Waiting for the Other Foot to Drop

Posted by Sara Fazio • June 7th, 2013

In the latest article in our Clinical Practice series, a  65-year-old man presented with a 4-month history of fevers, sweats, fatigue, and weakness. He also reported that pain in his feet and calves was sufficiently distracting that he could not enjoy reading.

Mononeuropathy multiplex is typically is manifested by findings in several focal, noncontiguous nerve distributions. The differential diagnosis for mixed motor and sensory multiple mononeuropathy includes hereditary neuropathy with a propensity for pressure palsies, diabetic neuropathy, vasculitides (systemic and nonsystemic), sarcoidosis, infectious processes (e.g., leprosy, Lyme disease, syphilis, cytomegalovirus infection, human immunodeficiency virus [HIV] infection), amyloidosis, and neoplastic infiltration (most commonly lymphomatous).

Clinical Pearls

What is polyarteritis nodosa?  

Classically, polyarteritis nodosa is a necrotizing vasculitis affecting medium-size or small arteries; in 50 to 75% of patients, the peripheral nervous system is involved. The incidence of polyarteritis nodosa is estimated at 5 to 77 cases per million persons per year, of which about one third of cases are attributable to HBV, although this fraction varies with local HBV burden. Clinical features overlap with those of microscopic polyangiitis, which targets arterioles, venules, and capillaries.

How is hepatitis B transmitted, and how should serologies be interpreted?     

HBV is a DNA virus transmitted through percutaneous, sexual, and perinatal routes. Nosocomial transmission is well documented. Subclinical infection can persist without detection for long periods, making it difficult to pinpoint the timing of viral acquisition.  Laboratory studies performed to distinguish acute infection from chronic disease flares are imperfect. The IgM antibody against hepatitis B core (HBc), classically considered an indicator of acute infection, can be present in reactivation and flares of chronic infection. Higher titers of IgM antibody against HBc (positive at >1:10,000) and relatively low HBV DNA levels (<0.5 pg per milliliter or <10[5] copies per milliliter) suggest acute infection in patients with symptomatic hepatitis.

Morning Report Questions

Q: How should patients with polyarteritis nodosa caused by HBV infection be treated?       

A: Polyarteritis nodosa caused by HBV infection generally requires both immunosuppressive and antiviral therapy, since the disease appears to be driven by viral replication and immune-complex formation and deposition. Although there is a paucity of data from clinical trials, observational data from patients treated with antiviral therapy in combination with immunosuppression suggest improved event-free survival relative to historical controls treated only with immunosuppression. Managing coincident HBV infection and polyarteritis nodosa is challenging. Immune suppression is warranted to arrest tissue damage caused by vasculitic inflammation but may promote uncontrolled viral replication and fulminant hepatitis. To balance these concerns, treatment strategies generally involve simultaneous immune suppression, targeted antiviral therapy, and plasma exchange to eliminate immune complexes.

Q: What is the duration of therapy in patients with concomitant polyarteritis nodosa and HBV, and how well do neurologic symptoms respond to treatment?

A: The duration of antiviral therapy is guided in part by seroconversion (i.e., negative antigen and positive antibody titers); after stopping treatment, HBV DNA levels are monitored to confirm eradication. Patients with neuropathic symptoms often have delayed responses to treatment, with clinically significant changes reported months to years after the initiation of therapy in many cases; improvements in motor deficits are often greater than improvements in sensory deficits.

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