Acute parvovirus B19 infection presenting as rheumatoid arthritis mimic

Abstract

Acute parvovirus B19 infection can cause acute symmetric polyarthritis indistinguishable from polyarticular rheumatoid arthritis. Most cases of acute arthritis due to parvovirus B19 are self-limiting and resolve with symptomatic treatment. We present a 65-year-old lady from Southern India who presented with history of fever and joint pain for 10 days. Clinical examination revealed symmetric inflammatory arthritis involving the appendicular skeleton with predominant involvement of bilateral metacarpophalageal joints. Laboratory investigations revealed elevated inflammatory markers with negative serology for rheumatoid arthritis. Parvovirus B19 IgM antibody tested positive. She was initiated on nonsteroidal anti-inflammatory drugs with which her symptoms resolved completely.

Introduction

Parvovirus B19 is known to cause clinical syndromes such as erythema infectiosum, aplastic crisis, and arthropathy.[1] However, most infections in adults are subclinical.[2,3] Here, we report a patient with fever and symmetric polyarthritis, later identified as acute polyarthritis due to parvovirus B19.

Case Presentation

A 65-year-old lady from Southern India presented with high-grade fever and joint pain with early morning stiffness for 10 days. She developed pain and swelling in metacarpophalangeal and proximal interphalangeal joints of both hands on day 4 of illness with sparing of distal interphalangeal joints. On day 5, she developed swelling and pain of bilateral knees followed by similar symptoms in both ankles on day 7, in an additive fashion.

She denied history of backache, breathlessness, uveitis, diarrhea, dysuria, rashes, weight loss, and consumption of unpasteurized milk. There was no history suggestive of connective tissue disorder or similar episodes in the past. She was febrile and tachycardic at admission (temperature: 102 F, pulse rate: 112/min). Arthritis involving bilateral proximal interphalangeal and metacarpophalangeal joints was present. The right knee and left mid-foot joints were swollen. Tender joint count was 21. Swollen joint count was 18. Examination of the abdomen, cardiovascular, and respiratory systems were unremarkable.

We made a syndromic diagnosis of acute febrile illness with symmetric polyarthritis. Differential diagnoses considered were noninfectious causes such as index presentation of rheumatoid arthritis, reactive arthritis, and mixed connective tissue disorder. Infectious etiologies such as viral arthritis (chikungunya/parvovirus B19 arthritis), Poncet's disease, and disseminated Brucella/Staphylococcus infections were also considered.

Investigations revealed leucocytosis with elevated inflammatory markers [Table 1]. Blood chemistries (electrolytes, liver, and renal function tests) were normal. X-rays of affected joints revealed effusion without chondrocalcinosis or erosions.

Table 1.

Relevant laboratory investigations

Test	Result	Normal range
White blood cells	11,300/µL	4,400-1,1000/µL
Neutrophils	78%	40%-70%
Lymphocytes	10%	20%-40%
Monocytes	9%	2%-6%
Eosinophils	2%	1%-6%
Basophils	1%	1%-2%
Hemoglobin	10.9 g/dL	12-15g/dL
Platelets	260×103/µL	150-450×103/µL
ESR (mm/h)	76	0-20
CRP (mg/L)	60	<3
Calcium (mg/dL)	9.2	8.5-10.2
Phosphorus (mg/dL)	3.4	2.5-4.4
Rheumatoid factor (IU/mL)	2	<15
ANA	Negative	Negative
Anti-CCP (IU/mL)	0	<20
Anti-streptolysin O (IU/mL)	140	<200

ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; ANA: Antinuclear antibody; CCP: C-reactive protein

Serology for rheumatoid arthritis, chikungunya (IgM), and Brucella (IgM) was negative. Serial blood cultures revealed no growth. Parvovirus B19 IgM ELISA sent during her evaluation tested positive.

She was initiated on nonsteroidal anti-inflammatory drugs. Fever resolved in 5 days followed by resolution of joint symptoms over the next 5 days. At 3-month follow-up visit, she was well, with nodeformities or restriction of joint mobility.

Discussion

Clinical manifestations of parvovirus B19 include hydrops fetalis, erythema infectiosum in children, and aplastic crisis in those with hemolytic anemia/lymphoproliferative disorders.[2,4] Clinical features may vary across different regions. Table 2 highlights the clinical profile of acute parvovirus infections in India.

