Rosacea: Pathogenesis and Therapeutic Correlates.

Rosacea is a chronic inflammatory condition of which there is no cure. The pathogenesis of rosacea is likely multifactorial, involving genetic and environmental contributions. Current understanding suggests that pro-inflammatory pathways involving cathelicidins and inflammasome complexes are central to rosacea pathogenesis. Common rosacea triggers modulate these pathways in a complex manner, which may contribute to the varying severity and clinical presentations of rosacea. Established and emerging rosacea treatments may owe their efficacy to their ability to target different players in these pro-inflammatory pathways. Improving our molecular understanding of rosacea will guide the development of new therapies and the use of combination therapies.

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

Microencapsulated Benzoyl Peroxide for Rosacea in Context: A Review of the Current Treatment Landscape.

Rosacea, a chronic skin condition affecting millions of people in the USA, leads to significant social and professional stigmatization. Effective management strategies are crucial to alleviate symptoms and improve patients' quality of life. Encapsulated benzoyl peroxide 5% (E-BPO 5%) is a newly FDA-approved topical treatment for rosacea that shows promise in enhancing therapeutic response and minimizing skin irritation. This review aims to assess the role of recently FDA approved E-BPO 5% in the current treatment landscape for rosacea management, as it is not yet included in clinical guidelines that predominantly rely on older approved therapies. The review focuses on randomized controlled trials conducted in English-speaking adults. It evaluates the efficacy, safety, and tolerability of various US Food and Drug Administration (FDA)-approved agents used for rosacea treatment, including E-BPO cream, metronidazole gel, azelaic acid gel and foam, ivermectin cream, minocycline foam, oral doxycycline, brimonidine gel, and oxymetazoline HCl cream. Existing therapies have been effective in reducing papulopustular lesions and erythema associated with rosacea for many years. E-BPO 5% offers a promising addition to the treatment options due to its microencapsulation technology, which prolongs drug delivery time and aims to improve therapeutic response while minimizing skin irritation. Further research is necessary to determine the exact role of E-BPO 5% in the therapeutic landscape for rosacea. However, based on available evidence, E-BPO 5% shows potential as a valuable treatment option for managing inflammatory lesions of rosacea, and it may offer benefits to patients including: rapid onset of action, demonstrated efficacy by Week 2, excellent tolerability, and sustained long-term results for up to 52 weeks of treatment.

Idiopathic aseptic facial granuloma: A retrospective study of 43 cases.

BACKGROUND: Idiopathic aseptic facial granuloma (IAFG) is an underrecognized pediatric skin disease, currently considered within the spectrum of rosacea. It usually manifests as a solitary, reddish, asymptomatic nodule on the cheek that resolves spontaneously. METHODS: Retrospective and descriptive observational study of 43 pediatric patients with a clinical diagnosis of IAFG, followed between 2004 and 2022, at two general hospitals in Argentina. RESULTS: IAFG predominated in girls (65%) and the average age of onset was about 6 years. A single asymptomatic nodule was seen in 79% of patients. The most common localization was the cheek (58%) followed by lower eyelids (41%). Family history of rosacea was present in 16% of patients. A concomitant diagnosis of rosacea and periorificial dermatitis was made in 14% and 9% of our population, respectively. Past or present history of chalazia was detected in 42% of the children. IAFG diagnosis was mainly clinical (88% of cases). Oral antibiotics were the most common indicated treatment (84%). Complete healing was achieved by the majority, but 18% of those with eyelid compromise healed with scars. CONCLUSIONS: IAFG is a benign pediatric condition that physicians should recognize in order to manage correctly. We herein refer to a particular morphologic aspect of IAFG lesions affecting the lower eyelids, where nodules adopt a linear distribution and have a higher probability of involute leaving a scar. Also, we consider that the concomitant findings of rosacea, periorificial dermatitis and chalazia in our patients, reinforce the consideration of IAFG within the spectrum of rosacea.

A Case of Tinea Faciei due to Trichophyton indotineae with Steroid Rosacea Related to Topical Over-The-Counter Drugs Purchased Outside of Japan.

A Filipino woman in her forties had facial erythema that was being self-treated with over-the-counter (OTC) drugs purchased outside of Japan. The drugs included clobetasol propionate, antibiotic, and antifungal components. Her facial erythema symptoms were worse during summertime. KOH direct examination of annular erythema was positive for fungal hyphae and negative for Demodex folliculorum. Fungal culture revealed Trichophyton indotineae based on internal transcribed spacer sequence analysis. Minimal inhibitory concentration for terbinafine was 0.06 µg/mL. We made a diagnosis of tinea faciei with steroid rosacea. We treated the patient with oral itraconazole. Physicians should be aware of increasing T. indotineae infections and increasing self-medication using topical OTC steroids combined with antifungals and antibiotics not only in India but also among foreign people living in other countries such as Japan.

