This describes a group of related inflammatory joint diseases distinct from RA, which show considerable overlap in their clinical features and shared immunogenic association with the HLA- B27 anitigen These diseases include:

Ankylosing spondylitis. Reactive arthritis( Reiter’s syndrome). Psoriatic arthritis. Arthropathy associated with IBD.

 the term seronegative RA is used to describe patients in whom the standard test for IgM rf's and ANA are persistently negative.  They have a limited pattern of synovitis ( affects joint capsule, periarticular periosteum, cartilage and subchondral bone)  rf's are not found in synovitis associated with psoriasis,ankylosing spondylitis,or IBD arthopathy or in reactive arthritis.

 These diseases have the following conditions in common:  They are in relation to HLA-B-27.  Inflammatory arthritis, generally sacroiliitis and spondylitis  Oligoarthritis, generally with asymmetrical presentation  Enthesitis.  familial aggregation occurs.  rheumatoid factor is not present.  Extra-articular features, such as involvement of eyes, skin and genitourinary tract.  Overlap is likely between several of the causative conditions.

 The common aetiological thread of these disorders is their striking association with HLA-B27, particularly ankylosing spondylitis (AS). This was the first demonstrated disease association of any HLA type (B27 is present in > 90% of Caucasians with AS). Its aetiological relevance remains unclear.

 There are clues that infections play a role, possibly by molecular mimicry, with parts of the organism which are structurally similar to the HLA molecule triggering cross-reactive antibody formation. This is unproven. AIDS is increasing the prevalence of reactive arthritis and spondylitis in sub-Saharan Africa even in the absence of HLA-B27. The explanation for this changing epidemiology is unclear.

 The specialized immune systems of the gut and genitourinary mucous membranes may also play a causal role, perhaps reacting to local infections or to antigens which cross the damaged mucosa.  The types of arthritis that follow a precipitating infection are called reactive arthritis.

 Ankylosing spondylitis : is a chronic inflammatory disorder of unknwon etiology, that affect axial skeleton (predominantly sacroiliac joint) and peripheral joints, and can progress to bony fusion. Peak incidence between Common in males more than females ( 3:1).) one f the few collagen vascular diseases that affect male more than female ) more than 90 % of PTs are HLA-B27 positive. Most of patients have a good quality of life.

- Unknown. - more than 90 % of PTs are HLA-B27 positive. - Thought to be exposure to a common pathogen in genetically susceptible individuals, although no specific trigger has been identified.

 Ankylosing spondylitis (AS) is a systemic rheumatic disease, meaning it affects the entire body. Approximately 90% of AS patients express the HLA-B27 genotype, meaning there is a strong genetic association. However, only 5% of individuals with the HLA-B27 genotype contract the disease. Tumor necrosis factor- alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with AS, but do not correlate with disease severity.

 Ankylosing spondylitis is one of a cluster of conditions known as seronegative spondyloarthropathies, in which rheumatoid factor tests are negative and the characteristic pathological lesion is an inflammation of the enthesis (the insertion of tensile connective tissue into bone).

- gradual in onset. - Low back pain & marked stiffness. - May radiate to the buttocks or post. Thigh (misdiagnosed with sciatica). - Marked at morning & after inactivity. - Relived by movement. - Whole spine can be involved. - Spinal rigidity & 2ndry osteoporosis. - Restriction of lumbar spine movement. - Failure to obliterate lumbar lordosis. - Pleuritic chest pain due to costocervical involvement. - plantar fasciitis & Achilles tendonitis.

- Up to 40 % of patients have peripheral arthritis. - Asymmetrical, mainly affecting hips, knees,ankles and shoulders. - Most commonly ankle,knee and elbow may precede the development of spinal symptoms in 10% of cases.

- Anterior uveitis (25%) and conjunctivitis (20 %). - Prostatitis (80%) (asymptomatic). - CHF - Amylodosis - Atypical upper lobe pulmonary fibrosis.

- Investigations: X-RAY study shows : sacroiliitis & fused sacroilliac joint. - MRI : more sensitive to sacroiliitis but is rarely required. - Chronic AS will eventually cause bamboo spine. - ESR and CRP usally raised in active disease. - RF and Abs are –ve. - HLA-B27 not commonly used.(juvenile arthritis).

 The major types of medications used to treat ankylosing spondylitis are pain- relievers and drugs aimed at stopping or slowing the progression of the disease. Pain- relieving drugs come in two major classes:  1-Anti-inflammatory drugs, which include NSAIDs such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain.  2-Opioid analgesics, which are addictive and not generally prescribed

 Drugs used to treat the progression of the disease include:  Disease-modifying antirheumatic drugs (DMARDs) such as cyclosporin, methotrexate, sulfasalazine, and corticosteroids, are used to reduce the immune system response through immunosuppression;  Tumor necrosis factor-alpha (TNFα) blockers (antagonists), such as the biologics etanercept, infliximab, golimumab and adalimumab, have shown good short-term effectiveness and trials are ongoing to determine their long-term effectiveness and safety.One drawback is the cost.  Anti-interleukin-6 inhibitors such as Tocilizumab, currently approved for the treatment of rheumatoid arthritis, and rituximab, a monoclonal antibody against CD20, are also undergoing trials.

 Reactive arthritis is a sterile synovitis, which occurs following an infection.  Seronegative spondyloarthropathy develops in 1–2% of patients after an acute attack of dysentery, or a sexually acquired infection – non- specific urethritis (NSU) in the male, non-specific cervicitis in the female. In male patients who are HLA-B27 positive the relative risk is 30–50.  Women are less commonly affected.  Ration men to women ( 15:1 )

Reiter's disease Classic triad :  Non-specific urethritis.  Conjunctivitis ( ∼ 50%).  Reactive arthritis.

Aetiology  A variety of organisms can be the trigger, including some strains of Salmonella or Shigella spp. in bacillary dysentery.  Yersinia enterocolitica causes diarrhea and a reactive arthritis. In NSU the organisms are Chlamydia trachomatis or Ureaplasma urealyticum.

Clinical features  The arthritis is typically an acute, asymmetrical, lower-limb arthritis,(ankles, midtarsal joints, metatarsophalangeal joints or knees) occurring a few days to a couple of weeks after the infection. The arthritis may be the presenting complaint if the infection is mild or asymptomatic.

 Enthesitis is common, causing plantar fasciitis or Achilles tendinitis.  In susceptible individuals with reactive arthritis, sacroiliitis and spondylitis may also develop.

Extra-articular features 1. Circinate balanitis. 2. Keratoderma blenorrhagica – the skin of the feet and hands develops painless, red and often confluent raised plaques and pustules. 3. Nail dystrophy may occur.

Other features 4. Bilateral conjunctivitis. 5. Mouth ulcers manifest as shallow red painless patches on tongue, palate, buccal mucosa and lips, lasting only a few days. 6. Uveitis is rare with the first attack but occurs in 30% of patients with recurring or chronic arthritis.

Investigations  The diagnosis is usually made clinically but joint aspiration may be required to exclude crystal arthritis and infection. Synovial fluid is inflammatory and often contains giant macrophages (Reiter's cells).  X-rays are seldom helpful during the acute attack, but in chronic or recurrent disease periarticular osteopenia, joint space narrowing and marginal proliferative erosions may be observed.  Large “fluffy” heel spurs may be seen.

Treatment  There is some evidence that treating persisting infection with antibiotics will alter the course of the arthritis, once it has developed.  Pain responds well to NSAIDs and local corticosteroid injections.  DMARDs (disease modifying antirhuematic drugs) should be considered for patients with persistent marked symptoms.

