Published: Oct 23, 2013 | Updated: Oct 23, 2013
By Michael Smith, North American Correspondent, MedPage Today

Full Story:  http://www.medpagetoday.com/Neurology/GeneralNeurology/42449

Patients made sick by contaminated steroid injections had a “broad spectrum of disease,” ranging from stroke to abscess, researchers reported.

The pattern of disease varied over time, with meningitis dominating early in the outbreak and noncentral nervous system (CNS) disease showing up later, according to John Jernigan, MD, of the CDC, and colleagues.

And illnesses varied in severity from mild to life threatening to fatal, Jernigan and colleagues reported online in the New England Journal of Medicine.

The outbreak included a total of 751 cases and 64 deaths in 20 states — all linked to epidural, paraspinal, or joint injections of contaminated methylprednisolone acetate from a single compounding pharmacy.

The most commonly identified contaminant was a black mold, Exserohilum rostratum,which only rarely causes human disease.

For this analysis, Jernigan and colleagues looked at records of patients admitted to a hospital or emergency room before Nov. 19, 2012, in Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia — the six states with the highest number of cases.

Those with peripheral joint infections were excluded, leaving 328 patients, including 265 who had CNS infection (sometimes with other conditions as well) and 63 who had only non-CNS infections.

All told, 122 patients had more than one disease type, with meningitis predominating, followed by epidural abscess and arachnoiditis, Jernigan and colleagues reported.

“The manifestation of disease and its progression is a complex blend of host immunological response, the site of infection and the etiological nature of the infecting pathogens,” commented David Perlin, PhD, of New Jersey Medical School in Newark.

“Today,” he told MedPage Today, “many patients who received tainted injections are struggling with severe and chronic pain but acute CNS disease is not observed.”

The current chronic phase of the disease “is difficult to diagnose with conventional radiological tools and equally difficult to manage in some patients,” he noted.

While suspicion has settled on E. rostratum as the causative agent, the researchers noted that it was detected in only a minority — 96 of 268 patients for whom samples were available for testing. Seven other fungal species were detected, most in a single case, although two species were found in three patients each.

“The clinical significance of these isolates is unknown,” the researchers noted, adding, “It is possible that one or more represent a contaminant.”

Highly sensitive tests based on polymerase chain reactions, including some recently developed, can detect fungal pathogens in blood, Perlin noted, and can be useful in the chronic stage of disease.

But, he cautioned, “a proper clinical study is required to assess their clinical value in managing patients.”

Jernigan and colleagues reported that 26 patients in the study population died, including 22 from stroke, four with arachnoiditis, one with meningitis, and two with meningitis combined with an epidural abscess.

Most died early in the outbreak — 58% of the fatalities took place before Oct. 15, 2012.

In those early days, the investigators noted, many patients often presented with severe meningeal inflammation (evidenced by a high white-cell count in the cerebrospinal fluid) that was complicated by stroke.

On the other hand, localized injection-site infections tended to occur later and in some cases, patients under antifungal therapy for earlier meningitis developed such infections.

Jernigan and colleagues cautioned that the analysis includes patients in only six states, and might not apply to the entire outbreak population.

Also, they noted, the data are a snapshot taken early in the outbreak, and are not a “full characterization of continually evolving clinical outcomes.”

UPDATE: This article, originally published Oct. 23, 2013, at 5:00 p.m., was updated with new material (Oct. 23, 2013, at 6:10 p.m.).