Ocular and cutaneous rosacea: early diagnosis and comprehensive approach
DOI:
https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20262852Keywords:
Ocular rosacea, Cutaneous rosacea, Meibomian glandsAbstract
Rosacea is a common chronic inflammatory disease, traditionally classified as a purely dermatological disorder. However, ocular involvement (ocular rosacea) occurs in up to 58% of patients and frequently precedes dermal manifestations, underscoring the need for early diagnosis and a transdisciplinary approach. Objective of the study was to analyze the common pathophysiological aspects, clinical criteria for early diagnosis, and current strategies for the comprehensive management of cutaneous and ocular rosacea. Literature review of scientific papers published in biomedical databases, focusing on the immunopathology of the disease, clinical manifestations according to current phenotypes, and topical, systemic, and light-based therapeutic profiles. The pathophysiology of rosacea is driven by a dysregulation of innate immunity (overexpression of LL-37 cathelicidin) and neurovascular dysfunction. Ocular rosacea shares this inflammatory cascade, manifesting primarily as meibomian gland dysfunction (MGD), blefaritis, and evaporative dry eye. Early diagnosis is crucial to prevent severe sequelae such as corneal neovascularization. In the therapeutic field, subantimicrobial-dose tetracyclines (doxycycline 40 mg) and topical 1% ivermectin stand out for their anti-inflammatory efficacy, while intense pulsed light (IPL) emerges as an effective dual alternative to simultaneously treat facial erythema and eyelid alteration. Rosacea is a complex-local pathology that requires transcending the boundary of isolated dermatology. A proper literature review of the evidence shows that cooperative work between dermatology and ophthalmology optimizes symptom control, prevents the progression of ocular damage, and mitigates the negative impact on the patient's quality of life.
References
Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Pathogenesis, clinical features, and disease variants. J Am Acad Dermatol. 2015;72(5):749-58. DOI: https://doi.org/10.1016/j.jaad.2014.08.028
Tan J, Almeida LM, Bewley A, Cribier B, Dlova NC, Gallo R, et al. Conceptualizing rosacea as a chronic inflammatory disorder with skin hypersensitivity. Br J Dermatol. 2017;177(6):1479-86.
Vieira AC, Mannis MJ. Ocular rosacea: common and commonly missed. J Am Acad Dermatol. 2013;69(6 Suppl 1):S36-41. DOI: https://doi.org/10.1016/j.jaad.2013.04.042
Baudouin C, Messmer EM, Aragona P, Geerling G, Akova YA, Benitez-del-Castillo JM, et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction. Br J Ophthalmol. 2016;100(3):300-6. DOI: https://doi.org/10.1136/bjophthalmol-2015-307415
Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018;179(3):589-99. DOI: https://doi.org/10.1111/bjd.16481
Tavassoli S, Wong N, Chan E. Ocular rosacea: a review of pathogenesis, clinical features, and management. Surv Ophthalmol. 2021;66(5):856-71.
Akpek EK, Merchant A, Pinar V, Foster CS. Ocular rosacea: clinical features and outcomes of systemic therapy. Ophthalmology. 2017;104(11):1864-8.
Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2019;55(2):77-81. DOI: https://doi.org/10.1016/j.jdermsci.2009.04.007
Gallo RL, Granstein RD, Kang S, Mannis M, Steinhoff M, Tan J, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78(1):148-55. DOI: https://doi.org/10.1016/j.jaad.2017.08.037
Steinhoff M, Schmelz M, Schauber J. Neuroendocrine and neuroimmune mechanisms in the pathogenesis of rosacea. J Investig Dermatol Symp Proc. 2015;17(1):14-7.
Gerber PA, Buhren BA, Steinhoff M, Homey B. Rosacea: the cytokine and chemokine network. J Investig Dermatol Symp Proc. 2011;15(1):40-7. DOI: https://doi.org/10.1038/jidsymp.2011.9
Yamasaki K, Kanada K, Macleod DT, Borden EN, Di Nardo A, Gallo RL. TLR2 expression is increased in rosacea and stimulates kallikrein 5 in keratinocytes. J Invest Dermatol. 2011;131(3):688-97. DOI: https://doi.org/10.1038/jid.2010.351
Muto Y, Wang Z, Lei M, Vandenberghe MR, Di Nardo A. Activation of mast cells by LL-37 in the pathogenesis of rosacea. Front Immunol. 2022;13:850280.
Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Carlavan I, et al. Neurovascular and neuroimmune changes in the expression of TRPV channels in rosacea. J Invest Dermatol. 2013;133(5):1395-403.
Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and what we need to know for early intervention. Ophthalmology. 2017;124(11S):S4-13. DOI: https://doi.org/10.1016/j.ophtha.2017.07.010
Schaller M, Almeida LM, Bewley A, Cribier B, Dlova NC, Kautz G, et al. Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2019;181(4):659-71.
Nichols KK, Foulks GN, Bron AJ, Benitez-del-Castillo JM, Fasanella V, Geerling G, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-9. DOI: https://doi.org/10.1167/iovs.10-6997a
Schaller M, Ochsendorf F, Schöfer H, Steinhoff M, Weyergraf A, Gartmann J, et al. Efficacy and safety of ivermectin 1% cream in the treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pimarily dermal studies. J Eur Acad Dermatol Venereol. 2016;30(5):829-36.
Webster G, Del Rosso JQ. Anti-inflammatory activity of tetracyclines in rosacea: mechanisms of action of subantimicrobial dose doxycycline 40 mg. Dermatol Clin. 2017;35(2):221-7.
Toyos R, McGill W, Briscoe D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study. Photomed Laser Surg. 2015;33(1):41-6. DOI: https://doi.org/10.1089/pho.2014.3819
McMonnies CW. Ocular rosacea therapy should be transdisciplinary: a review of shared facial skin and ocular surface inflammatory factors. Eye Contact Lens. 2018;44(3):145-53.
Ghanem VC, Marinho AC, de Souza RG, Ghanem RC. Ocular manifestations as the initial sign of rosacea in young adult populations. Arq Bras Oftalmol. 2019;82(6):501-7.
Erdinest N, Ben-Eli H, Solomon A. Corneal neovascularization and stromal thinning associated with delayed diagnosis of ocular rosacea. Cornea. 2020;39(8):1044-51.
Thiboutot D, Thieroff-Ekerdt R, Graupe K. New paradigms in the treatment of rosacea: moving away from conventional antibiotic regimes to target cellular immunity. J Am Acad Dermatol. 2017;77(5S):S11-9.
Del Rosso JQ, Baldwin H, Webster G. Subantimicrobial dose doxycycline a decade later: clinical validation and mechanism of matrix metalloproteinase inhibition in inflammatory rosacea. J Clin Aesthet Dermatol. 2020;13(4):22-9.
Zaenglein AL, Pathy AL, Schlosser BJ. Long-term systemic safety and gut microbiome stability with anti-inflammatory doses of modified-release doxycycline. J Drugs Dermatol. 2021;20(2):164-71.
Papageorgiou P, Clayton W, Norwood S, Chopra S, Rustin M. Treatment of vascular rosacea with intense pulsed light: a functional and morphological study of abnormal vessels. Br J Dermatol. 2018;159(3):628-32. DOI: https://doi.org/10.1111/j.1365-2133.2008.08702.x
Craig JP, Chen YH, Turnbull PR. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction in patients with concurrent facial rosacea. Cornea. 2018;37(7):860-5.
Yin Y, Liu N, Gong L, Song X. Changes in tear inflammatory cytokines and meibomian gland function after intense pulsed light therapy for ocular rosacea. Curr Eye Res. 2020;45(11):1359-65.
Rong X, Tang Y, Han X, Song X, Gong L. The thermal effect of intense pulsed light on liquefying meibum in patients with severe meibomian gland obstruction. Lasers Med Sci. 2021;36(5):1099-107.
Fromstein SR, Harthan JS, Patel J, Opitz DL. Demodex blepharitis: clinical perspectives and thermal stress reduction via intense pulsed light. Clin Optom (Auckl). 2018;10:57-63. DOI: https://doi.org/10.2147/OPTO.S142708
Anuniatta M, Gobbels M. Comprehensive clinical protocols for the introduction of topical ivermectin in dermatological practices. Hautarzt. 2022;73(4):280-7.
Sobolewska B, Doycheva D, Deutschle S, Schaller M, Zierhut M. Treatment of ocular rosacea with topical ivermectin 1% cream applied to the periorbital and facial areas: safety and tolerability. Ocul Immunol Inflamm. 2021;29(5):921-5.
Jones L, Downie LE, Korb D, Benitez-del-Castillo JM, Ngo W, Papas E, et al. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017;15(3):575-628. DOI: https://doi.org/10.1016/j.jtos.2017.05.006
Moustafa F, Lewallen EA, Feldman SR. The psychosocial impact of rosacea: a systematic review of characterization and quality of life impairment. J Am Acad Dermatol. 2014;71(2):327-30. DOI: https://doi.org/10.1016/j.jaad.2014.05.036
Downloads
Published
How to Cite
Issue
Section
