|
|
|
Treatment began immediately. Visits were made in quick succession to several specialists in an attempt to confirm the diagnosis and ensure there wasn’t something else occurring. After the additional screening was completed and GCA was proven via biopsy there was routine type follow-up with some of the specialists.
GCA/PMR must be managed with the judicious use of prednisone – enough to control inflammation but no more than necessary because of damaging side effects of long-term use of prednisone. So, how much is enough? That was a point of controversy we had with the Rheumatologists throughout her illness. Her rheumatologist initially used only sed rate to determine if GCA/PMR were being controlled. He established less than (<) 15 mm/hr as a normal range limit, yet when values higher than that were measured he didn’t always increase prednisone as would be expected. That inconsistency likely caused more arteritic damage to Pearl over the years.
C-rP measurement is another tool for GCA management – some think it is more important than sed rate measurement. The medical consensus at that time was that both should be used to manage the illness, along with symptoms. However, her rheumatologist used only sed rate (inconsistently) during the first year which was unfortunate for Pearl. We weren’t aware of C-rP or of its importance at the time.
Methotrexate is another prescription medication used sometimes in treating GCA/PMR. It was used on three different occasions by Pearl. Its purpose is steroid-sparing. The intent is to try to reduce the daily amount of prednisone needed by getting help from methotrexate to reduce inflammation. It is commonly used in treating Rheumatoid Arthritis.
The first use of methotrexate was for a year-long period starting in October, 2000. It was stopped at the recommendation of a Clinic Rheumatologist who considered it to be ineffective for GCA. Pearl sought the advice of the Clinic Rheumatologist when a second opinion was desired in 2001.
Methotrexate was started again for a four-month period starting in November, 2004. At that time an attempt was made to reduce prednisone from the normal management level on alternate days. Flare resulted so the methotrexate was stopped.
It was restarted in August, 2007, six weeks before her death. The reason it was tried once more was it had been demonstrated to be helpful after all. A medical journal article studied its past use on GCA patients and concluded methotrexate was beneficial but it took six months to a year to become effective. Review of Pearl’s use of it in 2000 and 2001 indicated a benefit did show up in the two years following its use. Prednisone requirements seemed to have been lower during that period.
The FPP insisted on a CT scan and liver biopsy to determine the cause of elevated alkaline phosphatase in the blood test a month before diagnosis. Several specialists did not want these done because management of Pearl’s illness was much more important at the time. These tests would involve an allergic dye, significant stress dose of prednisone and would be non-contributory - but the FPP had his way. The Gastroenterologist performed the tests in January, 1999, and results showed proper liver function as expected. Elevated alkaline phosphatase indicated GCA inflammation when elevated. Had that been recognized by the FPP in November Pearl wouldn’t have lost vision. Once prednisone treatment started the alk phos returned to normal. The alk phos would become elevated once again nine years later and would again be unrecognized by medical professionals as a potential indicator of GCA inflammation. At that time the oversight may have been vitally detrimental for Pearl.
Chronological overview of treatment
12/10/98 - Severe migraine-type headache occurred during which Pearl lost vision in right eye. I gave Pearl two injections of Imitrex, one hour apart. Waited until next morning to see if sight returned.
12/11/98 - Sight in left eye still hadn’t returned – called the FPP who advised she should go to the hospital at once to get it checked out. Still had sore muscles, was weak and had no vision in right eye. Arrived at Emergency Room at about 10:30am – took blood test and was referred to an Ophthalmologist; went to his office immediately, arriving at 1:30pm.
12/11/98 – The Ophthalmologist gave preliminary diagnosis of Temporal Arteritis affecting her right eye (biopsy of temporal artery still needed to confirm diagnosis). Temporal artery is bulging. Vision loss was determined to be permanent at about 3:30pm. Blood test results were faxed to Dr and several items were found to be significantly out of range. Dr discussed the situation and blood test results with the FPP and learned Pearl’s blood had changed since the previous test. Dr prescribed high doses of prednisone (120 mg/day) to be started immediately. Pearl was sent back to the FPP’s office – arrived about 4:15pm and was given prescriptions for ECG, doppler scans of carotid arteries, and referrals to other specialists – a Gastroenterologist, Hematologist, and Rheumatologist. Limit water intake to 1 liter/day. Stop taking Elavil (anti-depressant/sedative).
12/14/98 - Pearl had an echocardiogram and doppler scan of carotid arteries done at the hospital. Everything appeared to be normal – no indications of cause of loss of vision.
12/16/98 - Biopsy surgery was done by the Ophthalmologist who advised immediately after that the artery showed typical twisting and inflammation indications of temporal arteritis. Lab pathology results later confirmed presence of giant cells. Pearl’s temperature was running low during this surgery (95 degrees).
12/17/98 - Hematologist analyzed Pearl’s bone marrow – results were good.
