Ligneous conjunctivitis

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Rare chronic pseudomembranous conjunctivitis associated with type 1 plasminogen deficiency

Ligneous conjunctivitis
Synonyms Conjunctivitis lignosa, ligneous conjunctival disease, wood-like conjunctivitis
Pronounce N/A
Specialty Ophthalmology, Medical genetics, Hematology, Pediatrics
Symptoms Chronic red eye, tearing, foreign body sensation, thick woody pseudomembranes on the conjunctiva, eyelid swelling, recurrent conjunctivitis
Complications Corneal involvement, scarring, visual impairment, blindness, airway involvement, periodontal disease, systemic mucosal lesions
Onset Usually infancy or childhood, but can occur at any age
Duration Chronic and recurrent
Types N/A
Causes Most often type 1 plasminogen deficiency caused by pathogenic variants in PLG
Risks Family history, autosomal recessive plasminogen deficiency, minor trauma, eye surgery, infection, local inflammation
Diagnosis Eye examination, biopsy of pseudomembrane, plasminogen activity testing, plasminogen antigen testing, genetic testing
Differential diagnosis Chronic allergic conjunctivitis, vernal keratoconjunctivitis, ocular cicatricial pemphigoid, epidemic keratoconjunctivitis, membranous conjunctivitis, IgG4-related ophthalmic disease
Prevention Avoid unnecessary conjunctival trauma; genetic counseling in affected families
Treatment Plasminogen replacement therapy, topical plasminogen, fresh frozen plasma eye drops, membrane removal with adjunctive therapy, treatment of systemic disease
Medication Plasminogen human-tvmh, topical heparin, topical corticosteroids, topical cyclosporine, antibiotics when secondary infection is present
Prognosis Variable; recurrence is common without correction of plasminogen deficiency
Frequency Very rare
Deaths N/A


Ligneous conjunctivitis is a rare chronic form of conjunctivitis characterized by recurrent, firm, fibrin-rich, wood-like pseudomembranes on the conjunctiva, especially the tarsal conjunctiva of the eyelids. The word ligneous means wood-like, referring to the firm consistency of the lesions. Ligneous conjunctivitis is most often the ocular manifestation of type 1 plasminogen deficiency, also called congenital hypoplasminogenemia, a rare autosomal recessive disorder caused by pathogenic variants in the PLG gene.Congenital plasminogen deficiency(link). MedlinePlus Genetics.Plasminogen deficiency, type I(link). National Center for Biotechnology Information Genetic Testing Registry.

Ligneous conjunctivitis may appear similar to ordinary conjunctivitis at first, but it is usually persistent, recurrent, and poorly responsive to standard antibiotic or allergy treatment. Lesions may be white, yellow-white, red, or fleshy and may cause irritation, tearing, ptosis, corneal injury, scarring, or visual loss. Because plasminogen deficiency is a systemic disorder of impaired fibrin clearance, similar ligneous lesions can also affect the mouth, gums, respiratory tract, ears, female genital tract, kidneys, skin, and central nervous system."Ligneous conjunctivitis".Survey of Ophthalmology.2003;48(4)

369-388.doi:10.1016/S0039-6257(03)00056-0.PMID:12850227."An international registry of patients with plasminogen deficiency".Haematologica.2020;PMC:7049368.

Overview[edit]

Ligneous conjunctivitis is not simply an eye infection. It is usually a manifestation of defective wound healing due to reduced plasminogen activity. Plasminogen is converted to plasmin, an enzyme that helps break down fibrin. When plasminogen activity is severely reduced, fibrin accumulates at sites of mucosal irritation, inflammation, or trauma, forming thick pseudomembranes.

The conjunctiva is the most commonly affected site in type 1 plasminogen deficiency. In international registry data, ligneous conjunctivitis was the most frequent manifestation reported among patients with plasminogen deficiency and may lead to significant visual morbidity."An international registry of patients with plasminogen deficiency".Haematologica.2020;PMC:7049368.

Terminology[edit]

Cause[edit]

Most cases of ligneous conjunctivitis are caused by congenital type 1 plasminogen deficiency.

