Ophthalmologists can diagnose deadly disease at slit lamp
Corneal diagnoses and systemic disease
Ophthalmologists can diagnose deadly disease at slit lamp
A patient with Fabry's disease and a characteristic cornea verticillata
Amiodarone deposition in the cornea Source (all): W. Barry Lee, M.D.
Fabry's disease presents with corneal verticillata
Imagine looking into the slit lamp and seeing something that, without a doubt, tells you the patient sitting there is suffering from a debilitating disease that will kill him.
Now, imagine he has no idea. The patient has several seemingly unrelated symptoms, including a strange skin rash, nausea, unexplained pain, and hypertension.
When an ophthalmologist spots a characteristic cornea verticillata, the patient most likely is suffering from Fabry's disease, also known as Anderson-Fabry disease, angiokeratoma corporis diffusum, and alpha-galactosidase A deficiency. Fabry's disease patients lack an enzyme called alpha galactosidase A, without which the lipid ceramide trihexosidase builds up in the body and ultimately leads to renal failure and death. The chromosomal disease is X-linked recessive and affects mostly males.
"The eye doctor is often the first to find this condition based on the cornea verticillata," said W. Barry Lee, M.D., Eye Consultants of Atlanta. "If the disease is diagnosed and the patient is referred for enzyme replacement therapy, many of the symptoms of Fabry's that cause death can be delayed and prevented. These include renal failure and cardiomyopathy of the heart. The lipid, ceramide trihexosidase, builds up in the blood vessels, heart, and kidneys and ultimately leads to failure of these organs. With enzyme replacement, the lipid deposition is prevented. Without the enzyme, all patients ultimately die from renal failure and/or heart failure."
Cornea verticillata, also known as vortex keratopathy, is the most common sign of Fabry's disease. Medications, including amiodarone, which helps patients with heart arrhythmias, can cause verticillata in the cornea, but Fabry's disease has a characteristic finding, Dr. Lee said. A practitioner may "also see dilated conjunctival vessels, a characteristic spoke-like cataract, and retinal vascular tortuosity," he said.
Other medications that may cause cornea verticillata include chloroquine, hydroxychloroquine, indomethacin, and phenothiazines, Dr. Lee said.
Most Fabry's disease patients won't complain about the corneal findings, according to Henry S. O'Halloran, M.D., pediatric ophthalmologist, neuro-ophthalmologist, and clinical instructor, Rady Children's Hospital, San Diego, and professor of ophthalmology, University of Kentucky, Lexington.
"Most people are asymptomatic and won't notice [ocular symptoms] or complain of decreased visual acuity unless it becomes really severe," Dr. O'Halloran said.
Dr. O'Halloran said women may develop the disease, but it tends to be more benign in them. "If males get it, they have the worst course and worst outcome," he said. "If you diagnose it in a male, it's really bad news."
Left untreated, patients likely will experience renal deficiency or failure.
"That's very common," Dr. O'Halloran said. "People used to die from [renal failure] before kidney transplants became more common. This disease affects the cornea, but the bigger issue is it can cause all sorts of other diseases. [Patients] can pretty much get signs in any system of [their] body."
Another common finding is a skin rash called angiokeratoma corporis diffusum, which often is present in the lower back, buttocks, and near the umbilicus. In fact, "a lot of times the diagnosis is made by dermatologists because people come in with skin conditions," Dr. O'Halloran said.
Fabry's disease patients become increasingly frustrated as they experience a multitude of aggravating symptoms including pain, fatigue, and gastrointestinal distress and often seek out several doctors before landing on a correct diagnosis.
"As [patients] get older, it tends to get worse because it's a progressive disease," Dr. O'Halloran said. "There are some pretty severe manifestations by the time a patient hits his 20s. A lot of times with these patients, by the time they are diagnosed, they have been to a bunch of different doctors, and they're frustrated by the whole medical system. Their confidence is pretty much shattered. Early diagnosis makes it so much easier for them, and then there are treatment options."
Diagnosis can be confirmed by chromosomal analysis, punch biopsy of skin lesions, or renal biopsy.
"The easiest would be to do the skin punch biopsy," Dr. O'Halloran said. "It would show if there was an excessive buildup of lipids in the tissues."
Treatment involves replacing the enzymes that the patient is missing.
"Two enzyme supplements are available, with the most widely known one being Fabrazyme [agalsidase beta, Genzyme, Cambridge, Mass.]," Dr. Lee said. "The enzyme supplements delay and/or prevent severe renal and heart failure and can save a life. Unfortunately, the enzyme is extremely expensive, sometimes costing $250,000 annually. It is typically given as an IV infusion."
Ocular symptoms often can go untreated unless the patient develops cataracts.
"[Patients] don't usually get visual loss from the corneal changes," Dr. O'Halloran said. Ophthalmologists treating Fabry's disease patients will find themselves co-managing the patient with a multitude of other practitioners, including renal specialists, dermatologists, geneticists, and neurologists.
"Psychiatry would be good, too," Dr. O'Halloran said. "As with any chronic disease, especially when death is a pretty solid potential outcome, psychological counseling is definitely needed."
Dr. O'Halloran said a multispecialty hospital is a good place for Fabry's disease patients to be seen.
"They [will] have access to a lot of physicians, and it's easier to do tests. A diagnosis will come more quickly," he said.
The future of treating the rare disease is gene therapy and stem cells.
"This is one of the diseases that stem cell therapy has the potential to make a huge impact on," Dr. O'Halloran said.
Editors' note: The doctors mentioned have no financial interests related to this article.
Contact information
: 404-556-2202, lee0003@aol.com
O'Halloran: 858-309-7702, hohalloran@rchsd.org
--------------------------------------------------------------------------------
Ophthalmologists can diagnose deadly disease at slit lamp
by Jena Passut EyeWorld Staff Writer
A patient with Fabry's disease and a characteristic cornea verticillata
Amiodarone deposition in the cornea Source (all): W. Barry Lee, M.D.
Fabry's disease presents with corneal verticillata
Imagine looking into the slit lamp and seeing something that, without a doubt, tells you the patient sitting there is suffering from a debilitating disease that will kill him.
Now, imagine he has no idea. The patient has several seemingly unrelated symptoms, including a strange skin rash, nausea, unexplained pain, and hypertension.
When an ophthalmologist spots a characteristic cornea verticillata, the patient most likely is suffering from Fabry's disease, also known as Anderson-Fabry disease, angiokeratoma corporis diffusum, and alpha-galactosidase A deficiency. Fabry's disease patients lack an enzyme called alpha galactosidase A, without which the lipid ceramide trihexosidase builds up in the body and ultimately leads to renal failure and death. The chromosomal disease is X-linked recessive and affects mostly males.
"The eye doctor is often the first to find this condition based on the cornea verticillata," said W. Barry Lee, M.D., Eye Consultants of Atlanta. "If the disease is diagnosed and the patient is referred for enzyme replacement therapy, many of the symptoms of Fabry's that cause death can be delayed and prevented. These include renal failure and cardiomyopathy of the heart. The lipid, ceramide trihexosidase, builds up in the blood vessels, heart, and kidneys and ultimately leads to failure of these organs. With enzyme replacement, the lipid deposition is prevented. Without the enzyme, all patients ultimately die from renal failure and/or heart failure."
Cornea verticillata, also known as vortex keratopathy, is the most common sign of Fabry's disease. Medications, including amiodarone, which helps patients with heart arrhythmias, can cause verticillata in the cornea, but Fabry's disease has a characteristic finding, Dr. Lee said. A practitioner may "also see dilated conjunctival vessels, a characteristic spoke-like cataract, and retinal vascular tortuosity," he said.
Other medications that may cause cornea verticillata include chloroquine, hydroxychloroquine, indomethacin, and phenothiazines, Dr. Lee said.
Most Fabry's disease patients won't complain about the corneal findings, according to Henry S. O'Halloran, M.D., pediatric ophthalmologist, neuro-ophthalmologist, and clinical instructor, Rady Children's Hospital, San Diego, and professor of ophthalmology, University of Kentucky, Lexington.
"Most people are asymptomatic and won't notice [ocular symptoms] or complain of decreased visual acuity unless it becomes really severe," Dr. O'Halloran said.
Dr. O'Halloran said women may develop the disease, but it tends to be more benign in them. "If males get it, they have the worst course and worst outcome," he said. "If you diagnose it in a male, it's really bad news."
Left untreated, patients likely will experience renal deficiency or failure.
"That's very common," Dr. O'Halloran said. "People used to die from [renal failure] before kidney transplants became more common. This disease affects the cornea, but the bigger issue is it can cause all sorts of other diseases. [Patients] can pretty much get signs in any system of [their] body."
Another common finding is a skin rash called angiokeratoma corporis diffusum, which often is present in the lower back, buttocks, and near the umbilicus. In fact, "a lot of times the diagnosis is made by dermatologists because people come in with skin conditions," Dr. O'Halloran said.
Fabry's disease patients become increasingly frustrated as they experience a multitude of aggravating symptoms including pain, fatigue, and gastrointestinal distress and often seek out several doctors before landing on a correct diagnosis.
"As [patients] get older, it tends to get worse because it's a progressive disease," Dr. O'Halloran said. "There are some pretty severe manifestations by the time a patient hits his 20s. A lot of times with these patients, by the time they are diagnosed, they have been to a bunch of different doctors, and they're frustrated by the whole medical system. Their confidence is pretty much shattered. Early diagnosis makes it so much easier for them, and then there are treatment options."
Diagnosis can be confirmed by chromosomal analysis, punch biopsy of skin lesions, or renal biopsy.
"The easiest would be to do the skin punch biopsy," Dr. O'Halloran said. "It would show if there was an excessive buildup of lipids in the tissues."
Treatment involves replacing the enzymes that the patient is missing.
"Two enzyme supplements are available, with the most widely known one being Fabrazyme [agalsidase beta, Genzyme, Cambridge, Mass.]," Dr. Lee said. "The enzyme supplements delay and/or prevent severe renal and heart failure and can save a life. Unfortunately, the enzyme is extremely expensive, sometimes costing $250,000 annually. It is typically given as an IV infusion."
Ocular symptoms often can go untreated unless the patient develops cataracts.
"[Patients] don't usually get visual loss from the corneal changes," Dr. O'Halloran said. Ophthalmologists treating Fabry's disease patients will find themselves co-managing the patient with a multitude of other practitioners, including renal specialists, dermatologists, geneticists, and neurologists.
"Psychiatry would be good, too," Dr. O'Halloran said. "As with any chronic disease, especially when death is a pretty solid potential outcome, psychological counseling is definitely needed."
Dr. O'Halloran said a multispecialty hospital is a good place for Fabry's disease patients to be seen.
"They [will] have access to a lot of physicians, and it's easier to do tests. A diagnosis will come more quickly," he said.
The future of treating the rare disease is gene therapy and stem cells.
"This is one of the diseases that stem cell therapy has the potential to make a huge impact on," Dr. O'Halloran said.
Editors' note: The doctors mentioned have no financial interests related to this article.
Contact information
: 404-556-2202, lee0003@aol.com
O'Halloran: 858-309-7702, hohalloran@rchsd.org
--------------------------------------------------------------------------------
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