Reactive Arthritis
Reactive arthritis is a sterile inflammatory arthropathy that develops following a gastrointestinal or genitourinary infection, classically presenting with the triad of arthritis, urethritis, and conjunctivitis.
Reactive Arthritis
Reactive arthritis (ReA) is a form of sterile inflammatory arthritis that develops days to weeks following an extra-articular infection — typically of the gastrointestinal (GI) or genitourinary (GU) tract — in which the causative microorganism cannot be cultured from the affected joint [1][2][3].
The name tells you what it is: "reactive" = the arthritis is a reaction to a distant infection, not a direct bacterial invasion of the joint space. This distinguishes it fundamentally from septic arthritis, where organisms are actually present in the joint.
Formerly known as Reiter's syndrome (the eponym is now discouraged due to Friedrich Reiter's Nazi associations), classically described by the triad: "Can't see, can't pee, can't climb a tree" — conjunctivitis + urethritis/cervicitis + arthritis [2][3].
Reactive arthritis belongs to the spondyloarthritis (SpA) family — a group of inflammatory joint disorders sharing overlapping features [3][4]:
- Ankylosing spondylitis (AS): prototype, predominant axial involvement
- Psoriatic arthritis (PsA): associated with psoriasis
- Reactive arthritis (ReA): associated with prior extra-articular infection
- Enteropathic arthritis (EnA): associated with IBD
- Undifferentiated spondyloarthritis
- Juvenile-onset spondyloarthritis
Reactive arthritis is one of the four seronegative spondyloarthritis (SpA) — usually negative for RF — which is a family of disorders characterized by inflammation around the entheses (sites of tendon and ligament insertion into bone) [1].
Key Defining Features of Reactive Arthritis
- Temporal relationship: Arthritis appears 1–4 weeks after the antecedent infection
- Sterile joint: Organisms cannot be cultured from the joint (though bacterial DNA/antigens may be detected)
- Pattern: Monoarthritis or asymmetric oligoarthritis, often involving lower extremities
- Associated features: Dactylitis, enthesitis, and extra-articular manifestations (eyes, skin, GU tract)
2. Epidemiology
- Incidence: 0.6–26 per 100,000 per year; prevalence: 30–40 per 100,000 [3]
- The wide range in incidence reflects variation by geographic region, prevalence of triggering infections, and HLA-B27 prevalence in the population
- Post-enteric ReA occurs in approximately 1–4% of individuals following a documented enteric infection (e.g., Salmonella, Shigella outbreak)
- Post-chlamydial ReA occurs in approximately 4–8% of patients with Chlamydia trachomatis urethritis
- Male-to-female ratio ≈ 15:1 (marked male predominance) [2]
- This extreme male predominance is most apparent in post-venereal (post-chlamydial) ReA
- Post-enteric ReA has a more equal sex distribution (~1:1)
- Why the difference? Chlamydial urethritis is more commonly symptomatic and detected in males; the enteric route affects both sexes equally
- Age of onset: Typically 20–40 years old (young adults), coinciding with peak sexual activity and exposure to enteric pathogens
- Uncommon in children, though it can occur (especially post-enteric)
- HLA-B27 prevalence in Southern Chinese is approximately 6–8% [3] — lower than in Caucasians (~8%) but not negligible
- Enteric triggers are particularly relevant in Hong Kong given the high prevalence of:
- Salmonellosis (food-borne, from contaminated poultry, eggs)
- Campylobacter (undercooked poultry, unpasteurised dairy)
- Shigella (travellers returning from mainland China, Southeast Asia)
- Chlamydia trachomatis is the most common notifiable STI in Hong Kong, making post-chlamydial ReA an important consideration in young adults
- Overall, ReA is uncommon but not rare in Hong Kong clinical practice
3. Anatomy and Function: Relevant Joint and Entheseal Structures
Understanding reactive arthritis requires knowing the structures that become inflamed:
- A synovial joint consists of:
- Articular cartilage: Smooth hyaline cartilage covering bone ends — avascular, nourished by synovial fluid
- Synovial membrane (synovium): Lines the inner surface of the joint capsule; responsible for producing synovial fluid (which lubricates and nourishes cartilage)
- Joint capsule: Fibrous outer layer providing structural integrity
- Synovial fluid: Normally clear, viscous, contains < 200 WBC/mm³
In ReA, the synovium becomes the primary target of inflammation (synovitis), leading to effusion, pain, and — if chronic — potential erosive damage.
- The enthesis is the site where tendons, ligaments, or joint capsules insert into bone [1][3]
- Examples: Achilles tendon insertion at the calcaneus, plantar fascia insertion, patellar tendon insertion at the tibial tuberosity
- Enthesitis (inflammation of the enthesis) is a hallmark of all spondyloarthropathies, including ReA
- The enthesis is a biomechanically stressed structure with rich vascularisation at the bone–tendon junction, which may predispose to immune-mediated inflammation
- Why enthesitis in SpA? The enthesis is rich in resident immune cells (macrophages, innate lymphoid cells) and is subject to mechanical stress — a "danger zone" where microbial antigens may localise
- Dactylitis ("sausage digit") results from inflammation of the entire digit, involving the flexor tendon, tendon sheath, and surrounding soft tissues
- Distinguishes SpA from RA (where joint swelling is typically localised to the joint itself)
- Uvea = iris + ciliary body + choroid
- Anterior uveitis (iritis): Inflammation of the iris and anterior ciliary body — the most common ocular manifestation of SpA
- Conjunctivitis: Inflammation of the conjunctival membrane — classically part of the Reiter's triad
- A partly synovial, partly fibrous joint connecting the sacrum to the ilium
- Sacroiliitis (inflammation of the SI joint) is characteristic of axial SpA and may occur in reactive arthritis, though axial involvement is less common than peripheral
4. Etiology
4.1 Triggering Infections
Reactive arthritis is triggered by specific organisms that infect mucosal surfaces (GI or GU tract). The key organisms are:
| Organism | Notes |
|---|---|
| Salmonella spp. | Common in Hong Kong; food-borne (poultry, eggs) |
| Shigella spp. | More common in endemic areas; travellers |
| Campylobacter jejuni | Most common bacterial enteritis in HK; undercooked poultry |
| Yersinia enterocolitica | More common in Northern Europe; rare in HK |
| Clostridium difficile | Antibiotic-associated; increasingly recognised trigger [1] |
| Organism | Notes |
|---|---|
| Chlamydia trachomatis | Most common GU trigger worldwide and in HK; the leading cause of non-gonococcal urethritis [1][2][3] |
| Neisseria gonorrhoeae | Less commonly triggers ReA (more often causes disseminated gonococcal infection with direct septic arthritis); some sources list it [2] |
| Mycoplasma genitalium | Increasingly recognised [2] |
- HLA-B27 is strongly associated with reactive arthritis
- Present in approximately 60–80% of patients with ReA (vs. 6–8% in the general Southern Chinese population) [3]
- Present in >95% of ankylosing spondylitis and ~90% of reactive arthritis [3] — though the 90% figure varies by study; many sources cite 60–80% for ReA specifically
- HLA-B27 positivity predicts:
- More severe disease
- Greater likelihood of axial involvement (sacroiliitis, spondylitis)
- Increased risk of chronicity and progression to ankylosing spondylitis
- Increased risk of anterior uveitis
- However, HLA-B27 is neither necessary nor sufficient for disease — many HLA-B27+ individuals never develop SpA, and some ReA patients are HLA-B27 negative
5. Pathophysiology
The pathophysiology of reactive arthritis involves an aberrant immune response to a triggering infection in a genetically predisposed individual. The mechanism is incompletely understood but several hypotheses have been proposed:
- Certain bacterial antigens share structural similarity with self-antigens expressed in the joint, enthesis, or uveal tract
- The immune response initially directed against the infecting organism cross-reacts with self-tissue
- This is analogous to the mechanism in acute rheumatic fever (where anti-streptococcal antibodies cross-react with cardiac myosin) [6]
- Viable but non-culturable bacterial antigens (and sometimes bacterial DNA) have been detected in the synovial tissue and fluid of ReA patients
- Particularly demonstrated for Chlamydia trachomatis — chlamydial rRNA, DNA, and even metabolically active organisms have been found in affected joints
- The hypothesis: the triggering organism (or its components) disseminates to the joint via macrophages or dendritic cells, establishing a low-grade persistent infection that drives chronic inflammation
- This is NOT the same as septic arthritis — the organisms are not freely replicating and cannot be cultured by standard microbiological techniques
HLA-B27 contributes to pathogenesis through several proposed mechanisms [3]:
- Arthritogenic peptide hypothesis: HLA-B27 presents certain bacterial peptides to CD8+ T cells that cross-react with self-peptides in the joint (a form of molecular mimicry at the MHC level)
- HLA-B27 misfolding hypothesis: The HLA-B27 heavy chain has a tendency to misfold in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR), which activates NF-κB and pro-inflammatory cytokine production (particularly IL-23/IL-17 axis)
- HLA-B27 homodimer hypothesis: Misfolded HLA-B27 can form homodimers on the cell surface that are recognised by innate immune receptors (e.g., KIR3DL2 on NK cells and CD4+ T cells), promoting a Th17 response and IL-17 production
- This is the dominant cytokine pathway in spondyloarthritis (distinct from the TNF-α–dominant pathway in RA)
- IL-23 (produced by dendritic cells and macrophages in response to bacterial stimulation) drives differentiation of Th17 cells
- IL-17 produced by Th17 cells promotes:
- Neutrophil recruitment to the synovium and entheses
- Osteoclast activation → bone erosion
- Paradoxically, also new bone formation at entheseal sites (syndesmophytes)
- TNF-α also plays a role, which is why anti-TNF biologics are effective
- The enthesis is uniquely susceptible in SpA because:
- It is subject to mechanical stress (micro-damage → danger signals)
- It contains resident innate immune cells (γδ T cells, innate lymphoid cells type 3) that express IL-23 receptors
- Bacterial antigens may preferentially localise here
- The combination of mechanical stress + genetic susceptibility (HLA-B27) + bacterial antigen persistence creates a "perfect storm" for chronic inflammation
6. Classification
As noted above, reactive arthritis is one of the traditional subtypes of SpA. The ASAS (Assessment of SpondyloArthritis International Society) 2009 classification now divides SpA into [3][4]:
| New Classification (ASAS 2009) | Traditional Entities Encompassed |
|---|---|
| Axial spondyloarthritis (axSpA) | AS, early axial SpA (non-radiographic axSpA) |
| Peripheral spondyloarthritis (peripheral SpA) | ReA, PsA, EnA, undifferentiated peripheral SpA |
Reactive arthritis predominantly presents as peripheral SpA but can have axial features (sacroiliitis) — especially in HLA-B27+ patients.
