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Abstract
Psoriatic arthritis (PsA), an inflammatory seronegative spondyloarthropathy is the most common co-morbidity of psoriasis (PsO), in almost 30% of cases. Delayed diagnosis and treatment of PsA may result in irreversible joint damage, significant morbidity, impaired quality of life, and several cardiometabolic and cerebrovascular co-morbidities. Dermatologists are uniquely privileged to be able to diagnose latent PsA at an early stage, as almost 80% of these patients present with pre-existing cutaneous PsO. This review provides a detailed overview of PsA along with its salient clinical features, classification criteria, screening tools, simple physical examination maneuvers, imaging findings, and therapeutic options to acquaint dermatologists and other clinicians with this morbid musculoskeletal disorder. We hope to generate awareness about this condition among dermatologists to enable proactive screening of all PsO patients for early diagnosis, initiation of appropriate treatment, and prompt referral to a rheumatologist; thus, helping to arrest PsA disease progression, irreversible joint damage, and subsequent permanent disability.
Keywords: Co-morbidity, dermatologists, psoriasis, psoriatic arthritis
Introduction 
Psoriasis (PsO) is an immune-mediated disorder, primarily affecting the skin, characterised by well-defined, scaly, erythematous plaques, and frequent nail involvement. It is a relatively common dermatological disorder, with a global point prevalence of 1–3%.[1] Additionally, multiple systemic co-morbidities have been reported, including arthritis, metabolic syndrome (which can cause cardiovascular problems), depression, cardiovascular disease, chronic kidney disease, non-alcoholic fatty liver disease, ocular diseases (uveitis), and inflammatory bowel disease.[2] Thus, PsO is considered a systemic inflammatory disorder, not restricted to the skin alone. Despite being non-fatal, this condition is associated with considerable morbidity and affects the quality of life (QoL).[3]
Psoriatic arthritis (PsA) is a musculoskeletal disorder belonging to the seronegative (rheumatoid factor negative) spondyloarthropathy group, almost always associated with cutaneous psoriatic lesions. It is the most common extra-cutaneous co-morbidity of PsO, usually affecting middle-aged males and females.[4] PsA can involve any synovial joint, with a predilection for the distal extremities. The predominant symptoms are tender, swollen joints resulting in long-term erosion. Axial involvement of the spine, enthesitis (inflammation at insertion of tendons into bone), and dactylitis ('sausage digit') are typical features. Thus, it can cause physical disability and considerably worsen QoL.[5]
While 25% PsO patients may develop PsA in their lifetime,[5] 84% of PsA patients have a history of pre-existing skin lesions.[6]Thus, dermatologists have the unique opportunity to suspect and diagnose PsA in patients with skin lesions presenting with little or no joint symptoms; as they are often the first clinicians to be consulted. As a delayed diagnosis of PsA can worsen the functional outcome of patients and increase long-term disability,[7] the role of dermatologists has become extremely important at the early stage.
In this review, we have attempted to provide an overview of PsA that may help dermatologists in diagnosing PsA at the earliest instance, and refer such patients to a rheumatologist for appropriate therapy.
Immunopathology of PsO and PsA: The similarities
Both PsO and PsA have hereditary and genetic components, as evidenced by increased concordance in twins and immediate family members. PsO susceptibility loci are present on PSORS1-10, whereas an isolated PsA locus has been detected close to PSORS8 and is occasionally present.[8] In a few patients with a family history of PsO but no personal history, PsA has been reported, thus, indicating genetic predisposition.[9]
The inflammatory infiltrate in the skin of psoriatic lesions and joints of PsA is predominantly a lymphocytic one, localized to dermal papillae (skin) and sublining layer stroma (joint); a similar infiltrate has also been demonstrated in enthesis (tendon insertion).[10]
T lymphocytes are the predominant cells in skin and synovium. While CD4+ cells are more in tissues, CD8+ cells are abundant in synovium and enthesis.[10] In both PsO and PsA, angiogenesis is an early finding, with higher levels of angiopoetins, vascular endothelial growth factor, and other angiogenic factors detected in local tissues and synovial fluid. Formation of abnormal blood vessels is, thus, a common pathology in these conditions.[11],[12]
Tumour necrosis factor-alpha (TNF-alpha) has been implicated as a major pathogenic factor for both PsO and PsA, thus, explaining the therapeutic benefit of TNF-alpha inhibitors in both conditions.[10] The IL23/IL17 axis also participates in inflammation in skin and joints affected by PsO, although it is more active in skin than PsA, as evidenced by better resolution of skin lesions compared to joint manifestations when biologics targeting this pathway are administered.[13]
Risk factors and associations of PsA
As mentioned above, family history of PsO and PsA is a major risk factor for developing PsA.
