Fatal soft-tissue and bony complications following radiotherapy for HIV-negative Kaposi’s sarcoma: a rare case of post-radiation necrotizing fasciitis and osteomyelitis in a resource-limited setting

Abstract

Background:

Kaposi’s sarcoma (KS) is a vascular neoplasm strongly associated with HIV infection; however, HIV-negative KS is exceptionally rare, particularly in sub-Saharan Africa. Radiotherapy (RT) remains a standard local treatment for KS, providing excellent symptom relief and local control. Despite its efficacy, severe complications such as necrotizing fasciitis (NF) and osteomyelitis are exceedingly uncommon and scarcely reported in HIV-negative patients.

Case Presentation:

We report a 47-year-old HIV-negative man with biopsy-confirmed KS of the right thigh, initially treated with chemotherapy followed by external beam RT. Two months post-RT, he developed painful blistering lesions that progressed into extensive necrotic ulceration with foul discharge, fever, and progressive loss of limb function. Despite broad-spectrum antibiotics and multiple surgical debridements, recurrent necrosis persisted with poor granulation. Imaging and intraoperative findings confirmed femoral osteomyelitis with extensive destruction of periarticular soft tissues, tendons, and ligaments, resulting in a nonfunctional knee. The wound was too devitalized for grafting or flap reconstruction. Following multidisciplinary deliberation, above-knee amputation was performed as definitive salvage.

Discussion:

This case highlights a rare yet devastating iatrogenic complication post-RT NF with osteomyelitis in an HIV-negative KS patient. Distinguishing infection from radiation necrosis or tumor recurrence posed major diagnostic challenges. Radiation-induced obliterative microangiopathy and fibrosis likely predisposed the tissues to infection and impaired healing.

Conclusion:

Vigilant post-RT monitoring, prompt recognition of soft-tissue infection, aggressive multidisciplinary management, and timely radical surgery are essential. In resource-limited settings, limb salvage may be impossible, making amputation the only viable life-saving option.

Introduction

Kaposi’s sarcoma (KS) is a proliferative vascular tumor first characterized in 1872 by Moritz Kaposi. It is commonly linked with human herpesvirus 8 infection and typically arises in the setting of immune dysregulation, most notably in HIV/AIDS^[1]. Four epidemiologic variants are recognized: epidemic (HIV-associated), classic (Mediterranean), endemic (African), and iatrogenic (transplant-associated). HIV-negative KS encompassing classic or endemic types remains rare, particularly in resource-limited settings.

Radiotherapy (RT) is well established as a safe and effective modality for localized KS, achieving high rates of symptom relief and durable local control at relatively low to moderate doses^[2]. Most patients experience only mild cutaneous reactions, and significant late toxicity is infrequent^[2,3]. Severe RT-induced complications such as soft tissue necrosis or infection are rarely encountered, and the occurrence of necrotizing fasciitis (NF) after RT is exceedingly rare. NF is a fulminant infection of fascia and subcutaneous tissue characterized by rapid spread, systemic toxicity, and high mortality^[4]. When RT-induced tissue damage coexists with infection, outcomes worsen substantially. Osteomyelitis in irradiated bone offers additional complexity, as vascular compromise hinders antibiotic delivery and bony healing^[5].

In selected cases, chemotherapy may precede RT to reduce tumor burden and improve local response^[6]. Despite its favorable therapeutic profile, RT can induce soft-tissue and bony injury through endothelial damage, chronic hypoxia, and impaired tissue regeneration^[7,8].

Late complications such as nonhealing ulceration, radiation necrosis, and osteoradionecrosis occur in a minority of patients^[9]. NF following RT is extraordinarily rare, and to our knowledge, cases involving HIV-negative KS patients are virtually unreported^[10]. The combination of RT-induced vascular compromise, prior chemotherapy-induced tissue stress, and superimposed bacterial invasion creates a high-risk environment for fulminant infection, but such presentations are seldom documented in the KS literature.

Differentiating post-RT tissue necrosis, KS recurrence, and early soft-tissue infection can be diagnostically challenging. Clinical features often overlap, and advanced imaging modalities such as MRI, which can clarify fascial involvement or distinguish tumor from necrosis, may not be feasibly done due to financial constraints or resource-limited settings^[6,11]. These constraints can delay recognition of NF, complicate surgical decision making, and increase the risk of catastrophic outcomes.