| Type | Trigger | Sex Ratio | Notes |
|---|---|---|---|
| Post-enteric (post-dysenteric) ReA | Salmonella, Shigella, Campylobacter, Yersinia, C. difficile | M:F ≈ 1:1 | Equal sex distribution; common after outbreaks |
| Post-venereal (post-chlamydial) ReA | Chlamydia trachomatis | M >> F | Strong male predominance |
| Duration | Definition | Notes |
|---|---|---|
| Acute ReA | < 6 months | Majority of cases; self-limiting |
| Chronic ReA | ≥ 6 months | ~15–30% of patients; associated with HLA-B27 positivity |
7. Clinical Features
Reactive arthritis is characterized by two major clinical features [1]:
- An interval ranging from several days to weeks between antecedent infection and arthritis
- Monoarthritis or oligoarthritis pattern often involving the lower extremities and associated with dactylitis and enthesitis
The classic presentation evolves in a stereotypical sequence:
- Prodromal infection (GI diarrhoea or GU urethritis/cervicitis) — may be mild or subclinical
- Latent period of 1–4 weeks (typically 2–4 weeks)
- Onset of arthritis ± extra-articular features
7.1 Symptoms
i. Arthritis (the cardinal feature)
- Acute asymmetric oligoarthritis (typically 2–4 joints) — the classic pattern [2][3]
- Why asymmetric? Unlike RA (which is symmetric due to systemic autoantibody-driven synovitis), ReA results from local immune responses to disseminated bacterial antigens, which may be unevenly distributed
- Lower limbs > upper limbs, especially knees, ankles, midtarsal joints, and metatarsophalangeal joints (MTPJs) [3]
- Why LL predominance? The lower limb joints are weight-bearing, subject to greater biomechanical stress — this may increase blood flow and antigen deposition at these sites
- Onset: subacute (over days), unlike the explosive onset of gout or septic arthritis
- Joint pain with swelling and warmth — classic inflammatory features
- Pathophysiology: Synovial inflammation → increased vascular permeability → effusion (exudate rich in inflammatory cells)
- Morning stiffness lasting > 30–60 minutes (typical of inflammatory arthritis)
- Why? Overnight, inflammatory cytokines accumulate in static joints; movement flushes them out and promotes blood flow, reducing stiffness
- May present as monoarthritis in some cases — always consider ReA in the differential of acute monoarthritis (along with septic arthritis, crystal arthritis)
ii. Enthesitis
- Pain at tendon/ligament insertion sites — a hallmark of SpA [3][4]
- Most common sites:
- Achilles tendon insertion (posterior heel pain)
- Plantar fascia insertion (inferior heel pain — plantar fasciitis)
- Patellar tendon insertion (anterior knee pain)
- Mechanism: Inflammation at the bone–tendon junction where bacterial antigens localise and resident immune cells (ILC3s, γδ T cells) mount an IL-17–driven response
- Clinically: tenderness on palpation at the insertion point, not the tendon body
iii. Dactylitis ("Sausage Digit")
- Diffuse swelling of an entire toe or finger [3]
- Due to swelling of the flexor tendon, tendon sheath, and adjacent soft tissue [3]
- Uncommon but characteristic feature of peripheral SpA [3]
- More classically associated with psoriatic arthritis but also occurs in ReA [3]
- Differentiates SpA from RA (which causes discrete joint swelling, not diffuse digit swelling)
iv. Low Back Pain / Buttock Pain
- Suggests sacroiliitis or spondylitis (axial involvement)
- Characteristically:
- Insidious onset (over weeks)
- Worse with rest, improves with activity (inflammatory pattern)
- Alternating buttock pain (suggests bilateral sacroiliitis)
- More common in HLA-B27+ patients
- May evolve into full ankylosing spondylitis in a minority (5–10%)
- GI: Diarrhoea (may be bloody), abdominal cramping — may have resolved by the time arthritis appears
- GU: Dysuria, urethral discharge, pelvic pain (women: cervicitis, vaginal discharge) — Chlamydia may be asymptomatic in up to 50% of men and 70% of women
i. Ocular Symptoms
-
Anterior uveitis (iritis) [2][3]:
- Acute ocular pain with photophobia ± blurring of vision [3]
- Characteristically associated with ciliary flush and miotic pupils [3]
- Activity/severity of eye disease NOT related to disease activity [3]
- Occurs in ~10–20% of patients (more common in HLA-B27+ individuals)
- Mechanism: HLA-B27–mediated immune cross-reactivity targeting uveal tract antigens
- Can be sight-threatening if untreated (complications: posterior synechiae, cataract, glaucoma, macular oedema)
Seronegative spondyloarthropathy: most classically uveitis, conjunctivitis may also occur as part of Reiter's syndrome triad (conjunctivitis + arthritis + urethritis) in reactive arthritis [5]
ii. Genitourinary Symptoms
- Urethritis/cervicitis: May occur even in post-enteric ReA (i.e., sterile urethritis as a reactive phenomenon, not necessarily reflecting ongoing GU infection)
- Dysuria, urethral discharge, suprapubic discomfort
iii. Skin Symptoms
- Painless or mildly itchy vesicles/plaques on palms, soles, or glans penis (see Signs below)
- Oral ulcers (usually painless)
iv. Constitutional Symptoms
- Fatigue, malaise, weight loss as in other systemic inflammatory conditions [3]
- Low-grade fever (high fever should prompt concern for septic arthritis)
7.2 Signs
| Sign | Description | Pathophysiological Basis |
|---|---|---|
| Joint swelling/effusion | Warm, swollen, tender joint(s) — typically knees, ankles | Synovial inflammation → ↑vascular permeability → exudative effusion with inflammatory cells |
| Reduced range of motion | Limited active and passive ROM due to pain and effusion | Effusion distends joint capsule; pain-mediated reflex muscle guarding |
| Dactylitis | Diffuse "sausage-like" swelling of a digit | Inflammation of flexor tendon sheath + synovium + periosteum of entire digit |
| Entheseal tenderness | Tender Achilles insertion, plantar fascia, patellar tendon | IL-17–driven inflammation at bone–tendon junction |
| Sacroiliac joint tenderness | Tenderness on direct palpation or provocative tests (FABER, distraction) | Sacroiliitis from immune-mediated synovial + ligamentous inflammation |
| Sign | Description | Pathophysiological Basis |
|---|---|---|
| Conjunctival injection | Diffuse redness of the conjunctiva | Mucosal vascular dilatation from non-specific inflammation |
| Ciliary flush | Circumlimbal (perilimbal) injection | Inflammation of the iris/ciliary body → dilatation of deep episcleral/ciliary vessels |
| Miotic pupil | Constricted pupil on the affected side | Iris sphincter spasm secondary to iritis |
| Cells and flare (on slit lamp) | WBCs and protein in the anterior chamber | Breakdown of blood–aqueous barrier → leakage of cells and protein |
| Keratitic precipitates | Cellular deposits on corneal endothelium | Aggregation of inflammatory cells (WBCs, macrophages) on cornea |
These are characteristic extra-articular manifestations of ReA [2]:
| Sign | Description | Pathophysiological Basis |
|---|---|---|
| Circinate balanitis | Painless vesicles on the prepuce and glans penis, later forming superficial erosions/ulcers [2] | Mucosal immune-mediated inflammation targeting genital epithelium; histologically resembles pustular psoriasis |
| Keratoderma blennorrhagica | Hyperkeratotic skin lesions on palms and soles [2] — waxy, raised papules/plaques that may become confluent; histologically identical to pustular psoriasis | Keratinocyte hyperproliferation driven by IL-17/IL-23 axis (same pathway as psoriasis) |
| Subungual hyperkeratosis | Same as PsA [2] — thickened nails with subungual debris | Nail matrix inflammation with abnormal keratinisation |
| Oral ulcers | Painless shallow ulcers on the tongue, palate, buccal mucosa [2] | Mucosal immune dysregulation |
Keratoderma blennorrhagica vs. Psoriasis
The skin lesions of reactive arthritis — keratoderma blennorrhagica and circinate balanitis — are histologically indistinguishable from pustular psoriasis. This underscores the shared IL-17/IL-23 pathogenic pathway between ReA and psoriatic arthritis. In practice, if a patient presents with "psoriasis-like" skin lesions + asymmetric oligoarthritis + urethritis, think ReA first.
| Sign | Description | Pathophysiological Basis |
|---|---|---|
| Low-grade fever | Temperature 37.5–38.5°C | Systemic cytokine release (IL-1, IL-6, TNF-α) |
| Lymphadenopathy | Regional lymph node enlargement (uncommon) | Immune activation and lymphoid hyperplasia |
| Nail changes | Onycholysis, pitting, ridging | Nail matrix inflammation (overlap with PsA) |
The classic triad is actually present in only about one-third of patients. More commonly, patients present with incomplete forms [2][3]:
| Component | Frequency | Mnemonic |
|---|---|---|
| Arthritis | ~100% (by definition) | "Can't climb a tree" |
| Urethritis/cervicitis | ~50–70% | "Can't pee" |
| Conjunctivitis | ~30–50% | "Can't see" |
Important: The absence of the full triad does NOT exclude the diagnosis. Any patient with asymmetric oligoarthritis 1–4 weeks after a GI or GU infection should be considered for ReA.
| Feature | Reactive Arthritis | Ankylosing Spondylitis | Psoriatic Arthritis | Enteropathic Arthritis |
|---|---|---|---|---|
| Peripheral vs. Axial | Predominantly peripheral | Predominantly axial | Both | Both |
| Joint pattern | Asymmetric oligo, LL > UL | SI joints + spine | Variable (5 patterns) | Large LL joints |
| Dactylitis | Yes | Rare | Very common | Rare |
| Enthesitis | Common | Very common | Common | Less common |
| Skin | Keratoderma, circinate balanitis | — | Psoriatic plaques | Erythema nodosum, pyoderma gangrenosum |
| Eye | Conjunctivitis, anterior uveitis | Anterior uveitis (30%) | Anterior uveitis (7%) | Anterior uveitis |
| HLA-B27 | 60–80% | > 95% | ~50% (axial) | ~50% (axial) |
| RF/Anti-CCP | Negative | Negative | Negative | Negative |
High Yield Summary
Reactive Arthritis (ReA) — Key Points for Exams
-
Definition: Sterile inflammatory arthritis occurring 1–4 weeks after GI (Salmonella, Shigella, Campylobacter, Yersinia, C. difficile) or GU (Chlamydia trachomatis) infection
-
Classic triad: "Can't see, can't pee, can't climb a tree" = conjunctivitis + urethritis + arthritis (but full triad present in only ~1/3)
-
SpA family member: RF-negative, HLA-B27 associated (~60–80%), characterised by enthesitis and dactylitis
-
Epidemiology: M >> F (15:1 post-venereal; ~1:1 post-enteric), age 20–40y
-
Pathophysiology: Aberrant immune response to bacterial antigens in genetically susceptible (HLA-B27+) individuals — molecular mimicry + bacterial persistence + IL-23/IL-17 axis
-
Joint pattern: Asymmetric oligoarthritis, LL > UL (knees, ankles, MTPJs)
-
Extra-articular: Conjunctivitis (most common eye), anterior uveitis (more serious, HLA-B27 associated), keratoderma blennorrhagica (palms/soles, histologically = pustular psoriasis), circinate balanitis (glans penis), oral ulcers, nail changes
-
Skin lesions are histologically identical to psoriasis — shared IL-17/IL-23 pathway
-
Course: Self-limiting in 60–80% within 3–12 months; chronic in 15–30% (especially HLA-B27+)
-
HLA-B27 prevalence: Southern Chinese ~6–8%
Active Recall - Reactive Arthritis (Definition to Clinical Features)
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Reactive arthritis section (p.1713–1715) [2] Senior notes: Maksim Medicine Notes.pdf — Rheumatology, Reactive arthritis (p.328) [3] Senior notes: Ryan Ho Rheumatology.pdf — Chapter 2.7, Spondyloarthritis and Reactive arthritis (p.57–64) [4] Lecture slides: GC 074. Multiple joint pain.pdf [5] Senior notes: Ryan Ho Opthalmology.pdf — Rheumatological Disease and the Eye (p.131) [6] Senior notes: Ryan Ho Cardiology.pdf — Rheumatic Heart Disease, molecular mimicry (p.146)
Differential Diagnosis of Reactive Arthritis
The differential diagnosis of reactive arthritis (ReA) is essentially the differential of acute or subacute inflammatory mono-/oligoarthritis in a young adult, often with extra-articular features. The key clinical challenge is distinguishing ReA from conditions that either mimic its joint pattern or share overlapping extra-articular manifestations.
Before diving into the list, let's think about why certain conditions enter the differential. The features that define ReA — and therefore the features we must interrogate in every mimicker — are:
- Temporal relationship to infection (1–4 weeks prior GI or GU infection)
- Asymmetric oligoarthritis, predominantly lower limbs
- Sterile joint (no organism culturable from synovial fluid)
- Extra-articular features: conjunctivitis/uveitis, urethritis, mucocutaneous lesions
- Seronegative (RF−, anti-CCP−)
- Enthesitis and dactylitis (SpA hallmarks)
Any condition sharing one or more of these features is a potential differential.
