The
first description of Churg-Strauss syndrome (CSS) was
made by pathologists Jacob Churg and Lotte Strauss in
1951. It was first referred to as allergic granulomatosis,
allergic angiitis, having recognized it as a separate
clinical entity from polyarteritis nodosa.
They described it as a syndrome of asthma, fever,
and hypereosinophilia along with histologic findings of
eosinophilic systemic vasculitis, extravascular granulomas,
and necrotizing vasculitis.1
DIAGNOSIS
Since
then, several groups have put forth criteria to better
accurately recognize and diagnose this syndrome.
The definition of CSS has evolved over the years
in that it is now recognized that there may be a natural
course to the disease process. Lanham et al. was
the first to suggest such a sequence by noting the progression
of allergic rhinitis, followed by asthma, and then the
development of vasculitis. Their criteria included clinical findings with
or without pathological material: asthma, eosinophila
> 1.5x109/L,
and evidence of vasculitis that involves at least 2 organs.2
As of 1990, the American College of Rheumatology
established six criteria for the classification of CSS:
asthma, paranasal sinus abnormalities, eosinophila >10%,
neuropathy (mono or poly), pulmonary infiltrates (migratory
or transient), and a biopsy containing a blood vessel
with extravascular eosinophils.3 The presence
of four of more of these criteria has a sensitivity of
85% and a specificity of 99.7% for CSS.4
CLINICAL COURSE AND CHARACTERISTICS
To clarify
the sequential course of CSS, the clinical and pathological
aspects of this syndrome are divided into three phases
with the caveat that the sequence is not necessarily set
in stone nor do all patients present with all features. The
first is the prodromal phase that occurs in the second
and third decades of life and is characterized by atopic
disease, allergic rhinitis, and asthma. The second is
the eosinophilic phase, which includes peripheral eosinophilia
and eosinophilic infiltration of multiple organs. The
third is the vasculitic phase occurring in the third and
fourth decades of life which affects the medium and small
vessels and is often associated with vascular and extravascular
granulomatosis. During this last phase, patients would present
clinically with constitutional symptoms.
The
hallmark feature of CSS is asthma, which is noted to occur
in more than 95% of patients and often persists in at
least 80% of patients after treatment and remission of
the vasculitis. Allergic
rhinitis is another common finding (about 75%), as are
nasal polyps and sinusitis.
Typically, these may be the initial presenting
symptoms.
As one progresses through to the vasculitic phase of the
disease process many organ systems can be affected. Peripheral
neuropathy, of which mononeuritis monoplex is the most
frequent finding, is common and affects up to 75% of patients
with CSS. If left
untreated it can progress to polyneuropathy. Cerebral
hemorrhage and infarction are significant causes of morbidity
and mortality from CSS. Cardiac involvement includes acute pericarditis
(32%), constrictive pericarditis, heart failure (47%),
and myocardial infarction.
Approximately half of the mortality from CSS is
attributable to its manifestations of cardiovascular disease.
The gastrointestinal system is affected by an eosinophilic
gastroenteritis in which most patients present with abdominal
pain (59%), diarrhea (33%), bleeding (18%), and possible
intestinal perforation.
Pancreatitis and cholecystitis also have been reported
in association with CSS.
Cutaneous lesions can be seen in 2/3 of patients,
but present diversely in the form of vasculitic palpable
purpura, livedo reticularis, or tender subcutaneous nodules. Renal involvement is typical, but renal failure
is rare. On biopsy,
the characteristic lesion is focal segmental glomerulonephritis
often with necrotizing features and crescent formation.
Systemic hypertension can also be present (29%).
LABS AND STUDIES
Laboratory
findings are fairly non-specific for CSS. The most characteristic
finding is peripheral blood eosinophilia of greater than
10%. Other typical findings include a normochromic, normocytic
anemia and those markers reflecting an acute phase response,
such as leukocytosis and marked elevation in the erythrocyte
sedimentation rate. In addition, most patients have elevated
IgE levels. Some have low levels of circulating IgE immune
complexes, rheumatoid factor, and antinuclear antibodies. P-ANCA positivity, in which the antibody is
directed against myeloperoxidase, is present in more than
half the patients with CSS.
Nevertheless, the clinical utility of p-ANCA remains
poor because it does not adequately reflect disease activity.
Several serum markers have been found to correlate
better with disease activity: eosinophil cationic protein
(ECP), soluble thrombomodulin, and soluble interleukin
(IL)-2 receptor.5
Radiographic
findings are rather diverse as well. CT scan of the sinuses
can confirm sinusitis. Chest radiographs demonstrate transient
opacities or consolidations (75% of patients) that are
not in any particular lobar or segmental distribution.
Commonly, the infiltrates are seen in a peripheral
distribution. CT
scans of the chest may demonstrate pleural and pericardial
effusions, cavitating pulmonary nodules, bronchial wall
thickening, and thickened interlobular septa.
TREATMENT
The
mainstay of treatment for CSS is corticosteroids. Because corticosteroids are usually effective for most patients
without severe organ involvement, it is considered first-line
therapy. The recommended dosage of prednisone is 1mg/kg/day
for one month or until disease resolves, followed by a
gradual taper for up to one year.
Those patients who present with acute systemic
involvement or with indicators of poor prognosis can receive
adjuvant treatment with cyclophosphamide at 2mg/kg/day
or monthly intravenous pulse dosing of 0.6mg/m2. Other alternative therapies such as intravenous
immunoglobulin, cyclosporine, interferon-alfa, mycophenolate
mofetil, and azathioprine have been reported, but remain
unproven.6
The prognosis of CSS is unclear
because before the use of steroids, CSS was usually fatal.
But certainly we now know corticosteroid treatment improves
remission and survival greatly. Patients with limited
organ involvement respond well to corticosteroids alone. The two most significant predictors for a poor
outcome are cardiac involvement and gastrointestinal disease,
and hence, at the outset may need adjuvant cyclophosphamide
therapy.
In
conclusion, the diagnosis of CSS depends on the recognition
of several clinical syndromes along with confirmation
by biopsy of affected tissues.
Therapy is tailored to whether there is limited
or severe organ involvement. Most patients respond favorably
to corticosteroids and/or cyclophosphamide with fairly
good remission rates. Prognosis is generally good.
Patients will need further observation after remission
as well as treatment for asthma, which tends to persist.
