This document discusses systemic lupus erythematosus (SLE), including its pathophysiology, clinical manifestations, diagnostic criteria, and management. It outlines the 2019 EULAR classification criteria for SLE which uses 7 clinical and 3 immunological criteria weighted from 2 to 10, with a score of 10 or more required for classification. Treatment involves glucocorticoids, antimalarials like hydroxychloroquine, and immunosuppressives depending on disease severity.
SLE still an enigma where both patient and health care professionals are blind and do more harm than saving the patient. Hope in future anything can be done to save the patient from the grip of lupus,
SLE still an enigma where both patient and health care professionals are blind and do more harm than saving the patient. Hope in future anything can be done to save the patient from the grip of lupus,
This presentation encompasses SLE as well Lupus nephritis,Antiphospholipid Syndrome and other special situation related to SLE such as SLE and Pregnancy.
Systemic Lupus erythematous , is world wide health problem
Here we talk about criteria for diagnosis investigation , Management and complication
With some scenarios to about disease and complication
Recent advances in diagnosis & management of SLEShadab Ahmad
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue binding autoantibodies and immune complexes.
90 % of patients at diagnosis are women of childbearing age groups.
Highest prevalence is in black women and lowest is in white men.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
3. Introduction
• Systemic lupus erythematosus is a characterised
by abnormal immune response against body
organs and cells mediated by tissue binding
autoantibodies and immune complexes.
Source: Harrison textbook of internal Med, 20ed.
3
5. Genetic factors
• High incidence in monozygotic twins ( 24 to 57
percent)
• Sibling risk for developing SLE is 29 fold higher
than general population.
• Deficiencies of C1q,C2,C4 (rare)
• TREX1 mutations affecting DNA degradation
(rare)
5
6. GENES FOR LUPUS NEPHRITIS
HLA-DR3, STAT4, APOL1 (African Americans),
FCGR3A, ITGAM, IRF5, IRF7, TNFSF4
(Ox40L), DNAse1.
EPIGENETICS
Hypomethylation of DNA: In CD4+T, B and
monocytes.
Histone modifications: increased producton of
IFN.
6
7. Hormonal factors
Estrogen
1. Stimulates thymocytes, CD8+ and CD4+ T cells,
B cells.
2. Increased macrophage Proto-oncogene
expression.
3. Reduces apoptosis in self reactive B cells, thus
promotes maturation of autoreactive B cells.
7
8. • Progesterone
1. Down regulates T cell proliferation.
2. Increases CD8+ T cells.
3. Promotes Th2 response ->
autoantibody production.
8
9. Immune abnormalities
• Loss of self-tolerance.
• Autoantibodies against self-antigens.
• Phagocytosis and immune complex clearing are
defective in SLE.
• B cells are persistently activated by T helper
cells. (IL-6 and IL-10).
9
10. Environmental factors
• Epstein-Barr virus (EBV), trypanosomiasis or
mycobacterial infections- anti-DNA antibodies.
• Ultraviolet light- stimulates keratinocytes to
secrete more IL-1, IL-3, IL-6, TNF-alpha.
• Uv light interferes with T cell DNA methylation
(auto reactive T cells)
10
11. • Silica dust (cleaning powders, soil, pottery
materials, cement and cigarette smoking)-
increases risk of SLE.
• Allergic to antibiotics are more frequently seen in
SLE patients.
11
Environmental factors - cont’d
14. Clinical manifestations
• Clinical manifestations are mediated directly or
indirectly by antibody and immune complexes.
• These immune complexes will deposit in the
tissues with specific antigens.
• Compliment will act on these complexes causing
disease manifestations.
14
15. Major features
15
Constitutional symptoms
Fatigue is the most common complaint.
Fever - can be manifestation of active disease.
Myalgia and weight loss.
Arthritis and arthralgia occur in 90% of patients.
16. • Mucocutaneous involvement.
• Facial eruption (m/c) - acute cutaneous lupus.
• Oral and nasal ulcers.
• Non scarring alopecia.
• Scarring alopecia seen in discoid lupus.
16
17. Clinical manifestations- cont’d
Verrucous endocarditis with valvular vegetations
(arrows)
17
Cardiac manifestations.