Rule Number One — Septic Arthritis Until Proven Otherwise
Acute monoarthritis is treated as a semi-emergency problem in medicine. The first and foremost, acute monoarthritis should be considered as septic arthritis until proven otherwise. [7]
A hot, swollen tender joint = septic arthritis until proven otherwise, even without fever, ↑WBC, ↑ESR/CRP [8]
This is the single most dangerous mimicker because bacterial septic arthritis can destroy articular cartilage within days [8]. ReA, by contrast, involves a sterile joint. Joint aspiration with synovial fluid analysis is the investigation that separates the two.
| Differential | Key Distinguishing Features from Reactive Arthritis | Why It Enters the Differential |
|---|---|---|
| 1. Septic arthritis | Usually monoarticular; high fever; purulent synovial fluid with +ve Gram stain/culture; WBC > 20,000–50,000/mm³ with ≥75% PMNs [7][8]; organism culturable from joint. Most commonly S. aureus in adults, N. gonorrhoeae in sexually active young adults | Acute hot swollen joint — same presentation as ReA monoarthritis. Both may follow STI (gonococcal infection vs. chlamydial ReA) |
| 2. Disseminated gonococcal infection (DGI) | Two phases: (a) bacteraemic phase with migratory polyarthralgia, tenosynovitis, dermatitis (pustular/vesicular skin lesions); (b) septic arthritis phase with purulent monoarthritis. +ve GC culture from blood/joint/skin/mucosal sites. Responds dramatically to antibiotics | Young sexually active patient + arthritis + skin lesions + urethritis — very similar demographics and presentation to ReA. Sexually transmitted disease predisposes to localised gonococcal infection, which may disseminate to cause joint disease [9] |
| 3. Crystal arthritis (Gout) | Acute onset; first metatarsophalangeal joint affected first in 20%; diagnosis by demonstration of UA crystals in joint; serum UA level useful but not diagnostic [10]. Negatively birefringent needle-shaped MSU crystals on polarised microscopy. Typically intensely inflammatory, may have fever | Acute monoarthritis of LL joint (especially 1st MTP, ankle, knee) with systemic upset — overlaps with ReA |
| 4. Pseudogout (CPPD) | Most commonly affects the knee in elderly patients; +ve birefringent rhomboid-shaped calcium pyrophosphate crystals; chondrocalcinosis on X-ray | Acute mono/oligoarthritis of large LL joints |
| 5. Rheumatoid arthritis (RA) | Classically symmetrical polyarthritis involving small and large joints; starts in MCP, PIP, wrists and MTP joints and spares DIP joint; early morning stiffness ≥30 mins [4][11]; RF+ve and anti-CCP+ve in majority. No preceding infection, no enthesitis/dactylitis | Polyarticular arthritis — RA can occasionally present as oligoarthritis initially. RF/anti-CCP/ANA -ve: rule out RA/SLE [2] |
| 6. Psoriatic arthritis (PsA) | History of antecedent infectious illness with either genitourinary symptoms of urethritis or a dysenteric illness is absent in psoriatic arthritis [12]; presence of psoriatic skin plaques/nail changes (pitting, onycholysis); DIP involvement common; more classically associated with dactylitis [3]; RF−/anti-CCP− | Same SpA family — asymmetric oligoarthritis, dactylitis, enthesitis, nail changes, anterior uveitis. Keratoderma blennorrhagica of ReA is histologically identical to pustular psoriasis |
| 7. Ankylosing spondylitis (AS) | Predominant axial involvement — chronic inflammatory back pain (insidious onset, age < 45, improves with exercise, no improvement with rest, night pain); bilateral sacroiliitis on imaging; > 95% HLA-B27+; presence of psoriasis and radiological features distinguish AS from PsA [12] | Shared SpA family; ReA with axial involvement may evolve into AS; both HLA-B27 associated |
| 8. Enteropathic arthritis (IBD-associated) | Peripheral arthritis: large LL joints > small joints; type 1 coincides with exacerbation of underlying bowel disease [2][13]; GI symptoms (chronic bloody diarrhoea, weight loss); endoscopic confirmation of IBD. Peripheral arthritis occurs more frequently in CD than in UC [3] | Post-enteric ReA also follows GI symptoms; both are SpA family members; both may have sacroiliitis, anterior uveitis. IBD extraintestinal manifestations include arthritis, uveitis, erythema nodosum, pyoderma gangrenosum [13][14] |
| 9. Systemic lupus erythematosus (SLE) | Symmetrical small joint polyarthritis but usually NOT associated with evidence of synovitis; migratory pattern with predilection for knee, wrist and PIPJ; morning stiffness usually in minutes; typically non-deforming, non-erosive [11]; ANA+, anti-dsDNA+; multi-system disease (rash, serositis, renal, haematological) | Young patient with arthritis + mucocutaneous lesions + eye involvement — superficially similar demographics. RF/anti-CCP/ANA -ve: rule out RA/SLE [2] |
| 10. Acute rheumatic fever (ARF) | Migratory polyarthritis (not additive/persistent as in ReA); preceded by GAS pharyngitis (not enteric organisms or Chlamydia); Jones criteria; pancarditis; erythema marginatum; subcutaneous nodules; Sydenham's chorea; elevated ASO titre | Post-infectious arthritis in a young patient — conceptually similar (immune-mediated arthritis following infection). Key difference: ARF = post-streptococcal with migratory pattern; ReA = post-enteric/GU with additive/persistent pattern |
| 11. Post-streptococcal reactive arthritis (PSRA) | Arthritis following GAS pharyngitis that does NOT meet Jones criteria for ARF; latency period < 10 days after GAS pharyngitis; involves large joints like ARF but also peripheral joints and axial skeleton; non-migratory [15] | Very similar concept to ReA (sterile arthritis after infection); key differences: GAS trigger, shorter latency, risk of carditis |
| 12. Viral polyarthritis | Common associations: Hep B and C, EBV, parvovirus B19, Dengue virus, rubella, HIV; symmetrical, small joint arthritis ± rash and prodromal illness → usually self-limiting ≤6 weeks [11] | Acute arthritis following viral illness — temporal relationship to infection similar to ReA. Usually symmetric and small joints (unlike ReA) |
| 13. Behçet's disease | Recurrent oral aphthae (almost 100%), genital ulcers, pathergy, anterior/posterior/panuveitis, retinal vasculitis, arthritis (non-erosive oligoarthritis); usually ANA− [15] | Oral ulcers + uveitis + arthritis + genital lesions — significant overlap with ReA extra-articular features |
| 14. Lyme arthritis | History of tick bite in endemic area; erythema migrans; late-stage mono/oligoarthritis (especially knee); +ve Lyme serology (ELISA → Western blot) | Infection-triggered mono/oligoarthritis. Not relevant in Hong Kong (non-endemic) but may be tested in exam |
| 15. Sarcoid arthropathy | Acute: Löfgren syndrome (bilateral hilar lymphadenopathy + erythema nodosum + polyarthritis); chronic: dactylitis, bone cysts. Non-caseating granulomas on biopsy; elevated ACE | Oligoarthritis + dactylitis + uveitis — overlapping features with SpA |
Systematic Approach to Differentiating ReA from Key Mimickers
| Feature | Reactive Arthritis | Septic Arthritis |
|---|---|---|
| Fever | Low-grade or absent | High-grade (often > 38.5°C) |
| Joint pattern | Oligoarthritis (2–4 joints) | Usually monoarthritis (80–90%) |
| Preceding infection | 1–4 weeks before (and may have resolved) | Concurrent (ongoing bacteraemia) |
| Synovial fluid culture | Negative (by definition) | Positive |
| Synovial fluid WBC | 2,000–64,000/mm³ (inflammatory) | > 20,000–50,000/mm³ (septic range) |
| Response to antibiotics alone | Does not resolve arthritis | Dramatic improvement |
| Enthesitis/dactylitis | Present | Absent |
| Extra-articular features | Conjunctivitis, uveitis, skin lesions, urethritis | Usually absent (except in DGI) |
Out of all the investigations, joint aspiration with synovial fluid analysis for leucocyte, Gram stain, culture, and crystal, is the most important test [7]
This is a particularly important differential in sexually active young adults presenting with arthritis + urethritis + skin lesions:
| Feature | Reactive Arthritis | DGI |
|---|---|---|
| Timing | 1–4 weeks after GU infection | During active gonococcal infection |
| Skin lesions | Keratoderma blennorrhagica (hyperkeratotic, palms/soles) | Haemorrhagic/necrotic pustules (sparse, acral) |
| Joint pattern | Additive oligoarthritis | Migratory polyarthralgia → septic monoarthritis |
| Tenosynovitis | Can occur but less prominent | Very prominent (especially dorsum of hands/wrists) |
| Joint culture | Negative | Positive in ~50% of septic arthritis phase |
| Response to antibiotics | No improvement in arthritis | Dramatic improvement within 24–48h |
| Urethral Gram stain | No intracellular diplococci | Intracellular G− diplococci |
The lecture slide highlights the following clinical features of SpA [4][6]:
Spondylitis; Peripheral arthritis; Enthesitis (Achilles tendinitis, plantar fasciitis); Anterior uveitis; Aortitis; Associated with HLA-B27; Other associated features: psoriasis, inflammatory bowel disease, dysentery, sexually transmitted disease [6]
The key discriminator between SpA subtypes is the associated condition:
| SpA Subtype | "What comes with it?" |
|---|---|
| ReA | Prior GI/GU infection (the distinguishing feature) |
| PsA | Psoriasis |
| EnA | IBD |
| AS | Predominant axial disease (without associated extra-articular trigger) |
When features overlap (e.g., a patient with psoriasis who develops arthritis after Salmonella gastroenteritis), clinical judgement and the temporal relationship to infection guide the diagnosis.
Both are sterile arthritides triggered by infection, but they are fundamentally different diseases:
| Feature | Reactive Arthritis | Acute Rheumatic Fever |
|---|---|---|
| Triggering organism | Enteric bacteria or Chlamydia | Group A Streptococcus (GAS) |
| Site of infection | GI or GU tract | Pharynx |
| Latency | 1–4 weeks | 2–3 weeks |
| Arthritis pattern | Asymmetric, additive, persistent | Migratory (fleeting, moves between joints) |
| Carditis | No | Yes (pancarditis — endocardium, myocardium, pericardium) |
| Skin | Keratoderma blennorrhagica, circinate balanitis | Erythema marginatum, subcutaneous nodules |
| Eye | Conjunctivitis, anterior uveitis | Not a feature |
| HLA association | HLA-B27 | None established |
| Diagnosis | Clinical (no formal criteria) | Jones criteria |
The following constellation, when present together, is highly suggestive of ReA:
- Young male (20–40 years)
- Documented or reported GI/GU infection 1–4 weeks prior
- Asymmetric oligoarthritis predominantly in lower limbs
- Enthesitis (Achilles, plantar fascia)
- Conjunctivitis and/or anterior uveitis
- Mucocutaneous lesions: keratoderma blennorrhagica, circinate balanitis
- Sterile joint fluid (inflammatory but culture-negative)
- RF−, anti-CCP−, ANA−
- HLA-B27 positive (supports but not required)
High Yield — What Investigations Rule OUT the Mimickers?
Diagnosis of ReA is clinical (Ix mainly to rule out DDx) [2]:
- Joint aspiration: rule out septic arthritis (Gram stain, culture must be negative) [2]
- RF/anti-CCP/ANA -ve: rule out RA/SLE [2]
- Crystal analysis: rule out gout/pseudogout [7]
- Workup for preceding infection e.g. urethral swab (confirms the trigger but does NOT prove the arthritis is reactive — the diagnosis is clinical) [2]
- ESR/CRP markedly elevated (confirms inflammation but non-specific) [2]
The diagnosis of ReA is essentially one of inclusion (clinical pattern recognition) + exclusion (ruling out septic arthritis, crystal arthritis, RA, SLE).
Special Differential Considerations by Presentation
The common causes of monoarthritis include septic arthritis, crystal deposition arthritis e.g. gouty arthritis and pseudogout, haemarthrosis. Do include other polyarticular diseases with monoarticular presentation. Examples include rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. [7]
Differential hierarchy for acute monoarthritis [7][11]:
- Septic arthritis — exclude first, always
- Crystal arthritis (gout, pseudogout)
- Trauma / haemarthrosis
- ReA / SpA with monoarticular onset
- RA with monoarticular onset
- OA with acute flare
Clinical features of different arthritis — history [4]:
- Rheumatoid Arthritis: Younger age; insidious onset; polyarthritis; small hand joints; sparing DIP joints; early morning stiffness ≥30 mins
- Spondyloarthritis: Younger age; insidious onset; mono or polyarthritis; any joint could be involved; psoriasis, IBD, STD/dysentery, uveitis; back pain; family history
- Osteoarthritis: Insidious onset; DIP joints or weight-bearing joints; older age
- Gout: Acute onset; first metatarsophalangeal joint involvement; usually self-limiting; sometimes fever [4]
The differential of anterior uveitis in a young adult includes [3][5]:
- SpA (AS, ReA, PsA, EnA) — most common systemic association
- JIA (oligoarticular, ANA+)
- Behçet's disease (panuveitis, retinal vasculitis)
- Sarcoidosis (bilateral granulomatous uveitis)
- Infections (TB, syphilis, HSV, CMV)
- Idiopathic (~30%)
| Feature | ReA | Septic Arthritis | Gout | PsA | RA | DGI | ARF |
|---|---|---|---|---|---|---|---|
| Age/Sex | Young M | Any | M 30-60 | Any, M=F | F 35-55 | Young, sexually active | Children/young |
| Pattern | Asym oligo | Mono (80-90%) | Mono (initial) | Asym oligo/poly | Sym poly | Migratory → mono | Migratory poly |
| Joints | LL (knee, ankle) | Large (hip, knee) | 1st MTP, ankle | DIP, PIP, any | MCP, PIP, wrist | Knee, wrist, ankle | Large joints |
| Fever | Low-grade | High-grade | May occur | No | No | Yes | Yes |
| Synovial culture | −ve | +ve | −ve | −ve | −ve | +ve (~50%) | −ve |
| Crystals | None | None | MSU (+ve biref) | None | None | None | None |
| RF/anti-CCP | −ve | −ve | −ve | −ve | +ve | −ve | −ve |
| HLA-B27 | 60-80% | N/A | N/A | ~50% axial | N/A | N/A | N/A |
| Enthesitis | Yes | No | No | Yes | No | No | No |
| Skin | KB, CB | No | Tophi (chronic) | Psoriasis | RhN | Pustules | EM, SC nodules |
| Eye | Conj, AU | No | No | AU | Episcleritis | No | No |
KB = keratoderma blennorrhagica; CB = circinate balanitis; RhN = rheumatoid nodules; EM = erythema marginatum; SC = subcutaneous; AU = anterior uveitis; Conj = conjunctivitis
High Yield Summary — Differential Diagnosis of Reactive Arthritis
-
Always exclude septic arthritis first — joint aspiration is mandatory in acute monoarthritis. Culture-positive joint = septic, not reactive.