12/17/98 - Rheumatologist examined Pearl and earlier blood test sed rate readings and advised that Pearl has Polymyalgia Rheumatica (PMR) and Temporal Arteritis (Giant Cell Arteritis). Sed rate had been 124. He recommended the following regimen of prednisone: 100mg for 2 days, 80 for 2 days, then 60 till next visit. Pearl will need to be on Prednisone for 1 to 2 years. He prescribed Fosamax, 400 units of Vitamin D daily, 1500mg of Calcium supplements daily – and a Centrum-type multi-vitamin. He performed a bone density test in his office and determined her loss to be about 21% which is more than the average woman would lose at her age.
12/28/98 – The FPP is concerned about why alkaline phosphatase was high in 11/10/98 blood test. He wants the Gastroenterologist to pursue this and advise him, even though it is normal now.
1/16/99 - Weakness – Pearl fell three times Saturday night before bedtime – legs just buckled under her without warning as though she was weak.
1/18/99 - The Gastroenterologist performed a liver biopsy and CT Scan. Results were normal.
1/26/99 – The Rheumatologist, discussing sed rate, advised that anything below 15 mm/hr is normal.
10/2/00 – I suggested consideration be given for methotrexate to be used in conjunction with prednisone as a steroid-sparing medication. The Rheumatologist agreed and prescribed it advising it had no side effects and would require the same monitoring as is being done to manage GCA.
10/11/01 – I recommended stopping methotrexate so Pearl could use some other medications that were restricted while taking methotrexate. There didn’t appear to be any benefit to Pearl in taking methotrexate for the past year.
11/5/01 – Pearl visited a Clinic Rheumatologist who recommended stopping the methotrexate – he doesn’t have any GCA patients taking it. Both Rheumatologists concurred in stopping it at that time because of apparent lack of efficacy.
11/9/04 – The Rheumatologist agreed to a plan of reducing prednisone on alternate days from the 12 mg/day normally required to control inflammation, and restarting methotrexate to see if it might be beneficial under these circumstances.
3/12/05 – Methotrexate was stopped due to severe stomach irritation Pearl has been experiencing for several weeks. Alternate day dosing continued for two more weeks. It became apparent that she had been in a constant flare since before starting the alternate day dosing. Two weeks after restarting the daily dose of 12 mg/day her legs regained normal color and circulation had improved significantly.
8/7/07 – Restarted methotrexate based on benefit reported in a recent medical study which found that benefits are latent, sometimes not showing up for a year. Review of Pearl’s use of methotrexate in 2000-2001 showed prednisone required to manage her illness appeared to be significantly lower in the two-year period following the use of methotrexate. Pearl had difficulty with vomiting on occasion – this was attributed to use of supplemental folic acid when taking methotrexate. She stopped and restarted methotrexate and modified dosage of folic acid on occasion to reduce the vomiting.
10/9/07 – Pearl had an episode of vomiting, loose bowels, overheating then sudden cold. This was attributed to an injection of an anesthetic, possibly lidocaine, prior to receiving an injection of a corticosteroid for a swollen knee joint. Medical literature states that lidocaine can affect the central nervous system to cause vomiting, sensation of heat, cold; also it contains a sulfite component – Pearl is allergic to sulfa. Pearl continued to feel "out of sorts" 24 hours later but the vomiting and loose bowels subsided. The weekly dose of methotrexate had been taken three days earlier, on 10/6/07, so it wasn’t a suspected cause of the symptoms Pearl experienced.
10/17/07 – Pearl had an episode of vomiting, loose bowels, stomach pain and severe chills two hours after dinner consisting of baked fresh salmon filet. Cause was unknown if not an allergic reaction to iodine in the salmon. She had reduced daily prednisone from 12 to 11 ½ mg/day the day before so perhaps cortisol was too low resulting in an allergic reaction. Since methotrexate was taken four days earlier it isn’t suspected of causing the symptoms. Possible contribution of Folic acid which is taken daily remains an unknown but it doesn’t appear to be a likely cause in itself – it is taken daily. Severe dehydration resulted after 6 hours of vomiting, stomach pain persisted as did loose bowels – I couldn’t warm her as the chills continued. She was too weak to stand or move on her own so I called the paramedics to take her to the hospital ER. She died 30 hours later.
There was speculation about the cause of her death – one theory was methotrexate and prednisone had depressed her immune system such that an opportunistic viral infection overwhelmed her system. My theory is that Pearl’s system cortisol was very low and she needed a stress dose of hydrocortisone upon arrival at the ER. She was admitted to the ER at 4:00 am on 10/18/07 in an extremely dehydrated and weakened condition – her normal prednisone dosing time was at 9:00 am but she wasn’t given corticosteroids until 4:30 pm when she was finally given a stress dose. Two hours earlier she had already gone into shock– circulation to her limbs had ceased. Her major organs began to fail, lungs started to fill with fluid. She died 19 hours after shock set in. The role of methotrexate, if any, is indeterminate.
Details of events and Drs’ visits from 12/15/98 thru 3/8/99, 10/2 & 3 of 2000, 10/11/01 thru 11/5/01, 10/31/04 thru 11/17/04, 2/22/05 thru 4/13/05 and 8/7/07 thru 10/17/07 are provided in Appendix 1.