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PRURITUS

PRURITUS. Catriona Mayland July 2002. Definition Neuroanatomy Mediators Evaluation. General treatment Systemic disorders Specific treatment. Topics. Definition. Unpleasant sensation causing desire to scratch Normally protective function

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PRURITUS

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  1. PRURITUS Catriona Mayland July 2002

  2. Definition Neuroanatomy Mediators Evaluation General treatment Systemic disorders Specific treatment Topics

  3. Definition • Unpleasant sensation causing desire to scratch • Normally protective function • Sensation arises from superficial skin, mucous membranes, conjunctiva

  4. 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

  5. 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

  6. And there’s more… • Proteases e.g. tryptases, papain, kallikrein • Growth Factor • Neuropeptides • Substance P • CGRP, VIP, CCK • Bradykinin • Somatostatin, endothelin, neurokinin

  7. Histamine • Itching if applied to superficial damaged skin or injected intradermally • Dermal mast cells • Skin blood vessels, eccrine glands, basophils, hair follicles

  8. Action • Direct stimulation H receptors • ? stimulation formulation other mediators • Repeated injection – response decreases • ? role in chronic itch

  9. Serotonin • Action • Direct on peripheral serotoninergic receptors • C-fibres via 5-HT3 receptors

  10. 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

  11. Exacerbate Heat Anxiety Boredom Poor coping strategies Reduce Cold Relaxation Distraction Good coping stategies Other Mediators

  12. Evaluation • Primary dermatological disease • Systemic disease • History and examination • Drugs, onset, localised or systemic

  13. Non-drug Treatments • Discourage scratching – short nails • Avoid hot baths, overheating and sweating • Pat skin dry! Cool cotton clothes! • Avoid alcohol and spicy foods

  14. Skin Care • Emollient – aqueous cream & menthol • Calamine lotion - ?still recommended • Barrier cream • Consider hydrocortisone • NB Eurax and topical antihistamines

  15. Renal failure Hepatogenic Haematopoietic Endocrine Solid tumours HIV Opiod induced Neurogenic Aquagenic Inatrogenic Senile Psychogenic Systemic Disorders

  16. Chronic Renal Failure • Aetiology • Dry skin • Hyperparathyroidism • Mast cell proliferation • Loss opiod receptors and increased endogenous opiods

  17. Peripheral neuropathy • Increased • Histamine • Vitamin A • Magnesium, phosphate, aluminium • Serotonin • Substance P

  18. Hepatogenic Pruritus • PBC • drug induced cholestasis • Oral contraceptive, phenothiazines • Biliary obstruction

  19. Aetiology • ? Bile acids • ? Accumulation pruritogen intermediary • ? Histamine induced • ? Centrally activated pruritogenic opiod • ? Increased serotonin

  20. Haematopoietic Disorders • PCV • Increased histamine • Hodgkins • Others • ? Histamine • ? Autoimmune response • ? Infiltration • ? Release of leukopeptidase

  21. Endocrine Disorders • Thyrotoxicosis • ? Activate kinins • ? Reduced itch threshold • Hypothyroidism • xerosis • Diabetes mellitus • candida

  22. Solid Tumours • Paraneoplastic • ? Allergic reaction to Ag • ? Toxic products of necrotic tumour cells • Breast, stomach, lung, prostrate, colon

  23. 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

  24. Inatrogenic Pruritus • Aspirin • Hydroxyurea • Captopril • Antibiotics • Phenytoin • Allopurinol

  25. Neurogenic • Neuropathies • E.g. multiple sclerosis • Activation artificial synapses • Unilateral cerebral lesions • Effects on descending pathways • Post-herpetic neuralgia

  26. Senile Pruritus • Xerosis • Skin atropy • ? Age associated degeneration in nerve endings • ? Postmenopausal syndrome

  27. Psychogenic Pruritus • Feelings of hopelessness / helplessness • Secretion serotonin, dopamine • Elevated endogenous opiods • ? ‘depressive equivalent’

  28. HIV High prevalence skin disorders Abnormal levels cytokines Hypereosinophilia Peripheral neuropathy AQUAGENIC Contact with water Pathogenesis unknown Others

  29. 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

  30. Sequestrants Cholestyramine Charcoal Heparin Vaso-active drugs Alpha blockers Beta blockers Specific treatments

  31. Cholestatic disease Rifampicin Androgens Urso Stenting Uraemia Erythropoitin UVB phototherapy Parathyroidectomy Transplantation Disease Specific Interventions

  32. PCV – alpha interferon Fe deficiency – iron Thyroid disorder Disease Specific Interventions

  33. Miscellaneous • Phototherapy • TENS • Acupuncture • Psychotherapy • Relaxation

  34. Problems in Palliative Medicine • Most terminal phase • Changing organ function • Systemic treatment may be toxic, impractical

  35. Conclusions • Pathophysiology not fully understood • Peripheral and central mechanisms • Often associated with systemic diseases

  36. 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!

  37. 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

  38. 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

  39. Capsaicin • Anti-inflammatory • Reduces substance P from nerve endings • Inhibits itch transmission • Use : localised pruritus e.g. uraemia

  40. Thalidomide • Reduce TNF synthesis • Anti-inflammatory • ? Interfere with cytokine production • Use : uraemia

  41. Cimetidine • Role not established • Enhance effect anti-histamines • Use : uraemia haematological malignancies

  42. 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

  43. Role • CRF • Haematological malignancies • Depressive disorders • Neuroleptics / benzodiazepine use

  44. 5-HT3 Antagonists • Ondansetron • Serotonin mediator of itch • Use : cholestasis, uraemia, spinal opiods • Expensive • Often IV use

  45. Opiod Antagonists • Counteract endogenous opiods • Can be impractical • Naltrexone (oral preparation) • Use : CRF, hepatogenic & haematological pruritus • ‘opiod abstinence syndrome’

  46. Buprenorphine • Partial agonist • Nalbuphine • Mixed agonist-antagonist • Needs further evaluation • Opiod rotation

  47. Anaesthetic Agents • Lignocaine • Abnormal pattern cutaneous innervation • Associated peripheral neuropathy • Use : uraemia • Toxic adverse effects

  48. Propofol • Subhypnotic doses in hepatogenic pruritus • Opiod induced • ? Inhibit dorsal root transmission • ? Blocks

  49. Sequestrants • Cholestyramine • Reduce bile acids • Remove other pruritogens • Use : cholestasis • Unpalatable • Diarrhoea

  50. Charcoal • Use : uraemia • ?chelates metabolites • Heparin

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