Diagnostic tables for vasculitides and pseudovasculitides. Mikhail Valivach, MD, Pavlodar, Kazakhstan, 2015

1. Diagnosis of vasculitides and pseudovasculitides. A quick reference guide. Mikhail Valivach, Murat Makatov. Pavlodar.
2015. Usage instruction on pages 3 and 4
Table 1. Manifestations of vasculitides and pseudovasculitides.
Location Manifestations
Skin Skin necrosis. Purpura. Maculopapular rash (fixed palpable erythema). Superficial crust. Atrophy blanche.
Livedo reticularis. Livedoid scarring. Ulcer (s). Peripheral gangrene. Digital necrosis.
Mucous memb Erosions, ulcers, aphthae.
Eyes Significant proptosis. Scleritis / Episcleritis. Conjunctivitis / Blepharitis / Keratitis. Blurred vision. Visual loss.
ENT Bloody nasal discharge / crusts / ulcers / granulomata. Paranasal sinus involvement. Subglottic stenosis.
Conductive hearing loss. Sensorineural hearing loss.
Chest Wheeze.Nodules or cavities.Pleural effusion / pleurisy. Infiltrate. Endobronchial involvement. Massive
haemoptysis / alveolar haemorrhage. Respiratory failure.
Cardiovascular Loss of pulses. Valvular heart disease. Pericarditis. Ischemic cardiac pain. Cardiomyopathy. Congestive cardiac
failure.
Abdominal Peritonitis. Bloody diarrhoea. Ischaemic abdominal pain. Endoscopic: hyperemia, erosion, ulcer.
Kidneys Hypertension. Proteinuria. Haematuria. Increased serum creatinine.
Nervous
system
Headache. Meningitis. Organic confusion. Seizures (not hypertensive). Spinal cord lesion. Cranial nerve palsy.
Sensory peripheral neuropathy. Mononeuritis multiplex.
Table 2. Differences between small, medium, and large vessel disorders
Small vessels Medium vessels Large vessels
Skin Maculopapular rash (fixed palpable erythema).
Palpable purpura. Erosions, superficial ulcers
and crusting. Atrophy blanche.
Livedo reticularis. Necroses,
including distal necroses. Ulcers.
Цианоз
Изменения цвета
конечностей
GI Inflammation and erosions of mucous
membranes. GI hemorrhages.
Abdominal pains. Intestinal
perforations.
Ischemic abdominal pains
(abdominal angina).
Intestinal infarctions.
Lungs Chest imaging: pneumonia-like shadows,
ground-glass opacity, cavitating and
noncavitating nodules
Wedge shaped opacities on chest
x-ray (like pulmonary embolism)
Scanty lung pattern.
Respiratory failure.
Kidneys Hematuria with red blood cell casts.
Proteinuria. Renoparenchymal hypertension.
Hematuria without red blood cell
casts. Dull pain. Vasorenal and/or
renoparenchimal hypertension.
Vasorenal hypertension. No
blood and no protein in
urine.
Nervous
system
Brain lesions do not correspond to vascular
beds. Poly- and mononeuropathies.
Brain lesions correspond to
vascular beds or their segments.
Signs of affection of
common, external, internal
carotid or vertebral artery.
Muscles Myalgias Myalgias Intermittent claudication
Systematization of vasculitides is based on:
Vessel size (large, medium, small size vessels)
Lesion distribution (monoorganic, polyorganic, specific distribution)
Primary pathogenetic mechanisms (Anti-GBM antibody, ANCA, immune complexes, specific veriants of immune complexes,
including monoclonal gammopathies, cryoglobulins, hypocomplementemias)
Specific secondary immune reactions (macrophagal granulomas, eosinophilic reactions)
Large vessel vasculitides:
Takayasu's aortoarteritis – large +_ medium vessels (imaging and clinical picture). Location is not important. Nonspecific general
inflammatory symptoms.
Guiant cell (temporal) arteritis – Typically external and/or internal carotid artery. Also aorta and its first branches can be affected
(imaging and clinical picture). Nonspecific general inflammatory symptoms. Histology of granulomatous inflammation but not
in all patients.
Medium vessel vasculitides:
Polyarteritis nodosa – any distribution, rare lungs. Medium +_ small vessels (histology, angiography, clinical picture).
Nonspecific general inflammatory symptoms. Excluded Wegener’s and Churge-Stross diseases. ANCA – negative.
