Biologic therapies pose a risk for opportunistic infections, especially for reactivating latent tuberculosis infection (LTBI).
The aim was to describe the clinical features and mortality rate of ...active Mycobacterium tuberculosis (TB) in psoriasis patients receiving biologic therapies.
A systematic review of PubMed, Google Scholar, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases was performed. Studies describing active TB in patients with psoriasis receiving biologic therapy from inception to May 31, 2018 were included. Clinical data as well as mortality rates were recorded.
Fifty-one studies were included, evaluating 78 patients with active TB: 11 prospective studies, 13 retrospective, and 27 case reports/series. Most patients (73%) with active TB were male, the mean age was 48 ± 13 years, and 85% were of European or Asian origin. Pre-treatment LTBI screening was negative for 63% of patients. Disease presented in 33% of patients within the first 3 months of treatment, and in 51% within the first 6 months. Most patients (72%) presented with extra-pulmonary TB, and 49% had disseminated disease. The mortality rate was 7%.
Limitations of this review are its small sample size and inclusion of case reports.
Some patients develop active TB despite LTBI screening. Clinicians initiating biologic therapy in patients with psoriasis should be aware of the clinical features of active TB in this scenario.
Dilated cardiomyopathy (DCM) is a life‐threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4–30 months from four families, were diagnosed ...with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients’ fibroblasts and PPP1R13L‐knocked down human fibroblasts presented higher expression levels of pro‐inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l‐knocked down murine cardiomyocytes and hearts of Ppp1r13l‐deficient mice. The hypersensitivity to lipopolysaccharide was NF‐κB‐dependent, and its inducible binding activity to promoters of pro‐inflammatory cytokine genes was elevated in patients’ fibroblasts. RNA sequencing of Ppp1r13l‐knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l‐deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal‐recessive cardio‐cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.
Synopsis
A new cardio‐cutaneous syndrome associated with fatal dilated cardiomyopathy is discovered in children with sequence variations in PPP1R13L, which encodes for iASPP.
Patient skin‐derived fibroblasts are hypersensitive to inflammatory stimuli, responding with NF‐κB‐dependent high expression levels of pro‐inflammatory cytokines.
In a murine model, the affected hearts are associated with pro‐inflammatory transcriptional programs starting early after birth.
Further abnormal increase happens with age and in response to inflammatory triggers.
Sublethal doses of LPS are fatal in the murine model.
A new cardio‐cutaneous syndrome associated with fatal dilated cardiomyopathy is discovered in children with sequence variations in PPP1R13L, which encodes for iASPP.
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