Granulomatosis with polyangiitis (GPA) – skin manifestations

Definition

Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) is an ANCA-associated vasculitis with necrotising granulomatous inflammation, vasculitis of small and medium-sized vessels and focal necrotising glomerulonephritis. The upper and lower respiratory tract and the kidneys are typically affected; in principle any organ can be involved, including the skin.

Occurrence & epidemiology

In a large UK cohort the incidence was 11.8 per million person-years. Both sexes are affected equally, the mean age at onset is around 40 years; GPA is most common in people of European ancestry but occurs in all age groups and ethnic groups.

Aetiopathogenesis

The cause is unknown; it is an autoimmune disease in which antibodies against proteinase 3 (PR3-ANCA, cytoplasmic pattern c-ANCA) are thought to be pathogenic. Bacterial infection is discussed as a trigger; the disease is not inherited.

Clinical features

• Skin (in 40–50% of patients): palpable purpura, ulcers, tender subcutaneous nodules, papules, vesicles, livedo reticularis; rarely pyoderma gangrenosum and Raynaud phenomenon.
• Mouth and ENT (70% at onset, 92% during the course): sinusitis, nosebleeds, crusts, septal perforation, saddle nose, otitis, painful mouth ulcers, "strawberry gums", subglottic stenosis.
• Other organs: lungs (nodules, cavities, haemorrhage), kidneys, eyes (scleritis, proptosis), nerves, joints; fever, weight loss.

Histology

Granulomas of epithelioid histiocytes, often with multinucleated giant cells, central (geographic) necrosis rimmed by palisading histiocytes. Skin biopsies show granulomatous vasculitis, necrotising or leukocytoclastic vasculitis and extravascular palisading granulomas.

Diagnosis

• ANCA: most patients with active disease have c-ANCA with antibodies against proteinase 3; ANCA also occur in other conditions (e.g. bacterial endocarditis, cocaine use, systemic lupus erythematosus, tuberculosis).
• Biopsy of affected tissue (e.g. skin, lung, kidney) for confirmation; a skin biopsy is helpful if it shows granulomatous vasculitis.
• Laboratory tests (ESR, CRP, full blood count, creatinine, urine sediment with dysmorphic red cells), CT of the chest and paranasal sinuses.

Differential diagnoses

• Erythema nodosum
• Pyoderma gangrenosum
• Polyarteritis nodosa
• Martorell Ulcer
• Lupus erythematosus
• Cutaneous sarcoidosis
• Granuloma faciale
• Rosacea

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References (selection)

1. DermNet: Granulomatosis with polyangiitis
2. MSD Manual Professional: Granulomatosis with Polyangiitis (GPA)

Cross-references