the presentation of vasculitis is highly variable , with more severe cases resulting in hemorrhage , ischemia , or other complications depending on the degree of inflammation and to what extent the vascular architecture is compromised . for cutaneous vasculitis , up to 20% of cases are drug - induced with histology demonstrating leukocytoclastic vasculitis ( lcv ) .
the classic presentation of cutaneous vasculitis is palpable purpura , but ranges from erythematous lesions to deep ulcers or digital gangrene .
the identification of drug - induced lcv is critical since withdrawal of the offending agent can be life - saving .
we describe a case of levofloxacin - associated lcv and review the pertinent literature involving the association of fluoroquinolones with cutaneous vasculitis .
a 64-year old man presented for evaluation of a painful , erythematous , and violaceous rash on his left leg that had developed over the previous 24 h. the day before presentation , the patient had completed a 5-day - course of levofloxacin 500 mg twice daily for a presumed respiratory infection .
the patient had a history of severe varicose veins in his lower extremities which had led to chronic lower extremity edema after undergoing elective vein removal procedures .
other past medical history included benign prostatic hypertrophy , erectile dysfunction , and a distant history of left great toe osteomyelitis .
medications included felodipine 5 mg daily , hydrochlorothiazide 25 mg daily , terazosin 1 mg daily , vardenafil 5 mg as needed , and the recently prescribed levofloxacin .
patient 's vital signs on presentation were body temperature 96.8f , pulse 63/min , respiratory rate 18/min , blood pressure 155/95 mmhg , and pulse oximetry 98% on room air .
numerous purpuric papules coalescing into large plaques were present on the medial and anterior distal left leg with dark purple coloration centrally and non - blanching erythema around the periphery of the lesions .
there was an approximately 2 cm in diameter coalesced plaque of palpable purpura on the proximal left lateral leg with a few small bullae centrally as well as scattered purpuric papules on the left thigh . on the dorsum of the left foot there were numerous petechiae that were becoming confluent .
laboratory analysis revealed white blood cell count ( wbc ) 8.1610/l ( normal range 3.49.810/l ) with 71% neutrophils ( normal range 4173% ) , 20% lymphocytes ( 1846% ) , and 1% eosinophils ( 03.2% ) .
hemoglobin and hematocrit were 14.1 g / dl ( 1418 g / dl ) and 42.2% ( 4152% ) , respectively , while platelet count was 296x10/l ( 14236210/l ) .
since cutaneous vasculitis was suspected , based on clinical appearance of palpable purpura , diagnostic testing was carried out to determine the etiology .
complement levels were normal and other tests for potential causes of vasculitis were also negative , including ana , rheumatoid factor , anti - streptolysin - o , c - anca , p - anca , and testing for hepatitis b and c. serum protein electrophoresis demonstrated a normal electrophoresis pattern .
a punch biopsy was performed ( figure 1 ) and was consistent with leukocytoclastic vasculitis . upon review of the patient 's recent medications ,
after the patient confirmed that he was no longer taking levofloxacin , he was prescribed a 7-day course of prednisone 60 mg daily followed by a 14-day taper .
a 2-week course of clindamycin was also given for possible cellulitis due to bacterial super - infection of the area involving lcv .
fluoroquinolones were avoided due to suspicion of levofloxacininduced vasculitis and a concern for a potential cross - reaction among other agents in the same drug class . at follow up one month after his initial presentation , the patient had significant improvement in his lower extremity lesions .
in the area of his left lower extremity with the greatest skin involvement , a large but shallow ulceration remained and was treated with local wound care .
figure 1skin biopsy of left lower extremity with hematoxylin and eosin staining under a ) low and b ) high power demonstrating a predominant neutrophilic infiltration , presence of eosinophils , and the formation of subepidermal bullae consistent with leukocytoclastic vasculitis . 
 
skin biopsy of left lower extremity with hematoxylin and eosin staining under a ) low and b ) high power demonstrating a predominant neutrophilic infiltration , presence of eosinophils , and the formation of subepidermal bullae consistent with leukocytoclastic vasculitis .
after evaluation of the patient 's clinical history and physical examination findings , a drug - induced cutaneous vasculitis was suspected and later confirmed by biopsy . the interval between the first exposure to the drug and the initial onset of symptoms can range between hours and years , with onset occurring following an increased dose or re - challenge . in cases of drug - induced hypersensitivity vasculitis ,
re - challenge is not recommended due to the potential of recurrence with increased severity .
evaluation of a patient with suspected cutaneous vasculitis should include history , physical examination , and laboratory and histological evaluations .
the first step in classifying the lesion is based on caliber of the vessels involved ( small , medium , or large ) by performing a skin biopsy .
since neutrophils are replaced by lymphocytes and macrophages within 48 h after the appearance of a lesion , early biopsy is of highest diagnostic yield .
direct immunoflourescence confirms and further classifies the presence of vasculitis by identifying specific immunoglobulins . in drug - induced vasculitis , the offending drug can be hard to identify , and further laboratory tests can be helpful .
an anca testing is positive in some cases of drug induced vasculitis , including propylthiouracil , hydralazine , allopurinol , minocycline , penicillamine , and phenytoin which may induce systemic vasculitis syndromes with a life - threatening visceral involvement .
our patient was not prescribed any of the above agents and anca testing was negative . according to the naranjo adverse drug reaction probability scale with a score of 6 , levofloxacin was a probable cause of lcv in our case as the adverse event occurred after the suspected drug was administered , improved after discontinuation with addition of steroids , was proven by biopsy to be lcv , and no other alternative causes for the reaction were identified .
levofloxacin is a commonly prescribed antibiotic and is indicated for a number of infections , including community acquired and nosocomial pneumonia , uncomplicated or complicated urinary tract infections and pyelonephritis , acute bacterial sinusitis , acute or chronic bronchitis , as well as skin and skin structure infections .
adverse events commonly associated with fluoroquinolones as a class include : gastrointestinal and cns toxicity , ekg abnormalities including qt prolongation , dysglycemia , phototoxicity , tendon and joint disorders , hyper - sensitivity reactions , and hepatotoxicity .
while some structural components are clearly associated with adverse reactions , such as phototoxicity with the addition of chlorine or fluorine at the 8-position , and cns effects which are seen more commonly with the unsubstituted 7-piperazine derivatives , others do not appear to have any obvious structural associations including qt prolongation and tendon rupture .
in previous studies , ciprofloxacin , ofloxacin , levofloxacin , moxifloxacin and gatifloxacin have been associated with torsades de pointes .
however , the development of torsades de pointes is likely influenced by multiple risk factors in a patient already at risk .
all reported cases of fluoroquinolone - associated lcv in the literature involve ciprofloxacin , ofloxacin , and levofloxacin ( table 1 ) .
ciprofloxacin is distinguished by a cyclopropyl group at position 1 of the molecule and has other structural differences compared to ofloxacin and levofloxacin . while ciprofloxacin has an unsubstituted piperazine ring and levofloxacin and ofloxacin have a 4-methyl piperazine at position 7 , there is great variability at position 7 in other fluoroquinolones . despite some similarities in structure , the association of lcv with ciprofloxacin , ofloxacin and levofloxacin may also be attributed to their predominant use in clinical practice . 

