Infections and Autoimmune Disorders of the Eyelids – Difficult Differential Diagnoses and Therapeutic Challenges

Abstract

Various inflammatory diseases can occur in the eyelids. Infectious disorders – such as staphylococcal or demodex blepharitis, dermatological diseases such as seborrheic dermatitis, ocular rosacea or ocular cicatricial pemphigoid and rheumatological diseases such as dermatomyositis or sarcoidosis – are just some of these aetiologies. Clinically, these causes of blepharitis can manifest in inflammation of the eyelid margin with collarettes around the eyelash follicles, madarosis, meibomian gland dysfunction, erythema, and nodular tumour. Even if the clinical differential diagnosis between the various blepharitides is difficult, a correct diagnosis can significantly improve the prognosis. As most blepharitides are chronic in nature, regular and careful care of the eyelid margin is necessary to improve the patientʼs symptoms. Depending on the cause, local or systemic antibiotics or immunosuppressive agents can also help. If no improvement after treatment occurs, the previous diagnosis must be critically questioned so that masquerade syndromes such as sebaceous carcinoma are not overlooked.

Keywords

blepharitis - Meibomian gland dysfunction - demodex - rosacea - sebaceous carcinoma

Publikationsverlauf

Eingereicht: 18. Februar 2025

Angenommen: 20. August 2025

Accepted Manuscript online:
25. August 2025

Artikel online veröffentlicht:
12. Dezember 2025

• Literatur

• 1 Amescua G, Akpek EK, Farid M. et al. Blepharitis Preferred Practice Pattern(R). Ophthalmology 2019; 126: P56-P93
• 2 Wulc AE, Dryden RM, Khatchaturian T. Where is the gray line?. Arch Ophthalmol 1987; 105: 1092-1098
• 3 Farooq A, Reidy J. Blepharitis. A comprehensive clinical Guide. Springer Nature Switzerland AG; 2021
• 4 Nelson JD, Shimazaki J, Benitez-del-Castillo JM. et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011; 52: 1930-1937
• 5 Mathers WD, Shields WJ, Sachdev MS. et al. Meibomian gland morphology and tear osmolarity: changes with Accutane therapy. Cornea 1991; 10: 286-290
• 6 Alghamdi WM, Markoulli M, Holden BA. et al. Impact of duration of contact lens wear on the structure and function of the meibomian glands. Ophthalmic Physiol Opt 2016; 36: 120-131
• 7 Chhadva P, Goldhardt R, Galor A. Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease. Ophthalmology 2017; 124(11S): S20-S26
• 8 Nichols KK, Foulks GN, Bron AJ. et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 2011; 52: 1922-1929
• 9 McCulley JP, Dougherty JM, Deneau DG. Classification of chronic blepharitis. Ophthalmology 1982; 89: 1173-1180
• 10 Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye (Lond) 1991; 5: 395-411
• 11 Schaumberg DA, Nichols JJ, Papas EB. et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci 2011; 52: 1994-2005
• 12 Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul Surf 2004; 2: 149-165
• 13 Chan C. Dry Eye: A Practical Approach. Berlin, Heidelberg: Springer; 2015
• 14 Tao JP, Shen JF, Aakalu VK. et al. Thermal Pulsation in the Management of Meibomian Gland Dysfunction and Dry Eye: A Report by the American Academy of Ophthalmology. Ophthalmology 2023; 130: 1336-1341
• 15 Leng X, Shi M, Liu X. et al. Intense pulsed light for meibomian gland dysfunction: a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol 2021; 259: 1-10
• 16 Sandford EC, Muntz A, Craig JP. Therapeutic potential of castor oil in managing blepharitis, meibomian gland dysfunction and dry eye. Clin Exp Optom 2021; 104: 315-322
• 17 Al-Namaeh M. A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction. Ther Adv Ophthalmol 2020; 12: 2515841420952188
• 18 Donnenfeld E, Pflugfelder SC. Topical ophthalmic cyclosporine: pharmacology and clinical uses. Surv Ophthalmol 2009; 54: 321-338
• 19 Dougherty JM, McCulley JP. Bacterial lipases and chronic blepharitis. Invest Ophthalmol Vis Sci 1986; 27: 486-491
• 20 Knop E, Knop N, Millar T. et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011; 52: 1938-1978
