There are two sets of patient groups affected by an aHUS name change. Those who have had it and already been diagnosed with it and those who have not yet onset and would not be diagnosed with aHUS but would be given a different name from the start.
Of course those who are yet to onset do not know they will be patients but they are out there even now.( excluding predisposed family members of course!).
Like all of us they will gave little idea of what is going to hit them and what has happened. Many will not have the language to fully know what has happened.
Current aHUS patients know what it was like to be diagnosed with aHUS and for the majority getting a diagnose was not a good experience. It should be much better than it is. Making it better is or should be, the prime aim of name improvement.
The improvement suggested is that some of aHUS patients would be called cTMA patients in the future the remainder will have other names perhaps. So cTMA patients would be treated as aHUS patients are now and would be the lowest in the diagnosis hierarchy and the remainder will be regarded as the highest. Lets imagine what it would like for new patients’ diagnosis and prognosis who onset in a range of previous scenarios experienced by many aHUS patients. Remembering that these scenarios that are already giving clues for what is happening.
These are :
| Scenario | Trigger | Own TMA only | cTMA only | Own TMA plus cTMA after | Diagnosis priority change |
| Pregnancy | 1 | 2 | 3 | 4 | No |
| COVID infection | 5 | 6 | 7 | 8 | No |
| Vaccination | 9 | 10 | 11 | 12 | No |
| Kidney Transplant | 13 | 14 | 15 | 16 | No |
| B12 Deficiency | 17 | 18 | 19 | 20 | No |
PREGNANCY
- Pregnancy can be described as a clotty time during and immediately after delivery, It can trigger a TMA or TMA like symptoms for several conditions. Most commonly HELLP, Eclampsia , Pre-eclampsia , CAPS (Catastrophic Anti Phospholipid Syndrom)e, TTP. It also triggers aHUS.
- Each can trigger their own TMA through endothelial damage but disease names do not reflect that. Usually once sspected treatment is premature delivery or termination and the TMA subsides.
- Complement is naturally activated during pregnancy and its target is the foetus and it can be over active too, usually post partum but sometimes during. Termination is then sometimes chosen by parents to resolve it but complement inhibition treatment could permit full term delivery and baby survival and any post partum rescue therapy helps the mother.
- Increasingly an overlap can be found particularly for HELP patients where complement is partially implicated too,
So there can be a category of TMAs for pregnancy conditions, pTMAs. Each can be named as their own TMA e.g. HELLP TMA, CAPS TMA. etc but likely keeping their own existing disease names. HELPP is by far the most common and suspected TMA .But aHUS triggered by pregnancy would come under the complement mediated TMA category. New patients would have cTMA with maybe prefixes dependent on whether genetic cause is known , not known or anti factor HUS antibodies are involved. Each would respond to a complement inhibitor but the prognosis for treatment discontinuation would be different for each, particularly as pregnancy is a transitory trigger. On some extremely rare occasion both types of TMA can be be present but termination is needed for one, and complement inhibition is needed to save the child and mother for the other. .
Hard to say whether having a new name is going to make any difference in the diagnosis process but it would be helpful in the prognosis. Most other conditions would likely retain their existing names.
COVID Infection
5. COVID could trigger a TMA response to a infection like many infections which are the most common trigger of aHUS. Anti viral/biotics treatment would target the virus/bacteria along with steroid treatment for the inflammation.
6. COVID therefore can create it own TMA as a response to the inflammation it causes through the cytokines link to the innate immune system.
7. If someone is predisposed to it it can trigger aHUS via the alternative pathway and on its own. This would be treatable with complement inhibitors.
8. A complement TMA can begin secondary to an infection TMA to create a TMA caused by both.
A patient with this TMA would at first likely be told they had an Infection TMA, iTMA, and the infection would be COVID so it can be a COVID TMA complement treatment would be of no use as this has been tried and was found ineffective.. But if a complement mutation was implicated or overactive complement found their diagnosis would be thought to be a cTMA and in time one of three subgroups genetic, antibodies and no genetic found and all three would be treated with a complement inhibitor but again their prognosis would be different depending on the severity of the initial infection ( heard of long COVID) and discontinuation of any complement inhibitor. It hard to see how changing the name would make any difference to the way the new aHUS patients would be diagnosed.
VACCINATION
9. The contents of any vaccination can be a trigger of a TMA
10.The vaccination itself is meant to cause an immune system reaction sometimes that reaction can lead to a TMA for each of the disease covered by each vaccination. A vaccination is just to prevent or lessen the effect of a specific infection. The infection itself can also cause a TMA as seen in the COVID example. A vaccination is a drug and drugs will have their own TMA category subdivided by each drug. Normally stopping the drug can cease the TMA but with aa vaccination the contents are in the body and cannot be removed. Supportive treatment is needed and the condition is self limiting.
11. Complement itself can react to the contents of a vaccination and not just the bit that simulates the disease but also what the vaccination is made of. In those with a predisposition to aHUS this could result in uncontrolled MAC action injuring the micro vasculature and causing a complement TMA.
12. There is also the possibility that the vaccination starts the TMA action and then complement joins in with its own TMA secondary to the vaccinations TMA with with or without a genetic predisposition. Without presents a diagnostic conundrum.
As with an infection any Vaccination TMA, vTMA, suspected would be associated with the vaccination initially as it would be a very rare event. Even rarer would be that the individua’s TMA is complement related particularly if no genetic complement genetic reason is found. Or both TMAs can be in play at the same time. The prognosis for the treated cTMA patient would again be different depending on genetics but the vaccination reaction is transitory so treatment discontinuation is a possibility. It is hard to see however what advantage the new name would offer in the diagnosis process as the more common vaccination reaction condition is still the most likely and TTP which is suspected before aHUS normally can also be implicated in a vTMA and it has much worse outcomes than aHUS.
KIDNEY TRANSPLANT
13. A kidney transplant can trigger a TMA during and after a new graft operation. The same would apply to other solid organ transplants.
14. In addition to grafted organ rejection there can be an excessive inflammatory response by the immune system and that can lead to a TMA response. Or even the anti rejection drugs can trigger a TMA.
15. In those with a predisposition known or not complement can become over active and end up causing a complement TMA, a cTMA.
16. And of course both could occur together with cTMA secondary to a soxTMA.
Kidney transplant TMA , kxTMA, would be one of the solid organ transplant TMA category, soxTMAs. Anyone whose complement has been over active would be regarded as having cTMA with no reference to a specific organ even though kidney injury has been the bulk of aHUS symptoms. Prognosis for most patients because the transplant is a permanent trigger is to remain on complement inhibitor treatment for life. Again no advantage to the newly onsetting cTMA patients except perhaps for those non kidney organ transplant recipients with no evident kidney injury could still have a TMA and would not necessarily be seen as an aHUS patient anyway. A very rare advantage ofor a new name. .
B12 DEFICIENCY
17. Vitamin B12 deficiency a metabolic disorder that can trigger a TMA or TMA like symptoms.
18 It is predominantly its own TMA, b12TMA
19 If genetically predisposed B12 can trigger a cTMA too and patients frequently been called aHUS even without a genetic cause.
20. More likely if complement is involved it is secondary to b12TMA and can be resolved with a course of B12 vitamin supplements.
The simple treatment of vitamin supplement is more likely to succeed if this disease gets its own name and not become a cTMA. Again not an advantage to new cTMA patients.
Overall it is hard to see what improvement from name change benefits a new aHUS patient in getting a more rapid diagnosis tam they would have with aHUS The sub classification after a cTMA diagnosis would lead to a more precise prognosis and treatment which would be far better than now with comprehensive guidelines and clear and informed patient counselling.
These onsets should have been simplified yet still remain complex as they would be in the real world when time is of the essence..
It is a more rapid diagnosis that is the biggest challenge that remains for aHUS. That and along with finding the best name for the disease.
By their very nature, future patients will not have an opinion on nomenclature yet.
Though by aHUS awareness day on 24 September some new patients who are currently diagnosed with aHUS could be connecting with the aHUS community and give their view on name change./
VOTING IS TAKING PLACE ON WHETHER PATIENTS ARE FOR, AGAINST, CONDITIONALLY FOR OR UNDECIDED ABOUT NAME CHANGE
More information about participation in the aHUS Day Call to Action answer it HERE
Article No. 809
