1
To the Editor,
Sublingual immunotherapy (SLIT) is a successful treatment of allergic rhinoconjunctivis
by inducing clinical and immunological tolerance.
1
Compared to subcutaneous immunotherapy (SCIT), severe adverse reactions to SLIT are
less frequently seen.
2
In 2017, treatment with SQ house dust mite sublingual immunotherapy tablets (hereinafter:
SQ‐HDM) has been registered in many European countries. In this letter, we describe
two patients with acute systemic adverse reactions after administration of SQ‐HDM.
See Table 1 for patient characteristics. Both events occurred in our outpatient clinic.
TABLE 1
Patient characteristics
Patient 1
Patient 2
Gender
Female
Female
Age
35
19
Medical history
Well‐controlled moderate asthma
Allergic rhinoconjunctivitis due to house dust mite (HDM)
Eczema
Allergic rhinoconjunctivitis due to HDM, tree pollens, and grass pollens
Lung function
VC: 3,48 liter (91% of predicted), FEV1: 2,79 liter (88% of predicted), FEV1/VC: 80%,
DLCO: 78% of predicted, DLCO/VA: 84%
NA
Skin prick test
NA
Positive for HDM, tree pollens, grass pollens, and cat.
Serological test Reference kU/L: < 0.35
Reference ISU‐E: < 0.30
HDM 1.64 kU/L
Der f2 1.90 ISU‐E
Der p2 1.70 ISU‐E
Der p23 1.0 ISU‐E
HDM 30.0 kU/L
Der f2 23.70 kU/L
Der f1 17.10 kU/L
Der p1 10.20 kU/L
Der p2 23.50 kU/L
Birch pollens 48.30 kU/L
Hazel pollens 15.90 kU/L
Alder pollens 45.70 kU/L
Oak pollens 12.20 kU/L
Rye pollens 19.40 kU/L
Timothy grass 25.10 kU/L
Bermuda grass 35.50 kU/L
Sweet vernal grass 30.00 kU/L
Medication
Levocetirizine 5 mg b.i.d.
Azelastine/fluticasone nasal spray 137/50 µg per actuation.
Fluticasone/Salmeterol 250/25 µg/dose b.i.d.
Salbutamol inhalations
100 µg/dose if necessary q.i.d.
Fluticasone furoate 27,6ug q.d.
Levocetirizine 5 mg b.i.d.
Symptoms during acute reaction to SQ‐HDM
Dizziness, tachycardia, feeling of thick throat, dyspnea
Itchy mouth, dizziness, feeling of thick throat, dyspnea, excessive vomiting.
Hemodynamics
Blood pressure: 161/88 mmHg
Pulse: 150 beats/min
Temperature: 37.2°C
Saturation: 100% without oxygen therapy
Breathing: 16 times/min
Blood pressure: 109/86 mmHg
Pulse: 96 beats/min
Saturation: 96% without oxygen therapy
Breathing: 16 times/min.
Treatment
Adrenalin 0.5 mg IM
Clemastine 2 mg IV
Adrenalin 0.5 mg IM
Clemastine 2 mg IV
Serum tryptase 1‐2 h after reaction
3.30 µg/L (ref: 0.00‐11.4)
4.90 µg/L (ref: 0.00 ‐ 11.4)
John Wiley & Sons, Ltd
Patient 1 was a 35‐year‐old female with persistent allergic rhinoconjunctivitis due
to HDM allergy, which was serologically confirmed (Table 1). Furthermore, she was
known to suffer from moderate allergic asthma, well controlled with fluticasone/salmeterol
(Seretide 250/25 µg/dose b.i.d.) and salbutamol inhalations (Salbutamol 100 µg/dose
if necessary q.i.d.) without airflow obstruction (see pulmonary function testing in
Table 1). Due to uncontrolled allergic rhinitis, despite nasal corticosteroids (Azelastine/Fluticasone
Nasal Spray 137/50 µg per actuation) and antihistamines (Levocetirizine 5 mg b.i.d.),
immunotherapy with SQ‐HDM was initiated. She never had treatment with SCIT previously.
