Symptoms of juvenile chronic arthritis

Peculiarities of the course of juvenile chronic arthritis

The main symptom of juvenile chronic arthritis is arthritis. Pathological changes in the joint are characterized by pain, swelling, deformations and limitation of movement, increased temperature of the skin over the joints. In children, large and medium joints are most often affected, in particular, the knee, ankle, wrist, elbow, hip, and less often - small joints of the hand. Typical for juvenile rheumatoid arthritis is damage to the cervical spine and temporomandibular joints, which leads to underdevelopment of the lower, and in some cases the upper jaw and the formation of the so-called "bird jaw".

Depending on the number of affected joints, the following types of joint syndrome are distinguished:

• oligoarthritis (affecting 1 to 4 joints)
• polyarthritis (more than 4 joints affected)
• generalized arthritis (damage to all groups of joints)

A characteristic feature of rheumatoid joint damage is a steadily progressing course with the development of persistent deformations and contractures. Along with arthritis, children develop pronounced atrophy of the muscles located proximal to the joint involved in the pathological process, general dystrophy, growth retardation, and accelerated growth of the epiphyses of the bones of the affected joints.

The stages of anatomical changes and the functional class in children are determined in the same way as in adult patients with rheumatoid arthritis in accordance with the Steinbrocker criteria.

There are 4 anatomical stages:

• Stage I - epiphyseal osteoporosis.
• Stage II - epiphyseal osteoporosis, fraying of cartilage, narrowing of the joint space, isolated erosions.
• Stage III - destruction of cartilage and bone, formation of bone-cartilaginous erosions, subluxations in the joints.
• Stage IV – criteria of stage III + fibrous or bony ankylosis.

There are 4 functional classes:

• Class I - the functional capacity of the joints is preserved.
• Class II - limitation of the functional capacity of joints without limitation of the ability to self-care.
• Class III - limitation of the functional capacity of the joints is accompanied by limitation of the ability to self-care.
• Class IV - the child does not take care of himself, needs outside help, crutches and other devices.

The activity of juvenile chronic arthritis in domestic pediatric rheumatology is assessed in accordance with the recommendations of V.A. Nasonova and M.G. Astapenko (1989), V.A. Nasonova and N.V. Bunchuk (1997). There are 4 degrees of activity: 0, 1, 2, 3.

When determining the activity of the disease, the following indicators are assessed:

1. Number of joints with exudation.
2. Number of painful joints.
3. Ritchie Index.
4. Number of joints with limited movement.
5. Duration of morning stiffness.
6. Disease activity on an analogue scale, assessed by the patient or his parents.
7. Number of systemic manifestations.
8. Laboratory activity indicators: ESR, red blood cell count, hemoglobin level, platelet count, white blood cell count, white blood cell count, serum CRP, IgG, IgM, IgA concentration, RF, ANF.

The modified American Rheumatology Association criteria for clinical remission in rheumatoid arthritis can be used to assess remission.

Criteria for remission of juvenile chronic arthritis:

1. The duration of morning stiffness does not exceed 15 minutes.
2. Lack of weakness.
3. Absence of pain.
4. No discomfort in the joint, no pain during movement.
5. Absence of soft tissue swelling and joint effusion.
6. Normal levels of acute phase proteins in the blood.

The condition can be considered as remission if at least 5 criteria are present for 2 consecutive months.

Extra-articular manifestations

Fever

In the polyarticular articular variant of juvenile rheumatoid arthritis, the fever is often subfebrile, in the Still variant - subfebrile and febrile, in the allergic septic variant - febrile, hectic. Fever develops, as a rule, in the morning hours.

In the allergic septic variant, temperature rises are also observed during the day and evening hours, and may be accompanied by chills, increased arthralgia, rash, and increased intoxication. A drop in temperature is often accompanied by profuse sweating. The febrile period in this variant of the disease can last for weeks and months, and sometimes years, and often precedes the development of articular syndrome.

Rash

The rash is usually a manifestation of systemic variants of juvenile rheumatoid arthritis. It is of a spotty, maculopapular, linear nature. In some cases, the rash may be petechial. The rash is not accompanied by itching, localized in the area of the joints, on the face, chest, abdomen, back, buttocks and limbs. It is ephemeral, intensifying at the height of the fever.

