The clinical picture of JPA is heterogeneous, yet no consensus has been reached as to a possible classification of JPA subtypes. Several rheumatologists have proposed the distinction of at least two subgroups, namely those showing signs and symptoms reminiscent of early-onset ANA-positive juvenile idiopathic arthritis and others presenting with an adult-like form of psoriatic arthritis and spondyloarthropathy [1] [2] [3]:

• The former represents the classical type of JPA, which consists in asymmetric oligoarthritis involving both large and small joints. Dactylitis is universally present and does facilitate the diagnosis of JPA when affecting digits with psoriatic nail pits. Arthritis of the axial skeleton and enthesitis are rarely observed. In general, the disease tends to follow a progressive course, extending to as-of-yet uninvolved joints and turning into polyarthritis, and it may be complicated by chronic uveitis. The majority of patients are girls with symptom onset at preschool age. Antinuclear antibodies are frequently detected in these patients.
• The second type of JPA preferentially affects the joints of the vertebral column and is thus classified as spondyloarthropathy. Enthesitis may occur, but dactylitis is a rare feature. Most patients are male, and their age at symptom onset is superior to that reported for females with classical JPA.

This clinical duality may partially be explicated by the fact that some patients may indeed develop autoimmune arthritis as a complication of psoriasis, while others may suffer from concomitant psoriasis and unrelated arthropathy. The fact that the onset of psoriasis may either precede or follow the inflammation of joints seems to support this theory [3]. It should be kept in mind that the manifestations of psoriasis in young children are often atypical or unspecific, including erythema and scaling behind the ears [4]. Beyond that, psoriatic plaques are typically seen on the extensor sides of joints, haired skin, the umbilicus and the perineum [5].

Additionally, JPA is associated with an increased prevalence of obesity and comorbidities like hypertension, hyperlipidemia, diabetes, and Crohn's disease [6].

• Splenomegaly

  CID was strictly defined as: (1) no joints with active arthritis; (2) no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; (3) no active uveitis; (4) ESR in the normal range in the laboratory where tested; and [richtlijnendatabase.nl]

• Generalized Lymphadenopathy

  CID was strictly defined as: (1) no joints with active arthritis; (2) no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; (3) no active uveitis; (4) ESR in the normal range in the laboratory where tested; and [richtlijnendatabase.nl]

• Asymptomatic

  Although 40% were asymptomatic at follow-up, six patients required bilateral hip replacement, four within the first five years following the onset of arthritis. [ncbi.nlm.nih.gov]

  Children with psoriatic arthritis who have a positive ANA have an increased risk of developing asymptomatic eye inflammation (uveitis). [chop.edu]

  Asymptomatic erythematous scaly plaques developed on the trunk. A skin biopsy specimen revealed psoriasis. This is the first report of psoriasis developing in a patient with juvenile rheumatoid arthritis. © 2000 S. [karger.com]

  There is a high risk of asymptomatic uveitis which can, if undetected, result in visual loss from cataract and keratopathy (proteinaceous deposits over the eye) - early uveitis is invariably without symptoms - i.e., the eye is not red or painful and there [pmmonline.org]

• Reiter Syndrome

  syndrome) tends to involve feet > hands [radiopaedia.org]

  The other disorders are juvenile ankylosing spondylitis, inflammatory bowel disease, and Reiter's syndrome. [childrensnational.org]

  Similarly, a history of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis in a first-degree relative has been defined as an exclusion criterion for JPA. [symptoma.com]

• Nail Abnormality

  Often, if one has symptoms in the joints at the ends of the fingers or toes, then those nails will be affected. Many people with psoriatic arthritis have nail abnormalities. Some people with uncomplicated psoriasis have nail changes. [emedicinehealth.com]

  This reaction causes the synovium to thicken and grow abnormally, this abnormal growth eventually will cause damage to the bone and cartilage of the joint and surrounding tissues. [3] Researchers are beginning to believe that not all forms of JIA are [physio-pedia.com]

• Hepatosplenomegaly

  Migratory salmon colored light pink rash involving the trunk and/or extremities and hepatosplenomegaly are also frequently observed in patients with systemic onset. [radiopaedia.org]

  Lymphadenopathy and hepatosplenomegaly may be seen in systemic JIA. A careful cardiac and pulmonary examination must be done to look for pericarditis and pleuritis. [unboundmedicine.com]

  […] features, fever ( quotidian i.e. daily fever spikes - usually late evening to early morning and normal or below normal in between spikes), evanescent maculopapular rash or salmon pink rask ( which may appear at times of fever ), serositis, lymphadenopathy, hepatosplenomegaly [pmmonline.org]