• 21 Yoo SE, Lee DC, Chang MH. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol 2005; 19: 258-263
• 22 Rhee MK, Yeu E, Barnett M. et al. Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies. Eye Contact Lens 2023; 49: 311-318
• 23 Fromstein SR, Harthan JS, Patel J. et al. Demodex blepharitis: clinical perspectives. Clin Optom (Auckl) 2018; 10: 57-63
• 24 Yan Y, Yao Q, Lu Y. et al. Association Between Demodex Infestation and Ocular Surface Microbiota in Patients With Demodex Blepharitis. Front Med (Lausanne) 2020; 7: 592759
• 25 Gao YY, Di Pascuale MA, Li W. et al. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Ophthalmol Vis Sci 2005; 46: 3089-3094
• 26 Nicholls SG, Oakley CL, Tan A. et al. Demodex species in human ocular disease: new clinicopathological aspects. Int Ophthalmol 2017; 37: 303-312
• 27 Kara YA, Calis F, Gurel IB. Ocular Manifestations of Patients With Cutaneous Rosacea With and Without Demodex Infection. Cutis 2021; 108: 46-50
• 28 Aktaş Karabay E, Aksu Çerman A. Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis. An Bras Dermatol 2020; 95: 187-193
• 29 Huang J, Guo MX, Xiang DM. et al. The association of demodex infestation with pediatric chalazia. BMC Ophthalmol 2022; 22: 124
• 30 Cheung IMY, Xue AL, Kim A. et al. In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers. Cont Lens Anterior Eye 2018; 41: 513-517
• 31 Fulk GW, Murphy B, Robins MD. Pilocarpine gel for the treatment of demodicosis–a case series. Optom Vis Sci 1996; 73: 742-745
• 32 Navel V, Mulliez A, Benoist dʼAzy C. et al. Efficacy of treatments for Demodex blepharitis: A systematic review and meta-analysis. Ocul Surf 2019; 17 (04) 655-669
• 33 Savla K, Le JT, Pucker AD. Tea tree oil for Demodex blepharitis. Cochrane Database Syst Rev 2020; (06) CD013333
• 34 Martinez-Pulgarin DF, Avila MY, Rodriguez-Morales AJ. Interventions for Demodex blepharitis and their effectiveness: A systematic review and meta-analysis. Cont Lens Anterior Eye 2021; 44: 101453
• 35 Gaddie IB, Donnenfeld ED, Karpecki P. et al. Lotilaner Ophthalmic Solution 0.25 % for Demodex Blepharitis: Randomized, Vehicle-Controlled, Multicenter, Phase 3 Trial (Saturn-2). Ophthalmology 2023; 130: 1015-1023
• 36 Borda LJ, Wikramanayake TC. Seborrheic Dermatitis and Dandruff: A Comprehensive Review. J Clin Investig Dermatol 2015;
• 37 Ro BI, Dawson TL. The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff. J Investig Dermatol Symp Proc 2005; 10: 194-197
• 38 Wikramanayake TC, Borda LJ, Miteva M. et al. Seborrheic dermatitis-Looking beyond Malassezia. Exp Dermatol 2019; 28: 991-1001
• 39 Alofi RM, Alrohaily LS, Alharthi NN. et al. Ocular Manifestations in Seborrheic Dermatitis Epidemiology, Clinical Features, and Management: A Comprehensive Review. Cureus 2024; 16: e70335
• 40 Waldroup W, Scheinfeld N. Medicated shampoos for the treatment of seborrheic dermatitis. J Drugs Dermatol 2008; 7: 699-703
• 41 Pierard-Franchimont C, Pierard GE, Arrese JE. et al. Effect of ketoconazole 1 % and 2 % shampoos on severe dandruff and seborrhoeic dermatitis: clinical, squamometric and mycological assessments. Dermatology 2001; 202: 171-176
• 42 Rodrigues-Braz D, Zhao M, Yesilirmak N. et al. Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models. Mol Vis 2021; 27: 323-353
• 43 Ahn CS, Huang WW. Rosacea Pathogenesis. Dermatol Clin 2018; 36: 81-86
• 44 Gold LM, Draelos ZD. New and Emerging Treatments for Rosacea. Am J Clin Dermatol 2015; 16: 457-461
• 45 Abram K, Silm H, Maaroos HI. et al. Risk factors associated with rosacea. J Eur Acad Dermatol Venereol 2010; 24: 565-571
• 46 Koller B, Müller-Wiefel AS, Rupec R. et al. Chitin modulates innate immune responses of keratinocytes. PLoS One 2011; 6: e16594
• 47 Wanke I, Steffen H, Christ C. et al. Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol 2011; 131: 382-390
• 48 Rathi SK, Kumrah L. Topical corticosteroid-induced rosacea-like dermatitis: a clinical study of 110 cases. Indian J Dermatol Venereol Leprol 2011; 77: 42-46
