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toxic epidermal necrolysis ( ten ) is typically a drug - related fatal disease characterized by necrosis and destruction of the entire epidermal skin layer .
nephrotic syndrome ( ns ) is treated with steroids such as prednisolone ( pd ) . however , because of the adverse effects , such as osteoporosis , growth retardation , and weight gain , associated with pd treatment , other drugs with fewer side effects , such as deflazacort ( dfz ; an oxazoline derivative ) , have been recommended . among the 94 patients with ns who received steroid therapy in sanggye paik hospital , seoul , korea between 2001 and 2012 , three patients who received dfz developed ten .
we have reported one of these cases previously ; herein , we describe the two other cases of ten related to dfz in two boys aged 4 years and 14 years .
a 14-year - old boy , who was diagnosed with ns at 8 years of age , received pd as the initial treatment .
after 4 months of pd treatment , remission was achieved . however , because of ns relapse , the treatment was switched to dfz for 14 days ; dfz treatment was then tapered .
he was also receiving risperidone ( 0.5 mg , bid ) and atomoxetine ( 25 mg qd ) since 8 years of age for the treatment of mental retardation .
after 6 years , he again received dfz ( 24  mg tid ) daily owing to proteinuria .
after a 17-day treatment period , pruritic papules and patches appeared on the lower extremities .
he was admitted 19 days after medication was initiated , after the skin lesions indicated an extensive spread within 3 days .
laboratory tests revealed a white blood cell count of 7,040 cells / mm , c - reactive protein level of 0.3 mg / dl , and negative results for human immunodeficiency virus and mycoplasma pneumonia antigen . on hospital day 2 , the skin could be easily peeled off , similar to that noted in burn injuries ( fig .
hence , he was transferred to the intensive care unit for infection prevention and conservative care .
intravenous immunoglobulin - g ( iv - ig ; total , 4.51 g / kg ) was administered according to the severity of the skin lesions .
after discharge , the ns has been controlled by switching the treatment to pd , and the patient has consistently taken risperidone . thus far , he has not experienced any skin complications .
a 4-year - old boy who was diagnosed with ns was receiving dfz ( 24  mg tid ) and enalapril ( 5 mg qd ) .
after 41 days , he presented with papules and blisters around the mouth and on the palms and soles ( fig .
the initial white blood cell count was 14,720 cells / mm and the c - reactive protein level was 1.4 mg / dl .
erythematous papules and blisters rapidly spread on his body ( 50% ) within 3 days .
ceftriaxone was injected , and iv - ig ( total , 4 g / kg ) was administered for 13 days according to the extent of skin complications . from day 20 after hospital admission ,
thereafter , the medication was switched to pd , and he has not experienced a relapse thus far .
a 14-year - old boy , who was diagnosed with ns at 8 years of age , received pd as the initial treatment .
after 4 months of pd treatment , remission was achieved . however , because of ns relapse , the treatment was switched to dfz for 14 days ; dfz treatment was then tapered .
he was also receiving risperidone ( 0.5 mg , bid ) and atomoxetine ( 25 mg qd ) since 8 years of age for the treatment of mental retardation .
after 6 years , he again received dfz ( 24  mg tid ) daily owing to proteinuria .
after a 17-day treatment period , pruritic papules and patches appeared on the lower extremities .
he was admitted 19 days after medication was initiated , after the skin lesions indicated an extensive spread within 3 days .
laboratory tests revealed a white blood cell count of 7,040 cells / mm , c - reactive protein level of 0.3 mg / dl , and negative results for human immunodeficiency virus and mycoplasma pneumonia antigen . on hospital day 2 , the skin could be easily peeled off , similar to that noted in burn injuries ( fig .
hence , he was transferred to the intensive care unit for infection prevention and conservative care .
intravenous immunoglobulin - g ( iv - ig ; total , 4.51 g / kg ) was administered according to the severity of the skin lesions .
after discharge , the ns has been controlled by switching the treatment to pd , and the patient has consistently taken risperidone . thus far , he has not experienced any skin complications .
a 4-year - old boy who was diagnosed with ns was receiving dfz ( 24  mg tid ) and enalapril ( 5 mg qd ) .
after 41 days , he presented with papules and blisters around the mouth and on the palms and soles ( fig .
the initial white blood cell count was 14,720 cells / mm and the c - reactive protein level was 1.4 mg / dl .
erythematous papules and blisters rapidly spread on his body ( 50% ) within 3 days .
ceftriaxone was injected , and iv - ig ( total , 4 g / kg ) was administered for 13 days according to the extent of skin complications . from day 20 after hospital admission , the patient showed improvement in the symptoms , and was subsequently discharged . thereafter , the medication was switched to pd , and he has not experienced a relapse thus far .
ten is a rare but life - threatening disease that involves the skin and mucosa , and is usually caused by certain drugs .
