Bioderma Congress Reports AAD 2024

Speaker: Teri Seeberger Greiling MD

Report written by Dr. Chris Callewaert

The microbiota exists on all barrier sites of the body, including the gut, skin, lungs, vagina, mouth, and more. The microbiome refers to the collective genome of these microbes. Within this ecosystem, various types of relationships exist, including pathogens, commensals, mutualists, and pathobionts, the latter of which may become pathogenic depending on environmental factors. Our microbiome is shaped by numerous factors such as birth method, diet, exercise, hormones, geographic location, medication, cosmetics, and drugs, with many medications acting as antibiotics.

Humans have coevolved with the microbiome, and its absence can lead to a weakened immune system or an immune system that attacks harmless host cells. The rise of inflammatory diseases can be attributed to the immune system's inability to distinguish between friend and foe.

Lupus, for instance, is often overlooked in textbooks concerning the impact of the microbiome on immune pathways.

Mechanism 1 involves cross-reactivity, where the immune system cannot differentiate between host and bacterial antigens. Some bacteria, such as Ruminococcus, Roseburia, and Porphyromonas, produce antigens like Ro60, leading to cross-reactivity.

Mechanism 2 involves bacterial translocation, where bacteria from the gut leak into the bloodstream and migrate to other parts of the body, including the skin and organs affected by lupus. Even beneficial bacteria like Lactobacillus reuterii and Ruminococcus can translocate, exacerbating the autoimmune response.

Fecal microbiome transplant has shown promise in conditions like ulcerative colitis and lupus, with multiple studies demonstrating consistent results. The gut microbiota also influences melanoma survival after immune checkpoint inhibitor therapy, with poorer survival rates observed in patients who received antibiotics prior to treatment.

Innovative approaches include engineering Staphylococcus epidermidis to produce melanoma antigens, prompting T cells to attack distant melanomas. Additionally, imbalances in dopamine levels can contribute to neurological conditions like Parkinson's disease and formication, highlighting the intricate interplay between microbiota and human health.

Speakers: Alan Irvine, Tissa R Hata, Jonathan Silverberg and Lawrence Eichenfield

Report written by Dr. Chris Callewaert

The epidermal barrier and its role

Alan Irvine

The skin serves as the body's primary barrier, with the immune barrier represented by Langerhans cells acting as a secondary defense. 

Atopic dermatitis (AD) manifests through a complex interplay of three pathways:

• Barrier function: Essential for skin integrity.
• Type 2 inflammation: Characterized by immune responses.
• S. aureus colonization: Involving bacterial presence.

AD commonly induces itching.

Loss of function of filaggrin, critical for skin health, increases the risk of developing AD (Odds ratio 3.1), asthma (Odds ratio 1.5), and peanut allergy (Odd ratio 5.3). Filaggrin monomers are cleaved by bleomycin hydrolase (Caspase 14, Caspase 1) in to NMF (moisturizing factor which keeps the skin hydrated)

Microbiome interacts with the stratum corneum. Forms biofilm. S. aureus

• >70% of patients are colonized with S. aureus,
• S. aureus is associated with barrier dysfunction,
• S. aureus is associated with food allergy,
• S. aureus is associated with lack of response to CSA.

Stress exacerbates skin barrier dissolution, a trait with evolutionary roots for combating parasites and ticks.

Infant skin in pre-clinical AD: low NMF, ceramide, type2 skewing, microbiome alterations.

Many signs are there before AD kicks in.

Can barrier protection prevent AD?

Studies show no effect. Review by Kelleher & al. 2021

Yet, babies that received moisturizers had reduced AD incidence in the first year of life. But it’s a short-term effect.

Of the 3 major pathways that lead to AD, the immune targeting is the most tractable.

On Dupilumab, the skin barrier restores perfectly. 16 week study. Its like a house on fire: First solve the fire before fixing the roof.  

Normally, the skin serves as a robust barrier against pathogens. However, in AD, there's a notable decrease in the expression of antimicrobial peptides (AMPs). Additionally, AD-afflicted skin shifts from an acidic to a neutral pH environment, further hampering its protective capabilities. The deficiency in AMPs also impedes the induction of Th2 cytokines.

Caregivers serve as reservoirs for S. aureus, with a significant presence detected on both child-caregiver pairs and patients themselves, suggesting the potential need for caregiver treatment. Moreover, households harboring AD patients tend to exhibit higher S. aureus colonization rates.

Skin colonization by S. aureus often precedes clinical AD diagnosis in infants (Meylan et al., 2017). Interestingly, the presence of S. epidermidis on pediatric skin has been associated with protection against AD development (Kennedy et al., 2017).

Coagulase-negative staphylococci (CONS) produce their own bacteriocins, which inhibit the agr quorum sensing system in S. aureus, critical for its virulence and colonization (Nakamure et al., 2020). Infants who did not develop AD showed higher levels of S. aureus mutated in Agr quorum sensing virulence factors.

Research conducted by the Gallo lab identified commensal Staph strains capable of killing S. aureus. However, the prevalence of such strains was significantly lower on AD non-lesional skin compared to healthy skin, indicating a loss of beneficial commensals in AD-afflicted individuals. This loss may be attributed to the heightened sensitivity of CONS-AM+ strains to AMPs, leading to their rapid demise on AD skin (Nakatsuji & al., 2023).

The potential for microbiome manipulation to improve AD remains a subject of inquiry, with ongoing studies aimed at elucidating whether microbiome alterations alone can confer protection against AD development. Further research is needed to address this question conclusively.

