Bilateral ascending dry gangrene following documented smear-positive malaria in a patient with multivalvular rheumatic heart disease and normal CT angiography findings: a case report

Abstract

Introduction:

Symmetrical peripheral gangrene (SPG) is a rare syndrome characterized by distal ischemic necrosis affecting two or more extremities in the absence of major arterial occlusion or vasculitis. Malaria is an uncommon but recognized trigger, most often described in association with severe Plasmodium falciparum infection. Once ischemia progresses to dry gangrene, major amputation is often unavoidable.

Case presentation:

A 57-year-old woman presented with rapidly progressive bilateral lower-limb pain, swelling, blistering, discoloration, and tissue necrosis shortly after treatment for smear-positive malaria at a rural health center. The health center record noted malaria parasites with trophozoites graded 3 +, after which she was treated with dihydroartemisinin-piperaquine. Three days later, she developed sudden, severe bilateral leg pain and swelling, followed by blistering and progressive distal discoloration. Laboratory evaluation showed leukocytosis (11.2 × 10³/µL; neutrophils 82.5%), anemia (hemoglobin 8.9 g/dL), a normal platelet count (156 × 10³/µL), preserved renal function (creatinine 48 µmol/L), mild hyperkalemia (5.47 mmol/L), and negative blood cultures. PT/PTT/INR and D-dimer were unavailable locally. Transthoracic echocardiography demonstrated multivalvular rheumatic heart disease with preserved left ventricular systolic function. CT angiography showed no major arterial occlusion. She was treated with intravenous furosemide, ceftriaxone, metronidazole, oral azithromycin, and subcutaneous enoxaparin, but because the gangrene was already advanced, she ultimately underwent bilateral below-knee amputations.

Discussion:

The chronology, the bilateral distal ischemic pattern, and normal CT angiography support malaria-associated SPG or microvascular ischemia as the most plausible unifying diagnosis. However, malaria is cautiously presented as the likely trigger because alternative contributors, including DIC, low-flow ischemia related to rheumatic heart disease, cardioembolic disease, vasculitis, hypercoagulable states, and delayed presentation, could not be completely excluded.

Conclusion:

This case highlights malaria-associated SPG as a rare but devastating cause of bilateral lower-limb gangrene. In malaria-endemic settings, new distal pain, discoloration, or gangrenous change after malaria should prompt urgent evaluation because delayed recognition may result in irreversible necrosis and major amputation.

Introduction

Symmetrical peripheral gangrene is an uncommon clinicopathologic syndrome defined by symmetrical distal ischemic injury involving two or more extremities in the absence of major arterial obstruction or vasculitis^[1–6^]. It has been reported in association with sepsis, disseminated intravascular coagulation (DIC), low-flow states, vasopressor exposure, and several infectious conditions, including malaria^[2,5–7^]. Malaria-associated SPG is rare, but published reports consistently show that it may progress rapidly and culminate in irreversible necrosis and amputation^[1–4,7–14^].

HIGHLIGHTS

• Bilateral ascending dry gangrene developed shortly after documented smear-positive malaria.

• CT angiography showed no major arterial occlusion, supporting a microvascular ischemic mechanism.

• The presentation is most consistent with malaria-associated symmetrical peripheral gangrene.

• Individuals with underlying multivalvular rheumatic heart disease may have reduced perfusion reserve.

• The delayed presentation culminated in staged bilateral below-knee amputations.

The proposed mechanisms of malaria-associated peripheral gangrene include sequestration of parasitized erythrocytes in the microcirculation, endothelial activation, rosetting, platelet plugging, cytokine-mediated vascular injury, and coagulation abnormalities, including DIC^[1–4,7–10,15–18^]. Although Plasmodium falciparum is most commonly implicated, similar presentations have also been reported in P. vivax and mixed malaria infections^[9,10,13^].

This case report has been prepared and reported in line with the SCARE 2025 criteria^[19^]. We report a rare case of bilateral ascending dry gangrene occurring shortly after a documented smear-positive malaria infection in an adult woman with normal CT angiography and concomitant multivalvular rheumatic heart disease.

Case presentation

A 57-year-old woman presented with progressively worsening bilateral lower-limb pain, swelling, blistering, and discoloration, associated with heaviness in the legs and a burning sensation. Approximately 2 weeks before presentation, she had been evaluated at a peripheral health center, where a blood smear was reported as positive for malaria parasites with trophozoites graded 3+. + . She was treated with dihydro artemisinin-piperaquine. About three days after treatment, she developed sudden, severe bilateral leg pain, swelling, and discoloration of the toes. Traditional topical treatment was subsequently applied, after which blistering developed within 2 days, followed by progressive discoloration beginning at the toes (Table 1).

Table 1.

Clinical timeline of the patient’s presentation, management, and follow-up.