Retrospective analyses of classic KS patients report high response rates to moderate RT doses (20–30 Gy)^[3]. In localized disease, RT can be used alone or in conjunction with systemic therapy. However, radiation is not without risk; late adverse effects include fibrosis, chronic ulceration, necrosis, and impaired wound healing^[12].

We report an exceptionally rare case of post-RT NF with femoral osteomyelitis in an HIV-negative KS patient who had previously received systemic chemotherapy. This case is distinguished by:

1. the rarity of NF as a post-RT complication in KS,

2. rapidly progressive recurrent necrosis despite repeated debridements,

3. destructive involvement of periarticular soft tissues and bone, and

4. the contextual challenges of managing an aggressive post-radiation infection in a low-resource tertiary hospital.

We also discuss the pathophysiologic basis of radiation-injured tissue vulnerability, the diagnostic dilemmas encountered, and the multidisciplinary decision-making process that led to radical but life-saving surgery.

Case presentation

A 47-year-old HIV-negative man presented with a history of a violaceous nodular lesion on the right thigh, progressively enlarging and occasionally painful. A punch biopsy confirmed KS. He received multiple cycles of systemic chemotherapy before referral for RT. He completed a total dose of 30 Gy in 10 fractions over 2 weeks. No additional chemotherapy was given after RT. Approximately 3 weeks after completing RT, he developed increasing thigh pain, swelling, and darkening of the irradiated skin. The symptoms rapidly worsened over time, culminating in foul-smelling discharge, fever, and inability to bear weight. Oral antibiotics were tried repeatedly, with no improvement. He presented to our facility in septic condition.

HIGHLIGHTS

• Post-RT NF with osteomyelitis in HIV-negative KS is rare.

• Diagnostic overlap between infection, recurrence, and radiation necrosis complicates care.

• Multidisciplinary consensus led to life-saving hip disarticulation amputation.

• Limited wound care resources hindered limb salvage and reconstructive options.

• Highlights the need for vigilance and capacity building in post-RT wound care.

When he arrived at our tertiary referral center, he was febrile (38.5°C), tachycardic (123 bpm) and appeared systemically unwell. On local examination, the left thigh exhibited a large ulcer extending from the anterolateral thigh to the lower thigh, undermined edges, induration, and areas of necrotic slough (Fig. 1A and B). The posterior thigh showed exposed necrotic subcutaneous tissue (Fig. 2). No healthy granulation tissue was evident. The knee region was swollen, firm, and immobile. The wound depth varied unevenly with intervening pockets of purulent discharge. Initial laboratory investigations revealed leukocytosis (WBC 18.1 × 10⁹/l), neutrophilia (ANC 13.4 × 10⁹/l), elevated C-reactive protein (168 mg/l), and mild anemia (Hb 10.9 g/dl). Platelets were elevated (769 × 10⁹/l). Renal and liver function tests were within acceptable limits. HIV serology was negative. Pus cultures grew Gram-negative bacilli susceptible to a subset of antimicrobial agents. Repeat punch biopsy from the ulcer edge showed residual KS features with post-treatment changes but no evidence of aggressive tumor recurrence.

Figure 1.

(A) and (B): Chronic extensive ulcer (blue arrows) on the left anterolateral thigh, with surrounding induration (red arrow) and multiple areas of foul-smelling purulent discharge (black arrows). The ulcer extends distally toward the lower thigh, demonstrating significant soft-tissue involvement and progressive local tissue destruction consistent with chronic infection.

Figure 2.

Undermined and irregular wound edges (blue arrows) with surrounding erythema (black arrow). The posterior aspect of the thigh shows exposed necrotic subcutaneous tissue (red arrow), indicating severe local tissue damage and ongoing infection with poor wound healing characteristics.