Pericarditis
Endocarditis (libmann sach’s)
Myocarditis
Congenital heart block (anti-Ro,
anti-La/SSB)
Pericarditis, with or without an effusion, is the most common cardiac
manifestation of SLE, occurring in approximately 25 percent of patients at
some point during their disease course.
22. Renal manifestations
• They are usually asymptomatic.
• Urine analysis should be advised for all SLE
patients.
• Protein-creat ratio >/= 0.5.
• RBC casts.
22
29. ACLE -
malar rash
Erythematous maculopapaular
eruption involving primarily sun
exposed skin, extensor surface of
arm and hands more commonly
involved
Type to enter a caption.
29
34. Serological tests:
• antinuclear antibodies- ANA is screening test
because of its sensitivity (95%), low specificity.
• ANA negative lupus- other antibodies like anti-Ro
(SS-A), anti- ribosomal P.
• Typical features of lupus, negative ANA doesn’t
exclude diagnosis.
34
Source: EULAR textbook of rheumatic diseases.
35. Antibodies to extractable nuclear antigens
(ENAs)
• Autoantibodies to ssDNA, histones common in
SLE and drug induced lupus.
• ds-DNA found in 70% of SLE patients at some
point in course of illness- 95% specific for SLE.
• anti-Sm (smith) detected in 10-30% and
pathognomonic for SLE.
• anti-ribosomal- specific for SLE but less
sensitive.
35
Source: EULAR textbook of rheumatic diseases.
36. ACR criteria (1997)
36
Criteria Definition
alar rash
Fixed erythema, flat or raised, over malar eminences, sparing
nasolabial folds
iscoid rash
Erythematosus raised patches with adherent keratitis scaling
and follicular plugging.
erositis
Pleuritis: pleuritic pain or rub heard by physician or evidence of
pleural effusion
Pericarditis: documented ECG or rub or evidence of pericardial
effusion.
ral ulcers Oral or nasopharyngeal ulceration, usually painless.
37. 37
Criteria Definition
rthritis
Non erosive arthritis involving two or more peripheral joints-
tenderness, swelling or effusion.
hotosensitivit
y
Skin rash as a result of unusual reaction to sunlight.
Neurological Seizures, psychosis in the abscence of othe causes like
metabolic derangements and offending drugs.
enal disorder
Persistent protenuria- 0.5g/ day or >3+ if quantification not
performed.
Cellular casts: red call, hemoglobin, granular , tubular or mixed.
38. 38
Criteria Definition
NA
An abnormal titre of ANA by immunoflorescence or an
equivalent assay at any point in time and in the absence of
drugs associated with drug induced lupus.
mmunologic
Anti- DNA, Anti-Sm or positive findings of aPLs ( cardiolipin,
lupus anticoagulant)
aematologic
Haemolytic anemia with reticulocytosis
Leukopenia <4000/ mm3 total on two or more occasions.
Lymphopenia- <1500/ mm3 on two or more occasions.
Thrombocytopenia <100 000/ mm3 in the absence of
offending drugs.
Presence of any 4 out of 11 criteria is considered as SLE.
Sensitivity and specificity of 96%.
39. 39
EULAR criteria- (2019)
- early or new onset SLE
• seven clinical and
three immunological
criteria. Each
weighted from 2 to
10.
• Sensitivity 96.1%,
specificity 93.4%.
• Classify as SLE with
score of 10 or more.
Criteria for diagnosis.
Source: 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus
40. • Definite SLE - ACR 4/11 criteria or 2012 SLICC
4/17 including one in 1 in 11 clinical and 1/6
immunological
• Probable SLE- 2 or 3 criteria in ACR plus one
other feature 1) optic neuritis 2) glomerular
haematuria 2) pneumonic is 3 ) myocarditis 4)
raynaud phenomenon 5) abdominal vasculitis 6)
elevated ESR and CRP
• Possible SLE- Any one ACR or SLICC plus any
one above feature
40
42. Undifferentiated connective
tissue disorder
• Systemic rheumatic diseases have several
common features, making specific diagnosis
difficult.
• Only 10-15% patients with symptoms suggestive
of connective tissue disease fulfill classification
criteria of SLE after 5 years of follow up.
