Every year the AARS holds a Scientific Symposium at the Annual Meeting of the Society for Investigative Dermatology (SID). During the symposium, past AARS clinical research grant recipients present their findings and current AARS members convene from across the world highlight their work.
On May 7, 2013, the AARS held its third Scientific Symposium during the Annual Meeting of the Society for Investigative Dermatology (SID).
Below you can read summaries of what was presented and related commentary from the meeting.
Analysis of Distribution Patterns of Propionibacterium Acnes Phylotypes and Peptostreptococcus Species Identified by PCR-based Techniques in Association with Clinical Characteristics of Acne Vulgaris
Presenter: Dae Hun Suh,Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea
Suh, Dae Hun; Kwon, Hyuck Hoon; Yoon, Ji Young; Park, Seon Yong; Min, Seonguk. Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea and Acne Research Laboratory, Seoul National University Hospital, Seoul, Korea.
Precise roles of Propionibacterium acnes (P. acnes) and other anaerobic bacteria in the pathogenesis of acne are still unclear. Recent studies have shown that P. acnes can be further classified into several phylotypes with distinct phenotypes and virulences, while their correlation with clinical characteristics of acne has been rarely demonstrated.
To analyze relationships between distribution patterns of two major anaerobic bacteria and clinical acne manifestations, we identified P. acnes phylotypes and Peptostreptococcus species from various acne lesions. A total of 370 samples from acne patients and 65 samples from healthy controls was investigated. Three P. acnes phylotypes and Peptostreptococcus species were identified by practical PCR-based methods including the use of type-specific primers and restriction fragment polymorphism analysis, respectively.
Distribution patterns were analyzed from the perspectives of disease severity, subtypes of lesions, and sebum production. Proportions of type IA P. acnes and Peptostreptococcus species were higher in acne patients compared with healthy controls. Parallel distribution patterns were observed among acne patients as the disease severity aggravated. In addition, type IA P. acnes and Peptostreptococcus species comprised higher proportions in papules and pustules compared with comedones and skin surface.
Finally, there was no significant difference in sebum output between patients infected with type IA P.acnes and the other patients. Type IA P. acnes and Peptostreptococcus species are likely more closely associated with acne inflammation. These findings might partly clarify the functional contradiction between pathogens and ubiquitous inhabitants, providing insight into the development of new acne therapeutics.
Commentary from the meeting
Acne patients have more phylotype 1A and peptostreptococcus in the skin compared to normal controls that can lead to intensification of inflammation. Interesting future studies would look at the correlation between changes in these organisms and the clinical response to therapy.
Identification of Biofilm in Acne Vulgaris Is an Infrequent Occurrence, Seen More in Non-Inflammatory Comedones than in Inflammatory Papules
Presenter: Manisha Patel, Dermatology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Mentor: Sewon Kang
Patel, Manisha J.; Agostinho, Alessandra; James, Garth; Rosenthal, Ian; Chang, Nancy; Martin, Jo ; Leung, Sherry; Chien, Anna; Kang, Sewon. Dermatology, Johns Hopkins School of Medicine, Baltimore, MD, United States and Center for Biofilm Engineering, Montana State University, Bozeman, MT, United States.
Acne vulgaris is a common multifactorial disorder of the pilosebaceous follicles. In recent years the role of Propionibacterium acnes (P.acnes) in triggering an inflammatory response has gained much attention. Although P.acnes is known to colonize pilosebaceous units in all acne prone individuals, development of acne lesions is not universal. We hypothesized that a trigger for inflammation in pilosebaceous follicles may reside in biofilm vs. the planktonic state of P.acnes.
In this study we examined the presence of biofilm in non-inflammatory (comedones), inflammatory (papules), and uninvolved adjacent skin from acne patients. Fourteen patients with mild to moderate acne were enrolled (8 males, 6 females; mean age 28.6 years old [range: 18-40]). Skin specimens removed by punch instrument (3mm) were analyzed by confocal laser scanning microscope for the identification of biofilms (defined by large micro-colonies of > 100 cells) in the pilosebaceous unit.
Of the 42 (14 x 3) skin specimens studied, 9 (21%) contained biofilm. Amongst acne lesions, biofilm was present in 8 (5 comedones and 3 papules) out of 28 (29%). In clinically normal skin, biofilm was observed in 1 sample. Our data indicate that biofilm is not present in the majority of acne lesions. Furthermore, it is present more frequently (almost 2-fold) in non-inflammatory comedones than in inflammatory papules.
One speculation for this finding is that biofilm may be involved in the very early, rather than late stages of acne inflammation. Further elucidation of biofilm in acne will advance our understanding of its involvement in pathogenesis and the development of improved therapeutics.