MRI was not done due to financial constraints, limiting the assessment of muscular necrosis or early osteomyelitis. A plain radiograph of the femur and knee region demonstrated periosteal reaction, cortical irregularities, and subtle bone destruction consistent with osteomyelitis (no obvious fracture) (Fig. 3A and B). A wide, aggressive debridement was performed, removing all visible necrotic tissue and draining abscess cavities. The wound was left open and dressed with saline irrigation and antiseptic dressings. Initially, some reduction in discharge was noted, but within days, fresh slough formation and necrosis reappeared at the margins. Two weeks later, a second extensive debridement was done, excising additional devitalized muscle and fascia. Purulent tissue extended down to exposed bone and tendon stumps. Despite this, postoperative inspections revealed a persistent absence of granulation tissue, and new necrotic areas continued to emerge (Fig. 4).

Figure 3.

Lateral (A) and anteroposterior (B) views of the left tibia and femur show cortical irregularities with periosteal reaction (black arrows), indicative of osteomyelitis. No evidence of a pathological fracture is observed. These findings highlight localized bone involvement, supporting the clinical suspicion of infection.

Figure 4.

Images (A) and (B) depict the first and second surgical debridements, both removing necrotic and devitalized tissue. Postoperative inspection, however, revealed a persistent absence of granulation tissue and ongoing purulent discharge (black arrows). Knee joint soft tissue devitalized.

Over subsequent weeks, recurrent necrosis and slough formation spread further proximally and circumferentially. The wound became massive, with devitalized soft tissues extending to the thigh and knee. Tendons, ligaments, and the joint capsule were destroyed. The knee joint lost structural integrity and function.

Decision against reconstruction and planning for amputation

Due to the following factors, reconstructive options were considered infeasible: Repeated recurrence of necrosis despite two aggressive debridements.

1. Extensive soft tissue destruction spanning the thigh and knee.

2. Loss of all supportive structures making the knee nonfunctional.

3. Poor vascularity in irradiated tissue hindering graft take.

4. Unsustainable availability of advanced wound modalities [vacuum-assisted closure (VAC) and hyperbaric oxygen therapy (HBOT)].

A multidisciplinary team, including surgical, oncologic, orthopedic, and infectious disease specialists, reviewed the case. Given the life-threatening infection and non-salvageability of the limb, the decision was made to perform an above-knee amputation at the hip joint through hip disarticulation.

Surgery and postoperative course

Under general anesthesia, a hip disarticulation was performed. Intraoperatively, widespread necrosis extended proximally into the thigh musculature; femoral vessels were thrombosed in places. The acetabular region was spared. Tissue specimens confirmed osteomyelitis of the femoral segments and no viable KS infiltration at specimen margins.

Postoperative management included broad-spectrum IV antibiotics, analgesia, nutritional support, wound care, and physiotherapy. The stump healed without further necrosis or systemic infection. Over 3–6 months, the patient adapted to rehabilitation, with no evidence of KS recurrence.

Discussion

Radiotherapy in Kaposi’s sarcoma and its risks

RT remains a mainstay in the management of KS due to its high radiosensitivity, predictable local control, and generally favorable toxicity profile^[3,7]. Most patients treated with 20–30 Gy experience excellent clinical responses with limited late morbidity; in certain cases, systemic chemotherapy is administered prior to RT to reduce tumor burden and improve local response^[7]. However, chemotherapy may also contribute to transient tissue vulnerability through effects on local immunity and vascular endothelium, potentially compounding the risk of post-RT complications^[8,12]. The severity of late radiation injury depends on dose, fractionation, irradiated volume, and individual susceptibility^[8].

Radiation-induced tissue vulnerability

Radiation disrupts microvascular structures, damages endothelial integrity, reduces capillary density, and induces chronic tissue hypoxia^[8]. Fibroblasts become senescent and lose their capacity for collagen deposition and extracellular matrix repair. Over time, irradiated tissues exhibit reduced perfusion, impaired immune surveillance, and delayed cellular turnover^[5,8]. The coexistence of bone damage (osteoradionecrosis) further complicates outcomes^[4,5]. These changes, combined with prior chemotherapy effects, create a setting in which even minor bacterial contamination can progress to aggressive infection. Cases of post-RT osteomyelitis have been documented in anatomical regions such as the ribs and cervical spine^[4,5]. Radiation-induced osteonecrosis of the pelvis and hip has also been reported^[9].

