Neuro-Behcet's Disease¶

VERSION: 1.1 CREATED: February 2, 2026 REVISED: February 2, 2026 STATUS: Revised per checker/rebuilder pipeline (v1.1)

DIAGNOSIS: Neuro-Behcet's Disease

ICD-10: M35.2 (Behcet's disease), G09 (Sequelae of inflammatory diseases of central nervous system), I67.89 (Other cerebrovascular disease), I67.6 (Nonpyogenic thrombosis of intracranial venous system), G04.81 (Other encephalitis and encephalomyelitis)

CPT CODES: 70553 (MRI brain with/without contrast), 70551 (MRI brain without contrast), 72156 (MRI cervical spine with/without contrast), 72157 (MRI thoracic spine with/without contrast), 89050 (CSF cell count), 89051 (CSF differential), 84157 (CSF protein), 86235 (HLA typing), 85025 (CBC), 80053 (CMP), 85652 (ESR), 86140 (CRP), 36475 (venography), 70496 (CTA head), 70544 (MRA head without contrast), 70549 (MRA head with/without contrast), 95816 (EEG), 93000 (ECG), 95907-95913 (EMG/NCS)

SYNONYMS: Neuro-Behcet's disease, Neuro-Behcet disease, neurological Behcet's disease, Behcet's disease with neurological involvement, NBD, CNS Behcet's disease, cerebral Behcet's, brainstem Behcet's, Behcet neurovasculitis, Adamantiades-Behcet disease with CNS involvement, Behcet meningoencephalitis, Silk Road disease with neurological features, parenchymal Neuro-Behcet's, non-parenchymal Neuro-Behcet's

SCOPE: Diagnostic workup and management of suspected or confirmed Neuro-Behcet's disease across both parenchymal (brainstem predominant, hemispheric, spinal cord, optic nerve) and non-parenchymal (cerebral venous thrombosis, intracranial hypertension, meningitis) forms. Covers International Study Group (ISG) diagnostic criteria, International Criteria for Behcet's Disease (ICBD), HLA-B51 testing, pathergy test, acute immunotherapy, steroid-sparing agents, and biologic therapies (TNF inhibitors). Settings: ED, HOSP, OPD, ICU. For isolated mucocutaneous or ocular Behcet's disease without neurological involvement, defer to rheumatology/dermatology/ophthalmology. For other CNS vasculitides (e.g., PACNS, giant cell arteritis, neurosarcoidosis), use respective templates.

DEFINITIONS: - Parenchymal Neuro-Behcet's (pNBD): CNS parenchymal involvement, most commonly brainstem (diencephalic-brainstem junction), hemispheric white matter, or spinal cord; accounts for ~75-80% of NBD - Non-parenchymal Neuro-Behcet's (npNBD): Cerebral venous sinus thrombosis (CVT), intracranial hypertension, or meningitis without parenchymal lesions; accounts for ~20-25% of NBD - International Study Group (ISG) Criteria for Behcet's Disease (1990): Recurrent oral aphthous ulceration (>3 episodes in 12 months) PLUS at least 2 of: recurrent genital ulceration, eye lesions (uveitis, retinal vasculitis), skin lesions (erythema nodosum, pseudofolliculitis, papulopustular), or positive pathergy test - International Criteria for Behcet's Disease (ICBD, 2014): Point-based system (>=4 points diagnostic): oral aphthosis (2 pts), genital aphthosis (2 pts), ocular lesions (2 pts), skin lesions (1 pt), neurological manifestations (1 pt), vascular manifestations (1 pt), positive pathergy test (1 pt) - Mixed-type NBD:* Concurrent parenchymal and non-parenchymal involvement (rare, ~5%)

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CBC with differential (CPT 85025)	Baseline; infection screen; leukocytosis in active NBD; pre-immunotherapy	Normal; neutrophilia common in active disease	STAT	STAT	ROUTINE	STAT
CMP (BMP + LFTs) (CPT 80053)	Metabolic screen; hepatic function for immunosuppressant dosing; renal function	Normal	STAT	STAT	ROUTINE	STAT
ESR (CPT 85652)	Inflammatory marker; typically elevated in active Behcet's; monitor disease activity	Elevated in active disease	URGENT	ROUTINE	ROUTINE	URGENT
CRP (CPT 86140)	Inflammatory marker; correlates with disease activity; infection screen	Elevated in active disease	URGENT	ROUTINE	ROUTINE	URGENT
Blood glucose (CPT 82947)	Pre-steroid baseline; monitor during high-dose corticosteroid therapy	Normal	STAT	STAT	ROUTINE	STAT
HbA1c (CPT 83036)	Glycemic status before high-dose steroids	<5.7%	-	ROUTINE	ROUTINE	-
PT/INR, aPTT (CPT 85610+85730)	Coagulation status for LP; CVT workup; baseline for anticoagulation	Normal; prolonged aPTT prompts antiphospholipid screen	STAT	STAT	-	STAT
D-dimer (CPT 85379)	Elevated in CVT (non-parenchymal NBD); limited sensitivity/specificity but useful if negative	Normal (<0.5 mg/L); elevated supports CVT workup	STAT	STAT	-	STAT
Procalcitonin (CPT 84145)	Distinguish bacterial infection from autoimmune inflammation	Normal (<0.1 ng/mL)	URGENT	URGENT	-	URGENT
Blood cultures (x2 sets) (CPT 87040)	Rule out infection (endocarditis, bacteremia) before immunosuppression	No growth	STAT	STAT	-	STAT
Urinalysis with culture (CPT 81003+87086)	Infection screen; renal involvement	Negative	STAT	STAT	ROUTINE	STAT
Magnesium (CPT 83735)	Seizure threshold; metabolic screen	Normal	STAT	STAT	ROUTINE	STAT
Phosphorus (CPT 84100)	Metabolic screen	Normal	STAT	STAT	ROUTINE	STAT
TSH (CPT 84443)	Thyroid screen; autoimmune comorbidity	Normal	URGENT	ROUTINE	ROUTINE	URGENT
LDH (CPT 83615)	General marker; lymphoma screening	Normal	URGENT	ROUTINE	ROUTINE	URGENT

1B. Extended Workup (Second-line)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
HLA-B51 typing (CPT 86235)	Present in 50-70% of Behcet's patients (especially along Silk Road populations); supports diagnosis but not diagnostic alone; negative does not exclude	Positive supports diagnosis	-	ROUTINE	ROUTINE	-
Pathergy test (skin prick)	Positive in 40-60% of Behcet's (higher in Middle Eastern/Asian populations); needle prick causes papule/pustule >=2mm at 24-48h; part of ISG and ICBD criteria	Positive (>=2mm papule/pustule at 24-48h)	-	ROUTINE	ROUTINE	-
ANA (CPT 86235)	Lupus/vasculitis screen; SLE can mimic NBD	Negative or low titer (typically negative in Behcet's)	URGENT	ROUTINE	ROUTINE	URGENT
Anti-dsDNA (CPT 86225)	SLE exclusion if ANA positive; CNS lupus differential	Negative	-	ROUTINE	ROUTINE	-
ANCA (c-ANCA/PR3, p-ANCA/MPO) (CPT 86235)	GPA/MPA exclusion; CNS vasculitis differential	Negative	-	ROUTINE	ROUTINE	-
Anti-SSA/SSB (Ro/La)	Sjogren syndrome with CNS involvement exclusion	Negative	-	ROUTINE	ROUTINE	-
Antiphospholipid antibody panel (lupus anticoagulant, anti-cardiolipin, anti-beta2 glycoprotein) (CPT 86235+86147+86146)	Antiphospholipid syndrome as cause of CVT; thrombophilia screen for non-parenchymal NBD	Negative	-	ROUTINE	ROUTINE	-
Serum ACE level (CPT 82164)	Neurosarcoidosis exclusion (key differential for parenchymal CNS inflammation)	Normal	-	ROUTINE	ROUTINE	-
RPR/VDRL (CPT 86592)	Neurosyphilis exclusion (CNS vasculitis mimic)	Negative	-	ROUTINE	ROUTINE	-
QuantiFERON-TB Gold or PPD (CPT 86480)	TB exclusion before immunosuppression; TB meningitis differential	Negative	-	URGENT	ROUTINE	URGENT
HIV (CPT 87389)	Immunocompromised screen; aphthous ulcers differential	Negative	-	ROUTINE	ROUTINE	-
Hepatitis B surface antigen + core antibody (CPT 80074)	Reactivation risk before anti-TNF therapy or other immunosuppression	Negative	-	ROUTINE	ROUTINE	-
Hepatitis C antibody (CPT 80074)	Screen before immunosuppression	Negative	-	ROUTINE	ROUTINE	-
Lyme serology (CPT 86618)	Lyme neuroborreliosis as chronic meningitis/cranial neuropathy differential	Negative	-	ROUTINE	ROUTINE	-
Serum protein electrophoresis (SPEP) (CPT 86334)	Polyclonal gammopathy; lymphoproliferative disorder screen	Normal pattern	-	ROUTINE	ROUTINE	-
Quantitative immunoglobulins (IgG, IgA, IgM, IgD) (CPT 82784)	Baseline before immunotherapy; IgD elevation reported in some Behcet's studies	Normal	-	ROUTINE	ROUTINE	-
Thrombophilia panel (Factor V Leiden, prothrombin mutation, protein C/S, antithrombin III) (CPT 85306+85303+85300)	Non-parenchymal NBD with CVT: evaluate additional thrombotic risk factors	Normal	-	ROUTINE	ROUTINE	-
Ferritin (CPT 82728)	Inflammatory marker (acute phase reactant); iron status	Normal or elevated (acute phase)	-	ROUTINE	ROUTINE	-

1C. Rare/Specialized (Refractory or Atypical)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CSF neopterin	Marker of intrathecal immune activation; correlates with NBD disease activity; research use	Elevated supports active NBD	-	EXT	EXT	-
CSF IL-6 level	Elevated in active pNBD; more sensitive than routine CSF markers for disease activity monitoring	Elevated in active parenchymal disease	-	EXT	EXT	-
CSF S100B	Marker of CNS tissue damage; predicts severity in acute pNBD	Elevated in severe parenchymal disease	-	EXT	EXT	-
Anti-neuronal antibody panel	Autoimmune encephalitis exclusion if atypical presentation with cognitive/behavioral features	Negative	-	EXT	EXT	-
Aquaporin-4 (AQP4) antibody (CPT 86255)	NMOSD exclusion if longitudinally extensive myelitis or optic neuritis	Negative	-	EXT	EXT	-
Anti-MOG IgG	MOGAD exclusion if optic neuritis or myelitis	Negative	-	EXT	EXT	-
CSF metagenomics (next-generation sequencing)	Occult CNS infection exclusion when standard testing negative and diagnosis uncertain	No pathogens detected	-	EXT	EXT	-
Genetic testing (IL-10, IL-23R, ERAP1 variants)	Behcet's susceptibility genes; research/refractory cases; guides therapy	Informational	-	-	EXT	-
CSF 14-3-3 / RT-QuIC	Prion disease exclusion if rapidly progressive cognitive decline	Negative	-	EXT	EXT	-

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
CT head without contrast (CPT 70450)	Immediate (ED triage)	Rule out hemorrhage, mass, hydrocephalus; CVT shows hyperdense sinus sign	None significant	STAT	STAT	-	STAT
MRI brain with and without gadolinium (CPT 70553)	Within 24h	Parenchymal NBD: T2/FLAIR hyperintensities in brainstem (midbrain-pons junction extending to diencephalon -- "brainstem-diencephalic" pattern), basal ganglia, internal capsule, hemispheric white matter; enhancement variable; Non-parenchymal NBD: venous sinus thrombosis (absent flow void), dural enhancement	GFR <30; gadolinium allergy; pacemaker	URGENT	URGENT	ROUTINE	URGENT
MRV (MR venography) (CPT 70547)	Within 24h if non-parenchymal NBD or headache with papilledema	Cerebral venous sinus thrombosis (superior sagittal, transverse, sigmoid sinuses); absent flow signal; partial or complete occlusion	MRI contraindications	URGENT	URGENT	ROUTINE	URGENT
CTA head (CPT 70496)	Within 24h if CVT suspected and MRI unavailable	Empty delta sign; venous filling defect	Contrast allergy; renal insufficiency	URGENT	URGENT	-	URGENT
CT venography (CPT 70496)	Alternative if MRV unavailable	Venous sinus filling defects	Contrast allergy; renal insufficiency	URGENT	URGENT	-	URGENT
MRI spine (cervical and thoracic) with and without contrast (CPT 72156+72157)	Within 24-48h if myelopathy suspected	Intramedullary T2 hyperintensity; longitudinally extensive possible; cord enhancement; cervical and thoracic predominance	GFR <30; gadolinium allergy	URGENT	URGENT	ROUTINE	URGENT
Chest X-ray (CPT 71046)	Immediate	Hilar adenopathy (sarcoidosis exclusion); pulmonary infiltrates; pulmonary artery aneurysm (Behcet's vascular involvement)	Pregnancy (relative)	STAT	STAT	ROUTINE	STAT
ECG (12-lead) (CPT 93000)	Immediate	Baseline cardiac assessment; QTc before medications; cardiac Behcet's screening	None	STAT	STAT	ROUTINE	STAT

2B. Extended¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRA head and neck (CPT 70544+70549)	Within 48h	Arterial stenosis/occlusion (rare in NBD but reported); aneurysm; arterial vasculitis assessment	MRI contraindications	-	ROUTINE	ROUTINE	-
CT chest with contrast (CPT 71260)	Within 48h	Pulmonary artery aneurysm (pathognomonic for Behcet's -- Hughes-Stovin syndrome); mediastinal lymphadenopathy; sarcoidosis exclusion	Contrast allergy; renal insufficiency	-	ROUTINE	ROUTINE	-
Ophthalmologic slit lamp examination	Within 24-48h	Anterior uveitis; posterior uveitis (retinal vasculitis); hypopyon; optic disc edema; retinal vein occlusion; Ocular involvement in 50-70% of BD	None	URGENT	URGENT	ROUTINE	URGENT
Fluorescein angiography (retinal)	Within 1-2 weeks	Retinal vasculitis (both arteries and veins); capillary leakage; retinal ischemia; macular edema	Fluorescein allergy	-	ROUTINE	ROUTINE	-
OCT (optical coherence tomography)	Within 1-2 weeks	Retinal nerve fiber layer thinning; macular edema; monitor ocular disease activity	None	-	ROUTINE	ROUTINE	-
EEG (CPT 95816)	Within 48h if seizures or encephalopathy	Focal or generalized slowing; epileptiform discharges; subclinical seizures	None	URGENT	ROUTINE	ROUTINE	URGENT
Doppler ultrasound of extremities	If DVT suspected	Deep venous thrombosis (Behcet's has high thrombotic tendency); superficial thrombophlebitis	None	URGENT	ROUTINE	ROUTINE	-
CT abdomen with contrast	If abdominal vascular involvement suspected	Hepatic vein thrombosis (Budd-Chiari); mesenteric vein thrombosis; IVC thrombosis; aneurysms	Contrast allergy; renal insufficiency	-	ROUTINE	ROUTINE	-
Echocardiogram (CPT 93306)	If cardiac symptoms	Intracardiac thrombus; valvular disease; cardiac Behcet's	None	-	ROUTINE	ROUTINE	URGENT
EMG/NCS (CPT 95907-95913)	Within 1-2 weeks if peripheral neuropathy suspected	Axonal polyneuropathy; mononeuritis multiplex (rare in NBD)	Anticoagulation (relative for needle EMG)	-	ROUTINE	ROUTINE	-
Pulmonary function tests (PFTs) (CPT 94010)	If pulmonary symptoms	Restrictive or obstructive pattern; pulmonary vascular disease assessment	Unable to cooperate	-	ROUTINE	ROUTINE	-

2C. Rare/Specialized¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
Cerebral angiography (DSA) (CPT 36224)	When arterial vasculitis suspected or diagnosis uncertain	Arterial occlusion, stenosis, aneurysm (rare in NBD; more common in PAN, PACNS); normal in most NBD	Coagulopathy; contrast allergy; renal insufficiency	-	EXT	EXT	-
Brain biopsy (stereotactic)	Last resort for atypical parenchymal lesions when diagnosis uncertain	Perivascular lymphocytic infiltration; small vessel vasculitis; neutrophilic infiltration; no granulomas (distinguishes from sarcoidosis)	Coagulopathy; deep lesion location	-	EXT	-	-
Meningeal biopsy	When chronic meningitis of uncertain etiology	Lymphocytic meningeal infiltration; small vessel vasculitis	Coagulopathy; inaccessible location	-	EXT	-	-
FDG-PET/CT (whole body) (CPT 78816)	If occult malignancy or systemic vasculitis evaluation	FDG-avid vascular inflammation; exclude lymphoma; assess disease extent	Uncontrolled diabetes; pregnancy	-	EXT	EXT	-
CT pulmonary angiography (CTPA)	If pulmonary artery aneurysm suspected (Hughes-Stovin syndrome)	Pulmonary artery aneurysm; pulmonary embolism	Contrast allergy; renal insufficiency	-	EXT	EXT	-
Skin biopsy (pathergy site or skin lesion)	When tissue confirmation needed	Neutrophilic vasculitis; perivascular inflammatory infiltrate; supports Behcet's diagnosis	Coagulopathy	-	ROUTINE	ROUTINE	-

LUMBAR PUNCTURE¶

Indication: Essential for suspected Neuro-Behcet's disease; CSF abnormalities support diagnosis and help distinguish parenchymal from non-parenchymal forms; excludes infectious meningitis and other inflammatory CNS diseases. In pNBD: CSF typically shows inflammatory profile. In npNBD with CVT: CSF opening pressure often elevated; cell count is frequently normal.

Timing: URGENT in ED/hospital setting; ROUTINE for outpatient workup. Perform after CT head to rule out mass effect. Use caution with LP in CVT -- elevated ICP is common; perform under controlled conditions.

Volume Required: 15-20 mL (sufficient for comprehensive infectious, inflammatory, and cytology studies)

Study	Rationale	Target Finding	ED	HOSP	OPD	ICU
Opening pressure (CPT 89050)	Elevated ICP common in npNBD (CVT); also elevated in pNBD	10-20 cm H2O normal; often elevated >25 in CVT-type NBD	URGENT	ROUTINE	ROUTINE	-
Cell count with differential (tubes 1 and 4) (CPT 89051)	pNBD: Pleocytosis with mixed cellularity (neutrophils early, then lymphocytes); npNBD: normal or mild pleocytosis	pNBD: WBC 10-200 (early neutrophilic, then lymphocytic); npNBD: often normal	STAT	STAT	ROUTINE	STAT
Protein (CPT 84157)	Elevated in ~75% of pNBD; usually mildly elevated (50-150 mg/dL)	Normal to elevated; pNBD: elevated (50-150 mg/dL); npNBD: normal or mildly elevated	STAT	STAT	ROUTINE	STAT
Glucose with paired serum glucose (CPT 82945)	Usually normal in NBD (distinguishes from TB, fungal, bacterial meningitis); occasionally mildly low	Normal (>40 mg/dL; >60% of serum); low glucose argues against NBD	STAT	STAT	ROUTINE	STAT
Oligoclonal bands (CSF AND paired serum) (CPT 83916)	Intrathecal IgG synthesis; present in ~15-20% of NBD (less common than in MS); helps differentiate	CSF-specific bands present (less common than MS)	URGENT	ROUTINE	ROUTINE	-
IgG index (CPT 83787)	Intrathecal antibody synthesis	Mildly elevated	URGENT	ROUTINE	ROUTINE	-
CSF IL-6	Elevated in active pNBD; the most sensitive CSF marker for active NBD; correlates with disease activity and prognosis	Elevated in active pNBD (>20 pg/mL suggests active disease)	URGENT	ROUTINE	ROUTINE	-
Gram stain and bacterial culture (CPT 87205+87070)	Rule out bacterial meningitis	No organisms	STAT	STAT	ROUTINE	STAT
AFB smear and culture (CPT 87116)	TB meningitis exclusion (critical differential for chronic meningitis)	Negative	URGENT	URGENT	ROUTINE	URGENT
Fungal culture (CPT 87102)	Fungal meningitis exclusion	Negative	URGENT	URGENT	ROUTINE	-
Cryptococcal antigen (CPT 87327)	Cryptococcal meningitis exclusion	Negative	URGENT	URGENT	-	URGENT
CSF VDRL (CPT 86592)	Neurosyphilis exclusion	Negative	-	ROUTINE	ROUTINE	-
Cytology (CPT 88104)	CNS lymphoma/carcinomatous meningitis exclusion	Negative for malignant cells	-	ROUTINE	ROUTINE	-
Flow cytometry (CPT 88184)	CNS lymphoma exclusion	Normal	-	ROUTINE	ROUTINE	-
HSV PCR (CPT 87529)	Viral encephalitis exclusion (brainstem encephalitis differential)	Negative	STAT	STAT	-	STAT
TB PCR (GeneXpert)	Rapid TB meningitis exclusion; critical differential	Negative	URGENT	URGENT	ROUTINE	-
CSF ACE level (CPT 82164)	Neurosarcoidosis exclusion (important differential for pNBD)	Normal	URGENT	ROUTINE	ROUTINE	-

Special Handling: CSF IL-6 requires prompt processing; send AFB and fungal cultures in sufficient volume (minimum 2 mL each). Cytology requires rapid transport (<1 hour). Store extra CSF (frozen at -20C) for future testing. Note opening pressure carefully as it distinguishes pNBD from npNBD.

Contraindications: Elevated ICP without imaging (get CT first); coagulopathy (INR >1.5, platelets <50K); skin infection at LP site; obstructive hydrocephalus with risk of herniation. Use caution in CVT (LP is therapeutic for elevated ICP but risk of herniation exists).

3. TREATMENT¶

3A. Acute/Emergent¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Methylprednisolone	IV	Acute parenchymal NBD (brainstem syndrome, myelopathy, encephalitis, optic neuropathy); acute severe exacerbation	1000 mg :: IV :: daily :: 1000 mg IV daily for 5-10 days; infuse over 1-2 hours; transition to oral prednisone taper	Active untreated infection (especially TB); uncontrolled diabetes; active GI bleeding; psychosis from steroids	Glucose q6h (target <180 mg/dL); BP; mood/sleep; I/O; GI prophylaxis; electrolytes	STAT	STAT	-	STAT
Dexamethasone	IV	Cerebral edema from parenchymal mass-like lesion; acute elevated ICP	10 mg :: IV :: q6h :: 10 mg IV loading dose, then 4 mg IV q6h; taper over days-weeks as clinically improving	Active untreated infection; uncontrolled diabetes	Glucose; BP; neurological status; GI prophylaxis	STAT	STAT	-	STAT
Heparin (unfractionated)	IV	CVT (non-parenchymal NBD); therapeutic anticoagulation for cerebral venous thrombosis -- initiate even with hemorrhagic infarct	80 units/kg :: IV :: bolus then infusion :: 80 units/kg IV bolus, then 18 units/kg/hr continuous infusion; target aPTT 60-80 seconds (1.5-2.5x control)	Active major hemorrhage (relative in CVT with hemorrhagic infarction -- anticoagulation still indicated per guidelines); HIT; severe uncontrolled hypertension	aPTT q6h until therapeutic x 2, then q12-24h; platelet count (HIT screen); CBC; neurological status	STAT	STAT	-	STAT
Enoxaparin (LMWH)	SC	CVT (alternative to UFH); stable non-parenchymal NBD	1 mg/kg :: SC :: q12h :: 1 mg/kg SC every 12 hours; renally adjust if CrCl <30	Severe renal impairment (CrCl <30); active major hemorrhage; HIT	Anti-Xa level (target 0.5-1.0 IU/mL); CBC; renal function; platelet count	-	STAT	ROUTINE	-
Omeprazole	PO	GI protection during high-dose corticosteroid therapy	40 mg :: PO :: daily :: 40 mg PO daily during steroid course and oral taper; IV if NPO	PPI allergy	None routine	URGENT	STAT	ROUTINE	STAT
Insulin sliding scale	SC	Steroid-induced hyperglycemia management	Per protocol :: SC :: PRN :: Per sliding scale if glucose >180 mg/dL; adjust per glucose trends	Hypoglycemia risk	Glucose q6h; adjust per response	URGENT	STAT	-	STAT
Lorazepam	IV	Seizure secondary to cortical/parenchymal NBD	4 mg :: IV :: PRN seizure :: 0.1 mg/kg IV push (max 4 mg/dose); repeat x1 in 5 minutes if seizure persists	Respiratory depression; acute narrow-angle glaucoma	Respiratory status; sedation level; airway patency	STAT	STAT	-	STAT
Mannitol	IV	Acute elevated ICP from large parenchymal lesion or CVT with impending herniation	1 g/kg :: IV :: PRN ICP :: 1 g/kg IV bolus over 15-20 minutes; repeat 0.5 g/kg q6h; maintain serum osmolality <320 mOsm/kg	Anuria; severe dehydration; active intracranial hemorrhage	Serum osmolality q6h; electrolytes; renal function; I/O	STAT	STAT	-	STAT
Hypertonic saline 3%	IV	Acute elevated ICP from CVT or mass-like parenchymal lesion	250 mL :: IV :: PRN ICP :: 250 mL 3% NaCl IV over 15-30 minutes; repeat as needed; target sodium 145-155 mEq/L	Hypernatremia >155 mEq/L; severe CHF	Sodium q2-4h; serum osmolality; central line preferred for concentrations >3%	STAT	STAT	-	STAT
Acetazolamide	PO	Elevated ICP from CVT (adjunct to anticoagulation); intracranial hypertension secondary to NBD	250 mg :: PO :: BID :: Start 250 mg BID; increase to 500 mg BID as needed; max 2000 mg/day	Sulfa allergy; severe renal/hepatic failure; hypokalemia; metabolic acidosis	BMP (potassium, bicarbonate); renal function; paresthesias; kidney stones	-	ROUTINE	ROUTINE	-

Treatment Note: For parenchymal NBD, high-dose IV corticosteroids are the mainstay of acute treatment. For non-parenchymal NBD (CVT), anticoagulation is the primary acute treatment (heparin), with steroids added if significant inflammation is present. Anticoagulation is indicated in CVT-type NBD even with hemorrhagic venous infarction. Do NOT delay treatment if NBD is clinically suspected -- tissue confirmation proceeds in parallel. Exclude TB meningitis before or concurrently with initiating immunosuppression.

3B. Symptomatic Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Gabapentin	PO	Neuropathic pain; central pain from brainstem/spinal cord lesions	300 mg :: PO :: TID :: Start 300 mg qHS; titrate by 300 mg q1-3d; target 900-1800 mg TID; max 3600 mg/day	Renal impairment (adjust dose per CrCl)	Sedation; dizziness; peripheral edema; renal function	-	ROUTINE	ROUTINE	-
Pregabalin	PO	Neuropathic pain; alternative to gabapentin	75 mg :: PO :: BID :: Start 75 mg BID; increase q1wk; max 600 mg/day	Renal impairment (adjust dose); Class V controlled substance	Sedation; weight gain; peripheral edema; renal function	-	ROUTINE	ROUTINE	-
Levetiracetam	IV/PO	Seizures secondary to cortical/parenchymal NBD	500 mg :: IV/PO :: BID :: Start 500 mg BID (IV or PO); increase by 500 mg/day q1-2wk; max 3000 mg/day; transition to PO when tolerated	Renal impairment (adjust dose per CrCl)	Behavioral changes (rage, irritability); suicidality; renal function	STAT	STAT	ROUTINE	STAT
Lacosamide	IV/PO	Seizures; second-line ASM or adjunctive therapy	100 mg :: IV/PO :: BID :: Start 100 mg BID (IV or PO); increase by 50 mg/dose q1wk; max 400 mg/day; transition to PO	Second/third degree AV block; severe hepatic impairment	ECG (PR prolongation); dizziness; cardiac monitoring during IV load	URGENT	URGENT	ROUTINE	URGENT
Baclofen	PO	Spasticity from myelopathy or brainstem involvement	5 mg :: PO :: TID :: Start 5 mg TID; increase by 5 mg/dose q3-5d; max 80 mg/day	Renal impairment; seizure disorder (abrupt withdrawal lowers threshold)	Sedation; weakness; urinary retention; avoid abrupt discontinuation	-	ROUTINE	ROUTINE	-
Colchicine	PO	Recurrent oral/genital ulcers; mucocutaneous Behcet's manifestations (adjunct to CNS treatment)	0.5 mg :: PO :: BID :: 0.5 mg PO BID; adjust for renal/hepatic impairment	Severe renal impairment; concurrent strong CYP3A4 inhibitors; bone marrow suppression	CBC; LFTs; renal function; GI side effects (diarrhea)	-	ROUTINE	ROUTINE	-
Apremilast	PO	Oral ulcers of Behcet's disease (FDA-approved for this indication); adjunct to systemic immunotherapy	30 mg :: PO :: BID :: Titrate over 6 days to 30 mg PO BID; start 10 mg daily day 1, increase per schedule	Severe renal impairment (CrCl <30: reduce dose to 30 mg daily); depression/suicidal ideation	Weight; depression screening; GI side effects (nausea, diarrhea)	-	-	ROUTINE	-
Warfarin	PO	Long-term anticoagulation for CVT in non-parenchymal NBD (transition from heparin)	5 mg :: PO :: daily :: Start 5 mg PO daily; adjust per INR; overlap with heparin minimum 5 days and until INR 2-3 for 24h; duration 3-12 months (indefinite in Behcet's with recurrent thrombosis)	Active major bleeding; pregnancy; severe hepatic disease	INR q1-2 days initially; target INR 2.0-3.0; weekly then monthly once stable; drug interactions	-	ROUTINE	ROUTINE	-
Calcium + Vitamin D (bone protection)	PO	Bone protection during chronic corticosteroid therapy	500 mg :: PO :: BID :: Calcium 500-600 mg PO BID + Vitamin D 800-1000 IU daily	Hypercalcemia; nephrolithiasis	Serum calcium; 25-OH vitamin D; DEXA if steroids >3 months	-	ROUTINE	ROUTINE	-
Duloxetine	PO	Neuropathic pain; comorbid depression	30 mg :: PO :: daily :: Start 30 mg daily x 1 week, then increase to 60 mg daily; max 120 mg/day	Severe hepatic impairment; concurrent MAOIs; uncontrolled narrow-angle glaucoma	BP; hepatic function; serotonin syndrome risk; suicidality monitoring	-	ROUTINE	ROUTINE	-
Modafinil	PO	Fatigue from brainstem/parenchymal NBD involvement; disease-related fatigue	100 mg :: PO :: daily :: Start 100 mg PO every morning; increase to 200 mg daily after 1 week if needed; max 400 mg/day; take in morning to avoid insomnia	Severe hepatic impairment; arrhythmia; mitral valve prolapse with left ventricular hypertrophy	BP; heart rate; sleep quality; psychiatric symptoms; hepatic function	-	ROUTINE	ROUTINE	-
Oxybutynin	PO	Neurogenic bladder (urgency, frequency) from myelopathic NBD	5 mg :: PO :: BID :: Start 5 mg PO BID; increase to 5 mg TID as needed; max 20 mg/day; extended-release 5-30 mg daily available	Uncontrolled narrow-angle glaucoma; urinary retention; GI obstruction; myasthenia gravis	Anticholinergic effects (dry mouth, constipation, confusion); post-void residual; cognitive effects in elderly	-	ROUTINE	ROUTINE	-

Treatment Note: Symptomatic treatment addresses pain, seizures, spasticity, fatigue, bladder dysfunction, and mucocutaneous disease. Anticoagulation duration for CVT in Behcet's is controversial -- many experts recommend indefinite anticoagulation given the high recurrence rate of thrombosis in Behcet's disease. Co-manage mucocutaneous disease as mucocutaneous activity predicts neurological relapse.

3C. Second-line/Steroid-Sparing¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Prednisone	PO	Transition from IV steroids; maintenance corticosteroid therapy for pNBD	60 mg :: PO :: daily :: Start 1 mg/kg/day (max 60 mg) after IV pulse; taper by 10 mg every 2 weeks to 20 mg, then by 5 mg every 2-4 weeks; goal <10 mg daily by 6 months; taper over 6-12+ months	Active infection; uncontrolled diabetes; avascular necrosis; psychosis from steroids	Glucose; BP; weight; mood; bone density (DEXA if >3 months); ophthalmology (cataracts, glaucoma); adrenal function on taper	-	ROUTINE	ROUTINE	-
Azathioprine	PO	First-line steroid-sparing agent for NBD (strongest evidence among conventional immunosuppressants); prevents relapse in parenchymal and non-parenchymal NBD	50 mg :: PO :: daily :: Start 50 mg PO daily; increase by 50 mg every 2 weeks to target 2.5 mg/kg/day; onset of action 2-3 months; continue minimum 2-3 years	TPMT deficiency (check before starting); concurrent allopurinol (reduce dose 75%); pregnancy (relative -- category D but commonly used in Behcet's)	TPMT genotype/activity before starting; CBC q2 weeks x 2 months, then monthly; LFTs monthly; amylase if abdominal pain (pancreatitis)	-	ROUTINE	ROUTINE	-
Mycophenolate mofetil	PO	Steroid-sparing agent; alternative to azathioprine; relapsing NBD	500 mg :: PO :: BID :: Start 500 mg PO BID; increase by 500 mg every 2 weeks; target 1000-1500 mg BID (2000-3000 mg/day total)	Pregnancy (Category D -- teratogenic); active infection; concurrent live vaccines	CBC q2 weeks x 3 months, then monthly; LFTs; GI symptoms (diarrhea, nausea); infection surveillance; pregnancy prevention	-	ROUTINE	ROUTINE	-
Methotrexate	PO	Steroid-sparing agent; refractory mucocutaneous and neurological disease; alternative to azathioprine	10 mg :: PO :: weekly :: Start 7.5-10 mg PO once weekly; increase by 2.5-5 mg q2-4wk; target 15-25 mg weekly; co-prescribe folic acid 1 mg daily (except MTX day)	Pregnancy (Category X); severe hepatic/renal disease; active infection; bone marrow suppression	CBC q2 weeks x 2 months, then monthly; LFTs monthly; renal function q3 months; pulmonary toxicity (cough, dyspnea)	-	ROUTINE	ROUTINE	-
Cyclosporine	PO	Refractory ocular and neurological Behcet's; often combined with azathioprine; effective for uveitis; CAUTION: use with concurrent azathioprine only -- monotherapy worsens CNS disease	3 mg/kg :: PO :: BID :: Start 3-5 mg/kg/day in 2 divided doses; adjust per trough level (target 100-200 ng/mL)	Uncontrolled hypertension; renal impairment; concurrent nephrotoxic drugs; active infection	Cyclosporine trough levels; renal function (Cr) q2 weeks; BP q visit; Mg; lipids; K; uric acid; gingival hyperplasia	-	ROUTINE	ROUTINE	-
Cyclophosphamide	IV	Severe/refractory parenchymal NBD with progressive neurological decline; brainstem syndrome not responding to steroids + azathioprine	750 mg/m2 :: IV :: monthly x6 :: 750 mg/m2 IV monthly for 6 cycles; pre-hydrate with 1L NS; administer with MESNA for uroprotection; follow with azathioprine maintenance	Pregnancy (Category D); active infection; bone marrow failure; bladder outlet obstruction	CBC weekly x 4 weeks after each cycle (nadir day 10-14); urinalysis (hemorrhagic cystitis); BMP; LFTs; fertility preservation discussion; malignancy risk	-	URGENT	ROUTINE	URGENT

Treatment Note: Azathioprine is the first-line steroid-sparing agent for Neuro-Behcet's disease based on the landmark Yazici et al. trial showing prevention of new attacks. Initiate azathioprine early (within 1-2 months) for all patients with pNBD. Cyclosporine, while effective for ocular Behcet's, is associated with increased risk of neurological involvement when used alone -- combine with azathioprine if used. Cyclophosphamide is reserved for severe/refractory cases.

3D. Disease-Modifying / Biologic Therapies (Refractory)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Infliximab	IV	Refractory parenchymal or non-parenchymal NBD failing azathioprine/cyclophosphamide; progressive brainstem disease; severe myelopathy; refractory uveitis with CNS involvement	5 mg/kg :: IV :: q6-8wk :: 5 mg/kg IV at weeks 0, 2, and 6 (induction), then every 6-8 weeks (maintenance); increase to 10 mg/kg if inadequate response; infuse over 2 hours minimum; Pre-treatment: TB testing (QuantiFERON), Hepatitis B/C screening, CBC, LFTs, CMP, chest X-ray, age-appropriate cancer screening, heart failure assessment (NYHA class), pregnancy test	Active or latent TB (treat first); active serious infection; decompensated CHF (NYHA III-IV); demyelinating disease; live vaccines within 4 weeks	CBC with differential q2-4 months; LFTs q3 months; ANA/anti-dsDNA annually (drug-induced lupus); infection surveillance; infusion reactions; skin cancer screening annually; heart failure symptoms	-	URGENT	ROUTINE	URGENT
Adalimumab	SC	Refractory NBD; alternative to infliximab; preferred for outpatient self-administration; refractory uveitis (FDA-approved for non-infectious uveitis)	40 mg :: SC :: q2wk :: 80 mg SC at week 0, then 40 mg SC every other week; increase to 40 mg weekly if inadequate response; Pre-treatment: TB testing (QuantiFERON), Hepatitis B/C screening, CBC, LFTs, chest X-ray, pregnancy test	Active or latent TB (treat first); active serious infection; decompensated CHF; demyelinating disease; live vaccines within 4 weeks	CBC q2-4 months; LFTs q3 months; ANA annually; infection surveillance; injection site reactions; skin cancer screening	-	-	ROUTINE	-
Tocilizumab	IV	Refractory NBD failing anti-TNF therapy; alternative biologic for severe parenchymal disease (targets IL-6 pathway -- critical in NBD pathogenesis)	8 mg/kg :: IV :: q4wk :: 8 mg/kg IV every 4 weeks (max 800 mg/dose); infuse over 1 hour; Pre-treatment: TB testing, Hepatitis B/C screening, CBC, LFTs, lipids, GI perforation risk assessment	Active infection; ANC <2000; platelets <100K; ALT/AST >1.5x ULN; diverticulitis (GI perforation risk); concurrent live vaccines	CBC q4-8 weeks; LFTs q4-8 weeks; lipid panel q12 weeks; watch for masking of infection (suppresses CRP/ESR); GI perforation symptoms	-	URGENT	ROUTINE	URGENT
Rituximab	IV	Refractory NBD failing anti-TNF therapy; case reports of efficacy	1000 mg :: IV :: q2wk x2 :: 1000 mg IV x 2 doses (day 0 and day 14); re-dose based on CD19/CD20 repopulation or clinical relapse; premedicate with methylprednisolone 100 mg, acetaminophen, diphenhydramine; Pre-treatment: Hepatitis B serology, CBC, CMP, quantitative immunoglobulins, JCV antibody (PML risk), pregnancy test, vaccination update	Active hepatitis B; severe active infection; live vaccines within 4 weeks; severe hypogammaglobulinemia	Hepatitis B surveillance; CBC q2-4 weeks initially; immunoglobulin levels q3 months; CD19/CD20 B-cell counts q3 months; infusion reactions; PML surveillance	-	URGENT	ROUTINE	URGENT
Interferon-alpha 2a	SC	Refractory ocular and neurological Behcet's; particularly effective for refractory uveitis with CNS involvement	3 MIU :: SC :: TIW :: Start 3-6 million IU (MIU) SC three times weekly; increase to 6-9 MIU TIW as needed; taper to lowest effective dose once remission achieved; typically combined with azathioprine; Pre-treatment: CBC, LFTs, TSH, depression screening, ANA	Depression/suicidal ideation; decompensated liver disease; autoimmune hepatitis; severe cytopenia; uncontrolled thyroid disease	CBC q2 weeks initially, then monthly; LFTs; TSH q3 months; depression screening; ANA; triglycerides; injection site reactions; flu-like symptoms	-	-	ROUTINE	-

Treatment Note: Anti-TNF agents (infliximab, adalimumab) have the strongest evidence for refractory Neuro-Behcet's disease. Infliximab is preferred for severe/refractory CNS disease. Tocilizumab (anti-IL-6) is a promising alternative given the critical role of IL-6 in NBD pathogenesis (elevated CSF IL-6 is a hallmark of active pNBD). Exclude latent TB before starting biologics. Treatment duration is typically years; relapse is common on discontinuation. Interferon-alpha is particularly effective for refractory ocular Behcet's with concurrent neurological involvement.

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU
Neurology (neuroimmunology specialist) for diagnosis confirmation, immunotherapy guidance, and long-term management	STAT	STAT	ROUTINE	STAT
Rheumatology for systemic Behcet's disease co-management, mucocutaneous disease control, and immunosuppression coordination	URGENT	URGENT	ROUTINE	URGENT
Ophthalmology for urgent slit lamp examination (uveitis screening), fluorescein angiography, OCT; Ocular Behcet's occurs in 50-70% and causes blindness if untreated	URGENT	URGENT	ROUTINE	URGENT
Hematology if CVT (non-parenchymal NBD): anticoagulation management, thrombophilia evaluation	-	URGENT	ROUTINE	URGENT
Dermatology for skin lesion biopsy (erythema nodosum, pseudofolliculitis, pathergy test interpretation) and mucocutaneous disease management	-	ROUTINE	ROUTINE	-
Neurosurgery for ICP management (EVD/VP shunt) if refractory intracranial hypertension from CVT; brain biopsy if diagnosis uncertain	URGENT	URGENT	-	URGENT
Vascular surgery/interventional radiology if pulmonary artery aneurysm (Hughes-Stovin syndrome) or large vessel vasculitis	-	URGENT	ROUTINE	URGENT
Oral medicine/dentistry for recurrent oral aphthous ulcer management; topical therapies	-	ROUTINE	ROUTINE	-
Gastroenterology if GI Behcet's suspected (abdominal pain, GI bleeding, ulceration)	-	ROUTINE	ROUTINE	-
Physical therapy for gait training, balance assessment, and fall prevention given brainstem/spinal cord involvement	-	ROUTINE	ROUTINE	ROUTINE
Occupational therapy for ADL adaptation and functional rehabilitation	-	ROUTINE	ROUTINE	ROUTINE
Speech-language pathology for swallowing evaluation if brainstem involvement (bulbar symptoms) and cognitive-linguistic rehabilitation	-	ROUTINE	ROUTINE	ROUTINE
Neuropsychology for cognitive assessment and rehabilitation given parenchymal NBD cognitive impairment	-	-	ROUTINE	-
Social work for insurance navigation, disability resources, and psychosocial support	-	ROUTINE	ROUTINE	-
Infusion center coordination for IV methylprednisolone, infliximab, tocilizumab, rituximab, or cyclophosphamide infusions	-	ROUTINE	ROUTINE	-
Fertility specialist for reproductive counseling before initiating teratogenic immunosuppressants (methotrexate, mycophenolate, cyclophosphamide)	-	-	ROUTINE	-
Pain management for refractory headache or neuropathic pain not responding to first-line agents	-	-	ROUTINE	-
Urology for neurogenic bladder evaluation and management if myelopathic NBD	-	ROUTINE	ROUTINE	-

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD
Return to ED immediately for sudden vision loss, new weakness, difficulty walking, severe headache, seizures, difficulty breathing, or new oral/genital ulcers with neurological symptoms (indicates disease flare or complications)	Y	Y	Y
Neuro-Behcet's disease is a chronic, treatable condition -- improvement is gradual over weeks to months with appropriate immunotherapy; relapses are common and require prompt treatment	Y	Y	Y
Do NOT stop corticosteroids abruptly as this causes adrenal crisis and disease flare; taper under physician supervision only	-	Y	Y
Report signs of infection immediately (fever >100.4F, cough, dysuria, rash, wound redness) as immunosuppressive therapy increases infection risk	-	Y	Y
Avoid live vaccines while on immunosuppressive therapy (inform all physicians and pharmacists of immunosuppression status)	-	Y	Y
Monitor blood sugars if diabetic or on corticosteroids -- steroids significantly elevate blood glucose	Y	Y	Y
Do not drive until cleared by neurology if visual impairment, seizures, or significant neurological deficits are present	Y	Y	Y
Keep a symptom diary tracking oral ulcers, genital ulcers, visual changes, headaches, weakness, numbness, and skin lesions to monitor disease activity and treatment response	-	Y	Y
Take azathioprine with food to reduce GI side effects; report severe nausea, vomiting, or abdominal pain (indicates pancreatitis)	-	Y	Y
Take methotrexate on the same day each week; take folic acid daily EXCEPT on methotrexate day to reduce side effects	-	Y	Y
If on warfarin for CVT: attend all INR checks; report bleeding or bruising; avoid excess foods high in vitamin K; report any new medications	-	Y	Y
Avoid pregnancy during methotrexate, mycophenolate, or cyclophosphamide therapy; discuss contraception with neurology and OB/GYN	-	Y	Y
Attend all follow-up appointments -- Neuro-Behcet's requires regular monitoring with MRI, labs, clinical assessments, and ophthalmologic exams	-	Y	Y
Wear medical alert identification (bracelet/card) indicating Behcet's disease, immunosuppressive medications, and anticoagulation status if applicable	-	Y	Y
Use sun protection while on immunosuppressive therapy due to increased skin cancer risk	-	Y	Y

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Smoking cessation to reduce vascular risk and improve treatment outcomes	Y	Y	Y
Alcohol avoidance or strict limitation while on methotrexate, azathioprine, or other hepatotoxic immunosuppressants	-	Y	Y
Low-sodium diet to reduce fluid retention and hypertension from corticosteroid therapy	-	Y	Y
Calcium-rich diet for bone protection during chronic steroid use	-	Y	Y
Regular weight-bearing exercise as tolerated to prevent steroid-related osteoporosis and deconditioning	-	Y	Y
Adequate hydration (2-3 L/day) especially if on methotrexate or if thrombotic risk present	-	Y	Y
Fall prevention measures at home given brainstem/cerebellar involvement and balance impairment	-	Y	Y
Stress management and adequate sleep (7-8 hours nightly) as stress exacerbates Behcet's disease activity	-	Y	Y
Update all vaccinations before initiating immunosuppressive therapy (pneumococcal, influenza, hepatitis B, COVID-19); avoid live vaccines on immunosuppression	-	Y	Y
Sun protection (SPF 50+, protective clothing) during immunosuppressive therapy due to increased skin cancer risk	-	Y	Y
Dental hygiene with soft toothbrush and non-irritating toothpaste to minimize oral ulcer triggers	-	Y	Y
Annual ophthalmologic examination even if asymptomatic due to risk of subclinical uveitis, retinal vasculitis, and steroid-related cataracts/glaucoma	-	-	Y
Report any new venous thrombosis symptoms (leg swelling, chest pain, shortness of breath) immediately given systemic thrombotic tendency in Behcet's	Y	Y	Y

═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Multiple sclerosis	Relapsing-remitting course; periventricular/juxtacortical/infratentorial/spinal cord lesions (Dawson fingers); oligoclonal bands more common; NO oral/genital ulcers; NO pathergy; predominantly female	MRI pattern (MS: periventricular, Dawson fingers vs. NBD: brainstem-diencephalic); CSF OCBs (common in MS, uncommon in NBD); HLA-B51 negative; no mucocutaneous features
Neurosarcoidosis	Non-caseating granulomas; cranial neuropathies (especially CN VII); leptomeningeal enhancement; hilar lymphadenopathy; elevated serum ACE; no oral/genital ulcers	Chest CT (hilar adenopathy); serum ACE; biopsy (granulomas vs. vasculitis); CSF ACE; HLA-B51 negative; no pathergy
CNS vasculitis (PACNS)	Progressive headache; multifocal strokes; angiographic beading; no systemic mucocutaneous features; any age	Cerebral angiography (beading); brain/meningeal biopsy (transmural vasculitis); no oral/genital ulcers; no pathergy; HLA-B51 negative
Neurosyphilis	Cranial neuropathies; meningitis; Argyll Robertson pupils; cognitive decline; positive serology; sexual history	RPR/VDRL; CSF VDRL; FTA-ABS; no oral ulcers (chancre is different from aphthae); no pathergy
Systemic lupus erythematosus (CNS)	Female predominance; malar rash; arthritis; serositis; ANA/anti-dsDNA positive; cerebritis; strokes from antiphospholipid	ANA; anti-dsDNA; complement levels; anti-phospholipid antibodies; no pathergy; different rash pattern
Cerebral venous thrombosis (non-Behcet's)	No recurrent oral/genital ulcers; no systemic vasculitis features; often associated with prothrombotic states, OCP, pregnancy	Standard thrombophilia workup; no HLA-B51; no mucocutaneous features; no pathergy
Tuberculous meningitis	Subacute meningitis; basilar enhancement; CSF low glucose, high protein, elevated ADA; caseating granulomas; endemic areas	AFB culture/smear; CSF TB PCR; QuantiFERON-TB; biopsy (caseating granulomas); no oral/genital ulcers
CNS lymphoma (primary)	Progressive encephalopathy; periventricular enhancement; homogeneous enhancing mass; immunocompromised	CSF cytology/flow cytometry; brain biopsy; FDG-PET (intense uptake); no mucocutaneous features
Sjogren syndrome with CNS involvement	Dry eyes/mouth; anti-SSA/SSB positive; peripheral neuropathy more common than CNS; myelitis possible	Anti-SSA/SSB; Schirmer test; salivary gland biopsy; no oral ulcers (dry mouth instead); no pathergy
IgG4-related disease	Mass-forming lesions; pachymeningeal involvement; elevated serum IgG4; multi-organ fibrosis; orbital involvement	Serum IgG4; tissue biopsy (storiform fibrosis, IgG4+ plasma cells); no oral/genital ulcers; no pathergy
Anti-NMDA receptor encephalitis	Young women; psychiatric symptoms; seizures; movement disorder; ovarian teratoma	Anti-NMDA receptor antibody; ovarian imaging; no oral/genital ulcers; rapid onset
Granulomatosis with polyangiitis (GPA)	Sinusitis; pulmonary nodules/cavities; glomerulonephritis; pachymeningeal enhancement; c-ANCA positive	c-ANCA (PR3); biopsy (necrotizing granulomatous vasculitis); no aphthous ulcers; no pathergy
Lyme neuroborreliosis	Cranial neuropathy (CN VII bilateral); meningitis; radiculopathy; erythema migrans; endemic area	Lyme serology; CSF Lyme antibody index; travel history; no oral/genital ulcers
Acute disseminated encephalomyelitis (ADEM)	Monophasic; post-infectious; large multifocal demyelinating lesions; more common in children	Clinical context (post-viral/vaccine); no recurrent ulcers; no HLA-B51; typically monophasic vs. relapsing NBD

6. MONITORING PARAMETERS¶

6A. Acute Phase Monitoring (Inpatient)¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Neurologic examination (brainstem signs, motor, sensory, gait, cognition, cranial nerves)	Q4-6h (ICU); Q8-12h (floor)	Stable or improving	If worsening: urgent re-imaging; escalate immunotherapy; neurosurgery consult if ICP concerns	STAT	STAT	-	STAT
Visual acuity testing	Daily if ocular/optic nerve involvement	Stable or improving	Worsening: urgent ophthalmology; escalate steroids; add anti-TNF	URGENT	URGENT	ROUTINE	URGENT
Blood glucose	Q6h during IV steroids	<180 mg/dL	Insulin sliding scale; endocrine consult if persistent >250 mg/dL	STAT	STAT	-	STAT
Blood pressure	Q1h (ICU); Q4h (floor)	SBP <160 mmHg; MAP >65	Antihypertensive therapy; steroid dose adjustment if severe	STAT	ROUTINE	-	STAT
Temperature	Q4h; continuous in ICU	36.0-37.5C	Rule out infection; blood cultures if febrile on immunosuppression	STAT	ROUTINE	-	STAT
aPTT (if on heparin for CVT)	Q6h until therapeutic x 2, then q12-24h	60-80 seconds (1.5-2.5x control)	Adjust heparin infusion per protocol; watch for HIT	STAT	STAT	-	STAT
INR (if transitioning to warfarin)	Daily until target INR x 2 days	2.0-3.0	Adjust warfarin dose; overlap heparin until INR therapeutic	-	ROUTINE	-	ROUTINE
Renal function (BUN/Cr)	Daily during acute treatment	Stable	Adjust renally-dosed medications; hydration	URGENT	ROUTINE	-	URGENT
ICP monitoring (if EVD)	Continuous if EVD in place	ICP <20 mmHg	CSF drainage; escalate ICP management; repeat imaging	-	-	-	STAT
Oral/genital ulcer assessment	Daily	Healing or stable	Active new ulcers suggest systemic disease activity; escalate immunotherapy	-	ROUTINE	-	-

6B. Outpatient/Long-Term Monitoring¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Neurologic examination (comprehensive)	Monthly x 6 months; then q3 months x 2 years; then q6 months	Stable or improving; no new deficits	If relapse: repeat MRI; escalate immunotherapy; add biologic if on conventional agents	-	-	ROUTINE	-
MRI brain with and without gadolinium	3-6 months after treatment initiation; then q6-12 months x 2-3 years; then annually	Stable or decreased lesion burden and enhancement	New/worsening lesions: treatment failure; escalate; re-evaluate diagnosis	-	-	ROUTINE	-
MRI spine (if myelopathy)	3-6 months; then annually x 2-3 years	Stable or improved cord lesions	Worsening: escalate therapy	-	-	ROUTINE	-
MRV (if history of CVT)	3-6 months; then annually x 2 years	Recanalization; stable	Persistent or new thrombosis: reassess anticoagulation; escalate immunotherapy	-	-	ROUTINE	-
CBC with differential	Q2 weeks x 2 months on azathioprine/MTX; then monthly; q2-4 months on biologics	WBC >3.0; ANC >1.5; Plt >100	Hold/reduce immunosuppression; growth factor support if needed	-	-	ROUTINE	-
LFTs (ALT, AST, ALP, bilirubin)	Monthly on azathioprine/MTX; q3 months on other agents	ALT/AST <3x ULN	Dose reduction or switch agent; hepatology consult if persistent elevation	-	-	ROUTINE	-
Renal function (BUN/Cr)	Q3 months	Stable	Dose adjustment of renally-cleared drugs	-	-	ROUTINE	-
ESR/CRP	Q3-6 months	Trending down with treatment	Rising inflammatory markers: evaluate for disease relapse; repeat imaging; assess mucocutaneous disease	-	-	ROUTINE	-
Ophthalmologic examination (slit lamp, OCT, visual fields)	Q3-6 months initially; q6-12 months once stable	No uveitis flare; stable retina; no cataracts/glaucoma	Treatment escalation per ophthalmology; topical/systemic therapy	-	-	ROUTINE	-
INR (if on warfarin for CVT)	Weekly until stable; then monthly	2.0-3.0	Adjust warfarin dose; drug/diet interaction review	-	-	ROUTINE	-
DEXA scan (bone density)	Baseline if steroids >3 months; repeat q1-2 years	T-score >-2.5	Bisphosphonate therapy; calcium/vitamin D optimization	-	-	ROUTINE	-
TB screening (QuantiFERON)	Annually on anti-TNF therapy	Negative	If positive: infectious disease consult; TB prophylaxis; hold anti-TNF	-	-	ROUTINE	-
Quantitative immunoglobulins	Q6 months on rituximab or prolonged immunosuppression	IgG >400 mg/dL	Immunoglobulin replacement if recurrent infections with hypogammaglobulinemia	-	-	ROUTINE	-
Skin cancer screening	Annually on immunosuppression	No suspicious lesions	Dermatology referral	-	-	ROUTINE	-
Mucocutaneous disease activity assessment	Every visit	Ulcer frequency and severity decreasing	Increase mucocutaneous treatment; escalate systemically as mucocutaneous activity predicts neurological relapse	-	-	ROUTINE	-

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home	Stable or improving neurological exam; seizure-free (if applicable); oral medications tolerated; anticoagulation therapeutic and stable (if CVT); steroid taper plan established; follow-up with neurology and rheumatology within 1-2 weeks; outpatient labs and imaging scheduled; family/caregiver education completed
Admit to floor (neurology)	New-onset or worsening parenchymal NBD requiring IV methylprednisolone; new CVT requiring heparin anticoagulation; diagnostic workup requiring expedited imaging and LP; new seizures requiring medication optimization; progressive brainstem syndrome; new visual loss from ocular/optic nerve involvement
Admit to ICU	Severe brainstem syndrome with bulbar dysfunction or decreased consciousness; acute elevated ICP from CVT not responding to medical management; status epilepticus; severe myelopathy with respiratory compromise; rapid neurological decline; large hemorrhagic venous infarct; impending herniation
Transfer to higher level of care	Neurosurgery not available (ICP management, EVD, biopsy); neuroimmunology specialist not available; interventional radiology for endovascular CVT treatment; infusion center for biologic therapy not available
Inpatient rehabilitation	Significant functional deficits from brainstem syndrome, myelopathy, or hemispheric involvement; medically stable; expected to benefit from intensive PT/OT/ST; unable to safely return home
Outpatient follow-up	All discharged patients: neurology follow-up within 1-2 weeks; rheumatology within 2-4 weeks; ophthalmology within 1-2 weeks; hematology if on anticoagulation; labs per monitoring schedule; MRI per protocol
Readmission criteria	New or worsening neurological symptoms (vision loss, weakness, brainstem signs, seizures, severe headache); infection on immunosuppression; suspected disease relapse; uncontrolled oral/genital ulcers suggesting flare; new thrombotic event; severe steroid side effects

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
International Study Group (ISG) diagnostic criteria for Behcet's disease	Expert Consensus	International Study Group for Behcet's Disease. Lancet 1990;335:1078-1080. PubMed
International Criteria for Behcet's Disease (ICBD, 2014 revision)	Expert Consensus, Multicenter Validation	International Team for the Revision of the ICBD. J Eur Acad Dermatol Venereol 2014;28:338-347. PubMed
Consensus recommendations for management of Behcet's disease (EULAR)	Expert Consensus, Systematic Review	Hatemi G et al. Ann Rheum Dis 2018;77:808-818. PubMed
Updated EULAR recommendations for Behcet's disease management	Expert Consensus	Hatemi G et al. Ann Rheum Dis 2024;83:25-32. PubMed
Consensus statement on Neuro-Behcet's disease (International Neuro-Behcet Advisory Group)	Expert Consensus	Kalra S et al. J Neurol 2014;261:1662-1676. PubMed
Parenchymal Neuro-Behcet's: clinical features, MRI, and prognosis	Class II, Retrospective	Al-Araji A, Kidd DP. Brain 2009;132:714-724. PubMed
Azathioprine as first-line steroid-sparing agent in Behcet's (landmark RCT)	Class I, RCT	Yazici H et al. N Engl J Med 1990;322:281-285. PubMed
Azathioprine long-term prevention of new Behcet's attacks	Class II, Long-term Follow-up	Hamuryudan V et al. Arthritis Rheum 1997;40:769-774. PubMed
Infliximab for refractory Neuro-Behcet's disease	Class III, Case Series	Hirohata S et al. J Neurol 2015;262:338-344. PubMed
Anti-TNF therapy for refractory Behcet's disease	Class III, Retrospective	Vallet H et al. Autoimmun Rev 2015;14:693-698. PubMed
CSF IL-6 as biomarker in Neuro-Behcet's disease	Class II, Prospective Cohort	Hirohata S et al. Medicine (Baltimore) 2008;87:195-203. PubMed
CSF findings in Neuro-Behcet's disease	Class III, Retrospective	Akman-Demir G et al. Brain 1999;122:2171-2182. PubMed
HLA-B51 and Behcet's disease: meta-analysis	Class I, Meta-analysis	de Menthon M et al. Arthritis Rheum 2009;61:1287-1296. PubMed
Pathergy test in Behcet's disease: systematic review	Class II, Systematic Review	Davatchi F et al. Adv Exp Med Biol 2003;528:51-56. PubMed
Cyclosporine and neurological involvement in Behcet's disease	Class III, Retrospective	Kotter I et al. Rheumatology (Oxford) 2006;45:1461-1464. PubMed
Cerebral venous thrombosis in Behcet's disease	Class III, Retrospective	Aguiar de Sousa D et al. Stroke 2011;42:1153-1155. PubMed
MRI patterns in Neuro-Behcet's disease	Class III, Retrospective	Kocer N et al. Neuroradiology 1999;41:636-643. PubMed
Tocilizumab for refractory Behcet's disease	Class IV, Case Series	Atienza-Mateo B et al. Semin Arthritis Rheum 2019;49:126-135. PubMed
Adalimumab for non-infectious posterior uveitis (VISUAL-I trial)	Class I, RCT	Jaffe GJ et al. N Engl J Med 2016;375:932-943. PubMed
Interferon-alpha for refractory Behcet's disease	Class III, Prospective	Kotter I et al. Arthritis Rheum 2004;50:3628-3636. PubMed
Cyclophosphamide for severe Neuro-Behcet's disease	Class IV, Case Series	Kidd DP. J Neurol 2017;264:434-439. PubMed
Prognosis and long-term outcomes of Neuro-Behcet's disease	Class II, Retrospective Cohort	Noel N et al. Medicine (Baltimore) 2014;93:e68. PubMed
Hughes-Stovin syndrome: pulmonary artery aneurysm and thrombosis in Behcet's	Class IV, Case Series	Emad Y et al. Eur J Intern Med 2007;18:392-395. PubMed
Apremilast for oral ulcers in Behcet's disease (RELIEF trial)	Class I, RCT	Hatemi G et al. N Engl J Med 2019;381:1918-1928. PubMed
Rituximab for refractory Behcet's disease	Class IV, Case Reports	Zhao C et al. Orphanet J Rare Dis 2021;16:1-9. PubMed

CLINICAL DECISION SUPPORT NOTES¶

International Study Group (ISG) Criteria for Behcet's Disease (1990)¶

Required: Recurrent oral aphthous ulceration (>=3 episodes in 12 months)

Plus at least 2 of the following: - [ ] Recurrent genital aphthous ulceration - [ ] Eye lesions (anterior uveitis, posterior uveitis, cells in vitreous on slit lamp, or retinal vasculitis) - [ ] Skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions, or acneiform nodules) - [ ] Positive pathergy test (read at 24-48 hours)

International Criteria for Behcet's Disease (ICBD, 2014)¶

Point-based system (>=4 points = Behcet's disease):

Manifestation	Points
Oral aphthosis	2
Genital aphthosis	2
Ocular lesions (uveitis, retinal vasculitis)	2
Skin lesions (erythema nodosum, pseudofolliculitis, papulopustular)	1
Neurological manifestations	1
Vascular manifestations (arterial thrombosis, large vein thrombosis, phlebitis, superficial phlebitis)	1
Positive pathergy test*	1

*Pathergy test: where it is performed (validity varies by geographic region)

Parenchymal vs. Non-Parenchymal Neuro-Behcet's¶

Feature	Parenchymal (pNBD)	Non-Parenchymal (npNBD)
Frequency	75-80% of NBD	20-25% of NBD
Most common presentation	Brainstem syndrome (diencephalic-brainstem junction)	Cerebral venous thrombosis (CVT)
MRI findings	T2/FLAIR hyperintensities in brainstem, basal ganglia, hemispheric white matter	Venous sinus thrombosis on MRV; normal parenchyma possible
CSF findings	Pleocytosis (early neutrophilic, then lymphocytic); elevated protein; elevated IL-6	Normal or mild pleocytosis; elevated opening pressure
Primary treatment	High-dose IV steroids + azathioprine	Anticoagulation (heparin then warfarin) +/- steroids
Prognosis	Moderate-poor; 30-50% have residual disability; relapsing course common	Generally better; dependent on recanalization and ICP control
Brainstem atrophy	Progressive in severe/relapsing cases (poor prognostic sign)	Not applicable

Common Presentations of Neuro-Behcet's Disease¶

Presentation	Frequency	Key Features
Brainstem syndrome	50-60% of pNBD	Cranial neuropathies; pyramidal signs; ataxia; ophthalmoplegia; dysarthria; dysphagia; characteristic diencephalic-brainstem junction involvement
Hemispheric white matter	15-20% of pNBD	Hemiparesis; hemisensory loss; cognitive impairment; mimics MS or stroke
Myelopathy	5-15% of pNBD	Spastic paraparesis; sensory level; bladder dysfunction; longitudinally extensive possible
Cerebral venous thrombosis	60-75% of npNBD	Headache; papilledema; elevated ICP; superior sagittal sinus most common; hemorrhagic venous infarct possible
Aseptic meningitis	10-20%	Headache; fever; meningismus; CSF pleocytosis
Optic neuropathy	5-10%	Visual loss; optic disc edema; bilateral possible; often with concurrent uveitis
Seizures	5-10%	From cortical involvement; presenting feature of pNBD in some cases
Cognitive/psychiatric	20-30%	Memory impairment; behavioral changes; apathy; executive dysfunction; progressive course possible
Peripheral neuropathy	Rare (<5%)	Sensorimotor polyneuropathy; less common than in other vasculitides

Red Flags Suggesting Neuro-Behcet's Disease¶

HLA-B51 and Pathergy Testing¶

HLA-B51: - Present in 50-70% of Behcet's patients (varies by ethnicity; highest in Turkish/Middle Eastern populations) - Relative risk: 5-6x increased risk of Behcet's disease if HLA-B51 positive - NOT diagnostic alone (present in 15-20% of general population in endemic areas) - Absence does NOT exclude Behcet's disease - Correlates with more severe disease course (some studies)

Pathergy Test: - Sterile needle prick (20-gauge) to forearm skin; read at 24-48 hours - Positive: papule or pustule >=2mm at injection site - Sensitivity varies by geography: 40-60% in Turkey/Middle East; <10% in Western Europe/North America - Specificity ~95% in endemic populations - Part of both ISG and ICBD criteria - Less reliable with modern disposable needles (blunt-needle technique preferred)

CHANGE LOG¶

v1.1 (February 2, 2026) - Checker/Rebuilder pipeline revision (v1.1) - C1: Section 3D reformatted from 11 columns to 10 columns; merged Pre-Treatment Requirements into Dosing full_instructions field for all 5 biologic therapies - C2: Converted hedging/suggestive language to directive language throughout (removed "consider", "may", "should" from clinical directives; replaced with direct action statements) - C3: Corrected "LMWC" to "LMWH" (standard abbreviation) for enoxaparin in Section 3A - M2: Added modafinil to Section 3B for fatigue management in brainstem/parenchymal NBD - M3: Added oxybutynin to Section 3B for neurogenic bladder in myelopathic NBD - M5/M6: Updated levetiracetam and lacosamide Route columns from "IV" to "IV/PO" to reflect dual-route availability - R2: Section 3D Pre-Treatment Requirements integrated into Dosing column for all biologics (infliximab, adalimumab, tocilizumab, rituximab, interferon-alpha) - R4: Added urology referral to Section 4A for neurogenic bladder evaluation - R7: Treatment notes converted from asterisk format to "Treatment Note:" format with directive language - Section 4B and 4C: Confirmed 4-column format (Recommendation, ED, HOSP, OPD -- no ICU column) - Section 4A: Confirmed 5-column format (Recommendation, ED, HOSP, OPD, ICU) - Cyclosporine caution moved from note into the drug row itself for visibility - Updated version to 1.1; added REVISED date - Updated STATUS to "Revised per checker/rebuilder pipeline (v1.1)"

v1.0 (February 2, 2026) - Initial creation - Section 1: 15 core labs (1A), 18 extended labs (1B), 9 rare/specialized tests (1C) - Section 2: 8 essential imaging/studies (2A), 11 extended (2B), 6 rare/specialized (2C), 16 LP/CSF studies - Section 3: 4 subsections: - 3A: 10 acute/emergent treatments (IV methylprednisolone, dexamethasone, heparin for CVT, enoxaparin, GI prophylaxis, insulin, lorazepam, mannitol, hypertonic saline, acetazolamide) - 3B: 10 symptomatic treatments (neuropathic pain, seizures, spasticity, colchicine, apremilast, warfarin, bone protection, duloxetine) - 3C: 6 second-line/steroid-sparing agents (prednisone taper, azathioprine, mycophenolate, methotrexate, cyclosporine, cyclophosphamide) - 3D: 5 disease-modifying/biologic therapies with Pre-Treatment Requirements (infliximab, adalimumab, tocilizumab, rituximab, interferon-alpha) - Section 4: 18 referrals (4A), 15 patient instructions (4B), 13 lifestyle/prevention items (4C) - Section 5: 14 differential diagnoses with distinguishing features - Section 6: 10 acute monitoring parameters (6A), 15 outpatient/long-term monitoring parameters (6B) - Section 7: 7 disposition criteria - Section 8: 25 evidence references with PubMed links - Clinical Decision Support Notes: ISG criteria checklist, ICBD 2014 point system, parenchymal vs. non-parenchymal comparison, common presentations table, red flags checklist, HLA-B51 and pathergy test reference - Focus on parenchymal (brainstem predominant) and non-parenchymal (CVT) forms per physician request - Structured dosing format with :: delimiter throughout all treatment tables

APPENDIX A: ISG and ICBD Diagnostic Criteria Quick Reference¶

ISG Criteria (1990) -- Checklist¶

REQUIRED: Recurrent oral aphthous ulceration (>=3 episodes in 12 months)
Recurrent genital aphthous ulceration
Eye lesions (anterior/posterior uveitis; retinal vasculitis; cells in vitreous)
Skin lesions (erythema nodosum; pseudofolliculitis; papulopustular; acneiform)
Positive pathergy test (>=2mm papule/pustule at 24-48h)

Diagnosis: Required criterion + >=2 additional criteria

ICBD Criteria (2014) -- Point System¶

Score each:	Points	Patient Score
Oral aphthosis	2	[ ]
Genital aphthosis	2	[ ]
Ocular lesions	2	[ ]
Skin lesions	1	[ ]
Neurological manifestations	1	[ ]
Vascular manifestations	1	[ ]
Positive pathergy test	1*	[ ]
TOTAL		___/10

Diagnosis: Total >=4 points

*Pathergy where it is conducted and where considered valid

APPENDIX B: Treatment Algorithm for Neuro-Behcet's Disease¶

Parenchymal NBD (pNBD): 1. Acute attack: IV methylprednisolone 1g/day x 5-10 days 2. Oral taper: Prednisone 1 mg/kg/day, taper over 6-12 months 3. Steroid-sparing (START EARLY): Azathioprine 2.5 mg/kg/day (first-line) 4. If azathioprine fails: Add or switch to anti-TNF (infliximab preferred) 5. If anti-TNF fails: Cyclophosphamide IV monthly x 6 cycles, then azathioprine maintenance 6. Refractory: Tocilizumab, rituximab, or interferon-alpha

Non-Parenchymal NBD (npNBD / CVT): 1. Acute: Heparin anticoagulation (UFH or LMWH) -- even if hemorrhagic venous infarction 2. Transition: Warfarin (INR 2-3); duration 3-12 months (indefinite in recurrent thrombosis) 3. ICP management: Acetazolamide; LP if needed; VP shunt if refractory 4. If inflammatory component: Add corticosteroids 5. Recurrent CVT: Immunosuppression with azathioprine + continued anticoagulation 6. Refractory ICP: Neurosurgical evaluation for shunting

Key Principles: - Start azathioprine in ALL parenchymal NBD patients (prevents relapse) - Cyclosporine monotherapy is CONTRAINDICATED in NBD (worsens neurological disease) - Anti-TNF agents are the most effective biologics for refractory NBD - CSF IL-6 guides treatment response monitoring - Mucocutaneous disease activity predicts neurological relapse risk - Duration of immunosuppression: typically >=3-5 years; some require lifelong treatment

APPENDIX C: Behcet's Disease Organ Involvement Quick Reference¶

System	Manifestation	Frequency	Key Features
Oral	Recurrent aphthous ulcers	97-100%	Painful; multiple; round with erythematous border; heal in 1-3 weeks; >3 per year
Genital	Genital ulcers	60-90%	Painful; scarring (unlike oral); scrotum (males), vulva (females); pathognomonic scarring
Ocular	Anterior/posterior uveitis; retinal vasculitis	50-70%	Bilateral; recurrent; hypopyon; retinal vasculitis; leading cause of morbidity; causes blindness if untreated
Skin	Erythema nodosum; pseudofolliculitis; papulopustular	40-80%	Pathergy reaction; acneiform lesions; tender nodules
Neurological	Parenchymal; CVT; meningitis	5-25%	Brainstem predominant; CVT; see detailed sections above
Vascular	DVT; superficial thrombophlebitis; arterial aneurysm	15-40%	Venous thrombosis most common; pulmonary artery aneurysm (Hughes-Stovin)
Articular	Non-erosive arthritis	40-60%	Oligoarthritis; knees, ankles, wrists; non-deforming
GI	Mucosal ulceration	5-60% (varies by region)	Ileocecal predominance; mimics IBD; perforation risk
Cardiac	Pericarditis; endocarditis; intracardiac thrombus	<5%	Rare; intracardiac thrombus is characteristic