III./ 5.: Systemic spinal diseases – SeronegativespondylarthrosisIntroduction

The following chapter will discuss diseases that belong to the same groupbased on didactics and practical considerations.

III./5.1.: DefinitionThe concept of seronegative spondylarthritis (SNSA) as a group of diseasesis quite new, and was introduced by Wright and Reed in 1964.

This group of diseases is characterized by the absence of the rheumaticfactor, inflammation of the sacroiliac joints, calcification of the ligaments,and they usually asymmetrically affect the major joints of the lower limb, areaccompanied by skin and mucous membrane lesions, iritis, and may showfamilial cumulation.

III./5.2.: Spondylitis ankylopoeticaSpondylitis ankylopoetica is the most common SNSA disease, and has beenconsidered an independent entity for about a century. It is the progressive,chronic inflammation of the sacroiliac joints and the spine, leading tostiffness of the spine through calcification of the joints and ligaments.

Figure 1.: Multi-decade SPA with deformation of the spine and calcification of the ligaments.]]

III./5.2.1.: Incidence

Incidence is around 0.1-0.2 % in Caucasians. It affects around 20000 peoplein Hungary (incidence of 0.2%). Male to female ratio is 7:1. It usuallypresents in early adulthood, but may occur in childhood as well.

III./5.2.2.: Etiopathology

Familial cumulation of SPA is a well-known fact. There is evidence forpolygenic inheritance, the disease is associated with human leukocyte-antigen HLA B27 (90 % of patients are HLA B27 positive). Environmentalfactors play a role in HLA B27 positivity (i.e.: urogenital, and gastrointestinalinfections).

III./5.2.3.: Clinical symptoms

The disease usually presents in the 2nd decade of life, but juvenile and senileforms may also occur. In early stages symptoms are uncertain andnondescript, and hard to objectify. Typically the young man will complain ofpain presenting in the sacral region during the night with variable intensity,but becoming chronic and showing progression .Typical signs may beaccompanied by colorful symptoms: bilateral or alternating unilaterallumboischialgia (caused by the sacroileitis), transient coxitis – impairment ofthe hip joint that usually ceases spontaneously after a few days (with noobjectifyable symptoms), certain diagnosis may often be obtained followingmonoarthrites in the major joints of the lower limb, chest pain („it’s like I amwearing armor”), Tietze –syndrome –and painful swelling of thesternoclavicular joints.

Enthesites- characterized by pain, local tenderness and edema of thecalcaneus, the Achilles and the ischial bone are typical pathologies .

General symptoms are – fever, loss of appetite, weight loss, fatigue,especially if the disease presents at a young age.

Extraskeletal symptoms involve: acute anterior uveitis in one fourth of thepatients – iritis or iridocyclitis – 1-2 month episodes characterized byunilateral pain, tears, and avoiding the light, this requires emergencyophthalmic care.

Involvement of internal organs may include aortitis, aorta insufficiency,atrioventricular block, maybe even pericarditis, endarteritis. These symptomsrequire internal medicinal attention in young patients with only mild spinalsymptoms.

In 1-1.5% of the cases progressive fibrosis occurs in the upper lobes of thelung, which may be accompanied by an aspergillus infection. Symptoms maybe coughing, shortness of breath and haemaptoe.

Cauda equina syndrome may occur in chronic cases . Secondary amyloidosismay occur after several decades.

III./5.2.4.: On physical examination

We may find progressive stiffness and pain of the spine, sacroiliacinvolvement, and Mennel- sign positivity. Limited spinal motion may becharacterized by the lumbar Schober-sign examined in anteflexion (we mayalso measure finger-ground distance, and the limitation of side-to sidemotions, the involvement of costo-vertebral joints, and the decrease inthoracic expansion accompanying breathing, and monitor the above as thedisease progresses).

Video 1.: Examining a male patient suffering from SPA

III./5.2.5.: Radiological investigations

Confirming sacroileitis is the basis for diagnosis. Beside confirming thesacroileitis MRI or technetium bone isotope examinations are diagnostic inearly stages and objectify the activity of the disease with the sacroiliac index(in most cases values above 1.3- 1.4 are considered pathological).