Pathophysiologic mechanisms include

1. Microvascular obliteration and ischemia limiting oxygenation and nutrient supply^[8,12].

2. Fibrosis and extracellular matrix disorganization hindering inflammatory cell migration^[12].

3. Impaired neutrophil trafficking reducing host defense^[8].

4. Reduced antibiotic penetration contributing to persistent microbial reservoirs^[9].

5. Hypovascular bone predisposed to osteoradionecrosis and secondary osteomyelitis^[9].

Diagnostic dilemmas

Distinguishing early post-RT deterioration as recurrent KS, radiation necrosis, or evolving NF was challenging^[10,11]. All three may present with ulceration, pain, induration, and poor wound healing. MRI and PET-CT could have helped distinguish a viable tumor from necrotic tissue. Diagnosis relied on serial biopsies, progressive systemic toxicity, microbiologic evidence of infection, and radiographic findings^[6]. We relied on serial biopsies (which showed no aggressive KS), cultures, radiographic bone changes, and clinical progression.

Failure of wound healing and recurrent necrosis

Persistent absence of granulation tissue and rapid re-accumulation of necrotic slough after each debridement indicated irreversibly injured tissue, worsened by prior chemotherapy^[8,9]. Without vascularized tissue, even aggressive debridement could not shift the wound toward healing^[8,12].

Limb salvage versus amputation

Although VAC therapy and HBOT may allow limb salvage in well-equipped centers, the extent of soft-tissue destruction, nonviable knee joint, femur involvement, and poor vascularity eliminated reconstructive options. The multidisciplinary decision for hip disarticulation was based on:

1. ongoing life-threatening infection,

2. complete loss of limb function,

3. lack of advanced reconstructive modalities, and

4. risk of systemic sepsis^[10,11].

Postoperative recovery with resolution of infection validated this life-saving approach.

Comparison with literature

1. NF after RT is extremely rare, reported mainly in head-and-neck or pelvic malignancies^[4,10].

2. RT-associated osteomyelitis is documented in ribs, mandible, and cervical spine^[5,9].

3. No published reports describe simultaneous post-RT NF and osteomyelitis in HIV-negative KS.

Clinical learning points

1. Rapidly progressive ulceration after RT should prompt early suspicion of NF.

2. Advanced imaging is helpful, but clinical deterioration and basic radiography can guide urgent management.

3. Repeated failure of granulation tissue suggests underlying irreversible radiation damage, potentially worsened by chemotherapy.

4. Early multidisciplinary evaluation is critical in determining limb salvage feasibility.

5. In resource-limited settings, timely radical surgery may be the only life-saving intervention.

Conclusion

This case highlights a rare but catastrophic complication of RT in an HIV-negative KS patient, culminating in NF, osteomyelitis, and eventual hip disarticulation. Radiation-induced tissue injury compounded by prior chemotherapy, delayed presentation, diagnostic limitations, and aggressive soft-tissue necrosis can rapidly overwhelm limb-salvage strategies. In resource-limited settings, early recognition of disproportionate pain, progressive necrosis, and systemic deterioration is critical. Heightened vigilance, timely escalation from debridement to amputation, and clear multidisciplinary communication are essential to optimize survival.

The work has been reported in line with the SCARE criteria^[13].

Ethical approval

Ethical clearance was not necessary for a single case report.

Consent

Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the corresponding author of this journal.

Sources of funding

No funds were needed to publish this case.

Author contributions

M.S.: Perioperative care, conceptualized the case, methodology, and approved the final article. S.S.: Perioperative care, conceptualized the case, patient management, methodology, and approved the final article. N.S.M.: Imaging interpretation and diagnosis support. F.M.: Performed surgery, literature review, data curation, reviewed, and approved the final article. A.E.M.: Plastic and reconstructive surgeon, supervision, performed surgery, data curation, reviewed, and approved the final article. L.J.R.: Plastic and reconstructive surgeon, supervision, performed surgery, and approved the final article.

Conflicts of interest disclosure

All authors declare that there are no conflicts of interest.

Guarantor

All authors in the article accept full responsibility for the work, have access to the patient’s information, and decide to publish.

Research registration unique identifying number (UIN)

Not applicable.

Provenance and peer review

Not commissioned; externally peer reviewed.

Data availability statement

The datasets generated and/or analyzed during the present study are available from the corresponding author upon reasonable request.