Recurrent Meningitis and Its Rare Association With Ligneous Conjunctivitis and Congenital Plasminogen Deficiency.

This case report explores the rare association of recurrent meningitis, hydrocephalus, ligneous conjunctivitis, and congenital plasminogen deficiency in a term baby boy. Born at 39 weeks with a history of hydrocephalus, the neonate later developed ligneous conjunctivitis and a serious bout of meningitis. Genetic analyses confirmed a homozygous mutation in the PLG gene, indicative of congenital plasminogen deficiency. Despite intensive treatment, including a ventriculoperitoneal shunt for hydrocephalus and intravenous antibiotics for meningitis, the child succumbed to upper airway obstruction before reaching one year of age. This report underscores the medical complexity and severity of these interconnected conditions and advocates for further research to understand the interplay between them. Although this study is limited by its single-case nature and is not generalizable, it emphasizes the necessity for early recognition and a multidisciplinary treatment approach for better patient outcomes.

Combined medical and surgical approach in the management of ligneous conjunctivitis in a pediatric patient: A case report.

INTRODUCTION: Ligneous conjunctivitis (LC), a rare chronic conjunctivitis linked to plasminogen deficiency, poses challenges in research and management due to its complexity. This case report details the combined medical and surgical approach in managing LC in a 1.5-year-old female with congenital hydrocephalus, plasminogen deficiency, and glaucoma. CASE PRESENTATION: The patient's LC required a comprehensive treatment plan involving systemic and topical therapies, surgical intervention, and fresh frozen plasma (FFP) infusions via a central line. DISCUSSION: Managing LC necessitates a comprehensive, individualized approach due to its rarity and lack of standardized treatments. Various therapies have shown promise, but their availability, cost, and potential side effects vary. FFP infusions played a crucial role in managing plasminogen deficiency, but the potential complications associated with central lines must be considered. Ongoing clinical trials aim to improve LC treatment, but until results are available, clinicians must rely on existing evidence and clinical judgment. CONCLUSION: This case underscores the complexity of managing LC and the significance of adopting an individualized treatment strategy. Regular follow-ups are crucial for flexibility and adaptability in treatment plans to address potential recurrences. Further research is necessary to validate these findings and assess the long-term effectiveness of the combined approach.

Long-term follow-up in a pediatric patient with Ligneous Conjunctivitis due to PLG gene mutation in topical plasminogen treatment after successful use of ocular prosthesis for aesthetic rehabilitation: a case report.

BACKGROUND: Ligneous Conjunctivitis (LC) is the most common clinical manifestation of Type I Plasminogen deficiency (T1PD; OMIM# 217090), and it is characterized by the formation of pseudomembranes (due to deposition of fibrin) on the conjunctivae leading to progressive vision loss. In past times, patients with LC were treated with surgery, topical anti-inflammatory, cytostatic agents, and systemic immunosuppressive drugs with limited results (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022, Surv Ophthalmol 48:369-388, 2003, Blood 131:1301-1310, 2018). The surgery can also trigger the development of membranes, as observed in patients needing ocular prosthesis (Surv Ophthalmol 48:369-388, 2003). Treatment with topical purified plasminogen is used to prevent pseudomembranes formation (Blood 108:3021-3026, 2006, Ophthalmology 129:955-957, 2022). CASE PRESENTATION: We present the case of a sixteen-year-old girl with LC with severe left eye involvement. We reported the clinical conditions of the patient before and after the use of topical plasminogen eye drops and described the treatment schedule allowing the surgical procedure for the pseudomembranes debulking and the subsequent use of ocular prosthesis for aesthetic rehabilitation. CONCLUSIONS: The patient showed a progressive response to the topical plasminogen, with a complete absence of pseudomembrane formation at a twelve-year follow-up, despite using an ocular prosthesis.

A case of IgG4-positive ligneous conjunctivitis mistaken for a conjunctival mass.

