Corneal Toxicity after Self-Application of Calotropis procera (Ushaar) Latex: Case Report and Analysis of the Active Components.

Calotropis procera (ushaar) produces a copious amount of latex, which has both inflammatory and anti-inflammatory pharmacological properties. Local application produces an intense inflammatory response and causes significant ocular morbidity. We report corneal toxicity following self-application of latex from C. procera in a 74-year-old man. He reported painless decreased vision in the affected eye with diffuse corneal edema, and specular microscopy revealed a reduced endothelial cell count. After he was treated with topical corticosteroids, his visual acuity improved from hand motion to 20/80. The composition of the active compounds in the latex was analyzed. When topically administered, the latex may cause severe ocular injuries and a loss of endothelial cells over a period of time. Public education, early recognition of such injuries, and timely intervention may prevent permanent ocular damage.

Introduction

Herbal medicine and the use of plant and herb extracts are not uncommon in Saudi Arabia. Occupying four-fifths of the Arabian Peninsula, Saudi Arabia has a wide number of flora, including trees and herbs.[1] In the rural areas of Saudi Arabia, folk medicine is still actively practiced, and topical folk remedies are commonly used in the central and southern parts of the country.[2]

Calotropis procera (ushaar), a xerophytic shrub of the family Asclepiadaceae, is widely distributed in the tropics of Asia, Africa, and northwest South America.[3] It is medium branched and grows to a height of 4–5 m. The shrub has white or pink flowers[4] [Figure 1a and b] and produces latex throughout.

Figure 1

(a) Calotropis procera (ushaar). (b) Milky latex from the cut leaf of a Calotropis procera plant

The milky white endogenous latex exhibits a variety of effects in various animal models.[5] On oral administration, it produces potent anti-inflammatory and analgesic effects, as well as weak antipyretic effects, whereas on local administration, it induces an intense inflammatory response in animal models.[36] These antagonistic biological activities (inflammatory and anti-inflammatory) depend on the extraction medium and the route of administration of the latex in experimental animals.[3]

Ocular injury caused by this plant can be mechanical but more commonly results from toxic exposure to the latex. Accidental exposure has been reported to cause inflammation of the skin and eyes.[78]

We report the management of a case of self-application of C. procera latex that resulted in corneal toxicity as well as the analysis of the active compounds in the substance.

Case Report

A 74-year-old man presented to the Emergency Department at King Khaled Eye Specialist Hospital 3 days after self-application of latex from C. procera in his left eye (OS). He reported a painless decrease in vision. There was no history of previous trauma, surgery, or other ophthalmic disorder. Apart from hypertension, the patient had no medical illness.

Ophthalmic examination revealed best-corrected visual acuity of 20/40 in the right eye (OD) and hand motion vision in the OS. Intraocular pressure using applanation tonometry was within normal range in both eyes. Examination of the OD was unremarkable except for a mild cataract. Slit-lamp examination of the OS revealed quiet conjunctiva, no corneal epithelial defect, diffuse corneal edema with significant Descemet's folds and small pigmented keratic precipitates [Figure 2a and b], nuclear sclerosis of the lens, and a hazy view of the fundus. B-scan ultrasonography of the OS showed no pathology of the posterior pole. Specular microscope SP-3000 P showed 2224 endothelial cells/mm2 in the OD and 593 cells/mm2 in the OS, with abnormal morphology.

Figure 2

(a) Slit-lamp biomicroscopy of the left eye; (b) Diffuse corneal edema with Descemet's folds; (c) Complete disappearance of corneal edema after treatment

The patient was started on topical prednisolone acetate 1% four times a day for the first week, after which it was tapered. In addition, topical cyclopentolate 1% drops three times a day were prescribed for the first 2 weeks. In the first follow-up at 1 week after presentation, his best-corrected visual acuity in the OS improved to 20/300. Slit-lamp examination showed a reduction in corneal edema and an increase in clarity with fewer Descemet's folds. In the second follow-up at 2 weeks after presentation, his best-corrected visual acuity improved to 20/200. Slit-lamp examination showed a clear cornea with no residual edema [Figure 2c]. One month later, his best-corrected visual acuity was 20/80 in the OS. Six months later, the cornea remained clear with best-corrected visual acuity of 20/60 in the OS. The latex was sent for analysis and revealed the elements shown in Table 1. The result of phytochemical screening of petroleum ether and methanol leaf extracts of C. procera revealed the presence of glycosides, protein, triterpenoids, steroids, and flavonoids. The presence of these components in this species is an indication that it may have some medicinal potential. The latex of the C. procera was tested and was found completely varying in pH values. It has an acidic nature with pH of 4.2 at room temp of 25°C. The amount of magnesia was found in highest amount in latex. The level of chromium was completely absent [Table 2].

Table 1

Analysis of Calotropis procera (ushaar) using phytochemical screening

PhytochemicalScreening of Calotropis procera	Petroleum ether extract	Methanol extract
Alkaloids	-	-
Carbohydrates	-	+
Reducing sugars	-	-
Flavonoids	-	+
Glycoside	+	+
Tannin and phenolic	-	+
Saponin	-	-
Protein and amino acid	+	+
Fats and oils	-	-
Triterpenoids and steroids	+	+

-:Absent; +:Present

Table 2

Analysis of Calotropis procera (ushaar) using chromatography

Elements	Latex (mg/kg)
Al	200
Ca	340
CD	120
Co	80
Cr	ND
Cu	0
Fe	50
Mg	39,400
Mn	17
Ni	50
Pb	0
Zn	23
K	ND
N	ND
P	ND

ND: Not detected

Discussion

The irritant and pro-inflammatory properties of the milky white latex of C. procera have been well established.[3] Exposure to the latex irritates the mucous membrane and produces contact dermatitis and intense inflammation when injected locally in animal models.[89] The latex is known to contain several alkaloids (e.g., calotropin, catotoxin, calcilin, and gigantin) that are considered poisonous.[3] Spectrum analysis revealed the main elements of the latex, as shown in Table 1.

Shivkar and Kumar,[8] in their study of a rat paw model, found that injection of dried latex produces an intense inflammatory response involving edema formation and cellular infiltration. They showed that this response was caused by the presence of histamine in the latex itself, as well as the release of mast cell histamine by the latex. They also reported that latex induced prostaglandin synthesis through the induction of cyclooxygenase-2.[9] Both histamine and prostaglandins are key mediators in an inflammatory response.

In accordance with these findings, we believe that stromal keratitis is caused by inflammation induced by exposure to latex because of its strong pro-inflammatory property. The resolution of keratitis with local corticosteroid use supports such a mechanism. Another possible mechanism is a reduced endothelial count due to the direct toxic effect of the latex, as suggested by Al-Mezaine et al.[6]

Our patient developed transient corneal edema with permanent loss of endothelial cells as a result of the penetration of the latex into the corneal endothelium. The painless clinical course of our patient could be attributed to the analgesic property of the latex.[10] We conclude that C. procera latex causes immediate severe corneal damage with painless sudden dimness of vision. It may also reduce the endothelial cell count over a period of time.

Causes of visual impairment are numerous, but many are preventable through public education and provision of modern health care. Simple health education such as handwashing, protective eyewear, and avoiding rubbing of the eyes while plucking the Calotropis flower is important to prevent this kind of serious injury. Ophthalmologists should be aware of the acute side effects of some of these folk remedies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.