Human homozygous type I plasminogen deficiency and ligneous conjunctivitis

Abstract

Mingers A-M, Philapitsch A, Zeitler P, Schuster V, Schwarz HP & Kreth HW. Human homozygous type I plasminogen deficiency and ligneous conjunctivitis. APMIS 1999: 107:62-72.On the basis of a questionnaire sent to the ophthalmology departments of hospitals throughout Germany, 10 patients with ligneous conjunctivitis or pseudomembranous disease, ranging in age from 1 to 71 years were identified. All 10 patients had severely reduced plasminogen levels. Genetic analysis revealed homozygous type I plasminogen deficiency (which had not previously been described in humans) in 7 patients and compound heterozygous plasminogen deficiency in 1 patient. Clear differentiation was not possible in 2 patients. Most of the parents had heterozygous plasminogen deficiency. None of the patients had experienced any episodes of thrombosis. Additionally, the following observations were made: 1) Levels of polymorphonuclear (PMN)-elastase protein were markedly elevated in 6 of 6 patients and 10 of 1 1 parents tested, and levels were higher in homozygotes than in heterozygotes. 2) Hereditary factor XI1 deficiency was found in 3 of 6 patients tested. 3) CI-inhibitor was elevated in 2 of 4 patients, prekallikrein was elevated in 1 of 4 patients, and plasminogen activator inhibitor type 1 was elevated in 1 of 4 patients. Infusions of lys-plasminogen concentrate induced pronounced fibrinolytic activity as indicated by high levels of D-dimer, increases in plasmin-antiplasmin complex and decreases in polymorphonuclear elastase. C 1 -inhibitor, prekallikrein and PAI-1 normalized after repeated infusions of lys-plasminogen. In contrast to dysplasminogenemia, severe type I plasminogen deficiency might be seen as a problem of extravascular space, in particular of the mucous membranes, possibly triggered by mechanically induced or inflammatory lesions of the vessels supplying the tissue.We diagnosed homozygous type I plasminogen deficiency for the first time in 1994. This defect of the fibrinolytic system had not previously been seen in humans. The patient was an 18-month-old female infant who had ligneous conjunctivitis ( 1 4 ) as well as congenital hydrocephalus. Occlusions had repeatedly occurred at the tips of shunts inserted for drainage, but there was no other evidence of thrombus formation. The etiology of ligneous conjunctivitis was unclear at that time (5-17), and we hypothesized that it was related to the severe plasminogen deficiency. We therefore decided to study this condition in more detail.A questionnaire focusing on genetic aspects was

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].…”

Ligneous conjunctivitis, hydrocephalus, hydrocele, and pulmonary involvement in a child with homozygous type I plasminogen deficiency

“…However, the exact pathogenesis of this complication is still unclear. Histological examination of pseudomembranes from affected eyes or mucosal tissue from the genital tract exhibits a disrupted epithelium that is replaced by massive deposition of fibrin and amorphous hyaline-like eosinophilic material accompanied by an inflammatory cellular infiltration [9,13,18].…”

“…The severe forms of type I plasminogen deficiency may cause ligneous conjunctivitis, an unusual and rare form of chronic conjunctivitis characterised by pseudomembranes on the palpebral surfaces [18]. Furthermore, pseudomembranous lesions of other mucous membranes in the mouth, nasopharynx, tracheobronchoalveolar tree, and female genital tract as well as congenital occlusive hydrocephalus have been reported in patients with type I plasminogen deficiency [13,16,20,27].…”

Molecular pathogenesis of plasminogen Hakodate: the second Japanese family case of severe type I plasminogen deficiency manifested late-onset multi-organic chronic pseudomembranous mucositis

“…Granulocyte elastase levels were markedly increased and both D-dimer and PIC were low in all six homozygotes of type I PLG deficiency examined in the previous study [14].…”