Kawasaki disease. Mostly in preschool age. Diagnosis is based on clinical picture. In acute febrile phase four signs of the five:
(1) conjunctival injection, (2) lips and mouth (strawberry, redness and cracking of the lips, inflammation of oral and throat
mucosa), (3) extremities (erythema and swelling of the hands and feet, peeling of the fingertips), (4) polymorphic exanthem: the
skin eruption involves the trunk and extremities, (5) cervical adenopathy. Residual changes in the form of coronary and other
artery aneurisms. Thrombosis and ruptures are possible.
Small vessel vasculitides (listed in the order of diagnostic priority):
Secondary vasculitides in DCTD or autoimmune diseases. Vasculitis (clinical picture + histology) + clinical picture of DCTD or
autoimmine disease.
Vasculitis in monoclonal gammopathy. Vasculitis of small +_ medium vessels (clinical picture + histology). Any location.

2. Monoclonal gammopathy revealed by electrophoresis.
Goodpasture syndrome. Glomerulonephritis +_ pneumonitis. Other organs are not affected. Anti-GBM antibody.
Vasculitis limited to gloneruli (glomerulonephritis). Histological proof. Immune deposits in immunofluorescence. Variants are
determined in accordance with glomerulonephritis classification.
Vasculitis limined to skin. Small +_ medium vessels. Histological proof. Variants include ANCA-associated and immune
complex vasculitides.
Isolated CNS vasculitis. Small +_ medium vessels. Angiography +_ histology. ANCA-negative.
Henoch-Schonlein purpura (IgA vasculitis): Small +_ medium vessels (histology). Various distribution. Prevailing deposition of
IgA (immunofluorescence).
Wegener's granulomatosis. Small +_ medium vessels (histology). Various distribution with mandatory participation of upper or
lower airways. In most patients ANCA-positivity. Immune deposits are not characteristic but if present do not exclude WG.
Churge-Strauss syndrome. Small +_ medium vessels (histology). Various distribution with mandatory astma.Mandatory
eosinophilia (in histology and/or in blood >10% and/or in sputum >25%)/ In most patients ANCA-positivity. Immune deposits
are not characteristic but if present do not exclude CSS.
Microscopic polyangiitis. Small +_ medium vessels (histology). Various distribution. No eosinophilia. No granulomatosis.
Mandatory ANCA-positivity.
Cryoglobulinemic vasculitis. Small +_ medium vessels (histology). Various distribution. Cryoglobulinemia. Deposition of IgG
and/or IgM (immunoluorescence). ANCA – negative.
Hypocomplementemic vasculitis. Small +_ medium vessels (histology). Various distribution. Low C3 or C4. Deposition of IgG
and/or IgM (immunoluorescence). ANCA – negative.
Hypersensitivity vasculitis. Small +_ medium vessels (histology). Various distribution. Deposition of IgG and/or IgM
(immunoluorescence). ANCA – negative. Table 3. Pseudovasculitides
Pathogenetic
mechanism
Nosologies Key signs
Endothelial
infections
(endothelitis)
EBV Inflammatory angiopathy +EBV in blood PCR or very high antibodies in ELISA
CMV Inflammatory angiopathy +EBV in blood PCR or very high antibodies in ELISA
HSV 1 and 2 Inflammatory angiopathy +HSV in blood PCR or very high antibodies in ELISA
VZV Inflammatory angiopathy + VZV in blood PCR or very high antibodies in ELISA
Micro-
embolism
Septic embolism Inflammatory angiopathy + detected source of bacterial embolia
Atheroembolism
(unstable
atheromatous
plaques of aorta
or large vessels)
Signs of occlusion medium +_ small vessels in a patient > 45 y.o. Onset after
endovascular intervention, after anticoagulants, and rarely spontaneously. Imaging signs
of aortal atherosclerosis with unstable plaques. Atheroemboli detected in histology or
fundoscopy. Classical triade: livedo reticularis + renal failure + eosinophilia. Another
triade: livedo reticularis + pain in lower extremities + preserved pulse.
Atrial myxoma Occlusion of medium +_ small vessels. Atrial tumor detected by ultrasound.
Metabolic
vascular
damages
Diabtic
angiopathy
Signs of small vessel angiopathy with various distribution + microalbumin or protein in
urine and/ or retinal angiopathy in a patient with high blood glucose/
Homocystenemia Occlusion of medium +_ small vessels + high blood homocystein.
Calciphylaxis Occlusion of medium +_ small vessels + vascular calcification detected by histology or
x-ray. Causes: hyperparathyroidism, chronic renal failure, diabetes, etc.