  • PLG - Gene that provides instructions for making plasminogen.
  • Autosomal recessive inheritance - Most affected individuals have pathogenic variants in both copies of PLG.
  • Type 1 plasminogen deficiency - Quantitative plasminogen deficiency with low activity and low antigen levels.
  • Type 2 plasminogen deficiency - Dysplasminogenemia, usually reduced activity with normal antigen; not typically associated with ligneous lesions.
  • Hypofibrinolysis - Impaired fibrin breakdown.
  • Wound healing abnormality - Minor trauma or inflammation can trigger fibrin-rich lesions.
  • Mucosal surface - Lining tissue where ligneous lesions commonly develop.

The disorder is genetic and is not caused by poor hygiene or contagious infection. Secondary infection may occur, but infection is not the underlying cause in most cases.

Inheritance[edit]

Type 1 plasminogen deficiency is usually inherited in an autosomal recessive pattern.

  • Each parent of an affected child is usually an unaffected carrier.
  • When both parents are carriers, each pregnancy has a 25% chance of being affected.
  • Carrier testing is possible when the familial PLG variants are known.
  • Genetic counseling is recommended for affected individuals and families.
  • Consanguinity may increase risk in some families.

Pathophysiology[edit]

The key abnormality is impaired extracellular fibrinolysis. Normally, after mucosal injury or inflammation, fibrin deposition is temporary and is cleared by plasmin. In plasminogen deficiency, fibrin is not removed efficiently.

  • Plasminogen deficiency reduces formation of plasmin.
  • Reduced plasmin impairs fibrin clearance.
  • Fibrin accumulates under the conjunctival epithelium.
  • Recurrent inflammation and trauma lead to repeated pseudomembrane formation.
  • Histology shows amorphous eosinophilic subepithelial deposits rich in fibrin.
  • Lesions may recur after simple surgical removal unless the underlying fibrinolytic defect is treated.
  • Similar lesions may appear on other mucous membranes.

Triggers may include minor eye trauma, dust, foreign body exposure, surgery, infection, inflammation, and, in some cases, antifibrinolytic therapy.Hypoplasminogenemia(link). Orphanet.

Signs and symptoms[edit]

Symptoms can be unilateral or bilateral and may fluctuate over time.

Systemic manifestations[edit]

Because type 1 plasminogen deficiency is systemic, patients with ligneous conjunctivitis should be evaluated for other mucosal lesions and complications.

Older reviews reported that ligneous conjunctivitis is by far the most common manifestation of severe hypoplasminogenemia, with other lesions involving the gingiva, respiratory tract, ears, female genital tract, gastrointestinal tract, and central nervous system."Plasminogen deficiency".Journal of Thrombosis and Haemostasis.2007;PMID:17900274.

Diagnosis[edit]

Diagnosis requires recognition of the characteristic eye lesions and confirmation of plasminogen deficiency when suspected.

Ophthalmic evaluation[edit]

  • Slit-lamp examination - Evaluates conjunctiva, cornea, eyelids, and pseudomembranes.
  • Eyelid eversion - Important because lesions often occur on the tarsal conjunctiva.
  • Visual acuity testing - Assesses effect on vision.
  • Corneal staining - Detects epithelial defects or abrasions.
  • Intraocular pressure measurement when clinically indicated.
  • Photography - Useful for monitoring lesion response.

Laboratory testing[edit]

  • Plasminogen activity - Key screening test; usually low in type 1 plasminogen deficiency.
  • Plasminogen antigen - Low in type 1 deficiency.
  • PLG genetic testing - Confirms pathogenic variants.
  • Coagulation tests - Usually not diagnostic but may be checked in systemic evaluation.
  • Family testing - May identify carriers.

Histopathology[edit]

Biopsy is not always required if the clinical and laboratory findings are clear, but it may help in atypical cases.

  • Subepithelial eosinophilic amorphous material.
  • Fibrin-rich deposits.
  • Inflammatory cells.
  • Granulation tissue.
  • Epithelial ulceration or disruption.
  • Immunohistochemistry may show fibrin predominance.

Systemic evaluation[edit]

  • Dental and periodontal assessment.
  • Ear, nose, and throat evaluation if recurrent ear, nasal, throat, or airway symptoms exist.
  • Pulmonary evaluation if cough, wheeze, recurrent pneumonia, or breathing symptoms occur.
  • Gynecologic assessment in affected adolescents or adults with genital tract symptoms.
  • Neurologic evaluation and neuroimaging if hydrocephalus, headache, vomiting, seizures, or developmental concerns are present.
  • Hematology or genetics consultation for confirmed plasminogen deficiency.

