Contribution of fibroblasts to tunnel formation and inflammation in hidradenitis suppurativa/ acne inversa

The precise pathogenic mechanisms in the development, persistence and worsening of hidradenitis suppurativa (HS) remain ill‐defined. This chronic inflammatory dermatosis displays a strong Th1 and Th17 inflammatory signature with elevated levels of TNF‐α, IL‐1β, IL‐17 and IFNγ in lesional and perilesional tissue. HS significantly differs to other chronic inflammatory dermatoses due to the development of hypertrophic scarring and dermal tunnels. The development of scarring and tunnels suggests that fibroblastic stromal cells (including myofibroblasts, fibroblasts, pericytes etc) may be involved in the development and progression of disease. Heterogeneous populations of fibroblasts have been identified in other inflammatory disorders and malignancy which contribute to inflammation and present novel therapeutic targets for fibrotic disorders. Findings in HS are consistent with these fibroblast subpopulations and may contribute to tunnel formation, aggressive squamous cell carcinoma and the phenotypic presentation of familial HS variants. We describe the existing knowledge regarding these mechanistic pathways and methods to confirm their involvement in the pathogenesis of HS.     

A young male with epitheliolysis in the small bowel and colon

Abstract

Background: Toxic epidermal necrolysis (TEN) is characterized by epidermal necrosis of various degree, and can affect the entire body surface. Affection of small bowel and colon is a rare manifestation of TEN. We present a case with an unusual appearance of epitheliolysis of the small bowel and colon due to a toxic reaction.

Case report: A 19?year old male was diagnosed with ulcerative colitis (UC) after treatment with tetracyclines followed by isotretinoin due to acne vulgaris. Medical treatment did not lead to improvement of his UC, and an emergency resection of the colon was performed. Postoperatively his condition worsened due to small bowel epitheliolysis, and he recovered finally 6?months later after a partial small bowel resection.

Conclusion: The true cause of this very serious situation with severe gastrointestinal involvement is not fully understood. In this case, successive treatment with antibiotics and isotretinoin given to a patient with an inflamed colon might have triggered the destruction of the epithelial barrier, leading to an immense immunological reaction in the intestinal wall. We suggest that physicians should be aware of UC-like symptoms occurring prior to or during treatment with tetracyclines and/or isotretinoin.     

Acne in childhood

Acne is a common, chronic inflammatory disease of the skin. While it is primarily a skin disorder of adolescence, acne also occurs, less commonly, in children who have not yet reached puberty. This specific group of acne patients can be categorised into four categories, based on the time of onset; neonatal, infantile, mid-childhood and pre-pubertal acne. The presentation of acne in this younger population may be associated with systemic pathologies different from those in adolescent acne. Clinical assessment should focus on securing symptoms and signs of virilisation and early referral to a paediatric endocrinologist should be considered if these are identified. Treatment regimens should be adopted such that they target the underlying pathophysiology of acne as well as the presenting clinical lesions. Antibiotics should be used judiciously to avoid the emergence of antibiotic resistant bacteria as this can impact on treatment response and may also contribute to resistance in commensal bacteria beyond the skin.     

0.5% Liposome-encapsulated 5-aminolevulinic acid (ALA) photodynamic therapy for acne treatment

Abstract

Background: Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk. Objectives: To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin. Methods: Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5–6.0 J/cm² three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit. Results: The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter^® SM10. No serious adverse events were observed. Conclusion: Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.     

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes

Acne vulgaris is a prevalent cutaneous disease characterized by a multifactorial pathogenic process including hyperseborrhea, inflammation, over‐keratinization of follicular keratinocytes and Propionibacterium acnes (P acnes) overgrowth. Salicylic acid (SA), a beta‐hydroxy acid, is frequently used in the treatment of acne. SA has been found to decrease skin lipids and to possess anti‐inflammatory properties. However, few studies have elucidated the mechanisms and pathways involved in such treatment of acne. In this study, we initially investigated the anti‐acne properties of SA in human SEB‐1 sebocytes. Treatment with SA decreased sebocyte lipogenesis by downregulating the adenosine monophosphate‐activated protein kinase (AMPK)/sterol response element‐binding protein‐1 (SREBP‐1) pathway and reduced inflammation by suppressing the NF‐κB pathway in these cells. Salicylic acid also decreased the cell viability of SEB‐1 by increasing apoptosis via the death signal receptor pathway. Subsequently, histopathological analysis of a rabbit ear acne model after application of SA for three weeks confirmed that SA suppressed the levels of cytokines and major pathogenic proteins around acne lesions, which supports the mechanisms suggested by our in vitro experiments. These results initially clarified that therapeutic activities of SA in acne vulgaris treatment could be associated with the regulation of SREBP‐1 pathway and NF‐κB pathway in human SEB‐1 sebocytes.