Mucor mycosis of tibia: A case report of An unsolved entity

Abstract

Mucormycosis of tibia is a highly aggressive fungal infection. It is an uncommon affection especially in immunocompromised host who have more propensity for such affections.

The nonhealing ulcer of the left leg in an immunocompromised host status of a 45-year-old male presented with a radiological lytic lesion of the distal lower fourth of tibia. The initial biopsy confirmed tubercular affection which responded to antitubercular medications to allow radiological healing. However, the repeat biopsy showed Mucormycosis which remained recalcitrant to antifungal medications with unresponsive wound healing and persisting suppuration. The case presented unique scenario of superadded fungal infection in a healing tubercular osteomyelitis tibia with alcoholic liver disease compromised host immunity.

The fungal infection of tibia remains an unsolved entity with poor clinical and functional outcomes. An early detection, high degree of suspicion with an adequate dosage of antifungal medications may allow resolution of the dreaded infection though an effective treatment remains an unsolved entity.

1. Introduction

Mucor mycosis is an uncommon but highly aggressive fungal infection with a high mortality rate.¹ The fungi causing this infection belong to the class Zygomycetes and order Mucorales.^2,3 The reported incidence of Mucormycosis is 1.7 cases per 1,000,000 people per year in developed countries.⁴ Mucormycosis generally occurs in severely immunocompromised host in developed countries and in immunocompetent individuals following trauma.² The pre-disposition of Mucormycosis in trauma and burn cases presents a diagnostic challenge.¹

Fungal affections typically occur as rhino-cerebral infections. Few studies have reported local bone involvement, which is normally attributed to contiguous spread.² Mucormycosis of non-axial bones has rarely been reported, although any bone may be involved.^1,4 Only a few of the listed and documented cases of non-axial bone infection in the English literature involve the tibia with varied outcomes, and several cases have shown unfavorable responses to treatment.²

Herein, we report a case of Mucormycosis infection affecting the tibia in an immunocompromised host treated for a tubercular infection presenting as a pathological fracture. It initially progressed well; however, subsequent fungal infections ensued and did not resolve despite antifungal medications. This eventually led to the amputation of the affected limb, and the infection remains unsolved regarding its eventual management.

2. Case report

A 45-year-old male patient presented with a non-healing ulcer in the lower fourth of the left lower limb for 1.5 years. The patient had a history of alcoholic liver disease. He had undergone vascular surgery for an aortic bifurcation block approximately 1.5 years previously and had a history of multiple necrotic ulcers in the left lower limb, which were treated with split thickness skin grafting and eventual amputation of his left little toe. The patient continued dressing the wound for the non-healing ulcer on his left leg. He had recently sustained a low-energy trauma 15 days ago, thus making him unable to bear the load on the affected limb.

Upon examination, the patient was clinically pale, hemodynamically stable, and afebrile. Locally, the left lower limb showed grafted areas in the lower fourth of the leg and dorsum of the foot, along with an ulcer on the antero-medial aspect of the left tibia with exposed bone and underlying debris with an unhealthy collection (Fig. 1). The dorsalis pedis artery showed good pulsation; however, the posterior tibial artery was feeble.

Fig. 1.

Non-healing wound of the left leg with adjacent areas of previous scars.

