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Arch Soc Esp Oftalmol 2016;91:305-9 - DOI: 10.1016/j.oftale.2016.04.007
Original article
A curious fact: Photic sneeze reflex. Autosomical dominant compelling helio-ophthalmic outburst syndrome
Curiosidad: reflejo de estornudo fótico. Síndrome helio-oftálmico de estornudos compulsivos autosómico dominante
C. Sevillanoa, A. Parafita-Fernándeza,, , V. Rodriguez-Lopezb, M. Sampila, N. Morañaa, E. Visoa, F.J. Coresa
a Servicio de Oftalmología, Complejo Hospitalario de Pontevedra, Pontevedra, Spain
b Medicina Familiar y Comunitaria, Complejo Hospitalario de Pontevedra, Pontevedra, Spain
Received 18 November 2015, Accepted 12 January 2016
Abstract
Objective

To assess ocular involvement in the pathophysiology of autosomal dominant compelling helio-ophthalmic outburst syndrome (ACHOOs).

Methods

An interview was conducted with a Caucasian family that showed clinical features of ACHOOs. Twelve of them had photic reflex and were recruited. A complete eye evaluation was made.

Results

A dominant autosomal inheritance with mild penetrance was demonstrated, with 67% of the studied subjects showing some degree of prominent corneal nerves. No other eye changes were found.

Conclusions

Prominent corneal nerves may be associated with ACHOOs. The other eye structures studied do not seem to play a role in ACHOOs. Further studies are needed to understand the physiology of the ACHOOs.

Resumen
Objetivo

Evaluar la implicación ocular en la fisiopatología del síndrome helio-oftálmico de estornudos compulsivos autosómico dominante (ACHOOs).

Métodos

Una familia de raza caucásica, que muestra las características clínicas de ACHOOs, fue interrogada. De toda la familia, 12 pacientes presentan reflejo fótico y fueron seleccionados. Se realiza una evaluación oftalmológica completa.

Resultados

Se encuentra una herencia autosómica dominante con penetrancia parcial. El 67% de los sujetos estudiados mostró algún grado de prominencia en los nervios corneales. No se encontraron otras alteraciones oculares.

Conclusiones

Los nervios corneales prominentes pueden tener asociación con el ACHOOs. Las otras estructuras del ojo estudiados no parecen desempeñar un papel en el ACHOOs. Se necesitan más estudios para comprender la fisiología del ACHOOs.

Keywords
Photic reflex, Sneeze, Sunlight, Ocular, Dominant autosomal inheritance, Prominent corneal nerves
Palabras clave
Reflejo fótico, Luz solar, Estornudo, Ocular, Herencia autosómica dominante, Nervios corneales prominentes
Introduction

Autosomal Dominant Compelling Helio-ophthalmic Outburst Syndrome (ACHOO) is very widespread, but few published reports discuss the pathophysiology of the syndrome.1–17 The first reference is attributed to Aristotle.18,24 It consists of a variable amount of sneezing in uncontrollable outbursts after sudden exposure to bright light, usually sunlight.1–13,15,16 Inheritance is autosomal dominant,1,2,8–13,18 with high penetrance, without preference for gender or iris colour,8,11,12 but it is more common in Caucasians.11,15 Prevalence ranges from 11% to 35%.1,2,8–12,15 The aetiology is not fully understood but a number of theories have been suggested.1,2,4,7,9,11–13,18

Method

We studied a Spanish family that suffered from photic reflex, constructing the family tree to verify the number of patients affected and the pattern of transmission (Fig. 1). Like that published by Peroutka and Peroutka,10 our case is that of the author's own family (C. Sevillano). All the patients (30) were questioned about their sneezing, and only 12 people showed clear signs of ACHOO. Two more patients showed partial symptoms compatible with ACHOO (not included in the study), and another had pathological sneezing with alcohol consumption. A complete eye examination was performed looking for alterations that might be related to the syndrome in some way. When assessing the corneal nerve plexus, the classification proposed by Takai et al.14 was considered, where grade 0 is “invisible”, grade 1 is “visible in slit-lamp but not in photograph ×25” and grade 2 is “visible in both cases” (Fig. 2).

