Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic inflammatory disease of the eyelid margin. It is secondarily complicated by conjunctivitis and keratitis. Meibomian gland dysfunction (MGD) and staphylococcal blepharitis are central to the pathology1).
Previously, it was referred to by several names such as “staphylococcal blepharokeratitis,” “corneal phlyctenule,” and “childhood rosacea.” Recently, a unified definition and diagnostic criteria have been proposed by an expert panel1).
Corneal phlyctenule is a condition characterized by nodular cellular infiltration of the cornea and superficial vascular invasion toward it. It commonly occurs in children to young women and is often associated with meibomianitis. Many patients have a history of hordeolum or chalazion from early childhood, and a genetic predisposition is suspected.
The exact prevalence and incidence are unknown, but BKC accounts for approximately 15% of referrals to pediatric corneal specialty clinics 1). The age of onset shows a bimodal distribution, with the first peak at 4–5 years and a second peak in adolescence 1).
Children of South Asian or Middle Eastern descent tend to have more severe disease. In a large US retrospective study, Asian or Hispanic children had approximately twice the odds of developing BKC compared to White children 1).
Children are more likely than adults to develop corneal involvement and tend to have more severe disease. This is thought to be due to an excessive and immature adaptive immune response to bacterial antigens 1). Additionally, because it occurs during the critical period of visual development, there is an added risk of amblyopia, which differs from adults.
The condition follows a chronic course with repeated acute exacerbations.
Usually bilateral, but asymmetry may be present.
Eyelid Findings
Anterior blepharitis: Scales, crusts, and redness on the anterior lid margin. Collarettes form at the base of the eyelashes.
Posterior blepharitis: Obstruction and elevation of meibomian gland openings. Abnormal secretions are observed upon expression. Accompanied by telangiectasia of the posterior lid margin.
Thickening and irregularity of the lid margin: Progresses in chronic cases.
Corneoconjunctival findings
Conjunctival hyperemia and edema: Observed diffusely.
Phlyctenules: White to yellow nodular elevations on the conjunctiva or cornea.
Corneal infiltration and ulceration: Ranges from punctate keratitis to marginal infiltration, corneal neovascularization, and pannus formation. Corneal scarring is usually more common in the inferior and peripheral areas.
The frequency of corneal lesions varies widely from 5% to 100% depending on the report 1). In severe cases, scarring is extensive and central, and corneal perforation may rarely occur.
Skin symptoms of rosacea (facial erythema, telangiectasia, papules, pustules) are observed in 20–50% of children with BKC.
The etiology of BKC is multifactorial. The following factors are involved in combination 1).
Reported risk factors for severe disease include female sex, asymmetric lesions, diagnosis at an older age, and presence of photophobia. Poor hygiene, dietary and environmental factors, history of atopy, and seborrheic dermatitis are also associated1).
The diagnosis of BKC is primarily based on clinical findings. Although a universal severity grading system has not been established, diagnostic criteria have recently been proposed by an expert panel 1). The diagnosis requires at least one symptom or sign from each of the eyelid, conjunctiva, and cornea areas.
The main differential diagnoses are shown below.
| Differential Diagnosis | Key Points for Differentiation |
|---|---|
| Vernal Keratoconjunctivitis (VKC) | Onset in early childhood, giant papillae on the upper tarsal conjunctiva, Trantas dots |
| Atopic keratoconjunctivitis (AKC) | After puberty, predominantly lower palpebral conjunctiva, chronic/persistent |
| Herpetic keratitis | Unilateral, decreased corneal sensation, dendritic ulcer |
Vernal keratoconjunctivitis and atopic keratoconjunctivitis present with appearances similar to BKC and can lead to misdiagnosis. A history of atopic disease (dermatitis, asthma) or the presence of marked papillary reaction is useful for differentiation.
Treatment of BKC targets both inflammatory and infectious components, requiring a multifaceted approach 1). Early comprehensive treatment and management of amblyopia are key to preserving vision.
Improvement of MGD is the first step in treatment and is indicated for all patients regardless of severity 1). Due to the chronic nature of BKC, eyelid care should be continued indefinitely.
Used to reduce bacterial colonization of the eyelid margin 1).
Macrolide antibiotics have anti-inflammatory effects that suppress the release of inflammatory cytokines such as IL-1, IL-6, IL-8, and TNF-α, in addition to their antibacterial action1).
Systemic antibiotics are indicated when local treatment alone is insufficient to control eyelid inflammation1).
In addition to topical treatment targeting Propionibacterium acnes with cephem antibiotic eye drops, oral administration of cephem antibiotics or clarithromycin is a curative treatment that calms meibomian gland inflammation. Oral treatment is particularly effective in children, and it is important to continue according to the activity of meibomian gland inflammation to normalize the bacterial flora of the meibomian glands. Continuing antibiotic eye drops for several months or more after symptoms stabilize prevents recurrence.
Macrolides (can be used in all ages):
Tetracyclines (only in children aged 8–9 years and older):
Treatment usually continues for 3–6 months, with gradual tapering based on clinical course.
Used to control corneal inflammation and prevent scarring1).
In the early stage with severe ocular surface inflammation, a combination of betamethasone 0.5% ophthalmic solution and fluorometholone 0.1% ophthalmic solution, each 4 times daily, is an example prescription. Steroids should be used primarily with antibiotics until bacteria are sufficiently eradicated, then combined thereafter.
Used for long-term management in cases where inflammation recurs after steroid discontinuation1).
BKC is a chronic disease, and indefinite continuation of eyelid hygiene and warm compresses is recommended. Oral antibiotics are usually administered for 3–6 months and tapered according to clinical course1). Some cases are permanently cured before adulthood, but the rate of transition to adult rosacea is unknown.
The pathogenesis of BKC is a multifactorial process involving a complex interplay of MGD, bacterial blepharitis, immune abnormalities, and angiogenesis 1).
Hyperkeratinization of the meibomian gland ducts, gland atrophy, and changes in meibum secretion lead to chronic inflammation of the eyelid margin and tear film instability. In obstructive meibomianitis, obstruction and disorganization of gland openings and migration of the mucocutaneous junction are observed, with yellow solidified contents expressed upon compression. In seborrheic meibomianitis, periglandular vasodilation and meibomian foam are present.
S. aureus, C. acnes, S. epidermidis, and Corynebacterium species colonize the eyelids and induce inflammation through the following mechanisms 1).
Corneal phlyctenules are thought to result from inflammatory cell infiltration due to a type IV delayed hypersensitivity reaction to bacterial proteins. Because children have an immature adaptive immune response to bacterial antigens, they are more prone to excessive immune reactions than adults, and corneal lesions tend to be more severe1).
Demodex folliculorum and Demodex brevis are external parasites that infest hair follicles and sebaceous glands. They contribute to the worsening of blepharitis and MGD through direct tissue damage and changes in the bacterial flora (dysbiosis)1).
Wu et al. (2019) reported that BKC patients positive for Demodex had more severe eyelid margin inflammation and MGD compared to those negative for Demodex1).
Chronic ocular surface inflammation activates mast cells, promoting neutrophil recruitment and angiogenesis. Mast cells secrete pro-angiogenic factors including vascular endothelial growth factor (VEGF), directly contributing to corneal neovascularization1).
Topical administration of losartan (an angiotensin II receptor antagonist) is promising for treating corneal scars. In a rabbit model, losartan was reported to suppress myofibroblast activity and inhibit corneal scar formation 1). Its application is expected for residual scars after active inflammation in BKC is controlled.
IPL (intense pulsed light) therapy reduces telangiectasia of the eyelid margin and has anti-inflammatory effects 1).
Although data in children are limited, IPL therapy may be superior to conventional warm compresses for chalazion treatment and may be safe and effective for moderate to severe pediatric blepharitis 1). It may play a larger role in future PBKC treatment.
Thermal pulsation devices (such as LipiFlow®) heat and express obstructed meibomian glands, showing efficacy in adult MGD, but pediatric data are limited 1).
A “gut–eye microbiota axis” has been suggested between gut microbiota and ophthalmic diseases 1). Currently, no direct link with BKC has been demonstrated, but it is a focus of future research.
Lifitegrast 5% ophthalmic solution is an LFA-1 antagonist that suppresses inflammation by inhibiting T-cell activation and migration 1). It is FDA-approved for dry eye disease in adults, but there is growing interest in off-label use for BKC inflammatory conditions. Efficacy data in children are currently limited 1).
Topical losartan has been reported to suppress corneal scarring in a rabbit model 1). Although still in the research stage, it may become a new treatment option for central corneal scarring after BKC inflammation is controlled.
