Lupus II and Sjogren's Disease Flashcards
When do you consider autoimmune hemoltyic anemia in a Lupus patient?
- Increased unconjugated bilirubin
- Increased LDH
- Increased reticulocytes
- Reduced haptoglobin
- Positive Coomb’s test
Chronic, low level thrombocytopenia is a characteristic feature of . . .
. . . chronic anti-phospholipid antibody syndrome
Leukopenia occurs in __% of SLE patients.
Thrombocytopenia occurs in __% of SLE patients.
Leukopenia occurs in 50% of SLE patients.
Thrombocytopenia occurs in 25% of SLE patients.
Blood cell and thrombocyte deficiencies may . . .
. . . predate the full emergence of SLE by several years.
When an SLE patient develops leukopenia, what is the differential?
- Leukopenia secondary to chronic immunosuppressive treatment
- Myeloma
- True SLE-induced leukopenia
An SLE patient with renal insufficiency on ACE inhibitors should be monitored closely for ___.
An SLE patient with renal insufficiency on ACE inhibitors should be monitored closely for hyperkalemia.
Autoantibodies appear at a mean time of ___ prior to diagnosis with SLE.
Autoantibodies appear at a mean time of 3.4 years prior to diagnosis with SLE.
Progression of autoantibody development in SLE
Antiphospholipid : t - 3.4 years
Anti-dsDNA : t - 2.2 years
Anti-SM/Anti-RNP : t - 1 year
t = diagnosis with SLE
IF techniques for detecting SLE
- HEp-2 cell substrate technique, add patient’s serum exogenously, very sensitive
- ELISA with patient’s serum against a variety of nuclear antigens, less sensitive but tells you what antibodies you have
- In the clinic: Start w/ ELISA, if negative proceed to HEp-2 assay
- Note that neither of these tests is specific for SLE, ANA may be secondary to several autoimmune conditions or to cancer
- This test is used to rule OUT SLE, not rule it in, its negative predictive value is much greater than its positive predictive value
Anti-dsDNA antibodies correlate well with the presence of ___
Anti-dsDNA antibodies correlate well with the presence of lupus nephritis
If your SLE patient displays low complement levels, you should . . .
. . . test them for a complement deficiency.
While Lupus flares can cause hypocomplementemia through complement consumption, Lupus is also epidemiologically associated with heritable complement deficiencies. So, the complement deficiency may be secondary to the Lupus, or the Lupus may be secondary to the complement deficiency.
Deficiency in the complement components ___ are associated with SLE.
Deficiency in the complement components C4A, C4B, C1q, and C2 are associated with SLE.
___ biopsy may aid in the diagnosis of Lupus.
Histopathologic findings include ___.
Skin biopsy may aid in the diagnosis of Lupus.
Histopathologic findings include basal layer vacuolar degeneration of keratinocytes and interface dermatitis. Immunofluorescence demonstrates deposition of IgG, IgA, IgM, and complement components along the dermoepidermal junction
On skin biopsy, ___ may appear identical to Lupus.
On skin biopsy, dermatomyositis may appear identical to Lupus.
Differential for Lupus
- Viral etiologies
- Parvovirus B19 (sometimes also presenting with ANA and hypocomplementemia)
- Cytomegalovirus
- Epstein-Barr virus
- Acute HIV infection
- Hep B and C (especially with arthritis)
- Malignant etiologies
- Non-Hodgkin’s lymphomas (cytopenias, rash, ANAs)
- Other leukemias or lymphomas
- Other autoimmune diseases
- Dermatomyositis
- Rheumatoid arthritis (arthritis with joint involvement is the same as SLE, but anti-citrullinated antibodies absent in SLE)
- Scleroderma
- Polymyositis
Drug-induced Lupus
- Usually manifests as polyarthritis, myalgia, fever, and serositis
- Minocycline, procainamide, hydralazine, isoniazid, interferon α, and anti-tumor necrosis factor (TNF) agents are well known culprits
- All these drugs cause a positive ANA and, with the exception of minocycline, anti-histone antibodies
Complications of SLE
- Accelerated atherosclerosis
- End-stage renal disease
- Infection (prophylaxis to Pneumocystis jirovecii specifically should be offered)
- Osteoporosis and avascular necrosis (mostly from chronic glucocorticoids, so it is important to use minimum possible dose to control symptoms, but SLE alone is a risk factor for avascular necrosis esp. of femoral head)
- Malignancy (esp. lymphomas (Hodgkin’s and non-Hodgkin’s, lung cancer, cervical cancer)
The highest risk for SLE-induced (or -permitted) cancer is . . .
. . . in the early years after diagnosis, strangely enough. Possibly because pre-cancerous lesions are already present in these patients and are being controlled until SLE or SLE treatment messes with the immune system.
Sjorgen syndrome
a chronic autoimmune disease characterized by lymphocytic infiltration of the salivary, lacrimal, and other exocrine glands, dryness of the eyes and mouth, and circulating autoantibodies
Sjorgen triad
Dry mouth
Dry eyes
Evidence of autoimmune disease
Sjorgen’s syndrome tends to affect. . .
. . . peri-menopausal or postmenopausal women
Sjorgen’s syndrome is associated with a hightened risk for ___.
Sjorgen’s syndrome is associated with a hightened risk for non-Hodgkin’s B cell lymphoma.
Pathologically, Sjorgen’s is characterized by. . .
. . . the presence of anti-SSA and anti-SSB antibodies (against small ribonucleoproteins), B cell hyperreactivity, and chronic inflammatory lesions surrounding the lacrimal and salivary glands
Management of Sjorgen’s is focused on. . .