Fig. 1.
(0.06MB).

Family tree for the family studied.

Fig. 2.
(0.07MB).

CNT grade 2 in subject 11. Slit-lamp photomicrograph 25×.

The anterior segment images were taken with an ATE 600 DC1 camera (Topcon®), the optical coherence tomography scans with HD-OCT Cirrus (Carl Zeiss Meditec, Inc., Dublin, CA, USA), pachymetry measured with Pachette 2 model 500 SN-100096 (DHG Technology Inc., Exton, PA, USA) and pupillometry with the CA-100F topography corneal analyser (Topcon Medical Systems, Oakland, NJ, USA). All measurements were performed by the same person under the same circumstances (time, lighting conditions, eye drops, etc.).

Results

Twelve out of 30 members (40%) of the family clearly had the syndrome. The autosomal dominant inheritance pattern with partial penetrance was confirmed in the family tree (Fig. 1). The age range of the patients was broad (10–84 years), although onset of the syndrome is always before the age of 30. Of the patients in the sample, 76% had blue eyes and the ratio of male to female was 7:6. Four subjects (33%) had chronic sinusitis and only one of them also had a deviated septum. Two subjects had some type of allergy. One patient had Thygeson's superficial keratitis (Table 1).

Table 1.

Characteristics of the patients.

Patient  Age  Gender  Eye colour  Rhinitis  Other conditions  Medication 
84  Blue  No  Colon cancer  Iron supplements 
73  Blue  Yes  HBP, chronic sinusitis  ACE inhibitor, calcium antagonist 
43  Blue  No  Thygeson's keratitis  Topical fluorometholone 
12  Blue  No  No  No 
39  Blue  Yes  Chronic sinusitis  No 
32  Blue  No  Mite allergy  No 
71  Blue  No  No  No 
33  Blue  No  No  No 
35  Blue  Yes  Migraine with aura  No 
10  31  Brown  No  ASA allergy, chronic sinusitis  No 
11  29  Brown  No  No  No 
12  61  Brown  No  HBP, COPD, AMI, pacemaker  Acenocoumarol, beta-blocker, digoxin, atorvastatin, ACE inhibitor 
13  26  Brown  No  Nasal septum deviation, chronic sinusitis, asthma  No 

ASA: acetylsalicylic acid; COPD: chronic obstructive pulmonary disease; HBP: high blood pressure; AMI: acute myocardial infarction; ACE inhibitor: angiotensin-converting enzyme inhibitor.

The clinical features of the sneezes are shown in Table 2. The threshold13 is a particular feature that consists of looking into sunlight when they feel the need to sneeze in order to trigger the sneeze; that is, providing the sneeze reflex with a minimal light stimulus to trigger the response; 75% of the subjects had this feature.

Table 2.

Clinical characteristics of the sneezing.

Patient  Age at presentation  Frequency  Latency (min.)  Number of sneezes  Interval between sneezes (s)  Time  Threshold  Other 
<30  IV    2–4  30  First exposure  No   
30  II  10  30  9–12Yes  Temperature changes 
  IV             
  IV             
10  II  2–4  Continuous  No pattern  Yes  Eyebrow hair removal 
<25  First exposure  Yes  Nasal hair removal, artificial light 
20–30  III  1–2  3–5  30  No pattern  No  Only on drinking alcohol 
>6  III    In the morning  Yes   
>6  III  <1  2–3  30  First exposure  Yes   
10  <10  IV  1–2  1–2  120  9–12Yes   
11  <10    1–2  2–4  60  First exposure  No  Nasal hair removal 
12  <20  IV  <1  1–2  30  Morning  Yes   
13  <10  II  2–3  15  Morning  No   

The frequency was graded as I (sometimes, <25%), II (often, 25–50%), III (nearly always, 50–75%), IV (always, >75%). In our study, 70% had grades III or IV.

