Management of a Pilon Fracture Complicated by Drug-induced Hypersensitivity Syndrome, Fungal Infection and Limb Length Discrepancy: A Case Report

Abstract

Aim and background

Pilon fractures are rare but severe injuries associated with high-energy trauma, often resulting in significant articular and soft tissue damage. Their management is challenging due to complications such as infection, nonunion, and post-traumatic arthritis, which often require complex staged surgical interventions. Drug-induced hypersensitivity syndrome (DIHS), a life-threatening reaction characterised by rash and systemic involvement, presents additional challenges in orthopaedic contexts due to its association with high-dose corticosteroid therapy and increased infection risk.

Case description

We report the case of a 70-year-old man with a Gustilo–Anderson type IIIA open pilon fracture complicated by fungal infection, leg length discrepancy (LLD), and DIHS. Initial treatment involved debridement, and stabilisation with a modular external fixator. Due to fungal infection and LLD, the external fixator was replaced with a Taylor Spatial Frame (TSF) for limb lengthening at the proximal tibia. The patient subsequently developed a skin rash, fever and liver damage, and was diagnosed with DIHS. High-dose prednisolone (PSL) was started and gradually tapered over 2 months. During this period, limb lengthening progressed effectively, achieving a total elongation of 42 mm. During definitive reconstruction, plate conversion was performed to stabilise the lengthened bone. A tantalum spacer was used to correct the remaining LLD, and tibio-talo-calcaneal arthrodesis with retrograde intramedullary nailing was employed for distal reconstruction. Postoperatively, the patient achieved solid bone fusion, minimal LLD (5 mm), and independent ambulation at 1 year. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle–hindfoot score was 90 points.

Conclusion

This case highlights the complexities of managing pilon fractures complicated by infection, LLD, and DIHS. It underscores the importance of staged treatment strategies, including limb lengthening, and planning for definitive reconstruction.

Introduction

Pilon fractures are high-energy injuries typically resulting from mechanisms such as motor vehicle collisions or falls from significant heights. These fractures involve the distal tibial plafond and are frequently associated with substantial damage to both the articular surface and surrounding soft tissues. Although relatively rare, pilon fractures account for 1–10% of all tibial fractures.¹ Management of pilon fractures is challenging due to their high risk of complications, which can significantly impact functional outcomes and, in severe cases, threaten limb salvage. Reported complications include delayed wound healing, deep infections, nonunion, and post-traumatic osteoarthritis.^2–5 In some cases, these complications necessitate additional surgeries, and in the most severe scenarios, may result in limb amputation.⁶ The prolonged hospitalisation often required for these injuries can predispose patients, especially older adults, to systemic complications, thereby complicating recovery.

Among the potential postoperative challenges, drug-induced hypersensitivity syndrome (DIHS) presents a particularly rare and difficult obstacle. Drug-induced hypersensitivity syndrome is classified as a severe cutaneous adverse reaction (SCAR) and is distinguished by diffuse cutaneous eruptions accompanied by systemic involvement, including hepatic, renal, and haematologic abnormalities.^7,8 Unlike typical drug allergies, discontinuing the causative agent is rarely sufficient to achieve resolution, and management frequently necessitates high-dose, extended systemic corticosteroid therapy.⁷ However, corticosteroids are known to impair immune response and wound healing and are associated with increased risk of infection in surgical patients, making the management of DIHS in the context of surgical intervention particularly complex.^9,10

This case report aims to illustrate the decision-making process and staged reconstructive strategy used to achieve limb salvage in a complex open pilon fracture complicated by fungal infection, limb length discrepancy, and DIHS requiring systemic corticosteroid therapy.

Case Description

Patient Background and Initial Presentation

A 70-year-old man fell from a height of approximately 10 m while working as a window cleaner and was transported to our hospital via emergency services. On arrival, he was haemodynamically stable and had a 5 cm contaminated open wound on the medial aspect of the distal right lower leg (Fig. 1A). Sensory and motor functions of the toes were preserved. Computed tomography (CT) imaging revealed a comminuted intra-articular fracture of the distal tibia (pilon fracture) and a segmental fracture of the fibular shaft (Figs 1B to D). Additional findings included pelvic ring fractures, rib fractures, and lumbar compression fractures; however, no head trauma or visceral injuries were detected.

Figs 1A to D.