Damage to the heart, serous membranes, lungs and other organs

As a rule, it is observed in systemic variants of juvenile rheumatoid arthritis. It proceeds as myo- and/or pericarditis. Both processes can be observed in isolation and tend to recur. In case of severe exudative pericarditis, there is a risk of cardiac tamponade. Acute myopericarditis can also be accompanied by cardiopulmonary insufficiency.

The clinical picture of heart damage in juvenile rheumatoid arthritis: pain behind the breastbone, in the heart area, and in some cases - isolated pain syndrome in the epigastrium; dyspnea of a mixed type, forced position in bed (the child feels better in a sitting position). Subjectively, the child complains of a feeling of lack of air. If pneumonitis is added or there are congestions in the pulmonary circulation, there may be a wet unproductive cough.

On examination: the patient has cyanosis of the nasolabial triangle, lips, and terminal phalanges of the fingers; pastosity (or edema) of the shins and feet; work of the wings of the nose and accessory respiratory muscles (in cardiopulmonary insufficiency); expansion of the boundaries of relative cardiac dullness mainly to the left, muffled heart sounds; systolic murmur over almost all valves; pericardial friction murmur; tachycardia, which can reach 200 beats per minute; tachypnea up to 40-50 breaths per minute; hepatomegaly in case of insufficiency in the systemic circulation. In case of congestion in the pulmonary circulation, auscultation reveals numerous fine, moist rales in the basal parts of the lungs.

In rare cases of recurrent pericarditis, progressive fibrosis is observed with the formation of an "armored" heart. It is this manifestation of the disease that can lead to a fatal outcome. Along with pericarditis, patients with systemic variants of juvenile rheumatoid arthritis may develop polyserositis, including pleurisy, less often perihepatitis, perisplenitis and serous peritonitis.

Lung damage in patients with rheumatoid arthritis manifests itself as "pneumonitis", which is based on vasculitis of small vessels of the lungs and interstitial inflammatory process. The clinical picture resembles bilateral pneumonia with an abundance of moist rales, crepitations, pronounced dyspnea, and signs of pulmonary insufficiency.

In rare cases, the development of fibroaeating alveolitis is possible, which has scant clinical symptoms and is characterized by increasing respiratory failure.

Frequent extra-articular manifestations also include lymphadenopathy, hepato- and/or splenomegaly.

Lymphadenopathy

Lymph node enlargement is characterized by enlargement of lymph nodes of almost all groups, including cubital and even femoral and bicipital. Lymph node enlargement is most pronounced in systemic forms of the disease, when lymph nodes enlarge to 4-6 cm in diameter. As a rule, lymph nodes are mobile, painless, not fused with each other and with underlying tissues, soft or densely elastic consistency. In the presence of other extra-articular manifestations (febrile and hectic fever, rash, arthralgia and myalgia, hyperleukocytosis with a left shift), differential diagnostics with lymphoproliferative and heloblastic processes are required.

Lymphadenopathy develops not only in systemic variants of juvenile rheumatoid arthritis, but also in joint lesions, and is especially pronounced in polyarticular variants of the disease.

Hepatosplenomegaly

Hepatosplenomegaly develops mainly in systemic variants of juvenile rheumatoid arthritis. More often in combination with lymphadenopathy without affection of the heart, serous membranes and lungs in the Still's variant and in combination with other extra-articular manifestations in the allergic septic variant.

A persistent increase in the size of the liver and spleen, an increase in the density of the penchymatous organs of patients with systemic variants of juvenile rheumatoid arthritis may indicate the development of secondary amyloidosis.

Eye damage

Typical for young girls with mono- / oligoarthritis. Anterior uveitis develops. The course of uveitis can be acute, subacute and chronic. In acute uveitis, the patient develops injection of the sclera and conjunctiva, photophobia and lacrimation, pain in the eyeball. The process is characterized by damage to the iris and ciliary body, iridocyclitis is formed. However, most often uveitis in juvenile rheumatoid arthritis is subacute and chronic and is detected already with a decrease in visual acuity. In the chronic course, corneal dystrophy, angiogenesis in the iris develop, adhesions are formed, which leads to deformation of the pupil and a decrease in its reaction to light. Clouding of the lens - cataract - develops. Ultimately, visual acuity decreases, and complete blindness and glaucoma can also develop.