• 49 Two AM, Wu W, Gallo RL. et al. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol 2015; 72: 761-770
• 50 Maier P, Lapp T, Reinhard T. [Ocular involvement in atopic dermatitis: Clinical aspects and therapy]. Ophthalmologe 2017; 114: 514-524
• 51 Heinz C, Fanihagh F, Steuhl KP. Squamous cell carcinoma of the conjunctiva in patients with atopic eczema. Cornea 2003; 22: 135-137
• 52 Shah A, Espana EM, Singh AD. Ocular Surface Squamous Neoplasia Associated with Atopic Keratoconjunctivitis. Ocul Oncol Pathol 2017; 3: 22-27
• 53 Eichenfield LF, Tom WL, Berger TG. et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014; 71: 116-132
• 54 Rashid H, Lamberts A, Borradori L. et al. European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I. J Eur Acad Dermatol Venereol 2021; 35: 1750-1764
• 55 Yu H, Nagafuchi Y, Fujio K. Clinical and Immunological Biomarkers for Systemic Lupus Erythematosus. Biomolecules 2021; 11: 928
• 56 Naji Rad S, Vashisht P. Malar Rash. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023
• 57 Standardization of Uveitis Nomenclature (SUN) Working Group. Classification Criteria for Sarcoidosis-Associated Uveitis. Am J Ophthalmol 2021; 228: 220-230
• 58 Rajput R, Mathewson P, Mudhar HS. et al. Periocular cutaneous sarcoid: case series and review of the literature. Eye (Lond) 2019; 33: 1590-1595
• 59 Lundberg IE, Tjarnlund A, Bottai M. et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017; 76: 1955-1964
• 60 Didona D, Fania L, Didona B. et al. Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis. Int J Mol Sci 2020; 21: 2178
• 61 van den Hoogen F, Khanna D, Fransen J. et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013; 65: 2737-2747
• 62 Allali J, DʼHermies F, Renard G. Basal cell carcinomas of the eyelids. Ophthalmologica 2005; 219: 57-71
• 63 Wu A, Sun MT, Huilgol SC. et al. Histological subtypes of periocular basal cell carcinoma. Clin Exp Ophthalmol 2014; 42: 603-607
• 64 Dasgupta T, Wilson LD, Yu JB. A retrospective review of 1349 cases of sebaceous carcinoma. Cancer 2009; 115: 158-165
• 65 Prieto-Granada C, Rodriguez-Waitkus P. Sebaceous Carcinoma of the Eyelid. Cancer Control 2016; 23: 126-132
• 66 Knackstedt T, Samie FH. Sebaceous Carcinoma: A Review of the Scientific Literature. Curr Treat Options Oncol 2017; 18: 47
• 67 Schmitz EJ, Herwig-Carl MC, Holz FG. et al. Sebaceous gland carcinoma of the ocular adnexa – variability in clinical and histological appearance with analysis of immunohistochemical staining patterns. Graefes Arch Clin Exp Ophthalmol 2017; 255: 2277-2285
• 68 Sa HS, Tetzlaff MT, Esmaeli B. Predictors of Local Recurrence for Eyelid Sebaceous Carcinoma: Questionable Value of Routine Conjunctival Map Biopsies for Detection of Pagetoid Spread. Ophthalmic Plast Reconstr Surg 2019; 35: 419-425
• 69 Shields CL, Naseripour M, Shields JA. et al. Topical mitomycin-C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma. Ophthalmology 2002; 109: 2129-2133
• 70 Snow SN, Larson PO, Lucarelli MJ. et al. Sebaceous carcinoma of the eyelids treated by mohs micrographic surgery: report of nine cases with review of the literature. Dermatol Surg 2002; 28: 623-631
• 71 Tryggvason G, Bayon R, Pagedar NA. Epidemiology of sebaceous carcinoma of the head and neck: implications for lymph node management. Head Neck 2012; 34: 1765-1768
• 72 Thomas WW, Fritsch VA, Lentsch EJ. Population-based analysis of prognostic indicators in sebaceous carcinoma of the head and neck. Laryngoscope 2013; 123: 2165-2169
• 73 Sa HS, Rubin ML, Xu S. et al. Prognostic factors for local recurrence, metastasis and survival for sebaceous carcinoma of the eyelid: observations in 100 patients. Br J Ophthalmol 2019; 103: 980-984
• 74 Cicinelli MV, Kaliki S. Ocular sebaceous gland carcinoma: an update of the literature. Int Ophthalmol 2019; 39: 1187-1197
• 75 Kyllo RL, Brady KL, Hurst EA. Sebaceous carcinoma: review of the literature. Dermatol Surg 2015; 41: 1-15