Reactive Arthritis: Symptoms, Types, Causes and Treatment

Reactive arthritis is a fascinating yet often misunderstood condition that emerges after an infection elsewhere in the body. This immune-mediated inflammatory arthritis can cause a wide array of symptoms, affect people differently depending on various risk factors, and sometimes require comprehensive treatment. This article explores the key aspects of reactive arthritis, drawing from recent research to deliver an evidence-based and engaging overview.

Symptoms of Reactive Arthritis

Reactive arthritis does not present the same way in everyone. The classic triad—arthritis, conjunctivitis, and urethritis—remains a hallmark, but the actual range of symptoms is far broader, with many patients displaying only some features or experiencing extra-articular (outside the joints) manifestations. Recognizing the diversity of symptoms is crucial for timely diagnosis and management.

Symptom	Description	Common Sites/Features	Source(s)
Arthritis	Joint pain, swelling, and stiffness	Knees, ankles, feet, lower back	1,3,4,5,7,10,11
Conjunctivitis	Eye redness, pain, or discharge	Eyes	1,2,3,4
Urethritis	Painful urination, discharge	Urogenital tract	1,2,3,4,5
Skin lesions	Psoriasiform rashes, pustules	Palms, soles, genitals	1,4,5
Mucosal ulcers	Mouth or genital ulcers	Oral/genital mucosa	1,4
Back pain	Inflammatory lower back pain	Spine, sacroiliac joints	4,10,11
Cardiac signs	Rare: heart involvement	Heart	4

Table 1: Key Symptoms of Reactive Arthritis

Understanding the Symptom Spectrum

The Classic Triad—But Rarely Complete

Reactive arthritis is traditionally described by the triad of arthritis (joint inflammation), conjunctivitis (eye inflammation), and urethritis (urinary tract inflammation) 1,2,3,4. However, most patients do not have all three at once, and it is more common to see only some of these features 3,4.

Articular Symptoms

• Joint pain and swelling typically affect the large joints of the lower limbs, especially the knees, ankles, and feet 1,5,7,10.
• The arthritis is usually asymmetric and oligoarticular (affecting a few joints), but can sometimes be monoarticular or polyarticular 7.
• Some people experience inflammatory back pain involving the lower back and sacroiliac joints 4,10,11.

Extra-Articular Symptoms

• Eye involvement ranges from mild conjunctivitis to more serious uveitis 1,2,3,4.
• Urethritis or cervicitis presents as dysuria (painful urination) or discharge 1,2,3,4,5.
• Skin and mucosal findings include psoriasis-like rashes (especially on palms/soles), mouth ulcers, and genital lesions 1,4,5.
• Rarely, the disease may affect the heart or other organs 4.

Who Is Affected?

• Most commonly, young adults aged 20–40 are affected, with a higher frequency in males 5,7,10.
• Genetic predisposition, especially the presence of the HLA-B27 gene, increases risk and may influence the severity and pattern of symptoms 1,4,5,6,9.

Types of Reactive Arthritis

Reactive arthritis is not a singular disease but a spectrum of related conditions. Classification can be based on the triggering infection, genetic associations, or clinical features. Understanding the different types aids in tailored management and prognosis.

Type	Trigger/Infection Source	HLA-B27 Association	Source(s)
Urogenital ReA	Chlamydia trachomatis	Strong	4,5,6,9,11
Enteric ReA	Salmonella, Shigella, Campylobacter, Yersinia	Variable	4,5,6,8,9,11
HLA-B27+ ReA	Any, more severe if +	Yes	1,4,5,6,9
HLA-B27- ReA	Any, less severe/atypical	No	6
Reiter’s Syndrome	Classic triad (arthritis, conjunctivitis, urethritis)	Strong	2,4,5,6

Table 2: Main Types of Reactive Arthritis

Classification and Clinical Subtypes

By Infection Source

• Urogenital ReA: Most commonly follows Chlamydia trachomatis infection. Presents with arthritis, sometimes preceded by sexually transmitted infection symptoms. Strongly associated with HLA-B27 4,5,6,9,11.
• Enteric ReA: Develops after gastrointestinal infections, especially with Salmonella, Shigella, Campylobacter, or Yersinia 4,5,6,8,9,11. The incidence varies by pathogen; for example, about 12 per 1,000 following Salmonella or Shigella infection 8.

By Genetic Association

• HLA-B27 Positive ReA: Associated with more classic and severe forms, including the full triad. This form is considered part of the spondyloarthropathy family 1,4,5,6,9.
• HLA-B27 Negative ReA: Tends to be milder and may have atypical features 6.

By Clinical Presentation

• Reiter’s Syndrome: The term is sometimes used when the classic triad is present; however, most experts prefer “reactive arthritis” to encompass the broader spectrum 2,4,5,6.
• Monoarticular, Oligoarticular, Polyarticular: Classified by the number of joints involved. Oligoarticular (few joints) is the most common presentation 7.

