Coexistence of allergic bronchopulmonary aspergillosis and allergic aspergillus sinusitis in a patient without clinical asthma

Abstract

All patients with prolonged cough with a history of atopy, even if not clinically asthmatic, should be evaluated for allergic bronchopulmonary aspergillosis (ABPA); also, we suspect that we may miss the early diagnosis of ABPA if bronchial asthma is considered as a major criteria for the diagnosis of ABPA

Background

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction, which occurs predominantly in patients with asthma and cystic fibrosis. ABPA has been estimated to occur in 1–2% of patients with chronic asthma¹ and in up to 10% of patients with cystic fibrosis.² Its clinical and diagnostic manifestations originate from an allergic response to multiple antigens expressed by fungi, among which the most notable is Aspergillus fumigatus.³ ABPA is very rarely diagnosed in patients without a history of asthma and no data on the incidence of the disease in the general population are available.⁴ Association of allergic fungal sinusitis (AFS) and ABPA has been reported rarely in the literature.^{5 6}

We report a case of a 30-year-old non-asthmatic woman with coexisting ABPA and allergic aspergillus sinusitis (AAS).

Case presentation

A 30-year-old female resident of New Delhi, working as a clerk in a central government department presented with a 5-month history of dry cough. She had developed a dry cough which was gradually progressing in nature over a 4 month period. For the last 1 month, she had a cough throughout the day and during the night-time and this was not controlled even by a cough syrup. Her dry cough had no postural or diurnal variation or was not associated with any chest pain or breathlessness (dyspnoea) or wheezing, but occasionally associated with scanty expectoration. She had a history of dust allergy. She had a history of recurrent episodes of sneezing and nasal discharge for the past 5–6 years especially when exposed to dust. There was no history of night cough or wheezing on exercise or dyspnoea during childhood. There was no history of asthma, prolonged drug intake or no family history of asthma. A prolonged history of intake of antihistaminic drug, especially cetirizine, was present to control the episodes of sneezing and nasal discharge. The patient did not smoke and had experienced no previous diseases of this nature or pulmonary tuberculosis. For the last 1 month, she was in consultation with a local doctor who had prescribed her an inhaler containing salmeterol and fluticasone with an oral tablet of cetirizine, but even on taking medicines regularly her symptoms were not controlled.

On examination, she was afebrile with normal vital parameters. General physical examination and systemic examination including the respiratory system were unremarkable. An ear, nose and throat consultation was done for indirect nasal endoscopy, which did not reveal any postnasal drip.

Investigations

Her investigations revealed haemoglobin 12.2 g%, total leucocyte count 10 700/mm³ with eosinophil 36% on differential count, erythrocyte sedimentation rate 46 mm in the first hour, fasting blood sugar 118 mg/dl, liver and kidney function tests were within normal limits. Chest x-ray was done and it was within normal limits. We did pulmonary function test (PFT) on several occasions which was normal, forced vital capacity (FVC) of 2.83 litre (83% of predicted), forced expiratory volume in the first second (FEV₁) of 2.37 litre (86% of predicted) and FEV₁/FVC ratio of 83.7%. Postbronchodilator PFT revealed only 3–4% improvement in FEV₁. Sputum examination for Gram stain and Ziehl-Neelsen test was negative in several occasions, Mantoux test was negative. High-resolution CT (HRCT) of the chest (figure 1) revealed bilateral central bronchiectasis with mucus plugging of bronchi giving a finger in glove appearance and bronchocele formation. This finding of central bronchiectasis prompted further investigations in the line of ABPA and then we proceeded for skin test (figures 2 and 3) for immediate hypersensitivity reaction to A fumigatus which revealed a positive result with a wheal formation of 6 mm × 5 mm size. Serum IgG (256 IU/l) and IgE specific for A fumigatus were positive and serum total IgE level (2500 ng/ml) was markedly elevated. Thus, we established the diagnosis of ABPA in patients with non-asthma. As the patient was complaining of recurrent sneezing and rhinorrhoea, we planned for CECT of paranasal sinus (figure 4) which revealed a right maxillary polyp formation. Nasal mucosal washing revealed the growth of A fumigatus.

Figure 1.

High-resolution CT of the chest revealed bilateral central bronchiectasis with mucus plugging of bronchi giving a finger in glove appearance and bronchocele formation.

