Ligneous Conjunctivitis

All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.

Article initiated by:

Veena T. Mathew, MD, MPH

All contributors:

Gerami Seitzman MD, Brad H. Feldman, M.D., Alpa S. Patel, M.D., Veena T. Mathew, MD, MPH, Vatinee Y. Bunya, MD, MSCE, Maria A. Woodward, MD, Derek W DelMonte, MD, Colleen Halfpenny, M.D., Brandon Baartman, MD, Erica Bernfeld M.D.

Assigned editor:

Mary Daly, MD

Review:

Assigned status Update Pending

 by Erica Bernfeld M.D. on February 29, 2024.

add
Contributing Editors:	add

Ligneous conjunctivitis

DiseasesDB

33331

ICD-10

H10.5

OMIM

217090

Ligneous conjunctivitis is a rare form of chronic, recurrent conjunctivitis characterized by wood-like, fibrinous pseudomembranes, which may be associated with systemic disease manifestations.

Disease Entity

Ligneous Conjunctivitis ICD-10 H10.513

Disease

Ligneous conjunctivitis is a rare form of chronic, recurrent conjunctivitis characterized by fibrinous pseudomembranes on the palpebral conjunctivae. It may be associated with systemic pseudomembranous lesions of the gingiva, ears, tracheo-bronchial tract, female genital tract, and kidneys. It has also been linked to congenital hydrocephalus and juvenile colloid milium. 

Prevalence

Ligneous conjunctivitis is a rare condition. While the true prevalence is not known, in 2001, it was estimated fewer than 120 cases had been reported over the preceding 50 years

Etiology

Ligneous conjunctivitis may be inherited in an autosomal recessive pattern due to mutations in the plasminogen (PLG) gene and a variety of other genes, associated with type I plasminogen deficiency (hypoplasminogenemia), leading to impaired wound healing.

Risk Factors

There are no known risk factors for ligneous conjunctivitis, other than a genetic predisposition.

General Pathology

The histology shows ulcerated conjunctiva with sub-epithelial, amyloid-like, eosinophilic material containing clotted fibrinogen and immunoglobulins, accompanied by lymphocytes, granulocytes, and plasma cells .

Pathophysiology

The conjunctivae, more so than other mucous membranes, are susceptible to frequent exposure to irritants, such as dust, local infection, minor injury, and trauma, especially in young children. This trauma induces the wound-healing cascade, which begins with fibrin matrix deposition. The fibrin acts as scaffolding for granulation tissue and then collagenous tissue for wound remodeling and eventual healing. Plasmin acts to degrade the fibrin clots, and it is formed from cleavage of the plasminogen. Plasminogen deficiency leads to impaired healing of injured mucosa with accumulation of a serofibrinous material that forms the fibrin-rich pseudomembranes, which harden giving the characteristic “woody” appearance. Additionally, surgical excision of ligneous pseudomembranes, as the primary intervention, can precipitate further exacerbation of inflammation and perpetuate the formation of these pseudomembranes.

Primary prevention

There is no primary prevention for this disease entity as it is often inherited.

Diagnosis

The diagnosis of ligneous conjunctivitis may be clinical initially based on history and examination of the eye, but it may be confirmed with laboratory data demonstrating decreased plasminogen activity and pathology showing pseudomembranes with a fibrin-rich component. Involvement of another mucosal site or a positive family clinches the diagnosis.

History

Although this may occur at any age, the history for ligneous conjunctivitis typically involves an infant or child who is female more often than male, presenting with recurrent conjunctivitis symptoms including discharge and redness of the conjunctivae, which may coincide with systemic infection.

Physical examination

The ophthalmologic examination typically shows thick, firm pseudomembranous structures on the palpebral conjunctiva of the eye . Approximately 50% of cases are bilateral, and affected individuals have a predilection for upper-eyelid involvement followed by lower eyelid and bulbar involvement.

Signs and Symptoms

The most common initial signs of ligneous conjunctivitis are mucoid discharge, tearing, and redness of the conjunctivae. This is followed by palpebral conjunctival pseudomembrane formation , and it progresses to the mucosal thickening with a wood-like consistency, which replaces the normal eyelid mucosa. The patient may present with multiple recurrences or chronic pseudomembranous conjunctivitis, which may be preceded by or coincide with systemic signs, such as fever, upper respiratory tract infection, ear infections, or in females, urogenital tract infection.

