Diagnosing psoriatic arthritis: A case report and review highlighting the role of imaging despite normal CRP values

Diagnosing psoriatic arthritis: A case report and review highlighting the role of imaging despite normal CRP values | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Diagnosing psoriatic arthritis: A case report and review highlighting the role of imaging despite normal CRP values Ebru YILMAZ This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5668916/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Psoriatic arthritis (PsA) is an autoimmune disease characterized by the inflammation of the skin (psoriasis), entheses (enthesitis) and joints (arthritis). Although PsA is predominantly associated with peripheral arthritis and enthesitis, a subset of PsA patients have axial disease. Generally, nonspecific markers of active inflammation, such as elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), are recommended as laboratory markers to promote the diagnosis and measure disease activity in PsA. However, CRP levels do not correlate strongly with disease activity in PsA. This may delay treatment in patients who have active disease despite normal CRP levels. This article presents a case of a patient diagnosed with PsA despite normal CRP levels, emphasizing the importance of imaging in diagnosis and management. Rheumatology Psoriatic arthritis enthesitis imaging methods Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Psoriatic arthritis (PsA) is an autoimmune disease characterized by the inflammation of the skin (psoriasis), entheses (enthesitis) and joints (arthritis). Although PsA is predominantly associated with peripheral arthritis and enthesitis, a subset of PsA patients have axial disease ( 1 ). In approximately 85% of patients, PsA develops long after psoriasis, but in 10–20% of patients, PsA symptoms occur simultaneously or before psoriasis ( 2 ). There is no specific diagnostic test for PsA, and diagnosis is based on the presence of clinical features of inflammatory peripheral or axial arthritis, enthesitis, dactylitis, and skin/nail psoriasis (i.e. pittings and onycholysis) in the absence of rheumatoid factor (RF). Laboratory tests to assess inflammation and imaging can support the diagnostic process. Generally, nonspecific markers of active inflammation, such as elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), are recommended as laboratory markers to promote the diagnosis and measure disease activity in PsA ( 1 ). However, CRP levels have not been shown to increase consistently with disease activity in PsA ( 1 , 3 , 4 ). This may delay treatment in patients who have active disease despite normal CRP levels. CRP is an acute-phase protein produced by the liver in response to inflammation and regulated by pro-inflammatory cytokines, particularly interleukin(IL)-6. Elevated CRP levels are typically indicative of systemic inflammation and are used as a diagnostic and prognostic marker in various inflammatory diseases, including rheumatic diseases, infections, and cardiovascular diseases ( 5 ). A systematic review found that only about 40–50% of PsA patients had elevated CRP levels and CRP levels in PsA do not correlate strongly with disease activity ( 2 ). PsA has a distinctive pathophysiology that may explain the different behavior of inflammatory markers such as CRP. Firstly, PsA is predominantly driven by the interleukin(IL)-23/Th17 axis, with IL-17 and IL-23 playing crucial roles rather than IL-6 and tumor necrosis factor-alpha (TNF-α). In particular, beta-defensin 2 and lipocalin 2, mediators regulated by IL-17 produced by innate immune cells, are found in the circulation at much higher levels than IL-17. Both appear to be strongly associated with skin and entheseal disease, but not with joint disease. Moreover, IL-8, which is important for neutrophil activation, and molecules associated with innate immune system activation such as calprotectin, cathelicidin/LL-37, and pentraxin 3, which triggers macrophage activation, are involved in psoriatic disease ( 6 ). Secondly, PsA often involves enthesitis, the inflammation of entheses (the sites where tendons or ligaments insert into the bone). Enthesitis may not elicit a strong systemic inflammatory response, thus not significantly elevating CRP levels ( 7 ). Thirdly, PsA tends to have more localized rather than systemic inflammation. Localized inflammation might not provoke a substantial acute-phase response, leading to normal CRP levels ( 8 ). Since clinicians often rely on CRP in diagnosing inflammatory conditions, normal CRP levels can sometimes mask underlying diseases, leading to delays in treatment. This necessitates a comprehensive clinical evaluation, including imaging and other biomarkers, to accurately diagnose PsA. Moreover, understanding that CRP is not a reliable marker in PsA can influence treatment strategies. Clinicians should consider the whole clinical picture, including patient-reported symptoms, physical examination findings, and imaging results, rather than relying solely on CRP levels. This article presents a case of a patient diagnosed with PsA despite normal CRP levels, emphasizing the importance of imaging in diagnosis and management. Case report A 50-year-old female patient applied to the Physical Medicine and Rehabilitation department with complaints of knees, shoulders, hands, and feet pain for 3 years. At first, she experienced knee pain at rest (especially sitting) and in the night, but over time, she started to have knee pain while walking as well. She had heel pain when placing his feet on the ground. She also had a limitation in the right shoulder and morning stiffness in her hands for about 30 minutes. Her right shoulder pain got aggravated with movement. She only reported mild swelling in her right knee. She also stated that she had itching and peeling lesions on her palms for 3 years, triggered by stress and certain foods (especially tomatoes and hot spices). She had hypertension and hypothyroidism on history. Moreover, she had family history of psoriasis. On physical examination, there was a limitation at the end of the range of motion of the right shoulder; muscle strength and neurological examination were also normal. She had mild swelling in the right knee and there was tenderness in both pes anserinus and Achilles tendons. Squeeze test, sacroiliac compression tests, FABER (flexion-abduction-external rotation of the hip) and FADIR (flexion-adduction-internal rotation of the hip) tests were positive bilaterally. Her measures of modified Schober test, chest expansion, tragus-wall distance, occiput-wall distance, and hand-ground distance were normal. The laboratory test results were as follows: CRP 0.2 mg/L (0.0–5.0); erythrocyte sedimentation rate (ESR) 4 mm/min (0–20); rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), antinuclear antibody (ANA), anti-SSA (Ro), anti-SSB (La), anti-Scl70, anti-double-stranded DNA (anti-ds-DNA), anti-neutrophilic cytoplasmic antibody (ANCA) and HLA-B27 were all negative and complement dosage also was normal. The infective panels such as Brucella