lupus Flashcards
Lupus
what is lupus
● Inflammatory autoimmune disorder
○ 85% female (7-15:1 female:male)
■ sex hormones play a role – majority diagnosed between menarche and menopause
○ prevalence: 0.02-0.15% overall
■ ethnicity: 1:1000 in white females, 1:250 in black females
○ familial occurrence (HLA haplotypes, other)
■ serologic abnormalities (ANA+) without SLE manifestations
■ other rheumatic conditions
○ environmental:
■ smoking (trigger)
■ UV light (exacerbates)
estrogen is protective for gout, just like in cardiovascular disease. And as estrogen levels wane in menopause, then we see an increase in certain diseases in women. And so again, sex hormones play a role here can actually be a trigger for lupus. And the majority of people are diagnosed between menarche and menopause. Similarly for transgender women who are taking estrogen, they can, if they’re otherwise genetically predisposed, actually sort of spur the onset of a lupus diagnosis.
it does affect more black women compared to white women. And Latina. And women are also a little bit more affected as well. There is that familial occurrence. So again, we’ve got a genetic predisposition with these changes in the HLA haplotypes. And folks who are in the family but aren’t exhibiting any symptoms of lupus might also have a positive ANA, which is one of the autoantibodies and may never go on to actually get lupus. Or there’s such a familial sort of link between all of the rheumatic diseases. Somebody who’s got a positive and a might actually go on to have rheumatoid arthritis.
Lupus: Pathophysiology
● Production of antibodies to nuclear, cytoplasmic, cell surface, and
soluble antigens, leading to systemic inflammation
● Clinical presentation is variable:
○ Manifestations
■ simply skin & joint manifestations – Cutaneous Lupus Erythematosus
■ organ & life-threatening disease – Systemic Lupus Erythematosus
○ Pattern
■ usually relapsing-remitting
■ can be continuous
the low-grade fever, anorexia, weight-loss, malaise, or are really predominant in lupus.
damage to the DNA from UV light or any other type of environmental trigger that is causing these auto antibodies to any number of different cell types and various facets in the body. Because there can be a number of different types of auto antibodies and different systems can actually be affected. So some folks with a diagnosis of lupus will have more just skin manifestations with some joints being affected. And we would call that cutaneous lupus erythematosus. That can actually progress to be more systemic.
oregon life threatening diseases, tons of inflammation. So needing careful attention and quick treatment, the pattern is is usually relapsing and remitting. So not so much like rheumatoid arthritis, which can vary over time, but really quite quiescent periods of time. And then the relapses might be triggered by some type of environmental or other cause. But the pattern can also be continuous and progressive.
Lupus: Clinical Findings
constitutional
skin
● Constitutional: fever, anorexia, malaise, weight loss
● Skin (90%)
○ malar (‘butterfly’) rash (<50%) or discoid rash (most common)
○ photosensitivity (rash following sun exposure)
○ painless mucous membrane lesions (during exacerbation)
○ alopecia – patchy or diffuse
But you can see this outline across the bridge of the nose and into the cheeks. What’s really interesting is the nasal labial folds are spared. So that’s why it kinda looks more like a butterfly.
discoid rash. Which is red and raised and scaly and might be confused for some other type of subarea or some other type of keratitis.
, quick treatment and resolution of that rash can help to prevent some of that scarring (discoid).
it’s not like the little maculopapular itchy rash that happens with sun exposure within minutes to hours. This is an auto-immune reaction. So it takes a week to actually get started and going. And it’s almost like just the worst sunburn you could imagine across the whole body. And then it takes weeks to months to resolve with good treatment. So avoiding UVA and UVB light is incredibly important
it’s not like the little maculopapular itchy rash that happens with sun exposure within minutes to hours. This is an auto-immune reaction. So it takes a week to actually get started and going. And it’s almost like just the worst sunburn you could imagine across the whole body. And then it takes weeks to months to resolve with good treatment. So avoiding UVA and UVB light is incredibly important
painless mucus membranes. So I mentioned that allegiance MJ had all these lesions in her mouth and nose. She had no idea. So they’re there. They can flare up during exacerbations. discoid scars that are on the scalp, they will lose the ability to grow hair in that, in that area permanently.
Lupus: Clinical Findings
● Joint
muscles
● Joint
○ symmetrical, polyarticular, with or without active synovitis (>90%)
■ less severe, less swelling, shorter morning stiffness than RA
■ reducible swan-neck deformities (erosive changes rare)
● Muscles
○ myalgia (50-80%) or myositis (5-10%), tendonitis (10%)
Muscle soreness also really common, less so inflammation of the muscle or the tendons.
different than rheumatoid arthritis, tend to be less severe, less red-hot, squishy, but still the same kind of pattern in terms of which joints are affected.
