Vasculitis Reaction Pattern

VASCULITIS

There is a difference between vasculitis and vasculopathy. The latter is vascular occlusion without inflammation. The histological picture you see in vasculitis depends on the duration of the lesion when it is biopsied. Leukocytes may only be seen in the first 48 hours before they are replaced by lymphocytes so several biopsies are useful. An incisional biopsy will be needed to view a large vessel vasculitis.  

Vasculitis refers to damage to vessels and this damage can be very mild or can be very severe with all grades in between.  It can range from damage to capillaries or small post-capillary venules through to damage to large smooth muscled vessels.  When you first view a slide your eye is usually attracted to a peri-vascular infiltrate.  We have already dealt with those conditions which have mild peri-vascular infiltrates of lymphocytes which can give rise to capillaritis with leakage of red blood cells presenting as the  pigmented purpuric dermatoses.    However if you look more closely at a vessel and you see nuclear dust in the vessel wall or neutrophils penetrating the vessel wall, then you may have a leukocytoclastic vasculitis where the damage is to the post-capillary venule and usually this damage is a type of immunological reaction secondary to infectious agents or drugs.  If you look closer and you see pinkish material in the vessel wall, then you may be looking at fibrinoid necrosis.  This indicates a more severe vasculitic process and clinically behoves you to examine the patient looking for involvement of blood vessels elsewhere in the body, not just in the skin.  The quickest way is just to check the urine for blood. If present you have systemic disease. 
Involvement of large muscle walled vessels will usually give significant fibrinoid necrosis and damage to the endothelial lining of the vessel with narrowing of the vessel lumen.  In conditions such as polyarteritis nodosa this reduction in blood supply with give rise to the large necrotic areas that are commonly seen in the skin.  Blood vessels can also be involved not just in the dermis but in the fat tissue and will give rise to the panniculitides such as  erythema induratum or nodular vasculitis. See this Reference on Erythema induratum

What do you see?

1. Superficial peri vascular lymphocytic infiltrate with red cell extravasation 
2. Neutrophilic peri vascular infiltrate with passage through the vessel wall and endothelial cell thickening
3. Neutrophilic peri vascular infiltrate with fibrin in the vessel wall but it is a venule
4. Vessel wall damage, fibrin and granulomas in the dermis
5. Large muscle walled vessel in the dermis with fibrin in the vessel wall
6. Something occluding the vessel lumen - Vasculopathy

1. Superficial peri vascular lymphocytic infiltrate with red cell extravasation 

In capillaritis the patient will present with small brown areas of hyperpigmentation usually on the lower legs around the ankle. Clinically there may also be some red dots from rent haemorrhage. The histopathology will usually show a perivascular lymphocytic infiltrate with some extravasation of red cells.  It is the iron in the extravasated red cells that gives rise to the pigmentation.  There is usually little in the way of damage to the endothelial lining of the vessel. The commonest named disorder is Shaumberg's disease but also remember lichen aureus.

2. Neutrophilic peri vascular infiltrate with passage through the vessel wall and endothelial cell thickening
3. Neutrophilic peri vascular infiltrate with fibrin in the vessel wall but it is a venule

In leukocytoclastic vasculitis the epidermis is usually normal but there is a mixed perivascular infiltrate that is mainly made up of neutrophils and there will also be a few lymphocytes and sometimes eosinophils.  It is usually the vessels in the upper dermis that are involved.  Occasionally in the more severe types of leukocytoclastic vasculitis there will be destruction to the vessel wall and there will be broken up bits of neutrophils and nuclear dust called leukocytoclasis in the surrounding dermis.  Further damage leads to fibrin deposition with the extravasation of lymphocytes into the dermis as well.  Should you do immunofluorescence studies in vasculitis, you generally just get deposits of compliment and fibrinogen.  However in Henoch-Schoenlein vasculitis you will see IgA which is deposited around the vessels.  Occasionally you will get other immunoglobulins but IgA is the classic feature of Henoch -Schoenlein vasculitis. It is a waste of time doing DIF studies in cases other than suspected Henoch Schonlein  See this Reference

Henoch-Schoenlein purpura is the archetypical small vessel leukocytoclastic vasculitis.  The condition has a very characteristic clinical presentation with purpuric lesions on the buttocks, the lower legs around the ankles and sometimes associated with significant renal problems, but in children may present with gut involvement and intussuception  and with joint swelling.  Immunofluorescence of this type of vasculitis shows IgA deposition in the vessels and this also occurs in kidney vessels when there is renal involvement.  It is mainly the post capillary venules that are involved in Henoch-Schoenlein purpura and you rarely get endothelial necrosis.