and Salmonella tube agglutination, hepatitis panel, HIV/AIDS and VDRL tests were all negative. Tumor markers also were negative. Bilateral hand radiography was normal. There was a significant narrowing of the right medial joint space, calcifications in the medial aspect of the left knee, and enthesopathic changes in the left tuberosity of the tibia in plain and lateral radiographs of bilateral knee (Fig. 1 ). Moreover, plain radiographs of shoulders showed a calcification on the right greater tubercle (Fig. 2 ). There were bilateral heel spur and enthesopathic changes on the localization of the insertion of Achilles tendon in bilateral calcaneus in lateral radiograph of bilateral foot and ankle (Fig. 3 ). In the lateral cervical radiograph, there was a syndesmophyte between both C4-C5 and C6-C7 vertebrae (Fig. 3 ). Plain and lateral radiographs of the lumbar spine showed suspicious sacroiliitis at the bilateral sacroiliac joints and a syndesmophyte between both L3-L4 and L4-L5 vertebrae (Fig. 4 ). The magnetic resonance imaging (MRI) of sacroiliac joints was performed but no sacroiliitis was detected (Fig. 5 ). The patient was diagnosed with PsA according to the the CASPAR (Classification Criteria for Psoriatic Arthritis) criteria ( 9 ). The patients received Celecoxib (200 mg/day p.o.), methotrexate (15 mg/weekly s.c.) and folic acid (5 mg/weekly p.o.). After treatment, knee, shoulder, hand, and feet pain relieved and the limitation in the right shoulder and the itching in the palms also decreased. However, the patient complained of nausea in the second month of methotrexate treatment. Since the patient did not want to continue this treatment, methotrexate was discontinued and leflunomide (20 mg/day p.o.) was started. During the 1-year follow-up period, the patient's symptoms improved with this treatment. There were no side effects related to the drug. Discussion This case illustrates a critical point in the diagnosis of PsA: the reliance on CRP levels alone can be misleading. Many patients with PsA may have normal inflammatory markers, particularly in the early stages of the disease. Imaging techniques can play a crucial role in identifying inflammatory changes that may not be evident through traditional laboratory tests. Although inflammation in psoriasis and PsA is thought to be systemic in nature, the burden of systemic inflammation in psoriatic disease is difficult to quantify. Therefore, CRP levels, commonly used to quantify systemic inflammation, are often low or absent in psoriatic disease. This may depend on whether the skin, entheses, or joints are primarily affected and the specific mediators of inflammation at these sites. CRP is usually normal in skin and entheseal disease, whereas CRP elevations are generally limited to synovial disease (joint swelling). However, only about one-third of patients with arthritis have elevated CRP ( 6 ). A study by Gialouri et al found that more than half of PsA patients had normal CRP values that did not consistently indicate remission or low minimal disease activity. Therefore, it was stated that CRP should be interpreted with caution in clinical decision-making ( 8 ). The measurement of CRP levels has an indirect effect on disease activity and response to treatment, potentially guiding clinical decisions. Although elevated CRP levels are useful as an individual predictor of disease progression, response to treatment, and cardiovascular comorbidities, the current conflicting findings are not yet sufficient to allow CRP to play a significant role in the treatment decision-making process ( 3 ). In particular, IL-6, the primary inducer of CRP, does not play a critical role in these diseases. In daily practice, clinicians should be aware that CRP alone should not be an important factor in treatment decision-making because CRP may not be elevated in a large group of patients. Morever, CRP deficiency does not imply the absence of systemic inflammation, indicating that different tools and markers are needed to diagnose the disease ( 3 , 6 ). The assessment of radiographic progression in the long-term impact of disease is an important factor in considering available advanced treatment options ( 3 ). This case emphasizes the need for a comprehensive approach to diagnosing PsA, incorporating both clinical evaluation and imaging studies, especially when inflammatory markers are normal. The enthesis is thought to be the starting point of inflammation in PsA and then triggers secondary joint synovitis and subsequent joint damage ( 2 , 8 ). Furthermore, enthesitis in PsA patients is significantly associated with widespread pain, fatigue, poor functional status, and sleep disturbance ( 2 ). Therefore, the imaging of the enthesitis suggests that the inflammatory process may begin long before the clinical symptoms and signs of PsA are detected. Moreover, aging, increasing body mass index, and higher physical activity may lead to more entheseal inflammation and damage due to biomechanical forces. The approximately four times higher rate of entheseal attachment damage in patients with PsA than in ankylosing spondylitis supports the deep Koebner phenomenon at the level of the joints and enthesis ( 8 ). Enthesitis is emerging as an important marker that is necessary both to differentiate PsA from other types of arthritis and to determine the severity of the disease ( 2 ). The clinical assessment of entheses can be determined tenderness and general soft tissue swelling, but unable to detect more specific disease features such as tendon thickening, bursitis, bony erosions, enthesophytes, or calcifications being commonly associated with enthesitis pathology ( 2 , 10 ). Thus, imaging of the enthesis may potentially be helpful in investigating the preclinical phases of PsA ( 11 ). Based on clinical symptoms and imaging findings of widespread enthesitis, the case was diagnosed with PsA despite the normal CRP levels (Fig. 6 ). On conventional radiography, signs of enthesitis have been described as irregularities in the bone cortex, erosions, entheseal soft tissue calcifications, and new bone formation. These signs are advanced signs of enthesitis, and early signs of enthesitis can be detected by ultrasound (i.e. tendon thickening, hypoechogenicity, loss of fibrillar architecture, bony erosion, calcifications, enthesophytes, bursitis, and increased Doppler activity) and magnetic resonance imaging (MRI) (i.e. tendon enlargement, loss of flattened hypointense appearance, focal thickening and rounded configuration at the insertion site, and perienthesal bone marrow edema) ( 2 ). In the axial skeleton involvement of PsA, unlike ankylosing spondylitis, unilateral sacroiliitis and paramarginal syndesmophytes as well as vertical syndesmophytes are seen ( 1 ). Vertical syndesmophytes are the vertically oriented ossification process of the annulus fibrosis or anterior longitudinal ligament, whereas paramarginal syndesmophytes involve the horizontally oriented ossification of soft tissues around the vertebral corners. It should also be noted that paramarginal syndesmophytes can be confused with osteophytes ( 12 ). Especially in the aging population, it can be difficult to distinguish osteoarthritic changes from spondyloarthritis progression during the course of the disease ( 12 , 13 ). Improving the ability to distinguish these conditions radiographically will help clinicians approach patients correctly and make the correct diagnosis ( 12 ). Although sacroiliitis could not be detected with MRI in this case, paramarginal syndesmophytes were present in the cervical and lumbar vertebrae on X-ray imaging. PsA is a chronic disease that can lead to significant joint damage and disability. If PsA is diagnosed correctly, early diagnosis and treatment can have positive outcomes for patients. A 6-month delay in PsA diagnosis has been associated with poorer long-term radiographic and functional outcomes ( 2 ). A study conducted by Henkemans et al. found that patients with female gender, enthesitis, chronic low back pain, and normal CRP values ​​had a longer diagnostic delay, whereas patients with arthritis and dactylitis had a shorter diagnostic delay. Furthermore, patients with longer diagnostic delays had higher pain and patient-reported outcomes and were less likely to achieve remission in this study. The physician delay for PsA diagnosis was also significantly longer than patient delay. Therefore, they proposed that the most progress in shortening the delay may be made by reducing physician delay ( 14 ). In this case, a delay of nearly 3 years in diagnosis led to significant damage to the knee joint (Fig. 1 ). The pathogenesis of PsA is complex and multifaceted, interacting with genetic predisposition, environmental triggering factors, and activation of the innate and adaptive immune systems. Even in the absence of clinically apparent lesions, an underlying dysbiotic process has been demonstrated in the cutaneous surface of patients with psoriatic disease, which may contribute to disease progression. The heterogeneity of tissues and pathogenic pathways involved in PsA results in different clinical presentations, variable progression, and different responses to treatment, posing a challenge for the overall management of the disease. Studies have shown that peripheral PsA is more common in female patients, while axial disease is more common in male patients ( 15 ). Female patients with both axial SpA and PsA tend to have more swollen joints and enthesitis, more widespread pain, longer diagnostic delay, more severe disease activity due to lower treatment efficacy, poorer quality of life, and poorer functioning compared with males. The more severe disease activity in female patients may be due to gender differences in immune mechanisms and a greater disease burden due to more widespread involvement of peripheral joints and entheses ( 16 , 17 , 18 ). On the other hand, symptoms such as peripheral involvement, widespread pain, and fatigue, which are more common in women, may lead clinicians to misdiagnose fibromyalgia or nonspecific polymyalgia ( 19 ). In women with PsA and psoriasis, involvement of critical areas such as the scalp, nails, and creases may cause more severe disease ( 20 ). Moreover, the course, severity, and treatment of psoriasis in women with SpA may be significantly affected by hormonal fluctuations during different stages of life, such as menstruation, pregnancy, postpartum, perimenopause, and menopause ( 19 , 20 ). Estrogen is known to have anti-inflammatory and immunomodulatory effects that affect both innate and adaptive immune responses. Higher estrogen concentrations tend to be associated with milder psoriasis symptoms, whereas low estrogen levels after delivery or during menopause may trigger or worsen psoriasis. In addition to hormonal effects, genetic factors may also play a role in the gender-specific manifestations and skin symptoms of PsA. Women with PsA and psoriasis have a negative impact on their quality of life because of not only the physical symptoms but also the psychological burden of the disease ( 20 ). Although the symptoms started during the menopause process, there was widespread body involvement of the disease in this case. Conclusion This case underlines the notion that CRP is not a reliable marker for PsA inflammation. The absence of elevated CRP levels in PsA underscores the unique pathophysiology of this condition compared to other inflammatory diseases like rheumatoid arthritis. The distinct cytokine profiles, localized nature of inflammation, and specific involvement of entheses in PsA contribute to this phenomenon. Recognizing these differences is crucial for accurate diagnosis, monitoring, and management of PsA, ensuring that patients receive appropriate and effective care. As awareness grows regarding the limitations of standard laboratory tests, the role of imaging in the early detection and management of PsA will become increasingly important in clinical practice. Declarations "The author (Ebru YILMAZ) obtained a statement that the patient consented to participate and publish their clinical data. Informed consent was taken from the patient." Conflicts of interest: The author declared no conflicts of interest. Informed Consent Informed consent was taken from the patient. Funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. References Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376(10):957–970. 10.1056/NEJMra1505557 Kaeley GS, Eder L, Aydin SZ, Gutierrez M, Bakewell C, Enthesitis (2018) A hallmark of psoriatic arthritis. Semin Arthritis Rheum 48(1):35–43. 10.1016/j.semarthrit.2017.12.008 Houttekiet C, de Vlam K, Neerinckx B, Lories R (2022) Systematic review of the use of CRP in clinical trials for psoriatic arthritis: a concern for clinical practice? RMD Open 8(1):e001756. 10.1136/rmdopen-2021-001756 Ogdie A, Tillett W, Booth N, Howell O, Schubert A, Peterson S et al (2022) Usage of C-Reactive Protein Testing in the Diagnosis and Monitoring of Psoriatic Arthritis (PsA): Results from a Real-World Survey in the USA and Europe. Rheumatol Ther 9(1):285–293. 10.1007/s40744-021-00420-x Sproston NR, Ashworth JJ (2018) Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol 9:754. 10.3389/fimmu.2018.00754 Sokolova MV, Simon D, Nas K, Zaiss MM, Luo Y, Zhao Y et al (2020) A set of serum markers detecting systemic inflammation in psoriatic skin, entheseal, and joint disease in the absence of C-reactive protein and its link to clinical disease manifestations. Arthritis Res Ther 22(1):26. 10.1186/s13075-020-2111-8 Schett G, Lories RJ, D'Agostino MA, Elewaut D, Kirkham B, Soriano ER et al (2017) Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol 13(12):731–741. 10.1038/nrrheum.2017.188 Gialouri CG, Evangelatos G, Pappa M, Karamanakos A, Iliopoulos A, Tektonidou MG et al (2022) Normal C-reactive protein in active psoriatic arthritis: results from real-world clinical practice. Ther Adv Musculoskelet Dis 14:1759720X221122417. 10.1177/1759720X221122417 Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673. 10.1002/art.21972 Yilmaz E, Pasin Ö (2024) Conventional radiography and correlated factors of enthesopathies of the Achilles tendon and plantar fascia in patients with axial spondyloarthritis. Reumatismo (Early access) 76(4):1–13. 