  On physical examination the patient was somnolent, tachypneic (respiratory rate: 40cpm), tachycardic (heart rate: 127bpm), normotensive, febrile (axillary temperature: 37.8°C), with hepatosplenomegaly and bilateral ankle edema. [revportcardiol.org]

  […] the most severe type of JIA in that it has many extraarticular manifestations [2] Symptoms of Still's disease include [2] High-spiking fever Rash on thighs and chest (often dissipates within a few hours) Lymphadenopathy (enlargement of lymph nodes) Hepatosplenomegaly [physio-pedia.com]

• Visual Impairment

  Visual impairment may be caused by chronic uveitis. Boys, on the other hand, most commonly develop inflammations of the joints of the vertebral column. They rarely show dactylitis. [symptoma.com]

  These are usually the most unfortunate cases; since the disease is asymptomatic, late diagnosis may result in visual impairment. 2.3 Is the disease in children different from the disease in adults? Mostly yes. [printo.it]

• Oligoarthritis

  The need for disease-modifying antirheumatic drugs and/or anti-tumor necrosis factor agents was present in 33% of PsA versus 8% in oligoarthritis and 13% in either oligoarthritis or polyarthritis patients (p < 0.001 and p = 0.002, respectively). [ncbi.nlm.nih.gov]

  Of note, the intra-articular application of anti-inflammatory drugs seems to be an effective treatment modality but is usually discarded in the face of oligoarthritis or polyarthritis. [symptoma.com]

• Morning Stiffness

  Symptoms of joint pain and tenderness are worse in the morning in association with the previously described morning stiffness (see systemic onset JIA). [medicinenet.com]

  Symptoms may include: Inflamed, swollen and painful joints, usually in the fingers and toes Morning stiffness Reddened skin over the infected joint(s) Deformed joints from chronic inflammation Pitting of fingernails or toenails Eye pain Fatigue As stated [childrensnational.org]

  stiffness Back pain or stiffness Pitting or peeling of the nails Red nail beds or cuticles Young children with psoriatic arthritis are more likely to show symptoms in the small joints, have a positive ANA, experience finger or toe swelling, and are at [chop.edu]

  stiffness 0005197 Malar rash 0025300 Psoriasiform lesion 0025526 Reduced visual acuity Decreased clarity of vision 0007663 1%-4% of people have these symptoms Abnormality of the temporomandibular joint Abnormality of the jaw joint Deformity of the jaw [rarediseases.info.nih.gov]

• Osteoporosis

  Corticosteroids can have negative side effects, such as growth delays and severe osteoporosis. [juvenilearthritisnews.com]

  Potential complications Osteoporosis Having psoriatic arthritis increases the risk of developing osteoporosis. This link is strongest for the spondylitis subtype of psoriatic arthritis. [healthand.com]

  […] sparing of the facet joints General imaging differential considerations include: rheumatoid arthritis there is an MCP joint predominance in rheumatoid arthritis (RA) vs interphalangeal predominant distribution in PsA bone proliferation not a feature in RA osteoporosis [radiopaedia.org]

  Kids with juvenile psoriatic arthritis can have: shorter-than-normal bones slowed growth problems with the jaw that can make it hard for them to brush their teeth an increased risk for osteoarthritis and osteoporosis as they age Psoriatic arthritis can [healthline.com]

• Joint Stiffness

  Joint stiffness occurs primarily in the morning or after long periods of inactivity (gelling phenomenon). [childrenshospital.org]

  This causes the synovium to make extra synovial fluid, which leads to swelling, pain and stiffness in the joint. This process can spread to the nearby tissues, eventually damaging cartilage and bone. [my.clevelandclinic.org]

  Symptoms Juvenile idiopathic arthritis symptoms and signs can include: Joint swelling Joint pain Joint stiffness that is usually worse in the morning A high fever (systemic JIA) Salmon-colored skin rash (systemic JIA) Swollen lymph glands (systemic JIA [verywell.com]

  Arthritis is a general term describing over 100 different conditions that cause pain, stiffness, swelling and often inflammation in one or more joints. [arthritis.org.za]

• Back Pain

  These children may have joint pain without obvious swelling and may complain of back pain and stiffness. [the-rheumatologist.org]

  (sacroiliitis) Arthritis of the spine (spondylitis) Inflammation of the eyes (uveitis) Morning stiffness Back pain or stiffness Pitting or peeling of the nails Red nail beds or cuticles Young children with psoriatic arthritis are more likely to show [chop.edu]

  Those patients had less psoriasis but more features of SpA, such as enthesitis, inflammatory back pain, IBD, and uveitis. The evidence of asymptomatic enthesitis in patients with JPsA is additional support for this concept48. Table 2. [jrheum.org]

  Swollen fingers and nail pitting (psoriatic JIA) Lower back pain (enthesitis-related arthritis) Eye inflammation (oligoarthritis) Most importantly, to be diagnosed with JIA, a child should be younger than 16-years-old at the onset of arthritis and should [verywell.com]

As implied above, JPA may precede psoriasis by several years [3]. In line with this observation, the clinical diagnosis of JPA as a complication of psoriatic disease is not feasible. It has therefore been attempted to establish further criteria that allow for the diagnosis of JPA in the absence of scaling cutaneous lesions.