Differential diagnosis[edit]

The differential diagnosis includes common and rare causes of chronic conjunctival inflammation and pseudomembrane formation.

A rare case report described coexistence of ligneous conjunctivitis and IgG4-related disease, but IgG4-related disease should not be assumed to be the main cause of typical ligneous conjunctivitis. It is better considered a rare association, mimic, or differential diagnosis when clinical and histologic features suggest it."Co-existing ligneous conjunctivitis and IgG4-related disease".Indian Journal of Ophthalmology.2016;64(7)

532-534.doi:10.4103/0301-4738.190154.PMID:27609168.PMC:5026081.

Treatment[edit]

Treatment is challenging because lesions often recur after simple removal. Best outcomes usually require addressing the underlying plasminogen deficiency and controlling local inflammation and trauma.

Plasminogen replacement therapy[edit]

Systemic plasminogen replacement is now an important treatment option for type 1 plasminogen deficiency.

  • Plasminogen human-tvmh - Plasma-derived human plasminogen approved by the U.S. FDA for treatment of type 1 plasminogen deficiency.
  • Ryplazim - Brand name of plasminogen human-tvmh.
  • Intravenous plasminogen replacement - Can treat systemic disease and ocular lesions associated with plasminogen deficiency.
  • Individualized dosing - May be needed based on plasminogen activity levels and clinical response.
  • Monitoring - Patients require monitoring for bleeding, hypersensitivity, and response of lesions.

The FDA approved plasminogen human-tvmh in 2021 as the first treatment for patients with plasminogen deficiency type 1, a rare genetic disorder that can impair tissue and organ function and may lead to blindness.FDA Approves First Treatment for Patients with Plasminogen Deficiency, a Rare Genetic Disorder(link). U.S. Food and Drug Administration.RYPLAZIM(link). U.S. Food and Drug Administration.

Topical and local therapy[edit]

Local therapies may help ocular lesions, especially when systemic plasminogen replacement is not available.

  • Topical plasminogen concentrate.
  • Fresh frozen plasma eye drops.
  • Subconjunctival fresh frozen plasma.
  • Topical heparin.
  • Topical corticosteroids for inflammation under specialist supervision.
  • Topical cyclosporine in selected cases.
  • Lubricating eye drops.
  • Antibiotics when secondary bacterial infection is suspected.
  • Bandage contact lens in selected corneal epithelial defects.
  • Careful pseudomembrane removal only with adjunctive therapy.

Surgical excision alone often leads to recurrence. Surgery is usually combined with plasminogen replacement, fresh frozen plasma, heparin, or anti-inflammatory therapy when needed.

Systemic and multidisciplinary management[edit]

Prognosis[edit]

The prognosis depends on severity of plasminogen deficiency, extent of ocular disease, systemic involvement, treatment availability, and recurrence.

  • Localized mild ocular disease may be controlled with topical and systemic therapy.
  • Untreated disease can recur repeatedly.
  • Corneal damage can cause permanent visual impairment.
  • Severe systemic disease can involve airway, central nervous system, or other mucosal sites.
  • Plasminogen replacement therapy has improved the outlook for many patients with type 1 plasminogen deficiency.
  • Long-term follow-up is needed because recurrence can occur.

Complications[edit]

  • Recurrent conjunctival pseudomembranes.
  • Corneal abrasion.
  • Corneal ulceration.
  • Corneal scarring.
  • Symblepharon.
  • Dry eye.
  • Ptosis.
  • Amblyopia in children if vision is obstructed.
  • Permanent visual impairment.
  • Blindness.
  • Periodontal disease and tooth loss.
  • Airway obstruction.
  • Recurrent respiratory infection.
  • Hydrocephalus.
  • Hearing loss from middle ear involvement.
  • Genital tract lesions.
  • Psychosocial burden from chronic rare disease.

Epidemiology[edit]

Ligneous conjunctivitis is very rare. It occurs most often in people with congenital type 1 plasminogen deficiency, an ultra-rare autosomal recessive disorder. Onset often occurs in infancy or early childhood, but disease can appear later. Both males and females can be affected.