10.4081/reumatismo.2024.1709 Eder L, Aydin SZ (2018) Imaging in Psoriatic Arthritis-Insights About Pathogenesis of the Disease. Curr Rheumatol Rep 20(12):77. 10.1007/s11926-018-0793-6 Gazel U, Ayan G, Hryciw N, Delorme JP, Hepworth E, Sampaio M et al (2024) Disease-specific definitions of new bone formation on spine radiographs: a systematic literature review. Rheumatol Adv Pract 8(2):rkae061. 10.1093/rap/rkae061 Maatallah K, Ammar LB, Ferjani H, Kaffel D, Hamdi W (2022) Clinical, laboratory, and radiological characteristics of patients with late-onset spondylarthritis. Egypt Rheumatol 4(1):19–23. 10.1016/j.ejr.2021.07.005 Snoeck Henkemans SVJ, de Jong PHP, Luime JJ, Kok MR, Tchetverikov I, Korswagen LA et al (2024) Window of opportunity in psoriatic arthritis: the earlier the better? RMD Open 10(1):e004062. 10.1136/rmdopen-2023-004062 Azuaga AB, Ramírez J, Cañete JD (2023) Psoriatic Arthritis: Pathogenesis and Targeted Therapies. Int J Mol Sci 24(5):4901. 10.3390/ijms24054901 Ristic B, Bonetto C, Rossini M, Fracassi E, Carletto A, Tosato S (2024) Gender differences in clinical features and quality of life of patients with axial spondyloarthritis and psoriatic arthritis. Reumatismo 76(3). 10.4081/reumatismo.2024.1779 Almousa S, Alshamaa N, Wannous H, Khder K, Qasem H (2023) Gender-related differences in axial spondyloarthritis (axSpA) patients. Egypt Rheumatol 45:13–16. 10.1016/j,ejr.2022.08.003 Yilmaz E, Toluk Ö (2024) Clinical significance of human leukocyte antigen (HLA-B27) in patients with early and late-onset axial spondyloarthritis. Egypt Rheumatol 47(1):12–15. 10.1016/j.ejr.2024.10.001 Ramonda R, Oliviero F (2024) Women and spondyloarthritis. Reumatismo 76(3). 10.4081/reumatismo.2024.1760 Cassalia F, Belloni Fortina A (2024) Psoriasis in women with psoriatic arthritis: hormonal effects, fertility, and considerations for management at different stages of life. Reumatismo 76(3). 10.4081/reumatismo.2024.1775 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5668916","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":391862336,"identity":"90f787d2-febf-40a6-ad02-72e98ed60a0d","order_by":0,"name":"Ebru YILMAZ","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYDCCAzCGBBB/AGI2dlK0MM4AaWEmRQszD4hBSAvf7QOMD3/U2OXxS/c+k7b5tU2ej5mB8cPHHNxaJM8lMBtIHEsulpxz3Ew6t++2YRszA7PkzG24tRicYWCTMGxgTtxwI41NOrfnNiNQCxszLyEtiQ31iftBWix7btsTp+Vgw+HEDRJALQw/bicS1CJ5hrHZsOHY8cQZd44xW/Y23E5uY2ZsxusXvjPMB4EhVp3YP7uN8caPP7dt57c3H/zwEY8WYPw1ILHb0EUIgz+kKB4Fo2AUjIKRAgBMUU0R7ZIK8wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-2172-2742","institution":"Bezmialem Vakif University","correspondingAuthor":true,"prefix":"","firstName":"Ebru","middleName":"","lastName":"YILMAZ","suffix":""}],"badges":[],"createdAt":"2024-12-18 11:17:37","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5668916/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5668916/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72650087,"identity":"7541224b-4188-4538-9ec9-21cbc1dcaf68","added_by":"auto","created_at":"2024-12-30 18:05:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":578841,"visible":true,"origin":"","legend":"\u003cp\u003eThe plain and lateral knees X-Ray imaging of the patient (up picture: the enthesopathic changes in the left tuberosity of the tibia in 2020; down picture: a significant narrowing of the right medial joint space, calcifications in the medial aspect of the left knee, and enthesopathic changes in the left tuberosity of the tibia in 2023)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/81e3da16b79c75052140f411.png"},{"id":72649902,"identity":"37f69a87-bc6b-4bb1-9050-a4eece60aabd","added_by":"auto","created_at":"2024-12-30 17:57:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":362266,"visible":true,"origin":"","legend":"\u003cp\u003eThe plain shoulders X-Ray imaging of the patient (a calcification on the right greater tubercle)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/a2b998e9d4a66289c5d13a28.png"},{"id":72650674,"identity":"68f831d4-a968-48ca-93ec-7a6b65cc6e7a","added_by":"auto","created_at":"2024-12-30 18:21:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":510872,"visible":true,"origin":"","legend":"\u003cp\u003eThe lateral bilateral foot and ankle and cervical X-Ray imaging of the patient (right picture: bilateral heel spur and enthesopathic changes on the localization of the insertion of Achilles tendon; left picture: a paramarginal syndesmophyte between both C4-C5 and C6-C7 vertebrae)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/6e9ce60fdb29c3a8d261fb8e.png"},{"id":72650089,"identity":"b674f6c2-ee61-4722-8c6a-b18c5f77894d","added_by":"auto","created_at":"2024-12-30 18:05:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":284006,"visible":true,"origin":"","legend":"\u003cp\u003eThe plain and lateral lumbosacral X-Ray imaging of the patient (suspicious sacroiliitis at the bilateral sacroiliac joints and a paramarginal syndesmophyte between both L3-L4 and L4-L5 vertebrae)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/a7e44510dc81127f824689e2.png"},{"id":72649914,"identity":"7426cd77-a7ce-4dde-a0de-efc1bdfa0971","added_by":"auto","created_at":"2024-12-30 17:57:50","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":300524,"visible":true,"origin":"","legend":"\u003cp\u003eThe magnetic resonance imaging (MRI) of sacroiliac joints of the patient (respectively, T1, T2, fat suppression sequences)\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/5f5bd85961d43d7c7c7144eb.png"},{"id":72649909,"identity":"783345ee-ecc2-4dc8-97f4-d6bbe5b40b8a","added_by":"auto","created_at":"2024-12-30 17:57:50","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":90858,"visible":true,"origin":"","legend":"\u003cp\u003eThe laboratory findings of the patients (past and present ESR and CRP values)\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/bfa678941b888583af5d4b23.png"},{"id":72650955,"identity":"0890a0c0-6a57-40bb-a8f7-63a63f0f4746","added_by":"auto","created_at":"2024-12-30 18:29:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2918164,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5668916/v1/b78519c8-8d26-4722-9ad3-6d56e2ace380.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eDiagnosing psoriatic arthritis: A case report and review highlighting the role of imaging despite normal CRP values\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsoriatic arthritis (PsA) is an autoimmune disease characterized by the inflammation of the skin (psoriasis), entheses (enthesitis) and joints (arthritis). Although PsA is predominantly associated with peripheral arthritis and enthesitis, a subset of PsA patients have axial disease (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In approximately 85% of patients, PsA develops long after psoriasis, but in 10\u0026ndash;20% of patients, PsA symptoms occur simultaneously or before psoriasis (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There is no specific diagnostic test for PsA, and diagnosis is based on the presence of clinical features of inflammatory peripheral or axial arthritis, enthesitis, dactylitis, and skin/nail psoriasis (i.e. pittings and onycholysis) in the absence of rheumatoid factor (RF). Laboratory tests to assess inflammation and imaging can support the diagnostic process. Generally, nonspecific markers of active inflammation, such as elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), are recommended as laboratory markers to promote the diagnosis and measure disease activity in PsA (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, CRP levels have not been shown to increase consistently with disease activity in PsA (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This may delay treatment in patients who have active disease despite normal CRP levels.