Pruritis and sweating Flashcards

1
Q

Neurologic transmission of pruritus

A
  1. 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)
  2. 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
  3. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Clinical evaluation of pruritus

A
  1. Primary vs Secondary
    - Primary is idiopathic or essential
    - Secondary is due to dermatologic or systemic disease
  2. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Secondary pruritus - Systemic disease - Causes

A
  1. Biliary and hepatic disease
    - Cholestasis of any cause (pregnancy, drug, PBC, cholangitis, extrahepatic biliary obstruction)
  2. Chronic renal failure (uremia)
  3. Drugs
    - Opioids
    - Amphetamines
    - Cocaine
    - ASA
    - Subclinical drug sensitivity
  4. Endocrine disease
    - DM
    - DI
    - Parathyroid disease
    - Thyroid disease (hypo or hyper)
  5. Heme disease
    - Lymphoma
    - T cell lymphoma
    - Systemic mastocytosis
    - MM
    - PCV
    - Iron deficiency anemia
  6. Infectious disease
    - HIV
    - Syphilis
    - Parasitic infection
    - Fungi
  7. Malignancy
    - Carcinoid syndrome
    - Breast, stomach, lung, etc.
  8. Neuro conditions
    - Stroke
    - Distal small fibre neuropathy
    - MS
    - Brain abscess/tumours
    - Psychosis/parisitosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
  1. Dilute phenol (0.5-2%)
    - Anesthetizes cutaneous nerve endings
    - Potentially neurotoxic and hepatotoxic - avoid in pregnancy and infants
  2. Menthol and camphor
    - Counter irritation and anesthetic properties
  3. Topical anesthetics (EMLA - lidocaine and prilocaine)
  4. Amitriptyline and ketamine compounds
    - May be applied topically to <10% of body area
  5. Capsaicin
    - Useful for neurogenic pruritus of various causes but may create a burning sensation
    - Poor evidence
  6. Topical steroids
    - Effective if there is evidence of inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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:

  1. SSRIs or gabapentinoids (first line)
    - Paroxetine
    - Sertraline
    - Gabapentin
  2. Steroids
    - E.g. Pred 40mg/day tapered off over three weeks
    - Useful if not responding to other therapies
  3. Third line:
    - Aprepitant
    - Thalidomide
    - Naltrexone (caution with patients using opioids for analgesia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Therapies for cholestastic pruritus

A

*Stenting is always appropriate!

  1. Bile acid sequestrants
    - Cholestyramine
    - First line agents for moderate to severe cholestatic pruritis
    - Note that drug may interfere with other medications
  2. Rifampin
    - Second line drug to switch to if Cholestyramine is ineffective or intolerable
  3. Naltrexone
    - Can be added to rifampin, but caution advised if patients are using opioids for analgesia
  4. Antidepressants
    - Paroxetine
    - Sertraline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Therapies for uremic pruritus

A
  1. First line - topical emollients and optimize dialysis
  2. Gabapentin
    - Start at low doses (100mg after each dialysis session)
    - Avoid in patients who have stopped dialysis due to risk of toxicity
  3. Oral antihistamines (if not on dialysis)
    - Hydroxyzine
  4. Sertraline (if not on dialysis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Treatment for generalised pruritus of unknown cause

A
  • Topical therapy first
  1. Serotonin modulating drugs
    - Sertraline
    - Mirtazipine
    - Paroxetine
    - Gabapentin (alone or in addition to an SSRI)
  2. Consider steroid if pruritus is active, severe, and refractory - taper within 2-3 weeks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
  1. Endocrine disturbances
    - Acromegaly
    - DM
    - DI
    - Hypopituitarism
    - Hypoglycemia
    - Thyrotoxicosis
    - Pheochromocytoma
    - Menopause
  2. Drugs
    - Opioids (morphine, methadone, etc.)
    - Antidepressants (SSRIs, SNRIs)
    - Naproxen
    - Aciclovir
  3. Malignancy
19
Q

Localized hyperhidrosis: Causes

A
  1. Neurogenic
    - Spinal cord disease
    - Peripheral neuropathy
    - Stroke
  2. 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
  3. Cold-induced
  4. 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
  1. 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)
  2. Non-hormonal treatments: Gabapentin
    - Target dose of 900mg/day
    - Venlafaxine was a preferred agent in one study
  3. Non-hormonal treatments: Pregabalin
  4. 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)