Causes of Reactive Arthritis

Understanding what triggers reactive arthritis is key for prevention and accurate diagnosis. The disease results from a complex interaction between infectious agents and the host’s immune system, influenced by genetic and possibly environmental factors.

Cause	Description/Organism	Risk Factors	Source(s)
Chlamydia trachomatis	Common urogenital trigger	Young adults, HLA-B27	4,5,6,9,11
Salmonella, Shigella, Campylobacter, Yersinia	Enteric bacteria, GI infections	HLA-B27, recent GI illness	4,5,6,8,9,11
Host genetics	HLA-B27 and other genetic factors	Increases susceptibility	1,4,5,6,9
Immune response	Abnormal host immune activation	Th1/Th2 imbalance, molecular mimicry	1,9
Other infections	Rare: viral, HIV	Immunosuppression	5,11

Table 3: Common Causes and Risk Factors for Reactive Arthritis

The Role of Infection

Urogenital Infections

• Chlamydia trachomatis is the leading cause of urogenital reactive arthritis, particularly in sexually active young adults 4,5,6,9,11.
• Symptoms often begin 1–6 weeks after the initial infection, which may be asymptomatic 4.

Gastrointestinal Infections

• Salmonella, Shigella, Campylobacter, and Yersinia are the main enteric pathogens. Diarrhea or GI upset typically precedes arthritis 4,5,6,8,9,11.
• Not everyone exposed to these bacteria develops arthritis; only about 1–15% of infected individuals do 4,8.

Genetic and Immunological Factors

• HLA-B27: This genetic marker is present in the majority of those with severe or recurrent ReA, but not required for disease 1,4,5,6,9.
• The immune system appears to react abnormally to bacterial antigens, causing persistent inflammation even after the infection has resolved 1,9.
• Mechanisms such as molecular mimicry (where bacterial proteins resemble self-proteins) and imbalances in T-helper cell responses may play a role 1,9.

Other Considerations

• Rarely, other infections (like HIV) or non-bacterial triggers have been implicated 5,11.
• Changes in the microbiome may modulate risk and are under active investigation 15.

Treatment of Reactive Arthritis

Management of reactive arthritis focuses on relieving symptoms, controlling inflammation, and addressing the underlying infection when possible. While many cases resolve spontaneously, some patients develop chronic or severe disease requiring advanced therapy.

Treatment	Approach/Medication	Indication/Notes	Source(s)
NSAIDs	Ibuprofen, naproxen, etc.	First-line for pain/swelling	5,14,15
Antibiotics	Doxycycline for Chlamydia	May help if early urogenital ReA; less effective for enteric causes	5,13
Corticosteroids	Intra-articular or systemic	Severe joint inflammation	5,14
DMARDs	Sulfasalazine, methotrexate	Persistent or refractory cases	14,15
Biologics	TNF inhibitors, others	Severe, chronic, refractory ReA	14,15
Physical therapy	Exercise, mobility programs	Maintain joint function	14

Table 4: Main Treatments for Reactive Arthritis

First-Line and Supportive Treatments

• NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are the mainstay for most patients, rapidly reducing pain and swelling 5,14,15.
• Physical therapy and exercise help preserve joint mobility and muscle strength 14.

Targeting the Underlying Infection

• Antibiotics are effective if a persistent urogenital (Chlamydia) infection is identified and treated early 5. However, for enteric (gut) infections, antibiotics do not appear to change the course of arthritis 5,13.
• Meta-analyses suggest the benefit of antibiotics for established ReA is unproven and may increase side effects 13.

Advanced and Chronic Disease Management

• Corticosteroids (especially intra-articular injections) can be used for severe joint inflammation or when NSAIDs are inadequate 5,14.
• DMARDs (Disease-Modifying Anti-Rheumatic Drugs) such as sulfasalazine or methotrexate are reserved for persistent or chronic cases 14,15.
• Biologic agents (like TNF-alpha inhibitors) are considered for refractory or severe disease. Early open-label studies suggest good efficacy, though these are not yet standard and require specialist management 14,15.

Prognosis and Monitoring

• Most patients experience improvement within 6–12 months, but a subset develop chronic arthritis or extra-articular complications 14,15.
• Early diagnosis and intervention can reduce the risk of long-term disability 2,14.

Conclusion

Reactive arthritis is a complex, multifaceted condition that requires careful clinical attention. Here is a summary of the main points:

• Symptoms are diverse and may include arthritis, conjunctivitis, urethritis, skin and mucosal lesions, and sometimes cardiac involvement.
• Types of ReA are classified by the triggering infection (urogenital vs. enteric), genetic association (HLA-B27), and clinical presentation.
• Causes involve a mix of infectious triggers (mainly Chlamydia and certain gut bacteria), genetic predispositions (notably HLA-B27), and immune system factors.
• Treatment is stepwise, starting with NSAIDs and supportive care, targeted antibiotics for select cases, and advancing to DMARDs or biologics if chronic or severe.
• Early recognition and individualized management are key to improving outcomes and preventing complications.

Understanding the evolving science of reactive arthritis enables healthcare professionals and patients to work together for optimal care and better quality of life.