A Rare Cause of Hemoptysis in an Adolescent Female

Educational Objectives

• Consider rheumatologic cause on the broad differential for presentation of hemoptysis with peripheral and pulmonary eosinophilia.

• Prompt diagnosis and treatment of eosinophilic granulomatosis with polyangiitis significantly improves prognosis and is potentially life-saving.

Case Report

A 17-year-old obese female with allergies and eczema, with no history of asthma, presented with a 1 day of episodic, gross, small volume bright red hemoptysis. Her history was significant for travel to Italy and Puerto Vallarta within the past 3 months. Review of systems was positive for nasal congestion over the past 3 months but was negative for fevers, chills, night sweats, rash, arthralgia, myalgia, weight loss, respiratory distress, abdominal pain, hematochezia, hematuria, epistaxis, or headaches. She denied vaping or recreational drug use. Family history was significant for systemic lupus erythematosus in maternal grandmother. On physical exam she was breathing comfortably without respiratory distress and did not have congestion or rhinorrhea. Her lung exam was nonfocal with distant breath sounds likely secondary to body habitus. Nares were not obstructed, and no edema nor erythema of the nasal turbinates was present. Mucous membranes were moist, with no scleral icterus. No hepatomegaly, splenomegaly, or lymphadenopathy was noted.

Patient initially presented to an outside hospital where comprehensive metabolic panel (CMP) was normal, and complete blood count (CBC) was significant for mild anemia (hemoglobin 11.9 mg/dL) and eosinophilia (24%, absolute count 1.8 K/mcL). Chest X-ray revealed a wedge-shaped consolidation in the right upper lobe. Computed Tomography Angiography (CTA) chest was performed to rule out pulmonary embolism or infarction and showed no vascular malformations but was significant for multifocal right upper lobe consolidations (Figure 1A and B). The patient was transferred to pediatric children’s hospital for further evaluation and care.

Figure 1.

Lung histopathology from our patient demonstrating necrotizing eosinophilic granulomas.

Hospital Course

Initial differential for hemoptysis was broad and included community acquired pneumonia, fungal pneumonia (aspergillus, coccidiomycosis, or histoplasma given eosinophilia), tuberculosis, autoimmune process (including sarcoidosis, anti-glomerular basement membrane disease, granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [eGPA], and malignancy). Cardiac cause as cause of hemoptysis was less likely with normal circulation on CTA.

Complete blood count on admission did not show leukocytosis or leukopenia but did show eosinophilia (11%) which persisted throughout her hospital course. She had mild anemia with hemoglobin nadir of 10.9 mg/dL shortly after admission, however this remained stable throughout hospital course, and she did not require any transfusions. Inflammatory markers were notable for elevated erythrocyte sedimentation rate (67 mm) and mildly elevated c-reactive protein (1.9 mg/dL), prompting further infectious and inflammatory workup.

In collaboration with the infectious disease team, an extensive workup was performed. Respiratory viral panel and pneumonia panel were negative. Sputum culture was positive for microorganisms consistent with oropharyngeal contamination. Three sputum cultures were negative for acid-fast bacteria and interferon gamma release assay was negative. Cytomegalovirus, Adenovirus, Coccidioides, histoplasma, fungal culture, and legionella testing were negative. Karius test, which detects microbial cell-free DNA in the blood, was negative. She was given a 5-day course of Azithromycin while infectious workup was pending. Hemoptysis was persistent with the patient coughing up 1 to 3 mL of bright red blood 10 or more times per day. She was treated symptomatically with cold saline and tranexamic acid nebulized treatments with minimal improvement in hemoptysis frequency and volume. She underwent a bedside nasal endoscopy to assess for upper airway bleeding, which was normal.

Due to concern for malignant process in the setting of peripheral eosinophilia (which can in rare cases be a manifestation of paraneoplastic phenomenon), additional workup was pursued for leukemia and was reassuring. Peripheral smear containing no blasts, uric acid normal, and lactate dehydrogenase only slightly elevated (269 U/L). CT neck, chest, abdomen and pelvis showed no masses.

On hospital day 8, once tuberculosis rule out was complete, patient underwent bronchoscopy with bronchoalveolar lavage (BAL) which revealed no anatomic abnormalities but was significant for pulmonary eosinophilia. On BAL she was found to have low levels of aspergillus-specific IgG with negative aspergillus DNA PCR, unlikely to represent true aspergillosis.

Following negative infectious workup, extensive autoimmune workup was performed and was significant for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) positivity with proteinase 3 (PR3) antibodies. Urinalysis, urine protein: creatinine ratio, and urine microalbumin were normal. Given persistent symptoms and isolated lung involvement, video-assisted thoracoscopic lung biopsy was performed with histopathology demonstrating eosinophilic granulomas and active necrotizing vasculitis (Figure 1).

Final Diagnosis

Histopathology obtained from lung biopsy confirmed the diagnosis of eGPA.

