by Assunta Ginanneschi
This blog post is dedicated to Charlotte D.*, a neighbor of mine.
I met Charlotte few days after I’ve moved into my new apartment. I was wondering what the D button in the lift was and I pushed it. I realized it was Dach (roof, in German). As I got out of the lift I heard some music coming from upstairs and a voice calling “Who’s there? I cannot see”. Then suddenly she appeared, Charlotte, a fragile fine lady, around 60. She organized her ceramic atelier in the small room just below the roof. I presented myself as the new neighbor and she invited me to come along again for a cup of tea. During one of our chats I dared to ask Charlotte how she had become blind and she told me about her disease, Takayasu’s arteritis (TA).
Takayasu’s disease is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing. It mainly affects the aorta (the main blood vessel leaving the heart) and its branches, as well as the pulmonary arteries.
Due to obstruction of the main branches of the aorta, Takayasu’s arteritis can present as pulseless upper extremities (arms, hands, and wrists with weak or absent pulses on the physical examination). For this reason it is also known as “pulseless disease”.
Takayasu’s arteritis is rare, with only about 2 to 3 cases per million people diagnosed each year. Most often affects often young or middle-aged women of Asian descent. Females are about 8–9 times more likely to be affected than males. Those with the disease often notice symptoms between 15 and 30 years of age. The interesting thing is that my friend is Caucasian, with European parents and no Asiatic ancestors. She was born and grew up in India, where she stayed with her family till the age of 22, when she moved to Europe.
She told me that at the beginning she accused malaise, weight loss, joint pain, fatigue and fainting, but she didn’t pay too much attention, she had just to rest. This first stage is called the “inflammatory phase” .
Then things got worse and she began to have problems even hanging out the washing. This was the start of the “pulseless phase” when the physician couldn’t fill her pulse any more, and her blood pressure was very high. Something serious was happening. One day she was looking into the microscope and she saw some spots that the colleagues couldn’t see. What was wrong with her eyes? Actually one rare, but important symptom of Takayasu’s arteritis is the visual field defect, and at that moment Charlotte realized it affected her. She had surgery on one eye, without success. Ultimately she lost her vision in the other eye as well. So suddenly my friend got a lot of spare time and she started to create ceramics, very appreciated also from the local center for the blind.
Photos taken with the permission of the patient.
As explained in this video and as my neighbor can attest, a timely and accurate diagnosis is essential in managing the disease and minimizing damage that it can cause. For all rare disease actually is extremely important to get the right diagnosis from the beginning, find the treatment and access to the right care and support institutions.
The initial inflammation causes aren’t known. It’s an autoimmune disease in which the immune system attacks the body’s own arteries as if they were foreign substances. Apparently Takayasu’s arteritis is genetically associated with HLA region.
Anyway my friend told me about her twin (mono-ovular sister) who has never shown any symptoms of the disease. The only difference between the two is the amount of time they lived in India, Charlotte remained five years after her sister left . This suggests environmental influences may play a key role in the onset of the disease.
For patients with Takayasu’s arteritis, stress is a major factor that should be avoided at all costs, because an adrenaline surge can have a damaging effect on the heart.
There are some speculation that viral or other infections.
Connection to tuberculosis
A possible relationship between TA and tuberculosis (TB) has been suggested, although this potential relationship is not yet fully understood.Both diseases have similar chronic inflammatory lesions and occasional granulomas on the arterial walls.
Treatment and side effects
Takayasu’s arteritis is associated with substantial morbidity, causing poor health, and may be life-threatening.
Initially my neighbor had been treated with steroids. A primary side effect of treatment with corticosteroids is osteoporosis. For this reason the physicians recommended that she increase her intake of calcium and vitamin D to help prevent this problem. Charlotte became refractory, meaning after a while she stopped responding to steroid treatment, and the doctor prescribed second-line agents like methotrexate. The treatment was able to make the TA disappear, but such strong drugs led her to develop kidney cancer two years later.
Sometimes some surgical options (large vessel reconstructive surgery such as bypass grafting or stenting ) may need to be explored for those who do not respond to steroids, but this was not necessary for her.
Because of the strong side effects, new therapeutic approaches are needed for Takayasu’s arteritis. Flavonoids are a class of plant and fungal secondary metabolites used from the plants as pigments.
They have anti-oxidants and anti-inflammatory properties that may be effective against Takayasu’s arteritis. Studies are currently underway for reducing inflammation in the serum of HSP (Henoch Schonlein Purpura) patient.
I was wondering whether any clinical studies about the use of flavonoids against the TA exist, and eventually at which stage of the disease could they be useful for the treatment.
Otherwise, investigation has been done about biologic agents, in particular the anti-TNF agents, such as tocilizumab (recombinant humanized monoclonal antibody), rituximab (for the B-cell targeted therapy) and Infliximab (the most commonly studied anti-TNF).
Also in this case there are important side effects. The most common one is an increased risk of infection. Long-term use of anti-TNF agents may increase the risk of cancers such as lymphoma and skin cancer. There are also rare neurologic complications from the use of these medications.Which improvement are expected to reduce these risks?
The problem is quite complicated, that’s true, but I’m sure Charlotte will be happy to hear your suggestions and comments, which I’m happy to report to her during our next tea & chat afternoon.
*Name changed to protect the patient’s identity