Table 2.

Clinical profile of acute parvovirus B19 infections in India

Author	Patient population	Clinical features	IgM positive	IgG positive	PCR positive	Course and outcome
Ramanathan et al. (2018)[14]	Children with malignancies with clinical features of parvovirus infection/cytopenia/hemoglobin drop	-	-	-	45% (27/59)	All children treated with intravenous immunoglobulin; persistent parvoviremia - 30%; died - 37%
Viswanathan et al. (2017)[15]	100 immunocompetent pregnant women without hemoglobinopathy	Fever and rash in 2/3 with IgM positivity; rest asymptomatic	3% (3/100)	43% (43/100)	-	All with acute parvovirus infection had normal pregnancy outcome
Gupta et al. (2013)[16]	66 children with aplastic anemia	All asymptomatic	25% (17/66)	-	27% (18/66)	20 children followed up for 6 months; all with acute parvovirus infection survived
Mishra et al. (2012)[17]	14 immunocompetent male adults with hemophagocytic lymphohistiocytosis	-	14% (2/14)	0	14% (2/14)	Alive - 1; died - 1
Kishore et al. (2011)[18]	35 children with newly diagnosed hematological malignancies	Erythema infectiosum - 1; maculopapular rash in legs - 1; rest asymptomatic	17% (6/35)	34% (12/35)	5% (2/35)	All with parvovirus infection survived; prolonged anemia, increased blood transfusion in IgM+ group

Although usually asymptomatic in adults, parvovirus B19 infection can occasionally result in symmetric polyarthritis.[5] Differential diagnoses to be entertained include rheumatoid arthritis, systemic lupus erythematosus, and polymyalgia rheumatica.[6] Joint symptoms are immunologically mediated and associated with appearance of antibodies. In a review of patients with acute undifferentiated arthropathy, parvovirus B19 IgM positivity was 14%.[7,8]

Parvovirus arthritis involves the metacarpophalangeal joints (75%), knees (65%), wrists (55%), and ankles (40%) and is nonerosive.[9]

Distinction between acute parvovirus arthritis and index presentation of rheumatoid arthritis is imperative for prognostication and initiation of appropriate therapy [Table 3].

Table 3.

Clinical features and laboratory tests in rheumatoid arthritis and parvovirus B19 arthritis

Feature	Rheumatoid arthritis	Parvovirus B19 arthritis
Peak incidence	50-75 years	6-19 years
Pattern of joint Involvement	Small and large	Small > large
Number of joints	Polyarthritis	Polyarthritis
Presentation	Additive	Additive
Clinical course	Chronic	Acute (<6 weeks)
Erosions and deformities	Present	Absent
Nodules	Rheumatoid nodules	None
ESR, CRP	Elevated	Elevated
WBC count	Normal	Low/normal
Platelet count	High/normal	Low/normal
Rheumatoid factor, anti-cyclic citrullinated peptide antibody	Positive	Negative
Anti-streptolysin O, anti-deoxyribonuclease-B	Negative	Negative
Treatment	NSAIDs, DMARDs, biologicals	NSAIDs

ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; WBC: White blood cell; NSAIDs: Nonsteroidal anti-inflammatory drugs; DMARDs: Disease-modifying antirheumatic drugs

Serum IgM antibody is recommended in the diagnosis of acute parvovirus B19 infection in immunocompetent hosts. This test has a sensitivity of 89% and specificity of 99%.[10] IgG antibody testing is used for predicting progression of acute infection to chronic arthropathy.[11] Demonstration of viral DNA is important for diagnosis in immunocompromised hosts.[12,13]

Primary care physicians are the first medical contact for most patients with such a presentation. At primary care level, physicians should generate a syndromic diagnosis followed by stepwise evaluation of differential diagnoses. The nonavailability of advanced diagnostic tests can be challenging in primary care settings. In such instances, resolution with symptomatic therapy prior to initiation of disease-modifying antirheumatic drugs would indicate viral arthritis.

This case highlights the uncommon presentation of acute parvovirus B19 infection mimicking rheumatoid arthritis. Although an exception rather than the rule, a high index of suspicion is crucial in making a timely diagnosis and avoiding untoward outcomes.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.