Lupus: Other Clinical Findings
Ophthalmologic keratoconjunctivitis sicca, photophobia, blurred vision
Lung common: pleural effusion (50%), bronchopneumonia
rare: pneumonitis, restrictive lung disease, alveolar hemorrhage
Cardiovascular pericarditis, Raynaud phenomenon (20-30%), myocarditis (HF),
arrhythmia
Vasculitis medium sized vessels (aneurysm, narrowed)
Neurologic More Common: headache, mood changes, cognitive impairment,
seizures, stroke
Less Common: peripheral or cranial neuropathies
Renal glomerulonephritis
interstitial nephritis
high prevalence of Raynaud’s in people who have systemic lupus and then renal disease, both glomerulonephritis and interstitial nephritis. So vote 50% of folks with systemic lupus will have renal involvement and about 10% of them will go on to end-stage renal disease.
Lupus: Lab Findings
what autoantibodies are found
● Characterized by production of various autoantibodies:
○ ANA (antinuclear antibody): 95% sensitive (not as specific)
○ anti-dsDNA: 95% specific, 60% sensitive
■ levels also correlate with disease activity
○ Sm (Smith): 99% specific (30% sensitive)
○ antiphospholipid (APL):
■ lupus anticoagulant (7%)
■ anti-cardiolipin (25%)
● Hypocomplementemia: during active disease (60%)
● Other:
○ hematologic: anemia, leukopenia, thrombocytopenia
○ hematuria, proteinuria (renal disease)
○ mildly elevated ESR, CRP ( CRP and ESR don’t tend to be greatly elevated like they are in rheumatoid arthritis or in gout.)
The anti double-stranded DNA is incredibly specific, 95% specific. So we’re almost guaranteeing if that’s positive, that this is lupus. And the Smith antibody even more specific for lupus.
patients who have antiphospholipid antibodies will be more likely to have VTE are more prone to pregnancy loss. We need to think about anticoagulation depending what, what clots they present with. In
With lupus, the anti double-stranded DNA and complement levels actually vary with the disease. So in order to confirm that someone is in a flare, we can see whether they’re anti double-stranded DNA levels are increased and their complement levels are decreased. So the complement gets released and used up almost so that the normal level dips during active disease.
Lupus can also affect all three cell lines. So when it’s active, patients can have anemia, decreased hemoglobin, leukopenia, thrombocytopenia
Lupus: Rule Out Drug-Induced Lupus
Tnf inhibitors are interesting because they can actually spur real lupus in predisposed people, but they can also cause a drug-induced reversible lupus. So figuring that out obviously would be important, but TNF inhibitors are contraindicated for patients who have a diagnosis of lupus.
● Numerous drugs associated with lupus
○ Hydralazine, isoniazid, procainamide, chlorpromazine, minocycline
○ TNF inhibitors (RA > IBD)
○ PPIs
● Features distinguishing drug-induced from SLE:
○ Sex ratio equal, tends to affect older people
○ Renal, CNS features are absent
○ ANA positive – but:
■ No hypocomplementemia & dsDNA Ab negative
○ Clinical features & lab abnormalities disappear when drug withdrawn
Lupus: Complications
● Accelerated atherosclerosis (independent RF)
○ Recommend assessment of CV RF at diagnosis and periodically
● End-stage renal disease
● Infections
● Osteoporosis & Avascular Necrosis
○ Recommend assessment of OP risk and fractures every 1-3y, education on
osteonecrosis
● Malignancy
○ lymphoma, lung, cervical (annual screening) So anyone who has a cervix should have annual screening right from diagnosis no matter how old they are.
young people who have a diagnosis of lupus have a relative risk of cardiovascular complications that is just extraordinary but still quite rare
We want to think about treating any modifiable cardiovascular risk factors. End stage renal disease. Obviously we want to try and avoid. So for anyone who does have renal manifestations that monitoring every three months of, of GFR urinalysis is incredibly important.
Osteoporosis and avascular necrosis. So this is probably more treatment-related than disease related at this point. We use a lot of steroids in patients who have lupus. That regular use or higher dose over longer periods of time obviously increases the risk of osteoporosis.
avascular necrosis happens when these tiny little microthrombi cause micro fractures in the bone that over time add up. And that dead bone essentially creates a collapse in the joint. So this is luckily quite painful. And so you can tell patients that this is very rare, but if you have a new severe joint pain tends to be the hips, sometimes the shoulders but the hips or for some reason particularly predisposed to this. Then we want, we want to get people off of those steroids as quickly as possible.
Lupus: Treatment
goals
Ø Disease manifestations vary and activity waxes & wanes
○ Requires individualization of therapy!
● Goals:
○ Manage symptoms and prevent damage & complications
○ Control inflammation and autoimmune activation
○ Improve long term survival and quality of life
Lupus: Treatment – Most Patients
nonpharm
pharm?
