Aspergillus? or other fungal infection - Need infectious disease help!

[prayingrbc]

My father has been treated empirically for Aspergillus and has we have tried Voriconazole, however, it only showed promise of working for the initial first few days. - We really need an infectious disease specialists’ opinion. The current doctors can’t seem to figure it out.

Facts:
-He has an underline diagnosis for Aplastic Anemia, currently WBC’s generally 2+, Plts 12, HGB 6.5 (on cyclosporine 200 BID)
-Ongoing infection issues since initial immune suppression and original low WBC.
-CT showed fungal ball in lung
- bronchial washing showed CMV and Non MRSA Staph. (currently treating both)
-blood test was positive for*the Aspergillus antigen.
-skin test positive for TB (has always been that way since he was a kid.)

Symptoms of infection:
weakness/fatigue/lethargy
confusion (at times)
difficulty breathing
drooping eyelid (new symptom)
fever
chills
constant sleeping
lower back pain (said he had it before illness but is significantly worse now - at times)
despite 2000 calories of ensure and boost (blood tests showing malnourishment)

The most pressing is what appear to be a fungal infection. Twice in the last two months he has spiked high temps accompanied by weakness and difficulty breathing and confusion, constant sleeping and fever. He has been treated empirically for Aspergillus with Voriconazole, however it doesn’t seem to be working and it appears he may be intolerant to it.

Mid March he started Voriconazole and within 36 hours of being on the drug he seemed to snap back to “normal” walking, no shortness of breath, appetite back, clear mental state, staying awake. Within a week his weakness was returning and it was if the Voriconazole was no longer helping. If anything was worsening. He was becoming severely jaundice, vomiting, severe weakness in addition to all the other symptoms returning (except the fever). We stopped all drugs, including Immunosupressives for his Aplastic Anemia. After 10 days of being off all drugs he seemed to improve. He started to eat a little, was staying awake more, the jaundice went away and he wasn’t confused nearly as much.

We started Immunosupressives again for the Aplastic Anemia and within about a 4-5 days his symptoms were slowly returning - fever, weakness, shortness of breath, confusion. We resumed Voriconazole.

Again, within 36 hours he was showing significant improvement, but again within 4-5 days his symptoms are returning, so far the sleeping and confusion.
I feel like there is something to this - somehow, somewhere we are missing something. I realize they are treating empirically, but to me, seeing the dramatic improvement within 36 hours of being on the Voriconazole (twice) and seeing the decline after a few days (twice) means something. Somewhere there is a missing link or puzzle piece.

Is it a resistant strain of Aspergillus? Not a sufficient dose of Voriconazole? Another fungal infection that needs another drug? Should he be off the cyclosporine Immunosupressive drug to treat the Aplastic Anemia during the course of the Voriconazole treatment?

Any help or direction would be greatly appreciated.

[bailie]

Has anyone mentioned zygomycosis or mucormycosis? These fungal infections do not respond to voriconazole. Posaconazole might be necessary.

[Cheryl C]

I'm sorry I can't help you, but I'm sure there will be some on this forum who will be able to offer advice.

Bailie - how are you? You've gone quiet!

[bailie]

Cheryl, I'm on Vidaza and Sprycel in hopes of getting blast count down.

[Cheryl C]

Good to hear that something is being done to try and reduce your blasts, Bailie. How long before you know whether this is effective. How are you feeling?

[bailie]

I will have another BMB next Wednesday. I will say this, the Sprycel is beating me up. Eight hour headaches every night, overall weakness and a little nausea.

[prayingrbc]

Thanks for the tip. I am looking in to these now and will consult with the doctor. At this point I really think Voriconazole is the wrong drug.

Do you have experience with either zygomycosis or mucormycosis? From what I've read, my father has symptoms like fever, shortness of breath, drooping eyelid, lethargy/fatigue, confusion, body aches (specifically the back) and had a cavitary lesion but that's it.

thanks!

[bailie]

Yes, you need an infectious disease specialist. It is a very difficult diagnosis. They caught mine very early and that was extremely important.

[prayingrbc]

Thanks so much for your response.