Clinical diagnosis

The diagnosis of ligneous conjunctivitis can be challenging given the pseudomembranous presentation that can be associated with other diagnoses (see differential diagnosis below). However, the suspicion must be raised if there is recurrence or if systemic mucosal involvement is noted, especially in a child. Once there is a suspicion for ligneous conjunctivitis, evaluation of the ears, oropharynx, tracheobronchial tree, and female genital tract should be undertaken to look for pseudomembranes on those surfaces. Involvement of the airway can be life-threatening. Additionally, examination of sun-exposed skin may show juvenile colloid milium.

Diagnostic procedures

While this may be a clinical diagnosis based on recurrence and clinical appearance, surgically excised pseudomembranes should be sent to pathology to evaluate for the eosinophilic predominance due to the fibrin-rich deposition . Also, this tissue should be tested for amyloid, as this disease can mimic ligneous conjunctivitis.

Laboratory test

Low levels of serum plasminogen may be noted on laboratory studies.

Differential diagnosis

The differential diagnosis for ligneous conjunctivitis includes any infectious or inflammatory entity which can cause a chronic pseudomembranous conjunctivitis, not limited to the following:

• Viral conjunctivitis (adenovirus-type epidemic keratoconjunctivitis, herpes simplex virus, molluscum contagiosum)
• Bacterial conjunctivitis (staphylococcus, streptococcus, chlamydia, diphtheria)
• Toxic conjunctivitis, e.g., secondary to medication use
• Allergic or vernal conjunctivitis
• Amyloidosis

Management

General treatment

There is no consensus on the curative treatment for ligneous conjunctivitis. Numerous treatments paradigms have been pursued and most case reports demonstrate decreased recurrence with a combination of medical and surgical therapy. Schuster and Seregard (2003) reviewed the literature on treatment of ligneous conjunctivitis between 1966 to 2002 and suggested use of a topical fibrinolytic agent, such as plasminogen or plasminogen activator (tPA), followed by surgical excision, and a prolonged, intensive topical heparin course, which is tapered once wound healing is complete. This may be supplemented by topical corticosteroids with or without topical cyclosporine to decrease inflammation.

Medical therapy

Topical plasminogen concentrate has shown some success in effectively treating the pseudomembranes in a few cases; however, this is not commercially available in the United States. Many other individual and combination treatment approaches, listed below, have been tried in small studies; unfortunately, many show recurrence after withdrawal of the topical agent.

• topical fresh frozen plasma with systemic fresh frozen plasma   
• topical heparin with topical corticosteroids or alpha chymo-trypsin
• topical cyclosporine A with amniotic membrane
• topical plasminogen

Systemic plasminogen treatment can effectively control conjunctival membranes in addition to systemic ligneous manifestations . Plasminogen human-tvmh, sold under the brand name, Ryplazim, is commercially available in the United States, administered intravenously, and FDA-approved for the treatment of plasminogen deficiency type 1. The recommended dosage of intravenous plasminogen is 6.6 mg/kg body weight given every 2 to 4 days initially. Dosing frequency can be modified based upon site of involvement, clinical response, and plasminogen activity levels.

Medical follow up

These patients need to be evaluated frequently to monitor for recurrence of pseudomembranes. While the initial follow-up will be more frequent, once the treatment is tapered off, these patients are still at risk of recurrence soon after treatment or even many years later. Polycarbonate glasses may be helpful in protecting the eyes from environmental trauma and initiating the cascade of ligneous conjunctivitis.

Surgery

Surgical excision alone has a tendency to lead to rapid recurrence of pseudomembranes due to the trauma induced in these patients who have deficient wound healing. Thus, surgery should be accompanied by pre- and post-treatment topical plasminogen (if available), topical and/or systemic fresh frozen plasma, topical steroids, topical cyclosporine, or topical heparin to maximize the chance of recovery without recurrence.

Surgical follow up

These patients should be seen within days following excision of the pseudomembranes to evaluate for reformation, which can occur as early as 48 hours.

Complications

In the aforementioned studies, there was often recurrence upon withdrawal of the topical agents or with isolated surgical excision, contributing to the recurrent, recalcitrant course of ligneous conjunctivitis. Long-term inflammation can lead to scarring of the cornea, neovascularization, and corneal perforation, all of which may result in vision loss. In young children, these complications can also lead to amblyopia. Moreover, chronic steroid use can lead to steroid-induced ocular hypertension, and so this must be considered and monitored.

Prognosis

The prognosis of ligneous conjunctivitis depends on the ability to control the inflammation and recurrence of the pseudomembranes. Corneal involvement portends a poorer visual prognosis. Systemic involvement of respiratory tract pseudomembranes can be life-threatening.