++
Vasculitis affecting the lung is exceptionally uncommon in children.
The presentation may vary from mild, chronic respiratory symptoms to
an acute, catastrophic, life-threatening pulmonary hemorrhage. When
symptoms are indolent, diagnosis may be delayed by months or years.
Early, aggressive treatment is imperative in cases of pulmonary
vasculitis. Cumulative lung damage due to ongoing inflammation can lead
to pulmonary fibrosis.
++
The epidemiology of pulmonary vasculitis is varied, depending
on the underlying disease process. (Vasculitic diseases are discussed
in more detail in Chapter 203.) In general,
the autoimmune diseases affect females more than males in adulthood.
In childhood, the gender discrepancy may be less. Some vasculitic
syndromes can affect African Americans and Asians with greater frequency
and with greater severity of disease than Caucasians. Age of onset
in children is variable as well. For example, the mean age of onset
of Wegener granulomatosis (WG) in children is 13 years, with reports
of patients presenting before their first birthday.1
++
Vasculitis signifies blood vessel wall inflammation. Neutrophils
infiltrate the vessel walls and damage the endothelial cell layer.
Vessel walls thicken and result in luminal narrowing. Fibrinous
thrombi may further occlude capillary blood flow.2 Over
several weeks to many months, inflammation of the blood vessel wall
leads to fibrosis. Simultaneously, inflammation involves the pulmonary
interstitium and leads to fibrosis. The end result is destruction of
normal lung architecture with decreased gas-exchange capacity.2
++
The etiology of the diseases that result in pulmonary vasculitis
is unknown. The collagen vascular and granulomatous diseases are
felt to be complex genetic conditions. Numerous genes, most of which
are currently undefined, may lead to a predisposition to develop
a specific autoimmune condition. Environmental factors, such as
exposure to viruses, may serve as triggers to set off the cascade
of autoimmunity.
+++
Clinical Features
and Differential Diagnosis
++
A child with pulmonary vasculitis may present with indolent symptoms,
including fatigue, fever, weight loss, failure to thrive, pallor,
decreased appetite, or irritability. Respiratory symptoms may include cough,
dyspnea, chest tightness, or hemoptysis. Some present with acute
symptoms, including massive pulmonary hemorrhage, that can result
in respiratory failure and cardiovascular collapse. The slow, indolent
presentation of mild intermittent respiratory symptoms as seen in
the case of pulmonary capillaritis can lead to misdiagnosis (atypical
asthma) and delayed diagnosis (Fig. 517-1).3 The
child presenting with frank hemoptysis secondary to bleeding of
medium- or large-sized vessels is generally diagnosed more promptly.
The possibility of pulmonary vasculitis should be raised in any child
who has the triad of respiratory symptoms, anemia, and bibasilar
infiltrates on chest x-ray.4
++
++
Symptom presentation also varies, depending on the size of the
vessels involved and the pathophysiological mechanism affecting
the vessels. The differential diagnosis of small- and medium-vessel
vasculitis includes Wegener granulomatosis, Churg-Strauss syndrome
(CSS), microscopic polyangiitis (MPA), and polyarteritis nodosa.5 Large-vessel
vasculitis may be due to Takayasu arteritis or Behçet disease.6 In
many patients, the underlying disease process causing pulmonary
vasculitis is unknown, but as the illness evolves, the pattern of
organ involvement allows more definitive diagnosis. Diagnostic uncertainty may
also be due to the overlap of the vasculitic and autoimmune disorders.
++
Wegener granulomatosis is suggested by the triad of inflammation
of the upper respiratory tract, the lower respiratory tract, and
the kidney (see Fig. 517-2),7 as
discussed in Chapter 203. The triad associated
with CSS includes asthma, eosinophilia, and necrotizing vasculitis.
CSS is exceedingly rare in the pediatric population. Like Wegener,
CSS may involve the kidneys and cause inflammation of the sinuses,
the joints, and the skin. CSS is more likely to cause cardiac conduction
delays and gastrointestinal hemorrhage.7 In microscopic
polyangiitis, the kidneys are affected most commonly, while pulmonary
vasculitis occurs in less than one third of cases. When the lung
is affected, the inflammation affects small vessels.7
++
+++
Diagnostic Evaluation
++
A complete list of diagnostic studies to be considered in a vasculitis
patient is listed in Table 517-1. The diagnostic
approach varies, depending upon the symptom presentation.
++
++
The initial evaluation of suspected vasculitis includes evaluation
of inflammatory markers such as white blood cell count, platelet count,
sedimentation rate, and C-reactive protein in those with an indolent
or acute presentation. Evidence of other organ involvement should
include evaluation of renal function and liver function. If systemic
lupus erythematosus is suspected and a serum antinuclear antibody
test is positive, then testing should be done for other antibodies
such as double-stranded DNA, Ro, La, ribonuclear protein, and Smith.