Plain radiographs of the leg revealed a spiral fracture in the lower fourth of the tibia with a lytic cavity and adjacent rarefaction (Fig. 2). A color Doppler study of his left lower limb showed normal blood flow but with diminished/low pressure. Routine hematological tests showed low hemoglobin levels and a high erythrocyte sedimentation rate. Pathological fractures of the tibia were subjected to surgical debridement, wound toileting, curettage, and biopsy from the tibia supplemented by an autologous iliac crest bone graft utilizing the cortico-cancellous graft along with secondary closure of the skin with local flap coverage and plaster cast support. The initial biopsy report suggested tuberculosis, and anti-tubercular treatment was initiated with a four-drug regimen. The patient showed clinical wound healing without suppuration in the next 4 weeks and radiological non-progression of the cavitary lesion (Fig. 3). Radiologically, the fracture consolidated and united within approximately 4 months (Fig. 4). However, the wound exhibited dehiscence with minimal suppuration after 4 months (Fig. 5). Non-healing of the flap was observed, with persistent wound dehiscence, necessitating a repeat biopsy. A repeat biopsy showed fungal growth consistent with Mucorales infection (Fig. 6). Simultaneous amphotericin B and regular wound toileting were initiated along with the continuation of anti-tubercular medications. However, a persistent wound with occasional low-volume discharge was observed. At the last follow-up of the pathological fracture, at approximately 1 year postoperatively, the unhealed wound was persistently drained, the tibia remained exposed, the skin margins were unopposed, and the patient was ambulatory with crutches (Fig. 7). An above-knee amputation of his left lower limb was discussed as an option; however, he was lost to follow up.

Fig. 2.

Radiographs of the left leg in (a) anteroposterior and (b) lateral views showing spiral fracture of tibia with a lytic cavity and adjacent rarefaction (marked with a white arrow).

Fig. 3.

Radiographs of the left leg in (a) anteroposterior and (b) lateral views 3 weeks after curettage and bone grafting of the tibia (marked with a white arrow).

Fig. 4.

Radiographs of the left leg in (a) anteroposterior and (b) lateral views after 4 months showing fracture consolidation (marked with a white arrow).

Fig. 5.

Wound dehiscence of the left leg flap after 4 months of anti-tubercular medications.

Fig. 6.

The histopathological slide (a) showing fungal hyphae in bone marrow (marked with a white arrow) and (b) showing fungal hyphae in high resolution (marked with a black arrow).

Fig. 7.

Radiographs of the left leg in (a) anteroposterior and (b) lateral view showing lytic lesion recurrence in the left tibia.

3. Discussion

Bone fungal bone infections are rare. Fungal osteomyelitis may become an increasing problem because of the increase in patients who are immunocompromised.² Mucormycosis of the tibia remains a dilemma for achieving a favorable outcome. Men are affected twice as commonly as women.⁵ Mucorales infections are generally classified as rhino-cerebral, pulmonary, widely disseminated, gastrointestinal, cutaneous, or miscellaneous.^1,3 Mucormycosis lacks specific initial findings that aid in its diagnosis. Associated conditions that predispose individuals to infections may include diabetes, leukemia, lymphoma, malnutrition, prosthetic valves and vascular grafts, gastroenteritis, anemia, hepatitis, septicemia, myeloma and uremia.2, 3, 4

Bone involvement with Mucormycosis is rarely observed. Most infections are rhino-cerebral.^2,3 The tibia is the most commonly affected appendicular bone. Other bones affected include the femur, humerus, ulna, scapula, cuboids, metacarpals, phalanges, and elbow.^3,6 To date, few cases of vertebral osteomyelitis have been reported.⁷ Herein, we report a case of Mucormycosis of tibia in an immunocompromised patient with a history of alcoholic liver disease, tuberculosis and vascular graft surgery.

The route of infection was hematogenous in most cases with direct inoculation in an open tibial fracture and one secondary to cutaneous Mucormycosis.^3,5 In our case, direct inoculation in an open fracture was a strong possibility, as low-energy trauma was the inciting factor, followed by surgery as a secondary trauma to the local tissues.