Thrombophilias DIC syndrome
(chronic)
Occlusion of medium +_ small vessels + high d-dimer + manifestations of one of
diseases that can cause DIC.
Paraneoplastic
hypercoagulation
A variant of chronic DIC caused by malignancy.
Intake of estogens
or anabolic
steroids.
Occlusion of medium +_ small vessels + high d-dimer + intake of estrogens or anabolic
steroids.
Antiphospholipid
syndrome
Occlusion of medium +_ small vessels + high d-dimer + antiphospholipid antibodies
Thrombotic
thrombocytopenic
purpura
Occlusion of medium +_ small vessels with various distribution (the brain is affected
more than kidneys) + thrombocytopenia + anemia with schistocytosis and
reticulocytosis.
Hemolytic uremic
syndrome
Occlusion of medium +_ small vessels with various distribution (kidneys are affected
more than the brain) + thrombocytopenia + anemia with schistocytosis and
reticulocytosis.
Tests mandatory for diagnosis and differential diagnosis: Blood test with leukocyte count and ESR, Urine test, Blood plasma
electrophoresis for protein fractions, Blood tests for ANCA, ANA, RF, d-dimer, glucose, creatinine, cryoglobulins.
Additional tests in special situations: Cutaneous lesions: Biopsy, histology, immunofluorescence for immune deposits;
Cutaneous lesions + ANCA-negativity: Blood complement C3 and C4; Nephritis: Renal biopsy, histology, immunofluorescence
for immune deposits, Anti-GBM antibody; Age >45 y.o. + lesions of lower extremities: Imaging of aorta for unstable
atheromatous plaques , fundoscopy;Chronic renal failure or signs of hyperparathyroidism or diabetes: X-ray of affected soft
tissue for vascular calcification .

3. How to use the quick reference guide
I am M.D. Mikhail Valivach, who has worked with vasculitides for more than 10 years. There are numerous
vascular diseases. The problem with diagnosis is due to the fact that different vascular diseases affecting the
same organ can have similar clinical manifestations. And the same vascular disease in different patients
having different organ involvement can show different clinical pictures.
Vascular diseases can be divided into five groups depending on their pathogenetic mechanisms: (1) vascular
infections, (2) vasculitides, (3) metabolic angiopathies, (4) embolism, (5) thrombophilic disorders. Each of
these groups includes large lists of different nosologies. In addition, many manifestations of vascular
disorders are similar with infections and other diseases. Thus, to perform diagnosis of vascular diseases one
should keep in mind numerous criteria and data. To make this task easier I have created a quick reference
guide for myself. I hope that this guide will be useful to other doctors too. The guide contains several tables
that help to orient quickly in clinical situation. I have done my best to make these tables as short as possible
to make it possible to place them on two sides of an A4 sheet.
Table 1. Manifestations of vasculitides and pseudovasculitides contains a list of symptoms of vascular
disorders of different locations. This list has been taken from the Birmingham Vasculitis Activity Score
(BVAS) with some modifications (seehttps://www.rarediseasesnetwork.org/vcrc/documents/BVAS%20Assessment%20Training%20Manual.pdf ). If you are not
familiar with this subject you can find useful details and illustrations in my presentation “Manifestations of
vasculitides and pseudovasculitides” on the address
http://www.slideshare.net/MikhailValivach/manifestations-of-vasculitides-and-pseudovasculitides or find it
through yahoo.com using key words Valivach Manifestations of vasculitides and pseudovasculitides. If you
are going to work with vasculitides professionally, you should start from drilling these symptoms. You
should recognize them automatically.
Size of affected vessels is an important diagnostic criterion of vasculitides. Vessels are divided into large,
medium and small. Large vessels include aorta and its first branches. These vessels have cartilage in their
wall. More distal arteries have a muscular layer instead of cartilage. They are called muscular type or
medium size arteries. The most distant arteries, arterioles and capillaries have no muscular layer. These are
small size vessels. The first criterion of vasculitis classification is the size of affected vessels.
Imaging techniques including contrast angiography, sonograpy, MRI and CT are the most reliable methods
of detection of large vessel damages. Contrast angiography is the most sensitive method to reveal changes in
the medium size vessels. One can see small aneurisms, dilations and narrowing of vessels. It is also possible
to detect medium vessel changes with histology but one needs a deep biopsy. Small vessel affection is
evidently detected only by histology.
