Department of Dermatology, Afzalipoor Hospital, Kerman University of
Medical Sciences, Kerman, Iran
Corresponding Author: Najmeh Ahramiyanpour, M.D., Department of
Dermatology, Afzalipoor Hospital, Kerman University of Medical Sciences,
Kerman, Iran. Tel: +989173703643, E-mail:
najmeh.pour@gmail.comAbstract: Toxic epidermal necrolysis (TEN) is a serious drug
reaction. Its proper cure would be challenging especially during
COVID-19 outbreak because of a dilemma regarding selecting the
immunosuppressive drug. In this case presentation, we report a case of
TEN who treat successfully with cyclosporine during COVID-19 outbreak in
a referral COVID-19 hospital.Keywords: Toxic epidermal necrolysis, COVID-19,
immunosuppressant, cyclosporine, calcineurin inhibitors.Introduction: Toxic epidermal necrolysis (TEN) is a rare drug
reaction associated with high mortality rate [1].
TEN presents with erythematous and dusky maculopapular rash that
progresses to flaccid blisters, epidermal erosion, necrosis and skin
detachment. [1-3] Drug hypersensitivity is the
most common cause of TEN. TEN can be associated with infections,
systemic diseases, malignancies and autoimmune conditions[4-6]. While there is no gold standard treatment
for TEN, systemic corticosteroid, intravenous immunoglobulin (IVIG),
cyclosporine, and tumor necrosis factor (TNF) inhibitors are optional
drugs for the management of TEN [1-4].
Management of TEN is always challenging especially during COVID-19
outbreak because use of the immunosuppressive drugs might have both
beneficial and harmful effects on COVID-19 course[7]. As we know there is not any study to compare
the effects of different immunosuppressive drugs such as cyclosporine or
prednisolone on TEN patients who are predispose to COVID-19. Selecting
an immunosuppressive drug in a patient with TEN is challenging and
troublesome. Here, we report a case of TEN who treat successfully with
cyclosporine during COVID-19 outbreak in a referral corona hospital.Case Synopsis: A 24-year-old man came into the emergency
department with a 4-days history of painful generalized dusky rash on
his body associated mucosal surface involvement. His past medical
history was positive for bipolar mood disorder. He was on carbamazepine
and valproate sodium for the last two years and lamotrigine during the
last two weeks.
On arrival to the emergency room, the patient was oriented and his vital
signs were stable (Bp: 130/80 mmHg, pulse rate: 80 beats per minute,
temperature: 36.9℃, respiratory rate: 16 per minute, and O2 saturation:
99%). Physical examination described more than 50% of body surface
area involvement. skin lesions were as painful, dusky and purpuric
macules and patches of irregular size and shape on the trunk and
extremities. Flaccid blisters with serosal fluid and detached epidermal
surface on the neck and chest detected (Figure 1). The Nikolsky sign was
positive. Hemorrhagic crust, lips erosion, erythema of buccal mucosa,
conjunctivitis, and facial edema is seen He also complained of
photophobia and painful dysphagia. His SCORTEN (SCORs of Toxic Epidermal
Necrolysis) was 2.
Laboratory tests revealed exclusively a mild leukopenia while other
results were negative or in normal ranges: potassium: 4 mmol/L, serum
creatinine: 1.1 mg/dl, serum urea: 12 mmol/l, serum bicarbonate: 22
mmol/l, serum glucose: 10 mmol/l, white blood cells: 3.5 μl, hemoglobin:
13.7 g/dL, platelets: 420,000, aspartate transaminase: 24 U/L, alanine
aminotransferase: 16 U/L, albumin: 36 g/L.
The patient was admitted with a diagnosis of TEN into the dermatology
ward of Afzalipour hospital, of Kerman University of Medical Sciences,
Iran that also is a referral COVID-19 center hospital in Kerman.
Lamotrigine was stopped and he was managed with supportive care, wound
care, thrombotic prophylaxis. As corticosteroid is rather controversial
during covid-19 outbreak and IVIG which is the first choice of treatment
was not afforded for the patient, we worked up to start cyclosporine.
The blood pressure, electrolytes and cholesterol were normal. Therefore,
we started cyclosporine 4mg/kg/day.
Within the first 36 hours after starting cyclosporine, the patient
showed a dramatic response to the treatment. No new bullae formation was
detected and there was a reduction in erythema and erosion. The evidence
of re-epithelization was observed on the third day and the Nikolsky sign
became negative (Figure 2). Meanwhile, blood pressure and kidneys’
function were normal.
Eventually, he discharged after one week with prescription of the
cyclosporin 2mg/kg/day for another one week. He informed respecting the
possibility of relapse. One week later the patient referred to our
clinic. Skin and mucosal lesions improved and the cyclosporine therapy
was discontinued.Discussion: Although systemic corticosteroid, IVIG,
cyclosporine, and TNF inhibitors are optional drugs in managing TEN, it
is still controversial about the gold standard treatment for TEN[1, 4]. During COVID-19 outbreak, the management
of TEN has encountered an additive challenge. Because use of the
immunosuppressive drug, especially like prednisolone and cyclosporine,
are controversial [8]. It seems IVIG is the best
option for the management of TEN, because IVIG is human immunoglobulin
and can strengthens the immune system [9].
An important issue in patients that IVIG is not affordable, as it is the
case in our patient, or is contraindicated, is which one of
immunosuppressive drugs can be use in the management of TEN during
covid-19 outbreak. As we know, there is not any study in COVID-19
outbreak to compare the effects of different immunosuppressive drugs
such as cyclosporine and prednisolone on TEN patients.
Use of corticosteroid, which is the routine choice in treating TEN
patients, is controversial in COVID-19 outbreak especially amongst
critical patients, [10, 11]. Albeit, it appears
that corticosteroids can be effective in severe COVID-19 cases, its
routine use is not supported in the literature[12-14]. On the other hand, due to the increasing
mortality of seasonal epidemic of influenza among corticosteroid users,
administrating corticosteroids in TEN patients would be of concern[15]. Therefore, we discarded the use of
corticosteroid.
We decided to start cyclosporine, as it can be a good treatment option
in COVID-19 outbreak due to several reasons. First, in Kirchhof et al.[16] cohort study the relative mortality of TEN
patients who were treated with cyclosporine was lower than those with
IVIg. Second, cyclosporine might be associated with a rapid
re-epithelialization [17] and reduce duration of
hospitalization [17, 18], which can reduce the
risk of COVID-19 in critical patients during hospitalization. Third,
cyclosporine can inhibit influenza A virus [19].
forth, in-vitro studies showed that cyclosporine can inhibit
immunophilin pathway and by this way it can inhibit replication of
coronavirus [8, 19-22]. Fifth, COVID-19 mortality
is highly linked to the cytokine storm and cyclosporine can be
beneficial during the inflammatory phase of COVID-19[21, 22]. Sixth, Cavagana et al.[22] reported that clinical course of COVID-19
patients on calcineurin inhibitors (CNIs) is generally mild with a low
risk of superinfection. Finally, although cyclosporine is an
immunosuppressant agent, infections are not one of its common side
effects [23].Conclusion: IVIG is the best treatment option in the management
of TEN during COVID-19 outbreak. For those IVIG is contraindicated or is
not affordable, cyclosporine can be a better choice than other
immunosuppressant drugs. As, patients on cyclosporine can benefit its
antiviral effects and have a shorter hospital admission stay.Potential conflicts of interest: The authors declare no
conflicts of interest.References: