Leprosy (Hansen Disease)

Overview

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 357

Etiology & Pathogenesis

• M. leprae is an obligate intracellular pathogen - it cannot be cultured in vitro
• Replicates optimally at 32-34°C (temperature of human skin and superficial tissues), which explains why the CNS and vital organs are usually spared
• Transmission: mainly via respiratory droplet/secretion from untreated patients; rare zoonotic transmission from armadillos
• Virulence is determined by cell wall lipid PGL-1, which enables invasion of host cells
• M. leprae inhibits mitochondrial energy metabolism to evade immunity
• Similar enough to M. tuberculosis that BCG vaccination confers partial protection
• The spectrum of disease is determined by the host's T-helper lymphocyte response

Classification

Ridley-Jopling Spectrum

WHO Operational Classification

• Goldman-Cecil Medicine, Table 301-1

Clinical Features

Tuberculoid Leprosy (TT/BT)

• 1-3 skin lesions, well-defined erythematous plaques with raised edges sloping inward
• Surface is dry, scaly, hairless, and anesthetic (loss of sensation is hallmark)
• Asymmetric large peripheral nerve involvement dominates - nerves become enclosed in granulomatous reactions
• Nerve degeneration causes anesthesia, muscle atrophy, and susceptibility to trauma
• Contractures, paralyses, and autoamputation of digits can ensue
• Facial nerve involvement - eyelid paralysis, keratitis, corneal ulceration
• Histology: granulomas resembling tuberculosis; bacilli almost never found (paucibacillary)
• Strong Th1/Th17 response with IL-2, IFN-γ production

Lepromatous Leprosy (LL/BL)

• Symmetric widespread skin thickening and nodules
• Involves: skin, peripheral nerves, anterior eye chamber, upper airways (to larynx), testes, hands, and feet
• Macular, papular, or nodular lesions on face, ears, wrists, elbows, knees
• With progression: nodules coalesce to yield leonine facies
• Sensory loss in typical stocking-and-glove distribution
• Nasal involvement in up to 40%: crusting, bleeding, septal perforation, anosmia
• Testes extensively involved: destruction of seminiferous tubules, sterility, gynecomastia
• Peripheral nerves (ulnar, peroneal) symmetrically invaded with minimal inflammation
• Histology: lepra cells - large aggregates of lipid-laden macrophages filled with masses ("globi") of acid-fast bacilli (multibacillary)
• Weak Th1, relative increase in Th2/Tregs: poor bacterial control

Borderline (BB)

• Most clinically unstable form
• Annular skin lesions with "punched-out" inner edge and ill-defined outer edge

Histopathology

Lepra Reactions (Immunologic Complications)

Type 1 Reaction (Reversal Reaction - RR)

• Delayed hypersensitivity reaction; sudden alteration of cell-mediated immunity
• Mostly in borderline disease (~30% of borderline patients)
• Represents a shift toward the tuberculoid pole (enhanced CMI)
• Existing skin patches become erythematous, swollen, tender
• Rapid, painful swelling of peripheral nerves (acute neuritis); nerve abscesses possible
• Edema of extremities and face

Type 2 Reaction (Erythema Nodosum Leprosum - ENL)

• Immune complex (Ag-Ab) mediated reaction
• Occurs in lepromatous (LL) and borderline lepromatous (BL) disease (~50% LL, ~25% BL patients)
• Presents with red, evanescent, painful skin nodules; systemic features (fever, constitutional symptoms)
• Elevated CRP and acute-phase reactants; may cause acute neuritis
• Can cause vasculitis and glomerulonephritis through immune complex deposition
• Goldman-Cecil Medicine, pp. 3275-3276

Diagnosis

1. Slit-skin smear - most simple and valuable test; used to count and grade acid-fast bacilli (Bacteriologic Index 0 to 6+); Morphologic Index assesses viability (solid = live; granular/fragmented = dead)
2. Skin biopsy - confirms diagnosis and type; identifies reactions
3. Fine needle aspiration cytology - useful in neuritic leprosy
4. Clinical diagnosis is standard in endemic settings
5. M. leprae cannot be cultured in vitro - no in-vitro culture test available

Treatment: WHO Multidrug Therapy (MDT)

• Rifampicin: highly bactericidal; given monthly (as opposed to daily dapsone/clofazimine)
• Dapsone: bacteriostatic; daily; dapsone-resistance drove the move from monotherapy to MDT in the 1970s
• Clofazimine: bacteriostatic + anti-inflammatory; well-tolerated

