Churg-strauss syndrome presenting with salivary gland enlargement and respiratory distress

Authors

  • Francesco Boin,

    1. The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • James J. Sciubba,

    1. The Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • John H. Stone

    Corresponding author
    1. The Johns Hopkins Vasculitis Center, Johns Hopkins Bayview Medical Center, Baltimore, Maryland
    • The Johns Hopkins Vasculitis Center, 5501 Hopkins Bayview Circle, 1B.23, Baltimore, MD 21224
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    • Dr. Stone is a Hugh and Renna Cosner Scholar in the Center for Innovative Medicine at Johns Hopkins University.


Introduction

The full expression of Churg-Strauss syndrome (CSS) is characterized by eosinophilia, a necrotizing vasculitis of small to medium blood vessels, and extravascular granuloma formation. The development of CSS typically occurs on a background of asthma, allergic rhinitis, or nasal polyps (1). A number of allergic, infectious, neoplastic, and idiopathic diseases may present with blood as well as tissue eosinophilia, sharing patterns of organ involvement and clinical features that are similar to those of CSS (2). Prompt distinction of CSS from these other entities is essential to the timely institution of appropriate treatment and the prevention of the potentially devastating complications of this disorder: congestive heart failure, severe gastrointestinal ischemia, central nervous system involvement, crippling vasculitic neuropathy (i.e., mononeuritis multiplex), glomerulonephritis, and others (3).

In CSS, allergic manifestations and upper respiratory tract symptoms may occur anywhere from months to many years before the onset of systemic vasculitis. Empiric glucocorticoid treatment of the atopic features that characterize the disease's early phase may suppress the emergence of vasculitis, at least temporarily. Conversely, the introduction of more effective inhaled agents for the management of asthma (e.g., the leukotriene inhibitors) is believed to unmask latent CSS in many patients by permitting reductions in the systemic glucocorticoids used to treat reactive airway disease (4). In the absence of pathologic evidence of destructive inflammation within blood vessel walls, distinguishing early CSS from other forms of eosinophilia is challenging.

The pathologic diagnosis of CSS has traditionally been linked to the detection of necrotizing vasculitis accompanied by presence of eosinophilic granulomas (1). All of the patients described in 1951 by Churg and Strauss died from their conditions. Consequently, the clinical and pathologic features of the cases described in the original report of the disease were advanced. Moreover, complete postmortem examinations were available on all patients. In the current era, when awareness of CSS is higher, diagnostic testing is more facile, and the availability of effective therapy is widespread, the diagnosis of CSS is more likely to be suspected in the clinic than at postmortem.

The authors describe a case of CSS in a patient with long-standing asthma and rhinitis who developed enlarged salivary glands, lymphadenopathy, pulmonary infiltrates, and respiratory distress. Identification of nonvasculitic eosinophilic tissue infiltrates within the salivary glands and skin in the context of the patient's overall clinical picture led to the diagnosis of CSS at an early stage, the prompt institution of therapy, and a good outcome.

Case report

A 35-year-old African American man with a 2-year history of asthma and recurrent sinus congestion came to the emergency room with respiratory distress and an oxygen saturation of 78% on room air. He had experienced fatigue and low-grade fevers for several weeks, followed by progressive shortness of breath and chest tightness over several days. He had also developed sinusitis that was refractory to antibiotics, cervical adenopathy, and enlargement of minor salivary glands. His asthma had been difficult to control over the weeks preceding his presentation, requiring short courses of systemic glucocorticoids with relapse of symptoms upon discontinuation. He had never taken leukotriene inhibitors. Beta agonists and inhaled glucocorticoids were the basis of his current asthma regimen. He was employed as a construction worker and had smoked ∼10 cigarettes a day for 15 years, but denied ethanol abuse and illicit drug use.

On physical examination, the patient had a respiratory rate of 32/minute, a blood pressure of 150/95 mm Hg, a heart rate of 124/minute, and a temperature of 37.4°C. There was prominent sublingual and submandibular gland enlargement bilaterally (Figure 1), but the parotid glands were normal. The nasal mucosa was hyperemic but without crusts, bleeding, or ulcers. The cervical lymph nodes were enlarged, mobile, and nontender. A single palpable brown nodule was present on mid-shin of the right leg. Lung auscultation revealed crackles at the bases and scattered rhonchi, but no wheezing. The cardiac examination, remarkable only for tachycardia, showed no murmurs, rubs, or gallops. The musculoskeletal examination results were within normal limits. There was no evidence of motor weakness or other focal findings on neurologic examination.

Figure 1.

Sublingual salivary gland enlargement.

The chest radiograph (Figure 2A) demonstrated bilateral “fluffy” alveolar infiltrates, consolidation of upper lobes (more on the left than right), and hilar adenopathy. A high-resolution computed tomography of the chest (Figure 2B) was significant for diffuse, patchy bilateral nodular infiltrates without cavitations and adenopathy of the hilum and aorto-pulmonary window (largest lymph node 2.5 × 1.8 cm). The study was negative for pulmonary embolism. The complete blood count revealed a white blood cell count of 14,470/mm3 (33% eosinophils), a hemoglobin of 14.5 gm/liter, and a platelet count of 270,000/mm3. Test results of liver and kidney function were normal, including urinalysis and microscopic examination of the urinary sediment. The erythrocyte sedimentation rate was 68 mm/hour. Assays for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. The serum angiotensin-converting enzyme level was 21 mg/dl (normal 9–67 mg/dl).

Figure 2.

A, Chest radiograph showing bilateral alveolar infiltrates, consolidation of upper lobes (left > right), and hilar adenopathy. B, Computed tomography scan of the chest showing diffuse, patchy, nodular infiltrates (without cavitation) in both lung fields, as well as adenopathy in the hilum and aorto-pulmonary window (largest lymph node 2.5 × 1.8 cm).

