PRURITUS

Catriona Mayland

July 2002

Topics

• Definition

• Neuroanatomy

• Mediators

• Evaluation

• General treatment

• Systemic disorders

• Specific treatment

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