PAN is caused by a complex mixture of immunological factors. PAN may be triggered by infections, in particular hepatitis B virus. Other infections that may cause PAN include hepatitis C virus, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), parvovirus, cytomegalovirus (CMV), coxsackie B4 virus, streptococcus and mycobacterium fortuitum. Certain drugs (such as minocycline), malignancies (especially hairy cell leukaemia), and systemic disorders (such as lupus and inflammatory bowel disease) are also associated with PAN. Lastly, certain genetic factors can make an individual more prone to getting PAN.
On the skin, there may be deep nodules most commonly located on the lower legs or near the ankles, followed by the thighs, buttocks, arms or hands. The nodules may be painful and may ulcerate. There may also be radiating star-shaped purple bruises (retiform purpura) or lace-like reticulated rashes (livedo racemosa). Low blood supply to the fingertips causing tissue death can occur as well.
Both cutaneous PAN and systemic PAN may present with generalised symptoms such as weight loss, tiredness, myalgias, joint pains, fevers and nerve numbness.
In systemic PAN, other organs may be involved, leading to:
- Gastrointestinal involvement – abdominal pain
- Heart involvement – shortness of breath, peripheral oedema
- Kidney involvement – high blood pressure, kidney failure
- Testicular involvement – orchitis
- Brain involvement – stroke
- Lung involvement – this would be very rare in PAN, and if involved may suggest another diagnosis rather than PAN
The diagnosis is usually made by a specialised medical doctor such as a dermatologist or immunologist. When there’s skin lesions, a deep incisional skin biopsy is crucial in making the diagnosis of PAN. The sample will be examined under the microscope, which would likely show inflammation of the medium vessels. Blood tests and imaging needs to be ordered to rule out other types of medium vessel vasculitis, to look for the underlying cause of the PAN such as infections and to plan treatment.
When PAN is associated with an underlying cause, the underlying cause should be addressed e.g. HBV treated and minocycline stopped.
Cutaneous PAN
As cutaneous PAN follows a favourable prognosis, treatment for it is not as aggressive as treatment for systemic PAN. In mild or localised cutaneous PAN, topical or intralesional corticosteroids may be enough. However, progressive or extensive disease may warrant systemic corticosteroids. Second-line treatments for cutaneous PAN include methotrexate, dapsone, hydroxychloroquine, colchicine, azathioprine, mycophenolate and IVIg.
Systemic PAN
First-line treatment for systemic PAN is high dose systemic corticosteroids tapered over 3-6 months. Second-line treatment for systemic PAN include cyclophosphamide, Rituximab, plasmaphoresis and IVIg.
Cutaneous PAN is considered to have a favourable prognosis, despite that it may be potentially chronic. Systemic PAN associated with gastrointestinal track, renal heart and brain involvement are associated with higher mortality.
This information has been written by Dr Cathy Zhao and Dr Tanumay Raychaudhury