erythema multiforme ( em ) is an acute self - limited polymorphous eruption , probably mediated by deposition of immune complex in the superficial microvasculature of the skin .
about 50% of em cases are triggered by identifiable factors , that include drugs ( 20% of cases ) and a viral or bacterial agent ( i.e. , herpes simplex and mycoplasma pneumoniae ) .
approximately half the cases are idiopathic.[13 ] most commonly involved drugs include anticonvulsants , phenothiazines , nonsteroidal anti - inflammatory drugs , penicillins , and sulfonamides.[14 ] em minor presents with mildly itchy , erythematous , expanding macules or papules that may coalesce and become generalized .  target lesions 
a 34-year - old - woman was referred to our department because she had developed a macular  papular eruption involving the face , neck , arms , and trunk [ figure 1 ] .
the day before , the patient had been treated with oral prednisone and loratadine at the emergency room .
detailed clinical history did not reveal any significant medical disease , allergy , or skin manifestation .
twelve days before , she had started consuming a slimming drug preparation ( 2 or 3 pills twice a day before meals ) and pilosella tincture ( 40 drops / day ) , which is a herbal remedy used in cellulitis and obesity due to its diuretic properties .
the chemical composition of slimming preparation was pseudoephedrine hydrochloride 50 mg , theobromine 30 mg , caffeine 2 mg , vitamin c 100 mg , clorazepate dipotassium 1 mg , dehydrocholic acid 160 mg , magnesium stearate 2.4 mg , precipitated silica 0.8 mg , talc 0.8 mg , pregelatinized starch 156 mg .
we suggested her to discontinue these drugs and we performed allergological investigations on 4-weeks control . on this occasion ,
lesions had completely resolved , leaving moderate postinflammatory hyperpigmentation , especially on the neck area [ figure 2 ] .
patch tests ( pt ) performed with the sidapa 2005 standard series showed negative reactions . after 8 days we applied the second pt using the galenic preparations of the two drugs [ figure 3 ] : the pills were pulverized and then incorporated in vaseline 1% , and pilosella tincture was mixed in vaseline 1% too .
pills - pt tested positive on day 2 ( + / ) and 4 ( + ) and negative on day 6 .
intradermal test and oral challenge test were not performed : the patient 's mother , who was her guardian , refused because of the potential risk of immunologic reactions .
the laboratory tests showed normal blood cell count , protidogram , and liver enzymes , along with mildly elevated erythrocyte sedimentation rate .
the serological results excluded infections from hsv-1 , hsv-2 , ebv , and coxsackie virus a and b , borrelia burgdorferi , mycoplasma pneumonia , and klebsiella pneumoniae . given the absence of target lesions , a skin biopsy of a shoulder lesion was also carried out .
histopathological findings of an inflammatory pattern characterized by high - density lichenoid infiltrate rich in t cells , lymphocytes at the dermoepidermal junction , satellite cell necrosis , vacuolar degeneration of the basal layer , and dermal edema were suggestive of an em - type drug eruption[13 ] [ figure 4 ] .
the patient at presentation time : ( a ) face and neck involvement ; and ( b ) trunk and arms involvement ( a ) the patient at 1 month control , after having discontinued the slimming drug ; and ( b ) the patient at 1 month control , after having discontinued the slimming drug galenic preparations of the slimming drugs : pilosella tincture and thermogenic pills lesional biopsy of shoulder skin showing lymphocytic infiltrate at the dermal - epidermal interface and superficial dermis and vacuolar degeneration of the basal layer , likely a type of erythema multiforme eruption on 2 , 6 , 12 month follow - up , the patient had no more assumed slimming pills and similar eruptions never occurred .
the clinical history , the diagnostic investigations results and the 1-year follow - up findings indicate slimming pills as the triggering agent of the erythema multiforme -like eruption , excluding idiopatic em .
those slimming pills are also known as  food integrators with thermogenic activity ,  as they contain agents that are claimed to stimulate thermogenesis and increase metabolism and lipolysis ( ie , pseudoephedrine hydrochloride [ psh ] , theobromine [ tb ] , and caffeine [ cf ] .
the role of vitamin c ( vc ) is to hypothetically reduce the effects of the free radicals generated by lipolysis , whereas clorazepate dipotassium ( clp ) aims to mitigate possible side effects of psh .
the remaining substances ( ie , magnesium stearate , precipitated silica , talc and pregelatinized starch ) act as thickeners or as excipients . when considering these components , we focused our attention on those who were more likely to have immunogenic potential .
based on literature reports , we excluded cf , vc , and the four excipients / thickeners from analysis .
some reports indicate psh as the cause of severe skin reactions , including recurrent pseudoscarlatina and nonpigmenting fixed drug eruption .
tb ( 3,7-dimethyl-2,3,6,7-tetrahydro-1h - purine-2,6-dione ) , a methylxanthine , is a precursor molecule to pentoxifylline ( 3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1h - purine-2,6-dione ) .
pentoxifylline was reported to be associated with em in 12 people over the last 13 years .
in addition , theophylline ( 3,7-diidro-1,3-dimetil-1h - purina-2,6-dione ) , which is an isomer of tb , figures in the list of em - related drugs . given the chemical similarity between these three methylxanthines , we can hypothesize that the immunogenic potential of tb is similar to that of pentoxifylline and theophylline .
there are some reports of em appearing after intake of benzodiazepines and tetrazepam , which is structurally similar to clp . during the last 12 years
, 97 cases of em have been related to clp use : these cases were observed among a total of 4290 people who experienced clp side effects .
there are no reports specifically about em caused by a slimming drug preparation , and no studies have identified thermogenic stimulant pills as cause of either adverse skin reactions or em / em - like eruption .
our patient 's eruption probably resulted from the interaction between these four potentially immunogenic components ( ie , psh , clp , tb , and dha ) .
although tb has not been related with em or em - like eruption yet it could be considered as a possible cause , given its similarity with the other em - associated methylxanthines .
finally , psh and dha , which potentially cause rash and macular or papular rashes , may have contributed to the skin eruption too .
thus , our patient 's adverse reaction is likely to result from a possible summation effect : each component may have stimulated an immune response with different intensity and this interaction can have triggered the eruption development .
we then suggest that weight - loss compounds in slimming preparations should be kept in mind as a possible cause of drug - induced em - like eruption
. this would be particularly important in those countries where obesity is becoming a significant problem .
 we report a case of a 34-year - old woman presenting with an erythema multiforme ( em)-like eruption . 
 lesions developed after a 12-day treatment with a slimming drug preparation ( food integrator with thermogenic activity ) and a herbal remedy ( pilosella tincture ) . 
 serological investigations excluded viral or bacterial infections . 
 patch testing with galenic preparations of both drugs demonstrated sensitization to the slimming drug preparation . 
 according to literature reports and immune - chemical properties , those components that are likely to have triggered the skin eruption are clorazepate dipotassium and theobromine . 
 their interaction with other two constituents such as pseudoephedrine hydrochloride and dehydrocholic acid may have caused the adverse reaction by means of a summation effect . 
 there are no reports specifically about em caused by a slimming drug preparation and no studies have identified thermogenic pills as cause of em / em - like eruption . 
 weight - loss compounds in slimming preparations should be kept in mind as a possible cause of drug - induced em - like eruption . 
INTRODUCTION
CASE REPORT
DISCUSSION