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Vol. 28. Issue 3.
Pages 231-234 (May - June 2022)
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Vol. 28. Issue 3.
Pages 231-234 (May - June 2022)
Letter to the Editor
Open Access
Concomitant allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis after Aspergillus niger infection
I. Alen Coutinhoa,
, M. Lopesb,1, F. Limac, C. Venturab, E. Rabadãob, T. Alfarod, J.S. da Cunhab, F.S. Regateiroa,e,f
a Allergy and Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
b Infectious Diseases Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
c Internal Medicine Unit, Hospital Divino Espírito Santo de Ponta Delgada, Portugal
d Pulmonology Unit, Centro Hospitalar e Universitário de Coimbra, Portugal
e Faculty of Medicine, University of Coimbra, Portugal
f ICBR - Coimbra Institute for Clinical and Biomedical Research, CIBB, Faculdade de Medicina, Universidade de Coimbra, Portugal1contributed equally.
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Table 1. Diagnostic criteria of IPA, ABPA, EGPA. Criteria fulfilled by the patient are indicated by “+”, while unfulfilled criteria are marked “-“. NA, not assessed; NT, not tested.
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Aspergillus species can cause lung disease by direct infection, such as invasive pulmonary aspergillosis (IPA), aspergillosis, etc.; or by hypersensitivity reactions to fungal proteins, such as allergic bronchopulmonary aspergillosis (ABPA).1 We here describe a patient that simultaneously developed ABPA and eosinophilic granulomatosis with polyangiitis (EGPA) in the context of an Aspergillus niger airway infection and discuss the overlapping criteria of these conditions.

A 27-year-old Indian male, resident in Portugal for the past two years, presented mild intermittent bronchial asthma. He developed progressive non-productive cough and dyspnoea over the course of six weeks, and was admitted to the emergency department for the sudden onset of intense right chest pain.

Physical examination was unremarkable. Blood tests revealed leucocytosis (13.1 × 109/L), with neutrophilia (10.7 × 109/L), eosinophilia (1.5 × 109/L) and elevated C-reactive protein (CRP) 9.4mg/dL (normal <0.5). Imaging showed a 6 cm-long right hilar mass, extending to the pleura and enlarged hilar lymph nodes. Bronchoscopy observed bulky secretions obstructing the anterior segment of the right upper lobe (RB3). Cultures of bronchial aspirate, lavage and biopsies were all positive for Aspergillus niger. Eosinophils were abundant on bronchial aspirate, with Charcot-Leyden crystals, and in bronchial biopsies.

The patient was hospitalized and voriconazole was initiated. Two weeks later, voriconazole was changed to liposomal amphotericin B due to drug-induced hepatotoxicity. After three weeks of antifungal treatment, no clinical improvement was observed (increasing fever, neutrophilia 13.84 × 10^9/L, CRP 27.59mg/dL). Imaging showed a growing lung mass with suspected superinfection (Fig. 1A-D). Empirical piperacillin-tazobactam and vancomycin were initiated. After 10 days of antibiotic therapy, neutrophilia and CRP had diminished (8.9 × 10^9/L, 7.34mg/dL, respectively). However, anaemia developed (Hb 8.6g/dL, normal 13.0-17.5) and clinical manifestations continued to deteriorate, with asthenia, fever, dyspnoea and cough.

Fig. 1.

Comparison of chest X-ray and CT at admission (A-D, a 6 cm-long right hilar mass is observed, extending to the pleura and enlarged hilar lymph nodes) and 4 months after disease resolution (E-H, large varicoid bronchiectasis in both lungs can be observed, particularly in the right upper lobe.).


In view of the poor response to antifungals and antibiotics, alternative diagnoses were considered. Further investigations showed elevated total IgE (5175IU/mL, normal <100), eosinophilia (0.71 × 109/L), negative procalcitonin (while CRP again increased to 13.29mg/dL), positive p- antineutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase (MPO) (8.5IU/ml, negative <3.5), while c-ANCA and anti-proteinase 3 (PR3) were negative. Specific IgE (sIgE) and specific IgG (sIgG) to Aspergillus fumigatus were strongly positive (sIgE 9.16kU/L, normal <0.35; sIgG 281.00mgA/l, normal <83.00). Skin prick test to Aspergillus fumigatus was positive (3mm).

At this point, the patient fulfilled diagnostic criteria for both ABPA and EGPA (Table 1). Despite the initial evidence of fungal colonization/infection and subsequent bacterial superinfection, it was considered that T2 inflammation played the dominant role in the disease. Methylprednisolone was started at 1mg/kg/day, together with itraconazole. Nasal computed tomography (CT) scan during treatment with systemic glucocorticoids showed mild maxillary sinusitis.

Table 1.

Diagnostic criteria of IPA, ABPA, EGPA. Criteria fulfilled by the patient are indicated by “+”, while unfulfilled criteria are marked “-“. NA, not assessed; NT, not tested.