Oroxylin A suppress LL-37 generated rosacea-like skin inflammation through the modulation of SIRT3-SOD2-NF-κB signaling pathway.

Rosacea is a long-term inflammatory skin disease associated with the dysfunction of vascular and immunological systems. Treatment options for rosacea are difficult to implement. Oroxylin A(OA), a traditional Chinese medicine, has anti-inflammation effects in a variety of inflammatory diseases. However, it is not known that whether OA exerts protective effects against LL-37-induced rosacea. In this study, bioinformatics analyses showed that the mechanisms of rosacea and the pharmacological targets of OA were highly overlapped. Subsequently, it was shown that the administration of OA resulted in a notable amelioration of rosacea-like skin lesions, as evidenced by a reduction in immune cell infiltration, modulation of cytokine production, and inhibition of angiogenesis. Plus, it was shown that OA effectively suppressed the generation of ROS generated by LL-37, as well as the subsequent activation of NF-κB signaling pathway. To explore further, we found that OA inhibited LL-37-induced ROS production via SIRT3-SOD2 signaling pathway in keratinocytes. Based on the aforementioned evidence, it can be inferred that OA exhibits a mitigating effect on the inflammatory response in rosacea by modulating the SIRT3-SOD2-NF-κB signaling pathway.

Diagnostic Challenges of Ocular Rosacea.

OBJECTIVE: This study aims to address the issues surrounding the diagnosis of ocular rosacea and to evaluate the development of the patients' condition after treatment, as well as to distinguish between healthy and diseased patients using a glycomic analysis of tears. METHODOLOGY: A prospective study was conducted to assess a total of 68 eyes in 34 patients over a six-week period. These patients were diagnosed with ocular rosacea based on subjective symptoms and clinical examination. The study monitored the development of objective and subjective values. The difference between patients with the pathology and healthy controls was established by means of analysis of glycans in tears. RESULTS: Skin lesions were diagnosed in 94% of patients with ocular rosacea, with the most commonly observed phenotype being erythematotelangiectatic (68.8%). The mean duration of symptoms was 29.3 months (range 0.5­126 months) with a median of 12 months. Throughout the study, an improvement in all monitored parameters was observed, including Meibomian gland dysfunction, bulbar conjunctival hyperemia, telangiectasia of the eyelid margin, anterior blepharitis, uneven and reddened eyelid margins, and corneal neovascularization. The study also observed improvements in subjective manifestations of the disease, such as foreign body sensation, burning, dryness, lachrymation, itching eyes, photophobia, and morning discomfort. The analysis of glycans in tears partially separated tear samples based on their origin, which allowed for the differentiation of patients with rosacea from healthy controls. In the first sample, the pathology was determined in a total of 63 eyes (98.4%) of 32 patients, with further samples showing a change in the glycomic profile of patients' tears during treatment. CONCLUSION: The study demonstrated objective and subjective improvements in all the patients. Tear sampling and analysis could provide a means of timely diagnosis of ocular rosacea.

Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.

BACKGROUND: Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. MATERIALS AND METHODS: In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. RESULTS: DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. CONCLUSION: This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.

Treatment of ocular rosacea: a systematic review.

Rosacea is a common chronic skin disease distributed primarily around the central face. Ocular manifestations of rosacea are poorly studied, and estimates of prevalence vary widely, ranging from 6% to 72% in the rosacea population. Treatment options for ocular rosacea include lid hygiene, topical and oral antibiotics, cyclosporine ophthalmic emulsion, oral vitamin A derivatives, and intense pulsed light; however, a direct comparison of treatment methods for ocular rosacea is lacking. This review aims to compare treatment efficacy and adverse events for different treatment modalities in ocular rosacea. We performed a systematic review by searching Cochrane, MEDLINE and Embase. Title, abstract, full text screening, and data extraction were done in duplicate. Sixty-six articles met the inclusion criteria, representing a total of 1,275 patients. The most effective treatment modalities were topical antimicrobials and oral antibiotics, which achieved complete or partial response in 91% (n = 82/90) and 89% (n = 525/580) of patients respectively, followed by intense pulsed light (89%, n = 97/109 partial response), cyclosporine ophthalmic emulsion (87% n = 40/46), and lid hygiene (65%, n = 67/105). Combination treatments achieved a complete or partial response in 90% (n = 69/77). Results suggest that topical antimicrobials, oral antibiotics, intense pulsed light. and cyclosporine were the most efficacious single modality treatments.