International registry data show that ligneous conjunctivitis is the most frequent symptom reported in patients with plasminogen deficiency, and affected systems may include the respiratory tract, oropharynx, female reproductive tract, gingiva, middle ear, renal collecting system, skin, and central nervous system."An international registry of patients with plasminogen deficiency".Haematologica.2020;PMC:7049368.

Prevention[edit]

There is no general way to prevent congenital plasminogen deficiency, but complications may be reduced by early diagnosis and treatment.

  • Avoid unnecessary conjunctival surgery or trauma when possible.
  • Treat ocular inflammation early.
  • Use protective eyewear when appropriate.
  • Monitor for recurrence after surgery or infection.
  • Confirm plasminogen deficiency in suspected cases.
  • Provide genetic counseling for affected families.
  • Offer carrier testing when familial PLG variants are known.
  • Consider prenatal or preimplantation genetic testing in families with known variants.
  • Avoid antifibrinolytic therapy unless a specialist determines it is necessary.

Patient education[edit]

Patients and families should understand that ligneous conjunctivitis is usually a sign of an underlying fibrin-clearing disorder rather than a simple eye infection.

  • Recurrent woody eye membranes should prompt evaluation for plasminogen deficiency.
  • Routine antibiotic eye drops alone usually do not cure the disease.
  • Do not repeatedly peel or remove membranes without ophthalmology guidance.
  • Eye rubbing and trauma may worsen lesions.
  • Vision should be monitored closely, especially in children.
  • Dental, airway, ear, kidney, genital, or neurologic symptoms should be reported.
  • Family members may need genetic counseling or testing.
  • New treatments are available for type 1 plasminogen deficiency.
  • Urgent eye care is needed for pain, light sensitivity, corneal clouding, or vision loss.

When to seek medical care[edit]

  • Persistent red eye that does not improve with usual treatment.
  • Thick white, yellow, red, or woody membranes under the eyelid.
  • Recurrent pseudomembranes after removal.
  • Eye pain.
  • Light sensitivity.
  • Blurred vision.
  • Decreased vision.
  • Eyelid swelling or ptosis.
  • Corneal ulcer or suspected corneal injury.
  • Chronic gum disease or woody oral lesions.
  • Recurrent ear infections or hearing loss.
  • Breathing difficulty, hoarseness, or airway symptoms.
  • Recurrent pneumonia.
  • Headache, vomiting, developmental delay, or signs of hydrocephalus.
  • Family history of plasminogen deficiency.

History[edit]

Ligneous conjunctivitis has been recognized as a distinctive chronic conjunctival disease because of its recurrent wood-like pseudomembranes. Later research linked most cases to congenital plasminogen deficiency and impaired fibrinolysis. The understanding of the disease shifted from local conjunctival inflammation to a systemic disorder of mucosal wound healing. The approval of plasminogen replacement therapy in 2021 marked a major development in treatment of type 1 plasminogen deficiency.

See also[edit]

Further reading[edit]

  • "Ligneous conjunctivitis".Survey of Ophthalmology.2003;48(4)
369-388.doi:10.1016/S0039-6257(03)00056-0.PMID:12850227.
  • Congenital plasminogen deficiency(link). MedlinePlus Genetics.
  • Plasminogen deficiency, type I(link). National Center for Biotechnology Information Genetic Testing Registry.
  • Hypoplasminogenemia(link). Orphanet.
  • "An international registry of patients with plasminogen deficiency".Haematologica.2020;PMC:7049368.
  • FDA Approves First Treatment for Patients with Plasminogen Deficiency, a Rare Genetic Disorder(link). U.S. Food and Drug Administration.
  • RYPLAZIM(link). U.S. Food and Drug Administration.
  • "Plasminogen Deficiency: A Case Report and Review".Cureus.2023;PMC:10516443.
  • "Ligneous Conjunctivitis with Plasminogen Deficiency Treated With Plasma Infusions and Topical Fresh Frozen Plasma".Cureus.2025;PMC:12000895.
  • "Safety and Efficacy of Long-Term Treatment of Type 1 Plasminogen Deficiency With Intravenous Plasminogen Concentrate".Research and Practice in Thrombosis and Haemostasis.2025;PMC:12175110.

External links[edit]












Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
(2) Zinc finger
DNA-binding domains
(3) Helix-turn-helix domains
3.1
3.2
3.3
3.5
(4) β-Scaffold factors
with minor groove contacts
(0) Other transcription factors


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