BACKGROUND: Ligneous conjunctivitis (LC) is a rare inflammatory lesion of the conjunctiva with an unknown etiology. It is easily confused with conjunctiva lymphoma or other diseases in clinical diagnosis, and the lesion is very difficult to treat. CASE PRESENTATION: We presented a 41-year-old female patient presented with bilateral conjunctival masses for more than six months. The patient had no contributory history of ocular trauma, family history of tumor and drug allergy. Taking the patient's clinical and pathological features together, we considered this was a case of IgG4 + LC. Completely surgical resection combined with local glucocorticoid treatment might be effective. CONCLUSIONS: This is a very rare case report of immunoglobulin G4 positive LC with only one published case in literature. The typical manifestations of LC are with the appearance of a hard, fibrin-rich, woody pseudomembranous lesion. A large number of lymphocyte and plasma cell are infiltrated in the pathological tissue. Inflammation of LC may cause immune abnormalities, resulting in IgG4 increasing.

Ligneous conjunctivitis mimicking preseptal cellulitis in a 3-month-old infant.

BACKGROUND: Ligneous conjunctivitis is a very rare form of pseudomembranous conjunctivitis with few published cases in literature. We aim to describe the ocular findings and treatment in an infant with ligneous conjunctivitis resembling preseptal cellulitis on presentation. MATERIALS AND METHODS: Case report of a 3-month-old girl who was referred to a tertiary centre for ophthalmic assessment due to progressive eyelid oedema with no response to initiated topical and systemic antibiotics. Ethical approval has been achieved from the local ethics committee of the Ghent University Hospital and informed consent has been obtained from the parents of the child. RESULTS: Examination under general anaesthesia showed multiple, wood-like fibrinous pseudomembranes, originating from the conjunctiva, consistent with ligneous conjunctivitis. After careful removal of the coagulated exudate covering the cornea, a central corneal epithelial defect was evident without stromal infiltration. Histopathologic examination confirmed the predominance of fibrin within the pseudomembranes. Plasminogen activity was below the normal range. Genetic analysis did not identify a pathogenic variant in the PLG gene. The corneal epithelium re-epithelialised during the following days and the conjunctival lesions gradually subsided over the ensuing weeks whilst continuing heparin-containing artificial tears. CONCLUSION: A high level of suspicion is warranted in atypical cases of preseptal cellulitis which show no response to antibiotic treatment. Particularly in young children, examination under general anesthesia is warranted to allow diagnosis of rare causes of secondary eyelid oedema. We report an infant with unilateral ligneous conjunctivitis who responded well to topical, commercially-available heparin-containing artificial tears treatment. This approach is an effective and easy first-line treatment option in this condition, particularly in milder phenotypes.

Recurrent ligneous conjunctivitis after cataract surgery in a 67-year-old male patient: a case report.

BACKGROUND: Ligneous conjunctivitis is a rare form of chronic pseudomembranous conjunctivitis which usually starts during infancy. We report on an unsual case of recurrent ligneous conjunctivitis after cataract surgery in a 67-year-old male patient. METHODS: The equipment used for the slit-lamp images was a Haag Streit slit lamp BX900 Sn 00,406 with 16 × magnifications. The used batch number of the camera was sn00406 and the software was from the company CCS Pawlowski Merge Eye. There were no filters used. The images were saved with a resolution of 300 DPI. Neither downstream nor averaging was used to enhance the resolution of the image in the case presentation section or the figure legend. The equipment used for the cross-sectional histologic images was a Zeiss Axioskop 40 microscope with an objective lens Zeiss A-Plan × 20/0.45 (Zoom 6.3 × TV 2/3″″C). The used camera was AxioCam MRc5 and the software was ZEN 3.2. The cross-sectional histologic images were saved with a resolution of 2584 × 1936 Pixels. Neither downstream nor averaging was used to enhance the resolution of the image in the case presentation section or the figure legend. CASE PRESENTATION: This is a rare case report of ligneous conjunctivitis in a 67-year-old male patient who presented a recurrent conjunctival granuloma after five excisions following cataract surgery in his left eye. We performed a tumor excision with free conjunctival autograft. The histology showed a fibrin crust including macrophages, granulocytes, lymphocytes, and reactively altered squamous cell nests. These findings were consistent with a ″pseudomembrane in conjunctivitis lignosa″. We administered a topical combination of plasminactivator, heparin, cortisone and cyclosporine. CONCLUSION: This treatment with the combination of plasminactivator, heparin, cortisone and cyclosporine has proven to be effective in preventing the recurrence of ligneous conjunctivitis.