Evaluation of serum antineutrophil cytoplasmic antibodies (ANCAs)
is also useful. These antibodies are directed against antigens in
the cytoplasm of neutrophils and monocytes. Cytoplasmic-ANCA (c-ANCA)
is usually directed against proteinase 3 (PR3). Perinuclear-ANCA
(p-ANCA) is directed against myeloperoxidase (MPO). The ANCA-associated
vasculitides include Wegener granulomatosis, Churg-Strauss syndrome,
and microscopic polyangiitis.5 Adult Wegener’s
patients have a positive ANCA in 90% of cases (usually
c-ANCA). Over half of the adult patients with Churg-Strauss syndrome
and microscopic polyangiitis have a positive ANCA (usually p-ANCA).7
++
EKG and echocardiogram should be considered to evaluate cardiac
rhythm and function. Computerized tomography (CT) of the sinuses
may demonstrate inflammatory infiltration in cases of Wegener granulomatosis. Ophthalmologic
examination can demonstrate uveitis. An audiogram may demonstrate
sensorineural hearing loss.
++
In a patient who presents with hemoptysis, the initial workup
includes a hemoglobin and reticulocyte count to check for anemia
and a chest x-ray to identify evidence of bleeding in the lung.
If the x-ray is unrevealing, a CT scan may show pulmonary infiltrates
and pulmonary nodules. In most cases, the findings are bilateral.
Other radiographic findings may include atelectasis; mediastinal
lymphadenopathy; and in long-standing disease, calcification.6 If
the clinical picture is uncertain, bronchoscopy may be utilized
to prove bleeding in the lung. Hemosiderin-laden macrophages may
be found in the bronchial alveolar lavage fluid, especially in the setting
of chronic bleeding.4 In Wegener granulomatosis,
bronchoscopy may demonstrate upper airway disease such as bronchial
stenosis, inflammatory lesions, and ulcerations.5 Once
pulmonary hemorrhage is established, a tissue diagnosis should be
sought. Transbronchial biopsy specimens may be insufficient to make
a diagnosis of vasculitis. Video-assisted thoracoscopic or open-lung
biopsy offers the greatest chance of finding histopathologic evidence
of pulmonary vasculitis. If suspected pulmonary vasculitis is one
component of a systemic disease, then open-lung biopsy can be deferred. Tissue diagnosis
may be pursued with biopsy of involved skin, sinus, or kidney.
++
If an exhaustive workup for pulmonary hemorrhage is negative
for an autoimmune disease and lung pathology shows no evidence of
vasculitis, one must consider the diagnosis of idiopathic pulmonary hemosiderosis
(IPH). Pathological findings may include bland hemorrhage, well-preserved
pulmonary architecture, and minimal or no interstitial inflammation.8 The
etiology of IPH is poorly understood. The hemorrhage in IPH may
be due to a combination of factors such as autoimmunity, capillary
fragility, allergy, genetic predisposition, environmental exposure to
fungal toxins, and defective iron metabolism (see Fig.
517-3).8
++
++
Treatment for pulmonary vasculitis starts with stabilization
of the patient. Presentation with hypoxia, respiratory distress,
and ongoing bleeding is an emergent situation that may require mechanical
ventilation and blood transfusion. Less acute presentation may just require
oxygen supplementation and close monitoring. Once the diagnosis
of pulmonary vasculitis has been confirmed, the cornerstone of treatment
is aggressive immunosuppressive therapy, as detailed in Chapter 203. In most cases, the treatment consists of high-dose corticosteroids
and cyclophosphamide.5 The family must be educated
regarding the side effects of immunosuppression. Administration
of live vaccines is contraindicated. Annual influenza vaccination
is encouraged. Pneumocystis carinii pneumonia prophylaxis
should be initiated. The child should be supplemented with calcium
and vitamin D while on steroids. Menstruating girls should be given
leuprolide while taking cyclophosphamide to reduce the risk of infertility.
Male patients should consider sperm banking. Cyclophosphamide therapy
requires close monitoring for leukopenia and hemorrhagic cystitis.
Less toxic agents such as methotrexate, azathioprine, or mycophenolate
mofetil are used for maintenance therapy.7
++
Complications may arise from both ongoing inflammation and resulting
fibrosis and from the cytotoxic therapies used to treat vasculitis. Patients
may experience chronic fatigue, dependence on oxygen supplementation,
and gradual deterioration in lung function. The main complications
from the treatments include opportunistic infections and drug toxicity.
++
The implementation of aggressive therapies has reduced mortality
rates significantly in pulmonary vasculitis. In adult patients with
Wegener granulomatosis, what was once a 1-year mortality rate of
80% is now 10%. Although remission is achieved
in 90% of patients, relapse occurs in greater than 50% of
patients undergoing standard treatment.5 In children
with IPH, the mortality rate remains significant.9 Case
series report 3- to 5-year mortality rates of 15% to 33%.8