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CUTANEOUS Vasculitis
CUTANEOUS Vasculitis
management of Cutaneous
Vasculitis
Dr Deepshikha Khanna
Senior Resident
UCMS & GTB Hospital,
Delhi
What is vasculitis?
Inflammation of vessel wall
Presents as heterogenous mix of clinical syndromes
Clinical picture depends on
Classification
Size of vessel wall small/medium/large
American College of Rheumatology Criteria
Etiology
Drugs,
vaccines,
chemicals,
allergies (1015%
Neoplasm
(5%)
Connective
tissue & other
inflammatory
diseases (1520%)
Infection (1520%)
Idiopathic (4555%)
When to suspect?
Dependent palpable purpura
Livido reticularis
Punched out ulcers
Subcutaneous nodules
Bullae, necrosis & ulceration
Over dependent / pressure areas / trauma prone sites
Single / recurrent crops, resolving over 3-4 wks
Leaving ecchymotic stains / hyperpigmentation
Ask for
Duration of complaints
drugs / exposure to chemicals /
food allergies/travel
Look for
Cutaneous findings
Morphological type
Size of vessel involved
BP, peripheral pulses
Neurological examination
Central / peripheral
Diffuse / focal
Pleural effusion / pleuritis
Pericardial effusion
Musculoskeletal system
Palpable purpura
Splinter Hmg
Urticaria
Vesicles
Ulcers
Digital
infarcts
Nodules
Livedo
Necrosis
Gangrene in
an extremity
Hypertension
Aneurysm
Dissection
Cryoglobulinemic
vasculitis
Henoch Schonlein
purpura
Purpura, colic, diarrhoea,
nephritis
Raynauds phenomenon
Acrocyanosis
by cold
ANCA associated
vascilitidis
Pulm renal syndrome
Kawasaki disease
Maculopapular rash
Periungual & perineal
desquamation
CUTANEOUS
VASCULITIS
Urticarial vasculitis
Annular urticarial plaques
HUVS/SLE,NUV
Polyarteritis nodosa
Starbust livedo reticularis
S/C nodules
Digital gangrene
Purpura
Platelet deficiency
Drug-induced
Dermatoses
Schambergs disease
Miscellaneous
Insect-bite reaction
Cutaneous lymphoma
Infection
SABE
Embolism
Cardiac myxoma
Malignancy
Test for
Initial screening
CBC with DLC
ESR
Urine analysis
Stool for occult blood
Creatinine
Liver function tests
CXR
Infection screen
Hepatitis B and C
Cutaneous Bx - H&E & DIF
Additional evaluations
Serologocial
ANA
ANCA
Anti-ds DNA
RF
Histopathology/DIF
Kidney
bone marrow
lung
Serum-Cryoglobulins
Complement (CH50, C3, C4)
Protein electrophoresis
Immunofixation
Histopathology
Histopathological confirmation required in most cases
cannot stand by itself
considerable overlap in pathological patterns
not diagnostic for specific syndromes
Can be focal / segmental
Not all vessels may be involved
Ideal time -18-36 hrs of age of lesion
Adequate depth including subcutis if MVV
Non-ulcerated site / nodule / white centre of a livido
segment / active border of ulcer
Most proximal part of the limb
Histopathological subtypes
Polymorphonuclear-LCV
Lymphocytic- EM, EN (late stages)
Granulomatous-WG, infective, EI, nodular vasculitis
Eosinophilic-CSS, drug eruptions
Hyalanizing vasculitis- atrophie blanche
Endothelial swelling
Extravasation of RBCs
Karyorrhexis or leukocytoclasia
Direct immunofluorescence
Fresh non-infarcted most proximal lesion preferably <6 hrs
maximum upto 24 hrs old
Dependent areas NO
Lesional skin > non-lesional skin
IgA most frequent
Presence of IgA associated with renal involvement but not
Indications
Cryoglobulinemic
vasculitis
Abnormal LFT
High RF
Interpretation
high clinical suspicion- 3 ve
results during active flare up
False +ve
True +ve indicative of Hep C
infec 90% T-II & 70% T-III
Complement
Urticarial vasculitis
S/S of SLE
Cryoglobulinemic vasculitis
CTD-SLE/RV/SS
Anti C1q precipitins HUV
ANA
S/S of CTD
Systemic findings
Medium vs wall
Cryoglobulins
Pulmonary hemorrhage
Orbital mass
Glomerulonephritis
Granulomatous vasculitis
Interpretation
Indicate pauci-immune vasculitidis DIF -ve
ANCA
Seen in <5% of N population
