CME 2607

A child with an unusual cause of difficult asthma

 

T Kerbelker, MB ChB, FCPaed (SA), DCH (SA), Dip HIV Management (SA), Dip Allerg (SA)

Division of Allergy, Red Cross War Memorial Children’s Hospital, University of Cape Town


D Hawarden, BSc, MB ChB

Division of Allergy, Department of Medicine, Groote Schuur Hospital, Cape Town

 

Correspondence to: T Kerbelker (tamarakerbelker@yahoo.com)

 

Background

Patient UA is a 12-year-old boy who attends a tertiary allergy clinic. He was diagnosed with asthma at 4 years and followed up at medical outpatients.

Medication

Budesonide 200 µg bd (bottle spacer) – his asthma was controlled on this medication. He was sensitised to South African grass pollen and house dust mite and had co-morbid persistent allergic rhinoconjunctivitis. He was on intranasal steroids, antihistamines and topical eyedrops.

Disease progression

Disease progression is depicted in Fig. 1.

Fig. 1. Disease progression.


Special investigations

Pulmonary function tests (PFTs) are listed in Table 1. The PFTs showed mixed large and small airways obstruction, with residual reversibility despite therapy with a long-acting beta-agonist.

• FBC

• white cell count: 9.56 x 109/l (3.90 - 10.20)

• haemoglobin: 13.8 g/dl (11.8 - 14.6)

• MCV: 76.1 fl (77.1 - 91.5)

• platelets: 390 x 109/l (180 - 440)

• Differential

• eosinophils: 11.0%; 1.05 x 109/l (0.00 - 0.70). Significant peripheral eosinophilia was present.

• Erythrocyte sedimentation rate: 52 mm in 1 hour (normal <10). The raised ESR meant TB, intercurrent infection and that Churg- Strauss syndrome should be excluded.

• Immunoglobulins

• IgG: 9.92 g/l (6.00 - 20.00)

• IgA: 1.50 g/l (0.80 - 3.00)

• IgM: 0.85 g/l (0.40 - 1.80).

 

The HIV enzyme-linked immunosorbent assay (ELISA) was non-reactive.

The immunoglobulins were normal and so excluded IgA deficiency, which can present with recurrent infections and masquerade as uncontrolled asthma. HIV infection excludes a secondary immunodeficiency.

• Sweat test

• chloride 25 mmol/l (normal <40, suspicious 40 - 60, cystic fibrosis >60).

The sweat electrolyte test is the gold standard for the diagnosis of cystic fibrosis. In young children it is an important differential for recurrent wheeze.

• ANCA negative: antinuclear cytoplasmic antibody-negative excludes Churg-Strauss syndrome.

• Sputum-negative microscopy, culture and sensitivities for bacteria and tuberculosis.

• Nuclear medicine

• no reflux

• Total IgE 1 950 kU/l

• IgE Aspergillus 10.2 kU/l

• IgG Aspergillus 90.4 mg/ml

• Chest X-ray: the chest X-ray (Fig. 2) showed right middle lobe infiltrates.


Table 1. Pulmonary function tests

 
Pred
Pre
%Pred
Post
%Pred
%Diff

FVC

2.41

1.61

67

1.82

75

13

FEV1

2.17

1.22

56

1.45

67

19

FEV%FVC

86

75

88

80

93

6

PEF

5.18

3.06

59

3.17

61

3

FEF25

4.07

2.2

54

2.48

61

13

FEF50

2.88

1.17

40

1.6

56

37

FEF75

1.48

0.4

27

0.51

35

29

Pred = predicted; Diff = difference; FVC = forced vital capacity; FEV1 = forced expiratory volume in 1 second; FEF = forced expiratory flow; PEF = peak expiratory flow.


 


Fig. 2. Chest X-ray showing fine bilateral infiltrates.


Diagnosis

Based on the extensive workup, a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. The patient fulfilled the criteria for ABPA (see below), and was successfully treated with oral corticosteroids. He has not relapsed to date.

Diagnostic criteria for ABPA1

• Asthma

• Total serum IgE (>1 000 ng/ml or 417 kU/l)

• Raised Aspergillus fumigatus IgE levels or IgG A. fumigatus

• Skin prick positive A. fumigatus

• Chest X-ray infiltrates (not essential for diagnosis).

Discussion

With all cases of ‘difficult’ asthma the diagnosis should be reviewed to ensure that the correct diagnosis has been made and then treatable exacerbators sought.

ABPA is a hypersensitivity disorder to the mould A. fumigatus and occurs mainly in patients with asthma or cystic fibrosis.

Sensitisation to mould has been found to be associated with the development, persistence and severity of asthma.2 Aspergillus sensitisation has been found to be as high as 40% in adult asthma clinics, with a prevalence of ABPA at 12.9%.3

Historically the treatment of ABPA has been oral corticosteroids. However, they are fraught with inherent side-effects which are particularly prominent in children, especially when protracted courses are required. Azoles for ABPA have shown a synergistic role with prednisone for the treatment of the condition.

Antifungals

Itraconazole was the first antifungal to be used, but unfortunately a 40% failure rate was reported.3 This was either due to treatment failure, or unacceptable side-effects. More recently, voriconazole and then posaconazole have been shown to be efficacious in patients who had failed itraconazole. Voriconazole and posaconazole, as synergistic therapy with oral corticosteroids, have shown a clinical response in a significant number of patients.4  

 

References
    1. Greenburger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002;110:685-692.

    1. Greenburger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 2002;110:685-692.

    2. Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2004;(3):CD001108.

    2. Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev 2004;(3):CD001108.

    3. Pasqualotto AC, Powell G, Niven R, Denning DW. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009;14:1121-1127.

    3. Pasqualotto AC, Powell G, Niven R, Denning DW. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009;14:1121-1127.

    4. Chishimba L, Niven RM, Cooley J, Denning DW. Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. J Asthma 2012;49:423-433.

    4. Chishimba L, Niven RM, Cooley J, Denning DW. Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. J Asthma 2012;49:423-433.



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