If you don't mind a few more questions. in the past two weeks my father's one eyelid is drooping slightly. When he started the Voriconazole (emperically for aspergillus) this second time around it went away for about 5 days and now it's back, coincidentally the same time the weakness and lethargy worsened as well. (about a month ago - the last time they tried Voriconazole the same thing -helped at first, but then after about 5 days seemed to start to go back to the same symptoms.

What drug did they put you on for it?

I have been trying to email Infectious Disease docs but no luck so far. Can you recommend a specialist to try?

I have been researching a bit on this and his symptoms seem to fit this fungal infection the most but I don't see a specific diagnostic test. How did they diagnose yours? by simply weeding out the others? He had fever and chills before the Voriconazole but that's subsided now. He still has severe weakness, shortness of breath at times, but it's better, confusion at times and now a drooping eyelid.

What symptoms did you have and what specific kind was it diagnosed as? cutaneous? pulmonary? disseminated? rhino? gastro? other?

Thank you so very much for sharing. I truly appreciate it!

[bailie]

Voriconazole is effective for (I believe) 23 out of 25 fungal diseases. It does not work for mucormycosis and zygomycetes. Posaconazole is only effective for these. I had a dry cough and minor shortness of breath. I had a chest CT scan that showed (it looked like the cross section of a golf ball) what they thought was a fungal infection. I had a pulmonary biopsy which was not a problem, but did not reveal enough information. The surgeon decided that removal was the only option, which I agreed because zygomycetes is about the worst. I had it removed and spent about 3 days in the hospital. The surgeon felt it was a complete success and a subsequent CT scan confirmed his beliefs. They have tried to grow the culture to confirm what kind of fungal infection, but I haven't received results.

[prayingrbc]

Bailie,

They took my father off cylosporine and Voriconazle as of yesterday due to elevated kidney levels. It has only been 24 hours and his kidney level actually went up, but hopefully it's just a matter of time before the level resolves.

Since the Voriconazole appears to be doing little good on the chest infection and harm on his body, they are thinking biopsy at this point. If my father's kidney function improves they are talking about potentially doing a lung biopsy guided by CT, however, some of the doctors are don't want to do it and don't recommend it due to his low platelet count (typically 15).

There has been suggestions of tanking him up on platelets but the docs still are very concerned of a fatal bleed. Was that a big concern for your docs? do you know how much they tanked you up on prior to your biopsy? I'm not sure what your level was at the time of your biopsy.

thanks

[bailie]

My platelet levels (200) were fine for the pulmonary biopsy. The biopsy is not too invasive. There was zero pain for me and I was eating peanut butter and jelly sandwiches (which they made for me) an hour after the biopsy.

The disappointing thing for me is that they had trouble making a biopsy that was telling. It was the CT scan that ultimately decided that the surgery was necessary.

[Cheryl C]

Bailie - how are you going? Any improvement in the headaches? You are often in my thoughts and I'm praying for you along with all the others on this forum who are battling.

[bailie]

Cheryl, the headaches seem to be getting better each day since the start of the Sprycel. I still had to take one oxycodone pill last night to get some sleep. If the headaches keep getting better I will be able to handle it. I started on the Sprycel as I was finishing my cycle of Vidaza shots, so that might have been part of the initial problem. Both the Vidaza and Sprycel lower blood counts so I am feeling tired most of the time. WBCs at1.1, PLTs at 20, RBCs at 3.04. That first cycle of both the Vidaza and Sprycel brought my numbers straight down as expected. Hopefully counts will get better quickly as they did prior to SCT and blasts go down.

[Cheryl C]

That sounds hopeful Bailie. So glad the headaches are improving. Your blood is certainly taking a battering, after you had achieved such good counts. I hope you are able to rest and take it easy.

[evansmom]

Remember voriconazole is hard on the liver so your father's jaundice may have been caused by that. As far as the confusion and droopy eyelid go, I'd be concerned that the fungus has become disseminated meaning it has invaded his brain (confusion) and sinus cavities (droopy eyelid). I truly hope this is not the case but these are the things that come to my mind. If this were me, I'd rather come off all immunosuppression and try another antifungal as people here have suggested. Before starting posaconazole, I think a CT guided lung biopsy is entirely appropriate. This CAN be done safely immediately post several units of platelets. I'd want to see a platelet count of 80 or higher. Remember these platelets will survive 4-5 days so invasive procedures are safe.