Uveitis in combination with oligoarthritis can be a manifestation of reactive arthritis, in combination with spinal damage - spondyloarthritis.

Growth retardation and osteoporosis

Juvenile rheumatoid arthritis is one of the diseases that negatively affects growth.

Growth disturbance is one of the leading among many extra-articular manifestations of juvenile rheumatoid arthritis. Growth retardation in juvenile rheumatoid arthritis undoubtedly depends on the inflammatory activity of this disease and is especially pronounced in the systemic variant of the course. Systemic chronic inflammation causes a general slowdown and cessation of growth, local inflammation leads to increased growth of the epiphyses and premature closure of growth zones. In this case, not only the process of the child's growth itself suffers, but also an asymmetry in the development of the body is formed. It is manifested by underdevelopment of the lower and upper jaws, cessation of bone growth in length. As a result, older children retain body proportions characteristic of early childhood.

Polyarticular joint damage, destruction of cartilage and bone tissue, decreased motor activity, amyotrophy, chronic intoxication with subsequent development of dystrophy, which also inhibits the growth process, also have a negative impact.

Undoubtedly, an important factor influencing the growth of patients with juvenile rheumatoid arthritis is the development of osteoporosis. In juvenile rheumatoid arthritis, osteoporosis is of two types - periarticular - in bone areas near the affected joints and generalized. Periarticular osteoporosis develops mainly in the epiphyses of the bones that form the joints. In juvenile rheumatoid arthritis, it begins to manifest itself quite early and is one of the diagnostic criteria for this disease. Systemic osteoporosis is observed more often in children suffering from juvenile rheumatoid arthritis than in adults with rheumatoid arthritis. It develops in all areas of the skeleton, mainly in the cortical bones, accompanied by a decrease in the concentration of biochemical markers of bone formation (osteocalcin and acid alkaline phosphatase) and bone resorption (tartrate-resistant acid phosphatase). With the development of systemic osteoporosis, an increase in the frequency of bone fractures is observed. The decrease in bone mineral density develops most rapidly in the first years of the disease, and then slows down. Systemic osteoporosis is more often observed in children with polyarticular joint syndrome. Its severity directly correlates with laboratory indicators of disease activity (ESR, C-reactive protein, hemoglobin level, platelet count).

The development of osteoporosis is determined by the hyperproduction of resorption activators: IL-6, TNF-a, IL-1, granulocyte-macrophage colony-stimulating factor. On the one hand, these cytokine are proinflammatory and play a leading role in the development of acute and chronic inflammatory reactions in juvenile rheumatoid arthritis, and on the other hand, they cause proliferation of synoviocytes and osteoclasts, synthesis of prostaglandins, collagenase, stromelysin, activation of leukocytes, synthesis of enzymes, which leads to the development of local and systemic osteoporosis. Along with the hyperproduction of resorption activators, patients have a deficiency of resorption inhibitors (IL-4, gamma interferon, soluble IL-1 receptor).

Risk factors for the development of short stature in patients with juvenile rheumatoid arthritis are: early age onset of the disease, systemic variants of juvenile rheumatoid arthritis, polyarticular joint syndrome, high disease activity, treatment with glucocorticoids and the development of osteoporosis.

Identification of risk factors will allow us to predict and possibly prevent the development of such serious complications as dwarfism and osteoporosis at an early stage, as well as to develop differentiated and safe treatment plans for the disease.

In general, rheumatoid arthritis in children is characterized by a chronic, steadily progressing course with the development of often lifelong disability. Despite active therapy, by the age of 25, 30% of patients who developed juvenile rheumatoid arthritis at an early age still have an active process. Half of them become disabled. In 48% of patients, severe disability develops within the first 10 years after the onset of the disease. People who have suffered from rheumatoid arthritis since childhood are stunted. Osteoporosis is detected in 54% of them. By the age of 25, 50% of patients have undergone reconstructive surgery on the hip joints. Sexual dysfunction is detected in 54% of adults who developed juvenile rheumatoid arthritis in childhood. 50% of patients do not have a family, 70% of women do not become pregnant, 73% of patients do not have children.

