Definition

This is a disorder of the skin caused by small vessel vasculitis. It is part of the spectrum of vasculitides.

Pathogenesis

• The disorder can be acute or chronic and may also affect internal organs.
• The kidneys, gastrointestinal tract and joints may also be affected.
• The pathology is probably mediated by immune complexes.^[1]

Calibre and size of the vessels predominantly involved strongly influence the clinical features of the different forms of vasculitis and therefore are one major criterion for classification. Distinctions must also be made between IgG/IgM- and IgA-associated vasculitides and newer classifications exist to do so.^[2]

Aetiology

No cause is found in a third to half of all cases.^[3]

• Many drugs have been reported to cause the condition:
  • The most common are antibiotics, especially amoxicillin.^[4]
  • Non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics are also frequently implicated.
• Upper respiratory tract infections, especially with beta haemolytic streptococci, can cause the condition. As it does not present until after the illness, it is often impossible to know if it was the illness or the antibiotic that caused it.
• Severe bacterial infection, especially bacterial endocarditis.
• Food and food additives have been implicated.
• Hepatitis C has been implicated, especially when there is cryoglobulinaemia.
• Collagen diseases; these have been implicated and, if so, it tends to suggest a more severe course to the disease. It probably represents 10 to 15% of cases.^[5]
• Inflammatory bowel disease has been implicated.
• Malignancy probably accounts for around 1% of cases.^[6] Hairy cell leukaemia and Wegener's granulomatosis are the most common.
• Polyarteritis nodosa and Churg-Strauss syndrome have also been implicated.

Epidemiology

The disease is in many ways similar to Henoch-Schönlein purpura.

• Much of the literature comes from Spain where research has showed that the annual incidence is around 3 per 100,000 for hypersensitivity vasculitis and just under 1.5 per 100,000 for Henoch-Schönlein purpura.^[7]
• Most studies have found the number of men and women affected to be roughly equal.
• The condition does occur in children, but is often labelled as Henoch-Schönlein purpura, as the latter is more common in children. The opposite is true in adults.^[8]

Presentation

History

The patient may complain of itching, burning or pain but often the lesions are asymptomatic. The most common complaint is of the rash - purpura.

• Ask about possible associated symptoms such as fever, arthralgia, myalgia, abdominal pain or diarrhoea.
• There may be blood in the stool, chronic cough, haemoptysis, paraesthesia, weakness, or haematuria.
• Look at past medical history including possible intravenous drug use, hepatitis, transfusion, and travel.
• Ask about inflammatory bowel disease including Crohn's disease and ulcerative colitis along with collagen vascular disorders, particularly rheumatoid arthritis, systemic lupus erythematosis, or Sjögren's syndrome.

Examination

Examine the heart, lungs, and musculoskeletal system and perform abdominal examination to seek associated conditions:

• The most common lesion is palpable purpura.
  • The lesions are usually 1 to 3 mm in diameter but may coalesce to form plaques.
  • Rarely they may ulcerate.
  • The most common place for palpable purpura is the legs.
• Sometimes there is urticaria.
  • This is different from the usual pattern of urticaria in that it tends to last for more than 24 hours and may leave ecchymoses or pigmentation.
  • The sensation is burning rather than itching.
  • It may be helpful to mark the lesions by circling them with a marker such as a ball point pen and asking the patient to note how long they last.
• Livedo reticularis (pink-blue mottled, 'net-like' pattern) is rare but suggests small-vessel vasculitis.
  • It occurs with occlusive or inflammatory disease of small-sized vessels.
  • Nodular lesions may also appear.
• Ulceration suggests involvement of larger vessels but it can occur with very intense purpura.

Investigations

After the condition is confirmed, the purpose of investigation is to discover if there is systemic involvement and if there is an associated disease. As underlying causes are more common in adults, investigations are more appropriate in this group.

• Biopsy is the gold standard not only for diagnosis but also for detection of cutaneous vascular immune complexes by direct immunofluorescence.^[9] A list of relevant differential diagnoses can be generated from:
  • The type of vessel disrupted by inflammation (small and/or muscular)
  • The distribution of vasculitis in the dermis and subcutis
  • The predominating inflammatory cell-type mediating vessel wall damage
  It is often omitted in children.
• FBC, ESR, blood chemistry and urinalysis are basic. ESR is often raised and complement is low.
• Stool should be tested for occult blood. Further examination of the gut may be required if occult bloods are positive.
• Autoantibodies and ASO titre should be taken.
• Of the various forms of hepatitis that should be considered, hepatitis C is the most important.
• Positive rheumatoid factor may suggest possible cryoglobulinaemia.
• IgA levels are often raised in Henoch-Schönlein purpura.
• CXR may be carried out as part of the examination of the chest.

Management

General measures

• If there is an underlying cause that has been established, it needs to be managed.
• If a drug is implicated, its discontinuation usually results in resolution in around 2 weeks.
• As the legs are most commonly affected, elevation of the legs, or compression stockings, may be of value. Avoiding standing, cold temperatures and tight-fitting clothing is also advised.
• If there is a personal or family history of allergy, perhaps with immune complexes and complement consumption, an elimination diet may identify offending food or additives with long-term benefit.^[10]

Pharmacological

• If only the skin is involved with no systemic involvement, colchicine and dapsone have been recommended in the past, but data supporting their efficacy are lacking.^[11]
• Antihistamines may help pruritus. Sometimes the older, sedating ones, are better. NSAIDs are sometimes beneficial.
• The first-choice agents for mild recurrent disease are colchicine, dapsone, and prednisolone.^[12]
• If there is severe systemic involvement, high-dose steroid may be required. In addition, immunosuppressive drugs such as azathioprine, cyclophosphamide and methotrexate may be required.
• Plasmapheresis/plasma exchange and intravenous immunoglobulin are potential therapies for refractory disease.
• The new treatments that work via cytokine blockade or lymphocyte depletion such as tumour alpha inhibitor infliximab and the anti-B-cell antibody rituximab, are showing benefit in certain vasculitic conditions, and may also be options for the future.^[13]

Prognosis

The majority of cases are short-lived; in one paper around 60% of patients had symptoms resolving in less than 3 months.^[3] The outlook will depend on the underlying cause.^[8] If none is found and only skin and joints are affected, the prognosis is good, although recurrence is not uncommon.^[14]

• Paraesthesia, fever, and absence of painful lesions have been found to be risk factors for systemic involvement.
• Cryoglobulins, arthralgia, and normal temperature are risk factors for chronic cutaneous disease.^[15]
• Where the vasculitis presents on a background of Wegener's granulomatosis, polyarteritis nodosa, Churg-Strauss syndrome, or severe necrotising vasculitis, it can be fatal. Steroids and immune modulators may be life-saving.