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Questions and Answers
Which of the following genetic factors is associated with an increased risk of autoimmune diseases?
Smoking is considered a significant genetic risk factor for autoimmune diseases.
False
Name one environmental factor that is a known trigger for autoimmune diseases.
UV-B rays
A major environmental factor that can contribute to autoimmune diseases is __________.
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Match the following risk factors to their categories:
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What is the female to male ratio in SLE prevalence?
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Postmenopausal SLE generally has a poor prognosis.
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What are the two key serology markers for active SLE?
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SLE has a strong family history with positive concordance in ______% of identical twins.
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Match the symptoms or markers with their corresponding characteristics in SLE.
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What test is performed to confirm the presence of antibodies when ANA is positive?
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ANA positivity is diagnostic for rheumatoid arthritis.
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In which condition is ANA positive in 100% of cases?
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In Drug-induced Lupus Erythematosus (DILE), 100% of cases are ANA __________.
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Match the following conditions with their respective ANA positivity percentages:
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How long before the onset of clinical features do antibodies typically appear in Systemic Lupus Erythematosus (SLE)?
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Anti-nuclear antibody (ANA) patterns can help in identifying different connective tissue disorders.
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What antibody is associated with Drug Induced SLE?
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In Systemic Sclerosis (SSC), the likely antibody pattern observed is associated with __________.
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Match the following ANA patterns with their associated diseases:
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What is the most common presentation of Type 1 autoimmune pancreatitis?
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The sausage-shaped pancreas appearance on CT is characteristic of Type 2 autoimmune pancreatitis.
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What is the most common renal manifestation associated with Type 1 autoimmune pancreatitis?
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Enlargement of the lacrimal gland is known as __________.
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Match the manifestations with their corresponding details:
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Which toll-like receptors are associated with the immune response in SLE?
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Type I Interferon (IFNα) is a key pathogenic cytokine upregulated in SLE.
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What is the minimum score required for the diagnosis of Primary Sjogren's Syndrome?
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Histopathology showing focal lymphocytic sialadenitis with a focus of > 21/4 mm3 contributes 3 points towards the classification score for Sjogren's Syndrome.
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What type of immune response do plasmacytoid dendritic cells (PDCs) primarily activate?
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Hydroxychloroquine (HCQ) is primarily used to treat __________.
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What needs to be present alongside at least one symptom of ocular/oral dryness for the diagnosis of Primary Sjogren's Syndrome?
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The presence of anti-____ antibodies contributes 3 points towards the Sjogren's Syndrome classification score.
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Match the immune cells with their respective functions in SLE:
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Match the criteria items with their corresponding scores in the classification of Sjogren's Syndrome:
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Which of the following is NOT a clinical manifestation associated with IgG4 related disease?
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Elevated IgG4 levels are correlated with disease activity in IgG4 related disease.
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What is the first line treatment for IgG4 related disease?
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The presence of __________ is a better marker than elevated IgG4 levels.
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Match the following terms with their descriptions:
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Which of the following diseases is part of the IgG4 related disease spectrum?
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In which condition would the salivary gland enlargement response to steroid treatment be higher?
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Chronic sinusitis and nasal obstruction with eosinophilia are common history findings in IgG4 related disease.
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IgG4 is the most common type of immunoglobulin in the human body.
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What is the most potent fibrogenic cytokine associated with IgG4 related diseases?
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What is indicated by a good prognosis in patients with IgG4 related disease?
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The IgG4 predominant plasma lymphocytic infiltrate activates ______ which then produces fibrogenic cytokines.
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Match the following diseases with their associated conditions in the IgG4 related disease spectrum:
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Which antibody is positive in approximately 50% of Sjogren's syndrome cases?
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A negative ANA result in a suspected Sjogren's syndrome case rules out the disease.
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What is the gold standard investigation for diagnosing Sjogren's syndrome?
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In Sjogren's syndrome, the pattern described as 'fine speckled' suggests the presence of __________ antibodies.