-
Always exclude crystal arthritis — polarised microscopy of synovial fluid for MSU (gout) or CPPD (pseudogout).
-
DGI is the closest mimicker in sexually active young adults — distinguished by migratory polyarthralgia, pustular skin lesions, tenosynovitis, and dramatic response to antibiotics.
-
Other SpA subtypes (PsA, EnA, AS) share overlapping features — the key discriminator is the associated condition (psoriasis, IBD, or predominant axial disease).
-
RA and SLE are excluded by serology (RF+/anti-CCP+ in RA; ANA+/anti-dsDNA+ in SLE) and their symmetric polyarticular pattern.
-
ARF is another post-infectious arthritis but is post-streptococcal, migratory, and has carditis.
-
ReA diagnosis is clinical + exclusion — there is no single diagnostic test. The pattern of asymmetric LL oligoarthritis + preceding GI/GU infection + sterile inflammatory joint fluid + RF−/anti-CCP− + extra-articular features (conjunctivitis, uveitis, mucocutaneous lesions, enthesitis) = ReA.
Active Recall - Differential Diagnosis of Reactive Arthritis
References
[2] Senior notes: Maksim Medicine Notes.pdf — Rheumatology, Reactive arthritis (p.328) [3] Senior notes: Ryan Ho Rheumatology.pdf — Chapter 2.7, Spondyloarthritis and Reactive arthritis (p.57–64) [4] Lecture slides: GC 074. Multiple joint pain.pdf (p.4, p.31) [5] Senior notes: Ryan Ho Opthalmology.pdf — Uveitis (p.30–31) [6] Lecture slides: GC 074. Multiple joint pain.pdf — Clinical features of SpA (p.31) [7] Senior notes: Block A - Painful red joint_ monoarthropathy, gouty arthritis, septic arthritis, haemarthrosis.pdf (p.22) [8] Senior notes: Adrian Lui Pediatrics Notes.pdf — Septic Arthritis (p.453) [9] Lecture slides: GC 075. Pain red joint.pdf — Causes and risk factors of septic arthritis (p.20) [10] Lecture slides: GC 075. Pain red joint.pdf — Clinical features of gout (p.27) [11] Senior notes: Ryan Ho Fundamentals.pdf — Acute Monoarthritis and Polyarthritis (p.406–409) [12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Psoriatic arthritis DDx (p.1708–1710) [13] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf — Extraintestinal complications (p.34) [14] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf — Extra-intestinal manifestations of IBD (p.665) [15] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Post-streptococcal reactive arthritis (p.128); Behçet's syndrome DDx (p.712)
Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Reactive Arthritis
1. Diagnostic Criteria — An Important Caveat
Unlike many rheumatological conditions (e.g., RA with ACR/EULAR 2010 criteria, SLE with SLICC/ACR criteria, or ARF with Jones criteria), there are no universally accepted validated diagnostic criteria for reactive arthritis. The diagnosis is fundamentally clinical — pattern recognition supported by investigations that serve primarily to exclude mimickers rather than to confirm ReA itself.
Diagnosis: clinical (Ix mainly to rule out DDx) [2]
That said, several classification frameworks exist:
This is the most widely cited attempt at standardising the diagnosis:
Two requirements must be met:
- Arthritis: Mono- or oligoarthritis, predominantly lower limbs, asymmetric
- Evidence of preceding infection: Clinical diarrhoea or urethritis 1–4 weeks before onset of arthritis
Plus one of the following to confirm the infection:
- Positive urine ligase chain reaction/PCR for Chlamydia trachomatis
- Positive stool culture for enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter)
No Single Diagnostic Test Exists
Inability to identify the causative organisms does not exclude the diagnosis of reactive arthritis [1]. Many patients present weeks after the triggering infection has resolved, and stool/urine cultures may be negative by the time arthritis appears. The diagnosis can still be made clinically if the temporal pattern and clinical features are consistent.
Since reactive arthritis is classified as peripheral spondyloarthritis under the ASAS framework, the ASAS criteria for peripheral SpA can be applied [2][3]:
Entry criterion: Peripheral arthritis (usually lower limb, asymmetric) ± enthesitis ± dactylitis
Plus ≥1 of the following SpA features:
- Anterior uveitis
- Psoriasis
- IBD (Crohn's or UC)
- Preceding infection (within 1 month: urethritis/cervicitis or diarrhoea)
- HLA-B27 positive
- Sacroiliitis on imaging
OR ≥2 of the following:
- Arthritis
- Enthesitis
- Dactylitis
- Inflammatory back pain (ever)
- Family history of SpA
SpA features ×11 as listed in ASAS criteria — these are the key clinical and laboratory features that define the SpA spectrum [2]
The ASAS criteria conceptualise the SpA family as a spectrum, with reactive arthritis, PsA, EnA, and AS as overlapping entities rather than discrete diseases [4][6]
In practice, the diagnosis of ReA is made when all four of the following are satisfied:
| Criterion | Rationale |
|---|---|
| 1. Inflammatory arthritis (mono- or oligoarthritis, asymmetric, LL predominant) | Defines the articular manifestation |
| 2. Temporal relationship to GI or GU infection (1–4 weeks prior) | Establishes the "reactive" nature |
| 3. Sterile joint (negative synovial fluid culture and Gram stain) | Excludes septic arthritis |
| 4. Seronegative (RF−, anti-CCP−, ANA−) | Excludes RA and SLE |
The presence of extra-articular features (conjunctivitis, anterior uveitis, keratoderma blennorrhagica, circinate balanitis, enthesitis, dactylitis) strongly supports the diagnosis but is not required.
The algorithm below represents the clinical reasoning pathway from initial presentation to diagnosis. The overarching principle is: exclude dangerous mimickers first (septic arthritis, crystal arthritis), then establish the clinical pattern of ReA.
3. Investigation Modalities — Detailed
The Single Most Important Investigation
Out of all the investigations, joint aspiration with synovial fluid analysis for leucocyte, Gram stain, culture, and crystal, is the most important test [7][16]
Synovial fluid aspiration is key; fluid to be sent fresh for relevant stains and culture; prior to commencement of antibiotic therapy [17]
This is the investigation that separates septic arthritis from ReA, gout from ReA, and inflammatory from non-inflammatory causes. It must be performed before antibiotics are started.
What to send synovial fluid for [17][18]:
- Gram stain (urgent if septic arthritis suspected)
- Culture with sensitivity testing
- WBC count with differential
- Crystal analysis by polarised microscopy
- Glucose (low in septic arthritis compared to serum) [17]
Interpretation of synovial fluid results:
The synovial fluid classification table [1][19]:
| Measure | Normal | Non-inflammatory | Inflammatory | Septic | Haemorrhagic |
|---|---|---|---|---|---|
| Volume (mL, knee) | < 3.5 | > 3.5 | > 3.5 | > 3.5 | > 3.5 |
| Clarity | Transparent | Transparent | Translucent to opaque | Opaque | Bloody |
| Colour | Clear | Yellow | Yellow | Yellow | Red |
| Viscosity | High | High | Low | Variable | Variable |
| WBC/mm³ | < 200 | 0–2,000 | > 2,000 | > 20,000 (often > 50,000) | Variable |
| PMNs (%) | < 25% | < 25% | ≥ 50% | ≥ 75% | 50–75% |
| Culture | −ve | −ve | −ve | +ve | −ve |
Expected findings in reactive arthritis [1]:
- Inflammatory synovial fluid
- WBC count = 2,000–64,000/mm³ with neutrophil predominance [1]
- Culture negative (by definition — this is what makes it "reactive" rather than "septic")
- No crystals on polarised microscopy
Why is viscosity LOW in inflammatory fluid? Because inflammatory enzymes (notably hyaluronidase from neutrophils) degrade hyaluronic acid — the glycosaminoglycan responsible for the normal viscosity of synovial fluid. The "string test" (ability of fluid to form a long string when dripped) is reduced.
Septic Arthritis and ReA Can Coexist
Although ReA is by definition a sterile arthritis, always remember that patients with pre-existing inflammatory arthritis (including ReA) are at increased risk of septic arthritis. Finding inflammatory synovial fluid does NOT exclude concurrent infection — always send for culture.
3.2 Blood Tests
| Test | Expected Finding in ReA | Interpretation |
|---|---|---|
| ESR | Markedly elevated [1][2] | Non-specific marker of systemic inflammation; useful for monitoring disease activity and treatment response |
| CRP | Markedly elevated [1][2] | Acute-phase reactant produced by the liver in response to IL-6; more rapidly responsive than ESR; ↑ in infection and inflammation |
| CBC with differentials | Leukocytosis [1]; ± mild normocytic normochromic anaemia of chronic disease; ± thrombocytosis (reactive) | Leukocytosis reflects systemic inflammatory response; thrombocytosis is a common acute-phase reaction |
| Test | Expected in ReA | Purpose |
|---|---|---|
| RF (Rheumatoid Factor) | Negative [2] | Excludes RA (positive in ~70% of RA) |
| Anti-CCP (Anti-Cyclic Citrullinated Peptide) | Negative [2] | Excludes RA (more specific than RF, ~95% specific) |
| ANA (Anti-Nuclear Antibody) | Negative [2] | Excludes SLE and other connective tissue diseases |
RF/anti-CCP/ANA -ve: rule out RA/SLE [2] — This is a key principle: the diagnosis of ReA is partly one of exclusion.
| Test | Finding | Interpretation |
|---|---|---|
| HLA-B27 | Present in 30–50% of reactive arthritis [1] (some sources cite 60–80%) | Not diagnostic — present in 6–8% of normal Southern Chinese population. Prognostic value: HLA-B27 positive patients are more likely to develop a chronic spondyloarthropathy with radiographical changes [1]. Also predicts higher risk of anterior uveitis and axial involvement |
When to test HLA-B27?
- Helpful when the clinical picture is suggestive but the preceding infection cannot be documented
- Useful as a prognostic indicator — HLA-B27+ patients warrant closer follow-up for chronicity
- ALWAYS check HLA-B27 when evaluating anterior uveitis [20]
- Not useful as a screening test in the general population (low PPV given 6–8% prevalence)
- Order if gout is in the differential
- Caveat: Uric acid may be normal during an acute attack (cytokines increase renal urate excretion) — should be rechecked 2 weeks after resolution if gout is suspected
The purpose of infection workup is to identify the preceding infection that triggered the reactive process. This confirms the diagnosis but — critically — inability to identify the causative organisms does not exclude the diagnosis [1].
| Investigation | Target Organism | Notes |
|---|---|---|
| Stool culture | Salmonella, Shigella, Campylobacter, Yersinia [1] | May be negative if diarrhoea resolved weeks ago. In Hong Kong, Campylobacter and Salmonella are the most common enteric pathogens |
| Urine/genital swab PCR (NAAT) | Chlamydia trachomatis [1] | Nucleic acid amplification test (NAAT) is the investigation of choice — far more sensitive than culture. First-catch urine in males; endocervical or vaginal swab in females |
| Urinalysis / RFT | Non-specific | Evaluate for urinary infection [1]; may show sterile pyuria (from urethritis) |
| Urethral Gram stain | N. gonorrhoeae | If gonococcal arthritis is in the differential — look for intracellular Gram-negative diplococci |
| Blood culture | Various | Not typically positive in ReA (unlike septic arthritis where blood culture is +ve in 50% of cases [19]); order if high fever or diagnostic uncertainty |
| Serology for Yersinia | Yersinia enterocolitica | Useful when stool culture is negative and Yersinia is suspected (e.g., Northern European travel); paired acute and convalescent sera |
STI Screening — Don't Forget the Full Panel
If Chlamydia is identified, the patient should receive full STI screening including:
- HIV serology
- Syphilis serology (VDRL/RPR + TPHA)
- Hepatitis B/C serology
- Gonorrhoea NAAT
- Partner notification and treatment
This is both good clinical practice and required for public health.
