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Pathology Leading to Amputation

Original Editor - Maria Abela  as part of the World Physiotherapy Network for Amputee Rehabilitation Project

Top Contributors - Admin, Aicha Benyaich, Tarina van der Stockt, Rachael Lowe, Stacy Schiurring, Kim Jackson, Tony Lowe, Sheik Abdul Khadir, Wanda van Niekerk, Lauren Lopez, 127.0.0.1, Jess Bell and Khloud Shreif  

Introduction

Limb loss arises from a limited number of underlying pathological processes, most commonly: vascular disease, diabetes mellitus, trauma, infection, malignancy, and congenital limb deficiency. Establishing accurate global figures is difficult, since amputation-specific surveillance is inconsistent between countries and often absent altogether in low-resource settings where survival to the point of needing amputation is itself uncertain.[1]

The most robust current estimate comes from the 2019 Global Burden of Disease (GBD) study, which found that the global incidence of traumatic amputation rose from 11.37 million in 1990 to 13.23 million in 2019, with prevalence rising from 370.25 million to 552.45 million (a 49.2% increase) over the same period. This large prevalence figure is driven predominantly by digit (finger) amputations. Unilateral lower limb amputation is far less common but causes the greatest disability burden of any amputation type, accounting for 1.60 million years lived with disability (YLDs) globally. "YLD" is a standard epidemiological measure of the healthy life lost to a given condition, calculated by weighting the number of people affected by the severity of disability the condition causes. Notably, while the incidence of traumatic amputation correlates with a country's level of socio-demographic development, the disability burden it produces does not. This indicates that the functional impact of lower limb loss is consistently significant worldwide, regardless of setting.[2]

Non-traumatic (dysvascular) causes remain the leading driver of amputation in high-income countries. Peripheral vascular disease is the single most common cause of limb loss overall,[3] and dysvascular amputation now occurs at a rate roughly eight times that of the second leading cause, trauma-related amputation.[4]

Multi-limb loss was historically attributed mainly to trauma, cancer, and congenital anomaly. However dysvascular disease, driven by diabetes and peripheral arterial disease, has become an increasingly significant contributor. This reflects a broader shift seen across non-traumatic lower limb amputation generally: diabetic foot disease and peripheral vascular disease now dominate as causes in many healthcare systems, and this population skews toward older adults carrying a substantial comorbidity burden, with chronic kidney disease and heart failure among the strongest predictors of poor outcomes.[5]

This Physiopedia page will overview the major pathological pathways to amputation, and discuss the specific considerations relevant to amputation in children, including congenital limb deficiency.

Peripheral Vascular Disease

Peripheral vascular disease (also known as peripheral artery disease, PAD, or lower extremity occlusive disease) affects the arterial and venous systems distal to the chest and abdomen, supplying the arms, hands, legs, and feet.

Quick mention for the upper limb: The great majority of PAD-related content in this section, and PAD-related amputation generally, concerns the lower limb, reflecting where the disease overwhelmingly presents clinically. Atherosclerotic PAD can affect the upper limb (most often the subclavian, axillary, or brachial arteries), but it is considerably less common than lower limb disease, since the upper limb's richer network of collateral vessels around the shoulder girdle provides better compensation for a narrowing artery.[6] A blood pressure difference of more than 15mmHg between the two arms is a recognised clinical pointer toward subclavian artery disease.[7] Non-traumatic upper limb acute limb ischaemia follows the same emergency principles described below for the lower limb, but occurs at only around one-fifth the incidence.[8]

It is best understood as a manifestation of systemic atherosclerosis and atherothrombotic disease; meaning it is a local expression of a whole-body process, rather than a condition confined to the leg itself. This distinction matters clinically. For example, a patient presenting with leg symptoms from PAD has the same underlying arterial disease that could also be narrowing the coronary or cerebral arteries, which is why PAD is treated as a marker of overall cardiovascular risk, not just a local limb problem.[9][10]

Please see this Physiopedia Page to learn more about the peripheral vascular system.

Example of physiological changes in blood vessels caused by PVD.
The illustration shows how PVD can affect arteries in the legs.


Atherosclerosis affects multiple arterial beds, including coronary and peripheral circulation, which is why PAD is considered a form of cardiovascular disease rather than an isolated limb condition. Onset is typically gradual and frequently asymptomatic despite significant underlying pathology. In PAD, fatty deposits (atheromas) accumulate within arterial walls, progressively narrowing the arterial lumen and restricting distal blood flow.[10][11]

Clinical Pearl: Atherosclerosis vs Arteriosclerosis

These terms are often used interchangeably, but they describe different processes with different clinical implications for assessment.

Atherosclerosis is fatty plaque narrowing an otherwise normal vessel wall, which is the process underlying PAD. Arteriosclerosis is a distinct, age-related process in which the elastic tissue and muscle within the vessel wall itself degenerate and are replaced by fibrous tissue, with calcium deposition making the vessel stiffer and less compliant (ie. "hardening of the arteries").

Why this matters in practice: a patient can have both processes at once, and arterial calcification from arteriosclerosis is the main reason an older or diabetic patient can produce a falsely elevated ABI reading (>1.40) despite significant underlying PAD, ie. the calcified vessel resists compression by the blood pressure cuff, masking the true clinical picture. Therefore a measured "normal" ABI or a palpable pulse should not be taken as reassurance in this population without considering whether calcification could be obscuring the result.

Symptom: Intermittent (Arterial) Claudication

PAD affecting the lower limb arteries causes a mismatch between blood supply and demand. At rest, blood flow is typically adequate despite the arterial narrowing; walking increases the muscles' metabolic demand, and the narrowed vessels can not increase supply to match. This produces cramping muscle pain that comes on reproducibly with activity (particularly walking uphill or at an increased pace) and resolves within a few minutes of rest. This pattern is called intermittent (arterial) claudication, and it's the characteristic early presentation of PAD.[12]

As PAD progresses and arterial narrowing becomes more severe, this supply-demand mismatch can persist even at rest, producing pain without exertion (pain at rest) and eventually tissue damage in the form of non-healing wounds, ulceration, or gangrene. This tissue damage is the pathway by which PAD can lead to amputation.[12]

Clinical Pearl: Three Types of Claudication

"Claudication" simply means exertional pain that limits walking; but it has three distinct underlying causes, and telling them apart matters for both diagnosis and management.

  • Intermittent (arterial) claudication: caused by PAD. Reproducible calf, thigh, or buttock cramping brought on by walking a consistent distance, relieved simply by stopping and standing still; no need to sit or change position.[12] These terms are not two different conditions, rather they are two ways of describing the same one. "Intermittent" refers to the characteristic on/off pattern of the pain (ie. provoked by exertion, relieved by rest), while "arterial" (or "vascular") names the underlying cause: reduced blood flow from PAD. You will see both terms used interchangeably, and sometimes combined as "intermittent vascular claudication" in clinical literature and patient notes.
  • Neurogenic claudication: caused by lumbar spinal stenosis compressing nerve roots. Symptoms worsen with standing and spinal extension, and are relieved by flexion by either sitting down or bending forward (eg. leaning on a shopping trolley) rather than by simply stopping.
  • Venous claudication: a less common but important third type, arising from chronic venous outflow obstruction (most often post-thrombotic syndrome after an iliofemoral DVT). It typically causes a bursting or tight cramping pain, often thigh-dominant, with a slower build-up during exercise than the arterial type. Critically, relief takes considerably longer, 15 to 20 minutes or more, and requires rest combined with leg elevation. A history of prior DVT, and visibly prominent superficial veins or a sensation of swelling during the episode, are useful pointers toward this cause.

Because all three can present as reproducible exertional leg pain, a focused history is often the fastest way to narrow the differential before further vascular or spinal investigation.


The following short video explains the difference between the three types of claudication. Intermittent claudication is discussed first.

[13]

Vascular Investigations for the Ischaemic Limb

Several investigations are used to establish the presence and severity of lower limb ischaemia: pulse examination and measurement of the Ankle-Brachial Index (ABI).

Clinical Pearl: what's the ABI?

The Ankle-Brachial Index (or ABI, also known as the Ankle Brachial Pressure Index or ABPI) is the ratio of systolic blood pressure at the ankle to systolic blood pressure at the arm. It is quick, non-invasive assessment that can be performed at the bedside with a handheld Doppler, making it the most widely used first-line test for confirming and grading PAD severity.[14]

Why this matters in practice: A low ABI is also an independent marker of broader cardiovascular risk, not just limb-specific disease, so the result can prompt onward referral even when the patient's presenting complaint is unrelated to their legs. For rehabilitation professionals, it is a useful objective baseline: it can help clarify whether reduced exercise tolerance or leg pain is vascular in origin, and inform how aggressively to progress load-bearing activity.

Toe-Brachial Index (TBI) is an alternative to the ABI. It is calculated the same way as ABI, but using the systolic pressure at the great toe instead of the ankle (measured with a small toe cuff and photoplethysmography rather than a standard Doppler, since toe arteries are too small for that technique). Toe arteries are far less prone to the medial calcification that distorts ABI readings, so TBI remains reliable even when ABI is falsely elevated or non-compressible.[15] A TBI below roughly 0.7 is considered abnormal and indicates significant arterial insufficiency.[16]

Table 1.0: American College of Cardiology / American Heart Association and European Society for Vascular Surgery ABI classification guidelines[17][18]
ABI value Interpretation
1.00–1.40 Normal
0.91–0.99 Borderline
≤ 0.90 Abnormal — consistent with PAD
> 1.40 Non-compressible / calcified vessel


While a high ABI might intuitively read as reassuring, a result above 1.40 actually warrants caution. It usually reflects arterial calcification rather than genuinely healthy circulation, producing a falsely elevated reading and should prompt a toe-brachial index instead. This is a clinically important point for rehabilitation professionals reviewing vascular status in diabetic patients, since a calcified-vessel result can easily be mistaken for good perfusion.

Where pressure-based tests like the ABI and TBI indicate the presence and severity of PAD, imaging investigations can directly visualise the affected vessels. These procedures are useful for surgical planning or when a more precise anatomical picture is needed:

  1. Angiography: uses contrast injected into the bloodstream, combined with X-ray, CT, or MRI imaging, to directly visualise the arteries and pinpoint the exact location and severity of blockages. CT and MR angiography (CTA/MRA) are non-invasive and now typically used first; traditional catheter angiography is invasive (a catheter is threaded into the artery, usually via the groin) but carries the advantage of being able to treat a blockage in the same procedure it's diagnosed in, which is why it's now generally reserved for cases proceeding straight to intervention (such as angioplasty or stenting) rather than diagnosis alone.[19]
  2. Ultrasonic imaging (including Duplex and colour Doppler scanning: a well-established, non-invasive method for investigating lower limb vascular disease, and typically the first-choice investigation for arterial stenosis, occlusion, and venous incompetence. It can localise and grade the severity of narrowing and identify which of multiple stenoses is contributing most to restricted flow.[20]

Surgical options for the ischaemic limb include:

  1. Angioplasty/stenting: a balloon catheter is inserted and inflated at the site of stenosis or occlusion, often with stent placement.
  2. Bypass grafting: a graft is used to route blood flow around a diseased segment of vessel.

These represent two different approaches: angioplasty/stenting works within the existing artery to reopen it, while bypass grafting creates an entirely new pathway around the blocked segment.

Acute Limb Ischaemia

Acute limb ischaemia is a distinct pathway to amputation from the chronic progressive narrowing seen in PAD, and warrants separate recognition because it is a vascular emergency. Acute limb ischemia is considered an emergency because it involves a sudden reduction in limb perfusion that threatens limb viability within hours rather than years.[21] The two principal causes are arterial embolism (commonly cardiac in origin, such as from atrial fibrillation) and in-situ arterial thrombosis, typically at a site of pre-existing atherosclerotic plaque; less commonly, acute limb ischaemi results from popliteal aneurysm thrombosis, arterial trauma, or graft occlusion.[21][22] Estimates of the relative contribution of embolism versus thrombosis vary between studies, but both are common mechanisms, alongside a smaller proportion of cases from graft or stent thrombosis and trauma.[22]

Severity is graded clinically using the Rutherford classification, which distinguishes a viable limb from one with threatened or irreversible ischaemia; this distinction determines whether revascularisation (via thrombolysis, thrombectomy, or open surgery) or primary amputation is the appropriate course, since a limb with established irreversible ischaemia is not salvageable and delay risks systemic complications including hyperkalaemia and death.[21] Even with prompt treatment, acute limb ischaemi carries substantial risk: contemporary series report in-hospital amputation rates in the region of 6–8%, rising to around 11% at one year, alongside hospital mortality of roughly 6–9%.[21][23] For rehabilitation professionals, the key distinguishing feature from chronic PAD-related amputation is the acuity and the correspondingly compressed timeframe for both medical decision-making and, where amputation does occur, the patient's psychological adjustment.

Smoking

Smoking is an independent, modifiable risk factor for lower limb amputation, acting through both local and systemic effects on wound healing rather than through any single disease pathway; it actually compounds risk in PVD, diabetic ulceration, and post-traumatic or post-surgical healing alike. Nicotine is a vasoconstrictor, reducing cutaneous blood flow and worsening tissue ischaemia, while also increasing platelet adhesiveness and thereby raising the risk of thrombotic microvascular occlusion, which further compounds tissue ischaemia.[24] Buerger's disease, a peripheral arterial occlusive condition strongly associated with smoking and most prevalent in men under 50, accounts for a small proportion of major upper and lower limb amputations.[25]

Diabetes Mellitus and Diabetic Ulcers

Diabetes is a major, independent contributor to amputation risk: people with diabetes face around a ten-fold higher risk of amputation than the general population,[18] diabetes is a coexisting condition in around three-quarters of dysvascular amputations, and roughly half of these patients go on to have a contralateral limb amputation within two to three years.[5] This elevated risk arises through two distinct but interacting physiological pathways. First, diabetes accelerates the macrovascular disease process, worsening atherosclerosis and peripheral arterial disease. Second, and just as importantly, chronic hyperglycaemia drives a specific microvascular and metabolic process that leads directly to nerve damage and potentially to foot ulcer formation.