\u003c/p\u003e \u003cp\u003eCRP is an acute-phase protein produced by the liver in response to inflammation and regulated by pro-inflammatory cytokines, particularly interleukin(IL)-6. Elevated CRP levels are typically indicative of systemic inflammation and are used as a diagnostic and prognostic marker in various inflammatory diseases, including rheumatic diseases, infections, and cardiovascular diseases (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). A systematic review found that only about 40\u0026ndash;50% of PsA patients had elevated CRP levels and CRP levels in PsA do not correlate strongly with disease activity (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePsA has a distinctive pathophysiology that may explain the different behavior of inflammatory markers such as CRP. Firstly, PsA is predominantly driven by the interleukin(IL)-23/Th17 axis, with IL-17 and IL-23 playing crucial roles rather than IL-6 and tumor necrosis factor-alpha (TNF-α). In particular, beta-defensin 2 and lipocalin 2, mediators regulated by IL-17 produced by innate immune cells, are found in the circulation at much higher levels than IL-17. Both appear to be strongly associated with skin and entheseal disease, but not with joint disease. Moreover, IL-8, which is important for neutrophil activation, and molecules associated with innate immune system activation such as calprotectin, cathelicidin/LL-37, and pentraxin 3, which triggers macrophage activation, are involved in psoriatic disease (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Secondly, PsA often involves enthesitis, the inflammation of entheses (the sites where tendons or ligaments insert into the bone). Enthesitis may not elicit a strong systemic inflammatory response, thus not significantly elevating CRP levels (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Thirdly, PsA tends to have more localized rather than systemic inflammation. Localized inflammation might not provoke a substantial acute-phase response, leading to normal CRP levels (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSince clinicians often rely on CRP in diagnosing inflammatory conditions, normal CRP levels can sometimes mask underlying diseases, leading to delays in treatment. This necessitates a comprehensive clinical evaluation, including imaging and other biomarkers, to accurately diagnose PsA. Moreover, understanding that CRP is not a reliable marker in PsA can influence treatment strategies. Clinicians should consider the whole clinical picture, including patient-reported symptoms, physical examination findings, and imaging results, rather than relying solely on CRP levels. This article presents a case of a patient diagnosed with PsA despite normal CRP levels, emphasizing the importance of imaging in diagnosis and management.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 50-year-old female patient applied to the Physical Medicine and Rehabilitation department with complaints of knees, shoulders, hands, and feet pain for 3 years. At first, she experienced knee pain at rest (especially sitting) and in the night, but over time, she started to have knee pain while walking as well. She had heel pain when placing his feet on the ground. She also had a limitation in the right shoulder and morning stiffness in her hands for about 30 minutes. Her right shoulder pain got aggravated with movement. She only reported mild swelling in her right knee. She also stated that she had itching and peeling lesions on her palms for 3 years, triggered by stress and certain foods (especially tomatoes and hot spices). She had hypertension and hypothyroidism on history. Moreover, she had family history of psoriasis. On physical examination, there was a limitation at the end of the range of motion of the right shoulder; muscle strength and neurological examination were also normal. She had mild swelling in the right knee and there was tenderness in both pes anserinus and Achilles tendons. Squeeze test, sacroiliac compression tests, FABER (flexion-abduction-external rotation of the hip) and FADIR (flexion-adduction-internal rotation of the hip) tests were positive bilaterally. Her measures of modified Schober test, chest expansion, tragus-wall distance, occiput-wall distance, and hand-ground distance were normal. The laboratory test results were as follows: CRP 0.2 mg/L (0.0\u0026ndash;5.0); erythrocyte sedimentation rate (ESR) 4 mm/min (0\u0026ndash;20); rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), antinuclear antibody (ANA), anti-SSA (Ro), anti-SSB (La), anti-Scl70, anti-double-stranded DNA (anti-ds-DNA), anti-neutrophilic cytoplasmic antibody (ANCA) and HLA-B27 were all negative and complement dosage also was normal. The infective panels such as Brucella and Salmonella tube agglutination, hepatitis panel, HIV/AIDS and VDRL tests were all negative. Tumor markers also were negative. Bilateral hand radiography was normal. There was a significant narrowing of the right medial joint space, calcifications in the medial aspect of the left knee, and enthesopathic changes in the left tuberosity of the tibia in plain and lateral radiographs of bilateral knee (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Moreover, plain radiographs of shoulders showed a calcification on the right greater tubercle (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There were bilateral heel spur and enthesopathic changes on the localization of the insertion of Achilles tendon in bilateral calcaneus in lateral radiograph of bilateral foot and ankle (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the lateral cervical radiograph, there was a syndesmophyte between both C4-C5 and C6-C7 vertebrae (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Plain and lateral radiographs of the lumbar spine showed suspicious sacroiliitis at the bilateral sacroiliac joints and a syndesmophyte between both L3-L4 and L4-L5 vertebrae (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The magnetic resonance imaging (MRI) of sacroiliac joints was performed but no sacroiliitis was detected (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The patient was diagnosed with PsA according to the the CASPAR (Classification Criteria for Psoriatic Arthritis) criteria (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The patients received Celecoxib (200 mg/day p.o.), methotrexate (15 mg/weekly s.c.) and folic acid (5 mg/weekly p.o.). After treatment, knee, shoulder, hand, and feet pain relieved and the limitation in the right shoulder and the itching in the palms also decreased. However, the patient complained of nausea in the second month of methotrexate treatment. Since the patient did not want to continue this treatment, methotrexate was discontinued and leflunomide (20 mg/day p.o.) was started. During the 1-year follow-up period, the patient's symptoms improved with this treatment. There were no side effects related to the drug.