European Journal of Cardiovascular Medicine

Cutaneous vasculitis comprises of different clinical pathological spectrum with some of them leading on to serious multi systemic involvement. Skin biopsy always plays an important first line investigation for the above diagnosis. This study emphasises the role of histopathology in various differential diagnosis of cutaneous vasculitis as the treatment plan differs in each of them. Moreover, the relevance of clinical input is also important for correct diagnosis. The aim of this study is to emphasise the role of histopathology in the differential diagnosis of cutaneous vasculitis and to correlate it with clinicopathological findings.

This study was conducted in the department of Pathology in a teaching hospital of South India. There were 80 skin biopsies which were clinically diagnosed as primary and secondary cutaneous vasculitis. It is a retrospective study over five years. The clinical history and details were collected from the medical records section. The histopathological details were analyzed  by pathologists from the stained haematoxylin and eosin slides

Based on clinical presentation the lesions were classified according to their clinical symptoms and morphological appearance. The parameters used were based on clinical presentation as pustules, bulla, plaques, targetoid lesions, macules, purpuric spots and papules. Histopathological sections there were classified based on the size of the blood vessels, nature of cellular infiltrate, extravasation of RBC’s fibrinoid necrosis. The predominant cellular infiltrate was noted,whether it was neutrophils, eosinophils, lymphocytes or histiocytes.Presence of granulomas, extravasation of RBC’s and fibrinoid necrosis were also noted.

The total numbers of skin biopsies in a 5 year period  were 1835, out of which there were   80 cases of cutaneous vasculitis  .The clinical profile and histopathological study were analyzed on these 80 cases(4%). The clinical profile included  clinical symptoms and presentation, morphological appearance like hyper pigmented or hypo pigmented, multiple or single, papule, purpura, macules, pustules and  bulla. Histopathological classification  was based on size  of the vessel(large vessel, medium vessel or capillaries), nature of cellular infiltrate, extravasation of RBC’s and fibrinoid necrosis.

 Age wise distribution of cutaneous vasculitis showed that there were 26 cases (33%) in the age group of   more than 50 years and for less than 50 years of age,there  were 54 cases (65%). Sex  distribution showed a  slight female predominance with 43cases (54%) and males were 37 cases (46%). Patients who had  painful lesions  were 25 cases (31%) and without painless lesions were seen in 55 cases (69%). The location of the lesion were over the extremities  in 59 cases (75%) and central lesions were noted in  21 cases (25%). Multiple lesions observed  in 58 cases (72%) and single lesions were observed in 22 cases (28%). Some the patients had extra cutaneous manifestations,as seen in  47cases (59%) like hypertension, diabetes mellitus, rheumatoid arthritis, hyperthyroidism. Pure cutaneous manifestations were  seen in 33cases (41%). Purpura  were seen in 25cases (31% ), plaques  in 25cases (31% ), papules in 12 cases (15% ) , macules in7 cases (8% ), pustules in  6 cases (9% ), bulla in 5 cases (6% ).

Histopathological study showed all the 80 cases of cutaneous vasculitis were of small artery vasculitis. Microscopically inflammatory cells around the vessels were  neutrophils as seen in  99 cases (69%), neutrophils with eosinophils in  39 cases (27%), neutrophils with karyorrhexis  were seen in  5cases (4%), others like lymphocytes, plasma cells were rare accounting for 4%.Extravasation of RBC’s were seen in  72  cases(65%) and with fibrinoid necrosis in 38cases (35%)

Figure 1: Left foot showing multiple small hyperpigmented area with purpura,plaques, macules.

Figure 2: Haematoxylin and eosin stain 10x. Skin lined by keratinizing stratified squamous epithelium with adnexal structure and dermis showing some inflammation.

Figure 3: Haematoxylin and eosin stain 100x. Skin with underlying dermis showing showing blood vessels surrounded by inflammatory cells and extravasation of RBC’s

Figure 4: Haematoxylin and eosin stain 100x. The underlying dermis showing skin adnexal structures , blood vessels with fibrinoid necrosis and surround small arteries showing inflammatory cells.

Figure 5: Haematoxylin and eosin stain 400x.Blood vessel in the dermis surrounded by neutrophils, eosinophils

Figure 6: Haematoxylin and eosin stain 400x.Blood vessels showing fibrinoid necrosis with inflammatory cells and karyohexis around the small arteries with extravasation RBC’s.

