DERM IE2 Material: Fibro + Lupus

Fibromyalgia

how is diagnosis of fibromylagia based on

symptoms and requires ruling out other diseases

fibromyalgia: CNS-based or autoimmune/inflammation based disease

CNS based disease

core features of fibromyalgia

• widespread pain and tenderness that comes and goes, moving around body

• fatigue, non-restorative sleep

• memory/cognitive difficulties

associated symptoms of fibromyalgia

• depression/anxiety

• migraines

• GI issues

• irritable bladder

• pelvic pain

central pain amplification

nervous system’s volume for pain is turned up too high

• biologic factors

• psychosocial factors

fibromyalgia

• biologic

  • genetic polymorphisms

  • NT abnormalities

  • endocrine dysfunction

  • sleep disturbances

• psychosocial

  • stress

  • anxiety/depression

  • trauma

  • central pain amplification

diagnostic criteria

• pain and symptoms

• duration

• pain > 7 of 19 body parts (WPI) over past week

• PLUS severity of fatigue, unrefreshed sleep, cognitive problems (SSS; max score 12)

• ≥ 3 months

pathway 1

• WPI (0 -19)

• SSS (0 - 12)

WPI ≥ 7

SSS ≥ 5

pathway 2

• WPI (0 -19)

• SSS (0 - 12)

WPI 4 - 6

SSS 9

generalized pain in —-?

≥ 4 of 5 body regions

non-pharmacological treatment of fibromylagia

• exercise — very effective

• CBT stress reduction

• acupuncture/massage

  • specialist referral

  • sleep med, psychiatrist, therapist

FDA approved medications for fibromylagia

• Duloxetine (Cymbalta;SNRI)

• Milnacipran (Savella; SNRI)

• Pregabalin (Lyrica)

off label medications for fibromyalgia

• gabapentin (Neurontin)

• cyclobenzaprine (Flexeril)

• amitriptyline

pharmacological treatment aim to target central sensitization and decrease pain amplification by

• dampening release of excitatory NTs (glutamate, substance P)

  • target Ca++ channels

• boosting pain sensory inhibitory pathways by raising 5HT and NE levels

Pregabalin (Lyrica)

• MOA

• sx profile

• how it helps

• ADE

• MOA

  • bind to Ca channels → reduce glutamate and sub P release

• sx profile

  • widespread pain, insomnia, anxiety, sleep disturbance

• how it helps

  • decrease pain signal transmission, central sensitization

  • improve sleep quality

• ADE

  • renal adjustment CrCl ≤ 60 ml/min

Duloxetine (Cymbalta)

• MOA

• sx profile

• how it helps

• ADE

• MOA

  • SNRI = increase 5HT and NE in pain inhibitory pathways

• sx profile

  • pain w/ depression, anxiety

• how it helps

  • enhance body’s natural pain suppression pathways

  • treats depression and anxiety sx

• ADE

  • avoid in CrCl < 30 ml/min

  • no for dialysis

  • same BBW as antidepressants

  • avoid NSAIDs/ASA → bleeding risk

Milnacipran (Savella)

• MOA

• sx profile

• how it helps

• ADE

• MOA

  • SNRI w/ greater NE activity

• sx profile

  • pain w/ fatigue, low energy, impaired physical function

• how it helps

  • improve pain modulation

  • greater benefits for fatigue and daytime functioning

• ADE

  • renal adjustment required CrCl < 30 ml/min

  • no for dialysis

  • same BBW as antidepressants

  • avoid NSAIDs/ASA → bleeding risk

• ONLY FOR FIBROMYALGIA

medications to avoid for fibromyalgia

• opioids

  • except Tramadol (has SNRI effects)

• BZDs, Z-drugs

• APAP, NSAIDs

  • ineffective, but helps with pain triggers

additional treatments

• malic acid + Mg

• amino acids

• antioxidants

• herbs/supplements

living w/ fibromyalgia

• daily relaxation

• sleep hygiene

  • regular schedule, no daytime naps, limit caffiene, no smoking

• exercise

• education

Systemic Lupus Erthematosus (SLE) overview

• multisystem disorder: affect any organ in the body

• autoimmune disorder: chronic IFN over activation

• challenging to diagnose

• include mild joint an skin involvement

• can involve renal, hematologic, CNS

which population is SLE most common in?

