7 medicine rheumatology
DESCRIPTION
RheumatologyTRANSCRIPT
RHEUMAT & IMMUNOLOGY
DR.SRINATH.CHANDRAMANI
ASST PROF & ICU-INCHARGE
K.J.SOMAIYA HOSPITAL
MUMBAI
INTRODUCTION TO IMMUNE SYSTEM
• Immunity is broadly divided into :
- Innate immunity
- Adaptive immunity
• Individual constituents are the Monocyte-Macrophage system, Dendritic cells, NK cells and the Granulocytes (N, E and Basophils)
• T-Cells and B-cells respectively.
• Other Mediators of immunity are :
- Immunoglobulins
- Interferons
- Complement cascade
INTRODUCTION TO IMMUNE SYSTEM
Deficiencies of the Innate Immune System
Phagocytic cells: - Impaired production: severe congenital neutropenia (SCN) - Asplenia - Impaired adhesion: leukocyte adhesion deficiency (LAD) - Impaired killing: chronic granulomatous disease (CGD) Innate immunity receptors and signal transduction: - Defects in Toll-like receptor signaling - Mendelian susceptibility to mycobacterial disease Complement deficiencies: - Classical, alternative, and lectin pathways - Lytic phase
IMMUNO-DEFICIENCY DISORDERS
IMMUNO-DEFICIENCY DISORDERS
Deficiencies of the Adaptive Immune System
T lymphocytes:
- Impaired development Severe combined immune deficiencies (SCIDs) DiGeorge syndrome
- Impaired survival, migration, function
Severe combined immunodeficiencies Hyper-IgE syndrome (autosomal dominant) CD40 ligand deficiency Wiskott-Aldrich syndrome Ataxia-telangiectasia and other DNA repair deficiencies
B lymphocytes:
- Impaired development XL and AR agammaglobulinemia
- Impaired function Hyper-IgM syndrome Common variable immunodeficiency (CVID) IgA deficiency
AUTO-IMMUNITY Major Criteria
1. Presence of autoantibodies or evidence of cellular reactivity to self
2. Documentation of relevant autoantibody or lymphocytic infiltrate in the pathologic lesion
3. Demonstration that relevant autoantibody or T cells can cause tissue pathology
a. Transplacental transmission
b. Adaptive transfer into animals
c. In vitro impact on cellular function Supportive Evidence
Supportive Evidence
1. Reasonable animal model
2. Beneficial effect from immunosuppressive agents
3. Association with other evidence of autoimmunity
4. No evidence of infection or other obvious cause
Organ Specific
Graves' disease Vitiligo
Hashimoto's thyroiditis Autoimmune hemolytic anemia
Autoimmune polyglandular syndrome Autoimmune thrombocytopenic purpura
Type 1 diabetes mellitus Pernicious anemia
Insulin-resistant diabetes mellitus Myasthenia gravis
Immune-mediated infertility Multiple sclerosis
Autoimmune Addison's disease Guillain-Barré syndrome
Pemphigus vulgaris Stiff-man syndrome
Pemphigus foliaceus Acute rheumatic fever
Dermatitis herpetiformis Sympathetic ophthalmia
Autoimmune alopecia Goodpasture's syndrome
Organ Nonspecific (Systemic)
Systemic lupus erythematosus Granulomatosis with polyangiitis (Wegener's)
Rheumatoid arthritis Antiphospholipid syndrome
Systemic necrotizing vasculitis Sjögren's syndrome
FINALLY – THE FINAL TEN • HYPERSENSITIVITY REACTIONS
• SLE
• ANTIPHOSPHOLIPID ANTIBODY SYNDROME
• SYSTEMIC SCLEROSIS / SCLERODERMA
• RA
• SJOGREN’S SYNDROME / SICCA SYNDROME
• SPONDYLOARTHROPATHY
• VASCULITIS
• BEHCET’S
• MIXED CONNECTIVE TISSUE DISORDER
HYPERSENSITIVITY REACTIONS
TYPE 1 - ANAPHYLAXIS
TYPE 2 – ANTIBODY MEDIATED REACTION
TYPE 3 – SERUM SICKNESS
TYPE 4 - DELAYED HYPERSENSITIVITY
SLE • PROTOTYPE OF AUTO-IMMUNE DISORDERS
• EPIDEMIOLOGY
• DIAGNOSTIC CRITERIA
• ANTIBODIES
• TREATMENT
ANTIPHOSPHOLIPID AB SYNDROME
• EPIDEMIOLOGY
• ANTIBODIES
• CLINICAL FEATURES
• DIAGNOSIS
• TREATMENT
• IN PREGNANCY
Rheumatoid arthritis
