7 Medicine Rheumatology

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