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Match the following tests with their significance in Sjogren's syndrome:
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Study Notes
Etiology
-
Genetic Factors:
- HLA DR3 associated with Subacute cutaneous Lupus
- Non-HLA factors like early complement deficiency: C1q deficiency is the strongest risk factor, followed by C4 and C2 deficiency.
- Increased number of X-chromosomes associated with increased risk.
- IRAK gene on the X-chromosome.
- TREX gene on chromosome 3.
-
Environmental Factors:
- Oral contraceptive pills (OCP)
- Hormonal replacement Therapy (HRT)
- UV-B rays
- Epstein-Barr virus
- Silicosis: Exposure can stimulate pulmonary alveolar macrophages leading to an autoimmune trigger.
- Vitamin D deficiency
- Smoking
Features of SLE
- Predominantly affects women in reproductive age (20-40 years) with a 9:1 female to male ratio.
- There is a strong family history, with over 40% of identical twins having positive concordance.
Lupus Nephritis
- Occurs in 50-60% of adult cases.
- Almost 100% of children with SLE develop lupus nephritis.
Postmenopausal SLE
- SLE diagnosed after menopause has generally a good prognosis, especially if patients do not experience CNS or renal symptoms.
- Common symptoms include dryness, serositis, musculoskeletal symptoms, and presence of Anti Ro antibodies.
- Anti-dsDNA antibodies are usually absent, and complements are often normal.
Male SLE
- Often presents a poorer prognosis.
Active SLE
- Anti-dsDNA antibodies and decreased complement levels are good markers of active SLE.
Diagnosis
- ANA (Anti-Nuclear Antibody) is a screening test for connective tissue disorders (CTD).
- If positive:
- Quantitative assessment by ELISA
- Indirect IF: Titre higher than 1:80
- Hep 2: Positive
- If positive:
- IIF (Indirect Immunofluorescence) pattern helps differentiate potential CTD, based on antibodies.
- Dense fine speckled pattern: Suggest anti Ro/La, likely Sjogren's
- Fine speckled pattern: Suggestive of anti Smith (Sm) antibodies, likely pointing to SLE.
- Coarse speckled pattern: Associated with anti Ul RNP antibodies, indicating mixed connective tissue disease (MCTD).
- Nucleolar pattern: Associated with anti Jo I antibodies, likely polymyositis or dermatomyositis (antisynthetase syndrome)
- ANA profile: Provides information about the specific antibodies present.
- Done once, not repeated as it is costly.
- ENA profile (Extractable nuclear antigen): Tests for 6 antibodies.
- 100% of MCTD cases are ANA positive.
- 85% of Sjogren's syndrome cases are ANA positive.
- 50% of IgG4 related disease cases are ANA positive.
- ANA is not diagnostic for rheumatoid arthritis, although it can be found in 97% of SLE cases.
Clinical Approach in SLE
- Drug-induced Lupus Erythematosus is characterized by 100% ANA positivity, a homogenous pattern on IIF, and positive anti-histone antibodies.
- Procainamide is a common cause.
- Elderly SLE frequently shows positive Anti Ro antibodies even with negative ANA.
IgG4 Related Disease
- Presence of elevated IgG4 levels.
Associated findings with IgG4 Related Disease
- Primary sclerosing cholangitis in the bile duct.
- Non-specific interstitial pneumonia (NSIP) and thickening of the bronchovascular bundle in the lungs.
- Periaortitis and associated paravertebral mass in the aorta.
- Membranonephropathy is often associated with low complement levels.
- RCD 2020 criteria include pathologic findings, serology (elevated IgG4), and clinical features.
- Miklulicz Disease: Enlargement of salivary glands (parotid, submandibular, and lacrimal).
- High likelihood of chronic sinusitis, nasal obstruction with eosinophilia.
- IgG4/IgG ratio is often a better marker than just IgG4.
- Prognosis is good with a positive response to steroids.
Sjogrens Syndrome vs IgG4 Related Disease
- Salivary gland enlargement is present in both.
