Unilateral mydriasis due to Angel's Trumpet

Abstract

Introduction. There are many causes of bilateral and unilateral mydriasis. Common garden plants, such as Brugmansia (Angel's trumpet), contain tropane alkaloids. Case Report. An 11–year-old girl was brought to the Emergency Department because of discomfort and difficulty with near vision in the left eye, accompanied by unilateral mydriasis (pupil approximately 8 mm, unresponsive to both papillary light reflex and accommodation reflex). The consensual papillary light reflex of the right eye, the anterior chambers, the fundi, and the extraocular movements were intact. The history revealed that she had been playing in the garden and had just touched “a nice pink flower, similar to a trumpet.” Treatment was symptomatic and supportive, and the anisocoria resolved 48 hours after exposure. Morphological and chemical investigations showed high amounts of parasympatholytic tropane alkaloids in a corolla area rich in Dargendorff-positive glandular hairs. Discussion. Simple topical exposure to the flowers of Angel's trumpet, without instillation of plant sap into the eye, can produce self-limited unilateral mydriasis. Conclusions. This case adds to the differential diagnosis of acute anisocoria in otherwise healthy children. An accurate and detailed history will avoid unnecessary and expensive diagnostic tests. It is important for parents and garden suppliers have information about the potential adverse effects after handling Angel's trumpet plants.

Keywords:

• Auisocoria
• Brugmansia
• Child
• Glandular hairs
• Tropane alkaloids

Introduction

The cultivation of several Brugmansia species (B. arborea (L.) Lagerheim, B. suaveolens (Will.) Berchtold & Presl, and B. aurea Lagerheim) have become increasingly popular in Italy because they are ornamental plants with large trumpet-shaped flowers (Angel's trumpet). These plants, previously included in the genus Datura, are known to contain tropane alkaloids (1,2). The occurrence of a case of anisocoria following ocular exposure to an Angel's trumpet plant induced us to carry out morphological, histochemical and chemical investigations to get a better understanding of the conditions allowing poisoning through contact with the plant.

Case report

An 11-year-old girl was brought to the Pediatric Emergency Department because of sudden unilateral mydriasis observed by her mother. An hour before arriving, she experienced left eye discomfort and difficulty with near vision. No accompanying headache, diplopia, or other neurological symptoms were present. Past medical history was unremarkable. There was no history of trauma, fever, drug ingestion, or unintentional intoxication. Vital signs and mental status were normal. On examination, the general physical findings were unremarkable. The left pupil was dilated to approximately 8 mm and unresponsive to both papillary light reflex and accommodation reflex. The consensual papillary light reflex of the right eye, the anterior chambers, the fundi, and the extraocular movements were intact. Besides the anisocoria, the remaining neurological examination was non-focal. At first the mother was unaware of any cause for the anisocoria. When asked specifically, she said that in the afternoon the girl was playing in the garden with her friends and had just touched “a nice pink flower, similar to a trumpet.” A presumptive diagnosis of unilateral mydriasis caused by the handling of that flower and following local contamination of the eye was made. After two hours, the mother returned to the hospital with a trumpet flower of the same plant, immediately identified as Brugmansia suaveolens by the scientific staff of the Padua Botanical Garden. The patient's anisocoria resolved fully 48 hours after the exposure without any sequelae.

Analysis of Brugmansia suaveolens flowers

B. suaveolens has large pendent fragrant flowers; the corolla with a narrow basal part extending beyond calyx, widening abruptly, then campanulate (Fig. 1A). In order to understand why the child developed a significant mydriasis after just a brief touch with the plant, we performed morphological, histochemical and chemical analyses of the flower.

Fig. 1. B. suaveolens flower (1A); corolla tubulose part with prominent ribs and abundant glandular hairs (1B); ESEM image of the rib region with pluricellular stalks: the arrow points at a globose unicellular head (1C); Dragendorff positive reaction (indicated by the brown color) in a glandular head of a hair (1D).

Morphological analysis

Morphological investigations were performed using a light microscope and a ESEM (Environmental Scanning Electron Microscope), XL30 Philips. The main result was the presence of prominent ribs of corolla in the tubulose part of the flower, showing an abundant occurrence of glandular hairs (Fig. 1B) with a pluricellular stalk and a globose unicellular head, which can be easily broken (Fig. 1C).

Histochemical analysis

For the histochemical analysis, different pieces of flower were placed on a hanging-drop slide and covered with a few drops of Dragendorff's reagent. The samples were kept in the reagent at room temperature for five minutes and then rinsed with water and observed under a light microscope.

