Thread by @theliverdr

1/38 "Next patient is a nun referred from DM Hospital"
My OPD staff tells me

"Severe hepatitis without a cause"

I sit up excited, also terrified

Excited, I get to serve people who bought me into this world Terrified, as they were competent to diagnose hepatitis, but couldn't.

2/38 Nuns at DM hospital ensured my mother was taken care of when she delivered me, many decades before.
They were pleasant, caring, comforting. DM hospital was well known for its services; it catered to a lot of patients, many very sick

A direct referral was always challenging.

3/38 I watch as two nuns enter my room and seating in front, they show me a liver test - the enzymes - AST & ALT were in 2000's with a hind of jaundice - the bilirubin was 3.2 mg/dl (clinical jaundice is when bilirubin is >3)

"I was a young nun, the time when you were born,"...

4/38 ...the elder looking nun tells me

The one who bought me into this world, the senior nun at the time, had passed away a few years ago. But they all remember me, my family and they say, my presence here gave them hope.

100's tests later, they didnt have a cause for hepatitis

5/38 Many years before, Sr Christy (name changed) started developing weakness of one leg which progressed over months that she got clumsy while walking and her behavior changed.

Extensive tests done at the time & only one result stood out. Her brain had "white matter changes."

6/38 The brain is composed, broadly into white matter and gray matter areas, with each having its own special group of functions.

When various processes - genetic, inflammatory, infections or immune disorders affect the white matter, patients develop a myriad of problems.

7/38 Approach to white matter disease is focused and the brilliant doctors at DM hospital go through with the best thing there is, in medical science

Algorithms

Algorithms, WILL take you to a place eventually where you'll either heave a sigh of relief or enter a depressive void

8/38 The doctors get on with a battery of tests while Sr Christy was progressively deteriorating.

And they concluded..
She had post infectious triggered auto-immune acquired white matter disease
She was put on medicines to suppress her immune functions to reduce damage to brain

9/38 Immunosuppression works like magic in autoimmune disorders and within weeks, Sr Christy was walking again and back to the pink of her health.

But the steroids, used for immunosuppression could not be given in the long term, due to various side effect concerns.

10/38 So the good doctors, to protect her from side effects (yes, this is realistic practice of medical science - it aims to comfort, not to exploit the patient), start reducing steroids and then added a new drug which will act like steroids, but without the major side effects.

11/38 Enter, mycophenolate mofetil or MMF

An immunosuppression drug that takes over work from steroids and that can be used for long term. It is a wonder drug and is also used after organ transplantation to prevent rejection.

Sr Christy goes on MMF for many years and without..

12/38 ..further deterioration.

Meanwhile, she is diagnosed with low functioning thyroid disease (hypothyroidism) and started on the very safe thyroxine supplements

Until one day, she developed the same clumsiness in her legs, this time, on her right hand - she was suddenly..

13/38 ..she was finding it difficult to write or sign papers.

The doctors were distraught. She was having a breakthrough of her disease ON TREATMENT. This meant that her immunosuppression drugs were not acting up well. So they did something every caring doctor would do..

14/38 ..they PULSED her with a high dose of steroids.

Steroid pulse therapy is life saving in many situations. It is safe and given under monitoring to quickly improve clinical condition while doctors can usher in other supportive care

Two pulses later, Sr Christy's hands..

15/38 ..start functioning better! Her tremors and clumsiness is gone.

But there was something that needed to be done. A change in medicines because the MMF failed. So the doctors bring in the big gun. A drug so powerful, that it pulverizes the immune system ever so gently..

16/38 ..that it is like a surgical strike on the body, without major collateral damage.

Rituximab.

But Rituximab must be used cautiously

It can reactivate sleeping monsters in the human body - most importantly, in those who already have weak immune systems - like HIV-AIDS...

17/38 ..or Sr Christy here, who has had a low immune system since many years and many hidden terrors would be waiting to wake up once the immune system is hit hard

So before starting Rituximab, the doctors screen Sr Christy for hidden viruses and they are all negative.

18/38 They screen her specifically for 3 viruses -HIV, hepatitis B, hepatitis C

Rituximab can also awaken a terrible foe, called JC (John Cunningham) virus, which worsen brain disease -condition called PML which could kill patient
hindawi.com/journals/criid…

But the doctors were..

19/38 ..sure that she was protected from all of these and they start her on Rituximab
cp.neurology.org/content/7/6/534

One week after the Rituximab therapy, she felt uneasy, lost her appetite and her abdomen ached. Rapid tests showed only ONE abnormality. She had severe hepatitis.