In addition to imaging techniques, there are also indirect clinical signs of damages of different size vessels. They
are shown in Table 2 “Differences between small, medium, and large vessel disorders”. It is important to
remember that large vessel vasculitides can also affect medium vessels. Medium size vasculitis can spread to small
vessels. And small vessel vasculitis can also affect medium size vessels. To reliably keep in mind the table it is useful
to apply it to clinical situations several times. Besides I can recommend to see my presentation on pseudovasculitides.
It contains many illustrations. For training you can compare these illustrations with Table 2 and try to determine
which size vessels are affected. Go to http://www.slideshare.net/MikhailValivach/pseudovasculitides-mikhail-
valivach-2015 or find it through yahoo.com using key words Valivach Pseudovasculitides.
The part “Systematization of vasculitides” gives a short information on the subject. You can see more details in my
presentation “Systematization and diagnosing of vasculitides”
(http://www.slideshare.net/MikhailValivach/systematization-and-diagnosis-of-vasculitides-mikhail-valivach ). You
can find it through yahoo.com using key words Valivach Systematization and diagnosing of vasculitides.
One should remember that in those cases of small vessel vasculitides where biopsy is available it mandatory should be
made. Histology is the only evident proof of vasculitis. Histology reveals the character of inflammatory infiltrate.
Immune deposits are determined by direct immunofluorescence.
I would like to draw your attention that the items Primary pathogenetic mechanisms and Specific secondary immune
reactions are describing diagnostic criteria only of small vessel vasculitides. Determination of these mechanisms is
possible only through histology and direct immunofluorescence.

4. Considering skin biopsy one should remember that inflammatory reactions in vessels are transient and one reaction is
followed by another. For example, neutrophilic infiltrate that is an important diagnostic criterion is changed by
lymphocytes in a few days and even hours. The sign of previous neutrophilic infiltrate in the form of nuclear debris
(leukocytoclasis) will stay for a short time and then disappear. Later lymphocytic infiltrate will disappear too. Only
changes of vascular architecture will be left. It is critically important to determine correctly the time and location of
biopsy. To do this see my “Guide on skin biopsy” http://www.slideshare.net/MikhailValivach/guide-on-skin-biopsy-
mikhail-valivach . You also can find it through yahoo.com using key words valivach guide on skin biopsy. Technique
of punch biopsy you can see in youtube.com “the punch biopsy dermeducation” (https://www.youtube.com/watch?
v=gd7j-wYwryY ).
Immune deposits can be detected by direct immunofluorescence. Immune deposits are a very short term event and
their detection depends on the time of biopsy. For more details on skin biopsy I recommend you an excellent article
“Cutaneous Vasculitis Update: Diagnostic Criteria, Classification, Epidemiology, Etiology, Pathogenesis,
Evaluation and Prognosis by J. Andrew Carlson, Bernard T. Ng, Ko-Ron Chen. ARTICLE in
AMERICAN JOURNAL OF DERMATOPATHOLOGY· JANUARY 2006”. You can download this article
from the address
http://www.researchgate.net/publication/7453727_Cutaneous_Vasculitis_Update_Diagnostic_Criteria_Classification_Epidemiology_Etiology_Pathogenesis_Eval
uation_and_Prognosis
Below “Systematization of vasculitides” you see description of vasculitides. Vasculitides are listed in the order of
diagnostic priority. When you examine your patient you can find that he corresponds to criteria of two or even more
vasculitides. The vasculitis that is mentioned first is the most appropriate in such cases. Detailed information on
diagnosis of vasculitides is given in my presentation “Systematization and diagnosis of vasculitides”
(http://www.slideshare.net/MikhailValivach/systematization-and-diagnosis-of-vasculitides-mikhail-valivach ). Or
search for it through yahoo.com using key words valivach systematization and diagnosis of vasculitides.
If your patient has the symptoms listed in Table 1 but does not correspond to criteria of a vasculitis, please refer to
Table 3 “Pseudovasculitides”. The table gives key signs for each nosology. Lack of these signs is sufficient to reject
diagnosis but their presence is not sufficient to confirm diagnosis. Detailed data on pseudovasculitides you can see in
my presentation “Pseudovasculitides” (http://www.slideshare.net/MikhailValivach/pseudovasculitides-mikhail-
valivach-2015 ). You can find it through yahoo.com using key words valivach pseudovasculitides.
Thank you for your attention!
Hope that my short reference guide will be useful for you.
Mikhail Valivach, MD. Kasakhstan, Pavlodar. December 2015.
Dear colleagues, with questions and suggestions you can address to Mikhail Valivach valivach@mail.ru