Mucormycosis infections cause little tissue reaction and are often diagnosed late or misdiagnosed until tissue ischemia and necrosis have advanced owing to vascular invasion.^4,6 Any dysfunction in the activity of the host to generate sufficient macrophagic or neutrophilic activity against proliferating fungal hyphae may predispose the host to aggressive fungal infection.⁴ The clinical suspicion and early diagnosis of Mucormycosis are characterized by two facts.³ First, Mucorales invades the vascular walls and causes infarction and subsequent ischemia, which leads to the production of black necrotic pus. Second, Mucorales can be diagnosed most reliably by culture and can be identified by scraping and biopsy of the suspected area.³ Typically, broad, non-septate hyphal structures are visualized by staining with hematoxylin and eosin, and periodic acid Schiff, and best visualized after staining with Gomori methenamine silver nitrate.^2,4 Radiological imaging and evaluation with magnetic resonance imaging, computer tomography, and radio-nucleotide scans have indistinct features and may be insufficient to confirm the diagnosis.^4,5

Historically, medical treatment has been administered with high doses of lipid formulations of amphotericin B, and occasionally, flucytosine has been added in the treatment of the confirmed cases.^1,5 Although the duration of treatment has not been defined, renal toxicity needs monitoring, and occasionally, discontinuation of antifungal medications may be required.¹ In most cases, surgical debridement is performed with reported cases of tibial Mucormycosis, utilizing either debridement or amputation as the management option. However, recent therapeutic additions include other azoles, extended-spectrum triazoles, and echinocandins for managing fungal infections.⁸ Successful treatment of this uncommon, although potentially devastating, infection remains challenging. Mucorales osteomyelitis requires early diagnosis, systemic amphotericin B administration, and effective surgical intervention.3, 4, 5 Amputation of the extremities may be necessary for relentless progressive bone destruction.⁵ High mortality rates have been reported for Mucormycosis infections.^1,5

The current case was unique in that the infection was superadded to a tubercular osteomyelitis of the tibia with evidence of initial healing of the pathological fracture. The dehiscence and nonhealing nature of the wound warrant a repeat biopsy. Only one case of sacroiliitis, “provisionally” diagnosed as a tubercular infection, has been reported, with a history of disease progression despite anti-tubercular medications. A subsequent biopsy of the gluteal lesion confirmed the development of fungal osteomyelitis, consistent with Mucormycosis. However, treatment with antifungal medications resulted in only a partial response.¹ Chronic granulomatous infections in the male patient with alcoholic liver disease with anemia and vascular arteritis suppressed the ability to mount an effective immune response against a ubiquitous fungus. The need for discussing above-knee amputation resulted from a combination of factors, including delayed recognition and diagnosis of the Mucormycosis infection, immunocompromised host, and suboptimal clinical response to debridement and medical therapy.

4. Conclusion

Mucorales osteomyelitis is an unresolved disease with potentially fatal outcomes. The rarity of lesions in the appendicular bones, late diagnosis, and immunocompromised hosts necessitate early recognition and prompt treatment for an optimal response.

Learning point from the case

A repeat biopsy helped to identify the superadded fungal Mucormycosis infection in a non-healing tibial ulcer affecting the immunocompromised host with tubercular infection.

Learning points

• ❖An immunocompromised host has predisposition for tubercular and fungal osteomyelitis affection in a post-traumatic lower third pathological fracture of tibia.
• ❖A high index of suspicion needs to be observed and a repeat biopsy may be taken in a non-healing ulcer.
• ❖Mucormycosis of tibia remains an unsolved entity with fatal outcomes.

Consent for publication

The patient was informed that data from the case would be submitted for publication and the patient gave written consent. The patient understands that his name and initials will not be published, and due efforts will be made to conceal his identity.

Ethics approval

Not considered.

Authors contribution and declaration

LT and GG contributed to the study conception, design, investigation and methodology.

LT performed the surgery and GG was associated.

GG performed data collection and interpretation.

GG performed the literature search and prepared the original draft of the manuscript and reviewed the subsequent version with editing of the manuscript.

LT did review analysis.

All authors commented on the previous versions of manuscript.

All authors read and approved the final version of manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

Lavindra Tomar and Gaurav Govil reports a relationship with Max Super Speciality Hospital Patparganj that includes: employment.

Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.