Topical ivermectin 1.0% cream in the treatment of ocular demodicosis.

PURPOSE: Ocular demodicosis can cause debilitating ocular surface disease. As ivermectin is effective at reducing Demodex proliferation in rosacea, this study investigated the efficacy of topical ivermectin 1.0% cream in treating ocular demodicosis. METHODS: This retrospective single-centre clinical practice chart analysis involved the off-label treatment of patients who had ocular demodicosis with topical ivermectin 1.0 % cream (Soolantra, Galderma Ltd, UK) applied nightly to the lid margins of both eyes for 3 months. Ocular surface health was assessed at baseline when the treatment was prescribed and followed up at 3 and 12 months after baseline. Slit lamp biomicroscopy was used to take digital images of the upper eyelid lashes. Manual image analysis with ImageJ was conducted by a masked assessor to quantify signs of ocular demodicosis including the number of lashes with collarettes, with visible Demodex tails and with follicle pouting. RESULTS: Data from a total of 75 patients with ocular demodicosis were analysed for this study (mean age 66.6 ± 13.9 years, 44 female). The numbers of lashes with collarettes (Median [Interquartile range]: 8 [4-13] at baseline to 0 [0-2] at the final visit, p < 0.001) and lashes with follicle pouting (3 [1-5] at baseline to 0 [0-1.8] at the final visit, p < 0.001) decreased with treatment. Any sign of lashes with visible tails was eliminated by the final visit (p < 0.007). Fluorescein staining severity score also improved, particularly from baseline (1 [0-2]) to the second visit (0 [0-1], p < 0.001). CONCLUSIONS: The findings of this study show evidence for the efficacy of a 3-month course of topical ivermectin 1.0% cream in treating ocular demodicosis as indicated by reduction in collarettes, follicle pouting and visible Demodex tails. More research is warranted to improve the diagnosis, management and monitoring of this condition which is often overlooked or misdiagnosed.

Long-term maintenance treatment of rosacea: experts' opinion.

BACKGROUND: Rosacea is a chronic inflammatory dermatosis characterized by remissions and flares. Although the rosacea active treatment phase is well established, the long-term maintenance phase is still challenging. OBJECTIVE: To discuss and make recommendations on how to treat patients during the long-term maintenance phase for the main rosacea phenotypes. METHODS: A panel of six board-certified Brazilian dermatologists and one American dermatologist gathered to compose a consensus based upon an initial statement on how to treat rosacea during the long-term maintenance phase based on the methodology Nominal Group Technique. The experts discussed each factor based upon an initial statement on how to treat rosacea patients in the long-term maintenance phase. A sequence of comprehensive narrative reviews was performed; a questionnaire preparation about the definition of the maintenance phase and its management was presented; an interpersonal discussion and ranking of the ideas were conducted. Recommendations were made if the specialists had 75% agreement. RESULTS: The maintenance treatment phase, which starts by achieving IGA 0 or 1 grades at the active phase, should be considered at least during the 9-month period after remission. The recommendations of all treatments target this period. Daily skincare regimen and sunscreen are crucial. Active treatment phase should be recommended if signs or symptoms reappear or worsen. CONCLUSION: Maintenance phase success depends on patient's adherence to daily skin care, appropriate treatments, continued follow-up with dermatologist, and self-assessment to identify new signs and symptoms indicating disease relapse.

Adverse effects of topical photodynamic therapy in rosacea - Case report.

Rosacea is a chronic and inflammatory skin condition, with relapses being a common characteristic. Its treatments are based on cosmetics, drugs, and the application of procedures based on high-powered light. Photodynamic Cosmetic Therapy (PCT) combines light, a photosensitizer (PS), and molecular oxygen present in tissues, generating photochemical reactions capable of causing tissue and vascular destruction, stimulating tissue repair. We report a case with an adverse effect caused by applying PCT, using 2 % 5-aminolevulinic acid (ALA 2 %), and irradiated with amber LED light associated with infrared radiation for the control of rosacea. A patient with subtype II rosacea underwent PCT treatment of 3 sessions at 21-day intervals, being evaluated using photographic images and Wood's lamp. In the first session of the therapy, an exacerbated inflammatory process was observed. Such an adverse event is estimated to be as a result of the patient using ointment containing corticosteroids for a short period. With the use of medications, it was possible to recover the appearance of the skin thoroughly, and after 21 days, the treatment sessions were performed again. Despite the complication that affected the patient in this study, positive effects were found after the pharmacological therapeutic measures were adopted.

Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta-analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. METHODS: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. RESULTS: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self-limiting. CONCLUSION: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long-term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911).

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.