Speakers: Dr. Afsaneh Alavi, Dr. David Boudier, Dr. Christopher Bunick, Dr. Mauro Picardo, and Dr. Byong Seung Cho
Report written by Dr. Adrián Alegre Sánchez
Diagnostic and management challenge: Perianal HS and fistulising perianal IBD
Dr Afsaneh Alavi gave a presentation on the difficulty of differential diagnosis between perianal manifestations of inflammatory bowel disease (IBD, Crohn’s disease) and hidradenitis suppurativa (HS) in the same area. Dr Alavi reminded the audience that in most cases of HS-related fistulas, they are not truly fistulas as they don’t connect to internal organs. Rather, they should be considered tunnels. For their study, her research team selected two cohorts of patients: one with HS and the other with IBD, in both cases affecting the perianal area. The researchers found a few characteristics that may be used to differentiate the two diseases. Patients with HS tend to be younger, smokers, have a higher body mass index, more symptoms affecting the underarms and groin, a bilateral pattern of symptoms, and a greater frequency of tunnels. Patients with IBD, on the other hand, tend to be older, have worse systemic symptoms, be affected on the perineum, and present true fistulas. Analytically, both groups tended to be more anaemic, but there was a greater occurrence of neutrophilia in cases of IBD. In terms of radiological analysis, using MRI, you can see how IBD patients have intersphincteric fistulas and thickening of the rectal mucosa, while HS patients present tunnels and abscesses, with the rectum less affected.
In terms of markers, faecal calprotectin appears to be at higher levels in cases of IBD. In spite of all this, many cases cannot be differentiated and should be considered mixed cases called “perianal fistulising disease.”
Spesolimab for hidradenitis suppurativa: A proof-of-concept study
Spesolimab is a new biologic drug of interest for treating hidradenitis suppurativa. Dr Afsaneh Alavi spoke about its usefulness. It is an IL-36 receptor monoclonal antibody. The IL-36 pathway is hyperactivated in patients with HS. In the study presented, researchers tracked a treatment and a placebo group for 12 weeks, then provided maintenance treatment to both groups for an additional 12 weeks. The treatment group received spesolimab at 1200 mg IV as induction therapy at 0.1 and two weeks, then 1200 mg IV every two weeks thereafter as maintenance therapy, i.e., at four, six, eight, and 10 weeks. Following the initial 12 weeks, maintenance therapy was given at 600 mg subcutaneously every two weeks. As for the results, in the treatment group, all types of lesions were reduced at 12 weeks. The greatest difference was found in fistular lesions and tunnels, with a 40% reduction, compared to a worsening of 56.6% for the placebo group. A reduction of IHS4 scores was observed at week 12 and was maintained at week 24. As for the profile of adverse effects, most of those found in the spesolimab group were local injection site reactions or fatigue. With regard to the selection of spesolimab over other biologics, Dr Alavi indicated that spesolimab appears to be better than adalimumab for treating patients with many fistulas or tunnels.
The human-skin commensal Cutibacterium acnes induces epidermal lipid synthesis
Dr David Boudier presented a study on the ability of Cutibacterium acnes to induce lipid synthesis. The in-vitro study showed that the amount of lipids produced depends on the total amount of C. acnes and is not stimulated, for example, by S. epidermidis. Additionally, that stimulus of lipid synthesis does not depend on the C. acnes phylotype. Of the different molecules produced by C. acnes, it was shown that propionic acid is most responsible for the lipid production by keratinocytes. It appears that PPA receptors are responsible for this activation, especially PPAR-alpha. It also appears that there is feedback between the lipids generated by the keratinocytes and the strains of C. acnes to hinder their growth.
Unique molecular features of the Cutibacterium acnes 70S ribosome and its implications for antibiotic therapy in acne vulgaris
Dr Christopher Bunick reminded the audience that among all medical specialists, dermatologists prescribe the most antibiotics. Among those prescribed antibiotics, over 70% are tetracyclines because of their anti-inflammatory action. Tetracyclines can even have anti-oxidant, anti-lipase, and anti-metalloproteinase effects, among others. Their classic antibiotic action occurs when they bind with the 30S subunit of the bacterial ribosome to inhibit protein synthesis. The problem with tetracyclines is that they are broad-spectrum antibiotics and can have significant effects on the entire intestinal microbiome. Sarecycline, belonging to the tetracycline class, has a larger molecule size that allows it to be more selective for Gram-positive bacteria without as broadly affecting intestinal Gram-negative and other bacteria. Dr Bunick’s team was able to show that this is because sarecycline inhibits two different spots on the ribosome, both 30S and 50S, making it the only antibiotic to have this double effect. As such, sarecycline acts against both the decoding of mRNA and the translation into proteins by the ribosomes. This reduces the risk of bacterial resistance to negligible levels. Thanks to this, using sarecycline allows us to be more selective while having fewer adverse effects, both in the treatment of acne and, in the future, other dermatological conditions.
Successful modulation of the PPAR-γ receptor in the treatment of acne vulgaris: Results of an international phase 2b study with NAC-GED-0507 gel. The GEDACNE Study
Dr Mauro Picardo presented a study of a new topical drug with the ability to modulate PPAR-gamma in moderate to severe acne. The drug in question is N-acetyl-GED-0507-34-LEVO (NAC-GED) at 5% in a gel, used in a study for 12 weeks of treatment. The study compared treatment with 5% and 2% gel against a placebo group. With regard to the results, the research team saw a 57.1% reduction in total lesions with the 5% gel, versus 33.8% using the vehicle alone. The results were significant both for inflammatory lesions and non-inflammatory lesions, but the effect was greater for inflammatory lesions. Additionally, the results were dose-dependent, with the 5% concentration of the drug producing a greater effect. As an advantage over other topical drugs, the researchers did not find adverse effects such as irritation, dryness, peeling, etc.
Combination treatment with adipose stem cell exosomes (ASCE) and fractional CO2 laser for acne scars: A 12-week prospective, double-blind, randomized, split-face study
Dr Byong Seung Cho presented a study of treatment with adipose stem cell exosomes and fractional CO2 laser for acne scars. The exosomes act as intercellular messengers and contain fragments of RNA, DNA, and proteins. There are many different types of exosomes (as many as there are types of cells). Many of them have anti-inflammatory or regenerative effects, among others. Currently, they are being indicated for many different purposes. This study did a comparison of using fractional CO2 laser + 30% exosome gel versus fractional CO2 laser + placebo gel. In total, subjects received three sessions of treatment. The treatment group showed improvement of 32.2% on the ECCA acne scar grading scale, versus 19.9% for the placebo group. Additionally, in the treatment group, erythema and recovery time were reduced.
