Diagnosis of juvenile ankylosing spondylitis

When diagnosing juvenile spondylitis, one should be guided by existing classification and diagnostic criteria based on a combination of anamnestic data, clinical manifestations and the necessary minimum of additional studies:

• Radiography of the pelvis;
• X-ray, MRI and CT of the spine and peripheral joints (in the presence of clinical data);
• examination of the ophthalmologist on a slit lamp in order to verify the presence and nature of uveitis;
• functional examination of the heart;
• immunogenetic analysis (HLA-B27 typing).

The most acceptable, generally recognized classification criteria for the entire group of juvenile spondyloarthritis are the criteria proposed by the European Spondyloarthropathies (ESSG) group, which were highly evaluated for their sensitivity and specificity in international multicenter studies.

Classification criteria of the European Group for the Study of Spondyloarthropathies

• Pain in the spine and / or arthritis (asymmetrical, predominantly of the lower extremities).
• One or more of the following criteria (current or previous):
  • presence in relatives of the first or second degree of kinship of ankylosing spondylitis, psoriasis, reactive arthritis, Crohn's disease or ulcerative colitis;
  • psoriasis;
  • inflammatory bowel disease (Crohn's disease or ulcerative colitis, confirmed radiographically or endoscopically);
  • urethritis, cervicitis or acute diarrhea that occurred 1 month before the onset of arthritis;
  • intermittent pain in buttocks;
  • pain in the heels;
  • sakroileitis, confirmed radiographically (bilateral II-IV stage or one-sided III-IV stage).

The classification criteria for spondyloarthritis are optimal for distinguishing this range of diseases from juvenile rheumatoid arthritis; however, the adoption of this group term in the diagnosis formulation is not appropriate, since this means the concept of "undifferentiated spondylitis" and the diagnosis according to ICD-10, the diagnosis is coded as M46, ie outside the rubric of juvenile arthritis (M08). The diagnosis of juvenile chronic arthritis (UXA) is most acceptable for the designation of the pre-presonal stages of juvenile ankylosing spondylitis, when the disease can not yet meet the generally accepted criteria of AS. It is this diagnosis that makes it possible not to place a deliberately incorrect diagnosis of juvenile rheumatoid arthritis in those situations where the likelihood of further development of spondyloarthritis is high. To emphasize the predicted outcome, it is justified to make the definition of "HLA-B27-associated" in those patients who underwent an immunogenetic study and detected HLA-B27-antigen in the formulation of the diagnosis of UXA.

The verification of the diagnosis of juvenile ankylosing spondylitis is eligible only if the internationally recognized criteria for ankylosing spondylitis are met, the most common of which is currently the modified New York criteria. It should be borne in mind that these criteria are oriented, mainly, to the manifestation of the spine and x-ray confirmation of sacroiliitis. This circumstance makes the application of these criteria problematic for the diagnosis of early stages of the disease, especially in childhood, taking into account the delayed involvement of the axial skeleton in the process of juvenile onset and the difficulties in radiologic verification of sacroiliitis in children and adolescents due to incompleteness of skeletal ossification processes.

Modified New York criteria for ankylosing spondylitis

Criteria	Symptoms
Radiographic	Sacroiliitis: bilateral stage II or one-sided III-IV stage
Clinical criteria	Pain and stiffness in the lower back, lasting at least 3 months, decreasing in physical exercises and not passing after rest Limitation of mobility of the lumbar spine in the sagittal and frontal planes Reduction of the chest excursion in relation to the age norm
Criteria for the diagnosis of ankylosing spondylitis	The diagnosis of a certain ankylosing spondylitis is determined by the presence of an X-ray and at least one clinical criteria Probable ankylosing spondylitis can be suspected, based only on clinical criteria or only from radiological

There are also international diagnostic criteria (developed specifically for the diagnosis of juvenile ankylosing spondylitis by a group of German rheumatologists), known in the literature as Garmisch-Partenkirchen criteria, which, despite their high sensitivity and specificity, are not universally recognized today and do not allow verifying the diagnosis of juvenile ankylosing spondylitis .