3.4 Radiological Investigations
No specific findings on plain radiographs to establish a diagnosis of reactive arthritis [1]
- In acute ReA, X-rays are usually normal or show only:
- Soft tissue swelling
- Periarticular osteopenia
- Joint effusion
- In chronic or recurrent ReA, may show:
- Periostitis (fluffy new bone formation along shafts of metatarsals, phalanges, calcaneus)
- Erosions at entheseal sites (calcaneal erosion at Achilles or plantar fascia insertion)
- Asymmetric syndesmophytes [2] (paravertebral ossification — unlike the symmetric syndesmophytes of AS)
- Sacroiliac joint changes: may be unilateral (unlike AS where it is typically bilateral)
Plain x-ray should still be obtained as baseline radiograph is useful for comparison purposes to determine therapeutic response [19] and to exclude other pathology.
X-ray of involved joint(s) is part of the standard investigation panel for any acute arthritis [17]
MRI of joints: Identify changes consistent with peripheral synovitis, enthesitis or sacroiliitis [1]
- Far more sensitive than plain X-ray for early inflammatory changes
- Key MRI findings in ReA:
- Bone marrow oedema at entheseal sites (Achilles insertion, plantar fascia, SI joints)
- Synovial enhancement on contrast-enhanced MRI (indicating active synovitis)
- Sacroiliac joint inflammation: bone marrow oedema, joint space fluid, erosions — may be unilateral
- Tenosynovitis/dactylitis: enhancement of flexor tendon sheaths
- MRI is the most appropriate imaging where required [17]; also sensitive in detecting osteomyelitis [17] — important to exclude concurrent bone infection
- Increasingly used as a bedside/clinic tool
- Can detect:
- Joint effusion (guides aspiration)
- Synovial thickening and hyperaemia (Doppler signal)
- Enthesitis (thickened, hypoechoic enthesis with Doppler activity ± erosion/enthesophyte)
- Tenosynovitis/dactylitis
- Advantages: no radiation, real-time, can guide aspiration, available at bedside
- Limitation: operator-dependent; limited for deep joints (hip, SI joints)
| Investigation | Indication | Findings |
|---|---|---|
| Slit-lamp examination | Any patient with eye symptoms (pain, photophobia, redness, blurred vision) | Diagnosis of uveitis by demonstration of anterior chamber inflammation (cells and flare) [20]; keratitic precipitates; posterior synechiae |
| Dilated fundus examination | If posterior uveitis suspected | Vitritis, choroidal lesions, retinal vasculitis |
Slit lamp for chronic anterior uveitis should be part of the assessment in any SpA patient [8]
ALWAYS check HLA-B27 when evaluating uveitis — particularly if bilateral, severe, or recurrent [20]
| Category | Investigation | Key Finding in ReA | Primary Purpose |
|---|---|---|---|
| Arthrocentesis | Synovial fluid analysis | Inflammatory (WBC 2k–64k), culture −ve, no crystals | Exclude septic arthritis and crystal arthritis |
| Blood — inflammatory | ESR, CRP | Markedly elevated | Confirm inflammation, monitor Tx response |
| Blood — serological | RF, anti-CCP, ANA | All negative | Exclude RA and SLE |
| Blood — genetic | HLA-B27 | +ve in 30–80% | Prognostic; supports SpA diagnosis |
| Blood — general | CBC | Leukocytosis, ± anaemia, ± thrombocytosis | Assess systemic inflammation |
| Infection — GI | Stool culture | May grow triggering pathogen | Identify trigger |
| Infection — GU | Chlamydia NAAT (urine/swab) | May be positive | Identify trigger; guide Abx for urethritis |
| Imaging | X-ray | Usually normal acutely; entheseal changes chronically | Baseline; exclude other pathology |
| Imaging | MRI | Synovitis, enthesitis, sacroiliitis | Most sensitive for early inflammatory changes |
| Ophthalmology | Slit-lamp examination | Anterior chamber cells/flare (if uveitis) | Diagnose anterior uveitis |
| Scenario | Most Likely Diagnosis | Key Distinguishing Test |
|---|---|---|
| Inflammatory SF + culture +ve + high WBC > 50k | Septic arthritis | Gram stain and culture |
| Inflammatory SF + MSU crystals | Gout | Polarised microscopy |
| Inflammatory SF + CPPD crystals | Pseudogout | Polarised microscopy |
| Inflammatory SF + culture −ve + no crystals + preceding infection + RF−/anti-CCP− | Reactive arthritis | Clinical pattern + infection workup |
| Inflammatory SF + culture −ve + no crystals + RF+/anti-CCP+ + symmetric polyarthritis | Rheumatoid arthritis | RF, anti-CCP |
| Inflammatory SF + culture −ve + no crystals + ANA+/anti-dsDNA+ + multi-system features | SLE | ANA, anti-dsDNA, complement |
Common Pitfalls in Diagnosing Reactive Arthritis
-
Failing to aspirate the joint — You cannot diagnose ReA without first excluding septic arthritis by joint aspiration. Warfarin does not contraindicate needle aspiration [17].
-
Waiting for culture results before treating suspected septic arthritis — If clinically septic (high fever, toxic, extremely swollen single joint), start empirical antibiotics AFTER aspiration but BEFORE culture results return. You can always de-escalate.
-
Assuming negative stool/urine culture excludes ReA — Inability to identify the causative organisms does not exclude the diagnosis [1]. The infection may have resolved weeks before the arthritis appeared.
-
Over-relying on HLA-B27 — A positive HLA-B27 supports the diagnosis and has prognostic value, but 6–8% of normal Southern Chinese are HLA-B27+. It is neither necessary nor sufficient. Conversely, a negative HLA-B27 does NOT exclude ReA (30–50% of ReA patients are HLA-B27−).
-
Missing Chlamydia — Up to 50% of men and 70% of women with Chlamydia are asymptomatic. If ReA is suspected, always send Chlamydia NAAT even without overt urethral symptoms.
-
Forgetting that DGI and ReA can present identically — Both involve a sexually active young adult with arthritis + urethritis. DGI has a dramatic response to antibiotics; ReA does not.
High Yield Summary — Diagnosis of Reactive Arthritis
-
No validated diagnostic criteria exist — diagnosis is clinical (pattern recognition + exclusion of mimickers)
-
ASAS peripheral SpA criteria can be applied: peripheral arthritis + ≥1 SpA feature (uveitis, psoriasis, IBD, preceding infection, HLA-B27, sacroiliitis on imaging) OR ≥2 of arthritis/enthesitis/dactylitis/IBP/FHx SpA
-
Joint aspiration is the MOST important single test: inflammatory fluid (WBC 2,000–64,000), culture −ve, no crystals → excludes septic arthritis and crystal arthritis
-
Serology: RF−, anti-CCP−, ANA− → excludes RA and SLE
-
HLA-B27: positive in 30–80%, prognostic (predicts chronicity and axial involvement), NOT diagnostic
-
Infection workup: stool culture + Chlamydia NAAT — a positive result supports the diagnosis but a negative result does NOT exclude it
-
Imaging: X-ray usually normal acutely; MRI is most sensitive for synovitis, enthesitis, sacroiliitis
-
Ophthalmology: Slit-lamp for anterior uveitis if eye symptoms; always check HLA-B27 in uveitis workup
Active Recall - Diagnostic Criteria, Algorithm and Investigations for Reactive Arthritis
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Reactive arthritis, Diagnosis (p.1715–1717) [2] Senior notes: Maksim Medicine Notes.pdf — Rheumatology, Reactive arthritis and Spondyloarthritides (p.309, 323, 328) [3] Senior notes: Ryan Ho Rheumatology.pdf — Chapter 2.7, Spondyloarthritis overview and ASAS criteria (p.57) [4] Lecture slides: GC 074. Multiple joint pain.pdf — Concept of SpA (p.30–31) [6] Lecture slides: GC 074. Multiple joint pain.pdf — Clinical features of SpA (p.31) [7] Senior notes: Block A - Painful red joint_ monoarthropathy, gouty arthritis, septic arthritis, haemarthrosis.pdf (p.22) [8] Senior notes: Adrian Lui Pediatrics Notes.pdf — Inflammatory Joint Conditions, Investigations (p.456) [16] Lecture slides: GC 075. Pain red joint [Notes].pdf — Key learning points (p.1) [17] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025].pdf — Septic arthritis investigations (p.19); Lecture slides: GC 075. Pain red joint.pdf — Approach to septic arthritis investigations (p.23) [18] Senior notes: Ryan Ho Fundamentals.pdf — Joint fluid analysis (p.407) [19] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Septic arthritis, Diagnosis (p.1689–1691) [20] Senior notes: Ryan Ho Opthalmology.pdf — Uveitis diagnosis (p.31)
Management of Reactive Arthritis
The management of reactive arthritis rests on several key principles that flow logically from the pathophysiology:
- Treat the triggering infection — if still active (particularly Chlamydia), eradicate it with appropriate antibiotics
- Control articular inflammation — a stepwise escalation approach: NSAIDs → intra-articular steroids → systemic steroids → DMARDs → biologics
- Treat extra-articular manifestations — each organ-specific manifestation has its own treatment pathway (eyes, skin, GU tract)
- Supportive and rehabilitative measures — physiotherapy, patient education, functional preservation
- Monitor for chronicity — 15–30% develop chronic disease, requiring escalation to DMARDs or biologics
The vast majority (60–80%) of ReA cases are self-limiting within 3–12 months, so the initial approach is conservative. Aggressive immunosuppression is reserved for refractory or chronic disease.
3. Treatment Modalities — Detailed
3.1 Treatment of the Triggering Infection
Doxycycline and azithromycin are indicated for patients with Chlamydia trachomatis infection of the genitourinary tract [1]
| Regimen | Dose | Notes |
|---|---|---|
| Doxycycline | 100mg BD × 1 week [2][21] | First-line; also covers Mycoplasma genitalium |
| Azithromycin | 1g PO single dose [1][21] | Alternative; convenient single-dose regimen; slightly less effective for Mycoplasma |
- Why treat Chlamydia? Even though the arthritis is "sterile," viable Chlamydia organisms/antigens may persist in the joint. Eradicating the source infection removes the ongoing antigenic stimulus. There is also evidence that prolonged courses (e.g., doxycycline × 3–6 months) may reduce chronicity in chlamydial ReA, though this remains debated.
- Partner notification and treatment is essential — untreated partners will reinfect the patient.
- Full STI screening should be performed (HIV, syphilis, Hep B/C, gonorrhoea) [21].
Urethritis (Chlamydia): doxycycline [2]
- Antibiotics for the enteric infection do NOT shorten or improve the arthritis in post-enteric ReA
- Most enteric infections (Salmonella, Campylobacter) are self-limiting and have resolved by the time arthritis appears
- Antibiotics may be indicated for the infection itself if:
- Severe/complicated dysentery (e.g., Shigella with systemic toxicity)
- Immunocompromised patients
- Salmonella bacteraemia
- Key concept: Unlike chlamydial ReA, there is no evidence that treating enteric infections prevents or improves reactive arthritis
Antibiotics Do NOT Treat the Arthritis
A common misconception: antibiotics will fix the joint inflammation. They will not. The arthritis in ReA is immune-mediated, not infectious. Antibiotics treat the triggering infection (especially Chlamydia), but the articular inflammation requires anti-inflammatory therapy (NSAIDs, steroids, DMARDs). The exception is that some evidence supports prolonged doxycycline for chlamydial ReA to reduce chronicity.
NSAIDs are the 1st line therapy for anti-inflammatory effects in patients with reactive arthritis [1]
| Drug | Dose | Notes |
|---|---|---|
| Naproxen | 500mg BD | Good balance of efficacy and safety profile; commonly used in HK |
| Diclofenac | 50mg TDS | Effective but higher cardiovascular risk |
| Indomethacin | 50mg TDS | "Indo" = potent NSAID often favoured in SpA; higher GI side-effect profile |
| Celecoxib | 200mg BD | Selective COX-2 inhibitor; preferred if high GI risk |
Mechanism: NSAIDs inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis → decreased pain, swelling, and stiffness. In SpA, they have a modest disease-modifying effect — continuous use (even when asymptomatic) may slow structural progression, particularly in axial SpA [3].