The so-called "Vancouver criteria" have been published in 1989 and focus on the presence of confirmative findings [7]:

• Psoriasis-like rash as well as more subtle symptoms of psoriasis, such as dactylitis, nail pitting or onycholysis, and a family history positive for the condition may provide important clues as to the nature of the disease. Either three of these findings support the diagnosis of JPA, whereas two findings make the diagnosis probable.

More recent guidelines have been elaborated by the International League of Associations for Rheumatology and detail a series of exclusion criteria [8]:

• Because JPA is not usually associated with HLA-B27, positivity for this haplotype in a male patient aged >6 years or a family history of HLA-B27-associated disease argue against JPA.
• Rheumatologists further specified the presence of IgM rheumatoid factor, as detected on at least two occasions more than 3 months apart, and the presence of systemic arthritis as exclusion criteria for JPA.
• Similarly, a history of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis in a first-degree relative has been defined as an exclusion criterion for JPA.

The last point, however, remains a matter of controversy, since the exclusion of patients suffering from spondyloarthropathies is in contradiction with the hypothesis of phenotypic duality as described above [2] [4]. The Vancouver criteria are less restrictive in this context and don't include any criteria for exclusion [7]. According to the earlier guidelines, pediatric patients with adult-like psoriatic arthritis can be diagnosed with JPA.

• Enlargement of the Liver

  Other possible signs include inflammation of the heart or lungs or their outer linings; anemia; or enlarged lymph nodes, liver or spleen. About 10 percent of children with JIA will have the systemic form. [arthritis.org]

  Side effects may include: nausea mouth sores diarrhea low white blood cell count lung irritation sinus infection liver irritation. [orthop.washington.edu]

Synthetic disease-modifying anti-rheumatic drugs (DMARDs; e.g., methotrexate, sulphasalazine, leflunomide) and corticosteroids are the mainstays of pharmacological treatment, which aims at the elimination of active disease, the normalization of joint function, the prevention of long-term joint damage and the facilitation of normal growth [5]. Full therapeutic effects may be expected within 6-12 months of systemic therapy, and patients who remain unresponsive after this period of time may then be administered biological agents [9]. Inhibitors of tumor necrosis factor-α, interleukin-1, and interleukin-6 are most commonly applied to this end, and apremilast, an inhibitor of phosphodiesterase 4 and tumor necrosis factor-α, has specifically been approved for the treatment of JPA.

Beyond that, recent studies have revealed interleukin-23 and interleukin-17 signaling to promote skin and joint inflammation in psoriasis patients [10]. It has thus been hypothesized that these patients may benefit from specific antibody treatments: Secukinumab, ixekizumab, and brodalumab all target interleukin-17 and have all been shown to be safe and effective in JPA treatment; yet to date, only secukinumab has received approval. The current therapeutic spectrum also includes ustekinumab, a dual antagonist of interleukin-12 and interleukin-23, while BI655066, guselkumab, and tildrakizumab are still tested in clinical trials [11]. Irrespective of the specific treatment regimen, medical therapy is generally continued over a period of several months after complete remission. The precise timing of treatment discontinuation, however, remains a matter of debate [9].

Of note, the intra-articular application of anti-inflammatory drugs seems to be an effective treatment modality but is usually discarded in the face of oligoarthritis or polyarthritis.

JPA tends to follow a more severe course than other types of juvenile idiopathic arthritis and often demands aggressive therapy: According to a long-term study that followed patients for 15 years, about a third of JPA patients still required DMARDs or bDMARDs at the end of the follow-up [12]. Notwithstanding, Guzman and colleagues reported a very high probability of attaining a state of inactive disease within 5 years of therapy, and the vast majority of their patients was able to discontinue all anti-rheumatic and anti-uveitis treatments within this period of time [13].

Disease-defining factors as described above, namely psoriasis-like rash, dactylitis, nail pitting, and first-degree heredity for psoriasis or psoriatic arthritis, have separately been identified as unfavorable prognostic factors and are associated with lack of remission [4]. Furthermore, patients with polyarthritic disease have a worse outcome than those with oligoarthritis.