The criteria for juvenile ankylosing spondylitis (Garmisch-Partenkirchen, 1987)

Main criteria	Additional criteria
Asymmetric pauciarthritis (less than five joints), predominantly of the lower limbs in the debut of the disease (in the first 3 months)	Polyarthritis (more than four joints) in the onset of the disease
Enthesopathy	Male
Pain in the lumbosacral region	Age of onset of the disease more than 6 years
Acute Iridocyclitis	The presence of HLA-B27 antigen
	Family aggregation for diseases from the seronegative spondyloarthritis group

Two main criteria or one or two major and two additional ones are probable juvenile ankylosing spondylitis; the same criteria and radiologically valid sacroileitis (bilateral stage II or unilateral, at least stage III) - a certain juvenile ankylosing spondylitis.

Vancouver diagnostic criteria for juvenile psoriatic arthritis

Certain juvenile psoriatic arthritis: arthritis and a typical psoriatic rash or arthritis and three of the following ("small") criteria:

• changes in nails (symptom "thimble", onycholysis);
• psoriasis in relatives of the first or second degree of kinship;
• psoriasis-like rash;
• dactylite.

Probable juvenile psoriatic arthritis: arthritis and two of the four small criteria.

The main criteria for the diagnosis of Reiter's disease in children (triad of changes):

• arthritis;
• conjunctivitis;
• urethritis.

The diagnosis of enteropathic arthritis (against a background of chronic inflammatory bowel diseases) is put in the presence of:

• arthritis;
• chronic bowel disease (Crohn's disease, ulcerative colitis), verified by endoscopic and histological examination.

An important aspect of the diagnosis of juvenile ankylosing spondylitis - a physical examination with an assessment of the functional state of the spine. The ASAS working group (an international expert group that collects clinical and scientific data, using expert advice and statistical approaches to better assess and understand the evolution of AS) recommends that easily assessable measures that objectively reflect changes in all parts of the spine are used to assess the mobility of the spine.

To determine the limitation of movements in the sagittal plane, use the Tomeier symptom - the distance from the fingertips to the floor at the maximum inclination forward, without bending the knees. Normally, it should not exceed 5 cm. It should be taken into account that the patient with limited mobility of the spine, but with good mobility in the hip joints, can reach the floor, the lumbar spine remains straight, without a bulge that is normal for a healthy person. This test, as applied to the pediatric population, does not have the necessary specificity either, since it is often determined in children and adolescents with non-inflammatory orthopedic pathology and in the event of banal impairment of posture and physical detuning of the child.

To assess mobility of the lumbar spine, the Schober test is used: in the patient's position, standing on the midline of the back, mark a point on an imaginary line connecting the posterior upper tips of the ileum. Then mark the second point, 10 cm above the first. Then the patient is asked to bend forward as much as possible, without bending the knees, and in this position the distance between two points is measured. Normally, it should increase to 15 cm or more. It should be taken into account that in this test, the functional status of the lumbar spine proper is evaluated, which is later affected by juvenile ankylosing spondylitis after the lower thoracic department. More informative is the modified Shober's test, which differs from the previous one in that it marks two points 5 and 15 cm above the line connecting the posterior upper arms of the iliac bones. Foreign scientists on the basis of population studies in children and adolescents of different sex and age established and reduced to the appropriate tables the normal values for the modified Schober test.

In the diagnosis criteria, the limitations of mobility of the lumbar spine in two planes are taken into account, therefore it is necessary to evaluate the movements of the lumbar spine and in the frontal plane. For this, a lateral flexion measurement is used in this section. First, the distance between the tip of the middle finger and the floor is determined, after which the patient is asked to bend sideways (without tilting the body forward and bending the knees), and again measure this distance using a vertical ruler standing on the floor. In this case, the difference between the initial distance and the distance after the slope is estimated. Normally this difference should be at least 10 cm.

To assess the function of the thoracic spine, Ott's test is performed, determining the distance between two points: at the level of the VII cervical vertebra and 30 cm below. Normally, when tilted, it increases by 5-7 cm. It should be emphasized that it is necessary to correctly perform this test with the requirement of maximum straightening of the back before the measurement begins. It has low specificity, as patients with juvenile kyphosis (Scheuerman-Mau disease) often show lower values compared with patients with juvenile ankylosing spondylitis.

Restriction of the chest excursion is an important test made in the criteria for the diagnosis of ankylosing spondylitis, which may indicate involvement in the pathological process of the rib-vertebral and rib-chest joints. Excursion of the chest - the difference between its circumference during inspiration and exhalation at the level of the IV rib. In norm (in accordance with sex and age), it should be at least 5 cm.