She received her first treatment with SQ‐HDM in September. At the time of administration,
routine questioning confirmed that she was in a good clinical condition without any
signs of current infections, respiratory tract symptoms, oral lesions, emotional stress,
or sleep deprivation and the administration of SQ‐HDM was not during her menstrual
period. Within 5 minutes after sublingual administration of SQ‐HDM, she experienced
dizziness, shortness of breath, and feeling of thick throat. Examination showed a
blood pressure of 161/88 mmHg, a tachycardia of 150 beats per minute (an electrocardiogram
showed sinus tachycardia without other abnormalities). Her temperature was 37.2°C,
oxygen saturation of 100% without oxygen therapy, and she was breathing 16 times per
minute. There were no signs of urticaria, and no swelling of the tongue or lips was
observed (nasopharyngoscopy was not performed). Diffuse muscle fasciculations were
observed without signs of rough myoclonus. She was stabilized and treated with adrenalin
0.5 mg intramuscularly and clemastine 2 mg intravenously. After treatment, the symptoms
disappeared within an hour. She was admitted for a short period of observation. Serum
tryptase level 1‐2 hours after the event was 3.30 µg/L (ref: 0.00‐11.4).
Patient 2 was a 19‐year‐old female with refractory rhinoconjunctivitis with allergy
to tree pollen, grass pollen, and HDM, confirmed serologically (Table 1) as well as
by a skin prick test. She declined SCIT; therefore, treatment with SQ‐HDM was initiated
in September. She has not been treated with immunotherapy in the past. She confirmed
specifically that she was in a good clinical condition without any signs of current
infections, respiratory tract symptoms, oral lesions, emotional stress, or sleep deprivation,
and the administration of SQ‐HDM was not during her menstrual period. Within 3 minutes
after sublingual administration, she experienced a feeling of thick throat, shortness
of breath, dizziness, and excessive vomiting. Her vital signs showed a blood pressure
of 109/86 mmHg, a tachycardia of 96 per minute, and oxygen saturation of 96% without
oxygen therapy, and she was breathing 16 times per minute. She was stabilized and
treated with adrenalin 0.5 mg and clemastine 2 mg intramuscularly. Serum tryptase
level measured 1‐2 hours after reaction was 4.90 µg/L (ref: 0.00‐11.4). After 4 hours
of observation, she was discharged in a good condition.
Acute severe adverse reactions to SQ‐HDM have been described sporadically.
3
To our best knowledge, only 1 case of anaphylaxis to SQ‐HDM and 4 cases of systemic
reactions to grass SLIT have been reported.
3
,
4
However, physicians need to be aware of these reactions and should be able to stabilize
a patient with an acute reaction.
Both patients showed symptoms of a systemic reaction which occurred immediately after
sublingual administration of SQ‐HDM. According to the World Allergy Organization (WAO)
systemic allergic reaction grading system, both patients had a grading score of 3.
5
,
6
Even though grade 3 is not defined as anaphylaxis by WAO, anaphylaxis cannot be ruled
out, because this is a clinical diagnosis. The observation that serum tryptase 1 to
2 hours after the start of the reactions was low, does not exclude an IgE‐mediated
reaction.
7
Several risk factors have been described for developing systemic reactions, such as
decreased lung function, oral lesions, concurrent infections, or emotional stress.
8
In our patients, none of these risk factors could be identified. Patient 1 was known
with rhinoconjunctivitis and moderate asthma without signs of obstruction. Patient
2 only suffered from rhinoconjunctivitis and did not have symptoms of asthma. Both
patients were positive for Der p2 and Der f2, but further extended molecular sensitization
profile of HDM and pollens in both patients was different. The administration of SLIT
took place in the month September. In autumn, exposure to HDM in the Netherlands is
higher than in spring.
9
However, there are no studies showing that the onset of immunotherapy administration
with HDM should be determined by seasonal variation in HDM exposure.
In conclusion, acute systemic reactions to SQ‐HDM may occur. Awareness is important,
and patients should be monitored appropriately after taking SQ‐HDM.
CONFLICT OF INTEREST
Dr Janssens has nothing to disclose. Dr van Ouwerkerk has nothing to disclose. Dr
Gerth van Wijk reports personal fees from ALK Abello, outside the submitted work.
Dr Karim has nothing to disclose.
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