. . . amelioration of the salivary and lacrimal dysfunction and the use of immunomodulatory or immunosuppressive drugs for certain extraglandular manifestations.
Frequent comorbidities of Sjorgen’s
Lupus
RA
Systemic sclerosis
Histopathology of Sjorgen’s in salivary glands
- termed “focal lymphocytic sialadenitis”
- Loss of acini
- Infiltrate surrounding the intralobular ducts or blood vessels and consisting primarily of CD4+ T and B cells (mostly B cells)
- Starts focally, may become more widespread in late phases of disease
- Lymphoid follicles with germinal centers may develop nearby glands
Sjorgen salivary gland
Note the chronic inflammation and the arrow depicting a lymphoid follicle and germinal center that has been generated
Healthy minor salivary gland
Sjorgen’s ocular manifestations
- Dryness, burning sensation, pruritis, soreness, photophobia, lack of tear production
- Exacerbated by dry air, wind/breezes, eye strain (from reading or staring at screen)
- Possible ocular complications
- Bacterial conjunctavitis
- Corneal abrasion or ulceration
Sjorgen’s oral manifestations
- Xerostomia = dry mouth
- Difficulty chewing and swallowing dry food, speaking at length, or wearing dentures
- Impaired or altered sense of taste, thick saliva, intolerance to acidic oir spicy food, burning sensation in mouth and tongue
- Complications
- Dry lips
- Dental decay
- Oral infection
Hyperlobulation of tongue observed in Sjorgen’s
Differential for Xerostomia
- Sjorgen’s or other salivary gland disease
- Drug side effect (on-target or off-target, think parasympathetic blockers)
- Diabetes mellitus
- Dehydration
- Mouth breathing secondary to nasal obstruction
- Head and neck irradiation (sometimes secondary to thyroid cancer treatment)
- Psychological factors
On examination of Sjorgen’s with oral involvement, ___ characteristically ___.
On examination of Sjorgen’s with oral involvement, the tongue blade characteristically sticks to the tongue and oral mucosa.
___ very often accompanies Sjorgen’s with oral involvement.
Thrush very often accompanies Sjorgen’s with oral involvement.
Bilateral parotid gland swelling
Acutely painful parotid gland swelling usually represents a supervening bacterial parotitis.
Slowly progressive enlargement of the glands should raise concern for the presence of glandular lymphoma, particularly when asymmetric.
SS is termed “secondary” when . . .
. . . it occurs with another systemic rheumatic disease. In the absence of another rheumatic disease, it is simply primary SS.
SS can be diagnosed in __% of patients with SLE and in __% of those with RA
SS can be diagnosed in 9% to 14% of patients with SLE and in 7% to 25% of those with RA
Patients with SS have substantially elevated risk for ___.
Patients with SS have substantially elevated risk for non-Hodgkin’s B cell lymphoma.
Markers of severe disease are associated with increased risk and include persistent parotid gland enlargement, palpable purpura, cryoglobulinemia, monoclonal proteins, hypocomplementemia, CD4+ lymphocytopenia, and the presence of GC-like structures in baseline labial gland biopsy specimens.
Most SS-associated lymphomas are . . .
Most SS-associated lymphomas are the marginal zone B-cell subtype, particularly those of MALT origin, and arise in the salivary glands
SS progresses ___ in the majority of patients in the absence of treatment
SS progresses very slowly in the majority of patients in the absence of treatment,
Diagnosis of Sjorgen’s
The diagnosis of SS is most often established with an objective measure of ocular dryness or salivary hypofunction coupled with evidence of underlying autoimmunity (anti-SSA or anti-SSB)
Labial gland biopsy
Labial salivary gland biopsy is essential for definitive evaluation of patients with suspected SS who lack both anti-SSA or anti-SSB antibodies or have weakly positive test results. May also prove useful to rule other diagnoses out.
Genetic susceptibility to Sjorgen’s
- Mostly MHC II genes
Sjorgen’s diagram
Lymphomagenesis in Sjorgen’s
- Generation of a lymphoid follicle within a tissue that supplies antigen leads to excessive proliferation and BAFF production
- BAFF induces anti-apoptotic Bcl-2 expression, driving longevity
- May induce MALT lymphoma
Patterns of autoantibody IF staining in SLE and Sjorgen’s
Interpreting the ANA
Extractable Nuclear Antigens
- Term for more specific antigen-antibody systems that can be helpful in diagnosis and disease monitoring
- Often checked if ANA is positive
Full lab workup for SLE
- ANA test
- Antiphospholipid test
- Urinalysis
- WBC count and differential
- Complement measurement
- Biopsy
Jaccoud’s arthropathy
Occurs in Lupus and rheumatic fever. Appears to have deformities similar to rheumatoid arthritis, but patient may effortlessly snap it back into normal position on command. The resting position of the joints has been altered, but they are not occluded.
___ on ANA is associated with scleroderma.
Nucleolar staining on ANA is associated with scleroderma.
non-___ ANA is uncommon in uncomplicated rheumatoid arthritis
non-citrullinated ANA is uncommon in uncomplicated rheumatoid arthritis
The only neonatal symptoms of lupus come from ____.
The only neonatal symptoms of lupus come from anti-Ro/anti-SSA.
___ is a classic place to find discoid rash in lupus patients.
The conchal bowl of the ear is a classic place to find discoid rash in lupus patients.
If you are treating a patient with kidney disease, ___ are out of the question.
If you are treating a patient with kidney disease, NSAIDs are out of the question.
Acanthocyte
Blebbing erythrocyte
