Wednesday, 22 Jan 2020

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Part 1:  The “P” in Prednisone stands for Poison...and Other Pearls

Everyone has life hacks.  Years of experience and doing the same things repetitively allow us to figure out little tricks to make life easier. A rat in a maze, finding itself at a dead end, will back up and search for a clearing. If this rat encounters its neighbor, it will transmit that information so the second rat won’t make the same mistake. In our medical training, we have studied the pathophysiology of diseases, practiced clinical examination skills, and memorized medications and side effects, but these didactics will only cover issues we encounter with patients about 50% of the time. We are left to figure out the rest.

Thankfully, our professors, mentors and colleagues have traveled the road, found the openings and are excited to pass on their knowledge so we won't hit a dead end. This blog is the first of a trilogy on pearls shared by the world’s rheumatology experts. The following are pearls shared by Dr. Michelle Petri on her approach to patients with systemic lupus erythematosus (SLE) and the medications nuances she noticed after 81,000+ patient encounters. 

  1. Don’t be fixated on whether to dose hydroxychloroquine (HCQ) 6.5 mg/kg/day or 5 mg/kg/day; what matters is the HCQ blood level.  If your patients are taking 5 mg/kg/day and their levels are in therapeutic range, then keep them on that dose, but if your patients’ levels are subtherapeutic, then you need to increase their dose or examine their compliance.  The ceiling dose of HCQ she prescribes (even if the blood level is subtherapeutic) is 400 mg/day. If a patient is on hemodialylsis, she prescribed maximum 200 mg after dialysis only; in patients with hepatic impairment, chronic kidney disease, and the elderly (she did not define at what age elderly begins), give patients half dose and monitor levels.   Note that most HCQ retinal toxicity occurs in the upper tertile of therapeutic range. 

  2. HCQ blood level is the equivalent of a hemoglobin A1C. It gives us information about the HCQ concentration in the patient over the last month.  Order HCQ blood level, NOT HCQ plasma level because HCQ binds to blood, and plasma levels are too variable.   Monitoring HCQ blood levels will improve patient compliance to therapy.  

  3. If a patient has gastrointestinal side effects from HCQ, have them take it with food or split the dose.  You can also have them coat the pill in butter which will slow its dissolution (she did not clarify if oleo will do).  Another resort is to prescribe brand name Plaquenil. Plaquenil is coated and will dissolve slowly.   

  4. Patients on high dose glucocorticoids with proliferative glomerulonephritis can have central serous retinopathy (CSR).  CSR can look just like HCQ retinopathy. Don’t stop HCQ when the patient needs it the most!

  5. The goal blood pressure for a patient with SLE should be 120/80 regardless if they have renal involvement; lupus causes such high cardiovascular mortality/morbidity, and this is one way we can change that risk. 

  6. Minimize use of proton pump inhibitors (PPIs) in SLE.  PPIs have been associated with osteoporosis, renal insufficiency, cognitive impairment, and cardiovascular disease by raising asymmetric dimethylarginine (ADMA) levels; ADMA is an independent risk factor for major adverse cardiovascular event (MACE) and is an endogenous inhibitor of nitric oxide synthase (NOS).   An impairment in the endothelial NOS (eNOS) has been associated with increase vascular resistance (https://doi.org/10.1371/journal.pone.0124653)

  7. Neuropsychiatric lupus can present with gray matter and/or white matter changes. Gray matter changes are monophasic, often associated with higher disease activity scores (e.g, SLEDAI 9.8) and can mimic other disease like infections.  Patient can have fever, urinary retention, hyporeflexia, and flaccidity. In contrast, white matter disease is polyphasic presenting as spasticity, hyperreflexia, and with a lower disease score (SLEDAI 2). White matter disease also has been associated antiphospholipid antibodieds, anti-Ro, and neuromyelitis optics (NMO) antibodies. 

  8. Regarding DHEA—Dr. Petri still uses DHEA in her SLE patients to reduce fatigue, arthralgias, cognitive dysfunction and to minimize corticosteroid use. Her word of advice: do NOT give DHEA to a man or postmenopausal female.  DHEA can metabolize into estradiol. The side effects of DHEA are dose related and can include hirsutism, acne, and low HDL. 

  9. Lupus Low Disease Activity State (LLDAS) is the target.  Organ damage was reduced 52% in patients who are in LLDAS.   LLDAS was defined as a SLEDAI<4, PGA<1.0, no major organ activity with low dose prednisone and stable immunosuppressants. 

  10. The “P” in prednisone stands for poison; Dr. Petri has been championing the use of less prednisone for years especially since we have less toxic therapeutics.  When possible, reduce the dose of prednisone <6 mg/day if the patient is going to be on it chronically; higher doses will contribute to organ damage (e.g, glucocorticoid induced osteoporosis, infections, cataracts, avascular necrosis, diabetes, etc.).  

We appreciate the wisdom of Dr. Petri and for taking the time to share these pearls with us. Stay tuned for Pearls Part 2: Common Sense Rheumatology by Dr. Sterling West.

 

 

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