(A) Clinical photograph at the time of injury, showing an open wound on the medial malleolus of the right ankle; (B and C) 3D view of the right lower leg CT at the time of injury: (B) Anterior view and (C) lateral view, demonstrating a pilon fracture of the tibia and a segmental fracture of the fibula; (D) Axial slice of the right ankle CT at the time of injury, revealing comminution of the plafond and articular surface defects

First Surgery: External Fixation and Initial Management

A diagnosis of Gustilo–Anderson type IIIA open pilon fracture was made, and emergency surgery was performed. After thorough irrigation and debridement, the tibial nerve and posterior tibial artery and vein were found to be intact, but the flexor digitorum longus (FDL) was partially ruptured. The fracture was reduced and stabilised using a modular external fixator (GALAXY external fixator, Orthofix, Verona, Italy). Due to bone loss, a cement spacer was inserted into the defect (Fig. 2). The wound was successfully closed.

Figs 2A to C.

(A and B) Postoperative radiographs after the initial surgery: (A) Anteroposterior view; and (B) Lateral view. Two half-pins were inserted into the tibia and calcaneus, respectively, and connected with an external fixator. A cement spacer was placed in the defect of distal tibia; (C) Full-length radiograph of the lower limb taken 1 week after the initial surgery (supine position), showing a LLD of 22 mm

Postoperative Complications and Second Surgery

One week postoperatively, the wound exhibited persistent erythema and exudate. Laboratory findings showed white blood cell (WBC): 8,620/µL and C-reactive protein (CRP): 8.94 mg/dL. Wound cultures identified Candida parapsilosis, leading to a diagnosis of fungal infection, and fluconazole 400 mg/day was initiated. In addition, despite the cement spacer placement, a leg length discrepancy (LLD) of 22 mm was present, and removal of the distal bone fragment was projected to result in a 77 mm LLD (Fig. 2C). To address these issues, a second surgical procedure was performed. During surgery, the wound was reopened for irrigation and debridement. No abscess formation was observed, but the infected soft tissue contained necrotic debris, and both the posterior tibialis tendon and FDL tendon were weakened with longitudinal tears due to infection, requiring partial resection. A new antibiotic-loaded cement spacer containing vancomycin (1.0 gm), amikacin (400 mg), and liposomal amphotericin B (250 mg) per 40 gm of polymethyl methacrylate was placed (Fig. 3A). Additionally, to provide enhanced ankle stabilisation and enable limb lengthening, a Taylor Spatial Frame (TSF; Smith & Nephew, Watford, UK) was applied (Figs 3B to D). Osteotomy was performed just below the tibial tuberosity, and bone lengthening was started at a rate of 0.5 mm/day from 1 week after surgery. The infection was successfully controlled, and the wound completely healed within 2 weeks.

Figs 3A to D.

(A) Clinical photograph at the second surgery. The wound was reopened for irrigation and debridement, followed by the placement of an antibiotic-loaded cement spacer (indicated by the arrow); (B) Clinical photograph at the second surgery, showing the application of the TSF; (C and D) Postoperative radiographs after the second surgery: (C) Anteroposterior view; and (D) Lateral view. Taylor Spatial Frame is applied from the proximal tibia to the foot ring. An osteotomy for bone lengthening was performed at the proximal tibia

Drug-induced Hypersensitivity Syndrome and Management

Following the infection resolution, the patient developed an eczema with erythema and pruritus on the trunk and all four limbs, accompanied by fever. Laboratory findings included WBC: 10,510/µL, CRP: 12.18 mg/dL, alkaline phosphatase (ALP): 1,138 IU/L, gamma-glutamyl transpeptidase (γ-GTP): 232 IU/L, aspartate aminotransferase (AST): 74 IU/L, and alanine aminotransferase (ALT): 139 IU/L. Imaging ruled out cholangitis and gastrointestinal infection, raising suspicion of a drug-induced reaction. However, discontinuation of all suspected medications did not lead to symptom resolution. Further evaluation confirmed a diagnosis of DIHS. The serum thymus and activation-regulated chemokine (TARC) level, a marker associated with DIHS, showed over 30,000 pg/mL. The suspected drugs were celecoxib, fluconazole, and vancomycin (just contained in the cement spacer), but the drug-induced lymphocyte stimulation test was negative for all of them, and it was not possible to determine the causative drug. The patient was started on prednisolone (PSL) at 50 mg/day, with the dose gradually tapered every 2 weeks according to protocol. The symptoms improved quickly after the administration, but the final reconstructive surgery was postponed due to concerns about infection-related complications caused by high-dose steroids. However, gradual lengthening of the proximal tibia continued during the waiting period, achieving a total lengthening of 42 mm (distraction index: 26.4, external fixation index: 29.5). It took 2 months to reduce the dose to 10 mg/day, and we decided to perform the final reconstructive surgery.