When involving the cervical spine, it is necessary to evaluate mobility in all directions, since in juvenile ankylosing spondylitis, in contrast to osteochondrosis, all kinds of movements are disrupted. Bending in the cervical region is assessed by measuring the distance of the chin-sternum, which should normally be 0 cm. To determine the severity of the cervical kyphosis, the Forestier symptom is used, measuring the distance from the occiput to the wall when the patient is placed with his back against the wall with his shoulder blades, buttocks and heels pressed to it . Impossibility to get the back of the neck to the wall indicates a lesion of the cervical region, and the distance measured in centimeters can serve as a dynamic indicator of its severity.

Turns and inclinations in the cervical spine are measured with a goniometer, and normally the angle of rotation should be at least 70 °, and the lateral slope angle should be at least 45 °.

Instrumental studies assist in the detection of inflammatory and structural changes in the musculoskeletal system.

X-ray assessment of lesion of the axial skeleton in children and adolescents presents significant difficulties due to incompleteness of the processes of ossification of the skeleton. It is known that on the radiographs of the pelvis in childhood, the articular surfaces of the intact sacroiliac joints may not look even and clear, their slits often have uneven widths, which can be mistakenly interpreted as manifestations of sacroiliitis. At the same time, even with significant growth zones, it is possible to detect indisputable radiological changes in sacroiliac joints, for example, osteosclerosis with the so-called pseudo-expansion phenomenon of the joint gap or pronounced erosions with single bone "bridges" corresponding to stage III and even complete ankylosis.

There are several gradations of radiological evaluation of sacroiliitis. The most common and widely known division into four stages according to Kellgren (included in the diagnosis criteria).

X-ray stages of sacroileitis according to Kellgren (New York criteria)

Stage	Changes	Features
0	Norm	No changes
1	Suspicion of sacroiliitis	Suspicion of changes (blurred edges of the joints)
II	The minimum	Small local areas of erosion or sclerosis without changes in the width of the joint space
III	Moderate	Moderately or significantly pronounced signs of sakroileitis: erosion, sclerosis, enlargement, narrowing or partial ankylosis of the joint
IV	Significant	Significant changes with complete ankylosis of the joint

These criteria are similar to the five stages of sacroileitis proposed by C. Dale. Common features for both grades:

• Changes to the first stage are suspicious for sacroiliitis, i.e. Subchondral osteosclerosis, some unevenness and fuzziness of articular surfaces, which does not exclude the possibility of a normal age-related radiographic picture;
• to the second stage include obvious pathological changes (pronounced osteosclerosis, not only in the iliac, but also in the sacral part of the joint space, pseudoextension of the joint gap and / or limited areas with erosions).

According to the Dale classification, the stages of psoriatic arthritis (unilateral changes) and lib (bilateral changes) are distinguished; Stage III in more detail reflects the possibility of regression of subchondral sclerosis and the presence of erosion; IV stage - partial ankylosis (formally corresponds to stage III according to Kellgren); V stage - complete ankylosis. For the quantitative assessment of the lesion of the overlying departments of the spine, the ASAS expert panel proposed an index of the radiologic progression of BASRI, assessed in balls at the following positions.

• X-ray stage of sacroileitis (0-4 points).
• X-ray changes in the spine (direct and lateral projection of the lumbar and lateral projection of the cervical spine) with a score of the severity of changes in each segment in the following grades:
  • 0 is the norm (no change)
  • I - suspicion (there are no obvious changes);
  • II - minimal changes (erosion, quadratization, sclerosis ± syndesmophytes on two vertebrae and more);
  • III - moderate changes (syndesmophytes of more than three vertebrae ± fusion of two vertebrae);
  • IV - significant changes (fusion with the involvement of more than three vertebrae).

Use in diagnosis of axial skeletal lesions, especially sacroiliitis, CT provides invaluable help in determining changes in the case of insufficient information in radiography. The ability to obtain images of transverse sections of sacroiliac joints allows visualizing the structural changes of all parts of the joint gaps and to obtain a much more accurate picture of the first bone changes (disappearance of the continuity of the terminal bone plate, local erosion, subchondral osteosclerosis, pseudorangement of the cleft). Identifying early inflammatory changes in sacroiliac joints and overlying structures of the spine helps the MRI, however, the methodology for using this method in diagnosis of SUS still needs to be studied and refined.

Ultrasound imaging methods can confirm synovitis in the peripheral joints, which is important for assessing the activity and tactics of treatment.

