Transcript PRURITIS - Health Education YH | Home

PRURITUS
Catriona Mayland
July 2002
Topics
• Definition
• General treatment
• Neuroanatomy
• Systemic disorders
• Mediators
• Specific treatment
• Evaluation
Definition
• Unpleasant sensation causing desire to
scratch
• Normally protective function
• Sensation arises from superficial skin,
mucous membranes, conjunctiva
Neuroanatomy
•
•
•
•
•
•
Nerve endings – dermo-epidermal junction
Impulses – dorsal root ganglion
Synapse in dorsal horn
Efferents – contralateral spinothalamic tract
Somatosensory cortex
New concepts – peripheral & central
mechanisms
Mediators
• Physical stimulation
• Chemical mediators
–
–
–
–
Amines e.g. histamine, serotonin, dopamine
Opiods e.g. met-enkephalin, -endorphin
Eicosanoids
Cytokines e.g. IL-1 to 11, TNF
And there’s more…
• Proteases e.g. tryptases, papain, kallikrein
• Growth Factor
• Neuropeptides
–
–
–
–
Substance P
CGRP, VIP, CCK
Bradykinin
Somatostatin, endothelin, neurokinin
Histamine
• Itching if applied to superficial damaged
skin or injected intradermally
• Dermal mast cells
• Skin blood vessels, eccrine glands,
basophils, hair follicles
Action
• Direct stimulation H receptors
• ? stimulation formulation other mediators
• Repeated injection – response decreases
• ? role in chronic itch
Serotonin
• Action
– Direct on peripheral serotoninergic receptors
– C-fibres via 5-HT3 receptors
Central Transmitters
• Endogenous opiods
– Regulatory action
– Both excitatory and modulatory effects
– Inhibit presynaptic signals – modulate
secondary transmission
– Abnormal central settings – directly trigger itch
despite no peripheral input
Other Mediators
• Exacerbate
–
–
–
–
Heat
Anxiety
Boredom
Poor coping strategies
• Reduce
–
–
–
–
Cold
Relaxation
Distraction
Good coping stategies
Evaluation
• Primary dermatological disease
• Systemic disease
• History and examination
• Drugs, onset, localised or systemic
Non-drug Treatments
•
•
•
•
Discourage scratching – short nails
Avoid hot baths, overheating and sweating
Pat skin dry! Cool cotton clothes!
Avoid alcohol and spicy foods
Skin Care
• Emollient – aqueous cream & menthol
• Calamine lotion - ?still recommended
• Barrier cream
• Consider hydrocortisone
• NB Eurax and topical antihistamines
Systemic Disorders
•
•
•
•
•
•
Renal failure
Hepatogenic
Haematopoietic
Endocrine
Solid tumours
HIV
•
•
•
•
•
•
Opiod induced
Neurogenic
Aquagenic
Inatrogenic
Senile
Psychogenic
Chronic Renal Failure
• Aetiology
–
–
–
–
Dry skin
Hyperparathyroidism
Mast cell proliferation
Loss opiod receptors and increased endogenous
opiods
• Peripheral neuropathy
• Increased
–
–
–
–
–
Histamine
Vitamin A
Magnesium, phosphate, aluminium
Serotonin
Substance P
Hepatogenic Pruritus
• PBC
• drug induced cholestasis
– Oral contraceptive, phenothiazines
• Biliary obstruction
Aetiology
•
•
•
•
•
? Bile acids
? Accumulation pruritogen intermediary
? Histamine induced
? Centrally activated pruritogenic opiod
? Increased serotonin
Haematopoietic Disorders
• PCV
– Increased histamine
• Hodgkins
• Others
–
–
–
–
? Histamine
? Autoimmune response
? Infiltration
? Release of leukopeptidase
Endocrine Disorders
• Thyrotoxicosis
– ? Activate kinins
– ? Reduced itch threshold
• Hypothyroidism
– xerosis
• Diabetes mellitus
– candida
Solid Tumours
•
•
•
•
Paraneoplastic
? Allergic reaction to Ag
? Toxic products of necrotic tumour cells
Breast, stomach, lung, prostrate, colon
Opiod Induced Pruritus
•
•
•
•
•
•
•
Spinal > systemic
Peripheral – stimulate release histamine
Central – cephalad spread in CSF
Bupivicaine given
? Role serotoninergic pathways
? Antagonism of inhibitory transmitters
Opiod rotation
Inatrogenic Pruritus
•
•
•
•
•
•
Aspirin
Hydroxyurea
Captopril
Antibiotics
Phenytoin
Allopurinol
Neurogenic
• Neuropathies
– E.g. multiple sclerosis
– Activation artificial synapses
• Unilateral cerebral lesions
– Effects on descending pathways
• Post-herpetic neuralgia
Senile Pruritus
• Xerosis
• Skin atropy
• ? Age associated degeneration in nerve
endings
• ? Postmenopausal syndrome
Psychogenic Pruritus
•
•
•
•
Feelings of hopelessness / helplessness
Secretion serotonin, dopamine
Elevated endogenous opiods
? ‘depressive equivalent’