Final Surgery: Plate Conversion and Ankle Arthrodesis

The final surgery was performed 4 months after injury, when the PSL dose had been tapered to 10 mg/day. At first, definitive reconstruction using external fixation was planned. However, because the patient experienced substantial psychological distress and strongly wished to have the external fixator removed, conversion to internal fixation was planned to simultaneously stabilise the proximal lengthening site and reconstruct the distal bone defect.

First, plate conversion was performed at the proximal tibial lengthening site using a minimally invasive plate osteosynthesis technique (AxSOS Titanium proximal lateral tibia locking plate system, Stryker, Kalamazoo, MI, USA) (Fig. 4A). For distal reconstruction, the tibiotalar and subtalar joints were exposed through a lateral approach. The residual distal tibial fragments were excised, and the articular surfaces of the talus and subtalar joint were curetted and drilled. The excised bone fragments were used as autologous bone grafts at the fusion site. A 25 mm tantalum spacer (trabecular metal ankle interpositional spacer, Zimmer–Biomet, Warsaw, IN, USA) was inserted to compensate for the residual limb length discrepancy (Fig. 4B). Tibio-talo-calcaneal arthrodesis was performed using a retrograde hindfoot nail (T2 ankle arthrodesis nail, Stryker, Kalamazoo, MI, USA). The nail length was selected to overlap with the proximal tibial plate to reduce stress concentration. Finally, the distal fibula was fixed with cortical screws so as to bridge the tibiotalar arthrodesis site (Figs 4C to E).

Figs 4A to E.

(A) Clinical photograph at the final surgery, showing plate conversion performed using the MIPO technique via the proximal lateral tibia; (B) Clinical photograph at the final surgery, focusing on the distal lateral tibia. A TM spacer (indicated by the arrow) was inserted to correct the LLD, and the inverted fibula (indicated by the triangle) is shown; (C–E) Postoperative radiographs after the final surgery: (C) Anteroposterior view; (D) Lateral view of the proximal tibia; and (E) Lateral view of the ankle. The proximal plate and the hindfoot intramedullary nail were aligned to overlap as planned

Postoperative Course

The patient was kept non-weight-bearing but was allowed wheelchair mobilisation from postoperative day 2. Partial weight-bearing with a patellar tendon-bearing brace was permitted from postoperative day 31. He was discharged home on postoperative day 61 (approximately 7 months after injury). Four months after surgery, he was allowed to walk with full weight-bearing without a brace. At 1 year postoperatively, he was able to walk independently. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle–hindfoot score was 90 points (pain: 40 points, function: 40 points, and alignment: 10 points).¹¹ Radiographs confirmed solid bone union, with a mechanical axis deviation (MA%) of 27% and an LLD of only 5 mm (right < left) (Fig. 5). At this point, the patient was still taking 5 mg of PSL.

Figs 5A to D.

(A) Full-length radiograph of the lower limb 1 year postoperatively. The mechanical axis deviation (MA%) was 27% on the right, and the LLD was 5 mm shorter on the right side. Bone union in the lengthened segment was achieved successfully; (B and C) Radiographs of the ankle 1 year postoperatively: (B) Anteroposterior view; and (C) Lateral view. Bone union at the arthrodesis site was achieved successfully; (D) Clinical photograph 1 year postoperatively. Although mild oedema remained in the right lower leg, the surgical site had healed. The patient was able to maintain standing balance and walk independently

Discussion

Drug-induced hypersensitivity syndrome is a severe delayed drug reaction that typically develops between 2 weeks and 2 months after exposure to the causative medication.⁷ According to the Japanese SCAR diagnostic criteria proposed in 2006, DIHS is diagnosed as typical DIHS when all seven criteria are met and as atypical DIHS when five of the seven criteria are satisfied.¹² In the present case, the patient fulfilled six criteria, including delayed maculopapular eruption, persistent symptoms after drug discontinuation, fever, liver dysfunction, leucocyte abnormalities, and lymphadenopathy, supporting a diagnosis of atypical DIHS. The mortality rate associated with DIHS can reach 10%, depending on factors such as patient age, underlying diseases, and the specific drug involved. Early recognition of DIHS can be difficult, as the initial presentation may mimic infections, autoimmune conditions, or lymphoproliferative disorders. Furthermore, its delayed onset can lead to confusion with other severe drug eruptions, such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).⁷ TARC has been suggested as a useful biomarker for identifying acute DIHS and may help differentiate it from other conditions, given its elevated levels in DIHS compared to SJS/TEN.¹³