Figure 2.

Skin testing showing immediate hypersensitivity reaction to Aspergillus fumigatus, Aspergillus niger and Aspergillus flavus.

Figure 3.

Skin testing showing immediate hypersensitivity reaction to Aspergillus fumigatus, Aspergillus niger and Aspergillus flavus.

Figure 4.

CECT of paranasal sinus revealed right maxillary polyp formation.

Differential diagnosis

• Drug-resistant asthma

• Interstitial lung disease

Treatment

Tablet Prednisolone and Tablet Itraconazole

Outcome and follow-up

The patient became symptom-free on first follow-up after 2 weeks of starting treatment. At present, she is doing well, free of symptoms.

Discussion

Aspergillosis remains a significant cause of morbidity and mortality. The spectrum of disease is diverse and ranges from non-invasive disease with an excessive immune response, such as in ABPA, to a lack of an immune response as seen in patients with quantitative or qualitative granulocyte deficits and subsequent invasive pulmonary aspergillosis.⁶ ABPA is an important cause of bronchiectasis,⁷ and it may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis.⁸ The diagnosis of ABPA is based on haematological, radiological and immunological criteria along with the presence of longstanding asthma, and occasionally cystic fibrosis.^{9 10} However, ABPA occurring without asthma is very uncommon and such instances have been documented as case reports and deserves reporting.^11–14 Case reports are present in the literature of coexistent ABPA with AAS in patients with asthma, but our patient was a non-asthmatic, and having coexistent AAS, thus unique in that aspect.

Our patient was fulfilling six of the seven major criteria for the diagnosis of ABPA according to Rosenberg M et al,¹⁵ except bronchial asthma, thus diagnosed as a case of ABPA. As she had a history of atopy, thus predispose to become sensitised against aspergillus antigens thus can developed ABPA.¹⁶ According to Greenberger's criteria,¹⁷ asthma, immediate cutaneous reactivity to Aspergillus species or A fumigatus, elevated total serum IgE (>417 kU/l or 1 000 ng/ml), elevated serum A fumigates-specific IgE and/or serum IgG-A fumigatus, and proximal or central bronchiectasis are needed for the diagnosis of ABPA. Our patient had immediate cutaneous reactivity to A fumigatus, elevated total serum IgE level (2500 mg/ml), positive serum IgE and IgG specific for A fumigatus and central bronchiectasis with bronchocele formation in HRCT chest. She also had marked peripheral eosinophilia. Thus, our patient was fulfilling four major Greenberger's criteria.

The association of AFS and ABPA may be concomitant or not, with a possible time lag of several years between the onset of naso-sinal and bronchopulmonary disease, even after recovery from the original episode.¹⁸ Concomitant occurrence of ABPA and AAS seems to be infrequently recognised. Since asthma and sinusitis are often seen by two different specialties, the occurrence of AAS in ABPA and ABPA in AAS may easily be overlooked.¹⁹

Greenberger and Patterson²⁰ considered that patients with ABPA can be classified into five stages, namely acute stage, remission, exacerbation, corticosteroid-dependent asthma and fibrotic-end stage. Severe asthma with fungal sensitisation (SAFS) is not a well-recognised fungal complication of asthma. In ABPA, the total immunoglobulin E (IgE) is usually >1000 IU/ml, whereas in SAFS it is <1000 IU/ml; either skin prick tests or fungus-specific IgE tests are positive. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit. Production of mucous plugs and coughing paroxysms is more common in ABPA, but both the condition can be managed with high doses of corticosteroids and oral antifungal agents.⁸ Glancy et al⁴ reported that 11 of 42 patients with allergic bronchopulmonary fungal disease had no evidence of asthma. But, in those cases, some patients developed bronchial asthma later. These facts suggest that those patients might have been in a stage preceding bronchial asthma. These facts suggest that our patient might have been at a stage preceding bronchial asthma and may develop bronchial asthma later.

Learning points.

• Allergic bronchopulmonary aspergillosis (ABPA) may present without symptoms of clinical asthma.

• ABPA and allergic aspergillus sinusitis may coexist, but are infrequently detected.

• We should keep ABPA as a differential diagnosis in patients presented with prolonged dry cough without clinical asthma.