Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Human basal cell carcinoma: the induction of anagen hair follicle differentiation.

BACKGROUND: Consistent with cancer stem cell driven pattern of growth, human basal cell carcinomas (BCCs) demonstrate differentiation along hair follicle (HF) lineages. AIM: To define the pattern of differentiation and therapeutic targets that promote BCC differentiation and therefore BCC cancer stem cell exhaustion. METHODS: An alkaline phosphatase substrate kit was used to determine dermal papilla cells within the BCC stroma. Autonomous HF cycle-dependent gene expression was identified by analysis of the human homologues of a murine gene set (total 2289 genes) that is differentially expressed in hair cycle phases. The findings were validated by quantitative real-time PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)-ß2 stimulation of BCC cancer stem cell colonies. RESULTS: As in the HF, keratin expression in the inner root sheath and matrix in BCC correlated with proliferative index and was tightly regulated, despite the absence of dermal papilla cells. Cross-species microarray analysis comparing human BCC and murine synchronous HF growth cycle datasets revealed 74% concordance with telogen differentiation compared with anagen (23%, P < 0.01) and catagen (49%; P < 0.01). Incomplete anagen differentiation within BCC was characterized by reduced expression of the anagen master regulator DLX3 (-5.5-fold), and increased expression of telogen-associated genes: AEBP1 (2.2-fold), DEFB8 (35.3-fold), MMP3 (106.0-fold) and MMP12 (12.9-fold). Restoration of dermal papilla signals by in vitro addition of TGF-ß2 enhanced anagen differentiation. CONCLUSION: Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators.

Hair follicle differentiation-specific keratin expression in human basal cell carcinoma.

BACKGROUND: Identification of human basal cell carcinoma (BCC) cancer stem cells and cellular hierarchy inherently implies the presence of differentiation. By conventional histological analysis, BCC demonstrates tumour nodules that appear relatively homogeneous. AIM: As BCCs arise from hair follicle (HF) keratinocytes, we sought to define the pattern of HF differentiation. METHODS: BCC, squamous cell carcinoma (SCC) and normal skin tissues were analysed using a microarray chip. The expression of individual keratins, regulatory pathways and proliferative states were analysed using reverse transcription-PCR and immunofluorescence microscopy. RESULTS: Microarray analysis of BCC, SCC and normal hair-bearing skin revealed that BCCs express a wide range of HF genes, including HF- specific keratins. BCC demonstrated outer (KRT5, KRT514, KRT516, KRT517 and KRT519) and inner (KRT25, KRT27, KRT28, KRT32, KRT35, KRT71, KRT75 and KRT85) root sheath differentiation, but not hair shaft differentiation. As in the HF, differentiation-specific keratins in BCC keratinocytes correlated with a reduced proliferative index and regulatory pathway activation despite the oncogenic drive towards tumour growth. Our findings show the close correlation between HF and BCC keratinocyte differentiation. CONCLUSION: This work has defined the differentiation pattern within BCCs, enabling development of targeted therapies that promote differentiation and result in BCC cancer stem cell exhaustion.

Platelet Rich Fibrin in Management of Complex Endoperio Cases.

Endo-perio lesions have been a dilemma to the dental practitioner. Both tissues share the same anatomical origin. Sometimes exact etiological passage of disease process cannot be traced; nevertheless traditional and newer treatment modalities must be employed to ensure best treatment possibilities. Patient reported with pain and pus exudates in upper left anterior region. Past dental history revealed no history of trauma. Initial examination revealed draining sinus with respect to 22. However, no Caries and pockets could be detected. Tooth was nonresponsive to vitality test. Patient symptoms did not relieve even two months after completion of RCT. Apical surgery was planned. Apicectomy was done and osseous defect was filled with PRF coagulum. Patient was followed up every three months and showed complete resolution of all symptoms. Radiographs showed complete resolution of osseous defect in nine months. PRF can be used to enhance bone augmentation in treatment of periapical defects as a potential treatment alternative for faster healing.

Staphylococcus aureus re-colonization in atopic dermatitis: beyond the skin.

Patients with atopic dermatitis (AD) are often heavily colonized by Staphylococcus aureus, which adversely affects eczema severity. Strategies to control S. aureus in AD include antibiotic and or antiseptics. However long-term efficacy is unclear. In this study we consider extra-cutaneous factors that may cause S. aureus re-colonization in adult AD. Twenty-one patients with AD were recruited and were assessed for: duration of AD, use of topical or oral antibiotic within the preceding 3 months, the number of hospital admissions during the preceding year and current treatment. The types of topical treatments used, vehicle, container and the expiry dates were also recorded. The severity of AD was assessed by SCORAD index. Microbiological assessment for S. aureus carriage from affected skin, anterior nares, emollient and topical steroid was undertaken using culture, Staphaurex test and antibiotic resistance. Of the patients 86% had S. aureus colonization. The median SCORAD score were greater in those colonized with S. aureus (P = 0.02) and those with contaminated treatments (P = 0.05). Prior antibiotic treatment, prior hospital admission and nasal carriage did not influence the median SCORAD. Three extra-cutaneous mechanisms by which S. aureus can re-colonize the skin were identified: antibiotic resistance, nasal carriage and treatment contamination.

