the increasing number of patients with type 2 diabetes mellitus is a prominent health problem worldwide .
incretin - based therapy is one of the promising new treatments for type 2 diabetes mellitus , and has recently become a first - line drug .
although side effects do not often appear with this class of drug , several adverse events have been reported so far [ 1 , 2 ] . here
, the authors report a case of generalized drug - induced skin eruption with strong itching nearly 6  months after initiation of sitagliptin .
a 66-year - old male with untreated type 2 diabetes mellitus   was admitted to the authors hospital following the advice of the patient s daughter .
the patient s hemoglobin a1c ( hba1c ) level had been 7.4% in a general health check - up 3  years before .
one year prior to admission , the patient s fasting glucose had risen to 126  mg / dl and his hba1c level rose up to 8.6% .
a diet and exercise regimen was introduced , and sitagliptin phosphate 50  mg and metformin 500  mg were started .
two months later , the patient s hba1c level had improved to 7.0% and the patient continued on the medication , and diet and exercise therapy .
six months later , a rash with a locus on the upper limb began to appear .
the patient applied antihistamine ointment on the skin rash , which continued to spread gradually from chest to back , and abdomen to thigh ( figs . 
1a , 2a , 3a , b ) . in some areas of the back and chest
, lichenification also appeared . the itching associated with the rash also worsened , interfering with sleep during the night .
however , the rash was unchanged and pruritus gradually increased . since there is a possibility of skin malignancy in eczematous skin rashes lasting for a long period of time ,
four months after the eruption first appeared , and just before the skin biopsy , the authors stopped the dipeptidyl peptidase-4 ( dpp-4 ) , sitagliptin , to rule out the possibility of a drug reaction , although metformin was continued . itching caused by the rash
the emergence of new rash ended , and the rash itself withered after 1  week .
the spread of the rash gradually shrank and the skin lesions subsided , leaving pigmentation 1  month later ( figs .  1b , 2b ) .
although discontinuation of sitagliptin was significantly effective for the skin rash , a drug - induced lymphocyte stimulation test was negative for sitagliptin .
nonspecific radioimmunosorbent test for immunoglobulin e was increased to 532  iu / ml , and the percentage of eosinophil was 7.4% .
two months after cessation of sitagliptin , the skin eruption had subsided ( figs .  1c , 2c ) and
oral steroid medication was stopped , but some small eczematous eruptions continued to appear intermittently.fig . 
1chest just before discontinuation of sitagliptin ( a ) , after 1  month ( b ) , after 2  months ( c)fig . 
2back just before discontinuation of sitagliptin ( a ) , after 1  month ( b ) , after 2  months ( c)fig . 
3forearm ( a ) and thigh ( b ) just before discontinuation of sitagliptin chest just before discontinuation of sitagliptin ( a ) , after 1  month ( b ) , after 2  months ( c ) back just before discontinuation of sitagliptin ( a ) , after 1  month ( b ) , after 2  months ( c ) forearm ( a ) and thigh ( b ) just before discontinuation of sitagliptin
sitagliptin was the first dpp-4 inhibitor approved by the us food and drug administration ( fda ) in october 2006 , for the treatment of type 2 diabetes mellitus .
of the spontaneous adverse event reports of hypersensitivity reactions ( such as anaphylaxis , angioedema , and serious skin reactions ) , most have occurred within the first 3  months after initiation of the treatment , with many following the first dose . according to the uppsala monitoring centre ( a world health organization collaborating center ) causality assessment system , the category for the present case is  certain ,  although the appearance of the adverse event occurred about 6  months after sitagliptin initiation . in the literature ,
skin rash induced by sitagliptin has so far been reported in only two cases , one of persistent edematous - plaque photosensitivity   and another of bullous pemphigoid ; the former a cutaneous eruption induced by a photosensitive reaction to sitagliptin that appeared about 2  weeks after starting sitagliptin but continued for almost 2  years after cessation . in the present case ,
the eruption appeared almost 6  months after initiation of the drug and gradually subsided after the cessation , except for small itchy erythematous eruptions that continue to appear intermittently around the sun - exposed upper chest area .
because sitagliptin , like all known photosensitizers , has a phenyl ring , carbonyl group , and an absorption spectrum showing three absorption peaks ( 199.9 , 265.0 , and 400.1  nm ) , its photosensitive mechanism could well be responsible for the itchy edematous plaque . while both the 199.0 and 265.0  nm wavelengths are within the uv - c spectrum , the 400.1  nm absorbance peak indicates that sitagliptin also absorbs uv - a - visible light .
thus , sitagliptin could cause persistent photosensitive eruption after cessation of the drug even with protection from uv light by hapten formation with subcutaneous protein . in the present case ,
the distribution of skin rash differs from that of typical photosensitivity , of which there is no proof of involvement .
although a skin biopsy was not done in this case , varied sizes of bullae were not observed throughout the course of the rash , which contraindicates bullous pemphigoid .
although metformin was used throughout the affected period , the skin eruption occurred only during the use of sitagliptin .
the reports of drug - induced rash for metformin are very few despite its long history of use . in the literature , only psoriasiform   and leukocytoclastic vasculitis   have been reported to be induced by metformin .
more observation is required over a period of time to clarify use of this class of drug and also for the outcome of this case .
in the present case , the initial generalized skin eruption may have been induced by an allergic reaction to sitagliptin .
close attention should be paid to patients receiving this drug with a history of urticaria , and to the development of photosensitivity .
 a generalized skin eruption with strong itching was induced by sitagliptin , a dipeptidyl peptidase-4 ( dpp-4 ) inhibitor , in a patient almost 6  months after initiation of the drug . 
 physical examination revealed a spread of skin rash from chest to back , and abdomen and thigh . 
 discontinuation of the drug eliminated the skin rash immediately . 
 the emergence of new rash ended , and the rash itself withered after 1  week . 
 the spread of the rash gradually shrank and the skin lesions subsided , leaving pigmentation 1  month later . 
 two months after cessation of sitagliptin , the skin eruption had subsided and oral steroid medication was stopped , but some small eczematous eruptions continued to appear intermittently . although a drug - induced lymphocyte stimulation test was negative for sitagliptin , nonspecific radioimmunosorbent test for immunoglobulin e was increased to 532  iu / ml , with a percentage of eosinophil of 7.4% . 
 sitagliptin has a phenyl ring , carbonyl group , and an absorption spectrum showing three absorption peaks ( 199.9 , 265.0 , 400.1  nm ) , and its photosensitive mechanism could have been responsible for the itchy edematous plaque . in the present case , 
 the initial generalized skin eruption may have been induced by an allergic reaction to sitagliptin . 
 close attention should be paid to patients receiving this drug with a history of urticaria , and to the development of photosensitivity . 
Introduction
Case Report
Discussion
Conclusion