d - penicillamine has been known as one of the agents that are able to induce pemphigus ( 1,2 ) .
n-(2-mercapto-2-methylpropionyl)-l - cysteine ] is a thiol compound contained two free sulfhydryl groups , whereas d - penicillamine has only one sulfhydryl radical ( 3 ) .
while drug - induced pemphigus was not infrequently demonstrated in association with d - penicillamine , it has rarely been reported with bucillamine and has never been reported in rheumatoid arthritis ( ra ) and polymyositis ( pm ) overlap syndrome .
hereby , we report a case of bucillamine - induced pemphigus vulgaris in a patient with ra and pm overlap syndrome .
a 46-yr - old woman was referred to our rheumatology department due to polyarthralgia , and myalgia in may 2001 .
soft tissue swelling and tenderness were bilaterally noted at the proximal interphalangeal and metacarpophalangeal joints with morning stiffness lasting at least 1 hr .
proximal motor weakness on upper arms and legs has insidiously developed over three months and findings of magnetic resonance image on both thighs were compatible with myositis .
in addition , elevated level of muscle enzymes including creatine kinase ( ck ) , aldolase , alanine aminotransferase ( ast and alt ) , and lactate dehydrogenase was shown .
antinuclear antibody was positive at 1:80 of speckled pattern , and 1:2,560 of cytoplasmic pattern .
auto - antibodies including anti - jo-1 , anti - rnp , anti - double stranded dna , anti - sm , and anti - ss - a / ss - b were absent .
level of rheumatoid factor was 3,420 iu / ml , but level of c3 and c4 was 97.9 mg / dl ( normal range 79 - 152 mg / dl ) and 30.8 mg / dl ( normal range 16 - 38 mg / dl ) respectively .
chest radiograph showed pattern of interstitial lung disease and pulmonary function test revealed significantly decreased dlco .
she was diagnosed as ra and pm overlap , and had been treated with prednisolone , azathioprine and non - steroidal anti - inflammatory drug since may 2001 .
myositis became silent over time with above regimen , however she had continuous synovitis and joint pain on right knee and small joints on both hands .
blisters consisted of erythematous patches and superficial erosions with turbid bullae suggesting pemphigus vulgaris ( fig .
laboratory tests showed c - reactive protein 0.831 mg / dl ( normal range < 0.8 mg / dl ) , and erythrocyte sedimentation rate 66 mm / hr .
a skin biopsy revealed intraepidermal vesicle formation with acantholysis and the vesicle formation is suprabasal ( fig .
indirect immunofluorescence , performed by using serial dilutions of the patient 's serum , demonstrated no igg , iga and c3 staining along epidermis and papillary dermis .
bucillamine was discontin - ued and the patient was placed on oral prednisolone 20 mg daily .
d - penicillamine and bucillamine have been used for patients with rheumatoid arthritis as a disease modifying anti - rheumatic drug .
d - penicillamine can cause various autoimmune diseases including pemphigus , pm , and myasthenia gravis ( 4 - 6 ) .
although bucillamine has a chemical structure similar to d - penicillamine , autoimmune diseases are rarely associated with bucillamine .
some cases of bucillamine - induced interstitial lung disease , nephropathy , and myasthenia gravis were described ( 7 - 9 ) .
it was reported that the incidence of d - penicillamine - induced pemphigus was about 7% ( 5,10 ) and mean duration until the onset of pemphigus was 11 to 13 months ( 11,12 ) .
it has been suggested that the epidermal cell surface proteins play a role as an antigen to the host through a sulfhydryl radical and other unknown factors ( 1 ) . in d - penicillamine-
induced pemphigus , the prevalence of igg and iga antibodies directed against the intercellular region is lower than that in spontaneously occurring pemphigus ( 13 ) .
it has been shown that these antibodies might not be detected in some cases of drug - induced pemphigus like our case ( 13,14 ) .
to date , only 2 cases of bucillamine - induced pemphigus were reported in english literature .
one was drug - induced pemphigus foliaceus with features of pemphigus vulgaris and the other was subcorneal pustular dermatosis - type iga pemphigus induced by thiol drugs ( 12,14 ) .
the discontinuation of d - penicillamine may be inadequate in treatment because it frequently fails to stop disease progression.initial dose of corticosteroid is typically about 0.75 - 1 mg / kg / day .
it has been suggested that high - dose or pulse therapy with steroids usually clears blisters promptly .
prednisolone at a lower dose of 20 - 30 mg / day can maintain these patients without blistering but other adjuvant immunosuppressive drugs is need to achieve steroid - sparing effect or prevention of relapse ( 15,16 ) .
bucillamine may cause pemphigus even at a low rate therefore we have to keep in mind that skin lesions with blisters should be carefully investigated in patients with bucillamine treatment .
 bucillamine is a disease modifying anti - rheumatic drug , structurally similar to d - penicillamine . 
 although d - penicillamine - induced pemphigus has been not infrequently demonstrated , pemphigus associated with bucillamine was rarely reported . 
 we describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis ( ra ) and polymyositis ( pm ) overlap syndrome . 
 pm and ra overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months . 
 skin lesions including erythematous flaccid blisters on her chest , axillae , and back were occurred and were compatible with pemphigus vulgaris by typical pathology . 
 withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions . 
INTRODUCTION
CASE REPORT
DISCUSSION