• Type 1 (RR): oral corticosteroids
• Type 2 (ENL): thalidomide (drug of choice where available) or corticosteroids
• Goldman-Cecil Medicine, Table 301-3; Fitzpatrick's Dermatology; Goodman & Gilman's

Complications & Deformities

• Peripheral neuropathy (glove and stocking sensory loss)
• Claw hand, foot drop (ulnar, peroneal nerve palsy)
• Plantar ulcers from repeated painless trauma
• Facial disfigurement (leonine facies, nasal collapse)
• Blindness (corneal anesthesia, lagophthalmos, uveitis)
• Testicular destruction and infertility
• Amyloidosis in long-standing disease

Special Notes

• Pregnancy: cell-mediated immunity is suppressed during pregnancy, so leprosy becomes more active; relapse and reactivation can occur despite MDT; some drugs may be contraindicated
• Animals: nine-banded armadillos are the only known natural reservoir besides humans (relevant in the southern United States)
• Most patients die with leprosy rather than of it, given its extremely slow course spanning decades

Recent Evidence (PubMed, 2024-2026)

• A 2024 systematic review on leprosy immunopathogenesis (PMID 39308868) updates the immune mechanisms underlying the tuberculoid-lepromatous spectrum
• A 2024 systematic review on self-healing in leprosy (PMID 39264863) examines spontaneous resolution
• A 2026 systematic review on corticosteroid adverse effects in leprosy reactions management (PMID 41886473) is particularly relevant for treating Type 1 and Type 2 reactions safely

Hemiplegia

Definition

• Adams and Victor's Principles of Neurology, 12th Ed.

Anatomy: The Corticospinal Pathway

Note: attribution of a capsular hemiplegia solely to the pyramidal tract is not entirely correct - in the internal capsule, corticospinal fibers are intermingled with corticostriate, corticothalamic, corticorubral, corticopontine, and corticoreticular fibers. The term "upper motor neuron (UMN) paralysis" is more accurate.

• Adams and Victor's Principles of Neurology

Upper Motor Neuron (UMN) Features

1. Spasticity - velocity-dependent increase in muscle tone (due to corticoreticulospinal pathway involvement)
2. Hyperreflexia - exaggerated deep tendon reflexes
3. Extensor plantar response (Babinski sign) - upgoing toe on plantar stimulation
4. Clonus - rhythmic involuntary contractions, especially at ankle
5. No significant muscle atrophy (disuse atrophy only; no denervation atrophy)
6. Weakness in a pyramidal distribution - extensors weaker in arms, flexors weaker in legs
7. Preservation of bilaterally-innervated movements - eyes, jaw, upper face, pharynx, larynx, diaphragm, abdomen spared (bilateral cortical innervation)

Important: Acute lesions (hyperacute stroke, spinal shock) initially present as flaccid paralysis with absent reflexes - spasticity and hyperreflexia develop over days to weeks.

• Adams and Victor's Principles of Neurology; Bradley and Daroff's Neurology

Causes of Hemiplegia

By Frequency (Adams and Victor's)

1. Ischemic and hemorrhagic cerebrovascular disease - exceeds all others; most common cause
2. Trauma (brain contusion, epidural hematoma, subdural hemorrhage) - second most common
3. Brain tumors (primary or metastatic)
4. Demyelinating disease (Multiple Sclerosis)
5. Brain abscess
6. Vascular complications of meningitis/encephalitis
7. Migraine (hemiplegic migraine, migrainous infarction)
8. Functional/psychogenic (conversion disorder, malingering)

Additional Causes by Setting

• Lacunar infarct (posterior limb of internal capsule or base of pons) - pure motor hemiplegia
• Alternating hemiplegia of childhood - rare; ATP1A3 mutation; attacks before age 18 months
• Todd (postictal) paralysis - transient, contralateral to seizure focus; lasts minutes to 36 hours
• Ictal paralysis - weakness during the seizure discharge itself (rare)
• Hemiplegic migraine (familial) - CACNA1A, ATP1A2, SCN1A mutations

Localization Clues: Crossed Brainstem Syndromes

Rule of thumb: cranial nerve palsies on the same side as the lesion with limb weakness on the opposite side = brainstem localization.

• Adams and Victor's; Localization in Clinical Neurology, 8e

Pure Motor Hemiplegia (Lacunar Stroke)

• Complete contralateral hemiplegia (face, arm, leg equally affected)
• No cortical signs (no aphasia, no neglect, no visual field defect)
• No sensory loss

• Adams and Victor's Principles of Neurology

Cortical vs. Capsular vs. Brainstem Localization

• Bradley and Daroff's Neurology in Clinical Practice

Differential Diagnosis: Mimics of Hemiplegia

Migraine vs. TIA vs. Seizure

Psychogenic (Functional) Hemiplegia

• Give-way weakness (strength varies with effort/coaching)
• Inconsistencies on exam (e.g., unable to dorsiflex foot but can walk on heels)
• Hoover sign - patient supine: if a leg is truly paralyzed, the opposite heel should press down as the patient tries to lift it; absence of this downward pressure = Hoover sign positive for functional weakness
• Paralysis with normal tone and reflexes
• Obvious secondary gain
• Bradley and Daroff's Neurology

Special Patterns

Brown-Séquard Syndrome (Spinal Cord)

• Lesion in cervical spinal cord
• Ipsilateral hemiplegia + loss of vibration/proprioception
• Contralateral loss of pain and temperature
• Face spared

Infantile Hemiplegia

• Developmental failure of affected limbs/skeleton on the hemiplegic side
• Usually from ischemic necrosis in utero or perinatally
• Does not occur if paralysis develops after puberty

Alternating Hemiplegia of Childhood

• Attacks of unilateral weakness before 18 months; may alternate sides
• Associated dyskinesias, oculomotor abnormalities (nystagmus)
• Deficits accumulate over years; linked to ATP1A3 mutations

Complications of Established Hemiplegia

• Spastic equinovarus deformity (foot drop)
• Shoulder subluxation and hemiplegic shoulder pain (common post-stroke)
• Deep vein thrombosis from immobility
• Pressure ulcers
• Depression and cognitive impairment
• Contractures from prolonged spasticity
• In childhood onset: limb length discrepancy, scoliosis

Rehabilitation

• A 2025 network meta-analysis (PMID 41204516) found that combined rehabilitation approaches (e.g., task-oriented training + neurostimulation) outperform single modalities for upper extremity function and ADLs in hemiplegic stroke patients
• A 2025 systematic review and meta-analysis (PMID 40022760) found virtual reality therapy significantly improves upper limb motor impairments post-stroke
• A 2025 systematic review (PMID 39745590) supports repetitive transcranial magnetic stimulation (rTMS) for hemiplegic shoulder pain

• Physiotherapy (task-oriented training, constraint-induced movement therapy)
• Occupational therapy (ADL retraining, splinting)
• Spasticity management (baclofen, botulinum toxin, tizanidine)
• Speech therapy (if associated aphasia/dysarthria)
• Virtual reality and robot-assisted therapy (emerging evidence)

Peripheral Neuritis (Peripheral Neuropathy)

Terminology

Anatomy & Fiber Types

• Harrison's Principles of Internal Medicine 22E

Pathological Mechanisms

1. Wallerian Degeneration

• Follows focal nerve injury (compression, laceration, ischemia)
• Distal axon and myelin break down after axonal interruption
• EMG: loss of voluntary motor unit activity; CMAP amplitude falls from day 2, nadir by day 5-6
• SNAP loss delayed by 2-3 days further (nadir at day 10-11)
• Chromatolysis occurs in the cell body
• Regeneration from proximal stump at 2-3 mm/day; often incomplete
• Recovery depends on preservation of Schwann cell basal lamina tube

2. Axonal Degeneration ("Dying-Back" / Length-Dependent Polyneuropathy)

• The most common pathological reaction in peripheral nerve
• Distal axonal breakdown from metabolic derangement or vascular compromise (ischemia)
• Begins at the distal end of the nerve and works proximally
• Causes: systemic metabolic disorders (diabetes, uremia), toxins, vasculitis, inherited neuropathies
• Clinical result: symmetric distal sensory and motor loss, stocking-and-glove pattern; distal areflexia; distal muscle atrophy

3. Demyelinating Neuropathy (Myelinopathy)

• Primary damage to Schwann cells and myelin sheaths
• Nerve conduction velocity markedly slowed
• Causes: GBS, CIDP, CMT type I, leprosy, diphtheria
• Remyelination produces onion-bulb formation (seen histologically)
• Conduction block possible with focal demyelination

