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hypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease , especially in elderly patients .
granulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis . here , we report a 72-year - old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck .
topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes , being the underlying cause for hypercalcemia in this case .
in rare cases , symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction .
this is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation .
hypercalcemia is a quite common problem in clinical practice and includes endocrine disorders and malignant diseases , especially in older patients .
there have been reports that , dermal injections for cosmetic treatment and intravenous silicone derived from dialysis tubes have been reported to cause hypercalcemia due to local or systemic granulomatous inflammatory processes
. however , this pathomechanism seems to be rare and therefore is usually not considered by physicians treating hypercalcemia .
diagnosis is further complicated due to the fact that most patients are hesitant to report that they have had rejuvenation therapy .
a 72-year - old woman was referred to our hospital with progressive fatigue , loss of appetite and weight loss of 16 kg within the last 2 months .
medical history was remarkable for long - standing type 2 diabetes and osteoporosis with old spinal fractures .
her medication included amlodipine , acetylsalicylic acid , atorvastatin , metformin , insulin glargine and insulin aspart as required .
two months before presentation at our hospital a dpp-4-inhibitor , sitagliptin , was added to the therapy in order to improve glycemic control . however , this treatment was discontinued before presentation due to an evolving edema and erythema of the face and neck . at physical examination ,
edema and erythema of the face including the lips and neck with a quincke - like appearance were still present .
the laboratory results on admission revealed hypercalcemia ( 3.03 mmol / l , normal 2.12.65 mmol / l ) and normal levels for parathyroid hormone , phosphate , albumin , creatinine , 25-oh - vitamin d and 1,25-oh vitamin d. however , angiotensin converting enzyme ( 95 u / l , normal
< 65.7 u / l ) and urine calcium ( 10.9 mmol/24 h , normal 2.57.0 mmol/24 h ) were elevated ( table 1 ) .
the patient had started cosmetic treatment for age - related wrinkles of face and neck several months ago , which she did not initially mention to clinicians . in order to exclude a malignant process , scintigraphy of the bone , whole body computed tomography and a comprehensive endoscopic evaluation were performed .
strikingly , there were empty vacuoles within the cytoplasm of many giant cells , resembling silicone granuloma ( figure 1 ) .
when the patient was asked about silicone  exposure  , she finally confessed to having had cosmetic treatment months ago . in this procedure ,
a topical silicone - lipid formulation was applied to her face and neck with a transdermal ultrasound device ( as far as we could determine , ultrasound frequency was 1 mhz , intensity 0.51 w / cm ) .
this was done to reduce wrinkles of face and neck as a  gentle rejuvenation  of the 72-year - old woman .
based on these results , the patient was diagnosed with symptomatic hypercalcemia resulting from a granulomatous inflammation .
treatment with 30 mg oral prednisolone once daily was initiated and this treatment improved the facial edema .
the erythema and palpable infiltration of the skin still remained within the skin wrinkles . in a final follow - up after 8 weeks of treatment , after oral prednisolone was tapered , calcium levels ( 2.45 mmol / l , normal : 2.12.65 mmol / l ) and calciuria ( 6.8 mmol/24 h ; normal : 2.57.0 mmol/24 h ) were completely normalized and the patient was in good health
here we report a patient with symptomatic hypercalcemia related to a cosmetic treatment with liquid silicone applied topically with a focal ultrasound device .
differential diagnosis of non - pth - related hypercalcemia in older patients includes , in particular , malignant conditions .
when malignancy has been excluded , hypercalcemia due to granulomatous diseases needs to be considered . among them , sarcoidosis and tuberculosis are the most common ones , with inappropriate endogenous overproduction of 1,25-oh vitamin d by activated granulomatous tissue responsible for hypercalcemia .
. silicone may disseminate in lymph vessels and organs after ruptured breast implants or injections .
for many years silicone formulations have been used in aesthetic care settings as so - called injectable 
the pathomechanism of silicone - induced hypercalcemia is not entirely understood and seems to be somehow different from the mechanism of other granulomatous disease such as sarcoidosis .
some reports have suggested a vitamin d dependency , while others have not found this dependency , as in our case . in these cases
hypercalcemia might be related to some altered unspecified prostaglandin metabolism , but this remains speculative .
however , since removal of disseminated silicone seems to be impossible , cortisone treatment is a suitable therapy , as reported in all cases [ 24,6,7 ] .
the diagnosis of a granulomatous reaction to filler material in an aesthetic care setting may cause serious medical complications mimicking systemic diseases , and is challenging , especially since patients often deny having had rejuvenation therapy .
it is further complicated by the bewildering variety of new and unproven commercial treatments , but it seems that transdermal ultrasound combined with topical silicone - lipid gel can be harmful by inducing severe tissue inflammation and subsequent hypercalcemia .
whether such complications are frequent is not known due to the fact that controlled studies are lacking .
summarybackgroundhypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease , especially in elderly patients . 
 although rare , other causes can also be responsible.case reportgranulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis . here , we report a 72-year - old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck . 
 topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes , being the underlying cause for hypercalcemia in this case.conclusionsin rare cases , symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction . 
 this is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation .