Medicine Marrow Pg No 447-456 (Rheumatology)
53 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of the following genetic factors is associated with an increased risk of autoimmune diseases?

  • C4 deficiency (correct)
  • Epstein-Barr virus
  • UV-B rays
  • HLA DR3 (correct)

    • 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 __________.

    <p>Hormonal replacement therapy</p> Signup and view all the answers

    Match the following risk factors to their categories:

    <p>HLA DR3 = Genetic C1q deficiency = Genetic UV-B rays = Environmental Epstein-Barr virus = Environmental</p> Signup and view all the answers

    What is the female to male ratio in SLE prevalence?

    <p>9:1</p> Signup and view all the answers

    Postmenopausal SLE generally has a poor prognosis.

    <p>False</p> Signup and view all the answers

    What are the two key serology markers for active SLE?

    <p>Anti ds-DNA and low complements</p> Signup and view all the answers

    SLE has a strong family history with positive concordance in ______% of identical twins.

    <p>40</p> Signup and view all the answers

    Match the symptoms or markers with their corresponding characteristics in SLE.

    <p>Anti Ro+ = Good prognosis No CNS/renal symptoms = Good prognosis Low complements = Active SLE Anti ds-DNA = Active SLE</p> Signup and view all the answers

    What test is performed to confirm the presence of antibodies when ANA is positive?

    <p>Immunoblot</p> Signup and view all the answers

    ANA positivity is diagnostic for rheumatoid arthritis.

    <p>False</p> Signup and view all the answers

    In which condition is ANA positive in 100% of cases?

    <p>Mixed connective tissue disease (MCTD)</p> Signup and view all the answers

    In Drug-induced Lupus Erythematosus (DILE), 100% of cases are ANA __________.

    <p>positive</p> Signup and view all the answers

    Match the following conditions with their respective ANA positivity percentages:

    <p>Mixed Connective Tissue Disease = 100% Sjogren's Syndrome = 85% IgG4 Related Disease = 50%</p> Signup and view all the answers

    How long before the onset of clinical features do antibodies typically appear in Systemic Lupus Erythematosus (SLE)?

    <p>3 years</p> Signup and view all the answers

    Anti-nuclear antibody (ANA) patterns can help in identifying different connective tissue disorders.

    <p>True</p> Signup and view all the answers

    What antibody is associated with Drug Induced SLE?

    <p>Antihistone</p> Signup and view all the answers

    In Systemic Sclerosis (SSC), the likely antibody pattern observed is associated with __________.

    <p>Anti RNA polymerase 3</p> Signup and view all the answers

    Match the following ANA patterns with their associated diseases:

    <p>Cytoplasmic = SLE Nucleolar = Polymyositis, Dermatomyositis Homogeneous = CREST syndrome Fine speckled = Sjogren</p> Signup and view all the answers

    What is the most common presentation of Type 1 autoimmune pancreatitis?

    <p>Obstructive jaundice</p> Signup and view all the answers

    The sausage-shaped pancreas appearance on CT is characteristic of Type 2 autoimmune pancreatitis.

    <p>False</p> Signup and view all the answers

    What is the most common renal manifestation associated with Type 1 autoimmune pancreatitis?

    <p>Tubulointerstitial disease</p> Signup and view all the answers

    Enlargement of the lacrimal gland is known as __________.

    <p>dacryoadenitis</p> Signup and view all the answers

    Match the manifestations with their corresponding details:

    <p>Type 1 autoimmune pancreatitis = Obstructive jaundice Salivary gland involvement = Painless submandibular enlargement Lacrimal gland involvement = Dacryoadenitis CNS manifestations = Pachymeningitis</p> Signup and view all the answers

    Which toll-like receptors are associated with the immune response in SLE?

    <p>TLR-7 and TLR-9</p> Signup and view all the answers

    Type I Interferon (IFNα) is a key pathogenic cytokine upregulated in SLE.

    <p>True</p> Signup and view all the answers

    What is the minimum score required for the diagnosis of Primary Sjogren's Syndrome?

    <p>24</p> Signup and view all the answers

    Histopathology showing focal lymphocytic sialadenitis with a focus of > 21/4 mm3 contributes 3 points towards the classification score for Sjogren's Syndrome.

    <p>True</p> Signup and view all the answers

    What type of immune response do plasmacytoid dendritic cells (PDCs) primarily activate?

    <p>Innate immune response</p> Signup and view all the answers

    Hydroxychloroquine (HCQ) is primarily used to treat __________.

    <p>SLE</p> Signup and view all the answers

    What needs to be present alongside at least one symptom of ocular/oral dryness for the diagnosis of Primary Sjogren's Syndrome?

    <p>A total score of 24 from the classification criteria.</p> Signup and view all the answers

    The presence of anti-____ antibodies contributes 3 points towards the Sjogren's Syndrome classification score.