Others
• HIV
• High prevalence skin
disorders
• Abnormal levels
cytokines
• Hypereosinophilia
• Peripheral neuropathy
• AQUAGENIC
• Contact with water
• Pathogenesis unknown
Specific Treatments
• Anti-inflammatory
agents
– Antihistamines
(cimetidine)
– Steroids
– Salicylates (capsacin)
– Thalidomide
• Central / peripheral
nervous system agents
–
–
–
–
–
–
Antidepressants
Anaesthetic agents
Opiod antagonists
Serotonin antagonists
Neuroleptic agents
Tranquillizers
Specific treatments
• Sequestrants
– Cholestyramine
– Charcoal
– Heparin
• Vaso-active drugs
– Alpha blockers
– Beta blockers
Disease Specific Interventions
• Cholestatic disease
–
–
–
–
Rifampicin
Androgens
Urso
Stenting
• Uraemia
–
–
–
–
Erythropoitin
UVB phototherapy
Parathyroidectomy
Transplantation
Disease Specific Interventions
• PCV – alpha
interferon
• Fe deficiency – iron
• Thyroid disorder
Miscellaneous
•
•
•
•
•
Phototherapy
TENS
Acupuncture
Psychotherapy
Relaxation
Problems in Palliative Medicine
• Most terminal phase
• Changing organ function
• Systemic treatment may be toxic,
impractical
Conclusions
• Pathophysiology not fully understood
• Peripheral and central mechanisms
• Often associated with systemic diseases
Conclusions
• Importance of non-pharmacological
treatment
• Treat what is treatable
• Rare problem but impact on quality of life
• Likely that older drugs will be used
• Await our protocol review!
References
• Understanding pruritus in systemic disease
– Journal Pain & Symptom Management 2001
• Pathophysiology of itching
– Lancet 1996
• Oxford textbook of Palliative Medicine,
Symptom Management in Advanced
Cancer,Advanced Course in Pain &
Symptom Management
Antihistamines
• Useful where histamine release has role
• E.g. allergic rhinoconjunctivitis
• Lack activity in CRF, haematopoitic
disorders, opiod induced
• Pizotifen (antiserotoninergic action)
• Sedating doses e.g. hydroxyzine
Capsaicin
• Anti-inflammatory
• Reduces substance P from nerve endings
• Inhibits itch transmission
• Use : localised pruritus e.g. uraemia
Thalidomide
•
•
•
•
Reduce TNF synthesis
Anti-inflammatory
? Interfere with cytokine production
Use : uraemia
Cimetidine
• Role not established
• Enhance effect anti-histamines
• Use : uraemia
haematological malignancies
Antidepressants
• Signs depression / anxiety
• Failure to respond to standard therapy
• Tricyclics (doxepin)
– Antidepressant, antihistamine, sedative
• SSRI (paroxetine)
– Down-regulation post-synaptic receptors
– Reduce serotonin – receptor interaction
Role
• CRF
• Haematological malignancies
• Depressive disorders
• Neuroleptics / benzodiazepine use
5-HT3 Antagonists
•
•
•
•
•
Ondansetron
Serotonin mediator of itch
Use : cholestasis, uraemia, spinal opiods
Expensive
Often IV use
Opiod Antagonists
• Counteract endogenous opiods
• Can be impractical
• Naltrexone (oral preparation)
• Use : CRF, hepatogenic & haematological
pruritus
• ‘opiod abstinence syndrome’
• Buprenorphine
• Partial agonist
•
•
•
•
Nalbuphine
Mixed agonist-antagonist
Needs further evaluation
Opiod rotation
Anaesthetic Agents
•
•
•
•
•
Lignocaine
Abnormal pattern cutaneous innervation
Associated peripheral neuropathy
Use : uraemia
Toxic adverse effects
• Propofol
• Subhypnotic doses in hepatogenic pruritus
• Opiod induced
– ? Inhibit dorsal root transmission
– ? Blocks
Sequestrants
•
•
•
•
•
•
Cholestyramine
Reduce bile acids
Remove other pruritogens
Use : cholestasis
Unpalatable
Diarrhoea
• Charcoal
• Use : uraemia
• ?chelates metabolites
• Heparin
Disease Specific Drugs
•
•
•
•
•
Uraemia
Erythropoietin
UVB phototherapy
Parathyroidectomy
Transplantation
Disease Specific Drugs
• Cholestatic disease
• Androgens
– Stanazol, methytestosterone
• Rifampicin
• Biliary stenting definitive treatment
Ultraviolet Light
• UVB
• Reduce content vitamin A
• Inhibit release histamine & proliferation
mast cells
• Use : renal and liver disease, AIDS
•
•
•
•
•
•
PUVA
Ultrastructural changes in nerves
Increase sensory thresholds
Reduce end-organ responsiveness
? Stabilise mast cells
Use : pruritic dermatoses
Others
• TENS
– Induction on ‘lateral inhibition’ in spinal cord
•
•
•
•
Acupuncture
Plasma exchange
Psychotherapy
Relaxation