females of child-bearing age

SLE etiology

• genetic

• environmental

• genetic

  • predisposition

• environmental

  • viruses

  • UV light

  • silica dust

  • allergies to meds

pathophysiology of SLE

• Defective clearance of apoptotic cells → exposure of nuclear antigens 

• Innate immune, T cell, B cell activation, IC formation, inflammation/organ damage

what would you see on a physical exam for SLE?

• malar rash (butterfly rash across face)

• patchy alopecia

• polyarticular arthritis (symmetrical)

• abnormal breath sounds

• lower extremity edema

• HTN (suggest renal involvement)

routine labs for SLE

• CBC

• increased SCr

• urinalysis

specific labs for SLE (to support diagnosis if abnormal)

• antinuclear antibody (ANA)

  • positive → consider more specific antibody tests

    • anti-dsDNA antibodies

    • antiphospholipid antibodies

• C3 and C4 complement levels: decreased during flares

• erythrocyte sedimentation (ESR) and/or C-reactive protein (CRP) levels: inflammation.

Treatments for SLE

• hydroxychloroquine (HCQ)

• Belimumab (Benlysta)

• Anifrolumab (Saphnelo)

• Glucocorticoids (high dose, IV for initial/severe cases

HCQ

• MOA

• key points

• side effect

• monitoring

• MOA

  • anti-malarial drug

  • increase pH in lysosomes, interferes w/ antigen processing, TLR7 and 9 signaling

  • decrease cytokine release

• key points

  • gold standard for lupus

  • safe in pregnancy

• side effect

  • retinal toxicity (retinopathy) w/ long term use at doses 5 mg/kg

• monitoring

  • complete eye exam done at baseline and every 5 years thereafter

HCQ Therapy approach

• mild

• moderate

• mild

  • skin, joint invovlement

  • 200-400 mg/day (divide doses) + low dose glucocorticoids

• moderate

  • constitutional sx, muscoskeletal, hematologic

  • 200-400 mg/day (divide doses) + low dose glucocorticoids + steroid sparing agent once flare improved

Belimumab (Benlysta)

• MOA

• key points

• limitations

• MOA

  • BLyS-specific inhibitor

• key points

  • good if pt has more autoimmune driven lupus

  • approved for active, autoantibody positive SLE pts recieving HCQ

  • preferred w/ lupus nephritis

• limitations

  • not evaluated in severe lupus nephritis, CNS lupus, combo w/ other biologics/cycclophosphamide

Anifrolumab (Saphnelo)

• MOA

• key points

• limitations

• MOA

  • block IFN signaling → decreased JAK-STAT activation

• key points

  • good if pt has more inflammation IFN driven lupus

  • approved for active, autoantibody positive SLE pts recieiving HCQ

• limitations

  • same as Belimumab

steroid-sparing immunosuppressants

• mycophenolate mofetil

• azathioprine

• cyclophosphamide

• rituximab

• cyclosporine

treatment approach: mild

• characteristics

• treatment

• characteristics

  • rash, arthralgia, fatigue, mild serology

• treatment

  • HCQ

  • ± NSAIDs, topical steroids

treatment approach: moderate

• characteristics

• treatment

• characteristics

  • arthritis, cutaneous, serositis

• treatment

  • HCQ

  • + corticosteroids (lowest effective dose)

  • + steroid sparing immunosuppressant or biologic

treatment approach: mod-severe

• characteristics

• treatment

• characteristics

  • refractory disease

• treatment

  • HCQ

  • + immunosuppressant

  • ± biologic (belimumab or anifrolumab)

treatment approach: severe

• characteristic

• treatment

• characteristic

  • organ threatening

• treatment

  • high-dose steroids (IV glucocorticoids for inital therapy)

  • + immunosuppressive induction therapy

  • ± biologics