The first Moroccan case of severe type II congenital plasminogen deficiency with ligneous conjunctivitis.

Ligneous conjunctivitis (LC) is a rare form of pseudomembranous chronic conjunctivitis caused by a deficiency in plasminogen activity. Due to its rarity, little is known about this disorder. We hereby report a case of ligneous conjunctivitis, describing the clinical findings, the biological diagnosis and the treatment of this rare disease.

Ligneous conjunctivitis associated with type I plasminogen deficiency: A rare case.

Ligneous conjunctivitis is a rare form of chronic, recurrent conjunctivitis characterized by wood-like, fibrinous pseudomembranes, which may be associated with systemic disease manifestations. It has been associated with congenital plasminogen (PLG) deficiency that is inherited with an autosomal recessive pattern due to mutations in the PLG gene and a variety of other genes, leading to disturbed wound healing. In this case report, we present the clinical, laboratory, and histopathological findings of a 36-year-old female patient who presented at the ophthalmology department with complaints of redness, irritation for the previous few weeks, and appearance of membranous lesions mainly on the tarsal conjunctivae. During biomicroscopic examination we found thick, yellowish-white pseudomembranes, and conjunctival proliferation with ligneous induration on the conjunctiva, located on the upper eyelids. Histopathological evaluations showed up ligneous conjunctivitis and laboratory evaluation confirmed a severe plasminogen deficiency (PLG < 2%). The patient was treated with topical fresh frozen plasma (FFP), topical steroids, heparin eye drops, and artificial tear drops daily, without systemic therapy.

Ligneous conjunctivitis exacerbated by Pseudomonas aeruginosa - Diagnostic and therapeutic approach.

Ligneous conjunctivitis is a rare disease in which pseudomembranes develop on the mucosal surfaces of the eye. Only a handful of cases have been reported in the past 100 years. Although plasminogen deficiency is largely implicated in the pathogenesis of this condition, infectious agents are also thought to play a role in worsening the disease. Treatment is usually challenging. We present a case of 3-year-old female in whom a multidrug-resistant Pseudomonas aeruginosa was isolated from the culture of the pseudomembranes. To the best of our knowledge, this is the first time P. aeruginosa has been implicated as an exacerbation factor. Furthermore, we have given merit to the triple regimen of corticosteroids, heparin, and cyclosporine as being effective. We also added antibiotics to target the infectious organism.

[Pharmaceutical supply of human plasminogen replacement therapy for the treatment of ligneous conjunctivitis: Logistics for a university hospital]. / Approvisionnement hospitalier en plasminogène humain substitutif pour le traitement de la conjonctivite ligneuse : comment faire en pratique ?

In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.

Novel homozygous mutation of plasminogen in ligneous conjunctivitis: a case report and literature review.