Disease and diagnostic criteria  Present in this case 
Putative invasive pulmonary aspergillosis - all four criteria must be met (Blot SI, et al. Am J Respir Crit Care Med. 2012 Jul 1;186(1):56-64.1. Aspergillus-positive lower respiratory tract specimen culture (= entry criterion)2. Compatible signs and symptoms (one of the following)
  • Fever refractory to at least 3 days of appropriate antibiotic therapy

  • Recrudescent fever after a period of defervescence of at least 48 h while still on antibiotics and without other apparent cause

  • Pleuritic chest pain

  • Pleuritic rub

  • Dyspnoea

  • Haemoptysis

  • Worsening respiratory insufficiency in spite of appropriate antibiotic therapy and ventilatory support

3. Abnormal medical imaging by portable chest X-ray or CT scan of the lungs4. Either 4a or 4b4a. Host risk factors (one of the following conditions)
  • Neutropenia (absolute neutrophil count, <500/mm3) preceding or at the time of ICU admission

  • Underlying haematological or oncological malignancy treated with cytotoxic agents

  • Glucocorticoid treatment (prednisone equivalent, .20 mg/d)

  • Congenital or acquired immunodeficiency

4b. Semiquantitative Aspergillus-positive culture of BAL fluid (+ or ++), without bacterial growth together with a positive cytological smear showing branching hyphae Aspergillus respiratory tract colonization 
ABPA - ISHAM criteria (Agarwal R, et al. Clin Exp Allergy. 2013 Aug;43(8):850-73.)
  • Predisposing conditions

  • Bronchial asthma

  • Cystic fibrosis

  • Obligatory criteria (both should be present)

  • Total IgE>1000IU/ml*

  • Positive Aspergillus specific IgE or skin prick test

  • Other criteria (2 out of 3)

  • Raised Af IgG or precipitins

  • Eosinophils>500 cells/uL

  • Radiological features consistent with ABPA

ABPA - Rosenberg-Patterson criteria (Rosenberg M, et al. Ann Intern Med. 1977; 86:405-414)
  • Major criteria

  • 1. Asthma

  • 2. Presence of transient pulmonary infiltrates (fleeting shadows)

  • 3. Immediate cutaneous reactivity to A. fumigatus

  • 4. Elevated total serum IgE

  • 5. Precipitating antibodies against A. fumigatus

  • 6. Peripheral blood eosinophilia

  • 7. Elevated serum IgE and IgG to A. fumigatus

  • 8. Central/proximal bronchiectasis with normal tapering of distal bronchi

  • Minor criteria

  • 1. Expectoration of golden brownish sputum plugs

  • 2. Positive sputum culture for Aspergillus species

  • 3. Late (Arthus-type) skin reactivity to A. fumigatus

EGPA (Masi AT, et al. Arthritis Rheum. 1990 Aug;33(8):1094-100. & Jennette JC, et al. Arthritis Rheum. 1994 Feb;37(2):187-92).The presence of four or more criteria yields a sensitivity of 85% and a specificity of 99.7%.Four or more criteria:
  • Asthma (wheezing, expiratory rhonchi)

  • Eosinophilia of more than 10% in peripheral blood*

  • Paranasal sinusitis

  • Pulmonary infiltrates (may be transient)

  • Histological proof of vasculitis with extravascular eosinophils

  • Mononeuritis multiplex or polyneuropathy


Clinical recovery was rapid and occurred after two days of glucocorticoids, with resolution of fever and subsequently of asthenia and cough. On day 10, CRP (0.49mg/dL), blood eosinophils (0.09 × 109/L) and haemoglobin (13.8g/dL) were all normal.

The patient was discharged asymptomatic 20 days after initiating systemic corticosteroids. Itraconazole was maintained for 20 weeks and corticosteroids were tapered until suspension. At the end of antifungal treatment, the chest X-ray was normal (Fig. 1E) and there was no relapse of the symptoms. Four months after discharge, CT scan showed reduced lung mass but large varicoid bronchiectasis in both lungs, particularly in the right upper lobe (Fig. 1F-H).

This is a rare case of simultaneous development of ABPA and EGPA in the context of Aspergillus niger pulmonary infection. The identification of Aspergillus in airway samples complicated ABPA/EGPA diagnosis. On hospitalization, “proven IPA” could not be confirmed (no open lung biopsy was performed), but the patient fulfilled the criteria for “putative IPA”2 (Table 1). Novel criteria for invasive fungal disease were published by the EORTC/MSGERC consensus,1 after the described episode occurred.

Aspergillus is known to contribute to the development of ABPA3 and concomitant IPA and ABPA have been described.4 In contrast, the role of Aspergillus in the pathophysiology of EGPA remains largely speculative.5 The relationship between ABPA and EGPA is also incompletely understood. Several diagnostic criteria are common to both diseases and differential diagnosis is recommended.6 Recently, reports described the sequential occurrence of allergic bronchopulmonary mycosis (ABPM) and EGPA, or vice versa.7 How one established disease may be predisposed to the other is unknown but may include eosinophil recruitment by Th2-driven ABPM, or EGPA lung tissue damage and sequelae predisposing to fungal colonization and subsequent hypersensitivity.

Concomitant ABPA and EGPA at presentation seem to be rarer than sequential development. In the case described here, no past investigations were available. However, the patient was largely healthy before this episode, and we consider that ABPA and EGPA occurred simultaneously. To the best of our knowledge, only three other cases of simultaneous ABPA/EGPA have been reported.7

The possibility that EGPA and ABPA may co-exist in the same patient has important clinical implications. Besides differential diagnosis at presentation, long-term follow-up of one disease should explore for “de novo” development of the other disease. A fine understanding of the mechanisms involved in ABPA, EGPA, or their simultaneous presentation, will be required for the choice of targeted therapies.

Data availability

Informed consent was signed by the patient.

Authors' contributions

IAC and FSR were attending physicians during hospitalization and follow-up, collected the data and prepared the manuscript. ML, FL, CV and ER were attending physicians for the patient during hospitalization and collected patient's data. JSC and TA contributed to the diagnosis and the manuscript.

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contributed equally.


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