Ligneous Lesions Often Misdiagnosed in Rare Plasminogen Deficiency: Dr Amy Shapiro

Plasminogen deficiency type-1 is an extremely rare blood disorder that can prove difficult to identify and diagnose. Amy Shapiro, MD, Medical Director, Indiana Hemophilia and Thrombosis Center, joined The American Journal of Managed Care® for an interview to raise awareness of this uncommon disorder. In part 1 of this discussion, she explores in depth the prevalence, clinical manifestations, and diagnostic challenges associated with plasminogen deficiency type-1.

This transcript has been lightly edited for clarity and length.

Transcript

Can you contextualize plasminogen deficiency type-1 in the realm of rare blood disorders?

Plasminogen deficiency is a very rare disorder. The reported prevalence is 1.6 individuals per million population. Now, we don't know if that's actually completely accurate, but that's what is in the literature from a limited number of studies. Rare disorders are disorders that affect less than 200,000 Americans. This is far less than 200,000. Hemophilia, for example, is a rare disorder, and that's about 1 in 5000 male births. This is more rare than that. So it's a pretty rare deficiency. And because of that, the identification of it in affected individuals is often difficult because care providers who see these patients are unfamiliar with the disease. It may be something you read about in a cursory manner in your educational process, but rarely has anyone seen a patient with this disorder.

Another thing that complicates diagnosis of this disorder is that affected individuals tend to go to different care providers based upon the symptoms that they have. So they may go to an ophthalmologist, an [ear, nose, and throat doctor], a general practitioner, a pulmonologist, etc. That makes identification of the individuals even more difficult because there are far more common disorders that may manifest with some of those symptoms that providers often work through and plasminogen deficiency is near the bottom of the list.

The manifestations of this disorder are really fairly interesting from a medical standpoint when you think about plasminogen as a clotting factor. So plasminogen is important in the part of the coagulation system that helps break down clots after they form. So that helps limit the clotting from progressing and breaks down the clot that is there so that the normal architecture is restored. Now, you would think that based upon that role in coagulation that people would develop blood clots as a symptom of this disease, but they don't. And in fact, plasminogen has many other roles in physiology, and is very important in what we call the maintenance of the extracellular matrix. So it maintains that matrix in a healthy condition.

What people usually get as a symptom of this disease are what we call ligneous—which means “woody”—lesions on mucous membranes. They get them on the conjunctiva of their eye, they get them in the middle ear, the nose, the gingiva (or the gums), the tonsils, the respiratory tract, the [gastrointestinal] tract, the genital urinary tract, and they may have poor wound healing. So they have lesions that present in many different areas; hence, they end up going to different care providers because of symptoms in that area. They're often, for example, with the eye lesions, diagnosed initially as having conjunctivitis, which is attributed to either a bacterial or viral infection, and are often treated repeatedly for that until someone looks at the lesion itself and realizes that it's very fibrinous. Or, that someone stumbles upon the diagnosis in a list of what could present as persistent ligneous lesions or woody lesions in the eyes.