Pediatric Aspergillosis Clinical Presentation

Patient history depends on whether the Aspergillus infection is invasive or noninvasive. Invasive aspergillosis (IA) includes acute and chronic pulmonary aspergillosis, tracheobronchitis, sinusitis, and disseminated disease, such as CNS involvement. Disseminated disease is the more severe manifestation and is defined as involvement of 2 or more contiguous organs.

• Invasive aspergillosis

  • Acute invasive pulmonary aspergillosis: Pulmonary disease occurs in 80-90% of patients with invasive aspergillosis. Fever, dyspnea, nonproductive cough, mild hemoptysis, and pleuritic chest pain are the cardinal clinical manifestations of invasive pulmonary aspergillosis. Severely immunocompromised patients may have no initial symptoms but diagnosis warrants a high index of suspicion.
  • Chronic invasive pulmonary aspergillosis usually occurs in patients with underlying diseases (eg, advanced AIDS, chronic granulomatous disease, sarcoidosis, diabetes mellitus). Patients usually complain of chronic nonproductive cough, often with hemoptysis. Low-grade fever, weight loss, and malaise are also common.
  • Tracheobronchitis caused by Aspergillus species usually occurs in lung transplant recipients and patients with advanced AIDS. Most of these patients experience symptoms including fever, cough, hemoptysis, dyspnea, and chest pain. Occlusion of the airways may result in death if the condition remains undiagnosed and untreated.
  • Patients with sinusitis caused by Aspergillus species usually complain of headache. Other symptoms include fever, cough, epistaxis, nasal discharge, sinus pain, and sore throat.
  • Primary involvement of the skin rarely occurs; the skin is more commonly a secondary site of hematogenous spread from a pulmonary infection. Surgical wounds, burn wounds, vascular catheters, and adhesive dressing applied to the skin may predispose to the development of cutaneous aspergillosis, especially in immunocompromised patients. The usual presentation of skin involvement is the appearance of raised red lesions, which may progress to ulceration and eschar formation.
  • Cerebral involvement almost always occurs in patients who are neutropenic and in those undergoing bone marrow or solid organ transplantation. Patients that are severely immunocompromised usually present with altered mentation and seizures; prognosis is dismal. Fever is uncommon.
  • Patients with Aspergillus endophthalmitis may complain of pain, photophobia, and diminished visual acuity. Most of these patients have no other systemic symptoms. Orbital cellulitis may complicate invasive sinusitis. The patient may present with pain on lateral gaze and diplopia.
• Noninvasive aspergillosis

  • Patients with allergic bronchopulmonary aspergillosis (ABPA) often have histories of worsening respiratory symptoms in association with asthma or cystic fibrosis (CF). ABPA occurs in approximately 11% of patients with CF. The main complaints of these patients are wheezing and cough. As the disease progresses, patients may expectorate mucous plugs containing eosinophils, and they may develop bronchiectasis.
  • Exacerbation and remission characterize the natural history of disease. Progression to respiratory failure may occur occasionally because of irreversible airway obstruction and pulmonary fibrosis. It may mimic pneumonia with mucopurulent bloody sputum, fever, and respiratory distress. Predominant wheezing may be the only manifestation suggesting an exacerbation of bronchial asthma.
  • The staging system developed by Greenberger and Patterson (1986) classifies ABPA into 5 stages, as follows:^[2]
    • Stage I (acute): The patient exhibits moderate or severe asthma, a productive cough, and infiltrates on chest radiograph.
    • Stage II (remission): The patient has mild or no asthma following steroid treatment. Serum immunoglobulin E (IgE) levels decline. The patient may remain in Stage II permanently or may progress to further disease.
    • Stage III (recurrent exacerbation): Exacerbation with the appearance of new infiltrates, elevated IgE, and eosinophilia.
    • Stage IV (corticosteroid dependent asthma): Tapering doses of steroids leads to acute exacerbation or recurrence of disease.
    • Stage V (fibrotic lung disease): The diagnosis is based on pulmonary fibrosis on radiograph. Irreversible deterioration in pulmonary function occurs, which cannot improve, even with steroid therapy.
  • Patients with allergic fungal rhinosinusitis usually have symptoms of long-standing sinusitis. The patient may have a history of nasal polyposis, prior nasal surgery, or atopic disease. Rubbery particles composed of tenacious allergic mucin may be expectorated.
  • Aspergillomas may remain asymptomatic until hemoptysis occurs.

Physical signs of aspergillosis include the following:

• Pulmonary

  • Initially, 25-33% of patients with acute invasive pulmonary aspergillosis may have no obvious clinical signs. In some cases, physical findings may reveal a pleural rub.
  • Patients with extensive involvement may be hypoxemic.
  • Pneumothorax is occasionally a presenting feature, and breathing sounds on auscultation may decrease and exhibit hyperresonance on percussion.
  • Patients with chronic granulomatous disease may have local extension into the chest wall, brachial plexus, or vertebral column.
• Cutaneous: Cutaneous lesions present as erythematous papules or nodules, which progressively enlarge, ulcerate, and are covered by a black necrotic crust. Patients with central venous catheter associated aspergillosis may develop hemorrhagic bullous skin lesions. Disseminated disease may lead to multiple papulopustular or macular lesions in the extremities. These lesions may ulcerate with eschar formation.
• Cerebral

  • Severely immunocompromised patients who have cerebral aspergillosis may present with nonspecific findings (eg, altered mental status, seizures).
  • Patients with less immunocompromising conditions are more likely to present with focal features, such as hemiparesis, cranial nerve palsies, or focal seizures.
  • Papilledema and meningeal signs are uncommon.
• Sinusitis

  • Patients with sinusitis usually have dark nasal lesions, with or without nasal discharge.
  • Sinus tenderness, nasal or oral ulceration, and duskiness or necrosis of the nasal septum and inferior turbinates may occur.
  • Facial swelling is unusual, and extension into the brain or orbit may cause proptosis or focal neurological signs (eg, hemiparesis, cranial nerve palsies, focal seizures).
• Eye

  • Retinal examination of patients with fungal endophthalmitis may reveal focal retinitis, vitreitis, and retinal hemorrhage.
  • Periorbital edema and proptosis may occur with orbital cellulitis.

• Patients with granulocytopenia or defects in neutrophil function secondary to underlying illness have increased risk of developing invasive aspergillosis. Other predisposing factors for acquiring invasive aspergillosis include the following:

  • Corticosteroid and cytotoxic chemotherapy
  • Quantitative immunodeficiencies (eg, chronic granulomatous disease)
  • Advanced AIDS
  • Bone marrow transplant
  • Solid organ transplant
  • Graft versus host disease
  • Graft rejection
• ABPA usually occurs in patients with CF or underlying bronchial asthma.
• Aspergilloma usually occurs in preexisting pulmonary cavities such as in cysts caused by tuberculosis or sarcoidosis.