Discussion

Hemoptysis in children can be a concerning symptom with pathology arising from either the bronchial or pulmonary artery circulation. Bronchiectasis associated with cystic fibrosis, respiratory infections, or invasive infections can disrupt the high-pressure bronchial circulation system leading to substantial bleeding. ¹ Invasive infections causing hemoptysis such as Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Actinomyces infections should be also considered, especially in endemic regions such as in our case. Hemoptysis from pulmonary arterial hypertension, left-sided cardiac disease, or arteriovenous malformations is less common in children; however, bleeding arising from this low-pressure system is slow and more insidious.^1,2 Although rare in children, pulmonary embolism should be considered in adolescents with prolonged immobility, oral contraceptive use, or a history of thrombophilia, none of which our patient had. ¹ Tumors from the lung parenchyma or nearby structures such as carcinoid tumor, lymphomas, or metastatic lesions can present with hemoptysis. Given negative infectious and oncologic workup in our patient, peripheral and bronchial eosinophilia with positive c-ANCA suggested rheumatologic cause.

Rheumatologic causes of hemoptysis include sarcoidosis, Goodpasture syndrome, IgA vasculitis, microscopic polyangiitis, and eGPA/GPA. Sarcoidosis in children often presents with skin rash, uveitis, and arthritis without pulmonary involvement, which is more common in adults. Our patient’s lack of kidney involvement made anti-GBM disease and IgA vasculitis unlikely. Peripheral eosinophilia is characteristic of eGPA, but c-ANCA and PR3 positivity are rare and are more commonly associated with GPA. ³ With most patients having positive myeloperoxidase (MPO)-ANCA and PR3, GPA typically presents with organ involvement such as ear, nose, throat, kidney, skin, or nervous system. In our atypical case, our patient had positive c-ANCA and PR3 with only lung involvement, thus a lung biopsy was required to confirm the diagnosis of eGPA. Zwerina et al ⁴ described 33 pediatric eGPA patients and none of them had lung-limited disease. To our knowledge, we report the first case of lung-limited eGPA in a pediatric patient.

Pediatric eGPA, formerly known as Churg-Strauss syndrome, is a rare autoimmune vasculitis that primarily affects small to medium-sized blood vessels. The disease typically presents with a triad of asthma, allergic rhinitis, and eosinophilia. ⁵ Other common manifestations include rash, joint pain, cardiac, gastrointestinal, and neurological abnormalities. However, the disease can manifest in various ways depending on the organ systems involved. Microscopically, eGPA is characterized by necrotizing vasculitis with granulomas and extravascular eosinophilia. ⁴ The exact pathogenesis of eGPA is not fully understood, but a combination of genetic predisposition and environmental factors play a crucial role in triggering immune system dysregulation and leading to an inappropriate inflammatory response. ⁶ MPO-ANCA is present in about 40% of cases and associated with glomerulonephritis, peripheral neuropathy, and purpura. ³ PR3-ANCA positive presentations are rare and differ from MPO-ANCA-positive or ANCA-negative patients as they tend to present with lung nodules and skin manifestations and are less often to have asthma, hypereosinphilia, and peripheral neuropathy. ⁷

Treatment for pediatric eGPA aims to control inflammation, suppress the immune system, and manage symptoms which often involves a combination of corticosteroids and other immunosuppressive medications such as cyclophosphamide or azathioprine.^8,9 In our patient, she responded well to high dose systemic steroids with complete resolution of hemoptysis and cessation of bleeding. Pulmonary function tests were performed 3 months after admission while on prednisone that showed normal lung function. She has subsequently been treated with immune modulator therapy (rituximab, mepolizumab) with resolution of lung consolidations with minimal scarring on follow up chest X-ray 4 months posthospitalization (Figure 2C).

Figure 2.

Multifocal right upper lobe consolidation. (A) Pretreatment CT scan showing axial reconstruction and (B) showing coronal demonstration of the right upper lobe wedge-consolidation. (C) 4 months posttreatment X-ray showing resolution of the right upper lobe consolidation with minimal mid-lung scarring.

Prognosis for pediatric eGPA varies depending on the severity of organ involvement and the response to treatment. Early diagnosis and aggressive management are crucial in preventing long-term complications and improving outcomes. With appropriate treatment, many children with eGPA can achieve remission and lead relatively normal lives, although they may require ongoing monitoring and medication adjustments to maintain disease control.

Conclusion

We report an extremely rare case of lung-limited eGPA in a teenager with hemoptysis. She had complete resolution of hemoptysis and cessation of bleeding, with almost complete radiographic resolution after treatment with high dose systemic steroids, and ongoing immunomodulator therapy with rituximab and mepolizumab. eGPA should be suspected in patients with hemoptysis and peripheral and pulmonary eosinophilia, particularly in the setting of negative infectious workup. Lung biopsy is reserved for situations where extrapulmonary sites are absent, as in our patient. Prompt diagnosis of eGPA and treatment initiation significantly improves prognosis and is potentially lifesaving.

Author Contributions

KM helped with research conception and design, drafting the manuscript, and critically revising the manuscript. KM(2) helped with research conception and design, drafting the manuscript, and critically revising the manuscript. TM helped with research conception and design and critically revising the manuscript. AL helped with research conception and design and critically revising the manuscript. TR helped with research conception and design and critically revising the manuscript. All authors gave the final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.