Association between allergic conjunctivitis and provisional tic disorder in children

Previous studies on the risk factors for TS mainly focused on genetic [16] and environmental factors such as low birth weight [17] and maternal smoking or drug use during pregnancy [18]. Frequent blinking and eye rolling are common reasons for referral to pediatric ophthalmologists and pediatric neurologists. Frequent blinking is one of the most common and important symptoms of AC in children [8], but also one of the features of PTD [2], which is commonly seen during TS onset [3, 4]. In the present study, the frequencies of AC and dry eye in the PTD group were higher than in the control group. In one of our previous studies, the frequency of dry eyes was higher in children with AC than in healthy children [8]. In PTD, tics are preceded by an unpleasant “premonitory urge” characterized by the feeling that a tic is about to occur [19]. This unpleasant “premonitory urge” may be the feeling of dryness, foreign body sensation, itching, burning sensation, eyelid heaviness, and ocular fatigue from dry eyes induced by AC.

The results showed that AC was less prevalent than dry eye in the PTD group. In children with PTD, the ocular tics always include abnormal and frequent blinking and wrinkling. An incomplete blink leads to inadequate lipid distribution (thin lipid layer) as well as consequent exposure of the inferior ocular surface, which may increase evaporation [20]. The blink rate has a large influence on the tear film [21]. Incomplete blinking induced by ocular tics in children with PTD leads to instability of the tear film and dry eye, and in turn, the dry eyes trigger the unpleasant “premonitory urge” of PTD.

It was hypothesized that AC and dry eyes could be involved simultaneously in childhood PTD. The results showed that AC, dry eyes, and history of allergic rhinitis were strongly associated with PTD. This suggests that AC and dry eyes are both contributing to PTD in children. Ocular surface and tear film abnormalities, even minor, can normally increase blinking [22]. The corneal reflex has trigeminal afferents (nasociliary and supraorbital) and somatic efferent fibers from the facial nerve [21]. The facial nerve innervates orbicularis, resulting in eyelid closure and blinking [23]. In a previous study, the frequency of dry eyes assessed by TFBUT was up to 97.5% in young children with AC [8]. In addition, a form of dry eyes associated with AC has been found to be characterized solely by decreased TFBUT, without symptoms [9]. Dry eye associated with AC may play a direct role in PTD.

Dry eyes and ocular allergy are interrelated conditions that share clinical and biochemical factors [24]. The present study also found that Dermatophagoides pteronyssinus and Dermatophagoides farinae were the most frequent allergens in the PTD group, but that sensitization to food allergens was not common. Li et al. also showed that house dust mites are an important cause of perennial AR and AC, in which house dust mite sensitization due to Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis was prevalent [25]. Those allergens can trigger AC without seasonal specificity or difference. Nevertheless, symptoms of AC can relieve or disappear when the allergens disappear. In the pediatric age, AC occurs frequently, with a peak age in late childhood and young adulthood [13]. PTD is usually mild and will likely go away over a few months [26], and not all children with PTD progress to TS [27]. On the other hand, the results of the present study were different from those of Bruun et al. [28], who reported that symptom exacerbation of TS is often associated with seasonal allergic responses or ingestion of food allergens. Different populations and environment may be responsible for this discrepancy. In southwest China, air pollution is more serious than in developed country. Outdoor air pollution is a major risk factor for conjunctivitis, and the key contributors are fuel combustion and dust storms [29]. In addition, the climate is humid in southwest China, which provides favorable conditions for the growth of dust mites. These would explain why Dermatophagoides pteronyssinus and Dermatophagoides farinae were the most frequent allergens in the present study.

In addition, history of allergic rhinitis was higher in the PTD group than in the control group, and history of allergic rhinitis was associated with an increased risk of PTD. Previous studies showed that allergic rhinitis was associated with AC [13]. Cell mediators, cytokines, chemokines, chemotactic factors, and other factors released during allergic reactions can reach the nasal mucosa or conjunctiva through the nasolacrimal duct and lacrimal system or indirectly by their transport through the blood stream and could cause AC [30]. AR is characterized by sneezing, rhinorrhea, nasal congestion, and nasal pruritus, which are often accompanied by ocular pruritus, redness, and/or lacrimation in 60–70% of patients [31]. Facial tics in children with PTD may be associated with nasal itching and other abnormal feelings in AR. More data are needed to support this hypothesis.

The present study has several limitations. First, the patients were recruited from southwest China, which may lead to a selection bias. Because the frequency of AC in children varies geographically, studies are needed on whether AC plays an important role in PTD in children in other areas of the world. Second, we did not evaluate the effects of anti-allergy treatments and dry eye treatments in the PTD patients. The results of the current study only showed an association between AC and PTD, but could not determine the cause-to-effect relationship between dry eyes and PTD. In addition, the sample size was small and was from a single center. More patients from more hospitals would increase the statistical validity of the results. Finally, the present study did not examine inflammation and immunological markers of allergic reactions.