There are several variants of the course of juvenile rheumatoid arthritis: systemic, polyarticular, oligoarticular.

Systemic variant of the course of juvenile chronic arthritis

The systemic variant accounts for 10-20% of cases. It develops at any age. Boys and girls get sick with the same frequency. The diagnosis of the systemic variant of juvenile rheumatoid arthritis is established in the presence of arthritis accompanied by fever (or with a previous documented fever) for at least 2 weeks in combination with two or more of the following symptoms:

1. rash;
2. serositis;
3. generalized lymphadenopathy;
4. hepatomegaly and/or splenomegaly.

When diagnosing systemic juvenile rheumatoid arthritis, the presence and severity of systemic manifestations should be assessed. The course of the disease is acute or subacute.

Fever - febrile or hectic, with temperature rises mainly in the morning, often accompanied by chills. When the temperature drops, profuse sweating occurs.

The rash is spotty and/or maculopapular, linear, not accompanied by itching, not persistent, appears and disappears within a short time, intensifies at the height of the fever, is localized mainly in the area of the joints, on the face, on the lateral surfaces of the body, buttocks and limbs. In some cases, the rash may be urticarial or hemorrhagic.

In the systemic variant of juvenile rheumatoid arthritis, damage to internal organs occurs.

Heart damage often occurs as myopericarditis. The patient complains of pain in the heart area, left shoulder, left shoulder blade, and in the epigastric region with pericarditis; a feeling of shortness of breath, and palpitations. The child may be forced to sit. During examination, the physician should pay attention to the presence of cyanosis of the nasolabial triangle, acrocyanosis, and pulsation in the heart area and epigastric region. Percussion of the borders of relative cardiac dullness reveals expansion to the left. During auscultation of the heart, the tones are muffled, a pronounced systolic murmur is heard, often over all valves; tachycardia is characteristic, even paroxysmal, and pericardial friction murmur is determined with pericarditis. With recurrent pericarditis, progressive fibrosis develops with the formation of an "armored" heart.

Lung damage may manifest itself as pneumonitis or pleuropneumonitis. The patient complains of a feeling of shortness of breath, dry or wet unproductive cough. During examination, attention should be paid to the presence of cyanosis, acrocyanosis, dyspnea, the participation of accessory muscles and the wings of the nose in the act of breathing. During auscultation, abundant fine-bubble wheezing and crepitation in the lower parts of the lungs are heard.

With the development of fibrosing alveolitis, patients complain of rapid fatigue, dyspnea, which occurs first during physical exertion, then at rest; a dry, unproductive cough. During examination, cyanosis is detected, and during auscultation, intermittent fine-bubble rales are detected. The doctor should remember the possibility of fibrosing alveolitis developing in juvenile rheumatoid arthritis and be attentive to the patient, since the initial stages are characterized by a discrepancy between the severity of dyspnea and minor physical changes in the lungs (weakened breathing).

Polyserositis usually manifests itself as pericarditis, pleurisy, less often as perihepatitis, perisplenitis, serous peritonitis. Peritoneal damage may be accompanied by abdominal pain of various natures. In juvenile rheumatoid arthritis, polyserositis is characterized by a small amount of fluid in the serous cavities.

With systemic juvenile rheumatoid arthritis, vasculitis may develop. During examination, the doctor should pay attention to the color of the palms and feet. Palmar, less often plantar, capillaritis, local angioedema (usually in the hand area), the appearance of cyanotic coloring of the proximal parts of the upper and lower extremities (palms, feet) and marbling of the skin may develop.

Lymph node adenopathy is a common symptom of the systemic variant of juvenile rheumatoid arthritis. It is necessary to evaluate the size, consistency, mobility of the lymph nodes, and the presence of pain when palpating them. In most cases, an increase in the lymph nodes of almost all groups up to 4-6 cm in diameter is detected. The lymph nodes are usually mobile, painless, not fused with each other or with the underlying tissues, soft or dense elastic consistency.