Background:Ligneous conjunctivitis (LC) is a rare disease characterized by the development of a wood-like pseudomembrane on the tarsal conjunctiva secondary to type I plasminogen deficiency. Here we reported on a Chinese patient with LC in a consanguineous family and performed a literature review of all reported mutations for this disease. Methods: A 13-month-old girl diagnosed with LC and her parents were included in this study. Hematoxylin and eosin staining was used to perform histopathology examination. The plasminogen activity was determined by chromogenic assay. Sanger sequencing was performed to screen the mutation site for the disease. In silico analysis was applied to predict the pathogenesis of the identified mutation. In addition, we reviewed the literatures on PLG mutations of LC. Results: Histopathology examination revealed the infiltration of inflammatory cells on membranous lesions. Plasma plasminogen activity was severely decreased in the patient and moderately decreased in her parents (patient: plasminogen activity, 2.50%; father: plasminogen activity, 41.02%; mother: plasminogen activity, 54.07%). Co-segregation analysis indicated that the patient was homozygous for the c.763 G > A (p.Glu255Lys) mutation in plasminogen gene (PLG). Bioinformatics analysis strongly suggested that the mutation was damaging for the disease. The model analysis indicated the mutation might cause abnormal spatial structure and low stability, thus affecting functional activity. A literature review of the LC mutations indicated a strong genetic heterogeneity of the disease. Conclusions: LC exhibited strong genetic heterogeneity, and our study identified a novel homozygous missense mutation of plasminogen (c.763 G > A, p.Glu255Lys) in one Chinese patient with LC.

Prophylactic protocol for dental care in ligneous gingivitis due to severe plasminogen deficiency: Case report and review of literature.

INTRODUCTION: Severe plasminogen (PLG) deficiency causes ligneous conjunctivitis, a rare disease characterized by the growth of fibrin-rich pseudomembranes on mucosal surfaces; gums involvement leads to ligneous gingivitis (LG). Specific therapy for LG is not available yet. We report a prophylactic treatment with enoxaparin and fresh frozen plasma (FFP) for invasive dental procedures in a patient with LG, and a review of literature on LG treatment. METHODS: A 43-year-old female with LG was studied. In order to prevent LG recurrence after dental care, FFP before and the day after the procedure, and enoxaparin were administered in addition to proper minimally invasive dentistry techniques and implant surgery. RESULTS: Plasminogen deficiency was confirmed by reduced PLG antigen (25 µg/mL) and activity (20%) levels, and genetic analysis. PLG levels rose to 46% after FFP transfusion and returned to baseline after 48 hours. Minimally invasive dental procedures and implants were performed. Small gingival pseudomembranes developed soon thereafter in some cases but disappeared within a few weeks; no bleeding complications were observed. CONCLUSIONS: In our patient with LG, the adoption of combined haematological and dentistry protocols appeared to be safe and effective in preventing abnormal gingival pseudomembranes growth after dental interventions, maintaining a healthy periodontal condition.

Ligneous conjunctivitis in a Dandy-Walker syndrome: A rare case report.

Ligneous conjunctivitis (LC) is a rare form of pseudomembranous conjunctivitis seen in children, perhaps due to plasminogen deficiency, which manifest as a chronic refractory pseudomembranous conjunctivitis. LC cases are incapable in maintaining their fibrinolytic activity due to plasminogen deficiency; consequently, transudates of plasma assume as a thick, gelatinous, woody membranes over the mucosal surfaces. This is a short case report on a child with a LC, who presented with recurrent pseudomembranous conjunctivitis in conjunction with progressive congenital hydrocephalus due to aqueductal stenosis (Dandy-Walker syndrome). This rare association was clinically confirmed and prompt corrective surgical measures were instituted.

Ligneous conjunctivitis due to plasminogen deficit: Diagnostic and therapeutic approach. With literature review.

Ligneous conjunctivitis is a rare and poorly understood pathology. Infections and repeated microtraumas are often involved in acute disease flare-ups. This masquerade may lead to misdiagnosis and delayed treatment. We report two cases of ligneous conjunctivitis, describing various presentations of its natural history and focusing on the treatment of this rare disease.

Clinical, histopathological, and genetic aspects in one case of ligneous conjunctivitis.

