Setting: emergency department
CC: “My urine is dark, and I am so tired all the time.”
VS: BP: 160/95 mm Hg; P: 85 beats/minute; T: 101.4°F; R: 18 breaths/minute
HPI: A 23-year-old woman is brought by her family on a one-way ticket to New York City from out of the country because of urine and fatigue for the past few months. She had been told she had renal damage and needed a kidney biopsy but was not able to have it done. She is extremely fatigued with joint pain. She has had several spontaneous abortions and is very concerned about her ability to have children.
PMHX:
G2 P0020
Alopecia
Hypertension
Social History: visitor from Haiti who claims to be a medical student
Medications:
Ibuprofen
Hydralazine
PE:
General: tired, uncomfortable, sullen, and angry appearing
Skin: alopecia of scalp, no facial lesions
HEENT: oral ulcers present
Chest: clear
Cardiovascular: normal
Musculoskeletal: no joint deformity
Initial Orders:
Urinalysis (UA)
ANA
Double-stranded DNA (dsDNA)
CBC
CHEM-7
Which is the most specific test for systemic lupus erythematosus (SLE)?
a. ANA
b. Anti-dsDNA
c. Anti-Sm
d. Complement C3 and C4 levels
e. Anti-Ro (SSA)
Answer c. Anti-Sm
The only test for lupus (SLE) that is more specific than the dsDNA is the anti-Smith or anti-Sm antibody. Anti-Sm is present in only 20% to 30% of patients, but it is very useful to diagnose SLE in those with a positive ANA whose anti-dsDNA is negative. SLE can be a very difficult diagnosis to establish in patients. There is no one single presentation or physical finding that is pathognomonic for the disorder. You must combine at least four findings to consider a person to have SLE.
Reports:
UA: proteinuria 300 (3+), red blood cells (RBCs) and RBC casts present
ANA: positive at 1:160
dsDNA: positive
CBC: WBC 12,400/μL (elevated); hematocrit 32%; MCV 86 fL; platelets 156,000/μL
CHEM-7: BUN 28 g/dL (elevated); creatinine 2.4 mg/dL
Fever can be from lupus alone.
What is needed to confirm lupus in this patient?
a. Renal biopsy
b. Nothing
c. Bone marrow biopsy
d. Anti-Sm
e. Complement levels
Answer b. Nothing
This patient already has enough information to be diagnosed with SLE.
• Joint pain
• Renal involvement
• Oral ulcers
• ANA positive
• dsDNA positive
• Anemia
Only 4 of the 11 criteria for SLE are needed to establish a diagnosis of lupus. A renal biopsy is the most accurate test of lupus nephritis, but we already know she has renal involvement. A bone marrow biopsy is not needed. Any level of hematologic involvement is enough to be one of the criteria. It can be low levels of WBCs or platelets, or anemia.
Anti-Sm
• It is the best test when dsDNA is negative.
• It is the most specific of all SLE tests.
• It is present in only 20% to 30% of patients.
Which test is used to determine that increased disease activity (lupus flare) is present?
a. Increasing ANA
b. Decreasing complement level, increased dsDNA
c. Increasing anti-Sm
d. Rising urine protein level and decreasing hematocrit level
Answer b. Decreasing complement, increased dsDNA
Only two tests reliably determine if a sudden worsening of disease is from SLE. If the complement (C3 and C4) level is dropping or the dsDNA is increasing, this is the only clear laboratory evidence of a lupus flare.
SLE Skin Disease
• Malar rash
• Discoid lupus
• Oral ulcers
• Photosensitivity
Which is the most common hematologic manifestation of SLE?
a. Increasing WBC count
b. Anemia of chronic disease
c. Hemolysis
d. Thrombocytopenia
Answer b. Anemia of chronic disease
Anemia of chronic disease is more common than hemolysis in SLE. When there is WBC involvement, it is usually a decrease in WBC count, not an increase.
The patient is very tired and frustrated about her disease. The oral ulcers bother her, as well as her fatigue and reproductive issues.
What is next in the management of this patient?
a. Renal biopsy
b. Prednisone
c. Prednisone and cyclophosphamide
d. Belimumab
e. Hydroxychloroquine
Answer b. Prednisone
You do not need to wait for the results of a renal biopsy to give steroids. The patient will experience an immediate improvement in fatigue, cell counts, oral ulcers, and kidney involvement with steroids. You should not add additional immunosuppressive medication for lupus nephritis without a renal biopsy. Cyclophosphamide can cause hemorrhagic cystitis and bladder cancer and should not be used until you know precisely what type of renal disease you have. Hydroxychloroquine is for skin lesions only. Belimumab is an inhibitor of B-cell lymphocyte function. Belimumab is used when there is recurrent disease or the disease is refractory to steroids. Belimumab is the first new drug for SLE in nearly 50 years, but has limited efficacy.
Belimumab inhibits B-cell activating factor.
The patient is started on prednisone, and a renal biopsy is requested.
Joint x-ray is normal in SLE.
Why get a renal biopsy?
a. To prove that lupus nephritis is present
b. To determine the extent of treatment
c. To determine that RBC casts are not from lupus nephritis
Answer b. To determine the extent of treatment
The patient has lupus renal involvement, but you do not know if steroids alone are enough therapy or if either mycophenolate or cyclophosphamide is needed. The only way to determine if there is advanced-stage disease with proliferative glomerulonephropathy is with biopsy. A biopsy determines the need for additional therapy to steroids.
A renal biopsy is performed. Also, anyone with multiple first-trimester or one second-trimester spontaneous abortions needs evaluation for antiphospholipid (APL) syndrome.
Orders:
Continue prednisone
Prothrombin time (PT), activated partial thromboplastin time (aPTT)
Anticardiolipin antibodies
Venereal Disease Research Laboratory (VDRL) False Positive
• Fluorescent treponemal antibody (FTA) is negative.
• It is not needed if APL testing is to be done.
• It is the same as anticardiolipin antibody testing.
Reports:
Renal biopsy: proliferative membranous glomerulonephritis
PT normal; aPTT prolonged
Anticardiolipin antibody present
VDRL is a cardiolipin.
Drug-induced lupus does not have renal or cerebral manifestations.
What do you do for the next pregnancy?
a. Recommend an abortion.
b. Give aspirin and heparin.
c. Give warfarin.
d. Give prednisone.
e. Give belimumab.
Answer b. Give aspirin and heparin.
Aspirin and heparin therapy during the pregnancy is the standard of care for antiphospholipid syndromes such as anticardiolipin antibody or lupus anticoagulant causing spontaneous abortion. They are both treated the same way.
Prolonged aPTT
• Does not correct with mixing study.
• False positive results in VDRL testing.
• Russel viper venom test for lupus anticoagulant.
Drug-Induced Lupus
• Spares brain
• Spares kidney
As you move the clock forward, prednisone will have an effect in a day or two. You do not have to keep the patient in the hospital to await the results of the biopsy.