20/38 The doctors were flummoxed. They did everything by the book, but the hepatitis was unexpected. So they check her for all viruses and for autoimmune liver disease - because she already had autoimmune disease, including history of thyroid disease

But EVERYTHING was negative.

21/38 And so here she was, sitting in front of me, asking for a diagnosis, so that she can go back to serving her hospital, her patients and the children she cared for at her mission convent.

I call an old friend to help me with acute hepatitis this patient was suffering from..

22/38 ALGORITHM.

Acute hepatitis has many common causes - from viruses, to weird infections such as dengue, leptospirosis and even rarely, Covid-19.

We rule them out one by one

Until we have no cause left

I was on same page as the doctors before me

But someone had missed..

23/38 ..missed something in history. They must have. So I ask the sister about recent change in drugs - to diagnose drug induced liver injury or DILI

Only Rituximab was new
There were no reactivated viruses
She did not use pain killers, no new antibiotics
She DENIED..

24/38 ..using Ayurveda, Siddha, Homeopathic formulations - there were no other herbal and dietary supplements use. She was a smart and well-informed woman, and I knew that she would not use alternative medicines especially when she was on drugs that were improving her..

25/38 There was no other way but to ask liver directly. So I tell the nun, that we had to biopsy her liver. She said she knew this would happen. Because her previous doctors had mentioned it would come to this and only an expert team could interpret it.

So we biopsy her liver.

26/38 This was going way above our heads

We had a patient with history of autoimmune disease & hepatitis on immunosuppression

None of the viruses had reactivated

It COULD NOT be autoimmune hepatitis as she was already on treatment for autoimmune disease & drug history of clean

27/38 This was medical science.
It was factual.
It was curious.
It had clarity in the beginning and in the end.
It always found a reason.

And here we were, waiting for the results of the biopsy.
For me to give them back, what they gave my mother then.

And I get a call..

28/38 ..from the Pathology Lab and I rush in to discuss.

The liver biopsy did not show a virus damaging her liver. It did show MILD autoimmune damage. There was no cancer. And the biopsy did not show any disease affecting the blood vessels of the liver. But what it did show..

29/38 ..where hundreds of peculiar cells that were eating away at the liver - cells called Eosinophils.

Eosinophils are usually not expected inside the liver.

But they swarm to the liver when there was a special kind of injury

Drug-induced liver injury.

And I slump back..

30/38 ..because we had ruled out every drug possible, including alternative medicines that could harm the liver.

So with great difficulty, I go back and ask Sr Christy, if she was doing recreational drugs or using substance abuse. I sounded stupid and she looked calm.

31/38 ..she said, "No." and I apologized.

She said, she knew what I was doing and this was not awkward at all.

She again confirms her position on all the medicines she had taken in the last 3 months...
Steroids, Rituximab, an occasional medicine for "gas," and supplements..

32/38 ..for her bone health because she was on long term steroids and MMF and what not.

I sit & ask her
What supplements?
And she says, calcium and vitamin D and a bone strengthening commonly used supplement.

My ears sharpen like an elf's, assimilating information like a wolf

33/38 ..can you show me the prescriptions you have? Everyone of them since last 3 months? I ask her & she brings out multiple papers which I go through with attentiveness, taking over 40 mins to complete the review of drugs and then I find it.

I find it.
Hiding in plain sight.

34/38 Bisphosphonates are group of drugs that reduce bone turnover/increase bone mass, which makes them valuable agents for prevention and therapy of osteoporosis.

In patients on long term immunosuppressants and post menopause at high risk, this is used to improve bone health..

35/38 ..but bisphosphonates have also been linked to severe hepatitis with some immune mediated liver injury.

This was notable with Zoledronate and Ibandronate.

Sr Christy had just received her Ibandronate 3 days before Rituximab

Rituximab per say does not cause hepatitis

36/38 ...and coupled with the finding of eosinophils in the liver biopsy with some mild features of autoimmune damage in THE ABSENSE OF EVERY OTHER IDENTIFIABLE CAUSE

- the most probable diagnosis in Sr Christy was Ibandronate-induced liver injury

& restarted on pulse steroids.

37/38 After days of ordeal, her hepatitis resolved and her energy levels returned.

At discharge she thanked me & I held her hand

The elder nun tells me, Jesus has shown the way

I look at her & Sr Christy & smile

If they wanted to call my ALGORITHM, Jesus, I was ok with that.

38/38 I hope you've found this thread helpful.

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