Commentary from the meeting
This study shows that biofilms are contained in a minority of acne lesions. Interestingly fewer biofilms were found in inflammatory acne lesions compared to comedones. Examining the role of biofilms in early acne lesion development may be of interest in future studies.
Leptin Affects Sebaceous Lipid Formation and Intracellular Distribution and Induces Proinflammatory Signaling in SZ95 Sebocytes
Presenter: Daniel Torocsik, Department of Dermatology, University of Debrecen, Debrecen, Hungary.
Mentor: Lajos Kemeny, Department of Dermatology, University of Szeged, Szeged, Hungary
Torocsik, Daniel; Kovacs, Dora; Dozsa, Aniko; Posta, Edit; Molinaro, Raphael; Nagy, Gergely G.; Ruhl, Ralph; Tax, Gabor; Szabo, Kornelia; Kemeny, Lajos; Zouboulis, Christos C.; Remenyik, Eva. Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.;Department of Dermatology, Semmelweis Medical and Health Care Center, Miskolc, Hungary.;Department of Internal Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.;Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Department of Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary; MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary; Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
Sebaceous glands maintain the lipid barrier of the skin surface through the production of sebum. In addition, sebocytes also play an active role in innate immunity, natural photoprotection, steroidogenesis and skin inflammation. On the other hand, although leptin links lipid metabolism and inflammation in various cells besides adipocytes, its role in sebocytes has not been investigated yet.
We report here that leptin receptor was detected in sebaceous glands of histological specimens from normal and acne-involved human skin. Cultured human SZ95 sebocytes also expressed leptin receptor and exhibited biological responses to leptin. Leptin treatment induced lipid body formation in SZ95 sebocytes and altered lipid distribution within the cells.
Supporting its reported proinflammatory role, leptin induced COX2 expression in SZ95 sebocytes and the levels of secreted IL-8 by the cells. STAT3 pathway was found to be activated showing that this common leptin signaling pathway in macrophages and dendritic cells is also active in sebocytes. Our findings suggest that leptin signaling could have an important (patho)physiological role in sebocyte biology.
Commentary from the meeting
Leptin is a hormone secreted in response to feeding that induces the production of lipid. With questions regarding the role of diet and acne, it would be interesting to learn if dietary changes leading to decreased leptin secretion would modify the acne process.
Propionibacterium Acnes Induced IL-17 Response in Acne Vulgaris: A Potential Inflammatory Response Targeted by All Trans Retinoic Acid and Vitamin D3
Presenter: George Agak, Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States.
Mentor: Jenny Kim
Agak, George W.; Qin, Min; Nobe, Jennifer; Kim, Myung-Hwa; Krutzik, Stephan; Hermes, Garban; Kim, Jenny. Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States and Department of Medicine, Dankook University, Dankook, Republic of Korea
Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from immune responses targeting P. acnes plays a significant role in its pathogenesis. Our recent findings reveals that, P. acnes is a potent inducer of Th17 and Th1, but not Th2 responses in human PBMCs. P. acnes stimulated expression of genes known to directly signal Th17 responses including IL-17A, RORα, RORc, IL-17RA and IL-17RC. The subset of T cells identified to secrete IL-17 was primarily CD4+ and not CD8+ T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naïve CD4+CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6 and TGF-β neutralizing antibodies completely inhibited IL-17 production.
Importantly, we demonstrate that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors suggesting that IL-17-induced inflammation may have clinical relevance. Finally, we found that both all-trans retinoic acid (ATRA) and the biologically active form of vitamin D3 (1,25D3) inhibited P. acnes-induced Th17 differentiation. Together, our data suggest that IL-17 may play a role in acne pathogenesis and that both ATRA and 1,25D3 could be effective tools to modulate Th17-mediated diseases such as acne.
Commentary from the meeting
P. acnes induces a Th17 and Th1 response by monocytes. Increased numbers of Th17+ lymphocytes can be seen in acne lesions. The induction of Th17 responses by P. acnes in monocyte culture can be blocked by all trans retinoic acid and active Vitamin D. These and other data presented at the meeting suggest that IL-17 may be important in inflammatory acne.
Molecular Identification and Characterization of Rosacea as a Th1- and Th17-Dominated Disease
Presenter: Martin Steinhoff, Depts. of Dermatology and Surgery, University of California San Francisco, San Francisco, CA, United States
Correlation of Rosacea Lesions with Distribution of Skin Microflora in Face
Presenter: Ryoko Shimada-Omori,. Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Mentor: Kenshi Yamasaki
Shimada-Omori, Ryoko; Li, Na; Yamasaki, Kenshi; Aiba, Setsuya. Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Aberrant innate immune responses have been emerged into the pathogenesis of rosacea. Rosacea and rosacea-like dermatitis induced by corticosteroid and tacrolimus showed increase in TLR2 and cathelicidin antimicrobial peptide in lesional skin. Since these molecules are inducible by microbe stimuli and common rosacea lesion sites are relatively limited to malar, forehead and mandibular region, we examined the amount and composition of bacterial flora in face of 7 individuals with rosacea and 6 healthy controls.
