it is primarily used for the treatment of patients with progressive and potentially life - threatening fungal infections . its clinical use is often limited by adverse effects , especially dose - dependent nephrotoxicity , and infusion - related reactions . other adverse reactions include pulmonary reaction , nausea and vomiting , electrolyte imbalance , and allergic reactions . here , we report a case of a male patient who developed acrocyanosis and elevated serum creatinine after treatment with amphotericin b liposome . his medical history included senile degenerative valvular heart disease , premature ventricular contractions , heart function class ii ( new york heart association , nyha ) , and anemia . he did not have past history of acrocyanosis , pain , or allergies to other drugs , foods , and pollens . he consumed alcohol and smoking for about fifty years but had given up since 2 years . the patient was treated successfully for disseminated histoplasmosis 1 year ago with intravenous voriconazole , caspofungin acetate , itraconazole , and was prescribed oral itraconazole solution for 10 months on discharge . the patient presented with persistent pain in the right side of chest and back for 7 days to respiratory outpatient department . he had stopped taking oral itraconazole solution for 2 months . on admission , his vital signs were blood pressure 136/92 mmhg , heart rate 78 beats per min , respiratory rate 20 breaths per min , and tympanic temperature 36.5c . laboratory investigations showed total bilirubin of 7.3 mol / l ( normal range , 1.725 mol / l ) , alanine aminotransferase of 15 u / l ( normal range , 840 u / l ) , aspartate aminotransferase of 22 u / l ( normal range , 840 u / l ) , serum urea nitrogen of 7.6 mmol / l ( normal range , 1.77.1 mmol / l ) , serum creatinine of 98.3 mol / l ( normal range , 44133 mol / l ) , and c - reactive protein ( crp ) of 98.9 mg / l ( normal range , 03.3 mg creatinine clearance calculated using cockcroft - gault equation was 39.1 ml / min ( normal range , 80120 ml / min ) . a complete blood cell count revealed a platelet count of 225  10/l ( normal range , 100300  10/l ) , and a white blood cells count of 7.3  10/l ( normal range , 410  10/l ) , with neutrophils percentage of 67.1% ( normal range , 46.576.5% ) . computed tomography ( ct ) thorax suggested infection with peripheral soft tissue abscess in 35 thoracic vertebral body , involving the spinal canal and causing spinal cord compression and a pathological compression fracture of fourth vertebra thoracalis . lung ct and lung - enhanced ct scan revealed high - density shadow of spotted strip in a different shape with obscure boundaries in upper and lower lobes of both lung with pleural thickening and encapsulated effusion on the left side , and multiple bone ( right scapula , sternum midpiece , 35 thoracic vertebra ) destruction . patient received intravenous cefepime 2 g q12h for pulmonary infection after he was admitted to the respiratory ward . other medications administered included intravenous mannitol ( 125 ml q8h ) , oral alendronate sodium ( 70 mg once weekly ) , and loxoprofen ( 60 mg twice daily ) . however , patient did not improve and on day 9 , he had more pain in the right chest with raised crp ( 156.9 one year ago , patient suffered from disseminated histoplasmosis diagnosed with biopsy from the right lung and right scapula . since patient was not improving with cefepime , on day 12 , cefepime was switched to amphotericin b liposome for suspected histoplasmosis ( 10 mg on 1 day , 15 mg on day 2 , 30 mg on day 3 , 60 mg on day 4 , 120 mg on day 5 , and 150 mg on day 6 ) . patient showed an improvement with relief in pain and decrease in crp ( 32.1 mg / l on day 15 ) . however , on day 19 , patient developed pain and cyanosis on the right lower limb and both upper limbs as shown in figures 1 and 2 . on day 20 , crp increased to 158.7 mg / l , and on day 23 , patient had pain and acrocyanosis with the rise of serum creatinine 147.7 mol / l . at this , amphotericin b liposome was discontinued , and anisodamine was administered intravenously ( 20 mg q6 h ) for acrocyanosis and pain . after treatment with anisodamine for 9 days , patient showed clinical improvement , crp decreased to 41.6 mg / l , and serum creatinine was 116.3 mol / l . on day 29 , patient was discharged with a complete cure of acrocyanosis and pain and was prescribed oral voriconazole . cyanosis at patient 's hand cyanosis at patient 's foot causality assessment of the adverse drug reaction ( adr ) was carried out using the world health organization - uppsala monitoring centre ( who - umc ) criteria and naranjo 's scale . in the present case , thus , adr was probably caused by amphotericin b liposome ( who - umc criteria : probable ; naranjo 's score : 5 , probable ) since there were no other factors that could have caused this adr . amphotericin b liposome was discontinued , and anisodamine was used to treat acrocyanosis and pain induced by amphotericin b liposome , so the reaction was a severe adr with a severity level 3 according to modified hartwig and siegel scale . in the present case , acrocyanosis and pain appeared after treatment with amphotericin b liposome and improved when amphotericin b liposome was discontinued . naranjo adr probability scale score was 5 , the who - umc criteria : probable , indicating a probable relationship between acrocyanosis and amphotericin b liposome use . acrocyanosis and pain can result from spasm of peripheral vessels and intravenous anisodamine which relieves spasm of smooth muscle was effective to relieve pain and acrocyanosis in the present case . spasm of peripheral vessels mediated by thromboxane a2 could be responsible for the cyanotic phenomenon and nephrotoxicity by the amphotericin b. raynaud 's phenomenon is characterized by three - phase reaction , i.e. , white , purple , and red precipitated by cold and emotional stress . however , in the present case , only redness and pain were observed , which was different from raynaud 's phenomenon . our patient had impaired renal function ( decreased ccr 39.2 ml / min ) with increased age . patient did not receive concomitant -receptor blockers , which have been reported to potentiate the likelihood of raynaud 's symptoms but received mannitol which affects renal function . amphotericin b - related cyanotic raynaud 's phenomenon has been reported by zernikow et al . and ozaras et al . in the report by zernikow et al . , two young girls and one boy , without impaired renal function , developed adverse reaction due to intravenous , or inhalation of conventional amphotericin b , whereas a liposomal preparation was well tolerated . in report by ozaras et al . , a 50-year - old male developed cyanosis on fingers of hands and feet with amphotericin b deoxycholate and was given amphotericin b lipid complex thereafter without any complication . in the present case , advancing age and impaired renal function could be a possible predisposing factor for amphotericin b liposome - induced elevated serum creatinine because amphotericin b nephrotoxicity is associated with accumulation of the drug in the kidney . amphotericin b is eliminated by kidney , so potential of accumulation is high in patients with renal impairment and increased age . it was not clear whether amphotericin b liposome - induced acrocyanosis and pain were related with impaired renal function and increased age in the present case . smoking is associated with raynaud 's phenomenon and buerger 's disease and impaired peripheral vasculature endothelium - dependent vasorelaxation , which may be considered a risk factor . this report suggests us to pay close attention to the potential risk of amphotericin b - induced acrocyanosis and elevated serum creatinine , especially in elderly patients with impaired renal function and smoking .
a 77-year - old male patient developed acrocyanosis and pain after treatment with amphotericin b liposome 150 mg daily intravenously for disseminated histoplasmosis , and subsequently developed elevated serum creatinine . 
 amphotericin b liposome was discontinued , and anisodamine was used intravenously to treat acrocyanosis and pain induced by amphotericin b liposome for 9 days and patient was cured . 
 naranjo adverse drug reaction probability scale score was 5 , the world health organization - uppsala monitoring centre criteria : probable , indicating a probable adverse reaction to amphotericin b liposome .