An old woman, 28 years old, weighing 74 kg was referred for skin detachment associated with bubbles and mucosal erosions. This clinical picture had occurred 15 days after the institution of a triple combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 20-week gestation. The woman was in her third gestation. The second case is aged 26, weighing 65 kg. This clinical picture had occurred 20 days after the administration of a triple therapy combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 32-week gestation. It was the fourth gestation. The birth of a stillborn had occurred the day before his admission into our service. The diagnosis of Toxic Epidermal Necrolysis with nevirapine was selected on the basis of the clinical and anamnestic arguments. The biological tests showed the following results: transaminases (ALT and AST) were within normal limits, blood glucose, and urea > 10 mmol/l. The evolution was marked by the patient death to Day 9 (D9) and at D2 of hospitalization. Discussion: NET and the SJS have been reported in pregnant women as potentially dangerous complications that are often associated with suspected drugs. Among these drugs, antiretroviral drugs, prescribed to pregnant women to prevent mother to child transmission of HIV are often reported. Our case is an illustration of the problem of HIV management in pregnant women. It also focuses on the association between pregnancy and Toxic Epidermal Necrolysis. Nevirapine is an effective drug in the regimens proposed in the management of HIV patients in limited resources countries. But the high frequency of toxidermia with this drug should lead to its replacement by other antiretrovirals least providers of toxidermia as anti proteases in the context of PMTCT programs.
Lyell syndrome or Toxic Epidermal Necrolysis first described in 1956 by Allan Lyell [
The risk of cutaneous drug reaction is higher in patients infected with HIV than in the general population [2-4]. For a long time they were due mainly to sulfadoxin anti-infectious used to treat or prevent opportunistic infections [3,4].
Since the occurrence of HAART, there is an additional risk of cutaneous toxicity associated with some of these drugs [5-7], mainly nevirapine. Indeed, several studies have documented the high incidence of drug-induced dermatitis induced by nevirapine [6-9].
This medicine is a component of most HAART proposed in sub-Saharan Africa. It plays a vital role in one of the public health priorities of the continent, the prevention of mother to child transmission (PMTCT) of HIV.
We report two cases of nevirapine induced TEN with fatal outcome in two pregnant women having received it in the context of prevention of mother to child transmission of HIV.
An old woman, 28 years old, weighing 74 kg was referred to the Department of Dermatology-STD, Donka Teaching Hospital, by a PMTCT center of Conakry, for skin detachment associated with bubbles and a mucosal erosions.
This clinical picture had occurred 15 days after the institution of a triple combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 20-week gestation. The woman was in her third gestation.
At examination, there was a poor general condition, bullous eruption with flaccid bullae of clear content, a sign of Nikolski, erosive and oozing closets, an epidermal detachment with a surface of skin detachment covering up to 60% of the body surface area (BSA) (
Laboratory tests performed (urea, glucose and bicarbonate) in addition to clinical factors gave a SCORTEN of 5 with a predictive mortality of 90%. Transaminases (ALT and AST) and other haematological investigations were normal.
During hospitalization, she gave birth to a premature male baby weighing 700 kg who has been admitted in neonatology.
The evolution was marked by the death of the patient to Day 9 (D9) of hospitalization. The baby also died at D2 neonatal hospitalization.
This woman aged 26, weighing 65 kg, was referred to the Department of Dermatology-STD, Donka Teaching Hospital, by a peripheral PMTCT center, for skin detachments associated with bubbles and a mucosal erosions.
This clinical picture had occurred 20 days after the
administration of a triple therapy combination: AZT (300 mg) + 3TC (150 mg) and nevirapine (200 mg), during a pregnancy of 32-week gestation. It was the fourth gestation. The birth of a stillborn had occurred the day before his admission into our service.
At examination, there was flaccid bullae of clear content, a sign of Nikolski, closets erosive and oozing, epidermal detachment with an estimated surface of 70% of the body surface area. There was also a mucosal (oral, conjunctival and genital) lesions in type croûto-erosive and oozing. CD4 cell count at baseline and viral load were not performed. Other hematological and biochemical examinations were normal.
The diagnosis of Toxic Epidermal Necrolysis with nevirapine was selected on the basis of the clinical and anamnestic arguments. The biological tests showed the following results: transaminases (ALT and AST) were within normal limits, blood glucose, and urea > 10 mmol/l. These elements corresponded to a SCORTEN of 4. The evolution was marked by the patient death at D2 of hospitalization.
Lyell syndrome or Toxic Epidermal Necrolysis (TEN) is the most common and most serious adverse drug reaction. It is a real public health problem because of its high mortality and its important functional impact. Its occurrence during pregnancy is increasingly reported [10- 13].
Since its first description, the detailed pathogenesis of this syndrome is not yet completely understood. Immune modulation and different forms of metabolism of drugs and other factors have been suggested [1,14].
According to some authors, the pregnancy itself could possibly induce NET/SSJ by complex immunomodulatory reactions, but pathophysiologic details remain obscure [12,15]. Others authors [
NET and the SJS has been reported in pregnant women as potentially dangerous complications that are often associated with suspected drugs. Among these drugs, antiretroviral drugs, prescribed to pregnant women to prevent mother to child transmission of HIV are often reported.
Toxidermia Frequency due to nevirapine varies between 10 to 35 percent according to studies [5,9,17-22]. In a meta-analysis of different cohorts under nevirapine, the frequency of drug-induced dermatitis, regardless of severity, was estimated at 35 percent in 380 patients treated with nevirapine against 19 percent in the control group [
The degree of immune deficiency associated with taking nevirapine would play a role in the occurrence of TEN in pregnant women. Indeed, according to Boehringer Ingelheim [
Premature birth and low weight birth observed in our case, have been reported by other studies. Indeed, premature births and fetal hypotrophy are more common in cohorts of women infected with HIV than in the general population [
Although the treatment is largely symptomatic, Toxic Epidermal Necrolysis in pregnant woman is a challenge for the entire medical team, especially at an early stage of gestation. The mortality rate is very high during Toxic Epidermal Necrolysis and turn out to approximately 40 percent [
Our case is an illustration of the problem of HIV management in pregnant women. It also focuses on the association between pregnancy and Toxic Epidermal Necrolysis.
Nevirapine is an effective drug in the regimens proposed in the management of HIV patients in limited resources countries. But the high frequency of toxidermia with this drug should lead to its replacement by other antiretrovirals least providers of toxidermia as anti proteases in the context of PMTCT programs.