Article No. 433
9 May 2021
Each day there are tweets about aHUS on Twitter. Mostly clinicians informing clinicians about new articles on the subject. Recently two tweets were noticed because somehow they created a doubt about what it is believed to be aHUS.
The first tweet was an image of a slide from a talk about Thrombotic Microangiopathy or TMA. It was a diagram in which various disease names surrounded the term TMA. The usual suspects were included TTP, SLE, DIC etc. aHUS was also included but written as “Atypical” HUS.
The inverted commas/quotation marks surrounding atypical suggest that someone thinks the term is inaccurate or unacceptable.
The second tweet referred to a new article “Thrombotic microangiopathy in aHUS and beyond: clinical clues from complement genetics” by Fadi Fakhouri and Veronique Fremeaux- Bacchi, two well known French aHUS researchers and disease experts. The tweet linked to the abstract of their article ( the full article was not free to view!). A phrase in the final sentence stood out ” even complement-mediated aHUS is not a classical monogenic disease”. There is no typical “atypical” HUS”
aHUS seems to be indefinable. So how many patients can definitely call themselves “aHUS patients”. With TMA boundaries blurred and overlapping how many aHUS patients who thought they were classical are there really.
More than you would think given the uncertainties of the term “atypical” and how “not monogenic” raises the options. It increases the prevalence of a disease, whose prevalence was already on the up.
No one should be talking about an aHUS disease prevalence rate of 2 per million anymore, it is inaccurate and misleading. Many pregnancy TMAs, now Complement-mediated aHUS, would have not been counted in that statistic from than a decade ago. Neither is the impact of the advance in complement inhibition treatment increasing aHUS lives saved.
There are not 650 aHUS patients in the USA, there are three times that number at least, there are not 130 aHUS patients in UK there are more than 300. There are not 900 aHUS patients in the EU there are approaching 3000, there are not… you get the idea.
Things have changed and will continue to change.
After nearly 10 years of aHUS patient advocacy the author finds himself asking in conversations with others, “For clarity what aHUS are you talking about?”.
Complement-mediated aHUS involves Complement dysregulation and significant renal impairment. Complement-mediated TMA can include Complement-mediated aHUS but also other other Complement-mediated conditions, without significant renal impairment, and which are not aHUS.
Furthermore the Complement dysregulation is down to significant aHUS disease specific genetic defects in Complement components, or an external hampering of effective Complement control components. It is Complement-mediated when it is uncontrolled complement that is the primary cause of damage to the lining of blood vessels triggering the TMA, and Complement-mediated aHUS when the renal capillaries are damaged by Complement, and not the result of another inflammatory disease which are not aHUS.
aHUS is not typical HUS but “atypical””atypicalHUS” may not be aHUS?
Is this an identity crisis for the disease or will more specific identification result in better diagnosis , prognosis and treatment decisions for all when the clarity emerges.
Interpretation is complex.