    <p>Ro/SS-A</p> Signup and view all the answers

    Match the immune cells with their respective functions in SLE:

    <p>Macrophage = Professional Antigen Presenting Cell Langerhans dendritic cell = Professional Antigen Presenting Cell B-Lymphocyte stimulator (BLYS) = Stimulates B cells Plasmacytoid dendritic cells (PDCs) = Activates Innate immune system</p> Signup and view all the answers

    Match the criteria items with their corresponding scores in the classification of Sjogren's Syndrome:

    <p>Histopathology showing focal lymphocytic sialadenitis = 3 Presence of anti-Ro/SS-A antibodies = 3 SICCA ocular staining ≥5 = 3 Schirmer's test ≥5 mm/5 minutes = 1</p> Signup and view all the answers

    Which of the following is NOT a clinical manifestation associated with IgG4 related disease?

    <p>Diabetes mellitus</p> Signup and view all the answers

    Elevated IgG4 levels are correlated with disease activity in IgG4 related disease.

    <p>True</p> Signup and view all the answers

    What is the first line treatment for IgG4 related disease?

    <p>Steroid</p> Signup and view all the answers

    The presence of __________ is a better marker than elevated IgG4 levels.

    <p>19G4/IgG Ratio</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Mikulicz Disease = Enlargement of parotid and lacrimal glands Non-specific interstitial pneumonia (NSIP) = Lung manifestation in IgG4 disease Membranonephropathy = Associated with low complements in IgG4 disease Rituximab = Steroid-sparing agent to prevent relapse</p> Signup and view all the answers

    Which of the following diseases is part of the IgG4 related disease spectrum?

    <p>Type 1 autoimmune pancreatitis</p> Signup and view all the answers

    In which condition would the salivary gland enlargement response to steroid treatment be higher?

    <p>IgG4 related disease</p> Signup and view all the answers

    Chronic sinusitis and nasal obstruction with eosinophilia are common history findings in IgG4 related disease.

    <p>True</p> Signup and view all the answers

    IgG4 is the most common type of immunoglobulin in the human body.

    <p>False</p> Signup and view all the answers

    What is the most potent fibrogenic cytokine associated with IgG4 related diseases?

    <p>TGF-β</p> Signup and view all the answers

    What is indicated by a good prognosis in patients with IgG4 related disease?

    <p>Good response to treatment and management</p> Signup and view all the answers

    The IgG4 predominant plasma lymphocytic infiltrate activates ______ which then produces fibrogenic cytokines.

    <p>myofibroblasts</p> Signup and view all the answers

    Match the following diseases with their associated conditions in the IgG4 related disease spectrum:

    <p>Mikulicz disease = Lymphocytic infiltration of glands Riedel's thyroiditis = Fibrosis of the thyroid Primary sclerosing cholangitis = Fibrosis of bile ducts Periaortitis = Fibrosis around the aorta</p> Signup and view all the answers

    Which antibody is positive in approximately 50% of Sjogren's syndrome cases?

    <p>Anti Ro</p> Signup and view all the answers

    A negative ANA result in a suspected Sjogren's syndrome case rules out the disease.

    <p>True</p> Signup and view all the answers

    What is the gold standard investigation for diagnosing Sjogren's syndrome?

    <p>Minor salivary gland biopsy</p> Signup and view all the answers

    In Sjogren's syndrome, the pattern described as 'fine speckled' suggests the presence of __________ antibodies.

    <p>anti Ro/La</p> Signup and view all the answers

    Match the following tests with their significance in Sjogren's syndrome:

    <p>ANA = Screening test for connective tissue disease Sialography = Measures salivary flow rate Salivary gland USG = Assesses gland homogenicity Minor salivary gland biopsy = Gold standard for diagnosis</p> Signup and view all the answers

    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
    • 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.
    • Presence of elevated IgG4 levels.
    • 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.
    • 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.
    • Type 1 autoimmune pancreatitis: Most common manifestation, presenting with obstructive jaundice.
      • ERCP: Diffuse irregular narrowing of the pancreatic duct
        • Sausage pancreas on CT.
    • 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
    • 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.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    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.

    More Like This

    SLE
    30 questions

    SLE

    UserFriendlyIntelligence avatar
    UserFriendlyIntelligence
    Systemic Lupus Erythematosus Overview
    15 questions

    Systemic Lupus Erythematosus Overview

    PlushAloe avatar
    PlushAloe
    Systemic Lupus Erythematosus Definition Quiz
    31 questions

    Systemic Lupus Erythematosus Definition Quiz

    ComplementaryMachuPicchu avatar
    ComplementaryMachuPicchu
    Systemic Lupus Erythematosus (SLE): Symptoms, Autoimmune Response, and Diagnosis
    12 questions

    Systemic Lupus Erythematosus (SLE): Symptoms, Autoimmune Response, and...

    FieryFractal avatar
    FieryFractal
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser