August 2019: Onc and transplant ID

Here’s a nice descriptions of the natural history of anti-interferon-gamma antibody acquired immunodeficiency syndrome.  There are several case reports of this syndrome in the literature, but I thought this manuscript was worth a share because it collects nearly 100 cases and gives us some insight into the natural history of this disease.  You’ll recall that interferon gamma (IFNG) plays a critical role in macrophage activation, and hence, is of particular importance in control of intracellular pathogens & pathogens walled off in granulomas.  So, no surprise that when you start making antibodies that block the IFNG receptor you become much more susceptible to intracellular & granulomatous pathogens like histoplasmosis, salmonellosis, cryptococcosis, and mycobacterial disease.

This study reports the outcome of 74 patients with anti-IFNGR Ab disease from Thailand identified over an 8 year period, as well as 23 patients identified in the US through the NIH.  In the Thai cohort, the median age at presentation was 50, and two-thirds were women; in the US cohort, the median age at presentation was 45, 91% were women, and 91% were of southeast Asian descent.  In both cohorts, the most common infection was disseminated NTM disease (64% of the Thai cohort and 87% of the US cohort); other common opportunistic pathogens included herpes zoster, salmonella, histoplasma, cryptococcus , and tuberculosis.  In the Thai cohort, the most common sites of infection were lymph nodes (60%) and skin (41%), while in the US it was bone (70%) followed by lymph nodes (65%).  Interestingly, both cohorts had an unusually high incidence of Sweet’s syndrome as well (38% in the Thai cohort vs 9% in the US cohort).  Patients treated in Thailand were mostly given antibiotics alone, with cyclophosphamide given for antibiotic-unresponsive disease; 24% died.  In the US, 57% of patients received antibiotics alone and 39% received rituximab (i.e. to kill off the offending B cells and restore the activity of INFG); none of these patients died.  Patients took a median 3 years to clear their infections.  Autoantibodies decreased over time, and were hastened in their disappearance by both cyclophosphamide and rituximab.

I actually just sent testing for this disease on a patient with a disseminated mycobacterial infection.  For my colleagues in the US, serologies are available as a send-out lab through National Jewish Hospital in Denver; alternately, the NIH provides testing for this and an assortment of related diseases (e.g. GATA2 deficiency - worth knowing for the ID boards!). 31429907

A lateral flow antigen assay reliably detects Aspergillus in respiratory specimens.  The authors took 398 clinical respiratory samples and subjected them to fungal microscopy, fungal culture, or both, plus a novel aspergillus antigen lateral flow assay (LFA-IMMY).  They report that, compared to microscopy and culture, the LFA-IMMY was 91% sensitive and 92% specific.  Unfortunately, it does seem the assay cross-reacts with a number of non-Aspergillus pathogens.  I must admit I am cribbing directly from the abstract here as I couldn’t get accress to the full text. If ever do get full access, I’d like to come back and update this with a more thorough report - because the idea of a rapid and reliable test like the crytococcal serum antigen, but for aspergillus, is very intriguing. 31445208 

What is the risk of LTBI reactivation after hematopoietic stem cell transplantation (HSCT)? Not much. The authors performed a retrospective cohort study of all patients who had HSCT at the Dana Farber cancer center between Jan 2010 and Jan 2015, then collected data on their development of active TB disease through April 2018.  Dana Farber’s institutional protocol is that everyone planned to undergo HSCT gets PPD screening for latent TB, with optional IGRA testing to rule out false positives at the treating physician’s discretion.  All cases of LTBI begin treatment with isoniazid either at discharge or within 4 weeks of undergoing HSCT; if the patient can’t be treated with isoniazid, the ID team is brought onboard to manage the LTBI.

A total 2531 patients had an HSCT over the course of the study period, of whom 91 (4%) had positive screening for LTBI.  Of the patients with LTBI, the median age was 55, half were foreign-born, 60% were men, and after considering previous LTBI treatment and false positivity attributable to BCG vaccination, 63 patients were deemed candidates for post-HSCT LTBI treatment.  Of these, 34 ended up receiving LTBI treatment (30 within 90 days of transplant and 4 more than 90 days after transplant); of the remaining 29 patients, 18 died before LTBI treatment could be started, 9 were lost to followup, and 2 refused to undergo treatment.  There were no cases of active tuberculosis among the patients with LTBI during the followup period (total 342 person-years of follow-up).  The upper bound of the 95% confidence interval for the incidence of TB reactivation after HSCT was 1.66 cases per 100 person-years; for the incidence of TB after HSCT across the entire cohort, it was 0.05 cases/100 person-years.

So, (surprisingly to me!), reactivation TB does not appear to be much of a concern after HSCT, even when many patients with LTBI fail to receive timely treatment. 30689792