Leukocytoclastic vasculitis is the common presentation of most of the drug induced causes of vasculitis and vasculitis associated with the connective tissue diseases but again only if biopsied in the acute phase. Otherwise it may be lymphocytic. Other causes include cryoglobulinaemia, serum sickness and Henoch-Schoenlein purpura as we have already mentioned. Note though that type 1 cryoglobulinaemia will give pink vascular occlusion without much in the way of inflammation.

4. Vessel wall damage, fibrin and granulomas in the dermis

Wegener's granulomatosis and the Churg-Strauss syndrome can give rise to significant vascular damage but usually it is only mid-sized vessels that are involved here and the process is essentially a leukocytoclastic vasculitis.  With time the leukocytoclastic vasculitis can evolve into a palliading granuloma with central neutrophils and you may get giant cells present in the granuloma.  Typically these conditions will involve either the kidney in the case of Wegener's granulomatosis or the lung in the case of Churg-Strauss.  In the Churg-Strauss syndrome another characteristic feature is an increased number of eosinophils within the palisading granuloma and significant blood eosinophilia. See this Reference  and This For Wegeners

5. Large muscle walled vessel in the dermis with fibrin in the vessel wall

If a large vessel is involved in the vasculitic process it is important to work out whether it is an artery or a vein.  Arteries generally give a rounded central opening but veins are more oval.  Arteries also have an internal elastic lamina which veins lack.  In giant cell or temporal arteritis you may see granulomas beneath the internal elastic membrane in the sub-endothelial area and this iinflammation can extent throughout the vessel causing significant narrowing of the vessel and the clinical complications of blindness and sometimes severe stroke. Clinically patients have severe headaches and a high ESR.

In polyarteritis nodosa again it is a large vessel that is usually involved but it is going to be in the deep rather than the superficial dermis.  In the acute phase you are mainly going to see a neutrophilic infiltrate with leukocytoclasis but in a chronic case you may see granulomas in the vessel wall with significant narrowing of the vessel lumen and because these vessels are deep you may get surrounding fat necrosis.
See this Reference

It is rare for thrombophlebitis to be biopsied, but if you do, what you are going to see is the vein so that the lumen is going to be oval and often there will be clot in the centre of the vein.  There will be a prominent peri venular muscle layer but there won't be any internal elastic lamina, though special stains may have to be done to show this.

Other conditions possibly showing Vasculitis

Occasionally vasculitis can be seen in other conditions such as Sweet's syndrome which is essentially a neutrophilic dermatosis but it can have a  very mild vasculitis , usually just showing endothelial thickening but not fibrin deposition.

The histological changes in erythema elavatum diutinum are very similar to those in granuloma faciale, but this condition tends to affect the acral areas on the back of the hands with nodules rather than the face.  A curious feature is extracellular cholesterol clefts but this is only seen in very chronic cases and this may contribute to the yellowish nature of these nodules clinically.  See this Reference

Urticaria is not normally associated with significant vasculitis but there is a variant called urticarial vasculitis in which the lesions last longer than 24 hours and when they subside there is often purpura at the periphery of the welts.  In urticarial vasculitis you have to consider that it may be an early presentation of lupus erythematosus.  There may be fibrin in the vessel wall and some neutrophils and eosinophils surrounding the vessels early but later it is a lymphocytic vasculitis, but these features aren't seen in ordinary urticaria where there is really just dilatation of the vessels with some surrounding eosinophils but no damage to the vessels. See this Reference

There are some other very rare conditions that can have a vasculitis, but it is usually a lymphocytic vasculitis.  One of these is Degos disease which clinically begins as red papules but evolve into lesions with ivory white atrophic centres.  Classically these cases will begin with bowel perforation and perhaps stroke.  Histologically the vessels will show lymphoid infiltrate and there will be significant vascular damage.  The overlying white area will be sunken on the histology and the dermis will be pink in a wedge shaped pattern from vascular necrosis. Some people believe this condition is a manifestation of lupus.  See this Reference

Perniosis can also give rise to a lymphocytic vasculitis but with both superficial and deep perivascular infiltrate.  This can be quite florid. Occasionally there is even some basal layer damage and the histology resembles lupus erythematosus. Usually there is some oedema of the vessel walls but without fibrin deposition. See this Reference

Insect bite reactions can also give rise to lymphocytic  vasculitis, but again there is a wedge shaped perivascular lymphoid infiltrate.  Sometimes the lymphocytes can look a bit atypical in insect bit reactions and it is not the first time that they have been reported as a lymphoma.  Usually there is prominent eosinophilia in the tissues. Often there is prominent capillary dermal oedema but the lymphocytic vasculitis is relatively mild.

6. Vasculopathies

The last fairly distinctive histological picture of vasculitis is that due to cryoglobulinaemia and cholesterol embolization.  In cholesterol embolization arteries will show cholesterol clefts in the centre of them.  In cryoglobulinaemia the vessels may be occluded by pink jelly-like material and again there will be significant red cell extravasation.  View this reference on Cholesterol embolisation