Andrade et al.
, J Clin Case Rep 2013, 3:12
http://dx.doi.org/10.4172/2165-7920.1000323
Clinical Case Reports
Case Report Open Access
Tiapride Associated Toxic Epidermal Necrolysis in an HIV-Infected Patient
Paulo Andrade1*, Nuno Rocha Pereira1, Cndida Abreu1, Paula Egipto3, Daniel Moura2 and Antnio Sarmento1
1
Department of Infectious Diseases, Hospital de So Joo, Porto, Portugal
2
Burn Unit, Hospital de So Joo, Porto, Portugal
3
Department of Pharmacology, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
Abstract
Toxic epidermal necrolysis is a rare but severe and often fatal adverse cutaneous drug reaction. Early diagnosis
and prompt discontinuation of the culprit drug is of the utmost importance, making drug causality assessment the
mainstay when managing this condition. We present the first reported case of toxic epidermal necrolysis induced by
tiapride, in a 43 year-old male Caucasian with a history of liver cirrhosis and HIV infection. This case report should
raise awareness on the medical community to a potentially fatal reaction to a frequently prescribed drug in alcoholic
patients. It also underlines the importance of further research regarding HIV infection, immune deregulation and
adverse cutaneous drug reactions.
Keywords: Tiapride; HIV; Toxic epidermal necrolysis undetectable blood HIV viral load and a CD4+ T lymphocyte count of
312/mm3.
Abbreviations: TEN: Toxic Epidermal Necrolysis; SJS:
Stevens-Johnson Syndrome; BSA: Body Surface Area; SMX/TMP: At the emergency room (D1) the patient presented fever (38.8C),
Sulfamethoxazole/Trimethoprim; MHC: Major Histocompatibility tachycardia (110 hbpm) and tachypnea (24 cpm), as well as oral
Complex; HAART: Highly Active Antiretroviral Therapy; CMV: enanthem, bilateral conjunctivitis and a non-pruriginous coalescent
Cytomegalovirus; HSV: Herpes Simplex Virus; HBV: Hepatitis B maculopapular exanthema distributed to the face, neck, trunk, limbs,
Virus; HCV: Hepatitis C Virus hands and feet, including the palms and soles and sparing the scalp
and perineum. Laboratory results were the following: haemoglobin
Introduction 11.4 g/dL, white blood cell count 35109/L, thrombocytes 42109/L,
albumin 25.9 g/L, AST 51 U/L, ALT 48 U/L, total bilirubin 8.3 mg/L,
Toxic epidermal necrolysis (TEN) is a severe adverse cutaneous urea 1.8 mg/L, creatinine 7 mg/L, aPTT 37 sec, PT 13.7 sec and
drug reaction characterized by mucosal erosion and epidermal C-reactive protein 48 mg/L. His CD4+ T lymphocyte count was 71/
detachment [1]. It is usually distinguished from Stevens-Johnson mm3 and HIV viral load was 633.000 copies/mm3. He was admitted
Syndrome (SJS) by the extent of affected body surface area (BSA): SJS
to the Infectious Diseases Ward with a diagnosis of suspected TEN
when less than 10% of BSA is affected, TEN when BSA affected is more
associated to tiapride and all medication was discontinued. On D2 after
than 30% and when 10 to 30% of BSA is affected as SJS-TEN overlap
admission, due to cutaneous tenderness and dorsal bullae, the patient
[1,2]. TEN is a rare condition, with an estimated incidence of 0.4 to 1.9
started intravenous corticosteroids. On D4, diffuse bullae formation
per million people annually [3-5]. Reported incidence in HIV infected
patients is higher, as much as 1 per 1000 people annually [6]. Some of was observed and positive Nicholsky sign localized to the dorsum was
the most frequently implicated drugs are anti-infective sulfonamides, elicited. A skin biopsy was performed on D5, confirming epidermal
phenytoin, carbamazepine, phenobarbital and allopurinol [7]. We necrosis and detachment as well as discrete inflammatory infiltrate
present the first reported case of TEN attributable to tiapride, a in the superficial dermis. Blood, sputum and urine cultures were all
neuroleptic drug mainly used in alcoholic withdrawal syndrome. negative. Serological testing revealed past infection by CMV, HSV1,
Mycoplasma pneumoniae and Chlamydia pneumoniae and no prior
Case Report contact with HSV2, HBV, HCV, Treponema pallidum or Toxoplasma
A 43 year-old male Caucasian was admitted to the emergency room gondii. Serum cryptococcal and CMV antigens were negative.
of our tertiary care hospital with a two day history of fever, headache Peripheral blood polymerase chain reaction for HSV1 and 2, CMV,
and malaise, followed by bilateral conjunctivitis, oral enanthem and a Mycoplasma pneumoniae and Chlamydia pneumoniae were negative.
maculopapular exanthema in the entire body surface, except for the Clinical worsening ensued with sheet like epidermal sloughing which
scalp and perineum. He had been admitted to the emergency room of eventually covered about 90% of total body surface (Figures 1 and 2).
another hospital with acute alcohol intoxication 7 and 5 days earlier, On D7 corticosteroids were discontinued. The patient was transferred
had been treated with intravenous fluids, thiamine and pyridoxine on to the Burn Unit where hemodynamic stability was maintained with
both occasions and was started on tiapride.