A number of drugs have been identified as common triggers of DIHS, but the causative drug could not be definitively identified in our case. Several drugs used during treatment were considered potential triggers, including vancomycin, celecoxib, and fluconazole.^7,11,14 Vancomycin is a well-recognised cause of DIHS, although DIHS associated with vancomycin contained in bone cement has not, to our knowledge, been previously reported.^7,11,14 Celecoxib has also been described as a possible cause of DIHS in several reports.¹⁵ Although a direct association between fluconazole and DIHS is less established, antifungal agents can cause systemic adverse reactions, including liver injury. Importantly, all suspected drugs in this case are commonly encountered in orthopaedic practice. Therefore, orthopaedic surgeons should consider DIHS when delayed skin eruptions, fever, or liver enzyme abnormalities occur during the treatment of trauma or infection.

The management of DIHS complicated the reconstructive strategy in this case. Immediate discontinuation of suspected drugs and systemic corticosteroid therapy are central components of treatment.⁷ Corticosteroids often require gradual tapering over several weeks or months because relapse can occur with rapid dose reduction. However, systemic steroid therapy presents particular concerns in orthopaedic surgery, including increased risks of infection, wound complications, and impaired bone formation.^16–18 For this reason, definitive reconstruction was postponed until the PSL dose had been tapered to 10 mg/day. This decision reflected a balance between reducing perioperative risk and avoiding an excessively prolonged treatment course.

While no consensus exists on the optimal dose of PSL for safe orthopaedic surgery, several reports suggest that doses reduced to 10–15 mg/day are relatively safe.^19–22 A study using a mouse model demonstrated that 10 mg of PSL, equivalent to the human dose, positively affected postoperative recovery and the healing of intestinal anastomoses. This finding suggests that low-dose PSL may be safe for perioperative use.²⁰ In our case, we opted to proceed with surgery after reducing the PSL dose to 10 mg/day, balancing perioperative safety and the waiting period required for tapering. The interval between the initiation of PSL treatment and the final surgery was approximately 2 months. However, because the TSF was already in place, the intervening period could be used to continue gradual limb lengthening the length of the bone. Following the final surgery, no infections or other significant wound-related complications were observed.

Steroids have been reported to suppress osteoblast activity and negatively impact the formation of trabecular bone.²³ However, to the best of our knowledge, no studies have directly examined the effects of steroids on lengthened bones. Furthermore, recent reviews have reported no clear correlation between steroid use and the development of pseudarthrosis.^24,25 Therefore, although he was undergoing high-dose PSL treatment, gradual lengthening was considered feasible. Given concerns about potentially reduced bone formation, particularly because of advanced age and steroid treatment, we therefore selected a relatively slow lengthening rate of 0.5 mm/day and monitored callus formation carefully with serial radiographs. The progression of callus formation was smooth, and no adjustments to the extension rate were required.

A staged surgical strategy is widely advocated for the management of pilon fractures. In cases complicated by open fractures or substantial soft tissue injury, initial stabilisation with a temporary external fixator is commonly performed, followed by delayed internal fixation. Definitive fixation typically involves plate osteosynthesis. However, in situations where the articular surface is extensively compromised, primary arthrodesis may serve as a reasonable alternative.^26,27

