Reactive arthritis
According to the current definition of ReA, only infections with pathogens that affect the GI or
GU tract lead to a diagnosis of ReA.
Pathogens
Gastrointestinal: Campylobacter, Salmonella, Yersinia
UTI: Chlamydia trachomatis, Ureaplasma, Mycoplasma
TB
-ReA (‘Poncet’ disease)
-post-BCG intrabladder injections (usually self-limited and resolve within 6 months).
Other: Brucella, streptococci group A, Chlamydia psittaci, Chlamydia pneumonia, Clostridium
difficile, Giardia, HIV.
Epidemiology
Prevalence: 3.5-5/100.000, incidence: 30-40/100.000, usually at the age of sexually active
patients.
1.2% of SpAs are ReA.
Whites > Asians, M > F (role of prostate?), sexually acquired infections > GI infections (>50% of
ReA are by Chlamydia infections, but only 4-15% of those infections will develop ReA).
Prognosis
The average duration of acute ReA is 3-5 months and about 15-30% develop chronic sequelae
(lasting >6 months) or proceed into chronic SpA.
Recurrence: ≈50% of patients with sexually acquired infection experience subsequent
episodes. In contrast, recurrence after enteric infection is uncommon.
Risk factors for progressing to chronic ReA: not completely known, but they include
the type of infection (GI track infection), HLA-B27 (+), family history of SpA and the presence of
chronic gut inflammation.
Pathogenesis
T-cells play an important role in the pathogenesis, especially Th17.
Components of Yersinia and Salmonella recovered from synovial fluid of ReA patients
suggest that local persistence of microbial fragments could be the true culprit rather than
autoimmunity. It was found that certain glycosylation patterns of foreign antigen appeared to
correspond with the ability to induce experimental ReA by virtue of lingering as non-
biodegradable fragments in the joint. Fragments of the pathogen, LPS or peptidoglycan, interact
with TLRs (TLR4 recognizes LPS) on host cells triggering inflammation, as a consequence of
infection, that requires neither a viable pathogen nor even the intact organism. Decreased
bacterial gut diversity has been reported in IBD, PsO and SpA, but not in ReA.
The cytokine profiles of ReA patients suggest downregulation of proinflammatory
cytokines (TNF and IFN-γ) rather than upregulation. Animals that are susceptible to Chlamydia-
induced arthritis have diminished rather than enhanced production of TNF and IFN-γ within the
joint. This appears to relate to impaired capacity of host clearance of the organism in
susceptible strains of animals.
Association with HLA-B27, KIR and HLA-C.
According to the current definition of ReA, only infections with pathogens that affect the GI or
GU tract lead to a diagnosis of ReA.
Pathogens
Gastrointestinal: Campylobacter, Salmonella, Yersinia
UTI: Chlamydia trachomatis, Ureaplasma, Mycoplasma
TB
-ReA (‘Poncet’ disease)
-post-BCG intrabladder injections (usually self-limited and resolve within 6 months).
Other: Brucella, streptococci group A, Chlamydia psittaci, Chlamydia pneumonia, Clostridium
difficile, Giardia, HIV.
Epidemiology
Prevalence: 3.5-5/100.000, incidence: 30-40/100.000, usually at the age of sexually active
patients.
1.2% of SpAs are ReA.
Whites > Asians, M > F (role of prostate?), sexually acquired infections > GI infections (>50% of
ReA are by Chlamydia infections, but only 4-15% of those infections will develop ReA).
Prognosis
The average duration of acute ReA is 3-5 months and about 15-30% develop chronic sequelae
(lasting >6 months) or proceed into chronic SpA.
Recurrence: ≈50% of patients with sexually acquired infection experience subsequent
episodes. In contrast, recurrence after enteric infection is uncommon.
Risk factors for progressing to chronic ReA: not completely known, but they include
the type of infection (GI track infection), HLA-B27 (+), family history of SpA and the presence of
chronic gut inflammation.
Pathogenesis
T-cells play an important role in the pathogenesis, especially Th17.
Components of Yersinia and Salmonella recovered from synovial fluid of ReA patients
suggest that local persistence of microbial fragments could be the true culprit rather than
autoimmunity. It was found that certain glycosylation patterns of foreign antigen appeared to
correspond with the ability to induce experimental ReA by virtue of lingering as non-
biodegradable fragments in the joint. Fragments of the pathogen, LPS or peptidoglycan, interact
with TLRs (TLR4 recognizes LPS) on host cells triggering inflammation, as a consequence of
infection, that requires neither a viable pathogen nor even the intact organism. Decreased
bacterial gut diversity has been reported in IBD, PsO and SpA, but not in ReA.
The cytokine profiles of ReA patients suggest downregulation of proinflammatory
cytokines (TNF and IFN-γ) rather than upregulation. Animals that are susceptible to Chlamydia-
induced arthritis have diminished rather than enhanced production of TNF and IFN-γ within the
joint. This appears to relate to impaired capacity of host clearance of the organism in
susceptible strains of animals.
Association with HLA-B27, KIR and HLA-C.
