**1. Introduction**

Chronic arthritis is the most usual cause for joint pain, physical disability, and ocular invalidity worldwide. Juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) of the adult are two major groups with chronic joint inflammation, extra-articular manifestations, and high risk for comorbidities [1–5].

While in adults there are over 150 forms of chronic arthritis, in children, there are several dozen subtypes of the disease, but only juvenile polyarthritis with positive rheumatoid factor and the subtype of systemic arthritis also known as Still disease, which is more consistent with an autoinflammatory condition, have similar manifestations to adults [6].

Patients with systemic JIA require close keep under surveillance by a multidisciplinary team due to possible serious complications: macrophage activation syndrome, pericarditis, pulmonary hypertension, interstitial lung disease, infections, etc., which may be associated with increased mortality [7].

In the pathology of children, the oligoarticular manifestation is an entity that we do not find in the forms of rheumatic disease in adults and is characterized by often severe eye damage, localized growth disorders with elongation of a limb, and secondary posture disorders.

JIA is the type of chronic rheumatic disease that affects the child's daily activities due to pain, joint swelling, morning stiffness, and locomotor and possibly ocular infirmities, which causes short-term and long-term disabilities, until adulthood and sometimes throughout life [8].

Treatment available for patients with chronic arthritis aims to reduce pain, maintain joint function, improve well-being, and prevent disability and associated comorbidities.

Pharmacological therapy usually includes non-steroidal anti-inflammatory drugs, intra-articular or systemic steroids, to which will be added disease-modifying anti-rheumatic drugs (DMARDs) and biological agents administered on time in the "window of opportunity" to prevent irreversible complications [2].

Early use of intra-articular steroid therapy, methotrexate, and biological agents introduced in recent decades have improved the prognosis of children with arthritis, but those with polyarticular form can have serious problems with active disease as adults. Most children with the JIA oligoarticular subtype may enter remission, but a small number progress to a persistent polyarticular form as adults.

Concerns have been raised about the use of biological agents that may increase the risk of cancer in patients with chronic arthritis.

Based on the severity of the disease, which evolves progressively, the patient with chronic arthritis can become an important burden for the family, but especially for the society, through the enormous costs of direct health care, social assistance, loss in education, productivity, and jobs.

The first goal of this review was to update knowledge on molecular and cellular mechanisms through a parallelism between special forms of chronic arthritis present in both children and adults, for an introspection into the pathogenesis of these diseases, in an attempt to reveal to researchers and clinicians the latest discoveries regarding new molecules and signaling pathways.

The second objective of this review was to raise awareness and send a signal to rheumatologists on the need to change the treatment paradigms for arthritis through innovative therapies to stop the perpetuation of the disease from childhood to adulthood, the side effects, the inefficiency in some cases, and the high current costs, in order to overcome this human and economic burden.

The third purpose was to promote light or laser therapies (photobiomodulation) as an important complementary and alternative method, which has become increasingly known around the world in recent decades for reducing pain and sometimes even eliminating the cause of the pain itself, for inducing early remission before common destructive changes in joints begin, in all arthritis forms.

Last aim but not least is to signal that photobiomodulation (PBM) and the single-cell live tracking technology of immune cell activities are ready to precisely target the signaling pathways and to find the answers to the complex interaction of the laser with the immune system, for "undoing" arthritis!

Seeking and developing new treatments to interact smoothly with the immune system both in children and adults to handle immune-mediated diseases that are becoming more and more complex is urgently needed.

JIA, formerly known as juvenile rheumatoid arthritis in the Anglo-Saxon literature, and chronic juvenile arthritis for French speakers, is a chronic immune-mediated inflammatory disease of unknown etiology and a complex genetic component that is defined according to the criteria of the International League of Associations for Rheumatology (ILAR) as inflammatory arthritis in one or more joints, which begins before the age of 16, persists for at least six weeks, and all other conditions that cause similar symptoms have been excluded [1,4].

A better understanding of the pathogenesis and the latest diagnostic tools are challenges for rheumatologists to update the classification. Based on ILAR criteria, there are seven main subgroups of JIA defined by clinical and laboratory data: systemic arthritis, rheumatoid factor (RF) polyarthritis—positive or negative, oligoarthritis (persistent or extensive), enthesitis-related arthritis (ERA), psoriatic arthritis (PsA), and a seventh category, undifferentiated arthritis, which includes those patients who do not fit any of the above forms of criteria [4,9].

#### *1.1. RF-Positive Polyarticular JIA*

RF-positive polyarticular juvenile idiopathic arthritis is defined by the existence of at least 5 inflamed joints over a period of 6 weeks, in the presence of RF found twice, at an interval of at least 3 months in the first 6 months after the onset of the disease. This category is considered clinically and biologically similar to adult RA by progressive destructive polyarticular manifestations in the knee, elbow, and foot.

In this case, arthritis in children is symmetrical and predominantly peripheral; it affects particularly small joints of the fingers and toes, but it may also affect the large joints of the knees, hips, ankles, and fist.

Other manifestations may include lower-level fever than in systemic form, rheumatoid nodules (tumors under the skin, most common in the elbow), anemia, and thrombocytosis.

Factors that determine disability include early age at onset, female gender, the presence of rheumatoid factor, and the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP) [2,10].

As a peculiarity, it should be mentioned in children that it affects the temporomandibular joints and the upper cervical region (neck area).

Temporomandibular arthritis can limit mouth opening and discomfort in chewing. Arthritis of the neck area can cause instability or fusion of the cervical vertebrae, with a high potential for neurological injury of the spine to minor trauma.

Long-term studies show that the prognosis is severe in 50% of cases [11].

Most common complications are osteoporosis, vertebral collapse, dwarfism, pubertal delay, intercurrent viral, or bacterial infections in immunosuppressed children by disease or secondary to medication [12,13].