A key aspect of the present case was the need to individualise each stage of treatment according to the local soft-tissue condition, infection status, systemic complications, and patient preference. During the early phase, prolonged external fixation was anticipated because of the fungal infection and the need for wound management. Therefore, a circular external fixator was selected to provide greater stability than the modular frame and to allow simultaneous proximal tibial lengthening for 77 mm LLD. Drug-induced hypersensitivity syndrome was subsequently diagnosed and definitive reconstruction had to be postponed during high-dose systemic corticosteroid therapy and tapering. However, gradual limb lengthening could be continued during this waiting period. For the definitive reconstruction, osteosynthesis was not considered appropriate because of severe comminution of the articular surface, bone loss after debridement for infection, the difficulty of achieving anatomical reduction, and the high risk of subsequent post-traumatic osteoarthritis. Arthrodesis was therefore selected as the salvage procedure. Plate fixation around the distal tibia was also avoided because of the previous infection and the thin, compromised soft-tissue envelope. Although further gradual lengthening could theoretically have compensated for the residual LLD, only 42 mm of lengthening had been achieved when the PSL dose had been tapered sufficiently to permit definitive surgery. Given the patient's strong desire for early removal of the external fixator, an alternative strategy was required to simultaneously stabilise the proximal lengthening site and reconstruct the distal bone defect. A retrograde hindfoot nail combined with a tantalum spacer was selected because this construct allowed internal fixation, ankle arthrodesis, and acute compensation of the residual distal bone defect. Although retrograde hindfoot nailing sacrifices the subtalar joint, this was considered acceptable in the present case because the talus also had intra-articular fracture involvement and the risk of post-traumatic subtalar osteoarthritis was considered high.

Tantalum is a biocompatible, chemically inert metal with high porosity and mechanical strength suitable for structural support. Its porous architecture resembles cancellous bone and may facilitate osteointegration and new bone formation. Although tantalum spacers have traditionally been used in spinal procedures, their application in foot and ankle reconstruction, particularly in the hindfoot, has gained increasing attention in recent years.^28–30 In tibiotalocalcaneal (TTC) arthrodesis, a tantalum spacer combined with a retrograde intramedullary nail can help bridge bone defects, restore alignment, and provide hindfoot stability. Bone grafting around the spacer is generally recommended to promote fusion. In this case, resected distal tibial fragments were used as autologous bone graft material, avoiding additional donor-site morbidity. This staged strategy contributed to bone union, correction of the LLD, and restoration of independent ambulation at 1 year postoperatively.

The treatment strategy in this case should be interpreted with caution because several factors were highly case-specific, including fungal infection, DIHS requiring systemic corticosteroid therapy, substantial limb length discrepancy, and the patient's strong preference for early external fixator removal. Generalisable principles include aggressive debridement and dead-space management for infection, staged reconstruction based on soft-tissue and systemic conditions, and arthrodesis when joint preservation is not feasible because of severe articular comminution and infection-related bone loss. By contrast, simultaneous early limb lengthening, plate conversion of the lengthening site, and acute distal defect compensation using a tantalum spacer with a retrograde hindfoot nail were selected primarily to shorten the total treatment period and reduce the burden of prolonged external fixation. In future comparable cases, we would again prioritise infection control and staged decision-making, while carefully considering whether definitive reconstruction could be completed with a circular external fixator rather than conversion to internal fixation, depending on infection risk, soft-tissue condition, and patient tolerance.

Conclusion

This case illustrates the challenges of managing a pilon fracture complicated by infection, limb length discrepancy, and DIHS requiring systemic corticosteroid therapy. In this selected case, a staged strategy using circular external fixation for limb lengthening followed by ankle arthrodesis contributed to limb salvage and functional reconstruction. This experience emphasises the importance of individualised, staged decision-making in complex limb reconstruction under adverse local and systemic conditions.

Clinical Significance

This case illustrates the importance of individualised, staged decision-making in complex limb reconstruction under adverse local and systemic conditions. In selected patients with severe open pilon fractures complicated by infection, bone loss, limb length discrepancy, and DIHS requiring systemic corticosteroid therapy, staged reconstruction using circular external fixation, limb lengthening, and definitive arthrodesis may represent a feasible limb salvage option.

Ethical Approval

Ethical approval was not required because this manuscript is a single case report. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Data Availability Declaration

The data supporting the findings of this case report are available from the corresponding author upon reasonable request. Clinical data and imaging materials will be shared only to the extent permitted by patient confidentiality and institutional regulations.

Artificial Intelligence (AI) Disclosure

The authors used ChatGPT (OpenAI), for English language editing and proofreading of the manuscript. The authors reviewed and edited all AI-assisted text and take full responsibility for the content of the manuscript.

Authors' Contributions

Kanu Shimokawa was involved in the treatment of the patient and drafted the manuscript. Hidenori Matsubara was involved in the treatment of the patient and supervised and reviewed the manuscript. Yusuke Nakazawa was involved in the treatment of the patient and reviewed the manuscript. Satoru Demura supervised the treatment and reviewed the manuscript. All authors read and approved the final manuscript.