Clinical presentation in our patients was consistent with that reported in other articles: 9 patients (75%) reported suffering sneezing bouts at the first exposure or in the morning upon waking, with an average of 2–3 sneezes in 9 subjects (75%) and a latency time of 1min from exposure. The interval between sneezes was 30s in 5 patients (40%) and <10 in 33%. The refractory period was 24h in 66% of the subjects, similar to the data obtained in other studies.2 Other stimuli that caused sneezing were hair removal from nose and eyebrows (25%), temperature changes in one subject and consumption of alcoholic beverages in another; all may have been biases due to simultaneous exposure to light.

The ophthalmology examinations are shown in Table 3. The mean spherical equivalent was −0.884. The nerve fibre layer measured by OCT was within the 95th percentile (normal) in 100% of patients, with the macular thickness measured by OCT slightly thicker than expected, at an average of 244.5μm.20 Mean pachymetry measurement was 528.5μm, considered normal among the Spanish population.21 Mean pupillometry was 5.99mm in diameter under mesopic conditions, in line with previous studies.22,23 This could be relevant, since the larger the pupillary diameter, the greater the amount of light entering and stimulating the neural pathway.

Table 3.

Eye examinations.

Patient  VA (decimal scale)  Spherical equivalent  Mesopic pupillometry  Corneal examination  Tonometry (mmHg)  Pachymetry (μm)  Fundus examination  OCT macular thickness (μm) 
0.4  −2    Nuclear cataract  13       
−0.5  5.38  Pseudophakia, CNT 1  15  568  Oblique papilla   
             
             
0.25             
           
−0.5             
−1.5  5.47  CNT 1  13  494  C/D 0.3  254 
−0.75  5.81  CNT 1, persistent pupillary membrane, endothelial irregularity  14  508  C/D 0.2  264 
10             
11  −5.25  6.82  Meibomianitis, CNT 2  16  549  Normal  232 
12  0.9  −1.5  5.84  BUT<10, nuclear cataract, CNT 0  17  524    289 
13  6.09  BUT<10, meibomianitis, CNT 2  14  497  C/D 0.1  286 

BUT: Tear Break-up Time; C/D: cup/disc ratio; CNT: corneal nerve thickness (according to Takai et al. classification14).

With regard to the corneal nerves, according to the Takai classification of prominent nerves, our series had 33% grade 0, 33% grade 1 and 33% grade 2; these data being statistically significant compared to the healthy population.

Discussion

ACHOO is characterised by paroxysmal outbursts of sneezing after the sudden exposure of a subject adapted to the darkness to a bright light,1,15,16 and it is usually evident from childhood.2,9,10 There are 4 principal theories to explain this phenomenon.1,2,4,7,9,11–13,18

The first of these, the optic-trigeminal summation theory, suggests that there is some association between the optic and trigeminal nerves in the midbrain area, such that stimulation of the optic nerve (light) may be perceived as a nasal stimulus. Everett15 supports this theory stating that rubbing of the caruncle can cause sneezing.

The second theory, parasympathetic generalisation, supposes that adjacently-situated parasympathetic nerves are co-activated with the stimulation of just one of them.

Hypersensitivity to light is the basis of the third theory: it may be due directly to hypersensitivity of the trigeminal nerve4,13 or to parasympathetic hypersensitivity which, in the ciliary ganglion, stimulates the adjacent trigeminal corneal pathway.6 Authors like Katz et al.,4 among others,5,15 argue that keratitis intensifies this phenomenon, suggesting a role of corneal sensory innervation.

A supernumerary pathway has been suggested but not yet proven.13

Our focus is on the third theory, studying the ocular structures and attaching more relevance to the neural pathway. Although the number of patients studied is limited, the results are consistent with previous studies. Familial aggregation could be considered a bias in this type of study.