table 1prior case reports of fluoroquinolone - associated vasculitis.fluoroquinolone ( fq)dosetime to symptom onsetother medicationsclinical diagnosis or biopsy provenfinal diagnosistreatmentyear publishedciprofloxacin500 mg po bid3 daysnoneskin biopsyperivascular mononuclear - cell infiltratewithdrawal of fq1989ciprofloxacin500 po mg / day4 dayscephradineskin biopsylcvwithdrawal of fq1992ciprofloxacinunknown10 daysdiureticclinical diagnosishaemorrhagic vasculitisnone1992ciprofloxacin500 mg po bid4 daysfluoxetineclinical diagnosiscutaneous vasculitiswithdrawal of fq ; fluoxetine continued1997ciprofloxacinunknown10 daysnoneclinical diagnosis ; subsequent renal biopsycutaneous vasculitiswithdrawal of fq ; prednisone2007ciprofloxacinunknown7 daysrifampinclinical diagnosisdrug - induced vasculitiswithdrawal of fq ; rifampin given without recurrence2009ciprofloxacinunknown8 daysflucloxacillinclinical diagnosisdrug hypersensitivitywithdrawal of fq ; flucloxacillin continued2009ofloxacin200 mg po bid1 daynoneskin biopsy and mast cell degranulation test for ofloxacinleukocytoclastic angiitiswithdrawal of fq ; prednisone1989ofloxacin200 mg po bid5 daysbumetanide , spirinolactone 2 weeks priorskin biopsyvasculitisunknown1989ofloxacin200 mg po bid3 daysaspirin , digoxinskin biopsyleukocytoclastic vasculitiswithdrawal of fq ; prednisolone1995ofloxacin200 mg po bid3 daysnoneskin biopsyleukocytoclastic angiitiswithdrawal of fq1996levofloxacin500 mg po daily3 daysnoneclinical diagnosisnephrotoxicity and purpurawithdrawal of fq ; prednisone2002levofloxacin500 mg po daily5 daysazithromycine , piperacilline- tazobactamclinical diagnosislcvwithdrawal of fq ; prednisone2006levofloxacinunknown3 daysrifampinskin biopsylcvwithdrawal of fq and rifampin changed to rifampicin2009levofloxacin500 mg po bid5 daysnoneskin biopsylcvwithdrawal of fq ; prednisonecurrent case 
  for all reported cases in the literature , the duration of fluoroquinolone therapy was 4 - 10 days .
many were clinically diagnosed without histological confirmation , but they reveal a theme of recovery following withdrawal of the agent as seen in our case .
cutaneous vasculitis may be limited to skin which offers a better prognosis , but can involve other organs with small - vessels including the kidney , as has been reported in one case report involving ciprofloxacin and another involving levofloxacin . in comparison to previous reports of levofloxacin - induced vasculitis ,
our case had several additional elements that may have contributed to the patient 's risk of developing lcv . following review of medical records ,
the patient had previously been prescribed 2 courses of ciprofloxacin , eight months and five years prior to his course of levofloxacin , with no reported adverse effects .
it is not known whether previous courses of ciprofloxacin could have been sensitizing events for later development of lcv upon challenge with levofloxacin .
levofloxacin was noted as an allergy in the patient 's medical record and the patient was counseled to avoid fluoroquinolones in the future .
consistent with previous case reports involving ciprofloxacin and ofloxacin , levofloxacin was a probable cause of lcv in our patient according to the naranjo adverse drug reaction probability scale . as in previous case reports , our patient had a full recovery with prednisone treatment and withdrawal of levofloxacin .
recognition of drug - induced vasculitis is critical as lcv can be life - threatening without discontinuation of the offending agent .
review of current literature shows that lcv has been associated with fluoroquinolones including ciprofloxacin , ofloxacin , and levofloxacin , but has yet to be reported in association with other agents in the fluoroquinolone class .
 many cases of cutaneous vasculitis are drug - induced with histology revealing leukocytoclastic vasculitis ( lcv ) . 
 we present a case of levofloxacin - associated lcv successfully treated with prednisone and cessation of the offending drug . 
 although case reports describe a link between lcv and older fluoroquinolones , such as ciprofloxacin and ofloxacin , recent reports have implicated the newer fluoroquinolone levofloxacin . 
 recognition of fluoroquinolone - induced cutaneous vasculitis is important as continuation or re - exposure of the offending agent may have life - threatening consequences . 
Introduction
Case Report
Discussion
Conclusion