mucormycosis is an aggressive invasive opportunistic fungal infection belonging to the order mucorales , usually found in immunocompromised individuals .
it is a life and limb threatening fungal infection with high mortality rate of 40%.1 though mucormycosis presents as a spectrum of disease , it is very rare in the musculoskeletal system .
almost all the immunocompromised patients with osteomyelitis of long bones due to mucormycosis require aggressive debridement and may sometimes need amputation.2 we present a patient with acute myeloid leukemia , who was diagnosed to have mucormycosis osteomyelitis of right proximal femur and was treated with limb salvage surgery successfully .
a 41-year - old gentleman presented with sudden onset of pain and swelling over his right groin and upper thigh for a period of 10 days .
he was a known patient with type ii diabetes mellitus and acute myeloid leukemia m2 diagnosed on the basis of bone marrow morphology and immunophenotyping 2 years ago .
he received induction chemotherapy with cytosine and daunorubicin , followed by consolidation chemotherapy and peripheral autologous bone marrow transplant .
fourteen months post bone marrow transplantation , he had remission and developed the above complaints .
examination revealed mild tenderness over the right proximal femur with no significant restriction of movements .
magnetic resonance imaging ( mri ) of the right hip revealed altered signal intensity in the right proximal femur with no cortical breach or evidence of abscess .
his complaints gradually increased in the next 3 weeks and he had difficulty in weight bearing and walking . on clinical examination , he had severe tenderness over the right proximal femur with painful restriction of movements at the hip joint .
plain radiographs revealed a 6  3 cm , ill - defined osteolytic lesion in the proximal shaft of right femur extending into the greater trochanter with wide zone of transition and adjacent soft tissue swelling [ figure 1a ] .
mri showed altered signal intensity in proximal metadiaphysis of right femur , including greater trochanter , with focal collection of 5  2.6 cm with cortical breach .
there were two small abscesses measuring 1.5 and 0.7 cm , respectively , in the soft tissues [ figure 1b ] . ( a ) plain radiograph revealing an osteolytic lesion involving the right proximal femur ( b ) mri showing altered signal intensity in the proximal metadiaphysis of right femur with abscesses and cortical breach ( c ) bone scan demonstrating increased tracer uptake in the metadiaphyseal region of right proximal femur bone scintigraphy with technetium 99 m methylene diphosphonate ( tc 99 m mdp ) demonstrated intense increase in tracer uptake in the proximal third of right femur with normal tracer distribution in rest of the skeleton , suggestive of an infective pathology [ figure 1c ] .
intraoperatively , black discoloration of the right proximal femoral metaphysis with foul smelling discharge was noticed .
the tissue was smeared with 10% koh solution and calcofluor white solution initially and then cultured in sabraoud 's dextrose agar ( sda ) and lactophenol cotton blue ( lpcb ) mount which revealed broad aseptate fungal hyphae suggestive of mucormycosis .
histopathology of the cancellous bone and soft tissue exhibited large areas of necrosis and hemorrhage , replaced by inflammatory granulation tissue with dense infiltrates of lymphocytes , plasma cells , histiocytes , neutrophils , and few multinucleate giant cells .
there were many broad , twisted , and few branching fungal filaments suggestive of mucormycosis [ figure 2 ] .
histopathology with broad , twisted , and few branching fungal elements after the diagnosis of mucormycosis was confirmed , patient was evaluated for primary infection .
there was no history of gastrointestinal infections and previous biopsy from gastric mucosa was negative .
hence , primary source of infection could not be traced . in the immediate postoperative period ,
the patient developed pathological fracture at the same site and was put on skeletal traction for 19 days before definitive fixation .
he was treated with liposomal amphotericin 3 mg / kg / day for 19 days , following which radical debridement of the lesion proceeded by skeletal stabilization with 95 condylar blade plate for the right proximal femur .
considering the location of the pathological fracture ( proximal femur ) and the need for aggressive debridement and stable fixation , a 95 condylar blade plate fixation was achieved after adequate debridement . to prevent the usual complications of external fixation instead of infection such as pin tract infection , difficulty in mobilization and also considering adequate preoperative antifungal therapy and aggressive debridement , internal fixation was decided .
300 mg of fungitericin ( amphotericin b ) in powdered form was mixed with 40 g of simplex cement polymer and the mixture was then added with monomer , and while setting , cement beads were made into chains using stainless steel wire ( two strings with 15 beads each ) [ figure 3a ] .
