RheumatologyTier 2Disease (DEADMAN)

Viral arthritis

Description

Acute, usually self-limiting arthritis or arthralgia accompanying (or immediately following) a viral infection
*The most important differential of early rheumatoid arthritis - symmetrical small-joint polyarthritis with morning stiffness, but it resolves*
Mechanisms: direct viral synovial invasion (rubella, alphaviruses) vs immune complex deposition (hepatitis B, parvovirus)

A viral cause underlies ~10-15% of acute polyarthritis presentations
Parvovirus B19 - the commonest; F>M, typically a mother or teacher exposed to a child with slapped-cheek disease; outbreaks every 3-4 years, late winter/spring
Ross River and Barmah Forest virus - *endemic to Australia; ~5,000 Ross River notifications/yr, peaking in summer-autumn*, in coastal and riverine regions
Chikungunya - returning travellers from South/South-East Asia, the Pacific and Africa
Rubella - now rare in Australia (vaccination), but rubella VACCINE also causes arthritis, especially in adult women

Mechanisms

Direct synovial infection - rubella, alphaviruses (Ross River, chikungunya), HIV
Immune complex deposition - hepatitis B (prodromal serum-sickness phase), hepatitis C (via cryoglobulins), parvovirus B19
Molecular mimicry / bystander activation - post-viral reactive arthropathy
Chronic immune dysregulation - hepatitis C -> mixed cryoglobulinaemia -> arthritis, purpura, neuropathy, membranoproliferative GN

Parvovirus B19 specifically

Binds the P antigen (globoside) on erythroid progenitors -> hence aplastic crisis in patients with a shortened red cell lifespan
Arthritis is immune-complex mediated, coincident with IgM appearance and the rash
- *By the time the joints hurt, the patient is no longer infectious*

Joint distribution is the aetiological clue

Pattern	Viruses
SMALL joints, symmetrical, RA-like	Rubella (and rubella vaccine), *hepatitis B (with an urticarial rash in the prodrome), parvovirus B19*
LARGE joints	Mumps, varicella
Polyarthritis + severe, prolonged arthralgia	Ross River, Barmah Forest, chikungunya (alphaviruses)
Oligoarticular / enthesitis / reactive pattern	HIV (and HIV-associated reactive and psoriatic arthritis)

Clinical clues by virus

Parvovirus B19 - acute symmetrical small-joint polyarthritis + "slapped cheek" or lacy reticular rash; adults often have joints without the rash
- *Can be transiently RF, ANA and even anti-dsDNA positive - the classic mimic of early RA or SLE*
Hepatitis B - prodromal (pre-icteric) serum-sickness-like syndrome: fever + URTICARIA + symmetrical polyarthritis, settling as jaundice appears
- Also polyarteritis nodosa in chronic infection
Hepatitis C - chronic arthralgia/arthritis, cryoglobulinaemia (purpura, neuropathy, low C4, very high RF)
Ross River / Barmah Forest - fever, severe polyarthralgia, maculopapular rash, profound fatigue; arthralgia may last months
Chikungunya - abrupt high fever + excruciating symmetrical polyarthritis ("that which bends up"); chronic in up to 40%
Rubella - fine rash, posterior auricular and suboccipital lymphadenopathy
HIV - seroconversion arthralgia; also painful articular syndrome, reactive and psoriatic arthritis
EBV, CMV, mumps, varicella, adenovirus, enterovirus, SARS-CoV-2, dengue, Zika

Investigations

FBE, CRP/ESR, LFT, UEC
- Cytopenias, atypical lymphocytes, transaminitis point to a viral cause
Serology: parvovirus B19 IgM and IgG, hepatitis B (HBsAg, anti-HBc IgM) and C, HIV, EBV, CMV, Ross River and Barmah Forest IgM/IgG, rubella
- *Alphavirus IgM can persist for over a year - a single positive IgM does not prove recent infection; paired sera or rising titres are better*
RF, anti-CCP, ANA - interpret cautiously; anti-CCP is the discriminator - it is NOT raised by viral infection**
*Aspirate any effusion to exclude sepsis and crystals*
Travel, mosquito exposure, sexual history, childcare and occupational contacts, vaccination history

1. Symptomatic treatment is the treatment

NSAIDs at anti-inflammatory dose - first line
Paracetamol, rest, splinting, graded activity
*Avoid DMARDs and corticosteroids in the acute phase - most resolve, and immunosuppression in undiagnosed hepatitis B or HIV is harmful*
Short course of prednisolone only for severe, prolonged, disabling disease once infection is characterised

2. Treat the virus where treatable

Hepatitis C -> direct-acting antivirals (cure >95%); arthritis and cryoglobulinaemic vasculitis usually resolve with cure
Hepatitis B -> antiviral therapy if chronic and indicated; *always screen before immunosuppression - reactivation is life-threatening*
HIV -> antiretroviral therapy
Parvovirus, alphaviruses, rubella, mumps -> no antiviral; supportive only
- IVIG for parvovirus in the immunocompromised with pure red cell aplasia

3. Public health and counselling

Parvovirus B19 - *risk to pregnant contacts (hydrops fetalis, fetal anaemia, especially <20 weeks) and to patients with haemolytic anaemia (aplastic crisis) or immunodeficiency*
- Reassure: the patient is no longer infectious once the rash/arthritis appears
Ross River/Barmah Forest - notifiable; mosquito avoidance (repellent, screens, dusk/dawn); no vaccine
Chikungunya, dengue, Zika - notifiable; travel and mosquito advice; Zika - defer conception
Rubella - notifiable; check immunity in women of childbearing age

4. When to reconsider the diagnosis

*Persistent synovitis beyond 6 weeks -> reassess for rheumatoid arthritis*
- Anti-CCP, repeat examination for synovitis, hand and foot X-rays, ultrasound
Rheumatology referral if symptoms persist beyond 3 months or erosive change appears

Parvovirus B19 - aplastic crisis in haemolytic anaemia, pure red cell aplasia in immunodeficiency, hydrops fetalis, myocarditis, transient RF/ANA/anti-dsDNA positivity
Hepatitis B - polyarteritis nodosa, membranous nephropathy, serum-sickness prodrome
Hepatitis C - mixed cryoglobulinaemia (purpura, neuropathy, MPGN, very high RF, low C4), Sjogren-like sicca, porphyria cutanea tarda
HIV - reactive arthritis, psoriatic arthritis, diffuse infiltrative lymphocytosis syndrome (DILS), avascular necrosis, myositis
Ross River / Barmah Forest - prolonged post-viral fatigue
Rubella vaccine - arthritis in adult women
SARS-CoV-2 - post-COVID inflammatory arthritis, reactive arthritis, MIS-A

*Most resolve completely within 2-6 weeks* - the defining feature
Parvovirus B19: arthritis lasts weeks to a few months; ~10-20% have symptoms beyond 6 months; rarely evolves into true RA - but a small number of RA cases are triggered by it
Ross River / Barmah Forest: joint pain and profound fatigue commonly persist 3-6 months, occasionally longer; *non-erosive, and complete recovery is the rule* - say so, because the fatigue is frightening
Chikungunya: chronic arthritis in up to 30-40% at 1 year - the most likely alphavirus to persist
Hepatitis B prodrome: resolves as jaundice develops
Hepatitis C: chronic unless the virus is cured
*Erosive change means the diagnosis was never viral* - re-investigate

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