Plasminogen Deficiency

Clinical Manifestation

Plasminogen deficiency is associated with development of lesions in a variety of systems. A breakdown by area of presentation follows.

Ligneous conjunctivitis: By far the most common manifestation of low plasminogen levels is ligneous conjunctivitis (see Figures 2a and 2b).14

Figure 2aLigneous conjunctivitis_Fig 2B Figure 2bLigneous conjunctivitis_Fig 2A

Reprinted from Survey of Ophthalmology, vol 48, Schuster V & Seregard S, Ligneous conjunctivitis, p 369-88, Copyright (2003), with permission from Elsevier.

A review of reported patients in the literature suggests that almost 90% of patients who develop symptoms related to hypoplasminogenemia express ligneous conjunctivitis.14 These lesions usually affect the upper eyelid, and initially begin with erythematous conjunctiva with constant tearing. Pseudomembranes begin to form, become white or red lesions with a woody consistency and replace normal mucosal tissue.1 Importantly, while these lesions are classically called “pseudomembranes,” pathologically they are true membranous tissues. One study reported bilateral involvement in 65% of patients,14 which is consistent with a previous review.1 Significantly, approximately one-third of patients have corneal involvement, with a resultant potential for loss of vision.1,14

Although most patients present at a young age (median onset ~1 year),14 there are numerous reports of lesions that do not develop until adulthood. One case series reported an 85 year old individual, while another reported two sisters, aged 71 and 73 years.21,22

Ligneous gingivitis (periodontitis): The second most common manifestation is within the oral cavity, with 34-43% of patients expressing lesions (See Figure 3)13,14

Figure 3

Ligneous gingivitis_Fig 3

Reprinted from Survey of Ophthalmology, vol 48, Schuster V & Seregard S, Ligneous conjunctivitis, p 369-88, Copyright (2003), with permission from Elsevier.

Patients may present with only oral lesions, or may report other affected areas as well. Gingival lesions are commonly nodular, ulcerated and non-painful with associated hyperplasia.23,24

Respiratory tract: Both the lower and upper respiratory tracts have been reported to be affected with ligneous lesions. Laryngeal lesions may lead to life-threatening upper airway obstruction.25 Lower respiratory tract masses have been reported to form in the bronchi.1

Otic involvement: Plasminogen deficiency has been associated with chronic otitis media with pseudomembrane formation around the tympanic membrane or middle-ear with chronic lesions resulting in hearing loss.1

Genitourinary system: Two siblings with involvement of the renal collecting system have been reported.26 Both of these patients manifested ligneous lesions in multiple other sites.

Lesions within the female genital tract have been well documented,13,14,27,28 with involvement of the cervix (ligneous cervicitis), vagina, fallopian tubes, endometrium and ovary. Affected patients typically manifest ligneous lesions in other systems. In one series, 6 of 8 patients were infertile; of the remaining two patients, one was 2 years old, and the fertility of the other was unknown.28

Gastrointestinal tract: Ligneous lesions in the gastrointestinal tract have been reported. Interestingly, in one case, a patient with a duodenal ulcer had concomitant celiac disease; the association of these two disorders was unclear in terms of the area affected by a ligneous lesion.13,29

Cutaneous involvement: Juvenile colloid milium, a rare skin condition, has been documented in patients with hypoplasminogenemia (see Figure 4).1,13,30

Figure 4

Juvenile colloid milium_Fig 4

 

Reprinted from Journal of the American Academy of Dermatology, Vol. 49, Oskay T, Erdem C, et al. Juvenile colloid milium associated with conjunctival and gingival involvement, pp 1185-8, 2003, with permission from Elsevier.

These lesions typically occur in sun-exposed areas in childhood, and are characterized by small, translucent, yellow-brown papules.

Central nervous system involvement: An interesting complication of plasminogen deficiency is congenital occlusive hydrocephalus, which has been reported to occur in up to 14% of patients.14 In addition, these patients are at risk for development of a congenital Dandy-Walker malformation with resultant hypoplasia of the cerebellar vermis and cystic dilation of the fourth ventricle.13,14

Thrombophilia: While initial cases of dysplasminogenemia were reported in patients with venous thrombosis, the overall reported rate of thrombotic events in patients with plasminogen deficiency does not appear to be significantly greater than that in the general population. In the series of patients with Type I plasminogen deficiency, there were no reported cases of venous thrombosis.13,14 Furthermore, in a large series of patients with Type II plasminogen deficiency from Japan, there was no increase in the incidence of venous thrombosis.18

The development of ligneous lesions may be initiated or precipitated by local trauma, inflammation or infection. In ligneous conjunctivitis, upper respiratory infections appear to trigger development of these lesions. However, systemic infections, such as urinary tract infections, have also been associated with the development of lesions in the eye, or any of the other possible affected areas.1 Unfortunately trauma, including surgical excision, seems to stimulate regrowth of pseudomembranes complicating decisions regarding intervention.1