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates a critical point in the diagnosis of PsA: the reliance on CRP levels alone can be misleading. Many patients with PsA may have normal inflammatory markers, particularly in the early stages of the disease. Imaging techniques can play a crucial role in identifying inflammatory changes that may not be evident through traditional laboratory tests.\u003c/p\u003e \u003cp\u003eAlthough inflammation in psoriasis and PsA is thought to be systemic in nature, the burden of systemic inflammation in psoriatic disease is difficult to quantify. Therefore, CRP levels, commonly used to quantify systemic inflammation, are often low or absent in psoriatic disease. This may depend on whether the skin, entheses, or joints are primarily affected and the specific mediators of inflammation at these sites. CRP is usually normal in skin and entheseal disease, whereas CRP elevations are generally limited to synovial disease (joint swelling). However, only about one-third of patients with arthritis have elevated CRP (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). A study by Gialouri et al found that more than half of PsA patients had normal CRP values that did not consistently indicate remission or low minimal disease activity. Therefore, it was stated that CRP should be interpreted with caution in clinical decision-making (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The measurement of CRP levels has an indirect effect on disease activity and response to treatment, potentially guiding clinical decisions. Although elevated CRP levels are useful as an individual predictor of disease progression, response to treatment, and cardiovascular comorbidities, the current conflicting findings are not yet sufficient to allow CRP to play a significant role in the treatment decision-making process (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In particular, IL-6, the primary inducer of CRP, does not play a critical role in these diseases. In daily practice, clinicians should be aware that CRP alone should not be an important factor in treatment decision-making because CRP may not be elevated in a large group of patients. Morever, CRP deficiency does not imply the absence of systemic inflammation, indicating that different tools and markers are needed to diagnose the disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The assessment of radiographic progression in the long-term impact of disease is an important factor in considering available advanced treatment options (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). This case emphasizes the need for a comprehensive approach to diagnosing PsA, incorporating both clinical evaluation and imaging studies, especially when inflammatory markers are normal.\u003c/p\u003e \u003cp\u003eThe enthesis is thought to be the starting point of inflammation in PsA and then triggers secondary joint synovitis and subsequent joint damage (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Furthermore, enthesitis in PsA patients is significantly associated with widespread pain, fatigue, poor functional status, and sleep disturbance (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Therefore, the imaging of the enthesitis suggests that the inflammatory process may begin long before the clinical symptoms and signs of PsA are detected. Moreover, aging, increasing body mass index, and higher physical activity may lead to more entheseal inflammation and damage due to biomechanical forces. The approximately four times higher rate of entheseal attachment damage in patients with PsA than in ankylosing spondylitis supports the deep Koebner phenomenon at the level of the joints and enthesis (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Enthesitis is emerging as an important marker that is necessary both to differentiate PsA from other types of arthritis and to determine the severity of the disease (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The clinical assessment of entheses can be determined tenderness and general soft tissue swelling, but unable to detect more specific disease features such as tendon thickening, bursitis, bony erosions, enthesophytes, or calcifications being commonly associated with enthesitis pathology (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Thus, imaging of the enthesis may potentially be helpful in investigating the preclinical phases of PsA (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Based on clinical symptoms and imaging findings of widespread enthesitis, the case was diagnosed with PsA despite the normal CRP levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn conventional radiography, signs of enthesitis have been described as irregularities in the bone cortex, erosions, entheseal soft tissue calcifications, and new bone formation. These signs are advanced signs of enthesitis, and early signs of enthesitis can be detected by ultrasound (i.e. tendon thickening, hypoechogenicity, loss of fibrillar architecture, bony erosion, calcifications, enthesophytes, bursitis, and increased Doppler activity) and magnetic resonance imaging (MRI) (i.e. tendon enlargement, loss of flattened hypointense appearance, focal thickening and rounded configuration at the insertion site, and perienthesal bone marrow edema) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In the axial skeleton involvement of PsA, unlike ankylosing spondylitis, unilateral sacroiliitis and paramarginal syndesmophytes as well as vertical syndesmophytes are seen (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Vertical syndesmophytes are the vertically oriented ossification process of the annulus fibrosis or anterior longitudinal ligament, whereas paramarginal syndesmophytes involve the horizontally oriented ossification of soft tissues around the vertebral corners. It should also be noted that paramarginal syndesmophytes can be confused with osteophytes (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Especially in the aging population, it can be difficult to distinguish osteoarthritic changes from spondyloarthritis progression during the course of the disease (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Improving the ability to distinguish these conditions radiographically will help clinicians approach patients correctly and make the correct diagnosis (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Although sacroiliitis could not be detected with MRI in this case, paramarginal syndesmophytes were present in the cervical and lumbar vertebrae on X-ray imaging.