42
43. Treatment of non-renal SLE—recommended drugs with respective grading of recommendation. aPL, antiphospholipid
antibodies; AZA, azathioprine; BEL, belimumab; BILAG: British Isles Lupus Assessment Group disease activity index;
CNIs, calcineurin inhibitors; CYC, cyclophosphamide; GC, glucocorticoids; HCQ, hydroxychloroquine; IM, intramuscular;
MMF, mycophenolate mofetil; MTX, methotrexate; Pre, prednisone; PO, per os; RTX, rituximab; PLTs: Platelets; SLEDAI,
Systemic Lupus Erythematosus Disease Activity Index.
Source: Fanouriakis A, et al. Ann Rheum Dis 2019
43
44. Mild Moderate Severe
MAJOR ORGAN THREATENING
DISEASE (nephritis, celebrities,
myelitis, pneumonitis, mesentric
vasculitis
thrombocytopenia with platelets <20
x 103/mm3
TTP like disease or acute
hemophagocytic syndrome
SLEDAI >12
Source: Fanouriakis A, et al. Ann Rheum Dis 2019
44
46. Goals of treatment.
46
Recommendation LoE GoR
1 Treatment in SLE should aim at remission or low disease
activity and prevention of flares in all organs, maintained with the
lowest possible dose of glucocorticoids.
2b B
2 Flares of SLE can be treated according to the severity of
organ(s) involvement by adjusting ongoing therapies
(glucocorticoids, immunomodulating agents) to higher doses,
switching, or adding new therapies.
2b C
Source: 2018 EULAR recommendation for treatment
48. Glucocorticoids
48
Pharmacologic treatment- cont’d
Recommendation LoE GoR
1 Glucocorticoids can be used at doses and route of administration that depend
on the type and severity of organ involvement.
2b C
2 Pulses of intravenous methylprednisolone (usually 500–1000 mg per day, for
1–3 days) provide immediate therapeutic effect and enable the use of lower
starting dose of oral glucocorticoids.
3b C
3 For chronic maintenance treatment, glucocorticoids should be minimized to
less than 7.5 mg/day (prednisone equivalent) and, if possible, withdrawn.
1b B
4 Prompt initiation of immunomodulatory agents can expedite the
tapering/discontinuation of glucocorticoids.
2b B
Source: 2018 EULAR recommendation for treatment
49. Antimalarial- hydroxychloroquine
Recommendation LoE GoR
1 HCQ is recommended for all patients with SLE,
at a dose not exceeding 5 mg/kg/real BW.
1b A
3b C
2 In the absence of risk factors for retinal toxicity, ophthalmologic screening
(by visual fields examination and/or spectral domain-optical coherence
tomography) should be performed at baseline, after 5 years, and yearly
thereafter.
2b B
Pharmacologic treatment- cont’d
Source: 2018 EULAR recommendation for treatment 49
50. • Mild lupus (skin, joint, mucosal involvement)- HCQ with one
without prednisolone </= 7.5 mg/day.
• Moderate lupus (significant but non organ threatening-
constitutional , cutaneous, musculoskeletal or haematological) -
HCQ + prednisolone 5 to 15 mg/day +/- immunosuppressive Rx.
• Severe lupus (renal or CNS involvement)- methylprednisolone
0.5 to 1g/day for 3 days in acutely I’ll patients. Or 1 to
2mg/kg/day in stable patients.
50
Pharmacologic treatment- cont’d
Overview of Rx.
Source: Up-to-date
51. Source: 2018 EULAR recommendation for treatment
Recommendation LoE GoR
1 In patients not responding to HCQ (alone or in combination with glucocorticoids)
or patients unable to reduce glucocorticoids below doses acceptable for chronic
use, addition of immunomodulating/immunosuppressive agents such as
methotrexate 1b B
azathioprine 2b B
or mycophenolate should be considered. 2a B
2 Immunomodulating/immunosuppressive agents can be included in the initial
therapy in cases of organ-threatening disease.
2b C
3 Cyclophosphamide can be used for severe organ- or life-threatening SLE as well
as “rescue” therapy in patients not responding to other immunosuppressive agents.
2b C
Immunosuppressive treatment.