Approximate time point	Clinical event
Two weeks before hospital presentation	Evaluation at a rural health center documented smear positive malaria with trophozoites 3+; dihydroartemisinin-piperaquine was administered.
Three days after antimalarial treatment	Sudden severe bilateral leg pain and swelling developed, followed by discoloration of the toes.
Subsequent 2 days	Traditional topical treatment was applied; blistering developed and distal discoloration progressed proximally.
Hospital presentation	Bilateral lower-limb pain, swelling, wounds near the ankles, shrunken toes, distal sensory loss, weak dorsalis pedis pulses, and established dry gangrene were documented.
Inpatient evaluation	Laboratory tests, chest radiography, ECG, echocardiography, and CT angiography were performed. CT angiography showed no major arterial occlusion.
Definitive management	After optimization and multidisciplinary evaluation, advanced non-salvageable bilateral dry gangrene was managed with bilateral below-knee amputations.
Postoperative course and follow-up	The patient was discharged on postoperative day 15. Follow-up at 1 month and three months showed good stump healing and clinical recovery.

She had no known history of diabetes mellitus, smoking, previous surgery, or peripheral vascular disease.

Examination and diagnostic work-up

On examination, she had symmetric chest expansion with right basal crackles on auscultation. Cardiovascular examination revealed audible first and second heart sounds and a holosystolic murmur best heard over the mitral and tricuspid areas, with axillary radiation. Examination of the lower limbs showed bilateral dark-brown discoloration, wounds around the dorsal ankle regions, shrunken toes, distal sensory loss, and weak dorsalis pedis pulses (Fig. 1).

Figure 1.

Bilateral symmetrical peripheral gangrene involving the feet and distal lower legs. The image demonstrates dry gangrene with black, mummified distal tissues and a well-demarcated transition zone in the lower legs. Areas of superficial tissue breakdown are noted near the demarcation line. The symmetrical distribution and the absence of a clear large-vessel territory are consistent with microvascular occlusion.

Laboratory investigations revealed leukocytosis with a white blood cell count of 11.2 × 10³/µL and neutrophil predominance (82.5%). Hemoglobin was reduced at 8.9 g/dL, while the platelet count was within the normal range (156 × 10³/µL). Blood cultures showed no growth. Renal function was preserved, with a serum creatinine of 48 µmol/L. Electrolyte analysis demonstrated mild hyperkalemia (potassium 5.47 mmol/L) with normal serum sodium (135 mmol/L). The lipid profile showed low total cholesterol (2.28 mmol/L), low HDL cholesterol (0.47 mmol/L), and an LDL cholesterol of 1.13 mmol/L. Liver enzyme levels were AST 74.8 U/L and ALT 38.2 U/L. Available serological tests were negative. PT/PTT/INR and D-dimer testing were not available in our setting.

Chest radiography demonstrated bilateral lung opacities. Electrocardiography was normal. Transthoracic echocardiography revealed rheumatic multivalvular heart disease with moderate mitral stenosis, moderate aortic stenosis with aortic regurgitation, mild-to-moderate mitral regurgitation, and severe tricuspid regurgitation, with preserved left ventricular ejection fraction. CT angiography showed no evidence of major large-vessel occlusion.

Treatment and outcome

Following admission, the patient underwent initial medical stabilization and optimization. Volume overload was managed with intravenous furosemide 40 mg administered twice daily. Empiric broad-spectrum antimicrobial therapy was initiated with intravenous ceftriaxone 1 g twice daily in combination with intravenous metronidazole 500 mg three times daily, with additional oral azithromycin 500 mg once daily. The rationale for antimicrobial therapy was a suspected secondary soft-tissue infection around nonviable tissue and concomitant chest radiographic opacities. Venous thromboembolism prophylaxis was provided with subcutaneous enoxaparin 40 mg twice daily, in accordance with local inpatient thromboprophylaxis practice and given the perceived high thrombotic risk in a patient with extensive tissue necrosis and markedly reduced mobility.

Despite supportive treatment, the gangrene had already advanced, and the limbs were not salvageable. After multidisciplinary evaluation, bilateral below-knee amputations were performed as definitive treatment. The patient was discharged on postoperative day 15. At 1-month and 3-month outpatient follow-up visits, she was clinically stable, her amputation stumps were healing well, and she continued postoperative care, rehabilitation, and mobility support planning.

Discussion

This case is notable for the bilateral distribution of gangrene, the documented smear-positive malaria preceding symptom onset, and the absence of major arterial occlusion on CT angiography. SPG is classically described as symmetrical distal ischemic damage without demonstrable large-vessel obstruction or vasculitis, and this definition fits the clinical and imaging pattern in our patient^[1–6^].

Malaria-associated SPG remains rare, but the literature describes a recognizable pattern of distal ischemic injury occurring in the setting of systemic malaria-related vascular dysfunction^[1–4,7–14^]. Thanachartwet et al reported on adults with severe falciparum malaria complicated by peripheral gangrene, and other reports similarly document progression to tissue loss despite the absence of a surgically correctable proximal occlusion^[1–4,7–10,12–14^].

The most plausible mechanism in our patient is malaria-associated microvascular compromise. In falciparum malaria, parasitized erythrocytes adhere to vascular endothelium and sequester within the microcirculation, while reduced red-cell deformability, rosetting, platelet-mediated clumping, endothelial activation, and inflammatory injury can reduce tissue oxygen delivery and promote microvascular obstruction^[15–18^].