seen in RA, SLE, UC, Crohns, 1 biliary cirrhosis,
autoimmune hepatitis, chronic infection
Sensitivity 70%- may postpone need for invasive lung or
kidney biopsy
Necroptizing
granulomas
Asthma /
eosinophilia
Pulmonary
Renal
Cutaneous
ENT
Musculoskeletal
Neurologic
Gastrointestinal
WG
C-ANCA 75-80%
P-ANCA 10-15%
+
Microscopic
polyangiitis
C-ANCA 25-35%
P-ANCA 50-60%
-
Churg-Strauss
syndrome
C-ANCA 10-15%
P-ANCA 55-60%
+
+++
+++
++
+++
++
++
++
++
+++
++
+
++
+
++
+++
++
++
++
++
+++
++
Disease
C-ANCA (%)
P-ANCA (%)
Wegeners granulomatosis
75-80
10-15
Microscopic PAN
25-35
50-60
Churg-Strauss syndrome
10-15
55-60
Numbers small
RCT ???
Blinding?
How to eliminate spontaneous resolution?
Different etiologies, associations & systemic
involvement
Where are the follow up studies?
Why is there such under-reporting?
Management
Exclusion / treatment of systemic disorders
Remove / treat the cause if any
In the absence of systemic involvement, even cutaneous LCV of
long duration not life threatening
management strategies effective but with limited S/E
Aim of therapy
Comfort the patient / reduce symptoms
Prevent extensive cutaneous infarction & systemic
complications
Conservative therapy
Bed rest, elevation of lower extremities
Warming
Compression hosiery
NSAIDs
Anti-histamines
Avoid tight clothing / trauma
Elimination diet
Antibiotics suspected infection induced
(none of the conservative measures significantly modify the
disease course or prevent recurrences)
Callen JP. South Med J 1987; 80: 848-51.
Elimination diet
So
1.
2.
Antihistamines
Alleviate pruritus
Block histamine induced endothelial gap formation with
resultant trapping of immune complex
May be sometimes effective in controlling urticarial lesions
NSAIDs
Act by
COX chemotactic
metabolites for eos, neu
Used in
eosinophilic vasculitis, UV,
EN (case reports)
constitutional, jt
complaints
effect on skin lesion
indomethacin most often
used
Benefits
Cheap
Usually no severe S/E
Non-toxic
Problems
Drug induced vasculitis/
other reactions with
aspirin, salicylates
Common S/E GIT
and renal
Treatment modalities
Drug
Dapsone
Colcichine
Pentoxyphylline
Antimalarials
Thalidomide
Steroids
Immunosuppressives
I/V Ig
Plasmapheresis
Biological therapies
Dapsone
PGD2
alternative complement
lysosomal activation
active O2 metabolites
Laboratory testing
G6PD
CBC, LFT
caution in pts with CVS
or pulmonary
complications
Colchicine
Acts by
Inhibiting chemotaxis, leukocyte motility, adhesion &
lysosomal degranulation
Use in LCV
Two open trials shown good response but relapse on
withdrawl response on re-starting1,2
single prospective randomised study no response (LCV
was refractory to other therapies, trial not blinded, 3 patients
responded but relapsed on withdrawing colcichine)3
1.
2.
3.
Used for
HSP for cutaneous lesions alone / combined with aspirin
Behcets syndrome
HUV
NUV,
cryoglobulinemic vasculitis
Dose-0.6-1.8 mg/day
Side effects
GI, burning of throat / skin,alopecia,agranulocytosis,
aplasticc anemia, myopathy, peripheral neuritis, leukopenia,
teratogenesis, chromosomal non-disjunction, azopsermia
Pentoxyphylline
Acts by:
neutrophil adhesion, superoxide
Changes in cell membrane fluidity-Rheological agent
Inhibition of TNF-
Used in
Behcets disease
Cutaneous PAN,
LCV with polyeythema vera
Combined with Dapsone for UV and LCV
livedo vasculitis( atrophie blanche) PLEVA
Kawasai disease
Dose 400mg TDS
Only major S/E hypersensitivity
Antimalarials
Efficacy limited to urticarial vasculitis
no report of use in CSVV
Dose- 200-400 mg/day
Thalidomide
Anti-inflammatory, immunomodulating and anti-angiogenic
Effects on CD4 T cells, interleukin, IFN- & VEGF
Used in
Behcets disease
Lucio phenomenon
Cryoglobulinemic vasculitis
Refractory HSP
Recommended only for severe/refractory cases risk of side
effects
JAMA.1982; 247(14):1994-1998.