With Dragendorff reagent, alkaloids spontaneously give off a visible brown color (3). This reaction was strongly positive in the glandular head of the hairs (Fig. 1D).

Chemical analysis

For the chemical analysis, different parts of the flower were sampled and separately analysed: calyx; the entire corolla and different corolla parts, such as the prominent ribs and the inter-rib areas in the narrow basal part; and the distal corolla part. The samples (3 to 5 g fresh weight) were shaken for five minutes with 10 mL of 0.05 M sulphuric acid, then filtered; to 8 mL of the filtrates, 1 mL of concentrated ammonia solution was added. The mixtures were diluted to 10 mL with water and extracted by shaking with 10 mL peroxide-free ether. The ether phases were evaporated to dryness in a vacuum and the residues dissolved in 0.5 mL methanol. Thin layer chromatography was performed on silica gel plates (Merck, cat. 5715) using acetone, water and concentrated ammonia (90:7:3) as eluent system; plates sprayed with 5% ethanolic sulphuric acid (4). HPLC analysis was performed using a Spectra System UV6000LP (Thermo Finnigan); detection wavelength 254 nm; column Phenomenex Hypersil 5μ C18 (250x4.6); mobile phase phosphate buffer 25 mM pH 8 and ACCN (70:30); flow rate 0.6 mL/min. The total amounts of alkaloids were calculated by extrapolation from the atropine calibration curve (5). Hyoscyamine, atropine and scopolamine were identified by comparison with authentic standard solutions.

Hyoscyamine, atropine and scopolamine occurred in all the corolla samples, while in the calyx only scopolamine was detected. Quantitative analysis (total alkaloid content calculated as atropine) gave the following results: calyx 4.9 mg/g f.w, total corolla 4.5 mg/g f.w, upper corolla part 2.0 mg/g f.w, intra-rib area 5.2 mg/g f.w, rib area 10.0 mg/g f.w.

Discussion

Isolated unilateral mydriasis has been observed following contact with plants belonging to the genera Datura and Brugmansia, when pruning or removing the faded parts, and therefore attributed to ocular instillation of a drop of plant sap (6–10,11). This is consistent with the well known cellular storage of alkaloids within the vacuoles, so that they can be released following plant cells rupture. There could be a wide range of clinical expressions after local exposure to these type of plants; the severity and duration of effects depend on the amount and on the duration of the exposure to alkaloids; particularly, the more pronounced is the effect on the pupil, the longer is its duration, being reported to range from 24 hours to one week (8,11).

The uniqueness of our case was that the child had an important anisocoria after a brief touch with the flower. The analysis of the flower showed that the maximum alkaloid content is present in the corolla tissue along the ribs; the abundant occurrence of glandular hairs on the rib regions suggests that these alkaloids might be present not only in the epidermal cells but also in the glandular hairs, and this has been confirmed by a Dragendorff positive reaction of the glandular head of the hairs. These findings explain why intoxication may occur, as in our patient, following simple contact of the eye with Brugmansia plant surface, which is characterized by high densities of glandular hairs that can be easily broken. This must be particularly considered for children, who are particularly susceptibility to atropine toxicity; even a small amount may produce central nervous system manifestations (11).

A wide range of ocular and neurological disorders should be considered when dealing with a unilateral, dilated unresponsive pupil. Possible causes can be blunt trauma, trivial application - inadvertent or intentional - of a topical mydriatic drug, Adie's tonic pupil (caused by parasympathetic denervation at the myoneural junction of the papillary sphincter muscle), involvement of the intracranial third nerve (related to cerebral herniation or space-occupying lesions) (8,12). Instillation of topical pilocarpine 1% can be used to distinguish between paralytic mydriasis and pharmacological blockade of the iris sphincter due to topical exposure to Datura type plants. The pharmacologic dilated pupil will not constrict because pilocarpine is competitively inhibited by alkaloids such as atropine and scopolamine, paralysing the iris sphincter; on the other hand, pilocarpine 1% will contract the pupil in cases of paralytic mydriasis due to pre- or post-ganglionic nerve damage (6,7,13). However, false positive results have been reported in some conditions, such as contact with a low volume of plant extract, instillation of an excessive dose of pilocarpine, or a long time after exposure to alkaloids (12).

This case represents an interesting addition to the differential diagnosis of acute anisocoria in otherwise healthy children. Moreover, it emphasizes the importance of an accurate and detailed history in patients affected by unilateral mydriasis. This will avoid unnecessary and expensive diagnostic tests, usually indicated with a dilated unresponsive pupil of sudden onset. Finally, we want to emphasize the importance of information directed to parents and garden suppliers about the potential adverse effects after handling Angel's trumpet plants.