Pruritis and sweating Flashcards
1
Q
Neurologic transmission of pruritus
A
- 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
2
Q
Mediators of pruritus: Opioids (MOA)
A
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
3
Q
Mediators of pruritus: Serotonergic compounds (MOA)
A
Serotonergic compounds
- Peripheral serotonin receptors seem to play a role in mediating pruritus
- SSRIs (paroxetine) have been reported to be useful for pruritus
4
Q
Clinical evaluation of pruritus
A
- 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
5
Q
Primary pruritus - diagnosis, treatment
A
Diagnosis
- Diagnosis of exclusion
- May be an early sign of malignancy (especially hematologic), necessitating careful workup
Treatment
- Good skin care, topical soothing measures
6
Q
Secondary pruritus - Dermatologic disease - Common causes and management
A
- 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
7
Q
Secondary pruritus - Systemic disease - Causes
A
- 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
8
Q
Topical antipruritic medications
A
- 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
9
Q
Systemic therapies for itch
A
- 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
10
Q
Systemic therapies for itch: Pruritus of malignancy
A
- 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)
11
Q
Therapies for itch: Basic treatment for all patients
A
- Regular mosturizing with nonfragrant topical emolliants, especially after bathing
- Non-irritating, loose clothing
- Avoidance of skin irritants (perfumes)
- Cool, humidified environment
12
Q
Therapies for cholestastic pruritus
A
*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
13
Q
Therapies for uremic pruritus
A
- 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)
14
Q
Treatment of opioid-induced pruritus
A
- Rotation to a different opioid (especially those with lower histamine releasing properties, such as fentanyl or oxycodone)
- Trial of an oral antihistamine
15
Q
Treatment for generalised pruritus of unknown cause
A
- 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
16
Q
Physiology of sweating
A
- Sweating is a physiologic response of the skin, used as part of thermoregulation
- Inappropriate sweating may occur in palliative care due to malignant disease or its treatment
Physiology:
- Thermosensitive neurons located in the hypothalamus
- Warm sensitive neurons are more abundant than cold-sensitive neurons
- Thermoreceptors exist in the skin, spinal cord, and brain stem and are integrated in the hypothalamus, with temperature regulated to match a set point
- Set point and body temperature can be altered by hypercapnia, plasma osmolality, intravascular volume, and chemical mediators (e.g. in the fever response)
Autonomic control of thermoregulation
- Heat production (shivering, non-shivering thermogenesis)
- Heat dissipation (vasomotion, sweating)
Behavioural thermoregulation
- Posture
- Voluntary movement
- Selection of thermal environment
17
Q
Hyperhidrosis
A
- May manifest as simply excessive sweating, or as night sweats
- May be localized or general, primary or secondary
- May also be compensatory to anhidrosis at other sites
18
Q
Generalised hyperhidrosis: Causes
A
- Endocrine disturbances
- Acromegaly
- DM
- DI
- Hypopituitarism
- Hypoglycemia
- Thyrotoxicosis
- Pheochromocytoma
- Menopause - Drugs
- Opioids (morphine, methadone, etc.)
- Antidepressants (SSRIs, SNRIs)
- Naproxen
- Aciclovir - Malignancy
19
Q
Localized hyperhidrosis: Causes
A
- Neurogenic
- Spinal cord disease
- Peripheral neuropathy
- Stroke - Intrathoracic neoplasms or masses
- Causing anhidrosis distal to tumour due to peripheral neuropathy, for example pancoast tumour resulting in axillary anhidrosis
- Can result in compensatory hyperhidrosis elsewhere - Cold-induced
- Gustatory
20
Q
Treatment of sweating: Hot flashes
A
- Occurs in menopausal women and is associated with estrogen depletion
- May also occur in women with breast cancer, due to POF secondary to adjuvant chemo, anti-estrogens, or aromatase inhibitors
- In breast CA, hormone replacement therapy is not an option given risk of tumour response
- Non-hormonal treatments: SSRIs
- SSRIs (venlafaxine, paroxetine, descenlafaxine, citalopram) appear to be effective
- Note that tamoxifen is a substrate of CYP2D6, and inhibitors of this may reduce efficacy (e.g. fluoxetine) - Non-hormonal treatments: Gabapentin
- Target dose of 900mg/day
- Venlafaxine was a preferred agent in one study - Non-hormonal treatments: Pregabalin
- Hormonal agents
- Progestational agents decrease hot flashes
- Not advisable in women with hormone receptor positive breast CA
21
Q
Treatment of sweating: Tumour fever
A
- If patient is febrile, may use an antipyretic (acetaminophen or ASA)
