4] Urruticoechea-Arana, et al.
EULAR 2020.
#FRI0364.
[5] Nature Review rheumatology 2019.
[6] Wenhui Xie, Zhuoli Zhang.
Journal of American Academy of Dermotology.
2020.
[7]Wilson FC, et al.
Arthritis Rheum,2009,15:61(2):233-9.
[8]Ann Rheum Dis.
2012:71:553-558.
[9]Geng Y , et al.
EULAR 2021.
#SAT0562.
[10]Smerilli G,et al.
EULAR 2021.
#SAT0439.
[11]Gossec L,et al.
Ann Rheum Dis.
2020 Jun;79(6):700-712.
[12] Kerschbaumer, et al.
Ann Rheum Dis.
2020; 79:778-786.
[13] Benavent D.
, et al.
EULAR 2021.
#AB0741.
[14] Orbal, et al.
EULAR 2020.
#AB0619.
[15] Zhang Sigong,Tian Xiaolan, Shu Xiaoming, et al.
A new understanding of the pathogenic role of neutrophils in autoimmune diseases[J].
Chinese Journal of Rheumatology, 2013, 17(7):5.
[16]Borui Li,Guangtao Li,Zhuoli Zhang.
Arthritis Research&Therapy.
2021.
[17]ACR Aunnual meeting.
2021.
Expert Profile Professor Zhang Zhuoli, Director of the Department of Rheumatology and Immunology, Peking University First Hospital, and Doctoral Supervisor, Vice Chairman and Secretary General of the Chinese Society of Rheumatology, Vice Chairman of the Beijing Rheumatology Society The head of the imaging group of the Rheumatology and Immunology Committee of the Chinese Medical Association has received more than 20 scientific research grants, won many awards, and published more than 300 articles