Type 2 diabetes (DM2) accounts for the majority of diabetes-related amputations simply due to its far greater prevalence, but type 1 diabetes (DM1) carries its own, and per some evidence disproportionate, amputation risk. A large US inpatient study found that patients with DM1 were independently more likely to present with chronic limb-threatening ischaemia and ulceration, and to undergo amputation, than those with DM2 once hospitalised with peripheral arterial disease. This is plausibly explained by disease duration: DM1 is typically diagnosed at a much younger age, so by any given point in adulthood a person with type 1 has often accumulated more cumulative years of hyperglycaemic exposure. Duration of diabetes is itself one of the strongest known drivers of neuropathy and vascular complications.[26]

Please read this Physiopedia Page to learn more about DM1 and DM2.

Diabetic foot ulcer

The metabolic pathway from hyperglycaemia to ulceration. Persistently high blood glucose overwhelms nerve cells' normal glucose processing, forcing excess glucose down an alternative pathway (ie. the polyol pathway) that produces sorbitol and fructose. As these sugars build up, they impair the nerve's ability to conduct signals normally and increase oxidative stress within the cell. Together, this causes progressive nerve injury.[27]

This single mechanism explains why diabetic neuropathy typically affects motor, sensory, and autonomic nerve function all at once.

  • Motor involvement disrupts the balance between the intrinsic foot muscles' flexors and extensors, producing structural deformities such as claw toe or hammer toe. These create new, abnormal pressure points on the foot that are prone to skin breakdown under normal weight-bearing.
  • Sensory loss means minor trauma to the foot frequently goes unnoticed. Wounds that would normally prompt a person to change their behaviour instead progress unchecked, particularly under repetitive pressure or shear forces during walking.
  • Autonomic involvement reduces sweat and oil gland function, leaving the skin dry and prone to fissuring — creating a further point of entry for infection.

The combined effect of these three deficits is why diabetic patients face up to a 25% lifetime risk of developing a foot ulcer,[28] and why foot ulceration precedes an estimated 84% of diabetes-related lower limb amputations.[29] This metabolic-to-mechanical chain is the single most important target for amputation prevention in this population, which is why diabetic foot ulceration is best managed through a multidisciplinary approach encompassing structured foot care, glycaemic control, and ongoing monitoring for complications.[28]

Diabetic Charcot foot deformity

Charcot neuroarthropathy (also called neuropathic osteoarthropathy or Charcot foot) is a distinct diabetic complication that rehabilitation professionals should be able to recognise separately from straightforward ulceration, since it follows a different mechanical pathway and is frequently missed or misdiagnosed. It arises from a combination of peripheral neuropathy, repetitive unrecognised microtrauma, and neurovascular dysregulation that produce progressive bone and joint destruction, most often in the midfoot.[30][31] Onset is often insidious, presenting as a painless, warm, swollen foot that may be mistaken for cellulitis, gout, or osteomyelitis.[32]

The clinical significance for amputation risk is considerable. Charcot neuroarthropathy increases the risk of foot ulceration by up to 30%, and once present, multiplies amputation risk by a factor of roughly 7–12, affecting an estimated 25% of patients with the condition.[33] Outcomes are correspondingly serious: five-year mortality following diagnosis is around 30%, comparable to or worse than several malignancies, reflecting the burden of comorbidity in this population rather than the joint pathology itself.[33][34] Early recognition and prompt multidisciplinary referral are central to preventing progression to ulceration and amputation.[32]

Quick mention for the upper limb: The ulceration-to-amputation pathway described above is genuinely lower-limb-dominant, since it depends on the combination of insensate skin and repetitive weight-bearing pressure that has no direct upper limb equivalent. Diabetes does cause recognised upper limb musculoskeletal complications, most notably diabetic cheiroarthropathy (limited joint mobility of the hand, affecting a substantial proportion of patients with longstanding type 1 diabetes), but these are contracture and stiffness disorders rather than an ulceration or ischaemic pathway, and are not a recognised route to amputation in the way diabetic foot disease is.[35]

Trauma

Amputation may be needed immediately at the time of injury when the limb is too severely damaged to save. Alternatively, it may be delayed either because an initial attempt at reconstruction has failed to heal, or because, after assessment, reconstruction is judged likely to leave the patient with worse function than a well-fitted prosthesis would. Traumatic mechanisms include compound fracture, major vessel rupture, severe burns, blast injury, penetrating trauma, crush injury, and cold injury. Even minor trauma can precipitate amputation in a patient with diabetes. Population density and natural disasters, particularly earthquakes, are also recognised contributors to amputation incidence.[4]

Global burden of disease data identify the leading causes of amputation worldwide as: falls (36.2%), road traffic injury (15.7%), other transportation injury (11.2%), and mechanical forces (10.4%).[2] Trauma remains the dominant cause of amputation in many low- and middle-income countries, while PVD and diabetes now predominate in higher-income settings.[36]

Conflict-related amputation is a significant and growing global contributor, ranking among the top five causes of disability from traumatic amputation.[2] Casualty data during active conflict are rarely centralised, so estimates should be treated as indicative. Independent estimates for cumulative Ukrainian amputee numbers since 2022 range from the tens of thousands into six figures; clinicians and humanitarian organisations describe limb loss as one of the conflict's defining injury patterns, at a scale unseen in Europe since the First World War.[37][38] A similar pattern followed the Iraq and Afghanistan conflicts, where blast injury produced a substantial cohort of multi-limb amputees among service personnel, often with concurrent traumatic brain injury and PTSD.[39]

Landmines and explosive remnants of war caused 6,279 casualties globally in 2024, the highest in four years, with civilians accounting for 90% and children nearly half.[40] Victim-activated improvised mines were the leading mechanism, and casualties from factory-made antipersonnel mines have tripled since 2020, with rising contamination in Ukraine, Myanmar, and Syria.[40][41]

Frostbite is classified as either a traumatic or vascular cause of amputation depending on regional convention.[4]

Infections

Systemic bacterial infection can necessitate amputation both as definitive treatment and as a life-saving measure, particularly in previously healthy individuals. Relevant infections include meningococcal meningitis and septicaemia, staphylococcal and MRSA infection, and necrotising fasciitis. Amputation rates from infection are thought to be higher in lower-resource settings, plausibly reflecting reduced access to antibiotics and timely surgical care. Infection following joint replacement or other orthopaedic or vascular surgery is a further recognised cause.[4]

Tumours

Bone- and cartilage-forming malignancies (osteosarcoma and chondrosarcoma) are rare but clinically aggressive, often requiring extensive local or systemic treatment. Chondrosarcoma currently has no effective treatment beyond surgery, whereas osteosarcoma shows an approximately 50–80% response rate to adjuvant chemotherapy. Limb salvage surgery is now the predominant surgical approach, with amputation reserved for a smaller subset of cases; local recurrence risk is a key factor affecting prognosis relative to the primary tumour.[42] Amputation as a treatment for cancer is uncommon overall and has become less frequent as early detection has improved, and multiple amputations for malignancy are rare.[39]

Other Recognised Causes

The conditions above account for the substantial majority of amputations, but several less common pathways are worth recognising, since each presents differently and can otherwise be misattributed to a more familiar cause.

Condition Mechanism Clinical relevance to amputation
Sepsis-induced symmetrical peripheral gangrene(also termed purpura fulminans)[43][44]
  • Disseminated intravascular coagulation triggers microvascular thrombosis, typically in a symmetrical, acral distribution affecting distal limbs
  • Most often associated with severe bacterial sepsis (classically pneumococcal or meningococcal), though it also occurs after surgery or with malignancy
  • A rare but severe complication with mortality up to 25–40%
  • Among survivors, roughly half require amputation, and multi-limb amputation is common
Vasopressor-associated peripheral ischaemia[45]
  • High-dose vasopressor therapy during septic shock can cause intense peripheral vasoconstriction, contributing to (though not proven to independently cause) the same symmetrical gangrene process
  • This is an increasingly recognised iatrogenic contributor in ICU survivors
  • Case series describe patients requiring amputation of two or more limbs following prolonged vasopressor use in critical illness
Vasculitis and connective tissue disease

(eg. systemic sclerosis, ANCA-associated vasculitis)[46][47][48]

  • Chronic vascular inflammation and structural change (intimal proliferation, vasospasm, and thrombosis) compromise the digital and, less commonly, more proximal arterial supply
  • Raynaud's phenomenon is present in over 90% of systemic sclerosis patients and is a marker of the underlying vasculopathy
  • Distinct from Buerger's disease (thromboangiitis obliterans), which is itself classified as a vasculitis but is specifically smoking-associated rather than autoimmune
  • Digital ischaemia and ulceration are common in systemic sclerosis; amputation is a recognised, if less frequent, outcome in severe or overlap disease
  • Thromboangiitis obliterans carries a substantial amputation risk in its own right, reported at over a quarter of affected patients in some series
Hair-thread tourniquet syndrome[49]
  • A hair or fine thread wraps tightly around a digit (occasionally the genitalia), most often in infants aged around two weeks to six months
  • Soft-tissue swelling progressively tightens the constriction, producing a compartment-syndrome-like ischaemic injury
  • An easily missed cause of unexplained digit swelling or erythema in an otherwise well infant
  • Delayed recognition can progress to tissue necrosis and autoamputation, or surgical amputation of the digit
Tight casts, splints, or circumferential dressings
  • Post-injury or post-surgical swelling beneath a rigid or tightly applied covering is not anticipated, or the covering is not loosened or split in time, producing a compartment-syndrome-like ischaemic injury distal to the constriction
  • A recognised, largely preventable iatrogenic cause
  • Underpins standard practice around splitting casts and close post-application neurovascular monitoring
Tourniquet misapplication

(surgical, first-aid, or military)

  • A pneumatic or improvised tourniquet applied for haemorrhage control or intraoperative field exposure is left in place beyond a safe time window, or applied with excessive pressure, causing sustained arterial occlusion
  • Rare in modern practice given standardised time limits and monitoring protocols, but a recognised cause of limb loss where evacuation or transport delays prolong application
  • Particularly documented in military and battlefield medicine literature
Constricting rings or jewellery
  • A ring or band becomes acutely tight around a digit, most often due to unanticipated soft-tissue swelling from trauma, infection, or allergic reaction, and is not removed in time
  • Usually managed successfully as an emergency (ring-cutting)
  • Amputation is a rare but reported outcome of delayed presentation

The last four causes above are collectively termed acquired constriction, distinct from the congenital constriction band syndrome discussed later on this page (see Congenital Limb Deficiency). Reliable population-level incidence data is not available for acquired constriction as a group; these are reported almost exclusively via individual case reports, small case series, and narrative reviews rather than epidemiological studies.

Amputations in Children

Paediatric limb loss falls into two categories: acquired amputation and congenital limb deficiency.[50]

Acquired Amputation

Acquired amputation in children results from severe infection, cancer, trauma, or vascular/neural abnormality; including cases where a congenital abnormality is later treated by conversion amputation. Surgical, rehabilitative, and prosthetic management broadly mirrors adult practice, with the important caveat that the child is still growing. Trauma is[51] around three times more likely to cause amputation in children than other biological causes, most often related to power tools, vehicle collisions, lawnmowers, fireworks, farm equipment, or gunshot injury.[50]

Tumours. Bone malignancies such as Ewing sarcoma and osteosarcoma account for a small proportion of paediatric cancers overall, but treatment advances have substantially improved prognosis in recent decades. As survival has improved, an increasing number of childhood cancer survivors are living with the long-term physical and psychological consequences of limb loss.[51]

Emerging Risk: Youth-Onset DM2. Type 2 diabetes diagnosed in childhood or adolescence is not a traditional cause of paediatric amputation, but it represents a genuinely emerging risk pathway that rehabilitation professionals working with young adults should be aware of. Youth-onset DM2 has risen sharply in incidence in parallel with rising childhood obesity, and follows a more aggressive disease course than either adult-onset DM2 or DM1, with faster deterioration in insulin secretion and typically poorer glycaemic control.[52][53] Major vascular complications (eg. dialysis, blindness, and amputation) have been shown to begin emerging within roughly 10 to 13 years of diagnosis, meaning some patients face these outcomes while still in their twenties.[53][54] This shifts the relevant clinical population for diabetes-related amputation prevention younger than has traditionally been assumed, with direct implications for when structured foot care and vascular monitoring should begin.

Congenital Limb Deficiency

Congenital limb deficiency has a reported incidence of around 32 per 100,000 live births for lower-limb-specific deficiency, though estimates for congenital limb deficiency overall range more widely (roughly 20 to 70 per 100,000 births).[55] Multiple-limb involvement is possible but rare.[39] Where a residual limb requires surgical preparation for prosthetic use and weight-bearing, this is assessed on an individual basis.[50]

Recognised causes include teratogenic drug exposure (historically illustrated by thalidomide) and genetic/familial factors; recurrence risk rises substantially where a previous child was affected, particularly in combination with other congenital abnormalities or a family history of limb deficiency.[4]

A further recognised cause is constriction band syndrome (also termed amniotic band syndrome, or amniotic band sequence), in which fibrous strands from a ruptured amnion entangle a developing limb in utero. Where a band constricts tightly enough to compromise distal blood flow, this can result in anything from a shallow constriction ring to complete spontaneous intrauterine amputation of a digit or limb. Reported incidence varies considerably across studies, ranging from approximately 1 in 1,200 to 1 in 15,000 live births.[56][57] Unlike teratogenic exposure or genetic/familial causes, constriction band syndrome arises through a mechanical and vascular disruption of an otherwise normally developing limb, rather than a primary developmental abnormality. This distinction is clinically relevant, since it also means constriction band syndrome does not carry the same recurrence risk in future pregnancies as the genetic/familial causes above.

For congenital lower-limb deficiencies such as congenital fibular deficiency, the long-term treatment goal is to support development into an active adulthood with optimal function and minimal musculoskeletal pain. Surgical options include limb salvage or lengthening versus amputation, aimed at achieving equal limb length and a normal gait pattern, with or without a prosthesis.[58] Early amputation can achieve good functional outcomes, but the decision is individualised, depending on surgical judgement and informed parental understanding of the risks and benefits involved.[59]

This following optional video provided detailed information about paediatric limb deficiencies.