Wound-related osteomyelitis: a case of containment not cure.

Community nurses need to be aware that some patients with osteomyelitis are treated with antibiotics alone. Such patients often have co-morbidities and quality of life issues that directly impact on the decision to treat osteomyelitis surgically. However, adopting a conservative approach to osteomyelitis management is associated with an increased risk of osteomyelitis recurrence. The rationale for managing chronic wound-related osteomyelitis with antibiotics is discussed. Community nurses caring for patients that have received antibiotics alone to treat osteomyelitis need to be aware of the potential for osteomyelitis recurrence and how to make the diagnosis.

Successful treatment of pyoderma gangrenosum with topical 0.5% nicotine cream.

Pyoderma gangrenosum is potentially a devastating and destructive disorder. There is no uniformly effective or specific therapy for pyoderma gangrenosum. Previous reports of nicotine therapy for pyoderma gangrenosum have suggested it to be efficacious. Unfortunately, previous reports were restricted by the use of commercially available preparations of nicotine, either as a gum or patch formulation. We have used topical nicotine 0.5% w/w cetamacrogol formula A cream that enables direct application onto the lesion, as well as dose and concentration variation. Two patients with pyoderma gangrenosum treated with topical nicotine 0.5% w/w cetamacrogol formula A cream are described here, both of whom had dramatic clinical resolution of their pyoderma gangrenosum.

Intestinal bypass syndrome presenting as erythema nodosum.

Intestinal bypass was a popular surgical procedure for morbid obesity resulting, on average, in a 50 kg weight loss. We describe a 66-year-old woman who underwent the procedure 12 years earlier and subsequently presented with recurrent episodes of erythema nodosum-like lesions. Further investigations revealed hyperoxaluria, renal failure, deficiency of fat-soluble vitamins (causing night blindness, osteomalacia and easy bruising) and anaemia. Antibiotics led to only temporary remission and, as with 24-30% of similar cases, she underwent surgical reversal to prevent the complications from worsening.

An aggressive treatment for aggressive digital papillary adenocarcinoma.

Aggressive digital papillary adenoma (ADPA) and adenocarcinoma (ADPAca) are adnexal tumors that are not often recognized because of their rarity. We present a rare case of ADPAca involving the left middle finger of a 43-year-old man. Histopathological features of ADPAca are distinct from those of other eccrine sweat gland tumors; however, ADPAca may be misdiagnosed particularly for a metastasis of papillary adenocarcinoma originating in the colon, thyroid, or breast. Clinicopathological correlation is essential to ule out a possible risk of metastatic carcinoma of the skin. Recognition of these tumors is important because of a potential risk of local recurrence nd distant metastases. Aggressive surgical treatment consisting of digit amputation is advocated in the treatment of ADPAca.

Science, medicine and the future: healing chronic wounds.

Greater interest in wound healing is needed to ensure higher standards of basic care. Precise identification of the systemic, local, and molecular factors underlying the wound healing problem in individual patients should allow better tailored treatment. Allogeneic skin grafting and bioengineered skin equivalents are being used successfully in patients with venous leg ulcers and diabetic patients with foot ulcers.

Malignant atrophic papulosis (Degos' disease): clinicopathological correlations.

Malignant atrophic papulosis (MAP) is a rare disease characterized by pathognomonic cutaneous lesions and frequently fatal systemic involvement. Dermatologists should have a high index of suspicion for systemic complications in a patient presenting with MAP. We report a case of malignant atrophic papulosis to highlight the clinicopathological features and review this important dermatological diagnosis.

Rifampicin-induced lupus erythematosus.

Rifampicin has been prescribed throughout the world for over 20 years, yet only four cases of rifampicin-induced lupus erythematosus (LE) have been reported. Rifampicin-induced LE is associated with combination therapy with clarithromycin or ciprofloxacin. These drugs are all metabolized through the cytochrome P450 liver enzyme system and combined usage may lead to higher rifampicin blood levels. Drug-induced LE differs from systemic LE; cutaneous manifestations, although uncommon, are an important clue to the diagnosis. We report a case of rifampicin-induced LE presenting with florid cutaneous features.

Managing gravitational eczema and allergic contact dermatitis.

Venous leg ulceration is a common chronic problem in the community, and gravitational eczema is a common complication of it. The presence of gravitational eczema can lead to further ulceration and may also impair wound healing. Treatment often requires more than one topical preparation, to gain control and prevent relapse. Knowledge of the benefits and risks of these therapeutic modalities is essential, in this article we aim to provide a practical approach to the treatment of gravitational eczema. We also discuss allergic contact dermatitis, a common complication of gravitational eczema.