● Non-pharmacological
○ avoid prolonged sun exposure (SPF ≥30, physical)
○ tobacco cessation
○ calcium, vitamin D
● NSAIDs PRN
○ minor joint & MSK symptoms
○ pleuritis or pericarditis
● Antimalarials (hydroxychloroquine 200-400mg/d)
○ lupus rash and joint symptoms (constitutional symptoms)
○ core drug therapy for patients with lupus (max 5mg/kg/d)
s. So effective for the rash types of symptoms, joint symptoms really is the core drug therapy. So it will be more unusual to see a patient not on hydroxychloroquine
Lupus: Treatment – Some Patients
● Steroids
○ topical (hydrocortisone) for cutaneous manifestations
■ alternative: calcineurin inhibitors (tacrolimus, pimecrolimus)
○ oral for systemic complications
● Immunomodulators: systemic lupus erythematosus
○ methotrexate, azathioprine
○ belimumab (Benlysta) - BLyS inhibitor
○ anifrolumab (Saphnelo) – Type I Interferon inhibitor
○ deucravacitinib (Sotyktu) – TYK1 inhibitor (not yet marketed)
● Immunosuppressants: renal disease
○ cyclophosphamide, mycophenolate mofetil, cyclosporine
○ belimumab (new: lupus nephritis)
Lupus: Additional Treatments
● Anti-phospholipid Syndrome: anticoagulation
● Cardiovascular Disease
○ manage modifiable risk factors (DM, HTN, lipids, tobacco)
● Vaccination: influenza, pneumococcal, HPV
● PJP Prophylaxis
○ prednisone >20mg/d for 2 weeks
○ cyclophosphamide + additional RF
Case: Ms. Jones
● MJ is a 26yo nurse (she/her, sex assigned at birth female) (65kg) who
was recently discharged from hospital following her presentation to
emergency for chest pain and shortness of breath
○ Clinical Findings:
■ fatigue, malaise, 8lb weight loss
■ malar rash, photosensitivity, Canker sores in mouth & nose
■ arthritis of PIPs, wrists
■ Class II glomerulonephritis
○ New Medications:
■ hydroxychloroquine 400mg po daily
■ prednisone 15mg po daily
■ ramipril 5mg po daily
Are her prescribed medications reasonable?
Hydrxychlorquine: a little bit higher than the max 55 per kilos might be an intervention at this point that we would make to try and decrease that. So most commonly people would be on the 200 alternating with 401 tablet, alternating with two. To get within that range.
specifically the pericarditis inflammation can be quite painful. And so prednisone is incredibly effective. And as pharmacists, we would be thinking about how long is that prednisone being split, going to stay on. Do we have a plan to taper? So if you’re getting a prescription that just says 15 mg daily, you would want to figure out what that what that plan is. And I would say that MJ would have prednisone over weeks but not months.
Ramipril - renal protection, showing some risk for progression with with that glomerulonephritis. We want to do our best to protect the kidney function. We would want to see check in with her that she’s got lab work every three months to follow that renal function a
Adherence
I had to stop taking [my medicine]
because of insurance problems and
that’s when I got kidney failure…
That CellCept pill is not little at all! I can pop
my prednisones all day because they’re ittybitty. But just having to take 3 of those twice-aday, on top of all these other pills, it makes
you not want to do it.
I didn’t see the activity of my lupus. So, I’m
thinking, “Why do I need CellCept? I’m fine, I’m
great, I don’t have lupus, what are y’all talking
about?” It’s probably a mistake.
‘Are me and my son and my
family gonna eat or am I gonna
get this medicine?’
You have friends that do the Google research, or a
friend of a friend who has lupus, and they’re not
taking any medications. Numerous people try to tell
me, “Go gluten free, go vegan, you’ll be fine, you
don’t have to take all these medicines polluting your
body. That’s what’s making you sick.”
I’m always running, so I’m never at
home, so I’ll either run out, forget
to take my medicine, or I come
home and pass out.”
Lupus: Role of the Pharmacist
● Ensure symptoms related to SLE are not drug induced
● Support adherence
● Preventative measures important
○ Monitor and treat CV risk factors
○ Monitor prednisone dose and BMD if necessary
○ Monitor renal function regularly
○ Ensure patients are appropriately vaccinated
○ Counsel regarding sun block
● Be aware of:
○ potential skin rash or flare with use of sulfonamide drugs
○ potential flare (HRT) and clots (HRT, OCP) with estrogen therapy
And so if folks are particularly sensitive, they may not tolerate those sulfonamides drugs. So again, thinking about that for someone who might need PJP prophylaxis and using dapsone instead of trimethoprim sulfamethoxazole