Pharmacologic treatment- cont’d
51
52. 52
Methotrexate: Systemic lupus erythematosus, moderate to severe : Oral: Initial: 7.5
mg once weekly; may increase by 2.5 mg increments weekly (maximum: 20 mg once
weekly), in combination with prednisone.
source: Harrison 20ed, SLE, table 349-5
Azathioprine: 2–3 mg/kg per day PO for induction; 1–2 mg/kg per day for
maintenance; decrease frequency of dose if CrCl <50 mL/min
Mycophenolate mofetil: MMF: 2–3 g/d PO total given bid for induction therapy, 1-2
g/d total given bid for maintenance therapy; max 1 g bid if CrCl <25 mL/min.Begin with
low dose and increase every 1–2 weeks to minimize GI side effects. Start treatment at
0.5 g bid.
Cyclophosphamide: Low dose (for whites of northern European backgrounds):
500mg every 2 weeks for 6 doses, then begin maintenance with MMF or AZA. High
dose: 7–25 mg/kg q month × 6; consider mesna administration with dose.
Pharmacologic treatment- cont’d
53. 53
Calcineurine inhibitors
Tacrolimus: Trough blood level should not exceed 5.5 ng/mL to minimise toxicity.
Begin dose at 2 mg bid.
S/E infection, nephrotoxicity, neural toxicity.
Pharmacologic treatment- cont’d
Cyclosporine inhibits T-cell activation of transcript. It is used in refractory skin
involvement, lupus Nephropathy, bone marrow hypoplasia.
Dose: 2.5 mg/kg/day in 2 divided doses.
source: Harrison 20ed, SLE, table 349-5
54. 54
Recommendation LoE GoR
1 In patients with inadequate response to standard-of-care
(combinations of hydroxychloroquine, glucocorticoids, other
immunomodulating agents), defined as residual disease activity
not allowing tapering of glucocorticoids and/or frequent relapses,
add-on treatment with belimumab should be considered.
1a A
2 In organ-threatening disease refractory or with
intolerance/contra-indications to standard immunosuppressive
agents, rituximab can be considered.
2b C
Biologicals
Pharmacologic treatment- cont’d
Source: 2018 EULAR recommendation for treatment
55. 55
Belimumab:
• human monoclonal antibody inhibits soluble form of B cell survival factor known
as BLyS or BAFF.
• Levels are elevated in patients of SLE in whom it keeps in formation and survival
of memory B cells and plasma blasts making autoantibodies.
• It is used in resistant cases of cutaneous and musculoskeletal disease.
• Contraindicated in lupus nephritis and active CNS involvement.
IV: Initial: 10 mg/kg every 2 weeks for 3 doses; Maintenance: 10 mg/kg every 4 weeks
SubQ: 200 mg once weekly
Switching from IV therapy: Administer the first SubQ dose 1 to 4 weeks after the last IV
dose.
Pharmacologic treatment- cont’d
Source: up-to-date
56. 56
Pharmacologic treatment- cont’d
Rituximab
• chimeric B cell depleting monoclonal antibody.
• It is usually used in severe disease burden especially in lupus nephritis as
a last resort.
Dose: 375 mg/m2 q wk × 4 (or) 1 g q 2 wks × 2.
S/E: infusion reactions, Hep B reactivation, PML, mucocutaneous reaction.
Source: up-to-date
57. 57
Management of specific
manifestations.
Recommendation LoE GoR
1 First-line treatment of skin disease in SLE includes
topical agents (glucocorticoids, calcineurin inhibitors) 2b B
antimalarials (HCQ, quinacrine) 1a A
systemic glucocorticoids. 4 C
2 In non-responsive cases or cases requiring high-dose
glucocorticoids,
methotrexate, 3a B
retinoids, dapsone, or mycophenolate can be added. 4 C
Skin manifestations.
Source: 2018 EULAR recommendation for treatment
58. 58
Management of specific manifestations - cont’d
Recommendation LoE GoR
1 Attribution to SLE - as opposed to non-SLE - related neuropsychiatric
manifestations, can be facilitated by neuroimaging, investigation of
cerebrospinal fluid, consideration of risk factors [type and timing of the
manifestation in relation to the onset of lupus, patient age, non-neurological
lupus activity, presence of antiphospholipid antibodies (aPL)] and exclusion
of confounding factors.
2b C
2 Treatment of SLE-related neuropsychiatric disease includes
glucocorticoids/immunosuppressive agents for manifestations
considered to reflect an inflammatory process
1b A
and antiplatelet/anticoagulants for atherothrombotic/aPL-related
manifestations.
2b C
Neuropsychiatric manifestations.
Source: 2018 EULAR recommendation for treatment
59. 59
Management of specific manifestations - cont’d
Recommendation LoE GoR
1 Acute treatment of lupus thrombocytopenia includes high-dose
glucocorticoids (including pulses of intravenous methylprednisolone)
and/or intravenous immunoglobulin.
4 C
2 For maintenance of response, IS/GC-sparing agents such as
mycophenolate, azathioprine,
2b C
or cyclosporine can be used. 4 C
3 Refractory cases can be treated with rituximab 3a C
or cyclophosphamide. 4 C
Haematological manifestations.
Source: 2018 EULAR recommendation for treatment
60. 60
Management of specific manifestations - cont’d
Recommendation LoE GoR
1 Early recognition of signs of renal involvement and - when present -
performance of a diagnostic renal biopsy are essential to ensure
optimal outcomes.
2b B
2 Mycophenolate 1a A
or low-dose IV cyclophosphamide are recommended as initial
(induction) treatment, as they have the best efficacy/toxicity ratio.
2a B
3 In patients at high risk for renal failure (reduced glomerular filtration
rate, histologic presence of crescents or fibrinoid necrosis, or tubular
atrophy/interstitial fibrosis], mycophenolate
2b B
or high-dose IV cyclophosphamide can be used. 1b A
4 For maintenance therapy, mycophenolate or azathioprine should
be used.
1a A
Renal disease.
Source: 2018 EULAR recommendation for treatment
61. 61
Management of specific manifestations - cont’d
Recommendation LoE GoR
5 In cases with stable/improved renal function but incomplete renal
response (persistent proteinuria >1 g/24h after at least one year of
immunosuppressive treatment), repeat biopsy can distinguish chronic
from active kidney lesions.
4 C
6 Mycophenolate may be combined with low dose of a calcineurin
inhibitor in severe nephrotic syndrome
2b C
or incomplete renal response, 4 C
in the absence of uncontrolled hypertension, high chronicity index at
kidney biopsy, and/or reduced GFR.
Renal disease.
Source: 2018 EULAR recommendation for treatment
62. 62
Source: 2018 EULAR recommendation for treatment
Comorbidities
Recommendation LoE GoR
1 All SLE patients should be screened at diagnosis for aPL. 1a A
2 SLE patients with high-risk aPL profile (persistently positive
medium/high titres or multiple positivity) may receive primary
prophylaxis with antiplatelet agents, especially if other
atherosclerotic/thrombophilic factors are present, after balancing the
bleeding hazard.
2a C
3 For secondary prevention (thrombosis, pregnancy
complication/loss), the therapeutic approach should be the same as
for primary anti-phospholipid syndrome.
1b B
Antiphospholipid antibody syndrome.
63. 63
Comorbidities - cont’d
Recommendation LoE GoR
1 SLE patients should be assessed for general and disease-related
risk factors for infections such advanced age/frailty (–/D), comorbidities
(–/D), renal involvement (2b/B), immunosuppressive/biologic therapy
(1b-2b/B-C) and high-dose glucocorticoids (1a/A).
2 General preventative measures (including immunizations) and early
recognition and treatment of infection/sepsis are recommended (–/D).
- D
Infection and immunisation.
Source: 2018 EULAR recommendation for treatment
65. 65
Comorbidities - cont’d
Recommendation LoE GoR
1 Patients with SLE should undergo regular assessment for traditional
(1b/B-C) and disease-related risk factors for cardiovascular disease,
including persistently active disease (1b/B), increased disease duration
(1b/A), medium/high titres of aPL (1b/A), renal involvement (1b/B)
(especially, persistent proteinuria and/or GFR <60 ml/min) and chronic
use of glucocorticoids (1b/B).
2 Based on their individual cardiovascular risk profile, SLE patients may
be candidates for prevention with low-dose aspirin.
2b D
and/or lipid-lowering agents. (Atorvastatin or fluvastatin) 2b D
Cardiovascular.
Source: 2018 EULAR recommendation for treatment