Abstract
A 20-year-old girl referred with vision loss upon closantel use. Plasma
exchange and high-dose corticosteroid pulse therapy were administered. A
2.5-year follow-up showed improved vision and increased layer thickness
of the peripheral nerve fiber. Early treatment with plasma exchange and
high-dose corticosteroid therapy can be beneficial to reverse closantel
toxicity.
Keywords : Closantel, Blindness, Toxicity.
Introduction
Halogenated salicylanilides are well-known for their anti-parasitic
effects. The most famous medicine in this category is closantel, which
is used worldwide against Haemon chus spp. and Fasciolaspp. infestations in sheep and cattle (1, 2).
Animal studies indicate that the oral bioavailability of closantel in
sheep and cattle is about 50% and that the maximum plasma
concentrations (Cmax) are reached 24–48 h after administration with
extensive binding to plasma albumin (> 97%). Moreover, the
elimination half-life is from 7 days to 3 weeks depending on the animal
(3,4). Animals’ ocular studies after closantel intoxication have shown
edema in the intracanalicular portion of the optic nerve, causing
demyelinated axons, fibrosis of the optic nerve, and retinal
degeneration resulting in mydriasis, loss of pupillary reflexes, and
bilateral blindness (5,6). Besides, retina injury leads to the thinning
of photoreceptive cells (7).
This study reports a rare case of blindness after wrong administration
of closantel to treat Fasciola hepatica infection in a
young girl, who successfully managed with drug discontinuation,
plasmapheresis, and corticosteroids.
Case presentation
A 20-year-old girl with the primary complaints of bilateral blurred
vision and decreased color vision, progressing from 3 days earlier, was
admitted to the emergency department on Aug 16, 2018. She had a history
of Fasciola hepatica from 20 days earlier. Although her
specialist had prescribed triclabendazole, she was given closantel as an
alternative by mistake. She took 500 mg of closantel twice daily for
three days. On the second day of administration, she was unable to see
fine details and lost vision sharpness bilaterally. On the third day,
her problem progressed to blurred vision followed by color blindness.
There was no systemic illness and her physical examination was normal,
including central nervous system and abdominal examination. On primary
eye examination, the intraocular pressure of both eyes appeared normal
without any refractive error. Fundus examination showed a normal macula
appearance. She had the bilateral pale disc and optic atrophy with
sluggish papillary reaction to light, and negative RAPD (relative
afferent pupillary defect) was detected.
In the Humphrey visual field test, she showed a complete visual field
defect in the central 24-degree vision. Optical coherence tomography
(OCT) and retinal nerve fiber layer (RNFL) thickness in the
Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) map revealed a
thinning neural area of both eyes and a temporal fiber thinning in the
right eye (Fig. 1). Inferonasal and superonasal fiber had a good
condition in both eyes. However, the superotemporal and inferotemporal
peri-papillary fiber of the right eye had prominent thinning. Together,
RNFL thinning was dominant in the right eye. Inferior to superior
hemispheric asymmetry in the RNFL thickness and ganglion cell layer
thickness were not significant. Fundus autofluorescence was normal.
Fluorescein angiography of both eyes had no defects in the vascular
filling.
Plasmapheresis was performed immediately in an emergency department, and
the course of treatment consisted of five sessions of apheresis. She
also underwent corticosteroid pulse therapy with methylprednisolone
(1000 mg/day) for three consecutive days. At discharge, after 14 days of
treatment, she could see the shape of people or objects, and notice
their movement. In the course of the five-month follow-up, her visual
field was gradually improved with the defect being confined to central
10 degrees. The vision enhanced from counting fingers one meter to
counting fingers 6 meters. After an 18-month follow-up, her vision
improved to counting fingers 8 meters. Furthermore, after a 2.5-year
follow-up, the peripheral nerve fiber layer showed the highest
improvement in superior and inferior arcuate fibers in the thickness
analysis of the peri-papillary nerve fiber layer, a finding that was
compatible with the subjective data of visual field improvement (Fig. 1,
2).
Discussion
Closantel poisoning is usually accompanied by neurotoxicity, ophthalmic
toxicity, and hepatotoxicity in animals. There is no specific antidote
for poisoning, and information is scarce for humans (7). Recent findings
of closantel toxicity have shown that the toxic effects on retinae
ganglion cells may harm the central visual acuity and optic nerve (8).
According to our findings from RNFL and macula analysis (Fig 3), it
seems that the process of repairing damages to peripheral layers occurs
faster than that of damages to the central layers, which may explain the
reduction of the central visual field (Fig. 2).
Wrong prescriptions of closantel for 11 Lithuanian women was the first
human-documented closantel exposure, with temporarily visual acuity loss
after closantel exposure (9). After 22 years, the vision loss of five of
them was partially reversed without significant recovery over time (10).
According to our information, the use of plasmapheresis in one case and
systemic corticosteroid in another one showed significant recovery of
the vision (7,11). However, the literature also reports complete vision
loss because of closantel poisoning (12).
Systemic corticosteroids were used in two case reports of closantel
poisoning, with different results (7,12). It seems that the time of
treatment onset has a key role. Moreover, a recent case report of
reversible blindness upon accidental use of closantel highlighted that
immediate management with corticosteroids can have beneficial effects on
visual function (13).
Corticosteroid and vitamin B12 have been routinely prescribed for some
poisoning cases (7,12,14). Furthermore, plasmapheresis was used for two
cases, given the pharmacokinetic property and the high protein binding
of closantel (11,15).
In our case, the pre-treatment OCT scan of the macula showed a
generalized and uniform reduction in neural thickness of both eyes. Her
blindness was fairly treated with plasmapheresis and corticosteroid
pulse, and her vision improved significantly after an 18-month
follow-up. Vision improvement of both eyes may suggest that early
initiation of plasma exchange and corticosteroid pulse therapy can
reverse the destructive effects of closantel on retina ganglion cells
over time. Moreover, regarding pharmacokinetic characteristics (low
volume distribution and high protein binding), plasma exchange can be a
rational way to remove closantel.
Conclusion
This is a case report of successful treatment of closantel-induced
blindness. Early treatment with plasmapheresis and systemic
corticosteroid can be considered an effective intervention to reverse
the toxic effects of closantel. Besides, it seems reasonable to provide
education on the use of veterinary products and to relabel this drug as
forbidden for humans, given the lack of a definite antidote for it and
the possibility of irreversible blindness.