Paroxysmal sneezing is typical only with the first exposure,1,2 with a refractory period, suggesting a polysynaptic pathway.6 The previously described threshold feature13 means that it requires a minimal stimulus to trigger the response.6 In our study, 75% of the patients reported sneezing with first exposure to sunlight, or at least in the morning, and 75% had the aforementioned threshold feature. Furthermore, having only 2–3 sneezes suggests saturation of the neural pathway. The refractory period was 24h in 66% of the subjects, similar to the data published on other series.2

Autosomal dominant inheritance is demonstrated in the family tree (Fig. 1). We found no gender preference; however, while some authors did not find an association,8,11,12 others did2,15 (finding it to be more common in men). An association has been found with the single nucleotide polymorphism (SNP) rs10427255 at the locus 2q22.3, close to a gene (ZEB2) associated with epileptic seizures.24

García-Moreno et al.2 found that 76% had brown eyes, but Semes et al.11 found no association with eye colour. In our case, 75% of the patients had blue eyes, so the authors do not believe this has any relationship with the syndrome. As with other articles,8,11 we found no association with deviation of the septum or allergies.

Interestingly, patient 7 suffered episodes when he consumed spirits, as in another case reported by Whitman and Packer,13 although another article attributes the cause to the histamine in wine.19 This patient did not have vasomotor rhinitis; we do not know whether it could have the same nervous pathophysiology as ACHOO or whether it is an isolated factor.

The history of the sneezing was similar to that described previously: at first exposure in 75% (García-Moreno et al.2 78%; Katz et al.4 100%); 2–3 sneezes in 75% (García-Moreno et al.2 44%; Semes et al.11 90%), and only the latency and the interval between sneezes were different: 1–2min latency (Semes et al.11 found <20s in 80%; Morris6 9.6s; Forrester9 15s maximum, and García-Moreno et al.2 5s) and an interval between sneezes of 30s in 40% and <10s in 33% (Semes et al.11 reported <19s in 85%, García-Moreno et al.2 2s, Morris6 3.4s).

From the point of view of ocular involvement in ACHOO, Katz et al.4 suggest a role for corneal sensitivity in 5 patients with cystinosis. In the eye test (Ishihara test, corneal reflex, accommodation, iris and retina scanning), no abnormalities were found. Everett15 reports a patient with scrofulous keratitis, pointing to hyperaesthesia of the trigeminal nerve or one of its divisions, and Lewkonia16 presents 2 cases in which the stimulus was the slit-lamp itself; one with keratitis and one with a cataract in a blue eye.

We measured different eye structures, obtaining normal findings in visual acuity, refraction, mesopic pupillometry, pachymetry, OCT for macular and fibre layer thickness, autofluorescence and fundoscopy. We were unable to perform either aesthesiometry or confocal microscopy that might have provided objective information on corneal innervation.

The corneal examination did detect an increase in the size of the corneal plexus. Takai et al.14 state in their study that 75% of the normal population has grade 0 and only 25% grade 1. Accordingly, our series had 33% grade 0, 33% grade 1 and 33% grade 2; therefore higher than expected in a healthy population. We found statistically significant differences between our prevalence (66.67%; CI 95: 47.81–85.53) and that found by Takai in healthy subjects (prevalence 2.7%; CI 95: −0.99 to −6.4; p=0.000) using the chi-square test for difference of proportions.

The pupillometry measurements are not easily comparable with other studies due to the different systems used; even so, our series did not show high values, so there should be no bias when assuming greater light stimulation of the neural pathway by a large pupil.

We therefore conclude that the eye studies in our series show no differences with respect to the population without ACHOO, except in corneal nerve thickness, suggesting a possible hypersensitivity of the trigeminal branches playing a role in the pathogenesis of ACHOO.

Further studies are required to determine the aetiology of the syndrome. The study of the prominence (thickness) of the corneal nerves in the general population or use of the aesthesiometer in affected patients may provide more information about this syndrome.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Please cite this article as: Sevillano C, Parafita-Fernández A, Rodriguez-Lopez V, Sampil M, Moraña N, Viso E, et al. Curiosidad: reflejo de estornudo fótico. Síndrome helio-oftálmico de estornudos compulsivos autosómico dominante. Arch Soc Esp Oftalmol. 2016;91:305–309.

Corresponding author. (A. Parafita-Fernández alberto.parafita.fernandez@sergas.es)
Copyright © 2016. Sociedad Española de Oftalmología