Cutaneous vasculitis occurs in all age groups and has  an incidence ranging  from 15.4 to 29.7 cases per million per year. Slight female predominance is seen and adults are more affected than children(1,2) The mean age of adults  is 47 years and  in children it is 7 years.Cutaneous vascular injuries are divided into : Vasculitis and Vasculopathy .Vasculitis is characterized by damage and inflammation of the blood vessels related to inflammation, whereas in vasculopathy blood vessel damage is not evident .(3) Cutaneous vasculitis comprise of inflammation of blood vessel walls within the skin , their surrounding tissues and other organs like the kidney, lung and heart.(1)  There are two types of vasculitis as  seen in  patients, one is primary vasculitis- based on size of the vessel and without any identifiable causes and the secondary vasculitis which is stimulated by bacterial, viral infection, drugs, malignancy, connective tissue diseases and systemic autoimmune disease ,which is also  systemic or  with extra cutaneous manifestations .(4) 

 Approach to diagnosis to small vessel cutaneous vasculitis is a diagnosis of exclusion which needs a complete evaluation to rule out various multiple other causes. (10)(3) To start diagnosing a case of vasculitis a complete patient history, general examination, physical examination, selected laboratory studies, a skin biopsy- which is examined by light microscopy and direct immunofluorescence are much needed.(5)Clinical systemic symptoms of the patient like fever, malaise, weight loss, arthritis, arthralgias combined with cutaneous and extra cutaneous manifestations of sign and symptoms with association of metabolic diseases like diabetic mellitus, hypertension, hypo/hyper thyroid ,obesity, rheumatoid arthritis has to be considered too in the diagnostic panel. The most common site for a vasculitic lesion are the lower extremities ,which  is the dependent site. The other parts like the upper extremities , trunk, head and neck are less common.(8) The lesions can be single  or multiple in different parts of the body.                                    

The laboratory screening of the patient  must include complete blood count with differentials, erythrocyte sedimentation rate ,urine analysis, liver function test, renal function test, serum creatinine,hepatitis B and C cultures (blood and urine), skin biopsy (two biopsy one for H and  E staining another for direct immunofluorescence) , stool guaiac and antineutrophil cytoplasmic antibodies (ANCAs).In suspected cases of small vessel cutaneous  vasculitis, a skin biopsy is often done . Other site of biopsies are kidney ,lung and heart .The main reason for a skin biopsy is the necessity  to confirm vasculitis and is to exclude the other causes of the  skin lesion.(6) Skin biopsy plays an important role in few vasculitis syndrome having clinical, radiographic and laboratory findings, therefore accurate diagnosis of vasculitis requires histological confirmation. But skin biopsy  should always be correlated with clinical history, physical and laboratory findings to arrive at specific diagnosis. (1,2)

The procedure of a skin biopsy is simple with minimum risk of complications  like bleeding, ulceration or infection. A 4 mm punch or a shave biopsy extending to subcutis is sufficient for the diagnosis of cutaneous small vessel vasculitis of a purpuric papule, which has  presented  within 24 to 48 hours. The timing and type of the biopsy sample taken, are the two factors   which has an effect on the results, because skin biopsy taken too early or too late will not contribute to the histologic features. If possible two biopies specimen should be taken , one for haematoxylin and eosin  and light microscopic diagnosis, another biopsy for direct immunofluorescence (DIF) .(7) For direct immunofluorescence , maximum yield is obtained when biopsy of  the lesion is done in less than 48 hours. Skin biopsy older than a week is  less likely to contribute to diagnosis.(8)(9)

Histopathological findings that sub classify vasculitis are based on the size/caliber of the blood vessel affected . Cutaneous vasculitis  could be small vessel vasculitis, medium vessel vasculitis or large vessel vasculitis.The type of blood vessels may be  arterial or  venous .The anatomic location of the affected blood vessel can be dermal or subcutaneous(3). Among these the cutaneous small vessel vasculitis (CSVV) is the commonest  .(1) The vessels affected are arterioles, capillaries and post capillary venules.  The two important criteria essential for histological assessment of cutaneous vasculitis are perivascular inflammatory cell infiltrate within and around blood vessel (neutrophilic, eosinophilic, lymphocytic, histiocytic or mixed) and  fibrinoid necrosis within and around the vessel walls(necrosis of vessel wall with deposition of fibrinoid material) .Other changes often present are  disruption or destruction of the vessel walls, leuokocytoclasis (nuclear dust),  red cell extravasation(sign of damage), damage and swelling  of endothelial cells of the vessel walls and the surrounding tissue, edema and luminal thrombosis.(3)(1)

Direct immunofluorescence in a cutaneous biopsy is needed in cases where the diagnosis of the lesion is difficult. The lesions are associated with the immune complexes and also help in detection of very early lesions. The most common immunooreactants are IgM,C3 and fibrin. IgM  is important for Rheumatoid Factor(RF )associated disease;C3 is more suggestive of HUV (hypocomplementemic urticarial vasculitis) and fibrin .Long term follow up of the patient is necessary for the management of the patient as recurrence rate is  increased especially with chronic disease. .The treatment modalities include bed rest, NSAIDs, analgesics, antihistaminics , immunosuppressants,colchicine ,dapsone and corticosteroids ( predisone) for a definitive cure.

Clinicopathological co-relation and proper histopathological evaluation are necessary to arrive at a correct diagnosis to initiate appropriate treatment for the patient. Skin biopsy is the golden standard for diagnosis of cutaneous vasculitis. For a correct interpretation of the biopsy report, one should be aware of essential features of vasculitis and in doubtful cases can review with a dermatopathologist. Essential histological information from skin biopsy and direct immunofluorescence with clinical findings enables more precise and accurate diagnosis of localized and systemic vasculitis syndrome.

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