Ligneous conjunctivitis

Abstract

Ligneous conjunctivitis (McKusick 217090) is a rare form of chronic conjunctivitis characterized by the development of firm fibrin-rich, woody-like pseudomembraneous lesions mainly on the tarsal conjunctivae. Less frequently, similar lesions may occur on other mucous membranes of the body indicating that these manifestations are part of a systemic disease. Histopathological findings from affected humans and (plasminogen-deficient) mice indicate that wound healing, mainly of injured mucosal tissue, is impaired due to markedly decreased (plasmin-mediated) extracellular fibrinolysis. Pseudomembraneous lesions of the eyes and other mucosal tissue mainly contain clotted fibrin(ogen). Actually, systemic plasminogen deficiency has been linked to ligneous conjunctivitis in humans and mice. In one case, ligneous conjunctivitis has been induced by antifibrinolytic treatment with tranexamic acid. Further rare associated disorders of ligneous conjunctivitis are congenital occlusive hydrocephalus and juvenile colloid milium. This review outlines the historical background, clinical characteristics of ligneous conjunctivitis and its associated complications, histological abnormalities of pseudomembraneous lesions, inheritance, hemostasiologic and molecular genetic findings in affected patients, current treatment approaches, and the plasminogen-deficient mouse as an animal model.

Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency

“…In most patients, the first clinical manifestation occurred during infancy or early childhood. This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes.…”

“…This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes. 5 Once triggered, the clinical manifestations of congenital plasminogen deficiency can persist for several months to years, the duration likely dependent on the endogenous plasminogen levels and/or susceptibility for further injury.…”

Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency

“…In most patients, the first clinical manifestation occurred during infancy or early childhood. This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes.…”

“…This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes. 5 Once triggered, the clinical manifestations of congenital plasminogen deficiency can persist for several months to years, the duration likely dependent on the endogenous plasminogen levels and/or susceptibility for further injury.…”

Ligneous conjunctivitis: a clinicopathological, immunohistochemical, and genetic study including the treatment of two sisters with multiorgan involvement

“…Histopathological and immunohistochemical findings indicate that fibrinogen is the major constituent of the membranes in LC. As was referred to in the literature, and as we confirmed in our patients, severe type I PLG deficiency (hypoplasminogenemia) is a major cause of LC [23,24,38]. The observation of cases of LC developed during treatment with tranexamic acid, an antifibrinolytic drug, also supports this idea [12].…”

Plasminogen deficiency

“…In this report, plasminogen activity ranged from 4% to 51% [10]. Other reports have been consistent with these results [1]. Interestingly, these reports delineate family members with activity levels less than 50%, without the presence of ligneous lesions, thereby underscoring the variability of presentation of this disorder and making tight correlation of levels with clinical symptoms difficult.…”

Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency

“…In most patients, the first clinical manifestation occurred during infancy or early childhood. This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes.…”

“…This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes. 5 Once triggered, the clinical manifestations of congenital plasminogen deficiency can persist for several months to years, the duration likely dependent on the endogenous plasminogen levels and/or susceptibility for further injury.…”

Ligneous conjunctivitis: a clinicopathological, immunohistochemical, and genetic study including the treatment of two sisters with multiorgan involvement

“…Histopathological and immunohistochemical findings indicate that fibrinogen is the major constituent of the membranes in LC. As was referred to in the literature, and as we confirmed in our patients, severe type I PLG deficiency (hypoplasminogenemia) is a major cause of LC [23,24,38]. The observation of cases of LC developed during treatment with tranexamic acid, an antifibrinolytic drug, also supports this idea [12].…”

Plasminogen deficiency

“…In this report, plasminogen activity ranged from 4% to 51% [10]. Other reports have been consistent with these results [1]. Interestingly, these reports delineate family members with activity levels less than 50%, without the presence of ligneous lesions, thereby underscoring the variability of presentation of this disorder and making tight correlation of levels with clinical symptoms difficult.…”

Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency

“…In most patients, the first clinical manifestation occurred during infancy or early childhood. This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes.…”

“…This finding is consistent with the literature 3,5,19 and may partly be associated with a higher general susceptibility to external irritants (eg, dust, local infections, small foreign bodies, and minor injuries after scratching) and higher vulnerability of the mucous membranes at this early age. 5 Moreover, such irritants and/or vulnerability may initiate or serve to perpetuate local inflammation and formation of ligneous lesions on other mucous membranes. 5 Once triggered, the clinical manifestations of congenital plasminogen deficiency can persist for several months to years, the duration likely dependent on the endogenous plasminogen levels and/or susceptibility for further injury.…”

Ligneous conjunctivitis: a clinicopathological, immunohistochemical, and genetic study including the treatment of two sisters with multiorgan involvement

“…Histopathological and immunohistochemical findings indicate that fibrinogen is the major constituent of the membranes in LC. As was referred to in the literature, and as we confirmed in our patients, severe type I PLG deficiency (hypoplasminogenemia) is a major cause of LC [23,24,38]. The observation of cases of LC developed during treatment with tranexamic acid, an antifibrinolytic drug, also supports this idea [12].…”

Plasminogen deficiency

“…In this report, plasminogen activity ranged from 4% to 51% [10]. Other reports have been consistent with these results [1]. Interestingly, these reports delineate family members with activity levels less than 50%, without the presence of ligneous lesions, thereby underscoring the variability of presentation of this disorder and making tight correlation of levels with clinical symptoms difficult.…”