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You are here: Home / Articles / Fellows’ Forum Case Report: Progressive Multifocal Leukoencephalopathy and RA

Fellows’ Forum Case Report: Progressive Multifocal Leukoencephalopathy and RA

September 18, 2017 • By Eugene Jalbert, DO, MBA, Priyanka Murali, DO, Rakhee Shah, DO, Robert DiGiovanni, DO, FACOI, FACR, & Rubaiya Mallay, DO, FACOI, FACR

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Pharmaceuticals that have been associated with the development of PML include natalizumab, infliximab and rituximab. PML is a very rare, but serious, side effect of rituximab and even less frequently seen in those with underlying autoimmune disease.

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September 2017
TABLE 2: Lab & CSF Test Results

(click for larger image) TABLE 2: Lab & CSF Test Results

The risk for developing rituximab-associated PML in those with RA is estimated to be about one in 25,000.2 Most cases of PML associated with rituximab have been reported in those who receive it in combination with other immunosuppressive agents.3 A common example of combination rituximab therapy is when it is used with cyclophosphamide, doxorubicin, vincristine and prednisone. This is known as R-CHOP therapy, a common regimen used to treat non-Hodgkin lymphoma. Specifically, when PML is associated with RA, most patients have received other immunosuppressive agents before receiving the rituximab, such as in this case report.3

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Neurologic symptoms of PML are highly variable. These include multifocal deficits that lead to failure to thrive and inevitably to death.

MRI results typical for PML include white matter changes across numerous vascular territories without brain edema. Definitive diagnosis is made by CSF PCR for JC virus or brain biopsy.

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As mentioned previously, no FDA-approved therapies for PML exist. Many experimental therapies exist, but none have proved effective. Treatment of an HIV-infected PML patient with antiretroviral therapy was shown to be beneficial but not curative. Since the introduction of newer effective HIV therapies, a decline in the incidence of PML among HIV-infected patients and a decrease in one-year mortality have occurred.4

Conclusion

Biologic DMARDs have forever changed the landscape of RA treatment. With the advent of such therapies comes added responsibility, such as understanding their potential side effects. The cumulative and additive use of immunosuppressive drugs poses a risk for developing opportunistic infections.

In reference to our case, the use of methotrexate, etanercept and rituximab with steroids led to the development of PML. Currently, there are no ACR recommendations for screening RA patients for the JC virus before initiating rituximab. We believe there should be a call to action to develop appropriate prophylaxis and treatment of PML, especially in those who are immunocompromised. We are encouraged by reports of new therapies being developed.5

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Eugene Jalbert, DO, MBAEugene Jalbert, DO, MBA, is a second-year rheumatology fellow at Nova Southeastern University, Largo Medical Center in Largo, Fla. He is from Tampa, Fla.

Priyanka Murali, DOPriyanka Murali, DO, is a second-year rheumatology fellow at Nova Southeastern University, Largo Medical Center in Largo, Fla. She is from Abu Dhabi, UAE, and grew up in Palm Harbor, Fla.

Rakhee Shah, DORakhee Shah, DO, completed her rheumatology training at Nova Southeastern University, Largo Medical Center in Largo, Fla. She now serves as a clinical rheumatologist on staff at Suncoast Internal Medicine Consultants in Largo, Fla.

Robert DiGiovanni, DO, FACOI, FACRRobert DiGiovanni, DO, FACOI, FACR, completed his rheumatology training at the University of Arizona. He now serves as program director for the rheumatology fellowship at Nova Southeastern University, Largo Medical Center in Largo, Fla. He is also president of Suncoast Internal Medicine Consultants.

Rubaiya Mallay, DO, FACOI, FACRRubaiya Mallay, DO, FACOI, FACR, completed her rheumatology training at Nova Southeastern University, Largo Medical Center in Largo, Fla. She now serves as a clinical rheumatologist on staff at Suncoast Internal Medicine Consultants in Largo, Fla.

References

  1. Lamdhade S, Ashkanani A, Alroughani R. Prevalence of anti-jc virus antibody in multiple sclerosis patients in Kuwait. ISRN Neurol. 2014 Jan 22;2014:861091.
  2. Clifford DB, Ances B, Costello C, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011 Sep;68(9):1156–1164.
  3. Genentech Rituxan Prescribing Information: Package insert.
  4. Khanna N, Elzi L, Mueller NJ, et al. Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study. Clin Infect Dis. 2009 May15;48(10):1459–1466.
  5. Pavlovic D, Patera AC, Nyberg F, et al. Progressive multifocal leukoencephalopathy: Current treatment options and future perspectives. Ther Adv Neurol Disord. 2015 Nov;8(6):255–273.

Pages: 1 2 3 4 | Single Page

Filed Under: Conditions, Rheumatoid Arthritis Tagged With: Clinical, Diagnosis, fellow, outcome, progressive multifocal leukoencephalopathy, Research, Rheumatoid arthritis, rheumatologist, rheumatology, TreatmentIssue: September 2017

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