aspergillus fumigatus , the most frequent agent of fungal infection primarily affects the lower respiratory tract , with a 3-month mortality rate of 30% . invasive aspergillosis with osteo - articular involvement is rare and its prognosis may be even worse , due to additional diagnostic challenges and pharmacokinetics concern , as illustrated by the following case report . kidney transplantation for type i diabetic nephropathy in january 2008 , which was complicated by an early venous thrombosis of the pancreas . his maintenance treatment consisted of tacrolimus ( 5 mg bid ) and mycophenolate mofetil ( mmf ) ( 500 mg bid ) . hip radiographs were normal on admission but revealed a crescentic radiolucent zone on the femoral head when repeated 2 weeks later ( figure 1 ) . technetium tc 99-labelled bone scintigraphy revealed an increased uptake at the coxo - femoral joint and ruled out aseptic bone necrosis ( figure 2 ) . ultrasound - guided synovial biopsy was performed , but no pathogen was found despite specific staining and culture medium for bacteria , mycobacteria and fungi . histology revealed chronic , non - specific , inflammatory changes with lymphocytic infiltrates and fibrosis . despite empirical anti - bacterial treatment with a combination of ceftriaxone and fosfomycin , the patient remained febrile and pain increased . computed tomography ( ct ) initial ( left ) and 2 weeks later ( right ) x - rays : the circle around the radiological image indicates the crescentic radiolucent zone on the femoral head that led to continue with further examination . bone scintigraphy : increased uptake at the coxo - femoral joint ( inflammatory process aspect ) that ruled out the hypothesis of an aseptic bone necrosis . magnetic resonance imaging revealed severe joint degradation ( figure 3 ) , and a femoral head resection was performed in december 2008 , temporarily replaced by a spacer with a high - viscosity bone cement containing gentamycin . a treatment with oral voriconazole , 200 mg bid , was started along with a 50% reduction of tacrolimus doses in view of drug interactions through cytochrome p450 . the source of aspergillosis could not be determined , and no other infectious foci were found . the patient improved remarkably , and hip replacement by a prosthetic joint was performed 6 months after voriconazole was initiated . seven samples of bone and synovial tissue found no residual evidence of fungal infection , and voriconazole was discontinued 2 weeks after surgery . meanwhile , the patient was re - admitted in march 2009 for pneumonia due to haemophilus influenzae and branhamella catarrhalis , and in june 2009 for agranulocytosis , which led to decreasing mmf dosage . for these reasons , during a few months , tacrolimus plasma concentrations were maintained at low levels ( i.e. < 5 mg three days after voriconazole discontinuation , and despite an increase of tacrolimus dosage from 3 to 8 mg bid as we anticipated drug interaction consequences , the patient developed an acute cellular graft rejection . renal function did not improve , so the patient re - started maintenance haemodialysis and was registered again on the kidney transplant waiting list . aspergillus fumigatus arthritis is an uncommon infection , mostly observed in the setting of disseminated invasive aspergillosis affecting severely immunocompromised patients . only 16 cases of a. fumigatus arthritis have been reported thus far ( not including vertebral osteomyelitis ) , with the knees and shoulders being the most frequently affected joints . to the best of our knowledge , the main conditions associated with osteoarticular aspergillosis are haematological malignancies , stem cell transplantation and renal transplantation ( three cases reported ) . cases have also been reported following intra - articular administration of corticosteroids [ 1 , 2 ] . the source of aspergillosis may be a direct inoculation , as in the cases following intra - articular corticosteroid injections . alternatively , the haematogenous route is the most likely route , when aspergillus species seed via the bloodstream during disseminated invasive aspergillosis . surprisingly , there were neither arguments for direct intra - inoculation nor haematogenous seeding in our observation where no source was found and no other infectious foci were identified despite extensive investigations . of note , among the 16 cases of a. fumigatus arthritis reported , only two had no evidence of disseminated disease , similar to our patient [ 24 ] . the diagnosis of osteo - articular aspergillosis is difficult because of its rarity , the non - specific clinical and radiological findings and the difficult access to the infected tissue . the delay to diagnosis in this observation was long , due to failure of two attempts to come up with a diagnosis through ultrasound- and ct scan - guided bone and synovial samples . the low yield of microbiologic sampling and the failure of a wide spectrum , empirical anti - bacterial treatment are clues that should prompt clinicians to include invasive mycosis in the differential diagnosis of septic arthritis in immunocompromised patients . in this population , although limited data are available on the optimal medical treatment of osteo - articular invasive aspergillosis , voriconazole , the only azole agent licensed for use in invasive aspergillosis , has the most satisfactory profile for osteo - articular aspergillosis , including efficacy , diffusion and bioavailability allowing oral use for prolonged treatment . however , failure of azole anti - fungal agents has been reported , which lead to using amphotericin b as a salvage therapy [ 2 , 68 ] . two other points must be considered : ( i ) if possible , immunosuppressive treatment should be reduced , at least temporarily , as the degree of immunosuppression strongly influences the outcome of invasive aspergillosis ; ( ii ) drug interactions must be kept in mind , taking into account the effect of voriconazole , which interferes with p450 cytochrome oxidase . aspergillus fumigatus arthritis in immunocompromised patients requires a combination of surgery and the prolonged use of voriconazole .
we report a case of a kidney and pancreas transplanted patient , hospitalized for septic hip arthritis . 
 the whole diagnostic work - up including synovial and bone biopsies remained negative . after inefficient empirical anti - bacterial antibiotic treatment , femoral head resection was performed and tissue analysis revealed aspergillus fumigatus hyphae . 
 treatment with voriconazole along with hip replacement led to complete recovery . however , drug interaction between immunosuppressive and anti - fungal drugs was complicated by cellular acute graft rejection . 
 aspergillus fumigatus arthritis is an uncommon and serious infection that should be evoked especially in the case of resistance to anti - microbial antibiotics and/or an atypical clinical picture .