He noted that the pediatric population is much more prone to Staph toxins than adults. Their microbiome is also different. Kids have more commonly asthma, allergen-specific IgE and known genetic polymorphisms.

Set up approach of management of AD:

• Step 1: emollients, trigger avoidance, daily baths. 95% of dermatologists skip this step, go straight to medicines. Some patients are risk averse. Or they did all this already.
• Step 2: Prescription topical therapy: corticosteroids, calcineurin inhibitors, phosphodiesterase E4 inhibitors, Janus kinase inhibitors,
• Step 3: Systemic or phototherapy: phototherapy, biologics, oral systemic immunomodulators

Patient is often convinced that the onset of AD is a food. He thinks that is a very bad idea, as there are random positives. It is not clinically relevant. If you follow them in that story, you condemn patient to a lifelong allergy, which is not a good idea. You actually want to expose them more, so they become more tolerable. AAAAI guidelines advise against elimination diet.

Speakers: Richard Gallo, Hilary Baldwin, Linda Stein Gold and James Del Rosso

Report written by Dr. Chris Callewaert

Regarding the role of Cutibacterium acnes in acne, toxins produced by C. acnes, such as beta hemolysins and CAMP factors, are implicated in skin tissue damage. While C. acnes is equally abundant on healthy and acne-prone skin, certain ribotypes or subclasses may be more prevalent in acne. Some strains exhibit higher inflammatory responses, possibly due to plasmid-encoded factors, though the exact mechanisms remain unclear. Additionally, the inflammatory potential of C. acnes varies based on its location within the skin, with deeper layers associated with increased inflammation. The surrounding follicular cells also play a significant role, as they may become less effective in combating C. acnes, leading to heightened inflammation.

Diet and gut health also influence acne development. A questionnaire study on 300 acne patients and 120 controls have identified dairy as a potential trigger, while fruits and vegetables are considered beneficial. Commercial probiotics did not really help. The gut microbiome of acne patients suggests that certain bacteria, such as Bifidobacteria and Lactobacilli, may have a protective effect.

In light of these insights, the approach to combating C. acnes is evolving. Rather than relying solely on antibiotics, alternative strategies include neutralizing toxins through vaccination or antibody production, selective killing of C. acnes using beneficial skin bacteria like Staphylococcus capitis or Lactobacilli, minimizing fermentation, and exploring the potential roles of diet and probiotics. Future research will continue to refine these approaches.

Patients with rosacea have an elevated risk of cardiovascular diseases, as evidenced by significantly increased odds of diagnoses related to circulatory system diseases, hypertensive diseases, cerebrovascular diseases, and arterial disease compared to controls.

Metronidazole is commonly used by rosacea patients; however, there are more effective alternatives available. Topical anti-inflammatory creams such as ivermectin have demonstrated superior efficacy compared to metronidazole. They not only work better than antibiotics but also offer longer-lasting remission. Achieving nearly clear skin typically takes about three months for remission, while complete clearance may require a longer duration, often five months or more, emphasizing the importance of striving for complete clearance.

The effectiveness of antibiotics in rosacea treatment can be attributed to their potent anti-inflammatory properties rather than their antimicrobial effects, as Cutibacterium acnes (C. acnes) is not strongly associated with rosacea.

Oral minocycline has shown significant efficacy, particularly at higher doses, with no observed impact on the microbiome, making it a viable option for rosacea management.

Benzoyl peroxide, when microencapsulated to stabilize it and reduce direct skin exposure, has yielded excellent results in treating rosacea. This formulation is well-tolerated and associated with prolonged remission, providing approximately 58 days of disease-free period.

Oxymetazoline, known for its vasoconstrictive properties, can effectively alleviate symptoms of rosacea by reducing redness and inflammation.

Additionally, paroxetine has emerged as an effective treatment for refractory erythema associated with rosacea, offering new hope for patients with persistent symptoms.

Are antibiotics still important in dermatology?

James Del Rosso (future AAD president)

The short answer is yes. The use of antibiotics (Abx) in dermatology is prevalent, but the timing and indication for their use are crucial considerations. Often, antibiotics are prescribed as a precautionary measure, even when the etiology of the condition may be viral. Dermatologists tend to prescribe antibiotics more frequently and for longer durations compared to other healthcare specialties.

An overview of antibiotics in dermatology reveals several key points. Topical anti-inflammatory agents like Dapsone are utilized, while monotherapy with topical antibiotics such as erythromycin, clindamycin, and minocycline is discouraged due to concerns about antibiotic resistance. The efficacy of erythromycin diminishes over time with prolonged use, and the relevance of its anti-inflammatory effects in acne management is debated. Combination therapy with benzoyl peroxide alongside clindamycin or erythromycin helps mitigate the risk of antibiotic resistance.

Optimizing topical therapy for acne involves incorporating gentle and straightforward skincare routines. Benzoyl peroxide, with its direct antimicrobial and comedolytic properties, is favored, especially in combination formulations to improve compliance and reduce the number of products used. Topical retinoids play a significant role in acne management, while the introduction of topical clascoterone adds another important mode of action to treatment regimens. Antibiotic monotherapy is best avoided to minimize the development of resistance, emphasizing the need for simplified combination therapies.

Oral antibiotics have widespread systemic effects and can impact various areas, including the skin, nasal passages, and gastrointestinal tract. They may inadvertently select for more Streptococcus bacteria, although they don't necessarily lead to strep throat. Tetracycline-based antibiotics, including doxycycline, minocycline, and the more recently developed sarecycline, are commonly used due to their favorable safety profiles for chronic use.