[60]

Resources

References

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  2. ↑ 2.0 2.1 2.2 Yuan B, Hu D, Gu S, Xiao S, Song F. The global burden of traumatic amputation in 204 countries and territories. Frontiers in public health. 2023 Oct 20;11:1258853.
  3. ↑ Stewart CP, Jain AS. Cause of death of lower limb amputees. Prosthetics and orthotics international. 1992 Aug;16(2):129-32.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Barbara Engstrom and Catherine Van de Ven. Therapy for Amputees, 3rd ed. Churchill Livingstone; 1999. ISBN: 978-0-443-05975-9.
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  14. ↑ McClary KN, Massey P. Ankle Brachial Index. InStatPearls [internet] 2023 January 16. StatPearls publishing.
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  18. ↑ Nordanstig J, Behrendt CA, Baumgartner I, Belch J, Bäck M, Fitridge R, Hinchliffe R, Lejay A, Mills JL, Rother U, Sigvant B. European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Asymptomatic Lower Limb Peripheral Arterial Disease and Intermittent Claudication 5.
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  21. ↑ 21.0 21.1 21.2 21.3 Björck M, Earnshaw JJ, Acosta S, Gonçalves FB, Cochennec F, Debus ES, Hinchliffe R, Jongkind V, Koelemay MJ, Menyhei G, Svetlikov AV. Editor's choice–European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of acute limb ischaemia. European Journal of Vascular and Endovascular Surgery. 2020 Feb 1;59(2):173-218.
  22. ↑ 22.0 22.1 Elgendy IY. Acute Limb Ischemia Interventions. Peripheral Vascular Disease and Interventions, An Issue of Interventional Cardiology Clinics: Peripheral Vascular Disease and Interventions, An Issue of Interventional Cardiology Clinics, E-Book. 2025 Mar 11;14(2):273.
  23. ↑ Baril DT, Ghosh K, Rosen AB. Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population. Journal of vascular surgery. 2014 Sep 1;60(3):669-77.
  24. ↑ Hampton S, Collins F. Tissue Viability. John Wiley & Sons; 2006 Jun 14.
  25. ↑ Barbara Engstrom and Catherine Van de Ven, 1999, Therapy for Amputees, 3rd Edition, Churchill Livingston ISBN: 978-0-443-05975-9
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  27. ↑ Clayton,W. and Elasy, T.A. (2009). A Review of Pathophysiology, Classification, and Treatment of Foot Ulcers in Diabetic Patients. Clinical Diabetes, Vol 27, no 2, pp 52-58.
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  29. ↑ Reiber GE, Vileikyte LO, Boyko ED, Del Aguila M, Smith DG, Lavery LA, Boulton AJ. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes care. 1999 Jan 1;22(1):157-62.
  30. ↑ Rajbhandari S, Jenkins RD, Davies C, Tesfaye S. Charcot neuroarthropathy in diabetes mellitus. Diabetologia. 2002 Aug;45(8):1085-96.
  31. ↑ Trieb K. The Charcot foot: pathophysiology, diagnosis and classification. The bone & joint journal. 2016 Sep 1;98(9):1155-9.
  32. ↑ 32.0 32.1 Bagheri K, Anastasio AT, Krez A, Siewny L, Adams SB. Charcot neuroarthropathy of the foot and ankle in the acute setting: an illustrative case report and targeted review. Western Journal of Emergency Medicine. 2023 Aug 30;24(5):921.
  33. ↑ 33.0 33.1 Cellier N. Management of hindfoot and ankle in Charcot arthropathy. EFORT Open Reviews. 2025 Jun 1;10(6):327-35.
  34. ↑ Stergioti A, Manganas K, Tzeravini E, Kosta O, Eleftheriadou I, Tentolouris A. Charcot neuro-osteoarthropathy in diabetes: implications for diabetic foot ulcers, amputations, and survival. The International Journal of Lower Extremity Wounds. 2025 Dec;24(4):781-8.
  35. ↑ Abdalla E, Gamar AM, Taha ZI, Alfatih M. Diabetic cheiroarthropathy in uncontrolled type 2 diabetes with positive anti-nuclear antibodies: a case report from Sudan. Annals of Medicine and Surgery. 2024 Mar 21;86(6):3631.
  36. ↑ Wei B, Zhang J, Cheng Y, Wu H. Global, regional and national burden of traumatic amputations from 1990 to 2021: a systematic analysis of the Global Burden of Disease study 2021. Frontiers in Public Health. 2025 Jun 2;13:1583523.
  37. ↑ Sullivan D. The War Wounded: A Doctor Reports 62 Miles From Ukraine's Front Lines. Think Global Health, 2025. Available at: https://www.thinkglobalhealth.org/article/the-war-wounded-a-doctor-reports-62-miles-from-ukraines-front-lines (last accessed 20 August 2026).