PsA, like PsO is associated with several systemic disorders such as obesity and metabolic syndrome, diabetes, cardiovascular diseases, anxiety, inflammatory bowel disease, especially Crohn's (may indicate increased severity), and ocular involvement in the form of uveitis.[14]
For patients suffering from cutaneous PsO – disease severity, nail involvement with or without dactylitis, scalp, and perianal lesions are risk factors for PsA, although no specific type of PsO predisposes to PsA. Nail PsO has higher association with distal interphalangeal joint involvement.[15]
Many minor risk factors have been identified in different observational studies concerning PsA. One study identified trauma ('deep koebnerisation'), rubella vaccination, and shifting houses to be risk factors,[16] whereas another observed infections requiring antibiotics and injuries to be risk factors. Smoking showed an inverse association.[17]
Axial PsA is more common in cases with severe cutaneous PsO, severe peripheral arthritis, and a young age of onset of PsA.[14]
About 25% of PsA patients are HLA B27 positive, though testing for the allele is not mandatory. Specific HLA alleles are associated with different types of PsA, such as symmetric sacroiliitis with HLA-B*27:05, asymmetric sacroiliitis with HLA-B*08:01/HLA-C*07:01, enthesitis with HLA-B*27:05/HLA-C*01:02, dactylitis with HLA-B*27:05/HLA-B*08:01, and synovitis with HLA-B*08:01. Earlier age of onset of PsO is associated with HLACw*0602, which is more commonly seen in PsA than the general population.[18]
Clinical features, screening, and diagnosis of PsA
Inflammatory versus non-inflammatory arthritis
Dermatologists should be aware of the difference between inflammatory and non-inflammatory arthritis to question the patients when suspecting PsA.
PsA is an inflammatory arthritis, similar to other spondyloarthropathies and rheumatoid arthritis. Inflammatory arthritis is denoted by stiffness after 30–60 min inactivity (morning stiffness) that relieves following activity, inflammatory signs such as swelling, warmth, and redness, episodic flare-ups, and response to anti-inflammatory treatment. Non-inflammatory arthritis such as osteoarthritis has no complaints of stiffness with inactivity but worsen at day-end with continuous activity and no inflammatory joint signs.[19]
Clinical features and criteria of PsA
PsA is an inflammatory arthritis, seronegative for rheumatoid factor. It can have diverse presentations, the most common being a tender, red, swollen joint; any joint in the body can be involved. Synovitis is a universal association. The disease starts asymmetrically in one or few joints and gradually over time becomes polyarticular and more symmetric. In most cases, it has a relapsing-remitting nature but can occasionally be chronic or even rapidly progressive. With time, bone erosion and joint deformity occurs, causing the patient physical distress and functional limitation. The classical features include axial arthritis involving the spine, enthesitis, i.e., the inflammation of insertion of tendons/ligaments/joint capsules into the bones, and dactylitis which is the inflammation of a whole finger, i.e., the joints and enthesis ('sausage digit'). Enthesitis can involve any joint but more commonly seen in insertion of plantar fascia, Achilles tendon, and ligament attachments of spine, ribs, and pelvis.[1],[20],[21]
As mentioned earlier, >80% of patients have pre-existing cutaneous PsO involving skin and nails. In the rest, PsA can develop before or simultaneously with dermatological manifestations.
Moll and Wright laid the first diagnostic criteria for classifying PsA.[22] They denoted PsA as inflammatory arthritis negative for rheumatoid factor involving peripheral joints, sacroiliitis, spondylitis, and the concurrent presence of skin and nail psoriatic lesions. They also gave the five classical subtypes as detailed in [Table 1].
