Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Dermatology(saculitis)
2. Vasculitis- Inflammation of blood vessels
characterised by leucocytic infiltration of the
vessel walls
Different patterns of vessels’ involvement in
different entities
Vessel lumen compromisedischemia of the
corresponding organ
3. • 3 main groups of pathogenetic mechanisms
behind vasculitis-
1. Immune complex formation
2. ANCA mediated
3. T lymphocyte mediated with Granuloma
formation
4. • Henoch Schonlein purpura- IgA mediated
• SLE & other collagen vascular diseases-
ANA
• Serum sickness
• Polyarteritis Nodosa- Hepatitis B ag
• Essential Mixed Cryoglobinemia- Hepatitis
C virion
*deposition of immune complexes in the blood
vesselsactivation of
complementsdestruction of vessel wall
(acute & chronic inflammation)
5. • P-ANCA (anti-proteinase 3)- Wegener’s
• C-ANCA (anti-MPO)
- Churg Strauss vasculitis
- Microscopic Polyangiitis
- Wegener’s granulomatosis
* Aberrant expression of proteinase 3 and MPO
over the surface of the neutrophilsformation
of antibodiesdestruction of
neutrophilsvessel wall damage
7. • Giant cell arteritis
• Takayasu’s arteritis
• Wegener’s granulomatosis
• Churg Strauss vasculitis
*classical granuloma formation (giant cells and
epitheloid cells in a backround of fibrinoid
necrosis) can be demonstrated in the
corresponding vessel biopsy
26. Temporal arteritis
Elderly persons more than 50 yrs. of age
Non specific symptoms, Headache, Elevated
ESR
BLINDNESS-most serious complication
Jaw claudication, Scalp pain, Scalp Tenderness
Polymyalgia Rheumatica- different end of the
spectrum of Giant Cell Arteritis
28. Pulseless Disease
Middle aged females
Aorta and its branches mainly involved
Subclavian vessels, Carotid vessels, Mesentric
vessels
Chronic and Relapsing course
30. Renal arteries most commonly involved
leading to renovascular hypertension
Pulmonary vessels NEVER involved
Association with patients of
o Hepatitis B
o Hairy cell leukemia
31. MucoCutaneous Lymph node syndrome
Children < 5 years of age mostly
Desquamative erythematous rashes involving
the skin, mucus membranes, cervical
lymphadenopathy
25 % develop coronary artery aneurysms in the
convalescent stage of the illness
34. Usually Pulmonary capillaritis PLUS
Glomerulonephritis
•Granulomas +, Asthma + Churg Strauss
•Granulomas +, NO asthma Wegener’s
•NO granulomas, NO asthma Microscopic
Polyangiitis
35. • Classical triad URT + LRT + renal
• Chronis sinusitis, Pulmonary nodules,
Pulmonary cavities, Rapidly Progressive
Glomerulonephritis
• Cutaneous vasculitis, Eye lesions may be
present
• Non specific symptoms may predominate
37. • Asthma, Eosinophilia with pulmonary infiltrates ,
glomerulonephritis
• Myocardial involvement most common cause of
death
Microscopic Polyangiitis
• Pulmonary alveolar capillariitis,
glomerulonephritis
38. 2nd decade
Palpable purpura over lower limbs,
Gastrointestinal complaints (abd.colicky pain,
blood in stools),
Fever, polyarthralgia
Increased IgA levels in blood
40. 5 % of Chronic Hepatits C pts. Have EMC
Cryoglobulins formed agianst HCV RNA
Pulmonary, renal ( MPGN ), cutaneous
vasculitis
Thromb Angiitis Obliterans
• Chronic heavy Smokers
• Inflammation of arteries, veins, nerves
• Upper and lower limb gangrene, Instep
claudication, rest pain
41. Behcet’s disease (Recurrent OculoOroGenital
ulcerations with vasculitis)
Idiopathic Cutaneous vasculitis
Isolated Vasculitis of CNS
Relapsing Polychondritis
Polyangiitis overlap syndromes (features of
more than 1 vasculitis)
42. Step 1- Recognise vasculitis
Step 2- Rule out Sec. Vasculitis
Step 3- Study the pattern of vessels involved in
the patient
Step 4- Remember the characteristic
presentations of each primary vasculitis
44. • Mild Anemia – Anemia of Chronic Disease
• Differential Leucocyte Count:
Predominant eosinophils- Churg Strauss, HSP
ESR
• Non specific
• But useful test to suggest presence of
underlying inflammatory process
45. • Acute Phase Reactants
Highly sensitive C reactive Protein, Alpha 2
globulin
• Chest X ray / HRCT thorax:
-Pulmonary infiltrates- small vessel vasculitis
-Pulmonary cavities- Wegener’s granulomatosis
• Xray Para Nasal Sinuses
-Sinusitis of Wegener’s
47. • Urine routine- RBCs with active sediments
suggest Glomerulonephritis (Renal
involvement of small vessel vasculitis)
• Viral Markers
- Hep. B Poly Arteritis Nodosa
- Hep.C Essential Mixed Cryoglobulinemia
48. • Immunoglogulin levels (IgG, M, A)
- Usually hyper gammaglobulinemia seen
- Elevated IgA levelsHenoch Sconlein Purpura
• Cryoglobulins- Essential Mixed Cryoglobulinemia
• Rheumatoid Factors
-To detect secondary vasculitisRheumatoid Arthrits
-Significantly raised in Essential Mixed
Cryoglobulinemia also
49. • Complement levels (reduced in immune compex
mediated diseases)- EMC, HSP
• ANCA
P-ANCA: Wegener’s Granulomatosis
C-ANCA: Microscopic polyangiitis, Churg Strauss,
Wegener’s vasculitis
• ANA
-screening of SLE, collagen vascular disorders in
suspicion of secondary vasculitis
50. • Renal Biopsy- to detect glomerulonephritis
especially in small vessel vasculitis
RPGN- seen in pauci immune vasculitis
MPGN- seen in EMC
• Skin Biopsy- to detect “leukocytoclasis” in
cutaneous vasculitis all small vessel and
secondary vasculitides
51. • Temporal Artery Biopsy- Giant Cell Arteritis
• Pulmonary tissue Biopsy- Small vessel vascultides
• Upper Airway biopsies- Wegener’s Vasculitis
* Main purpose of biopsy is to study presence of
leukocytoclasis, characterisitc pathological
alterations in tissues, GRANULOMAS
* Immunofluorescence also helps to study immune
complex deposition, IgA deposition, Complement
deposition
52. Helps specially in in arteries that cannot be
biopsied easily like Aorta, Coronary artery,
Mesentric vessels
Presence of vascular patency, Aneurysms
• Aortic Angiography- Takayasu’s
• Cerebral Angiography- Isolated CNS vascultis
• Renal Angiography- PAN
• Coronary Angiography- Kawasaki’s
• Lower limb arteriography-Buerger’s Disease (TAO)
55. • Immuno Suppression
Glucocorticoids- oral / IV methyl prednisolone
Cyclophosphamide
Methotrexate
Azathioprine
Cyclosporine
Rituximab- anti CD 20 ab
AntiTNF therapies- Infliximab, Adalimumab,
Etanacerpt, Certulizumab
56. • Choice of therapy depends on
Severity of organ damage
Extent of Multi System Involvement
The vascular bed involved (renal, ocular,
coronary)
• Cyclophosphamide + Glucocorticoid therapy
preferred for severe / serious complications
• Glucocorticoids alone will suffice for isolated
mild vascultis like “idiopathic cutaneous
vascultis”
57. Wherever possible secondary causes
(infections, malignancies) should be sought
and treated
Anti viral therapy (HCV, HBV)
ASPIRIN therapy – Kawasaki’s, Giant cell
arteritis
Intravenous Immunogloguloin Therapy- Prevents
coronary aneurysms in Kawasaki’s
58. • Major toxic side effects of all prescribed drugs
need to be kept in mind
(Osteoporosis, growth retardation, bone marrow
suppression, hepatic toxicity, renal toxicity,
bladder cancer, cystitis …)
• Long term toxicities need to be prevented
• Long term prescription of a single group of
drug to be avoided change over to a drug
with lesser toxicity profile as soon as symptoms
are controlled
59. • Regular Monitoring of Blood Counts, Renal
and hepatic functions
• Most of the Primary vasculitides have one
thing in common
“Chronic, Responsive to treatment, But
Notoriously Relapsing”
60. Step 1- Recognise vasculitis
Step 2- Rule out Sec. Vasculitis
Step 3- Study the pattern of vessels involved in
the patient
Step 4- Remember the characteristic
presentations of each primary vasculitis
Step 5- How to Diagnose
Step 6- Principles of treatment