South Med J. 1987;80(7):848-851.
Advise
Immunosuppresives
As steroid sparing agents
Rapidly progressive disease with systemic involvement
refractory to steroids/adjuvant to steroids
Large vessel involvement
More recurrent chronic symptomatic disease
Azathioprine
Two studies
2.
Cyclophosphamide
Single study
1.
Drug
Mycophenolate
mofetil
Opinion
Helpful in systemic vasculitidis
Cyclosporine
Methotrexate
Dose
Upto 2 g total daily
Intravenous immunoglobulin
Pooled plasma of donors with
IgG, traces of IgA, cytokines and immunomodulators, normal
antibodies
Acts by neutralisation of Abs/interference with Ab production
Used for severe/ refractory /systemic disease /with
contraindications to other therapies
Used in:
Cutaneous PAN
EMC,HUVS, livedoid vasculitis
Gi and renal manifestations of HSP
FDA approved -Kawasaki disease (2g/kg single dose)
Plasmapheresis
Use in refractory cases of LCV
Recommended for systemic vasculitidis
Especially those with associated infection where
steroids and immunosuppressives contraindiacated
Biologicals
Infliximab
Chimeric monoclonal anti- TNF- antibody
cutaneous PAN
Deep cutaneous vasculitis
Rheumatoid vasculitis
ANCA associated vasculitidis
Infliximab but not eternacept may be for remission in refractory cases
Caution: reports of TNF- inhibitors induced vasculitis
Adalimuab
Human monoclonal anti-TNF- antibody
Used in Takayasu atreritis and rheumatoid vasculitis
Rituximab
Cryoglobulinemic vasculitis/nephropathy
Definition1
Restricted to upper and/or lower airways without constitutional
symptoms or systemic vasculitis
Localised WG with constitutional S/S
Multifocal WG
MPAN with threatened organ function
With constitutional symptoms
Threatened organ function
SCr <5.7 mg/dl
Rapid progressive renal failure with or without diffuse alveolar
hemorrhage
intolerant to standard therapy
Progressive despite 6 weeks of appropriate regime
1.Mayo Clin Proc.1997;72(8):737-747.
Methotrexate + Corticosteroids
Generalised organ
threatening disease
Induc. Cyclophosphamide + CS
Maintenance Azathioprine + CS
Plasma exchange no additional role
Diffuse pulmonary
hemorrhage
Disease state
FFS 1
FFS =0
Disease state
Refractory / relapsing
dis.
Histopathology
Categorize into a vasculitic syndrome
Sepsis
CTD
Malignancy
drug-intake
Treat
accordingly
HSP
Urticarial vasculitis
Cryoglobulinemic vasculitis
Cutaneous PAN
Kawasaki disease
Systemic involvement
Systemic involvement
Microscopic PAN
Churg Strauss
syndrome
No
Yes
PCSSV
ANCA +ve
ANCA -ve
Granulomatous
Takayasu arteritis
Giant cell arteritis
Asthma / eosinophilia
Wegeners granulomatosis
Second
line
LCV
Conservative
NSAIDs
Antihistamines
Dapsone
Colcichine
Steroids
UV
Antihistamins
Indomethacin
Dapsone
Pentoxyphylline
Antimalarials
Steroids
Colcichine
Azathioprine
Cyclosporine A
HSP
Conservative
Steroids
Steroids + Aza/ Cyclosporine
Renal
Steroids (Abd. Pain / arthritis)
Dapsone (Rash)
PEX
IVIg
Factor XIII
Prognosis
Poor if:
Risk factors
Paresthesias, fever, absence of painful lesions- systemic
involvement
1. Arch Dermatol.1998.134.309-315.