-chronic, non-inflammatory D. -inflamed lessions covered by silvary-white skin. -the Avg. PT. age is 28. -types % develop PsA, so you should examen the whole skin of the Pt. - Risk factors : - Famly his. - Corticosteroids. - Infections. Lesions.. - ….-

 The term ‘psoriatic arthritis’ describes a variety of different patterns of arthritis and enthesitis seen in people with psoriasis or with a family history of psoriasis.  5 – 8 % of individuals with psoriasis develop one of several different patterns of arthritis for which there is no serological marker.

Clinical features the presentation is ( J. pain, swelling, disability “ uncommen” ) 1) ASYMMATRICAL INFLAMMATORY OLIGOARTRITIES : 2) Affect 40% of pt. and often present abruptly, occurs mostly in the hands and feet. Large J. ( knee, ankle) also may be involved often with effusion. 3). 4).

1)Symmetrical polyarthrites : 2)Affect about 25% of cases,and predominates in women and may resemble RA with symmatrical involvment of S. & L. joints in both upper and lower limb.much of hand deformaty often resut from tenosynovitis and soft tissue contructures.

1)DISTAL INTERPHALANGEAL ARTHRITIES: 1.A distal interphalangeal arthritis is the most typical pattern of joint involvement in psoriasis. It is unsightly, but rarely disabling, and there is often adjacent nail dystrophy reflecting inflammation in the enthesis extending into the nail root. Psortic spondylities : Presents a clinical picture similar to AS but with less sever involvment..

Psoriatic arthropathy. A. 'Sausage' middle finger of a patient with psoriatic arthritis. B. Typical distal interphalangeal joint pattern with accompanying nail dystrophy (pitting and onycholysis). Downloaded from: StudentConsult (on 2 February :05 PM) © 2005 Elsevier

Arthritis mutilans : affects about 5% of patients with psoriatic arthritis and causes marked periarticular osteolysis and bone shortening (‘telescopic’ fingers) in which, despite the deformity, pain may be mild and function often surprisingly good.

Arthritis mutilans : affects about 5% of patients with psoriatic arthritis and causes marked periarticular osteolysis and bone shortening (‘telescopic’ fingers) in which, despite the deformity, pain may be mild and function often surprisingly good.

Investigation : The dig. Usually made clinically * CRP, ESR may be raised.

4. psoriatic arthritis is erosive but the erosions are central in the joint, not juxta-articular, and produce a ‘pencil in cup’ appearance. 5. A unilateral or bilateral sacroiliitis and spondylitis develops in 15% of patients with early involvement of the cervical spine; only 50% are HLA-B27 positive.

Treatment and prognosis NSAIDs help the pain but they can occasionally worsen the skin lesions. Local synovitis responds to intra-articular corticosteroid injections. Therapy with DMARDs should be considered for persistent synovitis unresponsive to conservative treatment. Methotrexate is the treatment of first choice since it may also help skin psoriasis.  The prognosis for the joint involvement is generally better than in RA.

 Enteropathic synovitis occurs in approximately 10–15% of patients with ulcerative colitis and Crohn’s disease.  The link between the bowel disease and the inflammatory arthritis is not clear.  It predominantly affects the large lower limb joints (knees, ankles, hips) but wrists and small joints of the hands and feet can also be involved.

 Patients with inflammatory bowel disease may also develop sacroiliitis (16%) and AS (6%), which are clinically and radiologically identical to classic AS. These can predate or follow the onset of bowel disease.  Remission of ulcerative colitis or total colectomy usually leads to remission of the joint disease, but arthritis may persist even in well-controlled Crohn’s disease.

Treatment  The inflammatory bowel disease should be treated.  the joint disease should be managed symptomatically with NSAIDs, although they may make diarrhea worse.  A monoarthritis is best treated by intra- articular corticosteroids. Sulfasalazine may help both bowel and joint disease.  The TNF-α blocking drug infliximab is used in inflammatory bowel disease and can help the arthritis.