In most patients, an increase in the size of the liver is determined, less often the spleen, which, as a rule, is painless upon palpation, with a sharp edge of a dense elastic consistency.

The systemic variant of juvenile rheumatoid arthritis can occur with oligo-, polyarthritis or with delayed articular syndrome.

In the systemic variant with oligoarthritis or delayed joint syndrome, arthritis is usually symmetrical. Large joints (knees, hips, ankles) are predominantly affected. Exudative changes predominate, and deformations and contractures develop at a later stage. Almost all patients, on average, develop coxitis with subsequent aseptic necrosis of the femoral heads in the 4th year of the disease (and sometimes earlier). In some cases, the joint syndrome is delayed and develops several months, and sometimes years after the onset of systemic manifestations. The child is bothered by arthralgia and myalgia, which intensify at the height of the fever.

In the systemic variant with polyarthritis, from the onset of the disease, a polyarticular or generalized joint syndrome is formed with damage to the cervical spine, predominance of proliferative-exudative changes in the joints, rapid development of persistent deformities and contractures, amyotrophy, and hypotrophy.

With the systemic variant of juvenile rheumatoid arthritis, the following complications may develop:

• cardiopulmonary failure;
• amyloidosis;
• growth retardation (especially pronounced when the disease begins in early childhood and with polyarticular joint syndrome);
• infectious complications (bacterial sepsis, generalized viral infection);
• macrophage activation syndrome.

Macrophage activation syndrome (or hemophagocytic syndrome) is characterized by a sharp deterioration in condition, hectic fever, multiple organ failure, hemorrhagic rash, bleeding of the mucous membranes, impaired consciousness, coma, lymphadenopathy, hepatosplenomegaly, thrombocytopenia, leukopenia, decreased ESR, increased serum triglyceride levels, transaminase activity, increased fibrinogen and fibrin degradation products (early preclinical sign), decreased levels of blood clotting factors (II, VII, X). Bone marrow puncture reveals a large number of macrophages phagocytizing hematopoietic cells. Development of macrophage activation syndrome can be provoked by bacterial, viral (cytomegalovirus, herpes virus) infections, drugs (NSAIDs, gold salts, etc.). With the development of macrophage activation syndrome, a fatal outcome is possible.

Polyarticular variant of juvenile chronic arthritis

The polyarticular variant of juvenile rheumatoid arthritis accounts for 30-40% of cases. In all classifications, the polyarticular variant is divided into two subtypes depending on the presence or absence of rheumatoid factor: seropositive and seronegative.

The rheumatoid factor seropositive subtype accounts for about 30% of cases. It develops at the age of 8-15 years. Girls are more often affected (80%). This variant is considered as early-onset rheumatoid arthritis of adults. The course of the disease is subacute.

The joint syndrome is characterized by symmetrical polyarthritis with damage to the knee, wrist, ankle, and small joints of the hands and feet. Structural changes in the joints develop during the first 6 months of the disease with the formation of ankylosis in the small bones of the wrist by the end of the first year of the disease. Destructive arthritis develops in 50% of patients.

The rheumatoid factor seronegative subtype accounts for less than 10% of cases. It develops between the ages of 1 and 15. Girls are more often affected (90%). The course of the disease is subacute or chronic.

The joint syndrome is characterized by symmetrical damage to large and small joints, including the temporomandibular joints and the cervical spine. The course of arthritis in most patients is relatively benign, while 10% of patients develop severe destructive changes, mainly in the hip and temporomandibular joints. There is a risk of uveitis.

In some cases, the disease is accompanied by subfebrile fever and lymphadenopathy.

Complications of the polyarticular variant:

• flexion contractures in joints;
• severe disability (especially with early onset);
• growth retardation (with early onset of the disease and high activity of juvenile rheumatoid arthritis.

Oligoarticular variant of juvenile chronic arthritis

The oligoarticular variant of juvenile rheumatoid arthritis accounts for about 50% of cases. According to the classification of the International League of Rheumatological Associations, oligoarthritis can be persistent and progressive. Persistent oligoarthritis is diagnosed when up to four joints are affected throughout the entire period of the disease; progressive oligoarthritis - when the number of affected joints increases after 6 months of the disease. The following criteria are used to characterize arthritis: age of onset, nature of joint damage (large or small joints affected, joints of the upper or lower extremities involved in the process, symmetrical or asymmetrical joint syndrome), presence of ANF, development of uveitis.