Figure 2.: Ankylosis occurs following long-standingsacroileitis, with disappearance of the joint gap

Figure 3.: Calcification in theligaments of the lumbar spine

Figure 4.: Calcification of the ligaments on the cervical spine, with characteristic SPA vertebrallesions]]

The criteria of spondylitis ankylopoetica, modified in 1984:

1.) Clinical criteria:

2.) Lower back pain for at least three months

3.) stiffness, that decreases to movement, but

4.) does not decrease when resting.

5.) Limited motion of the lumbar spine in the sagittal and frontalplane

6.) Decrease in the expansion of the chest while breathing comparedto normal values from a healthy group matched for age and sex.

7.) Radiological criteria:

8.) Bilateral stage II or unilateral stage III-IV sacroileitis.

9.) Definitive diagnosis of SPA may only be set-up, if a clinicalcriteria accompanies a radiological criteria.

III./5.2.6.: Treatment

Non-steroid anti-rheumatic medication must be administered to relieve painand inflammation, and continuous mechano-fiziotherapy ensures appropriateposture. If there is severe peripheral involvement, base therapy should begiven (mostly sulfasalasin, methotrexat).

In the past years the introduction of biological therapy has revolutionalizedtreatment. The proinflamatory cytokines, tumor necrosis-factor-alpha(TNF-alpha) is inhibited, and it seemed that this decreases both spinalinflammation and peripheral arthritis in spondylarthritis ankylopoetica. TheTNF-alpha cytokine, produced by T1 helper cells is involved in the disease inseveral points. It has been observed in HLA B27-positive sponisdylarthritisankylopoetica patients, that the expression of TNF-alpha decreases.Biological therapy may only be stared when disease is confirmed „for sure”by the modified New-York criteria, and the disease remains active despiteadequate medicinal treatment. Medicinal treatment is considered adequate, iftwo different types of non-steroid anti-inflammatory drugs, given inmaximum doses does not produce proven improvement, or if the diseaseshows progression in cases with peripheral involvement despite DMARDtherapy. Activity of the disease may be monitored with the BASDAI index.

III./5.3.: Arthritis psoriaticaArthritis psoriatica (AP) is a seronegative joint inflammation accompanyingpsoriasis.

The genetics of psoriasis are complex: skin lesions and AP show polygenicmultifactorial inheritance, with possible familial cumulation.

HLAB27 association is more frequent in cases showing spinal involvement.

Clinical symptoms:

1) ongoing psoriasis, or psoriasis in patient history.

2) peripheral polyarthritis, frequently symmetric

3) typical DIP-joint inflammation

4) nocturnal lower back (lumbar spine) pain

5) mutilating arthritis (telescopic fingers) – typical, but rare

6) dactylitis (sausage fingers)

7) enthesitis (especially in the Achilles-tendon)

The Moll-Wright (1973) classification is the most well-known one, despitemore current ones, that take extraarticular manifestations into consideration:

1) distal type

2) arthritis mutilans

3) symmetrical, polyarticular (”RA-like”)

4) asymmetrical oligoarticular or monoarthritis

5) spondylitis type

III./5.4.: Reactive arthritisThese are diseases that present following enteral, urogenital infections, orsterile joint inflammations.

Higher HLA B27 association, radiological sacroileitis, lower limboligoarthritis, skin and mucous membrane lesions, ocular involvement andentheses are typical.

Reiter’s disease has the most colorful symptoms, and it involves severalorgans. Reiter-triad: sterile joint inflammation following enteral or urogenitalbacterial infections, accompanied by sterile urethritis and conjunctivitis.

III./5.5.: Enteropathic arthritisEnteropathic arthritis is a collective concept for arthritis associated withnon-specific inflammatory bowel diseases (IBD).

The two forms of IBD are Colitis ulcerosa (CU), and Crohn’s-disease (CD)

Beside arthritis further extraintestinal manifestations may occur (i.e.erythema nodosum, pyoderma gangrenosum, uveitis etc.)

Epidemiology is characterized by genetic and environmental determination.The occurrence of both types of IBD is becoming more and more common ineconomically developed countries.

CD is slightly more common in females, and CU in males.

The presence of HLA B27 antigens is significant in case of sacroileitis andspondylarthritis.

Types of eneropathic arthritis:

1.) peripheral arthritis (is associated with IBD in 15-20% of the cases)

2.) axial arthritis (sacroileitis and spondylarthritis)

3.) other inflammatory lesions.