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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 37  |  Issue : 4  |  Page : 222-225

Ocular toxicity in human subjects through accidental exposure to latex of Euphorbia umbellata (Pax) bruyns


1 Animal and Mineral Origin Drug Research Division, Siddha Central Research Institute, Central Council for Research in Siddha, Arignar Anna Government Hospital Campus, Chennai, Tamil Nadu, India
2 Siddha Central Research Institute, Arignar Anna Government Hospital Campus, Chennai, Tamil Nadu, India

Date of Submission27-May-2019
Date of Acceptance23-Oct-2021
Date of Web Publication04-Jan-2022

Correspondence Address:
Dr. Shailaja Rajathurai
Animal and Mineral Origin Drug Research Division, Siddha Central Research Institute, Central Council for Research in Siddha, Arignar Anna Government Hospital Campus, Arumbakkam, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/asl.ASL_77_19

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  Abstract 


Two cases of ocular injury due to accidental exposure to latex and vapors of Euphorbia umbellata are described in this report. With the direct exposure of eyes to split drops of latex and inhalation exposure to vapors resulted in severe conjunctival congestion with bilateral peri-orbital edema without pain and inflammatory features with intense burning sensation of both the eyes, photophobia, blurred vision, severe redness with blepharospasm, intense thirst, nausea, and projectile vomiting. The symptoms reduced markedly after vomiting induced by the consumption of Nilavembu Kudineer, a Siddha poly herbal decoction. Redness of eyes relieved immediately with the instillation of mother's milk. It is construed that the presence of phorbol esters, a type of diterpenes in the latex of Euphorbia umbellata could have produced inflammatory responses by virtue of histamine, cytokine, and protease release which induced vomiting, pain, heat, and redness. This case report emphasizes the importance of using personal protective equipment such as goggles, gloves, and face mask while collecting and preparing medicines using the aerial parts of Euphorbia umbellata.

Keywords: Euphorbia umbellata, latex, ocular toxicity


How to cite this article:
Rajathurai S, Kannabiran P, Parameswaran S. Ocular toxicity in human subjects through accidental exposure to latex of Euphorbia umbellata (Pax) bruyns. Ancient Sci Life 2018;37:222-5

How to cite this URL:
Rajathurai S, Kannabiran P, Parameswaran S. Ocular toxicity in human subjects through accidental exposure to latex of Euphorbia umbellata (Pax) bruyns. Ancient Sci Life [serial online] 2018 [cited 2022 Jan 21];37:222-5. Available from: https://www.ancientscienceoflife.org/text.asp?2018/37/4/222/334724




  Introduction Top


The family Euphorbiaceae is diverse and contains 300 genera and 7000 species of plant and is spread worldwide.[1] The plant of discussion, Euphorbia umbellata (Pax) Bruyns or Synadenium grantii Hook f. is an ever-green shrub or small tree with poisonous milky latex, widely used in folklore medicines in the treatment of allergies, gastric disorders, cancer, leprosy, and menstrual cramps.[2] The leaves and latex of E. umbellata possess anti-cancer activities.[3],[4]

As per Siddha references, this plant has bitter taste, hot, and pungent potency. This plant is generally used by heating with varagu vaikol (straw of Paspalum scrobiculatum).[5] Makkar and Becker (1999) reported that heat treatment would reduce the phorbol ester content.[6] In spite of the presence of diverse phytoconstituents which accounts for the anti-cancer activity too, the latex contains phorbol type diterpenes which produces deleterious irritant and toxic effect.[7],[8] This report describes one such undesirable toxic effects, namely “ocular toxicity” an accidental exposure happened at our laboratory, while collecting and processing the leaves of E. umbellata.


  Case Reports Top


Case 1

A 33-year-old female had accidental ocular exposure of latex of Euphorbia umbellata while collecting the leaves of the herb for medicine preparation on July 1, 2018, at Kolli Hills (11° 17' 12.7” N and 78° 20' 15.3” E) Tamil Nadu, South India. After collecting the leaves, the victim had inadvertently touched her eyes with the contaminated fingers, which immediately led to serious symptoms of intense burning sensation and stinging pain in both eyes, severe redness, severe photophobia, irritation, blurred vision, nausea, vomiting, moderate giddiness, and intense thirst.

Both the eyes were thoroughly washed several times with fresh water immediately. Despite copious irrigation with water, the symptoms persisted. The patient had instilled topical corticosteroid 0.1% Betamethasone sodium phosphate and herbal refreshing eye drops once after an hour of exposure to latex, but the symptoms did not subside. External application of sliced fresh potato over both eyes had minimal relief from burning sensation and photophobia. After 3 h of exposure, pure cow's ghee was instilled into the eyes, which did not give any relief but it was followed by dysentery with abdominal pain and mild burning micturition. Then, patient was administered 200 ml of polyherbal Siddha formulation in a decoction form, called Nilavembu Kudineer containing Andrographis paniculata, Zingiber officinale, Piper nigrum, Santalum album, Vettiveria zizanioides, Trichosanthes cucumerina, Mollugo cerviana, Plectranthes ambionicus, and Cyperus rotundus. Soon after that, patient had suffered projectile vomiting, which brought moderate reduction in photophobia, burning sensation of eyes, and cessation of excessive thirst. After this, patient had consumed 350 ml of butter milk which was again followed by vomiting. Instantly after vomiting, the victim was relieved of the symptoms of photophobia, burning, and blepharospasm to a greater extent.

However, redness of the eyes, i.e. conjunctival congestion was reduced remarkably after instillation of mother's milk, it was then followed by the application of mother's milk with castor oil on the eyelids. Finally, lemon juice was consumed over-night, then gradually all the symptoms subsided on the next day, except the extreme fatigue which extended for the couple of days.

On the 20th day of exposure, complete ophthalmologic examination was carried out which revealed normal status of eyes. The details of events with timeline and therapy associated with case 1 are displayed in [Table 1].
Table 1: Details of events with timeline and therapy associated with Case 1

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Case 2

A 27-year-old male had accidental ocular exposure of vapors to Euphorbia umbellata while preparing related medicines. Although care was taken in the laboratory to prevent the toxic effect of the herb with toxic properties, the vapors from the ground leaves evolved pungent odor which resulted in nausea, projectile vomiting followed by conjunctival congestion with bilateral peri-orbital edema without pain, burning, and irritation. Followed by these symptoms, eyes and face were thoroughly washed with fresh water. Within 15 min of exposure, corticosteroid eye drops containing 0.1% Betamethasone sodium phosphate and 0.5% w/v Neomycin sulfate was instilled into both the eyes, but there was no significant reduction in redness.

Ophthalmologic examination was performed within 1 h of exposure, which revealed sub-conjunctival hemorrhages in both the eyes, more pronounced in right eye and the same topical eye drops was continued for a week. On the 15th day of exposure, eye check-up revealed punctate sub conjunctival hemorrhage of the right eye and is displayed in [Figure 1]a, [Figure 1]b and [Figure 2]a, [Figure 2]b.
Figure 1: (a and b) Shows diffuse haemorrhage in right and left eyes respectively on 1st day of exposure in case 2

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Figure 2: (a and b) Tiny sub-conjunctival haemorrhage (marked in the square) in right eye on 15th day in case 2

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  Discussion Top


The Siddha system of medicine is one among the indigenous medical systems of India with its roots founded in Tamil speaking regions of the world, especially in Tamil Nadu, South India. Usage of processed latex from Euphorbia species like Euphorbia antiquorum (Chathura kalli), Euphorbia tirucalli (Thirugukalli), Euphorbia neriifolia (Ilai kalli) Euphorbia hirta (Amman pacharisi), is indicated for warts, inflammatory swellings, knee arthritis, chronic nonhealing ulcer, infantile eczema, leucorrhoea, alopecia, skin diseases, etc., internally and externally.[5] Euphorbia ligularia, Euphorbia neriifolia, Euphorbia nivulia, and Euphorbia umbellata are different species in the same family but commonly called as Ilaikalli.

This case report describes the ocular toxicity due to Ilaikalli-Euphorbia umbellata. Fresh twig of the plant was identified and authenticated by the Pharmacognocist of Siddha Central Research Institute, Chennai with code E09071801U and is shown in [Figure 3].
Figure 3: Photograph of Euphorbia umbellata (Pax) Bruyns

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The latex of E. umbellata contains proteolytic enzymes, glycoproteins and terpenes.[9],[10],[11] Zayed et al. studied five different plants of Euphorbia family and reported irritant and tumor-promoting activity in mice is due to the presence of phorbol ester at very low concentrations in diverse range of organisms.[12] The threshold value of 15 μg/g of phorbol esters to cause adverse effects has already been reported in the literature.[13]

