Parvovirus B19 Infection

Answer: F, Viral Syndrome

Believing the symptoms to be a possible result of the recently prescribed metformin, the patient stopped taking that medication and visited the endocrinologist. The endocrinologist did not believe the patient had lactic acidosis from metformin—although myalgia is a symptom of lactic acidosis, the latter is a rare side effect of metformin in a relatively healthy patient with normal pH and kidney function.1 The endocrinologist ordered the following laboratory tests: urinalysis, blood urea nitrogen, creatinine, uric acid, creatine kinase, complete blood cell count, erythrocyte sedimentation rate, Lyme titers, cyclic citrullinated peptide IgG/IgA antibodies, albumin/globulin ratio, anti–double-stranded DNA, and complement. As her symptoms migrated and progressed over the next few days, the patient made an appointment with a rheumatologist, who additionally ordered tests for C-reactive protein (CRP) and antinuclear antibodies (ANA).

All of the patient’s laboratory test results were within normal limits, except for the following: platelet count, 432 × 103/µL (reference range, 150-379 × 103/µL); albumin to globulin ratio, 4.1 (reference range, 1.2-2.2); blood urea nitrogen (BUN) to creatinine ratio, 24 (reference range, 9-23); CRP, 6.1 mg/L (reference range, 0.0-4.9 mg/L); and ANA, positive, with a speckled pattern on immunofluorescence assay, which suggested the presence of anti-DFS70 antibodies, which has a low prevalence in systemic autoimmune rheumatic disease.

The rheumatologist subsequently ordered parvovirus B19 tests, the results of which were positive for IgG and IgM antibodies, indicating a more acute infection.

Differential Diagnosis

The signs and symptoms of carpal tunnel syndrome are more localized, with radiation to limbs involved, rather than generalized and migratory.

Lactic acidosis is a potential adverse effect of metformin use, although it is uncommon unless accompanied by excessive dehydration or intense exercise. The patient presented as minimally dehydrated, but BUN and creatinine levels individually were within normal limits. Upon further inquiry, the patient had been prescribed metformin, 500 mg twice a day orally, without incident in the past.

The patient had a 30-year history of a positive ANA titer but without further elevation over that time. Her 3 pregnancies and other stressors had not led to an exacerbation of systemic lupus erythematosus, so although it remained in the differential, it was unlikely. Still, autoimmune disease remained of high concern due to the inflammation of the joints of the hands and knees, suggesting the possibility of rheumatoid arthritis and warranting further diagnostic laboratory workup.

Lyme disease was unlikely, given that the patient had done no gardening or hiking or other outdoor nature activities over the preceding winter months, and she had no outdoor pets in the home.

Amyotrophic lateral sclerosis is a rare disease of the nervous system that presents with muscle weakness and loss of coordination with difficulty grasping items; it more often affects the male population, however.

Discussion. Parvovirus B19 infection is extremely common, with acquisition of immunity predominantly during childhood and adolescence, with antibody seroprevalence of 90% in adulthood.2 The viral syndrome is also referred to as fifth disease or erythema infectiosum and classically presents in children as a “slapped cheeks” appearance.2,3

Adults usually do not develop the slapped-cheek rash seen in children. The most common presentation in adults is a polyarthropathy syndrome characterized by symmetric joint soreness lasting days to weeks.2,4 For this reason, parvovirus B19 infection should be considered in the differential diagnosis for rheumatologic workup. Most commonly affected are the smaller joints of the hands, wrists, elbows, knees, and ankles.

The infection in adults often occurs in immunocompromised individuals with reactivation of latent virus and waning IgG antibody rather than new secondary infection.5 Secondary symptomatic parvovirus B19 infection in healthy adults is uncommon but may be seen in community outbreaks.

Outcome of the case. It is believed that this patient had a reinfection rather than reactivation of parvovirus B19. On further discussion with the patient, who is a practicing health care provider, she reported that she had recently worked on a hospital kidney transplantation floor for several weeks with many immunocompromised patients, which may have been the source of parvovirus exposure.

Although this case was frightening to the patient and a challenging diagnosis for the provider, her symptoms of inflammation, muscle weakness, myalgia, and fatigue resolved spontaneously within a week, consistent with a viral syndrome, and without any further sequelae or need for treatment.

References:

1. Huang W, Castelino RL, Peterson GM. Lactic acidosis and the relationship with metformin usage: case reports. Medicine (Baltimore). 2016;95(46):e4998.
2. Cennimo DJ, Dieudonne A. Parvovirus B19 infection. Medscape. https://emedicine.medscape.com/article/961063-overview. Updated December 6, 2018. Accessed May 24, 2019.
3. Parvovirus B19 and fifth disease. Centers for Disease Control and Prevention. https://www.cdc.gov/parvovirusb19/. Reviewed November 17, 2017. Accessed May 24, 2019.
4. Parvovirus infection. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/parvovirus-infection/symptoms-causes/syc-20376085. Published May 16, 2018. Accessed May 24, 2019.
5. Kaufmann J, Buccola JM, Stead W, Rowley C, Wong M, Bates CK. Secondary symptomatic parvovirus B19 infection in a healthy adult. J Gen Intern Med. 2007;22(6):877-878.