Pruritis and sweating Flashcards
Neurologic transmission of pruritus
- Release of pruritogenic stimuli
- Physical stimuli (pressure, thermal stimulation, low-intensity electrical stimulation, formation of suction blisters, caustic substances)
- Chemical stimuli (histamine, proteases, prostaglandins, neuropeptides) - Stimuli of nerve fibres
- Both Type A myelinated fibres and Type C unmyelinated fibres
- Appears to be a specific itch receptor in the C fibres and is separate from the dull, aching pain conducted by Type C fibres - Transmission to CNS
- Type A and C fibres synapse on second order neurons at the dorsal horn
- Transmitted via the spinothalamic tract to the thalamus and cerebral cortex
Mediators of pruritus: Opioids (MOA)
Opioids
- Opioids exert both excitatory and modulatory effects on pruritus
- Peripherally, opioids stimulate mast cell degranulation and release of histamine (producing itch)
- At spinal cord level, opioids are inhibitor
- In the CNS, opioids are known to directly trigger itch
Mediators of pruritus: Serotonergic compounds (MOA)
Serotonergic compounds
- Peripheral serotonin receptors seem to play a role in mediating pruritus
- SSRIs (paroxetine) have been reported to be useful for pruritus
Clinical evaluation of pruritus
- Primary vs Secondary
- Primary is idiopathic or essential
- Secondary is due to dermatologic or systemic disease - Localized versus generalised
- Localized more typically due to cutaneous infections or dermatologic disease
- Generalised can be related to a derm disorder affecting the entire skin surface, but some areas may be worse than others and symptoms may migrate or fluctuate
Primary pruritus - diagnosis, treatment
Diagnosis
- Diagnosis of exclusion
- May be an early sign of malignancy (especially hematologic), necessitating careful workup
Treatment
- Good skin care, topical soothing measures
Secondary pruritus - Dermatologic disease - Common causes and management
- Allergic contact dermatitis
- Scabies
- Folliculitis
- Insect bites
- Atopic dermatitis
- Urticaria
- Bullous pemphigoid
Treatment:
- Ensure appropriate treatment for underlying diagnosis
- May require skin biopsies and specialist consultation
Secondary pruritus - Systemic disease - Causes
- Biliary and hepatic disease
- Cholestasis of any cause (pregnancy, drug, PBC, cholangitis, extrahepatic biliary obstruction) - Chronic renal failure (uremia)
- Drugs
- Opioids
- Amphetamines
- Cocaine
- ASA
- Subclinical drug sensitivity - Endocrine disease
- DM
- DI
- Parathyroid disease
- Thyroid disease (hypo or hyper) - Heme disease
- Lymphoma
- T cell lymphoma
- Systemic mastocytosis
- MM
- PCV
- Iron deficiency anemia - Infectious disease
- HIV
- Syphilis
- Parasitic infection
- Fungi - Malignancy
- Carcinoid syndrome
- Breast, stomach, lung, etc. - Neuro conditions
- Stroke
- Distal small fibre neuropathy
- MS
- Brain abscess/tumours
- Psychosis/parisitosis
Topical antipruritic medications
- More practical for localized itch
- May still be useful for patients with generalised pruritus with areas that are particularly bothersome
- Dilute phenol (0.5-2%)
- Anesthetizes cutaneous nerve endings
- Potentially neurotoxic and hepatotoxic - avoid in pregnancy and infants - Menthol and camphor
- Counter irritation and anesthetic properties - Topical anesthetics (EMLA - lidocaine and prilocaine)
- Amitriptyline and ketamine compounds
- May be applied topically to <10% of body area - Capsaicin
- Useful for neurogenic pruritus of various causes but may create a burning sensation
- Poor evidence - Topical steroids
- Effective if there is evidence of inflammation
Systemic therapies for itch
- More appropriate for generalised pruritus
- Poor evidence for many drugs and may require trial and error prescribing
- Combinations of systemic and topical agents seem to provide best relief
Anti-inflammatories
- Steroids
- Histamine blockers
- Salicylates
Vasoactive drugs
- Propranolol
CNS agents: Anesthetics
- Ketamine
CNS Agents: Antidepressants
- Neuroleptics
- Sedatives
- Opioid antagonists
- SNRIs (Paroxetine)
- Amitriptyline
- SSRIs (sertraline)
CNS Agents: GABA agonists
- Gabapentin
- Pregabalin
Sequestrants
- Cholestyramine
Systemic therapies for itch: Pruritus of malignancy
- Can be severe and recalcitrant
- Single effective treatment plan unavailable
- Most associated with heme malignancies, lung cancers, gastric tumours, insulinomas, and laryngeal tumours
Agents to consider:
- SSRIs or gabapentinoids (first line)
- Paroxetine
- Sertraline
- Gabapentin - Steroids
- E.g. Pred 40mg/day tapered off over three weeks
- Useful if not responding to other therapies - Third line:
- Aprepitant
- Thalidomide
- Naltrexone (caution with patients using opioids for analgesia)
Therapies for itch: Basic treatment for all patients
- Regular mosturizing with nonfragrant topical emolliants, especially after bathing
- Non-irritating, loose clothing
- Avoidance of skin irritants (perfumes)
- Cool, humidified environment
Therapies for cholestastic pruritus
*Stenting is always appropriate!
- Bile acid sequestrants
- Cholestyramine
- First line agents for moderate to severe cholestatic pruritis
- Note that drug may interfere with other medications - Rifampin
- Second line drug to switch to if Cholestyramine is ineffective or intolerable - Naltrexone
- Can be added to rifampin, but caution advised if patients are using opioids for analgesia - Antidepressants
- Paroxetine
- Sertraline
Therapies for uremic pruritus
- First line - topical emollients and optimize dialysis
- Gabapentin
- Start at low doses (100mg after each dialysis session)
- Avoid in patients who have stopped dialysis due to risk of toxicity - Oral antihistamines (if not on dialysis)
- Hydroxyzine - Sertraline (if not on dialysis)
Treatment of opioid-induced pruritus
- Rotation to a different opioid (especially those with lower histamine releasing properties, such as fentanyl or oxycodone)
- Trial of an oral antihistamine
Treatment for generalised pruritus of unknown cause
- Topical therapy first
- Serotonin modulating drugs
- Sertraline
- Mirtazipine
- Paroxetine
- Gabapentin (alone or in addition to an SSRI) - Consider steroid if pruritus is active, severe, and refractory - taper within 2-3 weeks