- Sicca symptoms are more common in IgG4 related disease.
- Response to steroids is good in IgG4 related disease, and the symptoms are not responsive in Sjogren's.
Manifestations of IgG4 Related Disease
-
Type 1 autoimmune pancreatitis: Most common manifestation, presenting with obstructive jaundice.
- ERCP: Diffuse irregular narrowing of the pancreatic duct
- Sausage pancreas on CT.
- ERCP: Diffuse irregular narrowing of the pancreatic duct
- Salivary glands: Painless enlargement of the submandibular gland with minimal sicca symptoms.
- Orbital/periorbital lesions: Orbital inflammatory pseudo tumors
- Lacrimal gland: Enlargement known as dacryoadenitis.
- Retroperitoneal fibrosis:
- CNS: Lymphocytic hypophysitis (post-partum women, associated with increased intracranial pressure), Pachymeningitis (no parenchymal involvement).
- Kidney: Tubulointerstitial disease is most common, and it may lead to CKD.
- Image: Sausage-shaped pancreas with feathery borders on CT scan. Non-tender enlargement of the submandibular gland.
Pathogenesis of SLE
- Dysregulation of immune system arising from a combination of genetic and environmental factors.
- Defective clearance of apoptotic and neutrophil extracellular trap (NET) debris.
- Activation of innate immune system via TLR-7 and TLR-9, which are pattern recognition receptors.
- Hydroxychloroquine (HCQ) blocks these TLRs.
- Activation of plasmacytoid dendritic cells (PDCs).
- Anifrolumab targets type 1 interferons (IFNα) produced by PDCs.
- Activation of APCs (professional antigen-presenting cells): macrophages and Langerhans dendritic cells.
- Type I interferons (IFNα), a key pathogenic cytokine in SLE, leads to endothelial injury.
- Upregulation of CD40 ligand, involved in CD40 interaction, and B-lymphocyte stimulator (BLYS) in SLE.
- Belimumab targets BLYS, thereby inhibiting B cell activation.
- Formation of immune complexes leads to tissue deposition via type 3 hypersensitivity reactions.
- Deposition in glomerulus: causing glomerulonephritis
- Deposition in synovial cavity: causing synovitis
- Deposition in vessels: causing vasculitis
Pathogenesis of IgG4 Related Disease
- Antigenic stimuli trigger the infiltration of IgG4-predominant plasma lymphocytes.
- These cells activate myofibroblasts which then release TGF-β and PDGF, leading to fibrosis.
- TGF-β is the most potent fibrogenic cytokine.
Sjogren's Syndrome
- Associated with Lymphocytic Interstitial Pneumonitis (LIP), along with HIV.
- Anti-Nuclear antibodies are positive in 85% of Sjogren's cases.
- Anti Ro/La antibodies are often present when ANA is negative.
- Anti Ro is positive in 50% of cases.
- Anti LA is positive in 33% of cases.
- The fine speckled pattern of the ANA suggests anti Ro/La.
Investigations for Sjogren's Syndrome
- Minor salivary gland biopsy is the gold standard.
- Sialography is no longer commonly used.
- USG of salivary glands can demonstrate a loss of homogenicity.
Criteria for Diagnosis of Sjogren's Syndrome
- 2016 American College of Rheumatology/European League Against Rheumatism Classification:
- Primary Sjogren's diagnosis requires at least one symptom of ocular or oral dryness and a total score of 24 points based on specific criteria.
- Scoring system: Points are awarded for histological findings (focal lymphocytic sialadenitis), presence of Anti-Ro/SS-A antibodies, SICCA ocular staining, Rose Bengal score, Schirmer's test, and unstimulated whole salivary flow rate.
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Description
Test your knowledge on the etiology and key features of Systemic Lupus Erythematosus (SLE). This quiz covers genetic and environmental factors contributing to SLE, as well as its impact on different demographics. Dive into the specifics of Lupus nephritis and learn more about this complex autoimmune disease.
