REACTIVE ARTHRITIS

Question 1

DIFFERENCE

Answer 1

This is the only non-chronic and curable form of SpA.

Question 2

DEFINITION

Answer 2

Reactive arthritis (ReA) are a group of inflammatory diseases that develop after 1-6 weeks from an infection of the upper airways, of the genito-urinary (mostly 🡪 people affected are mostly sexually active young patients) or enteric tract in genetically predisposed subjects.

Question 3

IT AFFECTS MAINLY

Answer 3

This condition affects mainly young patients.

In the presence of signs of spondyloarthritis in a young individual we MUST ask if the patient suffered in the recent history of signs of previous infection (e.g. diarrhea or genitourinary disturbances).

Question 4

CLINICAL TRIAD

Answer 4

urethritis, arthritis and conjunctivitis

‘Reiter syndrome’.

Question 5

EDPIDEMIOLOGY

Answer 5

Prevalence- 30-40 cases/100.000 adults.
Age - Young adults (30-40 yrs.)
Sex- M/F 1:1
Annual incidence- 1-30 cases/100.000
Prevalence of HLA-B27 among these patients is 40-80%. Higher when the intervertebral joints are the main one to be involved, and lower when the periphery is more involved.

Question 6

ETIOLOGY

Answer 6

this disease arises after infections - mainly by gram negative bacteria.

The pathogenesis is multifactorial, and the genetic predisposition is responsible of the aberrant response to infections.

the risk to develop a ReA after an infection is about 1-4%, but in that patients with HLA-B27, the main genetic marker of SpA, the risk is up to 20-25%.

Question 7

Classical bacteria capable of triggering reactive arthritis

Answer 7

Gram-negative obligate or facultative intracellular aerobic bacteria with a lipopolysaccharide-containing outer membrane.

Question 8

LIST OF PATHOGENS

Answer 8

salmonella, shigella, Yersinia, campylobacter for the GI infections (search in the stool),

chlamydia and mycoplasma for the GU infections.

Only rarely streptococcus will be the cause of the infection.

Question 9

PATHOGENESIS

Answer 9

In ReA, the germs infect initially the mucosa and later, in susceptible individuals, a joint inflammation, with a sterile synovial fluid, can develop.

with the modern technologies (PCR) of molecular biology it’s possible to identify the presence of microbial antigens in a state of latency in synovial fluid and in the synovial membrane of patients.

Germs able to induce ReA can assume an atypical biological structure, that allow to evade immunity defense of the patient and to survive in the joint also after antibiotics 🡪 this allows them to survive in the joints and continuously stimulate the immune system in genetically predisposed individuals 🡪 chronicity of the disease.

Question 10

THIS PATHOGENIC MECHANISM HAS BEEN DEMONSTRATED FOR

Answer 10

Chlamydia that assume transcriptional aberrations resulting in the reduction of membrane antigens expression (MOMP, major outer membrane proteins) and hyperexpression of genes that encode for heat shock protein (HSP), especially HSP60, that give to infected cells the capability to elude apoptosis and antibiotics.

Question 11

IN HISTOLOGIC EXAMINATION

Answer 11

Inclusion bodies (picture) - in particular those that are associated with Chlamydia Trachomatis. These inclusions represent a latent form of the bacteria and are localized under the synovial lining.

Question 12

CLINICAL PRESENTATION

Answer 12

Reactive arthritis could present as a single episode or a chronic disease.

The average duration of arthritis is 4-5 months, but 2/3 of patients have mild musculoskeletal symptoms that persist for more than 1 year.

Recurrent attacks are more common in patients with Chlamydia-induced reactive arthritis.

Approximately 15-30% of patients develop chronic or recurrent peripheral arthritis, sacroiliitis or spondylitis.

Question 13

Joint involvement is primarily peripheral - usually oligo or even monoarthritis.

Answer 13

Acute Phase: Peripheral asymmetrical oligoarthritis of the joints of lower and upper limbs. Typical involvement of the DIP.

Synovial fluid: sterile, not specifically inflammatory

Chronic Phase: Arthrtitis can relapse in more than 60% of the cases, after variable distance from the onset. Recurrent arthritis flares, without a complete remission after the acute phase, with a permanent joint damage, or, more frequently: poliarthritis involvement of the upper and lower limbs joints.

Question 14

Extraarticular manifestations include –

Answer 14

Mucocutaneus manifestations:
Oral ulcer
Skin and tongue ulcers
Erythema nodosum
Onychopathy
Circinate balanitis: In 20-50% of cases. The onset is with small vesicles localized to the foreskin and to the margins of glans, that, with the break, cause erosions.
Blennorrhagica keratoderma- only in 20-30% of cases. The onset is with dark spots, usually localized to the hands palm, soles of the feet, scalp, scrotum and trunk. They can evolve in papular vesicles, brownish yellow, than in pustules and scales.

Ocular manifestation - especially conjunctivitis is very frequent.

Question 15

LAB TEST

Answer 15

PCR of the synovial fluids to find pathogenic mRNA allows to recognized specific pathogens and confirm a suspected diagnosis.
*only for research

Question 16

PROGNOSIS

Answer 16

The prognosis is good if the bacterial type is recognized and treated with the appropriate antibiotic. This means that if the anamnesis and following tests are well done, the arthritis will be completely cured

Remember that up to 1/3 of the patients will nevertheless develop sacroiliitis with possible evolution of ankylosing spondylitis. Bone damage of the peripheral joints is rare.

Question 17

TREATMENT

Answer 17

Acute reactive arthritis- NSAIDs, glucocorticoids (also intra articular injections)

Chronic reactive arthritis – immunosuppression (Hydroxychloroquine, methotrexate, sulfasalazine) and anti TNF.

Specifically, the treatment of Chlamydia t. infection includes azithromycin 2 g orally (only one administration), indicated also in the absence of arthritis.