Coagulation disturbance is another important mechanism to consider. DIC and depletion of natural anticoagulants are frequently discussed in SPG and in severe malaria-associated gangrene^[3,5–7^]. In our patient, the platelet count was normal at 156 × 10³/µL, which makes overt thrombocytopenia-associated DIC less likely at the time of hospital evaluation, but PT/PTT/INR and D-dimer were unavailable; therefore, DIC cannot be completely excluded^[5–7,20^].

Low-flow ischemia related to multivalvular rheumatic heart disease was also considered. Moderate mitral stenosis, moderate aortic stenosis with regurgitation, severe tricuspid regurgitation, and volume overload may reduce perfusion reserve and impair tolerance to an acute systemic microvascular insult; however, preserved left ventricular systolic function, bilateral distal symmetry, and normal CT angiography argue against isolated cardiogenic macrovascular limb ischemia as the sole explanation^[5,6^].

Cardioembolic acute limb ischemia was considered because rheumatic valvular disease may be associated with atrial arrhythmia, atrial thrombus, and systemic embolism. However, the patient had a normal ECG, no major large-vessel occlusion on CT angiography, and a symmetrical distal distribution rather than a single arterial-territory occlusion, making a primary cardioembolic mechanism less likely^[5,6^].

Vasculitis and primary hypercoagulable states were also considered in the differential diagnosis. The absence of a clear vasculitic clinical syndrome, negative results on available serologic tests, no reported prior thrombotic history, preserved renal function, normal platelet count, and normal findings on CT angiography reduce the likelihood of these diagnoses, but they were not exhaustively excluded because advanced immunologic and thrombophilia testing were not available^[5,6^].

Atherosclerotic peripheral arterial disease was less likely because the patient had no known diabetes mellitus, smoking history, or previous peripheral vascular disease; the lipid profile did not suggest severe dyslipidemia; and CT angiography did not show major arterial occlusion. Drug-related vasospasm or vasopressor-associated gangrene was also unlikely because there was no documented vasopressor exposure before the ischemic process^[5,6^].

The progression from ischemia to dry gangrene reflects a sustained perfusion failure leading to tissue necrosis and mummification, rather than a primarily suppurative process. In established dry gangrene with nonviable tissue and proximal extension, definitive amputation is often required after demarcation and optimization, particularly when presentation is delayed^[1,2,5,6,8,9^].

The chronology is clinically important but should be interpreted cautiously. The documented malaria smear, onset of bilateral ischemic symptoms shortly after antimalarial treatment, and normal CT angiography make malaria-associated SPG or microvascular ischemia the most plausible diagnosis; however, malaria cannot be proven to be the sole cause because coagulation studies, repeat parasitological testing, serial vascular assessment, and advanced thrombophilia/vasculitis work-up were limited^[1–10,15–18^].

Delayed presentation likely contributed to irreversible limb loss. Early symptoms of severe pain, swelling, and toe discoloration were compatible with evolving ischemia, but presentation occurred after progression to blistering, tissue necrosis, and established dry gangrene; similar reports emphasize that late recognition of malaria-associated SPG often culminates in major amputation^[1–4,7–10,14^].

Strengths and limitations

The major strength of this report is the documented smear-positive malaria at the rural health center before the onset of bilateral ischemic symptoms, supported by CT angiography, which excluded major arterial occlusion, and by echocardiography, which characterized the coexisting rheumatic heart disease. The main limitations are the absence of malaria species confirmation, repeat parasitemia testing, PT/PTT/INR, D-dimer, and advanced thrombophilia or vasculitis testing. Therefore, the report supports malaria as the most likely trigger in a susceptible patient, but it does not prove that malaria is the only cause^[1–10,15–19^].

Conclusion

We report a rare case of bilateral ascending dry gangrene developing shortly after documented smear-positive malaria in a patient with multivalvular rheumatic heart disease and normal CT angiography findings. The presentation is most consistent with malaria-associated symmetrical peripheral gangrene or microvascular ischemia, with rheumatic heart disease and delayed presentation likely contributing to the severity. In malaria-endemic settings, new distal pain, discoloration, or ischemic changes after malaria should prompt urgent evaluation and referral. Early recognition may reduce delays, but advanced presentations may still culminate in major amputations.

Ethical approval

The study was approved by the institutional Research Review Committee. Patient confidentiality was maintained throughout data collection and manuscript preparation.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review from the Editor-in-Chief of this journal on request.

Sources of funding

No funding was received for this work.

Author contributions

T.D.: writing – original draft, review and editing; B.H.: writing – original draft, review and editing; H.T.: writing – original draft, review & editing; D.C.: writing – original draft and review & editing; J.M.V.U.: review and editing.

Conflicts of interest disclosure

The authors declare no conflict of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Tilahun Deresse.

Provenance and peer review

Not commissioned; externally peer reviewed.

Data availability statement

All data generated or analyzed during this study are included in this published article. No additional datasets were generated or analyzed.

AI assistance statement

No artificial intelligence tools were used in patient care, clinical decision-making, diagnosis, or treatment. AI-assisted language editing was used during manuscript revision. The authors critically reviewed, verified, and approved all content and take full responsibility for the final manuscript.