Changes in laboratory parameters with juvenile ankylosing spondylitis are not specific and can not be of significant benefit either in diagnosis or in the development of treatment tactics. According to the data of different authors and our observations in 1/4 of patients with juvenile ankylosing spondylitis, as well as with ankylosing spondylitis of adults, the value of ESR and other acute inflammatory indices never exceeds the normal values. At the same time for the other 1/4 patients, high humoral activity is characteristic, often with a tendency to persistence and correlating, as a rule, with the severity of peripheral arthritis.

HLA-testing is of particular clinical importance, in particular, the detection of B27 and antigens that are part of the B7-CREG-rpynny ("cross reactive group"). It is important to note that the immunogenetic study performs not so much a diagnostic as a prognostic role, since B27 antigen is present in the genotype of not all patients with juvenile ankylosing spondylitis (75-90%), but its presence determines some features of the course of the disease. The carrier of HLA-B27 antigen is associated with a higher frequency of polyarthritis, tarsita, involvement of small joints of hands and feet, dactylitis, uveitis, persistence of high laboratory activity, and higher absolute indices of activity, especially ESR, C-reactive protein and IgA.

Differential diagnostics

At those stages when the clinical picture of the disease is represented by an isolated articular syndrome, an important differential diagnostic value is attached to the qualitative characteristic of arthritis, which primarily distinguishes juvenile ankylosing spondylitis and diseases of the spondyloarthritis circle.

The delineation of juvenile ankylosing spondylitis and other juvenile spondyloarthropathies is based primarily on anamnestic information on the chronological association of the disease with an acute episode of intestinal or urogenital infection, as well as the presence of skin psoriasis, Crohn's disease or ulcerative colitis in the patient or his immediate family. It should be emphasized once again that a clear distinction between juvenile ankylosing spondylitis and other spondyloarthropathies is not always possible due to the commonness of the main clinical signs, the tendency to form cross syndromes between the diseases of this group and the ability to form a clinical picture of juvenile ankylosing spondylitis in the outcome of any spondyloarthritis.

A necessary condition for differential diagnosis of juvenile ankylosing spondylitis is the exclusion of all non-rheumatic diseases that can cause clinical symptoms similar to juvenile ankylosing spondylitis: septic and infectious (tubercular, brucellosis, etc.) arthritis or sacroiliitis, a diverse pathology of the locomotor apparatus of non-inflammatory genesis (dysplasia, osteochondropathy, etc.). In rare cases, there may be a need for differentiation with hematological diseases or neoplasms. Among malignant neoplasms, "rheumatic masks", especially articular syndrome, ossalgia and back pain, most often occur with systemic blood diseases, neuroblastoma and a group of primitive neuroectodermal tumors (Ewing's sarcoma, etc.).

In acute local symptoms of axial skeleton lesions with significant pain syndrome and absence of peripheral arthritis, the child first of all requires the elimination of non-rheumatic diseases.

Acute manifestations of arthritis in a limited number of joints, especially combined with signs of periarticular lesion, require the exclusion of osteomyelitis, both acute, subacute, and chronic multifocal. For the latter, symptoms of axial skeletal lesions are also inherent, sometimes with a significant pain component, and with prolonged course - the development of destruction of not only the peripheral joints, but also the vertebral bodies.

Indications for consultations of other specialists

• The oculist. On the slit lamp, every 3-6 months, all patients with juvenile arthritis are examined to exclude subclinical development of uveitis and complications of drug treatment; with an oligoarticular variant of juvenile arthritis to exclude subclinical development of uveitis and complications of medication with early age debut and the presence of ANF.
• Endocrinologist. It is necessary to observe patients with juvenile arthritis in order to exclude the subclinical development of uveitis and complications of medication with marked signs of exogenous hypercorticism, growth disorders, impaired glucose tolerance.
• Otolaryngologist. Inspection is necessary to find and sanitize foci of chronic infection in the nasopharynx.
• Dentist. Identify tooth decay, dysplasia of the growth of the jaws, teeth and bite. Inspect patients with suspected "dry syndrome" (Sjogren's syndrome).
• Phthisiatrician. Consultation is necessary with a positive Mantoux reaction, lymphadenopathy, to address the possibility of using anticytokine treatment with TNF-a blockers.
• Orthopedist. Patients are examined with functional failure of joints, bone growth in length, subluxations, for the development of rehabilitation measures, determining indications for surgical treatment.
• Geneticist. Consultation is necessary for multiple small developmental anomalies, connective tissue dysplasia syndrome.

[1], [2], [3], [4]