147. • Churg-Strauss Syndrome has traditionally been classified as occurring in three
phases 2):
• The prodromal phase can start from months up to years before the other phases
and can last for a long time. Churg-Strauss Syndrome is characterized by upper
respiratory symptoms, asthma and general symptoms, such as arthralgia, myalgia,
malaise, fever and weight loss. Allergic rhinitis may also occur 3). Asthma is a
chronic inflammatory airway disease that is characterized by a specific
inflammatory cell response resulting in a swollen, oedematous, hyper-reactive
airway. It is the main manifestation during the prodromal phase of the disease. It is
present in 96–100% of Churg-Strauss syndrome (eosinophilic granulomatosis with
polyangiitis) patients 4). Asthma symptoms generally precede the onset of the
systemic disease by several years and generally become corticodependent 5). Other
upper respiratory symptoms are present in a majority of patients (47–93%). These
symptoms include allergic rhinitis, nasal polyps, recurrent or chronic sinusitis 6). In
this case report of a 38 year old man 7), the patient had an asthma diagnosis since
childhood, but with a recent worsening of the symptoms, cough and dyspnea,
which was followed by upper airway symptoms, hemoptoic sputum and
constitutional symptoms, representing the prodromal phase of Churg-Strauss
Syndrome. CT imaging of the paranasal sinus confirmed chronic sinusitis, which
evolved into the frontal and ethmoidal sinuses in this patient’s case.
148. • The eosinophilic phase is characterized by peripheral eosinophilia and organ
involvement, including lung, cardiac and gastrointestinal involvement. Eosinophilia
is one of the hallmarks of the development of this syndrome into ANCA-associated
vasculitis. It can be found in peripheral, sputum, bronchoalveolar lavage and tissue
eosinophilia. Eosinophilia has been associated with several diseases that affect the
small and large airways, as with many other lung diseases. Indeed, marked
eosinophilia observed during the course of lung disease is not a common event,
and thus, when it occurs, it generally indicates a specific diagnosis 8). A peripheral
blood eosinophilia >10% is one of the clinical criteria for Churg-Strauss Syndrome
diagnosis. Migratory infiltrates in lung imaging is another hallmark of Churg-
Strauss Syndrome and one of the diagnostic criteria of the American College of
Rheumatology. Chest CT scanning is a more sensitive method for evaluating the
infiltrates 9). Extravascular eosinophil can be evaluated by performing a tissue
biopsy. Histopathological analysis of the lungs has revealed that Churg-Strauss
Syndrome can present with an eosinophil-rich granulomatous inflammation of the
airways in addition to small- and medium-vessel vasculitis 10). Churg-Strauss
Syndrome was originally described as a pathological triad consisting of eosinophilic
infiltration, necrotizing vasculitis and extravascular granuloma formation. The early
phase of the disease is characterized by extravascular tissue infiltration by
eosinophils of any organ. In the vasculitis phase, signs of inflammation are
observed in small to medium vessel walls. Vasculitis is characterized by fibrinoid
necrosis and eosinophilic vessel wall inflammation 11). ANCA-positive patients
more frequently exhibit vasculitis in histological specimens 12).
149. • The vasculitic phase presents with constitutional symptoms, such
as fatigue, fever and weight loss. Paradoxically, an apparent
improvement of asthma symptoms can also occur. Peripheral
neuropathy can occur as multiplex mononeuritis or sensorimotor
peripheral neuropathy. Renal manifestations can range from
isolated urinary abnormalities to rapidly progressive
glomerulonephritis. The most common presentation is pauci-
immune focal and segmental necrotizing glomerulonephritis, with
or without crescents, which usually involve less than 50% of the
glomeruli 13). Skin lesions are also a prominent feature of the
vasculitic phase and occur most commonly as palpable purpura and
nodules 14). Neurologic involvement is observed in up to 60–70% of
patients 15). Patients may present with multiplex mononeuritis or a
mixed sensorial and motor peripheral neuropathy. The central
nervous system is involved in 25% of cases with neurological
involvement 16).
150. • Churg-Strauss Syndrome complications
• Churg-Strauss syndrome can affect many organs, including your lungs,
skin, gastrointestinal system, kidneys, muscles, joints and heart. Without
treatment, the disease may be fatal. Complications depend on the organs
involved and may include:
• Peripheral nerve damage. Peripheral nerves extend throughout your
body, connecting your organs, glands, muscles, and skin with your spinal
cord and brain. Churg-Strauss syndrome can damage the nerves in your
hands and feet (peripheral neuropathy), leading to numbness, burning and
loss of function.