Why NSAIDs work well in SpA/ReA: The inflammatory process in SpA is heavily prostaglandin-dependent (more so than in RA), which is why NSAIDs provide ~70–80% symptom relief in SpA [3].
Arthritis: NSAID / IA steroid [2]
Contraindications (unless contraindicated e.g. GI bleeding / CVS disease / renal failure [1]):
| Contraindication | Mechanism |
|---|---|
| Active GI bleeding / peptic ulcer disease | NSAIDs inhibit COX-1 → ↓ mucosal prostaglandins → impaired gastric mucosal defence → ulcerogenesis |
| Cardiovascular disease | NSAIDs (especially COX-2 selective) ↑ risk of MI, stroke, and HF exacerbation via ↑ thromboxane A2 relative to prostacyclin |
| Chronic kidney disease | NSAIDs cause renal vasoconstriction (via ↓ PGE2 and PGI2 at the afferent arteriole) → ↓ GFR → AKI in vulnerable kidneys |
| Pregnancy | Risk of premature closure of ductus arteriosus (especially in 3rd trimester) |
| Aspirin-sensitive asthma | Cross-reactivity with COX-1 inhibition → leukotriene shunting → bronchospasm |
NSAID with concurrent corticosteroids for treatment of arthritis/rheumatism of any kind: increased risk of peptic ulcer disease [22]
GI risk mitigation if NSAIDs must be used:
- Co-prescribe PPI (e.g., omeprazole 20mg OD) — PPI raises gastric pH, ulcerogenic effects become reduced [23]
- Or use a selective COX-2 inhibitor (e.g., celecoxib) — lower GI risk but still present
- Check and eradicate H. pylori if positive
3.3 Glucocorticoids — Second-Line for Refractory Arthritis
Intraarticular glucocorticoids for patients who do not respond adequately to NSAIDs [1]
Systemic glucocorticoids for patients who do not respond adequately to NSAIDs and intraarticular glucocorticoid injections [1]
| Drug | Dose | Notes |
|---|---|---|
| Triamcinolone acetonide | 20–40mg per large joint | Long-acting; commonly used |
| Methylprednisolone acetate | 40–80mg per large joint | Alternative |
- Indication: Mono- or oligoarticular ReA not responding to NSAIDs; excellent for 1–2 swollen joints
- Mechanism: Directly suppresses intra-articular inflammation — inhibits phospholipase A2 → ↓ arachidonic acid → ↓ prostaglandins and leukotrienes; also suppresses NFκB → ↓ pro-inflammatory cytokine transcription
- Advantage: Delivers high local steroid concentration without systemic side effects
- Requirement: Must have excluded septic arthritis by joint aspiration BEFORE injecting steroids — injecting corticosteroids into a septic joint is catastrophic (masks infection, promotes bacterial proliferation)
- Risks: Tendon rupture, osteonecrosis, acute crystal synovitis (steroid flare), septic arthritis (rare, ~1:10,000–50,000 injections), systemic absorption
Local glucocorticoid injections for enthesitis and dactylitis — but NOT into Achilles tendon due to increased risk of tendon rupture [3]
| Drug | Dose | Notes |
|---|---|---|
| Prednisolone | 15–30mg/day, taper over 4–8 weeks | Bridging therapy; should not be used long-term |
- Indication: Polyarticular or severe ReA not responding to NSAIDs + IA injections; used as bridging therapy while waiting for DMARDs to take effect
- Caution in SpA context: Note risk of psoriasis flare upon tapering → CAUTIOUS with starting oral steroids [3]. If the patient has concurrent psoriasis or psoriasis-like skin lesions (as in ReA with keratoderma blennorrhagica), systemic steroids may cause a pustular psoriasis flare on withdrawal
Long-term corticosteroids ( > 3 months) as monotherapy for rheumatoid arthritis: risk of systemic corticosteroid side-effects [22] — this principle applies equally to ReA. Steroids are NOT disease-modifying in SpA and should be short-term bridging only.
Non-biological DMARDs are indicated in patients who do not respond adequately to all initial therapy or in patients who develop refractory reactive arthritis defined as disease lasting > 6 months [1]
| Drug | Dose | Mechanism | Preferred When | Key Side Effects |
|---|---|---|---|---|
| Sulphasalazine | 2–3g/day [1][3] | Prodrug → 5-ASA (local anti-inflammatory) + sulphapyridine (immunomodulatory); inhibits NFκB and TNF-α | Preferred in non-psoriatic SpA and IBD-associated SpA [3]; effective for peripheral arthritis in SpA | Skin rash, haemolysis, neutropenia, male infertility (reversible), pancreatitis, hepatotoxicity |
| Methotrexate | Up to 25mg once weekly [3] | Folate antagonist → inhibits dihydrofolate reductase → ↓ purine synthesis → ↓ lymphocyte proliferation; also ↑ adenosine (anti-inflammatory) | Preferred in PsA to co-treat skin psoriasis [3]; useful for peripheral arthritis in ReA | Hepatotoxicity, BM suppression, interstitial pneumonitis, teratogenicity |
Key points about DMARDs in ReA:
- DMARDs are effective for peripheral arthritis but generally NOT effective for axial symptoms (sacroiliitis, spondylitis) or enthesitis [3]
- Onset of action is slow (weeks to months) — hence the need for bridging therapy with steroids
- Sulphasalazine is preferred in reactive arthritis specifically because it has fewer dermatological side effects than methotrexate (important given the skin manifestations of ReA)
- Methotrexate is contraindicated in pregnancy and CKD [24]; requires regular monitoring (FBC, LFT, RFT)
Sulphasalazine or methotrexate for patients with peripheral arthritis [24]
Name breakdown — Sulphasalazine: "sulpha" = sulphapyridine (sulphonamide antibiotic moiety) + "salazine" = 5-aminosalicylic acid (5-ASA, anti-inflammatory). The two moieties are linked by an azo bond and cleaved by colonic bacteria. Originally designed for RA (the sulphapyridine component) and IBD (the 5-ASA component) — hence its dual utility.
Biological DMARDs (Anti-TNF agents) are indicated in patients who are refractory to NSAIDs, glucocorticoid and DMARDs [1]
| Drug | Type | Dose | Mechanism |
|---|---|---|---|
| Infliximab | Chimeric anti-TNF-α monoclonal antibody | IV infusion, loading then Q6–8w | Binds and neutralises both soluble and membrane-bound TNF-α |
| Etanercept | Soluble TNF receptor fusion protein (p75-Fc) | 50mg SC weekly | Decoy receptor — binds TNF-α before it can engage cell surface receptors |
| Adalimumab | Fully humanised anti-TNF-α monoclonal antibody | 40mg SC Q2w | Binds and neutralises TNF-α |
There are three TNF inhibitors approved for use in RA. Infliximab and adalimumab are anti-TNF-α antibodies whereas etanercept is a recombinant soluble p75 TNF receptor:Fc fusion protein [25]
Why anti-TNF works in ReA: TNF-α is a key pro-inflammatory cytokine in the SpA inflammatory cascade. It drives synovial inflammation, enthesitis, and bone erosion. Blocking TNF-α interrupts this cycle.
Contraindications for anti-TNF agents [3][24]:
| Contraindication | Reason |
|---|---|
| Active infection | TNF-α is critical for immune defence; blocking it → overwhelming infection |
| Latent TB | Required exclusion of latent TB infection [1] — TNF-α is essential for maintaining TB granulomas. Anti-TNF → granuloma breakdown → TB reactivation and dissemination |
| Demyelinating disease (e.g., MS) | Anti-TNF may worsen or unmask demyelinating conditions |
| Heart failure (NYHA III-IV) | Anti-TNF can worsen HF |
| Malignancy | Theoretical ↑ risk of lymphoma (small but real) |
Anti-TNF-alpha is the classical example that can increase risk of developing TB, given the importance of TNF-alpha in confining TB to the tuberculoma [26]
Pre-biologic screening checklist:
- IGRA (Interferon-Gamma Release Assay) or tuberculin skin test for latent TB [26]
- Hepatitis B and C serology (risk of reactivation)
- HIV serology
- Chest X-ray
- CBC, LFT, RFT
- Vaccination review (avoid live vaccines on biologics)
Isoniazid chemoprophylaxis can be given to patients with latent TB, as demonstrated by tuberculin skin test or IGRA (3 months) [26]
Anti-IL-17A (Secukinumab) is an alternative biologic with similar efficacy in SpA, particularly effective for enthesitis and skin disease. However, it is contraindicated in IBD (may worsen gut inflammation) — an important distinction when choosing biologics in the SpA spectrum [3].
Choice of biologic in specific extra-articular settings [3]:
| Extra-articular Feature | Preferred Biologic | Avoid |
|---|---|---|
| IBD | Infliximab or adalimumab | Etanercept (ineffective for IBD) |
| Anterior uveitis | Infliximab or adalimumab | Etanercept (less effective for uveitis) |
| Psoriasis | Any anti-TNF; also anti-IL-17A, anti-IL-12/23 | — |
| ReA (general) | Infliximab, etanercept, or adalimumab | — |
3.6 Treatment of Extra-Articular Manifestations
Each extra-articular manifestation of ReA requires specific targeted treatment:
Anterior uveitis: topical steroid [2]
| Treatment | Detail | Mechanism |
|---|---|---|
| Topical steroid eyedrops | 1% prednisolone acetate solution [20] | Suppresses anterior chamber inflammation; reduces cells/flare |
| Topical cycloplegics | 1% cyclopentolate [20] | Paralyses ciliary muscle → relieves pain from ciliary spasm; dilates pupil → prevents posterior synechiae (adhesion of iris to lens) |
| Oral analgesics | Paracetamol | Symptom relief |
| TNF-α inhibitor | Infliximab or adalimumab preferred [3] | If refractory to topical therapy or recurrent severe uveitis |
Uveitis: topical glucocorticoids + cycloplegics → TNF-α inhibitor (if refractory, prefer infliximab/adalimumab) [3]
Why cycloplegics? The inflamed iris is in spasm (causing the miotic pupil seen in uveitis). If the iris remains in spasm against the lens, fibrinous inflammatory exudate causes the iris to stick to the anterior lens capsule (posterior synechiae). Cycloplegics keep the pupil dilated, preventing adhesion.
