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Synonyms: leukocytoclastic vasculitis, cutaneous vasculitis, urticarial vasculitis, small-vessel vasculitis
This is a disorder of the skin caused by small-vessel vasculitis. It is part of the spectrum of vasculitides.
- The disorder can be acute or chronic.
- Internal organs such as the kidneys, gastrointestinal tract and joints may also be affected.
- The pathology is probably mediated by immune complexes.
The calibre of the affected vessels predominantly involved strongly influences the clinical features of the different forms of vasculitis and therefore is one major criterion for classification. Distinction must be made between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) and non-ANCA vasculitides. Hypersensitivity vasculitis is an AAV. AAVs are classified according to the Chapel Hill classification revised in 2012.
No cause is found in a third to half of all cases.
Many drugs have been reported to cause the condition. Examples include:
Other implicated causes include:
- Upper respiratory tract infections. As symptoms do not present until after the illness, if an antibiotic is used, it is often impossible to know if it was the illness or the medication that caused them.
- Severe bacterial infection, especially bacterial endocarditis.
- Food and food additives.
- Hepatitis C has been implicated, especially when there is cryoglobulinaemia.
- Collagen diseases.
- Inflammatory bowel disease.
- Malignancy probably accounts for around 1% of cases. Granulomatosis with polyangiitis (Wegener's granulomatosis) and hairy cell leukaemia are the most common.
- Polyarteritis nodosa and Churg-Strauss syndrome have also been implicated.
The disease is in many ways similar to Henoch-Schönlein purpura.
- One study of 297 adults (over the age of 20) at a single centre between 1975 and 2012 found that 195 patients (104 men/91 women) were diagnosed with hypersensitivity vasculitis.
- 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[9, 10].
The patient may complain of itching, burning or pain but often the lesions are asymptomatic. The most common complaint is of the rash - purpura.
History may reveal an underlying cause with signs and symptoms both dependent on this and the disease process. They may include:
- Fever and flu-like symptoms.
- Abdominal pain, diarrhoea, blood in the stool.
- Chronic cough or haemoptysis.
- Paraesthesia, weakness, or haematuria.
- Arthralgia or myalgia.
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.
Take a full drug history, also enquiring into any recent changes in medication.
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 1-3 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 ballpoint 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.
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. 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.
- 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 anti-streptolysin O (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.
- 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 two 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 are 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.
- If only the skin is involved with no systemic involvement, colchicine and dapsone have been utilised.
- 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.
- 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.
- 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.
The majority of cases are short-lived; in one paper around 60% of patients had symptoms resolving in under three months. The outlook will depend on the underlying cause. If none is found and only skin and joints are affected, the prognosis is good, although recurrence is not uncommon.
- 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.
- Where the vasculitis presents on a background of granulomatosis with polyangiitis (Wegener's granulomatosis), polyarteritis nodosa, Churg-Strauss syndrome or severe necrotising vasculitis, it can be fatal. Steroids and immune modulators may be life-saving.
Further reading and references
Morimura S, Sugaya M, Sato S; Interaction between CX3CL1 and CX3CR1 regulates vasculitis induced by immune complex deposition. Am J Pathol. 2013 May182(5):1640-7. doi: 10.1016/j.ajpath.2013.01.023. Epub 2013 Mar 5.
Jennette JC; Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013 Oct17(5):603-6. doi: 10.1007/s10157-013-0869-6. Epub 2013 Sep 27.
Watts R; Hypersenstivity Vasculitis, 2016.
Digklia A, Tzika E, Voutsadakis IA; Cutaneous leukocytoclastic vasculitis associated with letrozole. J Oncol Pharm Pract. 2013 May 14.
Lazic T, Fonder M, Robinson-Bostom L, et al; Orlistat-induced bullous leukocytoclastic vasculitis. Cutis. 2013 Mar91(3):148-9.
Zurada JM, Ward KM, Grossman ME; Henoch-Schonlein purpura associated with malignancy in adults. J Am Acad Dermatol. 2006 Nov55(5 Suppl):S65-70. Epub 2006 Aug 28.
Gupta S, Handa S, Kanwar AJ, et al; Cutaneous vasculitides: clinico-pathological correlation. Indian J Dermatol Venereol Leprol. 2009 Jul-Aug75(4):356-62. doi: 10.4103/0378-6323.53130.
Calvo-Rio V, Loricera J, Ortiz-Sanjuan F, et al; Revisiting clinical differences between hypersensitivity vasculitis and Henoch-Schonlein purpura in adults from a defined population. Clin Exp Rheumatol. 2014 May-Jun32(3 Suppl 82):S34-40. Epub 2014 Feb 11.
Daripally VK, Shah NS; Henoch-Schonlein purpura: a rare vasculitis in older adults. J R Coll Physicians Edinb. 2012 Jun42(2):124-7. doi: 10.4997/JRCPE.2012.207.
Weiss PF; Pediatric vasculitis. Pediatr Clin North Am. 2012 Apr59(2):407-23. doi: 10.1016/j.pcl.2012.03.013. Epub 2012 Apr 6.
Leukocytoclastic vasculitis pathology; DermNet NZ
Cutaneous small vessel vasculitis; DermNet NZ
Businco L, Falconieri P, Bellioni-Businco B, et al; Severe food-induced vasculitis in two children. Pediatr Allergy Immunol. 2002 Feb13(1):68-71.
Brown K, Martin J, Zito S; Severe leukocytoclastic vasculitis secondary to the use of a naproxen and requiring amputation: a case report. J Med Case Rep. 2010 Jul 14:204. doi: 10.1186/1752-1947-4-204.
Chen KR, Carlson JA; Clinical approach to cutaneous vasculitis. Am J Clin Dermatol. 20089(2):71-92.
Tai YJ, Chong AH, Williams RA, et al; Retrospective analysis of adult patients with cutaneous leukocytoclastic vasculitis. Australas J Dermatol. 2006 May47(2):92-6.
Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, et al; Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients. Medicine (Baltimore). 1998 Nov77(6):403-18.
Bouiller K, Audia S, Devilliers H, et al; Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement: A retrospective study in 112 patients. Medicine (Baltimore). 2016 Jul95(28):e4238. doi: 10.1097/MD.0000000000004238.