Once in a lifetime: Eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome)

In the next in our series on rare conditions that GPs might only encounter once in a career, Dr James Chambers discusses this rare syndrome and how it should be diagnosed and managed

What is it?

Eosinophilic granulomatosis with polyangiitis (EGPA), more commonly known by its previous name Churg Strauss syndrome, is a rare inflammatory disease affecting both small and medium blood vessels.

First identified in 1951 by Jacob Churg and Lotte Strauss, EGPA has three key phases in its development. The first is driven by airway inflammation, resulting in late-onset asthma or treatment resistant allergic rhinitis.

This is shortly followed by peripheral blood eosinophilia. During this phase there may be no symptoms at all, but vague symptoms such as joint pain, malaise, fever and weight loss may be experienced.

The final phase typically develops 3-9 years after the start of symptoms with the development of vasculitis. By the nature of vasculitis, this affects multiple organ symptoms. Two-thirds of patients present with a vasculitic rash, which typically manifests as a purpuric or urticarial rash, nodules and/or ulceration or necrosis. Renal involvement is also common, experienced in a quarter of patients, presenting with visible haematuria or hypertension. Neurological involvement can manifest in peripheral neuropathy, specifically a mononeuritis multiplex (such as wrist or foot drop). Gastrointestinal involvement will present with abdominal pain, nausea or, very rarely, ulceration and even perforation of the bowel. The most fatal complication is cardiac disease, which presents in a variety of ways such as coronary artery disease, cardiomyopathy, restrictive pericarditis or pericardial effusions.

How rare is it and what causes it?

EGPA is thankfully quite rare, affecting approximately 1 to 3 per million adults worldwide. Men and women are equally as affected and it remains rare in children, being typically diagnosed between 38 and 54 years of age.

The specific cause remains unknown, but the working theory is that it is an autoimmune disorder. This is supported by the fact that many patients with EGPA are positive for an autoantibody called anti-neutrophil cytoplasmic antibodies (ANCA), frequently associated with other autoimmune disorders. However, there remains a subset of patients who are not ANCA-positive. In these patients, a dysregulated immune response resulting in an excessive allergic response is a likely factor, although the specific triggers for individuals remain unclear.

Clues for early detection

Due to the vague nature of the condition’s symptoms, EGPA is unlikely to be a diagnosis made on the first consultation. Instead, spotting a pattern of evolving symptoms, likely over a period of years, is essential to prevent serious complications developing. These early signs are important to keep an eye out for, especially when in combination:

Late-onset or difficult-to-treat asthma, especially when combined with nasal polyps.
Mononeuritis multiplex (motor or sensory deficits in a specific peripheral nerve causing asymmetrical presentation) – eg, foot drop.
Elevated blood eosinophil count (>1 x 10⁹/L).
Positive blood test for ANCA.
Haematuria (visible and non-visible).

May be confused with…

Many of the symptoms of EGPA have significant overlap with more common conditions we see every day. Conditions like asthma and allergic rhinitis can present with respiratory symptoms and blood eosinophilia. The key red flags in such cases would be the development of other multiorgan symptoms, as well as being resistant to typical treatments.

Vasculitis is itself a group of conditions that can have a variety of underlying causes or triggers, including infection, systemic lupus erythematosus (SLE), drug-induced vasculitis and dermatomyositis – which may cause the rash seen in EGPA. Granulomatosis with polyangiitis, previously known as Wegner’s granulomatosis, is probably the most well-known small/medium vessel vasculitis condition. It has a lot of similarities to EGPA, including respiratory and nasal involvement, as well as being associated with ANCA antibodies. However, the disease more typically causes nosebleeds and haemoptysis due to its pathophysiology being more inflammatory than allergic, as well as having other symptoms such as hearing loss not associated with EGPA.

Polyarteritis nodosa (PAN) is another form of medium vessel disease which typically causes the formation of microaneurysms which subsequently rupture resulting in haemorrhage, thrombosis and organ ischemia. Again, due to widespread involvement there is a lot of crossover in symptoms, but typically patients experience serious organ complications more frequently and quickly including renal failure, hypertension, gastrointestinal infarction and CNS involvement. The lungs are generally spared compared to EGPA, where they are often the first symptom that presents.

Isolated blood eosinophilia also has a plethora of other causes including parasitic infections, malaria, TB, drug induced, Addison’s disease and malignancy.

Red flags

In a patient presenting with asthma/nasal polyps and/or a raised blood eosinophil count above 1 x 10⁹/L consider the following as ‘red flag’ symptoms:

Haematuria – suggestive of glomerulonephritis.
Palpable purpura.
Breathlessness, chest pain, unexplained fever – suggestive of pericarditis.
Unexplained weight loss, fever or night sweats.
Polyarthritis.
Mononeuritis multiplex.
Recurrent or severe unexplained abdominal pain – suggestive of ischaemic bowel.

Usual treatment and prognosis

Early identification of EGPA is important and therefore suspected cases should be discussed with secondary care urgently, so that treatment may be started as quickly as possible. This will usually mean discussion with nephrologists but may require liaison with other specialities depending on symptoms, such as respiratory or ENT specialists.

As an autoimmune disease, steroids are the mainstay of inducing remission of the disease. Often requiring high doses of prednisolone such as 60mg, they are tapered down gradually over a period of weeks to months. This is often combined with nasal and inhaled steroids for symptomatic relief.

Immunosuppressive therapy has a role in aiding to taper down steroids and maintain disease remission. Cyclophosphamide is often used intravenously as pulse therapy but other immunosuppressants such as azathioprine and methotrexate can also be considered. Monoclonal antibody therapy remains an exciting area of development, with mepolizumab being approved as an add-on therapy for severe, resistant disease.

EGPA has an improving survival rate with widespread immunosuppressive therapy now widely available, with a quoted 5-year survival rate of more than 80%. However, it remains a challenging diagnosis to both live with and manage, as it has no cure and frequently relapses. It’s important as clinicians we recognise the signs of a relapse and are there to support our patients suffering with it.

Prompt recognition and treatment is the main factor which affects survival, underscoring the important role GPs have in managing this condition. Identifying these features early and improving our understanding of EGPA can hopefully improve survival rates even further.

Dr James Chambers is a GP Registrar in Staffordshire