The patient underwent bronchoscopy, which revealed eosinophilia (20%) of the lavage fluid. A transbronchial biopsy of the lung parenchyma was nondiagnostic. Fluid and tissue analyses (including culture) from this procedure were negative. Biopsy of the sublingual glands (Figure 3A) showed diffuse foci of chronic inflammation with concentric patterns of eosinophilic infiltration. Eosinophils were detected in the lumina of salivary ducts and were observed migrating through blood vessel walls, but there was no evidence of vascular wall destruction or fibrinoid necrosis. Biopsy of the skin nodule (Figure 3B) revealed intense perivascular and interstitial eosinophilic granulomatous infiltrates. Areas of basophilic collagen degeneration surrounded by palisading histiocytic granulomas and multinucleated giant cells were consistent with a Churg-Strauss granuloma, or cutaneous extravascular necrotizing granuloma (5).

Figure 3.

A, Concentric pattern of inflammatory infiltrate with dominant eosinophilic component surrounding acinar structures and ductal remnants. B, Forming Churg-Strauss granuloma: multinucleated giant cells and palisading hystiocytic elements with scattered eosinophils.

Because of his severe respiratory compromise at presentation, as the workup proceeded the patient was treated in the intensive care unit with 1 gm of methylprednisolone intravenously for 3 days, followed by prednisone 1 mg/kg/day. He improved promptly both clinically and radiologically, and was discharged only 6 days after admission. At a followup visit only 1 month after his hospitalization, he was noted to have developed a left foot drop consistent with the complication of vasculitic neuropathy (which occurs in 80% of patients with CSS [3]). This resolved completely over the ensuing weeks of treatment. Six months later, his CSS remained in remission on 5 mg/day of prednisone.

Discussion

This patient's presentation with late-onset asthma, chronic rhinitis, recurrent sinusitis, striking blood eosinophilia, pulmonary infiltrates, and, eventually, a foot drop was consistent with CSS, even in the absence of pathologic findings diagnostic for vasculitis (6). The recognition of compatible disease manifestations and pathologic features at sites considered unusual (the salivary glands and lymph nodes) made it possible to distinguish CSS from other disorders associated with eosinophilia. These sites, easily accessible by biopsy, offered appealing alternatives to more aggressive diagnostic procedures (e.g., lung or nerve biopsy).

CSS was first described in 1951 as an allergic angiitis and granulomatosis consisting of a primary systemic vasculitis with blood eosinophilia in patients with strong allergic background (asthma and rhinitis) (1). Since the original definition, subsequent classification schemes have invariably restricted the diagnosis of CSS to histologic or clinical evidence of eosinophilic vasculitis (7). As Lanham et al first observed, however, CSS often appears to unfold in 3 phases: a prodromal phase with allergic disease manifestations, a phase marked by peripheral eosinophilia and eosinophilic tissue infiltrates, and a vasculitic phase in which frank manifestations of necrotizing vasculitis become evident (8). Following the diagnosis of CSS, these 3 phases are often obvious in retrospect, although the duration of each individual phase may be quite variable.

Diagnosis during the second or prevasculitic phase of CSS remains challenging. Several other conditions associated with eosinophilia, including chronic eosinophilic pneumonia, eosinophilic gastroenteritis, hypereosinophilic syndrome, parasitic infections, myeloproliferative disorders (particularly lymphoma), and even severe asthma alone, may mimic CSS at this stage. Moreover, therapy for allergic manifestations during the earlier phases of CSS (i.e., asthma, allergic rhinitis) may mask the fully developing array of disease features. As noted recently by Dr. Andrew Churg, the son of the pathologist Jacob Churg after whom (with Dr. Lotte Strauss) the disease was named, tissue eosinophilia may be detected in nearly any organ during early stages of CSS (9).

Lymphadenopathy in CSS has been reported in at least 7 case reports over the past decade, but to the best of our knowledge, salivary gland involvement has only been reported in 1 (10). Lymphadenopathy and salivary gland enlargement, underappreciated features of CSS, may be overlooked frequently because of other clinical findings that in most cases are more striking. Fine-needle aspiration or biopsy samples of these organs may show only eosinophils or eosinophilic infiltration without vasculitis or other specific histopathologic features. In the proper setting, such findings may strongly suggest CSS and suffice for diagnosis, obviating the need for more invasive procedures.

The skin biopsy findings were consistent with the histopathologic lesion known as Churg-Strauss granuloma or, more precisely, cutaneous extravascular necrotizing granuloma. In their initial report of the disease, Churg and Strauss clearly described the presence of characteristic nodules on the extensor surfaces of the upper and lower extremities (particularly elbows) and within the scalp in their patients. Churg and Strauss also reported granulomatous nodules identical in histopathologic appearance within many internal organs (e.g., the heart, lungs, liver, spleen, kidneys, and connective tissues) of patients with CSS (1). Of note, Churg-Strauss granulomas may occur in conditions other than CSS. The lesions are particularly common in Wegener's granulomatosis as well. Although these nodules are usually innocuous in appearance and frequently go unrecognized (mistaken, for example, for rheumatoid nodules or even warts), Churg-Strauss granulomas are common clinical manifestations of CSS and their presence may provide a strong clue to the underlying diagnosis. Biopsy samples should be obtained from questionable lesions if the patient's diagnosis is not clear.

Finally, the subsequent recognition of a left foot drop provided further support for the diagnosis of CSS, illustrating that development of vasculitis may be asynchronous in different organs. This case illustrates the importance of identifying features compatible with early CSS and the role of biopsy of such organs as the salivary glands and the skin, sites generally not considered primary targets of CSS.

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