A 9-year-old boy presenting with hypothermia during specific immunotherapy for gramineae

Background:  Oral immunotherapy was first proposed as treatment for allergic diseases in the early 1900s. In 1998, the World Health Organization recognized that sublingual immunotherapy (SLIT) was a promising alternative route of subcutaneous immunotherapy (SCIT); in 2009, the World Allergy Organization officially stated that scientific cumulative evidence showed that SLIT represented an effective and safer alternative to SCIT. Nevertheless we have recently observed the first case of hypothermia during immunotherapy.

Methods: A 9-year-old boy with allergic rhinoconjunctivitis and monosensitized to Gramineae started oral immunotherapy for Gramineae in November 2013 (Phleum Pratense 75.000 SQ-T, one tablet daily). He tolerated the immunotherapy, with no local nor systemic reactions, until March. On 1^st April 2014, the patient was admitted to the emergency room for an episode of hypothermia (with an external axillary and tympanic temperature of 33.8°C, measured with different thermometers), characterized by frontal headache and asthenia; gastrointestinal and visual disorders, signs of infectious diseases and loss of consciousness never occurred. Neurological examination and cranial computerized tomography scan performed with urgency were not significant for organic pathologies. The clinical symptomatology improved in three days, after empirical immunotherapy suspension. The child underwent further medical examinations: body temperature monitoring, neuropsychiatric visits, magnetic resonance imaging and magnetic resonance angiography scan resulted to be normal or negative.  On 7^thApril the patient took one tablet again (without medical advice) and, after 9 hours, he presented an external temperature of 34.0°C and the above-mentioned symptoms. In both cases, the rectal temperature unexpectedly remained normal (36.0°- 36.5°C). Immunotherapy was immediately stopped at our centre.

Results: Endocrinological and genetic evaluations, standard haematological tests, blood chemistries and other hormonal assessments suitable for age were performed: no abnormalities were detected. The child has not presented clinical symptoms of respiratory allergy related to Gramineae pollens yet. No further hypothermia episodes occurred.

Conclusions: This is the first hypothermia reaction to be ever described during immunotherapy in literature. Immunotherapy is supposed to have somehow interfered with the thermoregulatory system at molecular level, leading to peripheral vasoconstriction. Nevertheless further clinical and laboratory studies are needed to clarify this phenomenon.