Similar ocular toxicity with the latex of Calotropis procera[14] and seeds of Annona squamosa[15] was reported earlier that produced violent kerato-conjunctivitis, corneal edema, and sudden dimness of vision. Even though Euphorbia species is known for its ocular toxicity, literature survey reveals that ocular toxicity with Euphorbia umbellata is not yet been reported. Ocular toxicity of sap of Euphorbia myrsinites,[16] Euphorbia grandcornis,[17] Euphorbia neriifolia,[18] Euphorbia milii,[18],[19] Euphorbia trigona,[18],[20] Euphorbia lactea,[21] Euphorbia cyparissias,[22] E. mili, E. characis, E. palustris, E. emarginata, E. plathyphyllos, E. robbiae, E. tirucalli, E. peplus, E. lathyris[19] were already published. The major clinical presentation reported with Euphorbia ocular toxicity is keratopathy, kerato-uveitis, severe corneal edema, corneal epithelial defect which is often self-limiting when managed with prompt treatment including topical corticosteroids, antibiotic eye drops, cycloplegics, and tear substitutes.[18] Most of the cases recovered in 4 or 5 days to 20 days. Neglected cases may lead to blindness.[23],[24],[25]

When compared with other species of Euphorbia, the present case report shows the toxic effect of the latex of E. umbellata with not only the ocular symptoms but also with systemic disturbances like intense thirst, nausea, vomiting, and dysentery. The clinical presentation of case 2 is quite different from case 1, may be due to the difference in route of entry (inhalation exposure) and amount of exposure. The inhalation of vapors of ground leaves brought giddiness and vomiting as initial presentation, followed by ocular symptoms which existed for a while and started reducing with copious irrigation and topical corticosteroids. However, the sub-conjunctival hemorrhage started reducing slowly in a week.

Siddha literature claims ilaikalli (E. umbellata) in raw form increases pittam (heat component) rapidly, due to which vomiting, giddiness, burning of eyes, and intense thirst were reported. This is the reason why the systemic effects are shown although the ocular and inhalation exposure were reported. Instillation of cow's ghee, human milk and induction of vomiting were all aimed to reduce the vitiated pittam, due to which the ocular symptoms such as burning, stinging pain, redness and photophobia reduced with vomiting, which might have helped to eliminate the toxins through vomitus.

It is construed that phorbol and its derivatives in the latex of Euphorbia umbellata induced inflammatory responses[26] and the modus operandi could be attributed to the release of histamine, cytokines, proteases which initiates acute inflammatory response with vascular remodeling and the concomitant leakage of plasma responsible for tumor, tissue damage, redness, and heat. Further this would have provoked the chemoreceptor trigger zone in medulla of the brain and resulted in projectile vomiting. In vivo studies in guinea pigs has revealed that the active phorbol ester, TPA (4b-12-0-tetradecanoylphorbol-13-acetate) was reported to induce inflammation and epidermal proliferation by inducing DNA synthesis through prostaglandin activation.[27] Instillation of human milk brought immediate action in reducing the redness of eyes due to its anti-inflammatory and anti-oxidant activity which is mediated through rich content of immunoglobulins and other anti-inflammatory agents.[28],[29]

It is also noted that case 1 was managed with available traditional medicines and the effect of toxicity was relieved within 12 h although the photophobia, chemosis, redness, and burning of eyes were relieved within 6 h of exposure. We have also noticed that case 2 who has received only the topical corticosteroid has taken increased duration to get rid of ocular symptoms.


  Conclusion Top


Two cases of human acute ocular injury due to accidental exposure to the latex of E. umbellata revealed that it is highly toxic and it resulted in conjunctival congestion with bilateral peri-orbital edema and acute inflammatory sequelae. However, there are reports available in the literature to detoxify the phorbol-ester containing plant. It is evident from this report that Euphorbia umbellata produces spectrum of ocular and systemic disturbances. This case report hopefully finds its purpose, emphasizing the need to have personal protective equipment such as goggles, gloves, and face mask compulsorily while handling toxic plants as the case of the plant reported here.

Consent

Written informed consent was obtained from the victims for the publication of the case report. The corresponding author of this article is the first case described in this case report.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for 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.



 
  References Top

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Hassan EM, Mohammed M, Mohamed SM. Two new phorbol-type diterpene esters from Synadenium grantii hook F. Leaves. Rec Nat Prod 2012;6:255-62.  Back to cited text no. 8
    
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Uzabakiliho B, Largeau C, Casadevall E. Latex constituents of Euphorbia candelabrum, E. grantii, E. tirucalli and Synadenium grantii. Phytochemistry 1987;26:3041-5.  Back to cited text no. 11
    
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Zayed SM, Farghaly M, Taha H, Gotta H, Hecker E. Dietary cancer risk conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). J Cancer Res Clin Oncol 1998;124:131-40.  Back to cited text no. 12
    
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[PUBMED]  [Full text]  
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Fleischman D, Meyer JJ, Fowler WC. Keratouveitis from Euphorbia cyparissias exposure is a temporal phenomenon. Clin Ophthalmol 2012;6:851-3.  Back to cited text no. 22
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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