According to the criteria of the American College of Rheumatology, the oligoarticular variant is divided into 3 subtypes.

The early-onset subtype (50% of cases) develops between the ages of 1 and 5. It occurs predominantly in girls (85%). Forarticular syndrome is characterized by damage to the knee, ankle, elbow, wrist joints, often asymmetrical. In 25% of patients, the course of articular syndrome is aggressive with the development of destruction in the joints. Iridocyclitis occurs in 30-50% of patients.

The late-onset subtype (10-15% of cases) is most often attributed to the debut of juvenile ankylosing spondylitis. It develops at the age of 8-15 years. Mostly boys are affected (90%). The joint syndrome is asymmetric. The joints are affected mainly in the lower extremities (heel areas, joints of the feet, hip joints), as well as the iliosacral joints, and the lumbar spine. Enthesopathies develop. The course of the joint syndrome is very aggressive, patients quickly develop destructive changes (especially in the hip joints) and disability. Acute iridocyclitis develops in 5-10%.

The subtype, which is found in all age groups, is characterized by onset at the age of 6 years. Girls are more often affected. The joint syndrome is usually benign, with mild enthesopathies, without destructive changes in the joints.

Complications of the oligoarticular variant of juvenile rheumatoid arthritis:

• asymmetry of limb growth in length;
• complications of uveitis (cataracts, glaucoma, blindness);
• disability (due to the state of the musculoskeletal system, eyes). The ILAR classification distinguishes three more categories of juvenile rheumatoid arthritis.

Enthesitis arthritis

The category of enthesitic arthritis includes arthritis associated with enthesitis or arthritis with two or more of the following criteria: pain in the iliosacral joints; inflammatory pain in the spine; the presence of HLA B27; a family history of anterior uveitis with pain, spondyloarthropathies, or inflammatory bowel disease; anterior uveitis associated with pain, redness of the eyeball, or photophobia. To characterize arthritis, the age of onset, the location of arthritis (small or large joints are affected), the nature of arthritis (axial, symmetrical, or progressing to polyarthritis) are assessed.

Psoriatic arthritis

The diagnosis of psoriatic arthritis is established in children with psoriasis and arthritis; children with arthritis and a family history burdened with psoriasis in first-degree relatives, with dactylitis and other lesions of the nail plate. The following criteria are used to characterize arthritis: age of onset, nature of arthritis (symmetrical or asymmetrical), course of arthritis (oligo- or polyarthritis), presence of ANF, uveitis.

Markers of poor prognosis in juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis is a disease with a poor prognosis in most patients.

The outcome of the disease is determined by the early administration of adequate immunosuppressive therapy based on the identification of markers of an unfavorable prognosis at the onset of the disease.

Long-term studies have shown that traditional treatment of juvenile rheumatoid arthritis with drugs that affect primarily the symptoms of the disease (non-steroidal anti-inflammatory drugs, glucocorticoid hormones, aminoquinoline derivatives) does not prevent the progression of bone and cartilage destruction and disability in most patients.

Long-term studies of the characteristics of the course of juvenile rheumatoid arthritis indicate that some indicators of disease activity are of significant importance and can be regarded as markers for the prognosis of an aggressive course of juvenile rheumatoid arthritis. The main ones include:

• onset of the disease before the age of 5 years;
• systemic variants of disease onset;
• debut as oligoarthritis of the first and second types;
• debut of the seropositive variant of juvenile rheumatoid arthritis;
• rapid (within 6 months) formation of symmetrical generalized or polyargicular joint syndrome;
• continuously recurring course of the disease;
• significant persistent increase in ESR, concentration of CRP, IgG and rheumatoid factor in the blood serum;
• increasing functional insufficiency of the affected joints with limitation of the patients' ability to self-care during the first 6 months after the onset of the disease.

In patients with the indicated markers, it is possible to predict the malignant course of juvenile rheumatoid arthritis already at the onset.

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