4. Neuronopathy / Ganglionopathy

• Damage to the cell body of the neuron (dorsal root ganglion for sensory; anterior horn for motor)
• Non-length-dependent; may affect arms > legs or asymmetrically
• Causes: paraneoplastic (anti-Hu), cisplatin, pyridoxine (B6) toxicity, Sjögren syndrome, HIV
• Bradley and Daroff's Neurology in Clinical Practice; Robbins Cotran & Kumar Pathologic Basis of Disease

Etiology - Classification

• Robbins & Kumar Basic Pathology; Textbook of Family Medicine 9e

Clinical Patterns (Harrison's 10-Pattern Classification)

• Harrison's Principles of Internal Medicine 22E

Key Specific Neuropathies

Diabetic Peripheral Neuropathy

• Most common cause of peripheral neuropathy globally
• Up to 80% of patients with DM >15 years have evidence of neuropathy
• Distal symmetric sensorimotor polyneuropathy: commonest form; sensory axons > motor axons; paresthesias, numbness; features of both axonal and demyelinating injury
• Autonomic neuropathy: orthostatic hypotension, bowel/bladder/sexual dysfunction
• Lumbosacral radiculopathy (diabetic amyotrophy): asymmetric pain, weakness, atrophy
• Pathogenesis: AGE accumulation, reactive oxygen species, microvascular changes, altered axonal metabolism
• Treatment: strict glycemic control is the best therapy

Guillain-Barré Syndrome (GBS)

• Rapidly progressive acute demyelinating polyneuropathy
• Ascending weakness; progresses over ~2 weeks, nadir by 4 weeks
• One of the most common life-threatening peripheral nerve diseases
• ~2/3 triggered by preceding infection: Campylobacter jejuni, EBV, CMV, Zika virus
• Mechanism: molecular mimicry - microbial antigens cross-react with nerve sheath antigens
• Treatment: IV immunoglobulin (IVIg) or plasmapheresis; ventilatory support if needed

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Chronic (>8 weeks) acquired demyelinating polyneuropathy
• Symmetric proximal + distal weakness; sensory involvement
• Treatment: IVIg, corticosteroids, plasmapheresis

Alcoholic Peripheral Neuropathy

• Combination of direct toxic effect of ethanol + thiamine (B1) deficiency
• Distal symmetric, predominantly sensory; painful paresthesias common
• Stocking-and-glove distribution

Thiamine Deficiency (Beriberi/Peripheral Neuritis)

• "Dry beriberi" - symmetric peripheral neuropathy of motor and sensory systems, diminished reflexes
• "Wet beriberi" - adds high-output heart failure and edema
• Wernicke encephalopathy (acute) and Korsakoff psychosis (chronic) are CNS manifestations
• Harrison's Principles of Internal Medicine; Harper's Illustrated Biochemistry

Charcot-Marie-Tooth Disease (CMT)

• Most common hereditary peripheral neuropathy
• CMT1 (demyelinating): presents 1st-3rd decade; foot drop, high arches, "inverted champagne bottle legs"; slowed NCV (20-25 m/s); onion bulbs on biopsy
  • CMT1A: most common (70%) - chromosome 17p duplication, PMP-22 gene triplication
  • CMT1B: MPZ (myelin protein zero) mutation
• CMT2 (axonal): presents 2nd decade; normal or near-normal NCVs
• No disease-modifying therapy; supportive and rehabilitative management

Investigations

1. Nerve Conduction Studies (NCS) / Electromyography (EMG)
   • Axonal neuropathy: reduced CMAP and SNAP amplitudes; normal or mildly reduced NCV
   • Demyelinating neuropathy: markedly slow NCV; conduction block; prolonged distal latencies
   • EMG: fibrillation potentials, reduced recruitment (axonal loss); normal or mild changes (demyelinating)
2. Blood tests: FBS/HbA1c, renal function, LFTs, B12, thiamine, TSH, serum/urine protein electrophoresis, ANA, ANCA, anti-Ro/La (Sjögren), paraneoplastic antibodies (anti-Hu), heavy metals
3. Nerve biopsy (sural nerve): for vasculitis, amyloidosis, leprosy, CIDP; axonal loss vs. demyelination; onion bulbs (CMT1)
4. Skin biopsy (punch biopsy): intraepidermal nerve fiber density - used for small fiber neuropathy
5. Genetic testing: for suspected CMT and other hereditary neuropathies
6. Lumbar puncture: GBS - albuminocytologic dissociation (high protein, normal cell count)