Ligneous conjunctivitis is an uncommon and recurrent type of chronic conjunctivitis. A prevalent cause of this disease is a Plasminogen deficiency, resulting from recessive mutations in the human encoding plasminogen (PLG) gene. This deficiency affects the conjunctiva and also other mucous membranes. Only few hundred cases have been reported in the literature. Here we report a case of a 9-year-old boy with diagnosis of ligneous conjunctivitis. Histopathological examination in hematoxylin-eosin (HE) staining and sequencing of PLG gene were performed to confirm diagnosis. Histopathological findings confirmed the diagnosis of ligneous conjunctivitis. The patient is compound heterozygous for c.1026T>G (p.Val342Gly) and c.2384G>C (p.Arg795Pro) mutations in PLG gene. Both mutations have not been described previously, and the bioinformatic analysis strongly suggests that are causative of the disease. To the best of our knowledge, this is the first case report of a Chilean patient with ligneous conjunctivitis.

Amniotic membrane transplantation for ligneous conjunctivitis in a doberman.

An approximately 2-year-old female Doberman Pinscher was referred for the evaluation of bilateral, chronic proliferative conjunctivitis. Ophthalmic examination revealed bilateral thick, opaque pseudomembranes originating from the conjunctivae that prevented visualization of the cornea and interior structures of the eye. Histopathological findings of biopsies of the pseudomembranes were consistent with ligneous conjunctivitis. Serum plasminogen activity levels were within the normal range. Treatment with topical and systemic anti-inflammatory and immunosuppressive drugs did not improve the conjunctival lesions. The pseudomembranes were surgically excised, and the conjunctival surfaces were reconstructed with amniotic membrane. At final re-examination two years postsurgery, there was no evidence of recurrence of the pseudomembranes. To the authors' knowledge, this is the first reported case of the successful treatment of canine ligneous conjunctivitis with amniotic membrane transplantation.

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

Plasminogenemia asociada a conjuntivitis leñosa / Plasminogen Deficiency and Ligneous Conjunctivitis

El artículo presenta el caso clínico de un joven de 18 años de edad sin antecedente familiares de enfermedad crónica o hereditaria, nacido a término, sin complicaciones, quien desde los dos días de vida presentó una lesión tipo masa en la conjuntiva tarsal. Inicialmente, recibió tratamiento farmacológico tópico y seguimiento por oftalmología, por conjuntivitis bilateral persistente, masas tarsales recidivantes y cataratas en ambos ojos, por lo que requirió siete intervenciones con pobre respuesta al manejo farmacológico y quirúrgico. A los seis meses de vida se le diagnosticó hidrocefalia, que requirió manejo con derivación del ventrículo peritoneal. Dada la persistencia de la sintomatología y la refractariedad al tratamiento, se ampliaron los estudios y en una junta médica se sugirió el diagnóstico de conjuntivitis leñosa asociada a alteración del plasminógeno. Este diagnóstico fue confirmado por laboratorio clínico, que mostró sus bajas concentraciones de plasminógeno en muestras tomadas con intervalos de dos meses en tres ocasiones: 16,9%, 11,1%, 18,6% (valores de referencia: 70-150%). Se le indicó heparina de bajo peso molecular antes de procedimientos quirúrgicos mayores y triamcinolona tópica según síntomas oculares.

We present a case of an 18-year-old patient without a family history of ocular disease, born full term without complications, within his first 2 days a mass in the tarsal conjunctiva appeared. Initially he received topical treatment and follow-up by the ophthalmology department with a diagnosis of persistent bilateral conjunctivitis, relapsing tarsal masses and cataracts in both eyes requiring a total of 7 surgical interventions with a poor response. At the age of 6 months he was diagnosed with hydrocephalus and required a ventricular-peritoneal shunt. Giren the persistence of the symptoms, further studies were made and a medical board made the diagnosis of ligneous conjunctivitis associated to low levels of plasminogen. The diagnosis was confirmed by decreased levels of plasminogen in serum measured three times with 2 months intervals: 16.9%, 11.1%, 18.6% (reference valúes 70'150%). Low molecular weight heparin was ordered before surgical procedures, and topical triamcinolone applied according to ocular symptoms.