Diagnosis of cutaneous vasculitis

Classification of cutaneous vasculitis, clinical features, suitable investigations and when to refer to secondary care.

Cutaneous vasculitis: classification of the condition can be challenging and is based on the size of blood vessel affected (author image)
Cutaneous vasculitis: classification of the condition can be challenging and is based on the size of blood vessel affected (author image)

Cutaneous vasculitis is defined as inflammation of the blood vessel walls within the skin. Classification of this condition can be challenging and is based on the size of blood vessel affected. A useful classification scheme is listed in box 1.1

Secondary vasculitis is commonly caused by medications, bacterial or viral infections, malignancy or connective tissue diseases. This condition can affect small or medium blood vessels.2

Box 1: Classification of cutaneous vasculitis1

Small vessel vasculitis

  • Cutaneous small vessel vasculitis
  • IgA vasculitis (Henoch-Schönlein purpura)
  • Urticarial vasculitis

Medium and small vessel vasculitis

  • Rheumatoid arthritis
  • Microscopic polyangiitis
  • Granulomatosis with polyangiitis
  • Eosinophilic granulomatosis with polyangiitis
  • Cryoglobulinaemic vasculitis

Medium vessel vasculitis

  • Polyarteritis nodosa
  • Cutaneous polyarteritis nodosa
  • Nodular vasculitis

History and clinical features

A full history is required for these patients, in particular to look for any systemic features or obvious triggers for the vasculitis, such as new medications.

Petechiae are frequently seen, but the most common feature is palpable purpura. This is caused by the weakened vessel walls allowing red blood cells to extravasate.

This process is exacerbated by increased pressure, which is why the lower legs are the most common sites affected. These areas can ulcerate and the size of the affected vessel tends to correlate with ulceration – the larger the vessel, the deeper the ulceration. Nodules and livedo reticularis can appear in medium and large vessel vasculitis.

Investigations

In all patients presenting with suspected cutaneous vasculitis, the following investigations should be carried out:2

  • FBC, which may indicate an underlying cause
  • LFTs to rule out hepatic involvement
  • U&Es to ensure no renal involvement
  • Urinalysis to look for haematuria or proteinuria, which would indicate renal involvement

If the cause of vasculitis is obvious, further testing is not required. If it remains unclear, further testing would involve:2

  • ANA and extractable nuclear antigens, which may indicate connective tissue disease
  • ANCA, which may indicate systemic vasculitis
  • Immunoglobulins and electrophoresis
  • Rheumatoid factor
  • Cryoglobulins
  • Hepatitis B, hepatitis C and HIV, which are associated with some rare types of vasculitis

Skin biopsy

A skin biopsy can be helpful to confirm the diagnosis of cutaneous vasculitis. Biopsy of a lesion that is 24 to 48 hours old is most likely to yield the relevant diagnostic information.

Features include inflammatory infiltrate around blood vessels, disruption or destruction of the vessel walls and fibrinoid necrosis.3 Other important histological features include the depth of the vasculitis, the presence of nuclear dust (breakdown of white blood cells) and red cell extravasation.2

The biopsy can also indicate the cause of the vasculitis, particularly if, for example, granulomas are present. Direct immunofluorescence is a useful adjunct when diagnosing Henoch-Schönlein purpura, because this will show perivascular IgA deposition.2

Cutaneous small vessel vasculitis

Cutaneous small vessel vasculitis is the most common type encountered in practice. This vasculitis is limited to the skin and has no other organ involvement, but it can be the first sign of systemic vasculitis, so surveillance is necessary.

Up to 50% of cases are idiopathic. Of those that are not idiopathic, medications are a common cause, including penicillins, loop and thiazide diuretics, anticonvulsants and allopurinol, among others.4

The next most common cause is viral or bacterial infection. It is important to exclude hepatitis B, hepatitis C and HIV. Finally, there is an association with solid organ malignancy, which needs to be considered when taking the history.5

In cutaneous small vessel vasculitis, the lesions commonly affect both lower legs and ankles, and are often asymptomatic, although burning and pruritus have been reported.6

Palpable purpura is the most common sign and this may be preceded by the early macular stage.6 Lesions can continue to appear for a few weeks, but resolve over a similar timeframe. Approximately 10% of patients will have recurrent flares.6 Investigation, as outlined above, is necessary to exclude any systemic involvement.

The condition is self-limiting, so treatment is often not required. Any causative medications need to be stopped. Measures to reduce venous stasis, along with NSAIDs, may improve symptoms.

A reducing regimen of prednisolone may be required for more severe cases, or where ulceration is involved. Antibiotics and topical corticosteroids are often used, but there is no evidence to suggest they are beneficial.

There is weak evidence for the use of colchicine second-line and if this fails, azathioprine and methotrexate can be considered.6

IgA vasculitis (Henoch-Schönlein purpura)

Henoch-Schönlein purpura is a small vessel vasculitis characterised by immune deposits of IgA. This disorder almost exclusively affects children and often presents with a triad of rash, abdominal pain and arthralgia.

Streptococcal infections are the most common trigger, but respiratory infections are also implicated.6 The purpura mainly affects the extensor aspects of the limbs and buttocks.