Other similar classifications and criteria have been proposed, but none have gained widespread acceptance.[23]
Recently developed Classification Criteria for Psoriatic Arthritis or CASPAR criteria [Table 2] are suitable for research but not in day-to-day practice. It is very specific but has a low sensitivity.[24]
Screening and diagnosis of PsA
For their subsequent management, it is of utmost importance for dermatologists to properly screen and diagnose PsA.
Screening tools have been formulated to aid physicians in screening for PsA in their clinical practice. These include patient-directed questionnaires to be filled up by the patients at their convenience. These include the Psoriasis-Arthritis Screening and Evaluation Questionnaire, the Psoriasis Epidemiology Screening Tool, the Early Psoriatic Arthritis Screening Questionnaire, the Toronto PsA Screen 2, the Simple Psoriatic Arthritis Screening Questionnaire, and the Screening Tool for Rheumatologic Investigation in Psoriatic Arthritis. [Table 3] summarises the tools. Even though these tools demonstrated good sensitivity and specificity in trials, they proved difficult and complex to carry out in real-life clinical practise. They are not used very frequently nowadays.[4],[19]
Clinical assessment
A simple mnemonic, PSA is suggested for the dermatologists to remember the main features of PsA: P for joint pain, S for stiffness after 30–60 min of inactivity and sausage digit (dactylitis), and A for axial involvement causing back pain and stiffness of spine. Joints to be examined include those of digits, spine, and entheses.[19]
Clinical lesions of PsO, especially nail PsO, need to be carefully evaluated as they are risk factors for PsA. The screening tool questions can be used to assess a patient for any kind of arthritic symptoms.
Joints should be examined for tenderness and swelling (synovitis). To elicit tenderness, pressure should be applied on the joint till the examiner's fingernail is bleached (4 kg/cm2 pressure). For examining joint swelling, bony swelling should be disregarded and swelling of soft tissue along the joint margins that can reduce the range of motion of the joint should be carefully examined.[18],[19] The 66 swollen and 68 tender joint count (68 TJC/66SJC),[26] 28-joint disease activity score (DAS28) with CRP,[27] and American College of Rheumatology (ACR) criteria[28] (measures % improvement in tender/swollen joints) can be used as indices of peripheral arthritis.
Dactylitis is usually a clinical diagnosis represented by a 'sausage-shaped' digit that is uniformly swollen because of a combination of enthesitis, synovitis, and soft tissue swelling. At least two of the small joints are swollen, and it is indistinguishable from surrounding soft tissue swelling. It may be red, hot and tender (acute inflammation), or less hot and not painful (chronic). Leed's dactylitis index measures the circumference of affected and unaffected digits (on the contralateral side) by a dactylometer for quantitative measurement of dactylitis.[19],[26]
Enthesitis can be assessed by applying pressure on insertion points of tendons and ligaments – Achilles tendon, knee, foot, pelvis, elbow, etc., and eliciting tenderness.[19] Leed's Enthesitis index measures tenderness at six sites, the humeral epicondyles, medial femoral condyles, and Achilles tendon insertion.[29] Maastricht Ankylosing Spondylitis Enthesitis Score[30] and Spondyloarthritis Research Consortium of Canada Enthesitis Index[31] are used to measure enthesitis at 13 and 16 bilateral points in ankylosing spondylitis and adapted in PsA.
Spinal or axial assessment is also required in PsA. An examination for decreased range of motion should be done.