• Skin scarring. The inflammation may cause sores to develop that can leave
scars.
• Heart disease. Heart-related complications of Churg-Strauss syndrome
include inflammation of the membrane surrounding your heart
(pericarditis), inflammation of the muscular layer of your heart wall
(myocarditis), heart attack and heart failure.
• Kidney (renal) damage. If Churg-Strauss syndrome affects your kidneys,
you may develop glomerulonephritis. This is a kidney disease that
hampers your kidneys’ filtering ability, leading to a buildup of waste
products in your bloodstream (uremia). Kidney failure is uncommon.
151. • The most frequent clinical settings that should alert physicians (and patients) to the
possibility of Churg-Strauss Syndrome are relatively easy to identify and remember.
• Asthma, especially late-onset asthma (i.e., starting in adulthood), that gradually worsens and
becomes refractory to usual antiasthma drugs, with increased eosinophilia on white blood
cell count. In most of these cases, allergic asthma or allergic bronchopulmonary aspergillosis
is diagnosed, but early stages of Churg-Strauss Syndrome can present in this way.
• Recurrent bronchitides and/or “pneumoniae” in a patient with background asthma,
especially late-onset asthma, with increased eosinophilia on white blood cell count. In most
of these cases, “simple” infection, allergic bronchopulmonary aspergillosis or eosinophilic
pneumonia is diagnosed, but early stages of Churg-Strauss Syndrome can present in this way.
• Worsening, lingering and/or recurrent sino-nasal polyposis and/or sinusitis, especially if
associated with (late-onset) asthma, with increased eosinophilia on white blood cell count.
These manifestations are not sufficient for a diagnosis of Churg-Strauss Syndrome because of
no vasculitis, but early stages of Churg-Strauss Syndrome can present in this way.
152. • Recurrent skin rash (any type) or hives with increased eosinophilia on
white blood cell count. In most of these cases, simple allergy or chronic
urticaria is diagnosed, but early 4 stages of Churg-Strauss Syndrome can
present in this way and many different types of skin lesions can occur in
Churg-Strauss Syndrome.
• In a patient with asthma and/or sino-nasal polyposis, any symptoms of
systemic vasculitis, including skin purpuric rash, numbness, tingling or
weakness in hands or feet (mononeuritis multiplex), scleritis (or
episcleritis), or renal disease (microscopic hematuria being the first
manifestation of glomerulonephritis). Other possible and/or more severe
manifestations, such as coronary arteritis or gut perforations due to
inflammation and occlusion of the small vessels of the bowels, are rare
features of Churg-Strauss Syndrome that are more easily considered
related to vasculitis (Churg-Strauss Syndrome or another type of
vasculitis).
• In a patient with asthma and/or sino-nasal polyposis, any new or
worsening general or constitutional symptoms, including fever, joint pain,
diffuse muscle pain, major involuntary weight loss, chest pain, palpitations
or abdominal pain. These symptoms are not specific but may be the first
signs of a vasculitis, including Churg-Strauss Syndrome
153. • .
• There is no specific blood test for Churg-Strauss Syndrome. Investigations usually include:
• Complete blood count
• Rheumatoid factor (RhF), antinuclear antibody (ANA), antineutrophil antibodies (ANCA)
• Kidney, liver and muscle function tests, as indicated by symptoms and signs
• Imaging studies may include X-rays of the lungs and sinuses, and electrocardiogram (ECG).
• Skin biopsy and/or kidney biopsy may demonstrate the diagnostic combination of tissue
eosinophilia, leukocytoclastic vasculitis and granulomas.
• In such cases, it is wise to check the blood cell count, including eosinophil count; check some
inflammatory signs such as level of C-reactive protein (CRP) and/or erythrocyte
sedimentation rate (ESR); and perhaps order an ANCA screening test as well as other
investigations according to the clinical presentation (e.g., chest X-ray or CT with respiratory
symptoms; CT scan of sinuses with ear nose, and throat manifestations; electromyography of
peripheral nerve conduction with numbness; electrocardiography and cardiac imaging).
Biopsies of skin lesions are easy to perform but may show non-specific leucocytoclastic
vasculitis. The sensitivity of sinus biopsy is low (<50%). Other biopsies, such as peripheral
nerve or lung lesion, may be considered depending on the clinical presentation and after
review of all obtained results, which may be sufficient to consider the diagnosis of Churg-
Strauss Syndrome highly probable for starting the appropriate treatment.
