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JAMA Clinical Challenge
December 27, 2018

Malar Rash and Polyarthritis

Author Affiliations
  • 1Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio
JAMA. Published online December 27, 2018. doi:10.1001/jama.2018.19498
Case

A 58-year-old woman with a history of cervical spondylosis and hypothyroidism presented with a 2-week history of joint pain. She noted pain and swelling in her right knee, which migrated to the right ankle and then affected the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of her fingers. About 2 weeks before her symptoms began, her 5-year-old grandson had a febrile illness characterized by headaches, body aches, malaise, and rash on the cheeks, trunk, and extremities but no arthritis. Ten days later, her 10-month-old granddaughter developed a similar febrile illness. Eight days ago, her 25-year-old daughter developed headaches, malaise, and significant arthralgias affecting her wrists and knees but no rash or fever. Manifestations in all of the family members resolved spontaneously within 1 week.

On examination, the patient was afebrile with normal vital signs. A malar rash was present (Figure), but there was no rash on the trunk or extremities. She had swelling and tenderness of the MCP and PIP joints and had difficulty making a fist and fully extending her fingers. Laboratory studies revealed a mild normochromic normocytic anemia with a hemoglobin level of 11.5 g/dL, normal white blood cell and platelet counts, and normal results for a comprehensive metabolic panel. She had a positive antinuclear antibody (ANA) result (1:160 [homogeneous pattern; negative <1:80 serum dilution]). Testing for rheumatoid factor was negative; levels of inflammatory markers were normal.

Figure.
Malar rash in a 58-year-old woman.

Malar rash in a 58-year-old woman.

Box Section Ref ID

What Would You Do Next?

  1. Check for anti–double-stranded DNA and anti-Smith antibodies

  2. Schedule bilateral hand radiographs

  3. Order serologic testing for parvovirus

  4. Order testing for anticyclic citrullinated peptide (CCP) antibody

Discussion
Diagnosis

Parvovirus-associated arthritis

What to Do Next?

C. Order serologic testing for parvovirus

The key to the correct diagnosis in this patient is the history of recent exposure to children with a febrile illness associated with a facial rash (“slapped cheek”), suggestive of erythema infectiosum, also known as fifth disease. Diagnosis of recent parvovirus infection requires detection of parvovirus B19–specific IgM antibodies. Therefore, option C is the correct answer. Given the recent history of similar illnesses in other family members, evaluation for chronic autoimmune diseases, eg, systemic lupus erythematosus (option A) and rheumatoid arthritis (option D), would be premature. Furthermore, given that after onset of rheumatoid arthritis, characteristic radiographic changes can take 6 to 12 months to develop, and that no radiographic changes are seen in systemic lupus erythematosus or parvovirus arthropathy, hand radiographs (option B) would not help establish the diagnosis.

Human parvovirus B19 belongs to the family Parvoviridae and genus Erythrovirus (because it preferentially replicates in human erythroid progenitor cells).1 Children are commonly infected first and then can infect healthy family members. The infectious phase begins 24 to 48 hours before the viral prodrome and lasts until the rash appears. Clinical presentation is variable, depending on age and immunologic status. The 5 well-established syndromes associated with parvovirus B19 include erythema infectiosum, arthropathy, transient aplastic crisis (TAC), transplacental fetal infection, and pure red blood cell aplasia.

Erythema infectiosum (fifth disease) is commonly seen in children, presenting with a febrile influenza–like illness for 5 to 7 days, followed by a classic “slapped cheek” rash with relative circumoral pallor. An erythematous, maculopapular rash sometimes follows 1 to 2 days later, covering the rest of the body and fading to produce a lacy appearance. The classic slapped-cheek rash, although less common in adults, can still occur, as in this case.2,3 A rash in a “gloves-and-socks” distribution can also appear.4

Joint symptoms attributable to arthropathy are rare in children but common in adults, and they occur more often in women than in men.5,6 Arthropathy is nonerosive and often symmetric, mainly affecting the small joints of the hands and feet.7,8 In children, however, arthropathy can be asymmetric, often involving the knees and ankles. Joint symptoms usually last for 1 to 3 weeks, although in some patients symptoms may persist for months.6

Transient aplastic crisis is classically described in chronic hemolytic disorders (eg, sickle cell anemia [90% of cases]) and causes abrupt cessation of erythropoiesis and a consequent self-limiting (4-8 days) anemia, which can be potentially life-threatening.9 Patients need to be isolated because they are highly contagious.9

Transplacental fetal infection occurs in about 30% of cases during pregnancy9 and is associated with a 2% to 6% risk of fetal loss.4,9 It can lead to nonimmune hydrops fetalis, intrauterine growth restriction, or isolated serositis.4

Pure red blood cell aplasia causes prolonged anemia in patients with congenital and acquired immunodeficiencies. Giant proerythroblasts can be seen on bone marrow biopsy.

The diagnosis of acute parvovirus infection is based on detection of circulating IgM antibodies to parvovirus B19.6 By the time the rash appears, 90% of cases are IgM antibody–positive.6 This antibody remains detectable for up to 3 months. The IgG antibody appears within 1 week of illness and remains detectable for life.6 Results of other laboratory tests, including tests for acute phase reactants, are usually normal. ANA and rheumatoid factor may be transiently detectable.6 Additional testing may include detection of viral nucleic acid (parvovirus B19 DNA) in blood by qualitative polymerase chain reaction. This test is critical in immunocompromised patients because they may not test positive for IgM and IgG antibodies.4,9,10

Treatment for acute parvoviral arthritis is symptomatic with nonsteroidal anti-inflammatory drugs. Treatment for other manifestations include blood transfusions for aplastic crisis and temporary cessation of immunosuppression and intravenous immunoglobulins for patients with chronic infection (persistent viremia associated with prolonged polyarthritis or anemia). Intrauterine blood transfusions can be performed for cases of hydrops fetalis.

Patient Outcome

Additional laboratory results showed significant titers of IgM (15.04 index value) and IgG (6.45 index value) antibodies to parvovirus B19 (interpretation for both IgM and IgG parvovirus B19 antibodies: positive >1.1 index value). Results of tests for antibodies to CCP, double-stranded DNA, and extractable nuclear antigens were negative. The patient was treated with prednisone starting at 35 mg daily and tapering over the course of 1 week, which resolved her joint symptoms. Six months later, results of repeat studies were negative for IgM antibodies to parvovirus B19 and for ANA.

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Article Information

Corresponding Author: Soumya Chatterjee, MD, MS, FRCP, Department of Rheumatic and Immunologic Diseases, Orthopaedic and Rheumatologic Institute, Cleveland Clinic, 9500 Euclid Ave, Desk A50, Cleveland, OH 44195 (chattes@ccf.org).

Published Online: December 27, 2018. doi:10.1001/jama.2018.19498

Conflict of Interest Disclosures: None reported.

Additional Contributions: I thank the patient for providing permission to share her information.

Section Editor: Mary McGrae McDermott, MD, Senior Editor.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at mdm608@northwestern.edu.
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