\u003c/p\u003e \u003cp\u003ePsA is a chronic disease that can lead to significant joint damage and disability. If PsA is diagnosed correctly, early diagnosis and treatment can have positive outcomes for patients. A 6-month delay in PsA diagnosis has been associated with poorer long-term radiographic and functional outcomes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). A study conducted by Henkemans et al. found that patients with female gender, enthesitis, chronic low back pain, and normal CRP values ​​had a longer diagnostic delay, whereas patients with arthritis and dactylitis had a shorter diagnostic delay. Furthermore, patients with longer diagnostic delays had higher pain and patient-reported outcomes and were less likely to achieve remission in this study. The physician delay for PsA diagnosis was also significantly longer than patient delay. Therefore, they proposed that the most progress in shortening the delay may be made by reducing physician delay (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In this case, a delay of nearly 3 years in diagnosis led to significant damage to the knee joint (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe pathogenesis of PsA is complex and multifaceted, interacting with genetic predisposition, environmental triggering factors, and activation of the innate and adaptive immune systems. Even in the absence of clinically apparent lesions, an underlying dysbiotic process has been demonstrated in the cutaneous surface of patients with psoriatic disease, which may contribute to disease progression. The heterogeneity of tissues and pathogenic pathways involved in PsA results in different clinical presentations, variable progression, and different responses to treatment, posing a challenge for the overall management of the disease. Studies have shown that peripheral PsA is more common in female patients, while axial disease is more common in male patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Female patients with both axial SpA and PsA tend to have more swollen joints and enthesitis, more widespread pain, longer diagnostic delay, more severe disease activity due to lower treatment efficacy, poorer quality of life, and poorer functioning compared with males. The more severe disease activity in female patients may be due to gender differences in immune mechanisms and a greater disease burden due to more widespread involvement of peripheral joints and entheses (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). On the other hand, symptoms such as peripheral involvement, widespread pain, and fatigue, which are more common in women, may lead clinicians to misdiagnose fibromyalgia or nonspecific polymyalgia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In women with PsA and psoriasis, involvement of critical areas such as the scalp, nails, and creases may cause more severe disease (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Moreover, the course, severity, and treatment of psoriasis in women with SpA may be significantly affected by hormonal fluctuations during different stages of life, such as menstruation, pregnancy, postpartum, perimenopause, and menopause (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Estrogen is known to have anti-inflammatory and immunomodulatory effects that affect both innate and adaptive immune responses. Higher estrogen concentrations tend to be associated with milder psoriasis symptoms, whereas low estrogen levels after delivery or during menopause may trigger or worsen psoriasis. In addition to hormonal effects, genetic factors may also play a role in the gender-specific manifestations and skin symptoms of PsA. Women with PsA and psoriasis have a negative impact on their quality of life because of not only the physical symptoms but also the psychological burden of the disease (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Although the symptoms started during the menopause process, there was widespread body involvement of the disease in this case.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case underlines the notion that CRP is not a reliable marker for PsA inflammation. The absence of elevated CRP levels in PsA underscores the unique pathophysiology of this condition compared to other inflammatory diseases like rheumatoid arthritis. The distinct cytokine profiles, localized nature of inflammation, and specific involvement of entheses in PsA contribute to this phenomenon. Recognizing these differences is crucial for accurate diagnosis, monitoring, and management of PsA, ensuring that patients receive appropriate and effective care. As awareness grows regarding the limitations of standard laboratory tests, the role of imaging in the early detection and management of PsA will become increasingly important in clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\"The author (Ebru YILMAZ) obtained a statement that the patient consented to participate and publish their clinical data. Informed consent was taken from the patient.\"\u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflicts of interest:\u003c/h2\u003e \u003cp\u003eThe author declared no conflicts of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInformed Consent\u003c/strong\u003e \u003cp\u003e Informed consent was taken from the patient.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRitchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376(10):957\u0026ndash;970. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra1505557\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1505557\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaeley GS, Eder L, Aydin SZ, Gutierrez M, Bakewell C, Enthesitis (2018) A hallmark of psoriatic arthritis. Semin Arthritis Rheum 48(1):35\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.semarthrit.2017.12.008\u003c/span\u003e\u003cspan address=\"10.1016/j.semarthrit.2017.12.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHouttekiet C, de Vlam K, Neerinckx B, Lories R (2022) Systematic review of the use of CRP in clinical trials for psoriatic arthritis: a concern for clinical practice? RMD Open 8(1):e001756. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/rmdopen-2021-001756\u003c/span\u003e\u003cspan address=\"10.1136/rmdopen-2021-001756\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgdie A, Tillett W, Booth N, Howell O, Schubert A, Peterson S et al (2022) Usage of C-Reactive Protein Testing in the Diagnosis and Monitoring of Psoriatic Arthritis (PsA): Results from a Real-World Survey in the USA and Europe. Rheumatol Ther 9(1):285\u0026ndash;293. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40744-021-00420-x\u003c/span\u003e\u003cspan address=\"10.1007/s40744-021-00420-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSproston NR, Ashworth JJ (2018) Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol 9:754. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2018.00754\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2018.00754\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSokolova MV, Simon D, Nas K, Zaiss MM, Luo Y, Zhao Y et al (2020) A set of serum markers detecting systemic inflammation in psoriatic skin, entheseal, and joint disease in the absence of C-reactive protein and its link to clinical disease manifestations. Arthritis Res Ther 22(1):26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13075-020-2111-8\u003c/span\u003e\u003cspan address=\"10.1186/s13075-020-2111-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchett G, Lories RJ, D'Agostino MA, Elewaut D, Kirkham B, Soriano ER et al (2017) Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol 13(12):731\u0026ndash;741. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrrheum.2017.188\u003c/span\u003e\u003cspan address=\"10.1038/nrrheum.2017.188\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGialouri CG, Evangelatos G, Pappa M, Karamanakos A, Iliopoulos A, Tektonidou MG et al (2022) Normal C-reactive protein in active psoriatic arthritis: results from real-world clinical practice. Ther Adv Musculoskelet Dis 14:1759720X221122417. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1759720X221122417\u003c/span\u003e\u003cspan address=\"10.1177/1759720X221122417\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665\u0026ndash;2673. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/art.21972\u003c/span\u003e\u003cspan address=\"10.1002/art.21972\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz E, Pasin \u0026Ouml; (2024) Conventional radiography and correlated factors of enthesopathies of the Achilles tendon and plantar fascia in patients with axial spondyloarthritis. Reumatismo (Early access) 76(4):1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4081/reumatismo.2024.1709\u003c/span\u003e\u003cspan address=\"10.4081/reumatismo.2024.1709\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEder L, Aydin SZ (2018) Imaging in Psoriatic Arthritis-Insights About Pathogenesis of the Disease. Curr Rheumatol Rep 20(12):77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11926-018-0793-6\u003c/span\u003e\u003cspan address=\"10.1007/s11926-018-0793-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGazel U, Ayan G, Hryciw N, Delorme JP, Hepworth E, Sampaio M et al (2024) Disease-specific definitions of new bone formation on spine radiographs: a systematic literature review. Rheumatol Adv Pract 8(2):rkae061. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rap/rkae061\u003c/span\u003e\u003cspan address=\"10.1093/rap/rkae061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaatallah K, Ammar LB, Ferjani H, Kaffel D, Hamdi W (2022) Clinical, laboratory, and radiological characteristics of patients with late-onset spondylarthritis. Egypt Rheumatol 4(1):19\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejr.2021.07.005\u003c/span\u003e\u003cspan address=\"10.1016/j.ejr.2021.07.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSnoeck Henkemans SVJ, de Jong PHP, Luime JJ, Kok MR, Tchetverikov I, Korswagen LA et al (2024) Window of opportunity in psoriatic arthritis: the earlier the better? RMD Open 10(1):e004062. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/rmdopen-2023-004062\u003c/span\u003e\u003cspan address=\"10.1136/rmdopen-2023-004062\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzuaga AB, Ram\u0026iacute;rez J, Ca\u0026ntilde;ete JD (2023) Psoriatic Arthritis: Pathogenesis and Targeted Therapies. Int J Mol Sci 24(5):4901. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms24054901\u003c/span\u003e\u003cspan address=\"10.3390/ijms24054901\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRistic B, Bonetto C, Rossini M, Fracassi E, Carletto A, Tosato S (2024) Gender differences in clinical features and quality of life of patients with axial spondyloarthritis and psoriatic arthritis. Reumatismo 76(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4081/reumatismo.2024.1779\u003c/span\u003e\u003cspan address=\"10.4081/reumatismo.2024.1779\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmousa S, Alshamaa N, Wannous H, Khder K, Qasem H (2023) Gender-related differences in axial spondyloarthritis (axSpA) patients. Egypt Rheumatol 45:13\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j,ejr.2022.08.003\u003c/span\u003e\u003cspan address=\"10.1016/j,ejr.2022.08.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz E, Toluk \u0026Ouml; (2024) Clinical significance of human leukocyte antigen (HLA-B27) in patients with early and late-onset axial spondyloarthritis. Egypt Rheumatol 47(1):12\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejr.2024.10.001\u003c/span\u003e\u003cspan address=\"10.1016/j.ejr.2024.10.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamonda R, Oliviero F (2024) Women and spondyloarthritis. Reumatismo 76(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4081/reumatismo.2024.1760\u003c/span\u003e\u003cspan address=\"10.4081/reumatismo.2024.1760\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassalia F, Belloni Fortina A (2024) Psoriasis in women with psoriatic arthritis: hormonal effects, fertility, and considerations for management at different stages of life. Reumatismo 76(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4081/reumatismo.2024.1775\u003c/span\u003e\u003cspan address=\"10.4081/reumatismo.2024.1775\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Psoriatic arthritis, enthesitis, imaging methods","lastPublishedDoi":"10.21203/rs.3.rs-5668916/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5668916/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePsoriatic arthritis (PsA) is an autoimmune disease characterized by the inflammation of the skin (psoriasis), entheses (enthesitis) and joints (arthritis). Although PsA is predominantly associated with peripheral arthritis and enthesitis, a subset of PsA patients have axial disease. Generally, nonspecific markers of active inflammation, such as elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), are recommended as laboratory markers to promote the diagnosis and measure disease activity in PsA. However, CRP levels do not correlate strongly with disease activity in PsA. This may delay treatment in patients who have active disease despite normal CRP levels. This article presents a case of a patient diagnosed with PsA despite normal CRP levels, emphasizing the importance of imaging in diagnosis and management.\u003c/p\u003e","manuscriptTitle":"Diagnosing psoriatic arthritis: A case report and review highlighting the role of imaging despite normal CRP values","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-30 17:57:45","doi":"10.21203/rs.3.rs-5668916/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"517707d1-0f4e-4566-95c5-aae713bed80a","owner":[],"postedDate":"December 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41769096,"name":"Rheumatology"}],"tags":[],"updatedAt":"2024-12-30T17:57:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-30 17:57:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5668916","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5668916","identity":"rs-5668916","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}