Tissue damage, gene defect also cause Necrotizing fasciitis

Necrotizing fasciitis not always caused by bacteria but by a combination of tissue damage and a gene defect, according to a new study.

A new Finnish-led study suggests that necrotizing fasciitis, a life-threatening inflammation of connective tissue that leads to tissue necrosis, may be caused by a gene defect, said the Helsinki-Uusimaa Hospital District (HUS) in a press release referring to the study.

The findings offer hope for an effective new treatment for the disease that could avoid repeated surgery and amputations.

Necrotizing fasciitis is a soft tissue infection that rapidly leads to tissue necrosis. Around 50 patients a year are hospitalized with the disease in the Helsinki Metropolitan Area.

The disease can be treated with antibiotics and immediate surgery. However, the tissue damage caused by a strong inflammatory reaction is difficult to stop and patients often need to undergo emergency surgery. Necrotizing fasciitis can lead to a rapid need to amputate limbs, for example, even in previously healthy individuals.

Severe fasciitis has previously been thought to be caused by so-called carnivorous bacteria. Previously, the same Finnish researchers discovered a form of fasciitis that occurs as a result of a routine procedure or tissue damage combined with a gene defect in the patient's genome. This is when the body overreacts to tissue damage and causes inflammation. Bacteria are often not found at all or the infection is of minor importance.

Researchers have found an inflammation-activating defect in the NFKB1 gene in three Finnish and three foreign pediatric and adult patients with severe fasciitis. NFKB1 is one of the most important genes regulating the immune system.

The study investigated the mechanism of how a gene defect causes an excessive and violent inflammatory response. In patients, mild injury, surgery or infection had triggered an uncontrolled inflammatory reaction leading to severe deep tissue inflammation. The immune cells of patients carrying the gene defect secreted large amounts of mediators greatly accelerating inflammation.

Several of the patients in the study have already been treated with immunosuppressive drugs. This has significantly reduced inflammation and prevented the disease from progressing and relapsing.

“With new gene-editing techniques, we were able to identify the nature of the inflammatory response and the mechanisms by which a gene defect causes a strong inflammatory response. We can control excessive inflammation with modern antirheumatic drugs. Due to the severity of their inflammation, some patients have already been treated with anti-inflammatory drugs with very promising results,” said Professor Kari Eklund from the HUS Inflammation Center who led the study.

"If these findings are confirmed, it will be important to investigate in the future whether targeting the mediators now found could help in the treatment of other necrotizing fasciitis."

In the next phase, the research team plans to find out how many people with fasciitis have a genetic predisposing factor to the disease.

Researchers from the University of Helsinki, the Institute of Biotechnology, Oulu University Hospital, the University of Oulu, the Finnish and Norwegian Institutes of Molecular Medicine, Argentina, the UK, and Germany also participated in the study led by HUS researchers.