Symptoms & Signs

• Numbness, tingling, paresthesias (pins and needles)
• Burning pain (especially small fiber neuropathy)
• Loss of proprioception and vibration (large fiber)
• Positive Romberg sign; sensory ataxia

• Distal weakness (foot drop, wrist drop)
• Muscle atrophy (distal)
• Loss of deep tendon reflexes (areflexia/hyporeflexia) - particularly ankle jerks first

• Orthostatic hypotension
• Anhidrosis or hyperhidrosis
• Gastroparesis, constipation, diarrhea
• Urinary retention or incontinence
• Erectile dysfunction

Treatment

Treat the Underlying Cause

• Diabetes: strict glycemic control
• Nutritional: replace thiamine, B12, B6 as appropriate
• Toxic: remove offending drug or toxin
• GBS/CIDP: IVIg or plasmapheresis
• Vasculitis: immunosuppression (corticosteroids, cyclophosphamide)
• Leprosy: WHO multidrug therapy (rifampicin, dapsone, clofazimine)

Neuropathic Pain Management

• Pregabalin and duloxetine - FDA approved for diabetic peripheral neuropathy pain
• Gabapentin - widely used, effective
• Tricyclic antidepressants (amitriptyline, nortriptyline)
• SNRIs (venlafaxine)
• Tramadol - effective in two multicenter trials; use if refractory to first-line
• Opioids - only in consultation with pain specialist
• NSAIDs are generally not effective for neuropathic pain
• Topical capsaicin - possibly effective

Rehabilitative Care

• Foot care education (especially in diabetes)
• Podiatry referral for structural foot abnormalities
• Orthotic devices (ankle-foot orthoses for foot drop)
• Physical and occupational therapy
• Screening for peripheral arterial disease (ankle-brachial index)
• Symptom to Diagnosis, 4th Ed.; Harrison's Principles of Internal Medicine 22E

Recent Evidence (PubMed 2024-2026)

• A 2025 Lancet Neurology systematic review and meta-analysis (PMID 40252663) provides updated evidence comparing pharmacotherapy and non-invasive neuromodulation (TMS, tDCS, TENS) for neuropathic pain - both approaches have efficacy, supporting their combination
• The first-line pharmacological agents (gabapentinoids, SNRIs, TCAs) remain consistent with prior guidelines

Buerger's Disease (Thromboangiitis Obliterans - TAO)

Definition

• Schwartz's Principles of Surgery 11e; Robbins & Kumar Basic Pathology

Epidemiology

• Predominantly affects young male smokers (age 20-50 years, typically onset before 40-45 years)
• Women now account for nearly 20% of cases, likely reflecting increased tobacco use among women
• Worldwide distribution: highest prevalence in Eastern Europe, Mediterranean, and Asian countries
• Incidence in the US: ~20 per 100,000; accounts for <1% of severe limb ischemia cases in North America
• In young adults with lower limb ischemia at the Mayo Clinic (1953-1981), Buerger's disease was diagnosed in 24%

Pathogenesis

• Tobacco (cigarettes, cigars, smokeless/chewing tobacco, snuff) - all forms are implicated
• Endothelial dysfunction: reduced endothelium-dependent vasodilation + release of prothrombotic substances
• Direct endothelial cell toxicity from tobacco components
• Immune/hypersensitivity response: most patients are hypersensitive to tobacco extracts; tobacco antigens may modify vessel wall components and trigger an immune response
• Genetic predisposition: association with certain HLA haplotypes

Key point: Unlike atherosclerosis, there is no association with diabetes, hyperlipidemia, or hypertension (these are exclusion criteria).

• Robbins & Kumar Basic Pathology

Pathology / Morphology

• Sharply segmental acute and chronic vasculitis of small- and medium-sized vessels
• Luminal thrombosis with a mixed inflammatory infiltrate
• Small microabscesses (sterile), occasionally rimmed by granulomatous inflammation within the thrombus
• Polymorphonuclear leukocyte aggregation and multinucleated giant cells

• Decrease in hypercellularity
• Recanalization of the vessel lumen
• Inflammation extends into adjacent veins and nerves (this extension into nerves is rare in other vasculitides and explains the severe pain)
• End-stage: organized thrombus + blood vessel fibrosis; artery and adjacent structures encased in fibrous tissue

• Schwartz's Principles of Surgery 11e; Robbins & Kumar Basic Pathology

Clinical Features

Symptoms in order of progression:

Key clinical hallmarks:

1. Instep/foot claudication - pain in the arch of the foot on exertion (caused by infrapopliteal arterial occlusion) - distinguishes TAO from atherosclerotic PAD (which typically causes calf claudication)
2. Superficial migratory thrombophlebitis (phlebitis migrans) - painful tender nodules over peripheral veins; occurs in up to 16% and indicates systemic inflammatory response; often an early feature
3. Raynaud phenomenon - triphasic color response (white-blue-red) to cold in ~50% of patients
4. Intense rubor of the affected extremity, especially with dependency
5. Foot pulses absent in the presence of normal femoral and popliteal pulses
6. Severe rest pain (due to neural involvement - the extension of inflammation into adjacent nerves is unique to TAO)
7. Upper extremity: digital arteries more involved than radial or ulnar arteries; fingertip ulcers

Diagnostic Criteria (Clinical)

1. Age < 45-50 years at onset
2. History of tobacco use (essential)
3. Distal extremity ischemia in two or more limbs
4. Angiographic findings suggestive of TAO
5. Absence of atherosclerotic risk factors other than smoking (no DM, no hyperlipidemia, no hypertension, no hypercoagulable state)

Investigations

Laboratory (to exclude other diagnoses):

• CBC with differential, BMP, LFTs, fasting glucose, urinalysis
• ESR, CRP (usually normal or mildly elevated in TAO)
• Hypercoagulability screen + antiphospholipid antibodies
• ANA, rheumatoid factor, complement, anti-Scl-70, anti-centromere (CREST)
• All expected to be negative/normal in true TAO

Vascular studies:

• Ankle-brachial index (ABI) - reduced; segmental pressures; arterial waveform analysis
• Allen test - positive in a young smoker with distal upper limb ischemia is suggestive
• Echocardiography + CT/MR angiography - to exclude proximal embolic sources

Angiography (gold standard imaging):

• Disease confined to the distal circulation (infrapopliteal; distal to brachial artery in upper limb)
• Segmental occlusions with "skip" lesions
• "Corkscrew" collaterals - pathognomonic appearance of extensive collateralization
• No atherosclerotic changes (smooth vessel wall between lesions)
• All four limbs should be imaged even if only one is symptomatic

Biopsy:

• Rarely necessary; reserved for atypical presentations
• The only means of definitive diagnosis
• Shows the characteristic segmental inflammatory thrombosis with microabscesses

Differential Diagnosis

Treatment

First-line and Only Definitive Treatment: Complete Tobacco Cessation

• Patients who quit: benign clinical course, disease remission, impressive amputation avoidance
• Patients who continue smoking: 67% limb loss vs 35% in those who quit
• No disease progression with tissue loss after tobacco discontinuation (Oregon Health Sciences Center experience)
• Established arterial occlusions do not reverse after cessation, but further progression is halted

Medical Therapy (adjunctive):

Surgical Options:

Key surgical limitation: The distal nature of the disease means there is often no acceptable target vessel for bypass. Autogenous vein conduits are also limited due to coexisting migratory thrombophlebitis damaging the veins.

• 31% limb loss over 15 years reported even with surgical management (Mayo series)

• Current Surgical Therapy 14e; Schwartz's Principles of Surgery 11e; Rosen's Emergency Medicine

Prognosis

• Patients who completely abstain from tobacco: disease arrests, excellent prognosis, most avoid amputation
• Patients who continue smoking: relentless progression with alternating exacerbations, severe rest pain, tissue loss, and eventual amputation
• Rare large-vessel involvement (coronary, cerebral, mesenteric arteries) carries poor prognosis - mesenteric TAO warrants prompt surgery for bowel ischemia

Recent Evidence (PubMed 2024-2026)

• A 2025 systematic review and meta-analysis (PMID 39847853) on treatment options for Buerger's disease confirms that smoking cessation remains the cornerstone, with prostanoids (iloprost) showing the best evidence for limb salvage among medical therapies
• A 2026 systematic review and meta-analysis (PMID 41887323) comparing open surgical vs. endovascular revascularization in TAO with chronic limb-threatening ischemia found that neither approach shows clear superiority, reinforcing that smoking cessation is the primary determinant of outcomes
• A 2024 Mendelian randomization study (PMID 38788766) identified causal relationships between specific circulating inflammatory proteins and TAO, supporting the immune/inflammatory pathogenesis hypothesis