Supportive care is the mainstay of treatment, but occasionally, systemic prednisolone is required. Following resolution, about a quarter of patients will relapse and up to half will have renal abnormalities on follow-up.6

Urticarial vasculitis

Urticarial vasculitis is a rare condition that involves the development of indurated wheals, which differ from usual urticaria because they tend to be painful, last longer than 24 hours and resolve with bruising. The wheals may contain purpuric foci and angioedema may coexist.

Evidence of treatment efficacy is limited, but most patients will respond to systemic steroids. Second-line treatments shown to be effective in some cases include dapsone, colchicine and hydroxychloroquine.6

Microscopic polyangiitis

Microscopic polyangiitis is an ANCA-associated vasculitis predominantly affecting small vessels, although medium vessels can also be involved. It is a necrotising form of vasculitis with very little immune deposition in the vessel walls.7

There are no granulomas, which helps to differentiate this condition from other ANCA-associated vasculitides. Glomerulonephritis and pulmonary capillaritis often coexist and constitutional upset is often present.7

Management involves strong immunosuppression with systemic steroids and cyclophosphamide to induce remission.6

Granulomatosis with polyangiitis

Granulomatosis with polyangiitis is an ANCA-associated necrotising granulomatous inflammation of small and medium vessels. It commonly involves the upper and lower respiratory tract and causes glomerulonephritis.7

Dermatological features include palpable purpura, subcutaneous nodules, digital infarcts and ulceration. Oral ulcers are common and other symptoms include epistaxis, cough, haemoptysis, dyspnoea and nasal deformity.6

The mainstay of treatment is high-dose prednisolone and cyclophosphamide.6 In severe renal disease, plasmapheresis may be indicated.8

Eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis is an ANCA-associated granulomatous and necrotising vasculitis that is eosinophil rich, involving small to medium vessels.7

Glomerulonephritis is common and is associated with adult onset asthma.7 Peripheral eosinophilia is present and the vasculitis can affect almost any organ.6

The mainstay of treatment in these patients is high-dose prednisolone and cyclophosphamide.6

Cryoglobulinaemic vasculitis

Cryoglobulins are abnormal proteins that spontaneously precipitate when blood is cooled below 37°C. The immune complexes formed cause vasculitis and can affect peripheral nerves, joints and kidneys, as well as the skin.6

Acute episodes are triggered by a cold environment and periods of immobility. Hepatitis C is the cause in 80% of cases.6

Management involves a combination of systemic steroids and other immunosuppressive agents. Importantly, if hepatitis C is present, this will need genotyping and treating appropriately.9

Polyarteritis nodosa and cutaneous PN

Polyarteritis nodosa (PN) is a rare form of necrotising vasculitis of medium vessels, which does not cause glomerulonephritis and is not associated with ANCA.7 Systemic PN can affect almost any organ; cutaneous PN has no systemic involvement.6

A variety of viral infections, including hepatitis B, have been implicated in causing the condition. Tender nodules of the lower leg are the most common feature and these can ulcerate.6

Cutaneous polyarteritis can often be managed with NSAIDs and tapering high-dose prednisolone. Polyarteritis with systemic involvement should be managed with a combination of prednisolone and cyclophosphamide. Hepatitis B, if present, will require active treatment.6

When to refer to secondary care

Mild cases of cutaneous small vessel vasculitis can be managed in primary care.

If the case is cutaneous, with significant skin involvement, urgent referral to the dermatology team is required. Renal involvement should be discussed with the nephrology team. Patients who are unwell, with suspected systemic involvement, should be referred to the medical team on call.

In any case of cutaneous small vessel vasculitis, four- to eight-week follow-up is required, so the GP can check BP, U&Es and urinalysis and make sure that late presentation renal disease is not missed.

  • Dr James Miller is a dermatology specialist registrar at University Hospitals of Leicester; Dr Anton Alexandroff is a consultant dermatologist and honorary senior lecturer at Nuffield Health Leicester Hospital, Spire Leicester Hospital, BMI Manor Bedford Hospital and Nuffield Health Cambridge Hospital

References

  1. Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology 2010; 56: 3-23
  2. Fett N. Evaluation of adults with cutaneous lesions of vasculitis. UpToDate April 2016
  3. Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. Am J Dermatopathol 2005; 27(6): 504
  4. Carmen G. Overview of cutaneous small vessel vasculitis. UpToDate October 2016
  5. Podjasek JO, Wetter DA, Pittelkow MR et al. Cutaneous small vessel vasculitis associated with solid organ malignancies: the Mayo experience, 1996 to 2009. J Am Acad Dermatol 2012; 62(2): e55-65
  6. Single-organ small-vessel vasculitis; cutaneous small-vessel vasculitis. In: Griffiths C, Barker J, Bleiker T et al (eds). Rook's Textbook of Dermatology. Chichester, Wiley, 2016
  7. Jennette JC, Falk RJ, Bacon PA et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65(1): 1-11
  8. Jayne DR, Gaskin G, Rasmussen N et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18(7): 2180–8
  9. Mukhtyar C, Guillevin L, Cid MC et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009; 68(3): 310-17

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