January 2019: Onc and transplant ID

Blastomyces helicus, a newly recognized dimorphic fungus endemic throughout the Western US and Canada, causes fatal pulmonary and disseminated infections in immunocompromised patients.  After recognizing an initial case of infection with this organism (previously classified as Emmonsia), researchers at the University of Alberta identified 9 additional isolates of the pathogen in their library, then worked with collaborators at the UT-San Antonio fungus laboratory and ARUP reference laboratory (the latter based on a tip from Twitter – who says social media is a waste of time?) to identify an additional 6 isolates.

B. helicus has a wide distribution that doesn’t match the range of B. dermatitidis, with the former extending as far north as Alberta, as far west as the California coast, as far south as the southern tip of Texas, and as far east as the Nebraska/Iowa border.  Cases occurred in humans, cats and dogs; among the human cases, 6/7 patients for whom information was available had some sort of immunocompromising condition, which included alcoholism, diabetes, leukemia, HIV, lupus, and liver transplantation.  The exposure history appears to involve soil: the one clear exposure history in humans was in a snake farmer from rural norther California who trapped small mammals to feed mammals, while among the veterinary cases one dog was known to burrow in pursuit of prairie dogs and one cat was known to be fond of playing in potting soil. 

(let’s all take a moment to appreciate the veterinarians who obtained social histories from a cat and a dog)

Diagnoses were made by culture (blood in 5 cases, BAL fluid in 5 cases, and pleural & cerebrospinal fluids in 2 cases each). When used, a commercial DNA probe for B. dermatitidis returned with low-positive results below the threshold of positive, and in 1 case each clinical samples were sent for Histoplasma and Blastomyces antigen testing and returned positive.  On histology (see figures 3 and 4), the yeast phase results in cells of variable size which adhere in short branched chains, producing complex configurations (to me, they look a little bit like Christmas tree branches), while the mold phase is characterized by absent conidia and unique coiled helical hyphae.

The infections were primarily pulmonary, most often with pulmonary nodules on imaging, though one patient with HIV and a CD4 count of 5 cells/ul demonstrated cavitary disease; in the one pediatric case (1/10 human cases), the patient presented with meningitis and the organism was isolated from CSF.  Most (human) patients received liposomal amphotericin and then fluconazole; ultimately half died.  Antifungal susceptibility testing showed low MICs for amphotericin B, itraconazole, voriconazole, and posaconazole, but variable activity for fluconazole and the echinocandins.

To summarize: if you see pneumonia and/or fungemia in an immunocompromised patient in western North America with an organism that looks like Blastomyces, think about B. helicus and treat with liposomal amphotericin B, probably followed by itraconazole or another late-gen azole rather than fluconazole.  29878145

What’s the risk of genital warts after renal transplantation?  Genital warts (GWs) are driven by the human papillomavirus (HPV), so you might expect that immunosuppression for the sake of organ transplantation might weaken immune control of HPV and be associated with worsening GW disease.  Using data from a national clinical database in Denmark, the authors performed a prospective cohort study comparing the risk of incident GW in patients undergoing renal transplantation versus sex and age-matched controls.  Patients, none of whom had had GW in the year prior to inclusion in the study, were enrolled over a 19-year period; in total, the cohort included 3268 patients who underwent renal transplantation and 162,910 who did not.  The authors found that renal transplant recipients had a higher incidence of GW (HR 3.3 wth 95% CI 2.8-3.9 in a multivariate model adjusting for sex, age, education, and income), and that this risk persisted for more than 10 years after transplantation and was more pronounced in women than men. 

GW are a cosmetic concern and rarely the source of ID consultation, so you may be wondering why I bothered mentioning this study. The reason is because this study suggests to me a second and IMO much more important question: since HPV is also associated with cervical, penile, and oropharyngeal cancers, all of which can be disabling and/or deadly, should men women who undergo renal transplantation receive more aggressive screening for HPV-related cancers?  30080315

Here is a nice review and meta-analysis of mucormycosis in the modern (post-2000) era.  The authors gathered case reports and case series describing proven or probable mucormycosis published after 2000 via Ovid MEDLINE and EMBASE, including a total 600 articles  

A total 851 individual patients with mucormycosis have been described in the recent literature; the median age of this cohort was 51, and 63% were men. The researchers found that the most common underlying disease was diabetes (present in 40%), which was associated with rhino-orbital-cerebral mucormycosis (OR 2.5; p<0.001).  Hematologic malignancy (of which AML was most common) was associated with disseminated infection (OR 3.9; p=0.001), and solid organ transplantation was associated with disseminated (OR 4.2; p=0.002), gastrointestinal (OR 4.5; p=0.003), and pulmonary (3.2; p=0.003) mucor. 

A specific organism was identified in about half of cases, and of those was Rhizopus about half the time; Rhizopus was more often found in rhino-orbital-cerebral disease than other manifestations (35% vs 15%; p<0.001).  Death occurred in 46% of patients, and was associated with Cunninghamella infections (71% vs 44%; p < 0.001), though most patients with Cunninghamella had pulmonary or disseminated infections, a likely confounding factor.  The authors do not present data on treatment strategies and their associations with mortality.  At our large cancer center, patients with invasive and disseminated mucormycosis often receive combination therapy (sometimes an azole, amphotericin, and an echinocandin all at once!), but probably the main determinant in outcome for these patients is whether their underlying state of immunodeficiency can be reversed in a timely manner.  30036666