He had HIV infection and alcoholic liver cirrhosis, both diagnosed
*Corresponding author: Paulo Andrade, Department of Infectious Diseases,
6 years earlier when he was also diagnosed with pulmonary tuberculosis Hospital de So Joo, Porto, Portugal, Tel: +351967247061; E-mail:
and was started on isoniazid, rifampin, pyrazinamide, ethambutol and [email protected]
pyridoxine, as well as highly active anti-retroviral therapy (HAART), Received November 20, 2013; Accepted December 16, 2013; Published
sulfamethoxazole/trimethoprim (SMX/TMP) for opportunistic December 18, 2013
infection prophylaxis and oxazepam for alcohol withdrawal syndrome. Citation: Andrade P, Pereira NR, Abreu C, Egipto P, Moura D, et al. (2013)
He had been treated previously with thiamine, due to several prior Tiapride Associated Toxic Epidermal Necrolysis in an HIV-Infected Patient. J Clin
Case Rep 3: 323. doi:10.4172/2165-7920.1000323
episodes of acute alcohol intoxication. He was compliant for 5 years
(until 12 months before emergency room admission), when he Copyright: 2013 Andrade P, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
abandoned follow-up and resumed alcohol consumption. At that unrestricted use, distribution, and reproduction in any medium, provided the
time he was on tenofovir, emtricitabine and efavirenz, presented original author and source are credited.
J Clin Case Rep Volume 3 Issue 12 1000323
ISSN: 2165-7920 JCCR, an open access journal
Citation: Andrade P, Pereira NR, Abreu C, Egipto P, Moura D, et al. (2013) Tiapride Associated Toxic Epidermal Necrolysis in an HIV-Infected Patient.
J Clin Case Rep 3: 323. doi:10.4172/2165-7920.1000323
Page 2 of 3
weeks ahead the onset of reaction, tiapride was the only one to which
he had never been exposed to before. Since cutaneous testing or re-
introduction was not done, as they were deemed unnecessary risks,
drug causality was assessed using the ALDEN algorithm, with a
result of possible [11]. Several mechanisms have been proposed to
explain increased incidence of TEN and SJS in HIV infected patients
[6]. Genetic predisposition seems to play an important role in adverse
drug reactions, as is the case in the association between abacavir
hypersensitivity and the presence of class I major histocompatibility
complex (MHC) allele HLA-B5701 [12]. Other possible explanations
include viral infection and reactivation, increased use of certain
drugs, immune reconstitution, elevated serum IgE levels, a Th2 type
of cytokine pattern, slow acetylation and decreased anti-oxidant levels
[13-16]. Our case report seems to contradict some of these hypotheses.
This patient had no acute viral infection or reactivation, HAART
Figure 1: The patient upon transfer to the Burn Intensive Care Unit. had not been started and, therefore, no immune reconstitution
Notice sheet like epidermal sloughing of the trunk and left arm. occurred. Type 1 hypersensitivity responses are not attributable to
the sulfonamide functional group. However it is not known whether
T-cell-mediated TEN is related to the sulfonamide moiety [17]. Our
clinical report suggests that the immune determinant for TEN may also
be different from the sulfonamide functional group because our patient
was later treated with SMX/TMP without any adverse effect. Though
we cannot advance a completely satisfactory overall explanation, it is
worth noticing that in this case report TEN occurred during severe
immunesuppression, due to exposure to an unsuspected drug and not
while the patient was on HAART, with increasing CD4+ cell count and
exposed to high-risk drugs such as SMX/TMP [7,11].
Conclusion
This is the first reported case of TEN attributable to tiapride. As
it is a frequently used medication in alcoholic patients the medical
Figure 2: Close-up of the patient`s hand upon transfer to the Burn Unit.
Notice epidermal detachment originating a glove-like appearance.
community as a whole should be aware of this occurrence. Adverse
cutaneous drug reactions in HIV infected patients are yet to be
thoroughly understood, though the pathophysiologic mechanism
fluid therapy and inotropic support. Neither invasive mechanical
seems to be multifactorial.
ventilation nor parenteral nutrition was required. Wound care, under
intravenous sedation and analgesia, was performed with the use of Acknowledgment
topical antiseptics and hydrotherapy on a daily basis. No surgical The authors would like to thank Dr. Ctia Caldas for her assistance.
debridement was necessary. Gradual clinical improvement with
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J Clin Case Rep Volume 3 Issue 12 1000323
ISSN: 2165-7920 JCCR, an open access journal
Citation: Andrade P, Pereira NR, Abreu C, Egipto P, Moura D, et al. (2013) Tiapride Associated Toxic Epidermal Necrolysis in an HIV-Infected Patient.
J Clin Case Rep 3: 323. doi:10.4172/2165-7920.1000323
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Citation: Andrade P, Pereira NR, Abreu C, Egipto P, Moura D, et al. (2013) Tiapride Authors, Reviewers and Editors rewarded with online Scientific Credits
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