Hidradenitis Suppurativa: Can biofilm research support treatment?

Personal stories of people living with skin conditions like Hidradenitis Suppurativa touch us inevitably, stronger than reporting of research findings. Last week, the British Skin Foundation published Bethan’s moving story about life with this biofilm-driven skin disease. We wanted to highlight some of the current research taking place to reassure those like Bethan that the industry is working hard to tackle the problems associated with the disease.  

As Bethan shared with us, all skin diseases involve an element of stigmatisation but few have such a psychosocial impact on the patient. The inflamed lesions progressing to non-inflamed nodules and abscesses are not only perceived as unclean, by the patients, they also cause pain and scarring. The disease has negative impact on quality of life, due to the pain, but also associated anxiety, depression, loneliness, social isolation, and lower self-esteem. Management strategies consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as stopping smoking and weight loss, as well as antidepressants.[i] 

Hidradenitis Suppurativa is a distressing, recurrent skin disease and an integrated approach with psychosocial help through patient group support offers relief from isolation and an opportunity to share common experiences.[ii]

 

The Interplay of Factors in Hidradenitis Suppurativa Pathology

Hidradenitis Suppurativa is a chronic inflammatory skin disease, also known as acne inversa, mainly affecting the intertriginous regions. Clinically, it is characterized by painful recurrent nodules under the skin, abscesses, fistulas and tunnels secreting pus and later scarring. Prevalence is up to 4% of the general population, affecting more women. The pathogenesis of Hidradenitis Suppurativa is not fully understood; it seems to involve genetic factors as well as alterations in the skin microbiome. Several inflammatory cytokines are upregulated in Hidradenitis Suppurativa, i.e. tumor necrosis factor (TNF), interleukin (IL)-1, IL-17, and IL-23, suggesting it has an auto-inflammatory element affecting innate immune system. There is association with metabolic diseases and obesity as well as the environmental factors, such as smoking and mechanical friction. Also keratinocytes may be intrinsically activated, contributing to the inflammation.

 

The Presence of Hidradenitis Suppurativa Biofilms

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of Hidradenitis Suppurativa, most likely a biofilm-driven disease. Skin microbiome dysbiosis, in particular the increase in microbes with a capability for biofilm formation has been reported; the microbiome of lesions differs from the normal appearing skin.[iii] [iv] Chronic, either non-healing or recurrent inflammatory lesions are recalcitrant to antibiotic therapy and exhibit the characteristics of a biofilm infection. Biopsies from chronic lesions from axilla and groin, studied using peptide nucleic acid-fluorescence in situ hybridization and confocal laser scanning microscopy, have shown biofilm presence in both lesions and peri-lesional skin. Large biofilms (aggregates > 50 μm in diameter) found primarily in the inflamed lesions likely occur as a secondary event. This is due to changes in local anatomy e.g. tunnels, keratinous detritus and dilated hair follicles.[v] Research examining axillary skin microbiota found differences in non-lesional skin of Hidradenitis Suppurativa patients compared with people with healthy skin. Surprisingly, reduced microbiota and less biofilm presence prior to the Hidradenitis Suppurativa onset may play an important role in the early course of this disease.[vi] The first study attempting to fully characterise skin microbiome by next-generation sequencing confirmed that the Hidradenitis Suppurativa microbiome lesional and non-lesional skin is truly different from healthy skin. Five microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome type I or type IV were predominant. Propionibacterium was identified as species that may play a role in Hidradenitis Suppurativa skin microbiome dysbiosis.[vii]

As research in this field of dermatology progresses, the identification of specific skin microbial signatures will advance in terms of diagnosis but may also ultimately drive personalised treatment strategies capable of impacting on cases of Hidradenitis Suppurativa such as that described by Bethan.

 

 

[i] Quality of life considerations and pain management in Hidradenitis Suppurativa
[ii] Quality of Life and Psychosocial Implications in Patients with Hidradenitis Suppurativa.
[iii] The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa – Light at the End of the Microbiological Tunnel.
[iv] Hidradenitis Suppurativa: infection, autoimmunity, or both?
[v] Bacterial biofilm in chronic lesions of Hidradenitis Suppurativa. 
[vi] Normal Skin Microbiota is Altered in Pre-clinical Hidradenitis Suppurativa. 
[vii] The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls. 

 

Dr Katerina Steventon, NBIC Senior Innovation Consultant

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