( a ) postoperative plain radiograph with proximal femur stabilized with condylar blade plate and augmented with antifungal cement beads ( b ) three years followup plain radiograph with no evidence of osseous lesion with abundant callus intraoperatively , he had torrential blood loss amounting to 2.53 litres and went into hypovolemic shock .
he was resuscitated with five units of packed red cells , eight units of cryoprecipitate , and eight units of fresh frozen plasma .
radical debridement , inability to use the tourniquet , and difficulty in differentiating infected and uninfected marrow were the causes for unexpected blood loss .
after aggressive debridement , bone to bone cortical contact was achieved for healing which led to loss of metaphyseal bone loss of 3 cm .
postoperatively , liposomal amphotericin 3 mg / kg / day ( 180 mg / day ) was given for 3 weeks and downgraded to 1 mg / kg / day ( 60 mg / day ) for the next 9 weeks .
patient had received a total dosage of 7560 mg of liposomal amphotericin for a total period of 12 weeks .
he was advised postoperatively physiotherapy and toe - touch weight bearing crutch walking for 12 weeks .
bone grafting was done along with beads removal and the tissue sent during surgery for histopathology and microbiological review was negative for mucormycosis . at 3-year followup
, there was 3 cm limb shortening noticed for which a shoe raise was given .
plain radiographs revealed healed fracture with no residual / recurrent lesion in the metadiaphysis region of right proximal femur [ figure 3b ] .
the common predisposing factors are uncontrolled diabetes , hematological malignancies like leukemia , lymphoma , etc . , organ transplantation , severe burns , diseases like tuberculosis and aids , post bone marrow transplantation , neutropenia , renal failure , immunosuppressive medications , etc .
mucormycosis has been described in various sites like cranium , hands , and feet , humerus , tibiae , femur , vertebrae , and joints.1 the etiopathogenesis of mucormycosis follows after entry into the host via ingestion , inoculation , or inhalation . in the immunocompromised host ,
the spores undergo angioinvasion leading to local necrosis and necrotizing infection , ultimately leading to systemic inflammatory response syndrome , multiorgan dysfunction , and death .
surgery includes radical debridement , mostly amputation , followed by high doses of amphotericin b. role of antifungal cement beads is limited mainly due to its cement elution properties and high local concentration leading to toxicity .
multiple in vitro studies have reported amphotericin b impregnated pmma beads to have a successful role in the management of fungal infections.37 goss et al . in their study on elution and mechanical properties of amphotericin concluded that amphotericin was released from cement at a clinically insignificant level.8 
 in vitro studies on amphotericin beads have shown to provide adequate release of its concentration ( 1.75 - 2.0 microgm / ml ) up to 110 days from all bone cements.3 excessive local concentration of amphotericin b above 100 microgm / ml is lethal and concentration between 5 - 10microgm / ml causes abnormal morphology and reduced proliferation.4 of the seven cases of mucormycosis of tibia described in the literature , five were immunocompromised and 60% of those patients underwent amputation.9 the causes of amputation may be related to delayed diagnosis of mucormycosis , compromised immune status , inadequate debridement , or inadequate antifungal therapy .
we present this case in view of the unusual site of presentation , limb - threatening osteomyelitis which was treated with radical debridement , liposomal amphotericin therapy , and using antifungal beads to enable limb salvage .
high index of clinical suspicion , early diagnosis , aggressive debridement , and adequate liposomal amphotericin b are the key treatment modalities in the successful management of musculoskeletal mucormycosis .
 mucormycosis is one among the aggressive , invasive fungal infections usually seen in immunocompromised patients . 
 mucormycosis osteomyelitis is very rare . 
 we present a patient with acute myeloid leukemia who complained of pain over the right proximal thigh . 
 plain radiograph revealed ill defined osteolytic lesion of proximal femur . 
 mri showed altered signal in proximal femur with focal collection and cortical breach . 
 biopsy and tissue culture diagnosed mucormycosis both histologically and microbiologically . 
 he was treated with aggressive debridement , skeletal stabilization , and amphotericin antifungal cement beads . 
 he recovered with no residual pain , minimal limb shortening , and no clinical or radiological evidence of recurrence at 3 years followup . 
 the high index of suspicion , early diagnosis , aggressive surgical debridement , and adequate antifungal therapy play a significant role in the treatment of musculoskeletal mucormycosis . 