- Usually self-limiting within days to weeks [3]
- Supportive: lubricant eye drops, cold compresses
- Rarely requires treatment beyond reassurance
| Lesion | Treatment | Notes |
|---|---|---|
| Keratoderma blennorrhagica | Topical corticosteroids, emollients, keratolytics (salicylic acid) | Histologically identical to pustular psoriasis; treat like psoriasis |
| Circinate balanitis | Topical corticosteroids (mild potency), hygiene | Usually painless and self-limiting |
| Severe/widespread skin disease | Methotrexate, biologics (anti-TNF, anti-IL-17A) | As for psoriasis |
| Treatment | Detail |
|---|---|
| NSAIDs (1st line) | Same as for arthritis |
| Local steroid injection | Effective for focal enthesitis (e.g., plantar fascia); NOT into Achilles tendon due to increased risk of tendon rupture [3] |
| TNF-α inhibitor | If refractory; conventional DMARDs not effective for extra-articular manifestations [3] |
- Treat the underlying Chlamydia infection (doxycycline / azithromycin) — see 3.1 above
- Sterile urethritis (reactive, without active Chlamydia) is self-limiting and does not require specific treatment beyond NSAIDs for symptomatic relief
- Usually painless and self-limiting
- Supportive: oral antiseptic mouthwash, topical corticosteroids if symptomatic
General measures: education, stretching exercise, physiotherapy, smoking cessation [3][8]
| Measure | Purpose |
|---|---|
| Patient education | Understanding the natural history (self-limiting in majority); recognising warning signs (eye symptoms, worsening joints) |
| Physiotherapy | Maintain joint mobility and muscle strength; prevent contractures; ROM exercises for affected joints |
| Occupational therapy | Splints for acutely inflamed joints; ADL assessment; workplace modifications if needed |
| Smoking cessation | Smoking worsens SpA outcomes and predicts poor response to treatment |
| Safe sex education | Prevent reinfection with Chlamydia (partner notification, condom use) |
| STI screening for partners | Essential public health measure [21] |
| Step | Treatment | Indication | Duration |
|---|---|---|---|
| 1 | Treat triggering infection (Doxycycline for Chlamydia) | Active Chlamydia identified | Standard course (1 week) or prolonged (debated) |
| 2 | NSAIDs (1st line for arthritis) | All patients with symptomatic ReA | Continue while symptomatic; reassess at 2–4 weeks |
| 3 | Intra-articular glucocorticoid | NSAID-refractory mono/oligoarthritis | Single injection; may repeat if needed |
| 4 | Systemic glucocorticoids (bridging) | Polyarticular or severe disease not responding to NSAIDs + IA steroids | Short course (weeks), taper; NOT for long-term use |
| 5 | Conventional DMARDs (Sulphasalazine / Methotrexate) | Refractory reactive arthritis lasting > 6 months [1] | Long-term if effective; slow onset (weeks–months) |
| 6 | Biological DMARDs (anti-TNF: Infliximab / Etanercept / Adalimumab) | Refractory to NSAIDs, glucocorticoid and DMARDs [1] | Long-term; requires pre-biologic TB screening |
Disease duration is typically 3–5 months. Most patients may either remit completely or have little active disease within 6–12 months [1]
| Outcome | Proportion | Details |
|---|---|---|
| Complete remission | ~60–80% | Self-limiting within 3–12 months |
| Chronic persistent arthritis | ~15–20% [3] | Ongoing synovitis > 6 months; more common in HLA-B27+ |
| Recurrent episodes | ~15–50% (varies by study) | Triggered by re-exposure to same or different organism |
| Progression to AS | ~5–10% | More likely in HLA-B27+ patients with axial involvement |
Poor prognostic factors (predicting chronicity) [3]:
- HLA-B27 positive
- Male sex
- Early onset
- Hip involvement
- Dactylitis
- Poor NSAID response
- High acute-phase reactants at presentation
- Smoking
High Yield Summary — Management of Reactive Arthritis
-
Treat the infection: Doxycycline 100mg BD × 1 week (or azithromycin 1g stat) for Chlamydia; enteric antibiotics do NOT improve arthritis
-
NSAIDs are 1st line for arthritis (naproxen, indomethacin, diclofenac); effective in ~70–80% of SpA; C/I: GI bleeding, CKD, CVD
-
Intra-articular steroids for NSAID-refractory mono/oligoarthritis; must exclude septic arthritis first
-
Systemic steroids only as short-term bridging; risk of psoriasis flare on tapering
-
DMARDs (sulphasalazine, methotrexate) for chronic ReA > 6 months; effective for peripheral arthritis but NOT for axial or entheseal disease
-
Anti-TNF biologics (infliximab, etanercept, adalimumab) for DMARD-refractory disease; must screen for latent TB before starting (IGRA/TST + CXR)
-
Anterior uveitis: topical steroid + cycloplegic (to prevent synechiae); anti-TNF if refractory (prefer infliximab/adalimumab)
-
Enthesitis: NSAIDs → local steroid injection (NOT Achilles) → anti-TNF if refractory
-
Prognosis: Self-limiting in majority (3–12 months); 15–20% chronic; HLA-B27+ predicts worse outcome
-
Supportive: Physiotherapy, smoking cessation, safe sex education, partner notification/treatment
Active Recall - Management of Reactive Arthritis
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Reactive arthritis, Treatment (p.1716–1718) [2] Senior notes: Maksim Medicine Notes.pdf — Rheumatology, Reactive arthritis, Management (p.328) [3] Senior notes: Ryan Ho Rheumatology.pdf — Spondyloarthritis, axSpA management (p.62), peripheral SpA management (p.66), reactive arthritis (p.64) [8] Senior notes: Adrian Lui Pediatrics Notes.pdf — JIA management (p.456) [20] Senior notes: Ryan Ho Opthalmology.pdf — Uveitis management (p.31) [21] Senior notes: Ryan Ho Urogenital.pdf — Urethritis management (p.249–250) [22] Lecture slides: GC 079 (supp-2)STOPP-START-V3.pdf — STOPP criteria Section H (p.8) [23] Senior notes: Block A - Upper abdominal pain_ peptic ulcer; pancreatitis and gallstone.pdf — NSAID GI risk prevention (p.25) [24] Lecture slides: Handbook of Internal Medicine 2024.pdf — SpA treatment (p.435); RA treatment (p.433) [25] Senior notes: Block A - Treatments for skin diseases (eczema, psoriasis and urticaria).pdf — TNF inhibitors (p.34) [26] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf — Effect of biologics on tuberculosis (p.37)
Complications of Reactive Arthritis
Reactive arthritis, while self-limiting in the majority (60–80% remit within 3–12 months [1][3]), can lead to significant complications. These complications arise from three broad sources:
- Chronicity and progression of the arthritis itself (articular complications)
- Damage from extra-articular inflammatory manifestations (ocular, mucocutaneous, cardiovascular)
- Consequences of treatment (iatrogenic complications)
Understanding why each complication occurs requires linking back to the underlying pathophysiology: an aberrant, genetically driven (HLA-B27) immune response that targets joints, entheses, eyes, skin, and other organs via the IL-23/IL-17 axis and TNF-α pathways.
1. Articular (Musculoskeletal) Complications
- Prognosis: variable, majority remit ≤6–12 months but 15–20% have chronic persistent arthritis [3]
- Why does chronicity develop? In HLA-B27+ individuals, the aberrant immune response becomes self-perpetuating — bacterial antigen persistence in the joint (particularly Chlamydia) drives ongoing IL-17/TNF-α production even after the triggering infection has cleared. The unfolded protein response from HLA-B27 misfolding provides a continuous pro-inflammatory stimulus independent of the original infection.
- Chronic ReA is defined as disease lasting > 6 months [1]
- Manifests as persistent synovitis, ongoing joint pain and swelling, progressive functional limitation
- Risk factors for chronicity:
- Approximately 15–50% of patients experience recurrent attacks
- Recurrences may be triggered by re-exposure to the same or a different triggering organism (e.g., re-infection with Chlamydia in a patient who originally had post-chlamydial ReA, or a new Salmonella exposure)
- Each recurrence carries a risk of cumulative joint damage
- Approximately 5–10% of patients with reactive arthritis progress to established AS
- This occurs almost exclusively in HLA-B27-positive patients with axial involvement (sacroiliitis)
- The pathophysiology: recurrent inflammatory insults to the sacroiliac joints and spine trigger a cycle of erosion followed by new bone formation (syndesmophytes, ankylosis) — the same mechanism that drives AS
- Represents a transition from "peripheral SpA with reactive trigger" to "axial SpA" along the SpA spectrum [4]
The concept of SpA as a spectrum: reactive arthritis can evolve over time into other SpA subtypes, particularly axial SpA/AS [4]
- In chronic ReA, persistent synovitis (mediated by pannus — a mass of proliferating synovium) can lead to:
- Cartilage destruction — inflammatory cytokines (TNF-α, IL-1, IL-17) activate metalloproteinases (MMPs) that degrade the cartilage matrix
- Periarticular bone erosion — osteoclast activation driven by RANKL (upregulated by TNF-α and IL-17)
- Joint space narrowing — secondary to cartilage loss
- However, erosive disease is less common in ReA than in RA or PsA — rarely erosive in early disease [2]
- X-ray findings in chronic ReA: characteristically periostitis with fluffy calcaneal spurs (sacroiliitis and syndesmophytes, if present, tend to be asymmetrical) [3]
- Chronic enthesitis at weight-bearing sites can lead to:
- Achilles tendon thickening and calcification — reactive new bone formation at the enthesis (enthesophyte)
- Plantar fascia calcification and calcaneal spurs — fluffy calcaneal spurs [3]
- Achilles tendon rupture — particularly if treated with local corticosteroid injection (which weakens collagen cross-linking) or fluoroquinolone antibiotics
- The new bone formation at entheseal sites is paradoxical — the same IL-17 that drives erosion also stimulates osteoblastic activity, leading to pathological ossification
- Chronic inflammation → fibrosis of joint capsule and periarticular soft tissues → flexion contractures
- Particularly problematic at the hip and knee — reduces mobility and independence
- May lead to secondary osteoporosis from disuse
- Joint contracture/erosion is a recognised complication of chronic inflammatory arthritis [8]
2. Ocular Complications
Ocular complications are among the most clinically significant in ReA because they can be sight-threatening if missed or undertreated.
Persistent uncontrolled anterior uveitis can be sight-threatening and lead to complications [27]:
| Complication | Mechanism | Consequence |
|---|---|---|
| Posterior synechiae | Posterior adhesion of iris to lens [20] — fibrinous inflammatory exudate in the anterior chamber causes the inflamed iris to adhere to the anterior lens capsule | Irregular pupil; if 360° (seclusio pupillae) → pupillary block → secondary angle-closure glaucoma |
| Cataract | Due to inflammation or topical steroid use [20] — chronic inflammation disrupts lens metabolism; prolonged topical steroids cause posterior subcapsular cataract | Progressive visual loss; requires surgery |
| Secondary glaucoma | Intraocular hypertension ± glaucoma [20] — from (a) trabecular meshwork clogging by inflammatory debris, (b) posterior synechiae causing pupillary block, or (c) steroid-induced IOP rise | Optic nerve damage; irreversible visual field loss |
| Band keratopathy | Band keratopathy [20] — calcium deposition in the superficial cornea (Bowman's layer) in chronic anterior segment inflammation | White band across the cornea; reduced visual acuity |
| Cystoid macular oedema (CME) | Cystoid macular oedema [20] — inflammatory mediators breach the blood–retinal barrier → fluid accumulation in the macular region | Central visual loss; may be irreversible if chronic |
Activity/severity of eye disease is NOT related to disease activity [3] — meaning uveitis can flare or persist even when the arthritis is in remission. This is why ongoing ophthalmological surveillance is essential.
- Conjunctivitis in ReA is usually mild and self-limiting [3]
- Rarely leads to significant complications
- May occasionally progress to keratitis (corneal involvement) if severe or untreated, but this is uncommon
3. Mucocutaneous Complications
- Usually self-limiting, but in severe cases the hyperkeratotic lesions on palms and soles can become:
- Confluent and widespread — covering large areas of the body
- Functionally disabling — thick plaques on the soles impair walking
- Secondarily infected — cracked, fissured skin provides a portal of entry for bacteria
- Histologically identical to pustular psoriasis — may be treated with psoriasis-directed therapies (methotrexate, biologics) if severe
- Usually painless and self-limiting
- In uncircumcised men, the moist environment may promote secondary candidal or bacterial infection
- Rarely causes phimosis (scarring of the prepuce) in severe chronic cases
- Nail dystrophy with subungual hyperkeratosis [3]
- Similar to psoriatic nail disease — onycholysis, pitting, ridging, subungual debris
- May cause cosmetic concern and functional impairment (pain, difficulty with fine motor tasks)
- Subungual hyperkeratosis can be a site for secondary fungal infection (onychomycosis)
4. Cardiovascular Complications
Cardiovascular involvement in ReA is rare but recognised as part of the broader SpA spectrum:
- Aortitis is listed as a clinical feature of SpA [4][6]
- Mechanism: chronic inflammation of the aortic root → aortic wall fibrosis and dilatation → aortic valve ring dilatation → aortic regurgitation
- More commonly seen in ankylosing spondylitis (part of the "6A" extra-articular manifestations) but can occur in any SpA subtype, including chronic ReA
- Usually develops only after years of chronic disease
- Aortic root fibrosis can extend to the AV node and bundle of His → heart block (1st degree → complete)
- Again, rare in ReA but important to recognise in the context of chronic SpA
5. Renal Complications
- IgA nephropathy has been reported in association with SpA, including ReA
- Mechanism: mucosal immune dysregulation (the same mucosal immune system implicated in ReA pathogenesis) → overproduction of polymeric IgA → mesangial IgA deposition → glomerulonephritis
- Presents with haematuria ± proteinuria
- Usually mild and self-limiting but may rarely progress to CKD
- A rare complication of any chronic inflammatory condition, including chronic ReA
- Mechanism: persistent systemic inflammation → sustained elevation of serum amyloid A (SAA) protein (an acute-phase reactant produced by the liver in response to IL-6) → SAA misfolding and deposition in organs as AA amyloid fibrils
- Target organs: kidneys (nephrotic syndrome, renal failure), liver, spleen, GI tract
- Only occurs after years of poorly controlled chronic inflammation
- Prevention: aggressive treatment of the underlying inflammation to keep acute-phase reactants suppressed
Often overlooked but significant:
| Complication | Mechanism |
|---|---|
| Depression and anxiety | Chronic pain, functional limitation, impact on sexual life (due to circinate balanitis, urethritis), uncertainty about disease course |
| Impaired ADLs | Arthritis of weight-bearing joints + enthesitis (heel pain) → difficulty walking, climbing stairs, working |
| Impact on employment | Young working-age adults are the typical demographic — chronic disease may impair occupational capacity |
| Sexual dysfunction | Urethritis, circinate balanitis → pain and embarrassment; psychological impact of STI diagnosis |
| Social stigma | STI-associated trigger (Chlamydia) may cause stigma and relationship difficulties |
These arise not from the disease itself but from its treatment:
| Treatment | Complication | Mechanism |
|---|---|---|
| NSAIDs | GI bleeding, peptic ulcer, AKI, cardiovascular events | COX-1 inhibition → ↓ mucosal prostaglandins → ulcerogenesis; renal vasoconstriction |
| Corticosteroids (systemic) | Cushing's, osteoporosis, DM, infection, AVN, psoriasis flare on tapering | Immunosuppression; metabolic effects; bone resorption; HPA axis suppression |
| Corticosteroids (IA injection) | Tendon rupture, septic arthritis, osteonecrosis | Collagen weakening; introduction of infection; local bone ischaemia |
| Methotrexate | Interstitial pneumonitis, hepatotoxicity, nephrotoxicity, bone marrow suppression [8] | Folate antagonism → cytotoxicity to rapidly dividing cells (hepatocytes, BM, pulmonary epithelium) |
| Anti-TNF biologics | TB reactivation, serious infections, lymphoma (rare), demyelination, HF exacerbation | TNF-α is critical for granuloma maintenance (TB), immune surveillance (infections, malignancy), myelin repair |
Anti-TNF-alpha is the classical example that can increase risk of developing TB, given the importance of TNF-alpha in confining TB to the tuberculoma [26]
| System | Complication | Frequency | Key Risk Factor |
|---|---|---|---|
| Musculoskeletal | Chronic persistent arthritis | 15–20% | HLA-B27+, male, hip involvement |
| Recurrent episodes | 15–50% | Re-exposure to triggering organism | |
| Progression to AS | 5–10% | HLA-B27+, axial involvement | |
| Joint erosion/destruction | Uncommon | Chronic disease | |
| Enthesopathy (calcaneal spurs, Achilles thickening) | Common in chronic disease | Weight-bearing entheseal stress | |
| Flexion contractures | Variable | Chronic synovitis, inadequate physiotherapy | |
| Ocular | Posterior synechiae | Common if uveitis untreated | Recurrent anterior uveitis |
| Cataract | Common with chronic uveitis/steroids | Prolonged topical steroid use, chronic inflammation | |
| Secondary glaucoma | Moderate | Posterior synechiae → pupillary block; steroid use | |
| Band keratopathy | Uncommon | Chronic anterior uveitis | |
| CME | Uncommon | Severe/recurrent uveitis | |
| Mucocutaneous | Severe KB, secondary infection | Uncommon | Extensive skin disease |
| Nail dystrophy | Common | Chronic disease | |
| Cardiovascular | Aortitis, AR | Rare | Chronic SpA |
| Heart block | Rare | Aortic root fibrosis | |
| Renal | IgA nephropathy | Rare | Mucosal immune dysregulation |
| AA amyloidosis | Very rare | Prolonged uncontrolled inflammation | |
| Psychological | Depression, functional disability | Common | Chronic pain, STI stigma |
| Iatrogenic | GI/renal/CV from NSAIDs; TB from biologics | Variable | Drug-specific |
High Yield Summary — Complications of Reactive Arthritis
-
Most important concept: ReA is self-limiting in 60–80%, but ~15–20% develop chronic arthritis and 5–10% progress to AS — almost all chronicity predictors relate to HLA-B27 positivity.
-
Ocular complications are potentially sight-threatening: posterior synechiae, cataract, glaucoma, band keratopathy, CME — all from undertreated anterior uveitis. Eye disease activity does NOT correlate with joint disease activity.
-
Enthesopathy causes chronic heel pain (fluffy calcaneal spurs on X-ray), Achilles tendon thickening — do NOT inject steroids into the Achilles tendon.
-
Cardiovascular (aortitis → AR, conduction defects) is rare but part of the SpA spectrum.
-
AA amyloidosis is a late complication of any chronic uncontrolled inflammation — prevent by keeping CRP/ESR suppressed.
-
Iatrogenic: Always remember anti-TNF → TB reactivation risk (screen with IGRA before starting); methotrexate → BM suppression, hepatotoxicity, lung toxicity; NSAIDs → GI bleeding, AKI; systemic steroids → psoriasis flare on tapering.
-
Psychological impact is real and under-recognised — young men with STI-triggered arthritis, chronic pain, and urethritis/balanitis suffer significant psychosocial morbidity.
Active Recall - Complications of Reactive Arthritis
References
[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — Reactive arthritis, Treatment and Prognosis (p.1716–1718) [2] Senior notes: Maksim Medicine Notes.pdf — Spondyloarthritides overview and ReA (p.323, 328) [3] Senior notes: Ryan Ho Rheumatology.pdf — Reactive arthritis, Ix and Prognosis (p.64); axSpA management and prognosis (p.62) [4] Lecture slides: GC 074. Multiple joint pain.pdf — HLA-B27 diagnosis and prognosis (p.38); Concept of SpA spectrum (p.30) [6] Lecture slides: GC 074. Multiple joint pain.pdf — Clinical features of SpA (p.31) [8] Senior notes: Adrian Lui Pediatrics Notes.pdf — JIA complications and management (p.454, 456) [20] Senior notes: Ryan Ho Opthalmology.pdf — Uveitis complications (p.31) [26] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf — Effect of biologics on tuberculosis (p.37) [27] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — JIA complications including uveitis sequelae (p.697)
High Yield Summary
Reactive Arthritis (ReA) — Key Points for Exams
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Definition: Sterile inflammatory arthritis occurring 1–4 weeks after GI (Salmonella, Shigella, Campylobacter, Yersinia, C. difficile) or GU (Chlamydia trachomatis) infection
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Classic triad: "Can't see, can't pee, can't climb a tree" = conjunctivitis + urethritis + arthritis (but full triad present in only ~1/3)
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SpA family member: RF-negative, HLA-B27 associated (~60–80%), characterised by enthesitis and dactylitis
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Epidemiology: M >> F (15:1 post-venereal; ~1:1 post-enteric), age 20–40y
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Pathophysiology: Aberrant immune response to bacterial antigens in genetically susceptible (HLA-B27+) individuals — molecular mimicry + bacterial persistence + IL-23/IL-17 axis
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Joint pattern: Asymmetric oligoarthritis, LL > UL (knees, ankles, MTPJs)
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Extra-articular: Conjunctivitis (most common eye), anterior uveitis (more serious, HLA-B27 associated), keratoderma blennorrhagica (palms/soles, histologically = pustular psoriasis), circinate balanitis (glans penis), oral ulcers, nail changes
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Skin lesions are histologically identical to psoriasis — shared IL-17/IL-23 pathway
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Course: Self-limiting in 60–80% within 3–12 months; chronic in 15–30% (especially HLA-B27+)
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HLA-B27 prevalence: Southern Chinese ~6–8%
High Yield Summary — Differential Diagnosis of Reactive Arthritis
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Always exclude septic arthritis first — joint aspiration is mandatory in acute monoarthritis. Culture-positive joint = septic, not reactive.
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Always exclude crystal arthritis — polarised microscopy of synovial fluid for MSU (gout) or CPPD (pseudogout).
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DGI is the closest mimicker in sexually active young adults — distinguished by migratory polyarthralgia, pustular skin lesions, tenosynovitis, and dramatic response to antibiotics.
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Other SpA subtypes (PsA, EnA, AS) share overlapping features — the key discriminator is the associated condition (psoriasis, IBD, or predominant axial disease).
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RA and SLE are excluded by serology (RF+/anti-CCP+ in RA; ANA+/anti-dsDNA+ in SLE) and their symmetric polyarticular pattern.
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ARF is another post-infectious arthritis but is post-streptococcal, migratory, and has carditis.
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ReA diagnosis is clinical + exclusion — there is no single diagnostic test. The pattern of asymmetric LL oligoarthritis + preceding GI/GU infection + sterile inflammatory joint fluid + RF−/anti-CCP− + extra-articular features (conjunctivitis, uveitis, mucocutaneous lesions, enthesitis) = ReA.
High Yield Summary — Diagnosis of Reactive Arthritis
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No validated diagnostic criteria exist — diagnosis is clinical (pattern recognition + exclusion of mimickers)
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ASAS peripheral SpA criteria can be applied: peripheral arthritis + ≥1 SpA feature (uveitis, psoriasis, IBD, preceding infection, HLA-B27, sacroiliitis on imaging) OR ≥2 of arthritis/enthesitis/dactylitis/IBP/FHx SpA
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Joint aspiration is the MOST important single test: inflammatory fluid (WBC 2,000–64,000), culture −ve, no crystals → excludes septic arthritis and crystal arthritis
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Serology: RF−, anti-CCP−, ANA− → excludes RA and SLE
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HLA-B27: positive in 30–80%, prognostic (predicts chronicity and axial involvement), NOT diagnostic
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Infection workup: stool culture + Chlamydia NAAT — a positive result supports the diagnosis but a negative result does NOT exclude it
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Imaging: X-ray usually normal acutely; MRI is most sensitive for synovitis, enthesitis, sacroiliitis
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Ophthalmology: Slit-lamp for anterior uveitis if eye symptoms; always check HLA-B27 in uveitis workup
High Yield Summary — Management of Reactive Arthritis
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Treat the infection: Doxycycline 100mg BD × 1 week (or azithromycin 1g stat) for Chlamydia; enteric antibiotics do NOT improve arthritis
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NSAIDs are 1st line for arthritis (naproxen, indomethacin, diclofenac); effective in ~70–80% of SpA; C/I: GI bleeding, CKD, CVD
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Intra-articular steroids for NSAID-refractory mono/oligoarthritis; must exclude septic arthritis first
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Systemic steroids only as short-term bridging; risk of psoriasis flare on tapering
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DMARDs (sulphasalazine, methotrexate) for chronic ReA > 6 months; effective for peripheral arthritis but NOT for axial or entheseal disease
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Anti-TNF biologics (infliximab, etanercept, adalimumab) for DMARD-refractory disease; must screen for latent TB before starting (IGRA/TST + CXR)
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Anterior uveitis: topical steroid + cycloplegic (to prevent synechiae); anti-TNF if refractory (prefer infliximab/adalimumab)
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Enthesitis: NSAIDs → local steroid injection (NOT Achilles) → anti-TNF if refractory
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Prognosis: Self-limiting in majority (3–12 months); 15–20% chronic; HLA-B27+ predicts worse outcome
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Supportive: Physiotherapy, smoking cessation, safe sex education, partner notification/treatment
High Yield Summary — Complications of Reactive Arthritis
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Most important concept: ReA is self-limiting in 60–80%, but ~15–20% develop chronic arthritis and 5–10% progress to AS — almost all chronicity predictors relate to HLA-B27 positivity.
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Ocular complications are potentially sight-threatening: posterior synechiae, cataract, glaucoma, band keratopathy, CME — all from undertreated anterior uveitis. Eye disease activity does NOT correlate with joint disease activity.
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Enthesopathy causes chronic heel pain (fluffy calcaneal spurs on X-ray), Achilles tendon thickening — do NOT inject steroids into the Achilles tendon.
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Cardiovascular (aortitis → AR, conduction defects) is rare but part of the SpA spectrum.
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AA amyloidosis is a late complication of any chronic uncontrolled inflammation — prevent by keeping CRP/ESR suppressed.
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Iatrogenic: Always remember anti-TNF → TB reactivation risk (screen with IGRA before starting); methotrexate → BM suppression, hepatotoxicity, lung toxicity; NSAIDs → GI bleeding, AKI; systemic steroids → psoriasis flare on tapering.
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Psychological impact is real and under-recognised — young men with STI-triggered arthritis, chronic pain, and urethritis/balanitis suffer significant psychosocial morbidity.
Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory seronegative spondyloarthropathy associated with psoriasis, characterized by joint inflammation, enthesitis, and dactylitis affecting peripheral and/or axial joints.
Septic Arthritis
Septic arthritis is an acute infection of a joint space, most commonly caused by bacteria such as *Staphylococcus aureus*, leading to rapid cartilage destruction and joint damage if not promptly treated.