Microflora were determined by PCR o fextract from tape-strip samples (6.9 cm2) from 7 points in the face; forehead, lower eyelid, cheek, nose, nasolabial fold, philtrum, and mandibular. VISIA™ Evolution scored skin redness and porphyrin amounts reflecting P.acnes. The overall ratio of detected bacteria was P.acnes 79.87 ± 35.86%, S.epidermidis 6.47 ± 13.61%, MRSA 1.3 ± 3.18%, and MSSA was undetectable. Average amount of bacteria (CFU/cm2, mean ± SD) in rosacea skin was 1.79 ± 2.07 in forehead, 0.72 ± 0.92 in lower eyelid, 1.27 ± 1.63 in cheek, 7.29 ± 8.09 in nose, 2.72 ± 3.09 in nasolabial fold, 5.80 ± 6.41 in philtrum, 2.19 ± 2.26 in mandibular.
The bacteria amounts in each site of rosacea group were not significantly different from control. The redness scores of rosacea were higher than control (14.92 ± 5.38 and 4.517 ± 3.37, respectively), but no correlation was observed between redness and the amount of bacteria. The porphyrin scores positively correlated with the amount of P.acnes, and no correlation between redness and porphyrin score was observed in both rosacea and control group.
A rosacea individual that improved redness 14% in the course of treatments showed more than 90% decrease in both the porphyrin score and P.acnes amount. The results suggested that the microflora did not correlate with the severity of skin redness in rosacea though improvement of symptom was accompanied with the decrease in P.acnes. Thus, increased sensitivity to innate immune stimuli by aberrant TLR2 expression would be more associated with rosacea pathogenesis than altered microflora.
Commentary from the meeting
This interesting study shows that rosacea skin has a higher proportion of P. acnes compared to normal skin but the amount of bacteria did not correlate to severity of facial redness, supporting the idea that rosacea may be more influenced by the innate immune response to bacteria that is mediated by aberrant TLR2 expression.
Subtype Progression in Rosacea: A Retrospective Survey of a Rosacea Cohort
Presenter: Jerry Tan, Windsor Hospital Clinical Inc., Windsor, ON, Canada
Martel, Philippe; Rivier, Michel1; Tan, Jerry. Galderma R&D, Sophia Antipolis, France and Windsor Hospital Clinical Inc., Windsor, ON, Canada.
Rosacea is an enigmatic condition of unclear pathogenesis presenting as a chronic persistent facial dermatosis. For the purposes of research and clinical reference, it has been divided into 3 cutaneous subtypes (ST 1-3; erythematotelangiectatic, papulopustular and phymatous, respectively) and an ocular subtype (ST 4). The natural history of rosacea is unknown. The concept of rosacea progression between subtypes (STs) has been previously implied but not formally studied.
Our objective was to evaluate the potential for progression of rosacea between subtypes. Rosacea subjects completed a survey regarding onset of rosacea-associated signs and symptoms. For the 113 rosacea subjects in this study, mean duration of rosacea was 21 years. For those with ST1, 31% also fulfilled criteria for ST2 at some time in the course of their disease while 69% did not. Of the former, 66% developed ST1 before ST2.
Additionally, for those with ST1, 20% also fulfilled criteria for ST3 at some time in their disease while 80% did not. In those who did, 92% developed ST1 before ST3. For ST2 subjects, 34% also fulfilled criteria for ST3. Of the latter, ST2 developed prior to ST3 in the majority (83%). Ocular symptoms were reported by 35%, of which the majority developed after onset of rosacea-associated cutaneous features. This study suggests that a proportion of rosacea subjects progress from ST1 to ST2 and to ST3; and from ST2 to ST3. Differences exist between ST1 and ST2 in rosacea-associated features. ST2 was more frequently associated with ST3.
In conclusion, the findings in this survey are unique in characterizing the temporal features and duration of flushing and papulopustules; differences between ST1 and ST2 in rosacea-associated features; and differential associations between subtypes.
Commentary from the meeting
Progression from one subtype to another does occur but in a minority of patients. The majority of those with ocular rosacea, developed this after skin findings. These data are helpful in understanding the magnitude of overlap or subtype progression in rosacea patients.