The etiology of JPA remains poorly understood, and the disease is still classified as a type of juvenile idiopathic arthritis. Both genetic and environmental factors may contribute to the development of the disease, and these factors are likely to be different in early-onset JPA and adult-like psoriatic arthritis [3]. MHC class I alleles and infections with Streptococcus spp. have received major attention to this end, but virtually any event that generates a danger signal may trigger JPA in the proper, as-of-yet poorly defined genetic context. Trauma, mechanical stress, and dysbiosis, among others, may all be interpreted as danger signals by the innate immune system, thereby initiating an auto-inflammatory loop [14].

JPA accounts for approximately 6-8% of all cases of juvenile idiopathic arthritis, a highly heterogeneous condition whose overall prevalence has been estimated at 7-150 per 100,000 children [5] [15]. With regard to the age of onset, Martini et al. reported a bimodal distribution for JPA, with a first peak in early childhood, before the age of 6, and a second near adolescence, after the age of 10. Interestingly, girls with psoriasis seem to be predisposed to develop early-onset JPA, while male predominance has been observed in late-onset, spondyloarthropathic JPA [1]. Even though the early-onset type of JPA is generally considered the classical variant of the disease, spondylarthropathic JPA may account for up to 60% of all cases and may thus not be considered a rare exception from the common phenotype [16].

The pathophysiological mechanisms leading to JPA remain unclear. Recently, cytokines interleukin-17 and interleukin-23, as produced by CD4-/CD8+ T-cells and innate lymphocytes, have been implied in the pathogenesis of the disease [11]. Tumor necrosis factor-α and interleukin-22 had previously been identified as key players in JPA [14]. These cytokines are involved in the activation of a Th1 and Th17 response that ultimately leads to synovitis, axial inflammation, and altered bone homeostasis characterized by impaired bone resorption and new bone formation.

Due to lack of understanding of the disease' etiology and pathogenesis, no recommendations can be given to prevent the development of JPA.

JPA has first been defined by Lambert and colleagues as "arthritis beginning before the age of 16 years, associated with psoriasis either preceding the onset of arthritis or occurring within the subsequent 15 years, and usually with the absence of rheumatoid factor in the serum" [17]. Yet, both the definition of JPA as well as the general classification of pediatric arthritis have since undergone multiple changes - and this process is set to continue. The current debate is about the inclusion or exclusion of late-onset male cases with spondyloarthropathy but without dactylitis, which largely contrast with the classical type of JPA that preferentially affects girls and comprises asymmetric oligoarthritis of the appendicular skeleton and dactylitis [7] [8]. What's more, due to frequent changes in the diagnostic criteria for JPA, it is difficult to compare studies realized at different times.

Doubts regarding the classification of juvenile idiopathic arthritis are closely linked to knowledge gaps in the pathogenesis of JPA and its presumed subtypes. Pathophysiological differences may eventually justify the formulation of specific treatment recommendations, and the optimum management of the disease may rather depend on molecular parameters than on the presence of psoriatic lesions. Thus, some authors have suggested to remove the category of JPA and to define psoriasis as a possible extra-articular manifestation of different types of arthritis [2].

Psoriasis vulgaris is an autoimmune disease of the skin, but it is associated with comorbidities like metabolic syndrome, cardiovascular disease, inflammatory bowel disease, and arthritis. With regard to the latter, joint inflammation in psoriasis patients may be diagnosed as psoriatic arthritis or, in the case of minors, juvenile psoriatic arthritis (JPA). Girls are more likely to manifest symptoms in early childhood. They frequently suffer from asymmetric oligoarthritis involving both large and small joints, but the axial skeleton is typically spared. Dactylitis or "sausage digits" are rather common, and psoriatic nail pits may be observed. Visual impairment may be caused by chronic uveitis. Boys, on the other hand, most commonly develop inflammations of the joints of the vertebral column. They rarely show dactylitis. This variant of JPA tends to manifest in late childhood or early adolescence.

The identification of JPA is largely facilitated by the co-occurrence of psoriatic skin and joint lesions, but arthritis precedes cutaneous psoriasis in about half of children with JPA, which poses a major diagnostic challenge. Laboratory analyses thus have to be carried out to complement clinical findings. In detail, patients undergo screenings for rheumatoid factor and molecular HLA allele typing. Furthermore, it is important to know whether there are close relatives who have previously been diagnosed with psoriasis or psoriatic arthritis.

Once the diagnosis of JPA has been confirmed, a treatment plan can be elaborated. Most patients initially receive corticosteroids plus disease-modifying anti-rheumatic drugs like methotrexate, and the majority of affected children favorably responds to therapy. Those who don't may be administered additional drugs, namely so-called biological agents that inhibit the underlying immune response.

While JPA tends to follow a progressive course, affecting more and more joints, complete remission can be achieved. There is a very high probability that a state of inactive disease can be attained within five years, and most patients may eventually discontinue their medication. Nevertheless, symptoms may persist into adulthood, and some patients require medical therapy for a prolonged period of time.

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