Differential diagnoses of PsA include rheumatoid arthritis, osteoarthritis, gout, fibromyalgia, and other spondyloarthropathies such as ankylosing spondylitis.[18]
Investigations
Imaging
Imaging includes conventional X-rays, ultrasound, MRI, and CT scans. Imaging helps in ruling out differential diagnoses, deciding on prognosis, and therapy options as well as monitoring progression. It can particularly help discover the details of axial disease and assess the severity of peripheral involvement.[5]
Conventional X-rays can show bone resorption, new bone/osteophyte formation, bony fusion or ankylosis, and typical bony erosion. New bone deposition with erosion at joint margins is classical of PsA. Radiography is the first and best choice to detect axial disease; commonly seen are asymmetrical sacroiliitis, syndesmophytes with paravertebral ossification.[19],[20]
Ultrasound is more useful in detecting peripheral disease as it cannot demonstrate axial disease reliably. It can be used to assess inflammation in joints, entheses, and even skin and nails. Tenosynovitis and enthesitis can be detected early by ultrasound. It can detect subclinical cases when performed by a skilled physician and be used for monitoring disease progression and response to therapy. It can help assessing edema and dactylitis, although not diagnose it with certainty.[32],[33]
MRI can help detect new bone deposition, edema, tenosynovitis, and synovitis with joint inflammation in peripheral PsA. Coronal and sagittal T1- and T2-weighted images with fat suppression or short TI for fat suppression (STIR)/Turbo inversion recovery magnitude (TIRM) are recommended. T1-weighted imaged with gadolinium contrast can help differentiate synovitis and synovial effusion. For axial disease, MRI is the second choice of investigation after X-rays.[20],[34]
CT scan is only used if X-rays are not helpful and MRI cannot be performed for axial disease.[20]
Blood tests
Blood tests are not helpful in diagnosis of PsA. Rheumatoid factor and anti-cyclic citrullinated peptide antibody testing are usually negative, but may occasionally be positive as well. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein may be raised.[19]
Treatment overview
The treatment of PsA falls under the purview of rheumatologists, and a detailed discussion is beyond the scope of this article. However, a brief outline of treatment options is given below.
There are certain general principles to follow when a patient is newly diagnosed with PsA. The treatment is to be guided by the presence of pre-existing plaque PsO and other co-morbid conditions, and targeted toward limiting disease severity and degree of joint erosion, while also taking patient preference into account. This is further complicated by the fact that drugs effective in PsO and rheumatoid arthritis may not be as effective in PsA.[19],[35]
The treatment options are tabulated in [Table 4].
For peripheral arthritis, mild cases may be started on non-steroidal anti-inflammatory drugs (NSAIDs); corticosteroids at very low doses and for very short time (to prevent cutaneous flare-up) and even intra-articular injections may be given for symptom control. In case of uncontrolled or more severe cases, we can start with conventional disease-modifying anti-rheumatic drugs (DMARDs) or TNF inhibitors or even apremilast. Early escalation to biologics is recommended for long-term disease control.[38],[39]
For axial disease, physiotherapy, NSAIDs, and intraarticular injections into sacroiliac joint are the first choice. If not controlled, TNF inhibitors are next.[38],[39] For enthesitis and dactylitis, primary treatment can be started with NSAIDs and intraarticular injections, but usually TNF inhibitors and other biologicals are required and are highly efficacious.[38]
The ACR/NPF guideline of 2018 recommends starting a TNF inhibitor as first choice of therapy in all cases; alternatively a conventional DMARD can be used. In case of inadequate response, IL 17 inhibitors followed by IL23 or IL 12/23 inhibitors are introduced. Apremilast can be added on with TNF inhibitors. Abatacept is usually a later choice. Tofacitinib is given if the patient prefers an oral therapy.[39]
The disease response can be monitored by indices such as QoL measures, 68TJC/66SJC, Disease Activity Index for Psoriatic Arthritis, Minimal Disease Activity (MDA), etc., A treat-to-target approach to achieve remission or MDA is recommended.[35]
Conclusion PsA was earlier believed to be a benign arthritis associated with cutaneous PsO; but in recentl decades, it has been re-identified as a debilitating disease causing significant morbidity in a patient's life by placing functional restrictions on day-to-day life. The progressive nature of the disease can be arrested or at least slowed if the disease is identified early and treated aggressively with biologicals.
Because most cases of PsA have pre-existing PsO lesions, dermatologists may often encounter latent cases in their clinics, thus, providing them a unique opportunity to diagnose PsA at the early stages by careful assessment and evaluation. Thus, dermatologists should be acquainted with the clinical and diagnostic pointers of this disease. Once diagnosed, appropriate patient counselling is essential regarding possible prognosis and available treatment options, before referral to a specialist. A multidisciplinary team work involving rheumatologists is critical to address the skin and nail manifestations of such patients that are quite bothersome in the long run. We hope this review would be helpful for dermatologists to suspect and diagnose PsA in the early course of disease, to initiate appropriate therapy and referral to improve its outcome in the long run.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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