a few recently published cases indicate that ten might be induced by steroid use , , . in particular , at our center , 40 patients treated with pd did not develop ten , but three of 54 patients treated with dfz developed ten . in case 1 , despite the initial treatment with pd and dfz , no skin complications developed at that time .
however , after readministration of high - dose dfz for more than 2 weeks , ten developed .
after remission was achieved , rashes did not reappear even after switching the treatment to oral pd .
the reaction severity decreases following the discontinuation of drug administration and develops more rapidly on drug readministration . in case 1 ,
however , these drugs were administered 6 years previously and the patient did not present side effects at that time .
consistent with the findings in case 2 , kim et al   reported that ten developed in a patient with ns treated with dfz and enalapril .
after approximately 4 weeks of treatment , the condition progressed from erythematous papules to ten .
captopril was reported to possibly cause ten , whereas enalapril may be a causative agent for ten when combined with dfz .
enalapril and captopril have been suggested to be powerful acantholytic drugs in vitro , and the active amide group of both drugs could induce acantholysis .
however , papay et al , in their extensive review of sjs / ten , have classified both drugs as 
 kim   and kim et al   also reported cases of sjs and ten caused by the use of dfz ( table 1 ) .
their patients did not receive any other medication , except for dfz , over 8 weeks .
ten is considered to be associated with exposure to an agent during an 8-week period prior to disease onset . to confirm the relationship between ten and dfz
kim   has suggested that dfz may be a possible cause of sjs , based on the results of skin tests and provocation tests using dfz . in the present cases , a rechallenge with dfz
the relationship between corticosteroids , especially dfz , and ten remains controversial , and its exact mechanism is not known .
roujeau et al   suggested that the risks were particularly increased for patients who had recently started receiving therapy ( within 2 months ) with most of the commonly questionable agents , including corticosteroids .
an immunosuppressive mechanism involving corticosteroids might play a role in the pathophysiology of sjs / ten . in numerous cases of sjs / ten
, the use of multiple medications or co - use of drugs may cause the development of sjs / ten .
however , most importantly , the only medication that was common between the cases and was taken within 8 weeks prior to disease onset was dfz .
therefore , we hypothesized that dfz was more likely to be the potential cause of ten , compared with other medications , although we could not exclude the possible additional role of enalapril in case 2 . in most cases ,
ten is almost exclusively attributed to drugs ; however , infections by viruses , bacteria , and mycobacteria could trigger the development of ten in association with drugs . because infection tests , such as herpes simplex virus tests , other than those for m. pneumonia and human immunodeficiency virus , were not performed in the present cases
nevertheless , from the viewpoint of immune suppression , it should be noted that ten did not develop in patients treated with pd .
several cases have demonstrated an association between secondary glomerular nephritis such as that in systemic lupus erythematosus and ten . in the present cases ,
renal biopsies were not performed owing to the parents refusal to undergo this examination ; however , no serological abnormalities were noted with regard to the rheumatoid factor , antinuclear antibody , and complement levels .
iv - ig likely affects a combination of many pathways that results in blocking of the interaction of fas with fasl . in patients with ten , an iv - ig dose of 24 g / kg
the patients were administered a total dose of 4.51 g / kg over 18 days and 4 g / kg over 13 days .
g / kg during the first 5 days of the onset of skin eruption , which was reduced depending on the severity of the skin lesions .
no adverse effects related to iv - ig therapy , including cephalgia , low - grade fever , flushing , chills , and myalgia , were noted .
the patients needed to be isolated and to be administered supportive care such as wound management , fluid replacement , respiratory and nutritional support , careful monitoring , and pain management .
the reason for the development of ten in dfz patients and not in pd patients is not yet clear .
moreover , the effect of the combination of medications or infection on the development of ten is unclear . nevertheless ,
because of the rapid , progressive , and fatal course of ten associated with dfz , we believe that it is essential to perform additional multilateral research and safety evaluations of dfz , and that clinicians should be aware of the serious side effects of this drug when treating cases of ns .
toxic epidermal necrolysis ( ten ) is a drug - related fatal disease . 
 extensive necrosis of the epidermis can lead to serious complications . 
 this report describes two cases of ten , associated with deflazacort ( dfz ) , in two boys , aged 4 years and 14 years , with nephrotic syndrome ( ns ) . 
 the 14-year - old male teenager received dfz following ns relapse . 
 after 17 days , pruritic papules appeared on the lower extremities . 
 another case involved a 4-year - old boy receiving dfz and enalapril . after a 41-day dfz treatment period 
 , erythematous papules appeared on the palms and soles . within 3 days 
 , both boys developed widespread skin lesions ( > 50% ) and were admitted to the intensive care unit for resuscitative and supportive treatment . 
 the patients showed improvement after intravenous immunoglobulin - g therapy . 
 owing to the rapid , fatal course of ten , clinicians need to be aware of the adverse effects of this drug when treating cases of ns .