• Definition
• Epidemiology
• Diagnostic Criteria – 4/7 : arthritis > 6 weeks
symmetric joint involvement
> 3 small joint involvement - MCP, Wrist, PIP
morning stiffness > 1 hour
Subcutaneous nodules
RA factor
X-ray suggestive of joint erosions
SCLERODERMA
• Epidemiology
• Diagnostic criteria ( next slide )
SCLERODERMA LOCALSISED
SCLERODERMA DIFFUSE SCLERODERMA
SKIN INVOLVEMENT DISTAL TO ELBOWS, FACE GENERALISED, TRUNK
RAYNAUD’S PHENOMENON
PRECEDES SKIN, PROMINENET
LATE
PULMONARY INVOLVEMENT
LATE/NEVER EARLY
RENAL RARE EARLY/FLORID
CALCINOSIS CUTIS EARLY LATE
ANTIBODY ANTI CENTROMERE ANTI TOPOISO 1
Mixed Connective Tissue Disease
• Patients who have lcSSc coexisting with features of SLE, polymyositis, and rheumatoid arthritis may have mixed connective tissue disease (MCTD).
• This overlap syndrome is generally associated with the presence of high titers of autoantibodies to U1-RNP.
• The characteristic initial presentation is Raynaud's phenomenon associated with puffy fingers and myalgia. Gradually, lcSSc features of sclerodactyly, calcinosis, and cutaneous telangiectasia develop. Skin rashes suggestive of systemic lupus erythematosus (malar rash, photosensitivity) or of dermatomyositis (heliotrope rash on the eyelids, erythematous rash on the knuckles) occur.
• Arthralgia is common, and some patients develop erosive polyarthritis. Pulmonary fibrosis and isolated or secondary PAH may develop.
• While anti-U1RNP antibodies are detected in the serum in high titers, SSc-specific autoantibodies are not found. In contrast to SSc, patients with MCTD often show a good response to treatment with glucocorticoids, and the long-term prognosis is better than that of SSc. Whether MCTD is a truly distinct entity or is, rather, a subset of SLE or SSc remains controversial.
Sjogren’s syndrome
• Also called Sicca syndrome
• Lymphocytic infiltration of exocrine glands leading to its manifestatikons.
• The diagnostic criteria are as follows :
ACR Classification Criteria for Sjogren syndrome 2012
SPONDYLOARTHROPATHY
• ANKYLOSING SPONDYLOSIS
• REACTIVE ARTHRITIS
• INFLAMMATORY BOWEL RELATED ARHTRITIS
• GOUT
PSOARITIC ARTHROPATHY The Caspar (CLassification Criteria for Psoriatic Arthritis) Criteriaa
To meet the CASPAR criteria, a patient must have inflammatory articular disease (joint, spine, or entheseal) with 3 points from any of the following five categories: 1.Evidence of current psoriasis,b, c a personal history of psoriasis, or a family history of psoriasisd 2.Typical psoriatic nail dystrophye observed on current physical examination 3.A negative test result for rheumatoid factor 4.Either current dactylitisf or a history of dactylitis recorded by a rheumatologist 5.Radiographic evidence of juxtaarticular new bone formationg in the hand or foot
GOUT
• Gout – Mono Sodium Urate crystals
• Pseudo-Gout – CPPD
• Calium apatite crystals.
VASCULITIS • Classification based on caliber of blood vessel involved: • I. Large vessel vasculitis:
Giant cell arteritis Takayasu’s arteritis
• II. Medium vessel vasculitis: Polyarteritis nodosa Kawasaki disease III. Small vessel vasculitis: Microscopic polyangiitis Leukocytoclastic vasculitis Wegener’s granulomatosis Churg-Strauss disease
BEHCET’S SYNDROME
Behçet's syndrome is a clinicopathologic entity characterized by recurrent episodes of oral and genital ulcers, iritis, and cutaneous lesions. The underlying pathologic process is a leukocytoclastic venulitis, although vessels of any size and in any organ can be involved.
Miscellaneous Disorders
• Fibromyalgia
• Periarthritis – Frozen shoulder