  38. ↑ Hope for Ukraine. Ukraine Amputation Crisis: Tens of Thousands Need Care. 2025. Available at: https://hfu.org/ukraine-amputation-crisis-rehabilitation-shortage/ (last accessed 28 August 2026).
  39. ↑ 39.0 39.1 39.2 Pasquina PF, Miller M, Carvalho AJ, Corcoran M, Vandersea J, Johnson E, Chen YT. Special considerations for multiple limb amputation. Current physical medicine and rehabilitation reports. 2014 Dec;2(4):273-89..
  40. ↑ 40.0 40.1 International Campaign to Ban Landmines – Cluster Munition Coalition. Landmine Monitor 2025. Available at: https://icblcmc.org/our-impact/landmine-monitor-2025-civilian-landmine-casualties-escalate-while-five-countries-take-dangerous-step-away-from-humanitarian-mine-ban (last accessed: 28 August 2026).
  41. ↑ The HALO Trust. Landmine Monitor 2025. Available at: https://www.halotrust.org/news/landmine-monitor-2025/ (last accessed 28 August 2026).
  42. ↑ Rozeman LB, Cleton-Jansen AM, Hogendoorn PC. Pathology of primary malignant bone and cartilage tumours. International orthopaedics. 2006 Dec;30(6):437-44.
  43. ↑ Davis MD, Dy KM, Nelson S. Presentation and outcome of purpura fulminans associated with peripheral gangrene in 12 patients at Mayo Clinic. Journal of the American Academy of Dermatology. 2007 Dec 1;57(6):944-56.
  44. ↑ Chen Y, Liu K, Xu X, Wu G, Zhu L, Zha J, Cheng C. Symmetrical peripheral gangrene caused by urosepsis: Case reports and literature review. Medicine. 2024 Oct 4;103(40):e39508.
  45. ↑ Ang CH, Koo OT, Howe TS. Four limb amputations due to peripheral gangrene from inotrope use–case report and review of the literature. International journal of surgery case reports. 2015 Jan 1;14:63-5.
  46. ↑ Schiopu E, Impens AJ, Phillips K. Digital ischemia in scleroderma spectrum of diseases. International journal of rheumatology. 2010;2010(1):923743.
  47. ↑ Önaloğlu Y, Gümüş ÖF, Karakılıç B, Özlük AV, Balcı EC, Talmaç MA, Civan M. Predictors of Reamputation in Patients With Advanced‐Stage Thromboangiitis Obliterans Ulcers: A Retrospective Cohort Study. International Wound Journal. 2026 Feb;23(2):e70853.
  48. ↑ Herrick AL, Oogarah PK, Freemont AJ, Marcuson R, Haeney M, Jayson MI. Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation. Annals of the rheumatic diseases. 1994 May;53(5):323-6.
  49. ↑ Arkoubi AY, Salati SA. Hair-thread tourniquet syndrome: a comprehensive review. Cureus. 2024 May 22;16(5).
  50. ↑ 50.0 50.1 50.2 Smith DG. Congenital limb deficiencies and acquired amputations in childhood, part 3. Motion. 2006;16(1):41-5.
  51. ↑ 51.0 51.1 Loucas CA, Brand SR, Bedoya SZ, Muriel AC, Wiener L. Preparing youth with cancer for amputation: A systematic review. Journal of psychosocial oncology. 2017 Jul 4;35(4):483-93.
  52. ↑ Lim LL, Jones S, Cikomola JC, Hivert MF, Misra S. Understanding the drivers and consequences of early-onset type 2 diabetes. The Lancet. 2025 Jun 28;405(10497):2327-40.
  53. ↑ 53.0 53.1 TODAY Study Group. Long-term complications in youth-onset type 2 diabetes. New England Journal of Medicine. 2021 Jul 29;385(5):416-26.
  54. ↑ Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes care. 2014 Feb 1;37(2):436-43.
  55. ↑ Congenital Lower Limb Deficiency. PM&R KnowledgeNow. Available at: https://now.aapmr.org/congenital-lower-limb-deficiency/ (last accessed: 28 August 2026).
  56. ↑ Pape K, Gorla SR. Amniotic Band Syndrome. InStatPearls [internet] 2025 July 7. StatPearls publishing.
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  58. ↑ Kaastad TS, Tveter AT, Steen H, Holm I. Physical function and health-related quality of life in young adults with unilateral congenital lower-limb deficiencies. Journal of children's orthopaedics. 2017 Oct;11(5):348-57.
  59. ↑ Calder P, Shaw S, Roberts A, Tennant S, Sedki I, Hanspal R, Eastwood D. A comparison of functional outcome between amputation and extension prosthesis in the treatment of congenital absence of the fibula with severe limb deformity. Journal of Children's Orthopaedics. 2017 Aug;11(4):318-25.
  60. ↑ YouTube. Limb Deficiencies | Global HELP Organization. Available from: https://www.youtube.com/watch?v=pUFSKYt-ACE [last accessed 28 August 2026]


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