Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory...
Transcript of Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory...
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Just an Itch?Beyond Benadryl™
Michael Greenwald, MDAssistant Professor, Pediatrics
Emory UniversityChildren’s Healthcare of Atlanta
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Objectives
• Understand the relationship between pain (sensation and treatment) and pruritis
• Understand basic pathophysiologic mechanisms for itching
• Identify effective treatments for various causes of itching
• Psychologically induce everyone here to scratch themselves at least once
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#1 Help this patient
• A 12 y/o with Sickle Cell Disease presents to the ED with an acute vaso-occlusive crisis. After his first dose of morphine he experiences generalized intense itching. His pain is still high (7/10).
• So now you have 2 problems - what do you recommend?
![Page 8: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/8.jpg)
#2 Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 9: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/9.jpg)
Part I: Understanding the Itch
• Definition
• Epidemiology
• Pathophysiology
• Why We Scratch
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Part II: How to treat an Itch(Understand the Cause!)
• Inhibit mediators of itch
• Block chemicals that induce pruritis
• Treat effects of diseases which induce itching
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Defining Pruritis
An unpleasant localized or generalized sensation on the skin, mucus membranes or conjunctivae which the patient instinctively attempts to relieve by scratching or rubbing
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Diversity of Causes and Presentation
Many Causes, Many Treatments
Trivial to to Life threatening
(mosquito bite) (malignancy)
10-50% of cases with generalized itching have systemic disease
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Diseases & Itching
• Infections• Infestations (scabies)• Inflammatory skin
conditions (eczema, contact derm, psoriasis)
• Chronic Renal Failure• Cholestatic liver
disease• Depression/anxiety
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Assessment Challenges
• No assessment tool validated to study levels of distress from itching
• Most rely on 0-10 VAS similar to pain scores
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Poorly Understood & Managed
• Relies on similar components of the pain system: receptors, neurotransmitters, spinal pathways and centers in the brain
• Stimulating pain can relief itching• Treating pain with some analgesics
relieves itching, others trigger itching• Pruritis is a common side-effect of opioid
administration, sometimes worse than the pain
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Pruritogenic Stimuli
• Pressure
• Low-intensity electrical or punctate stimuli (TENS)
• Histamine: acts directly on free nerve endings in skin
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Itch Pathways
• Cutaneous (pruritoceptive)
• Neurogenic
• Neuropathic
• Mixed Psychogenic
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Pain vs Itch Nerves
• Itch transmitted from specialized pain receptors: a subclass of C-nociceptors– Mechano-insensitive– Histamine sensitive
• Nerve endings cluster around “itch points” which correspond to areas very sensitive to pruritogenic stimuli
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Itch pathways
• Fibers originate @ dermal/epidermal jxn • Thin unmyelinated axons, lots of branching • Ipsilateral dorsal horn of spinal cord • Synapse with itch-specific secondary neurons• Cross to opposite anterolateral spinothalamic
tract to thalamus • Somatosensory cortex of postcentral gyrus SLOW transmission and BROAD receptor field
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Itch Mediators
• Histamine• Prostaglandins• Leukotrienes• Serotonin• Acetylcholine
• Substance P• Proteases• Peptides• Enzymes• Cytokines
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Why do you scratch?
• Histamine activates both the anterior cingulate cortex (sensory, emotions) and the supplemental motor area
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Lateral Inhibition: “Gate Theory”
• Noxious stimuli of skin adjacent to pruritic trigger attenuates initial itch sensation
• Scratching stimulates large fast-conducting A-fibers adjacent to slow unmyelinated C fibers
• A-fibers synapse with inhibitory interneurons and inhibit C-fibers
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Pain & Itch
• Painful stimuli (thermal, mechanical, chemical) can inhibit itching
• Inhibition of pain (opioids) may enhance itching
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Part II: How to Treat an Itch(Understand the Cause!)
Inhibit mediators of itch: histamine, prostaglandins, substance P, serotonin, cytokines
Block chemicals that induce pruritis: opioids, antimicrobials
Treat effects of diseases which induce itching: eczema, CRF, LF, heme, neuro, endo
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Itch Mediators: Histamine
• Different effects on different H receptors• applied into epidermis itch • applied into dermis pain
• Only a few types of itch relieved by anti-histamines (i.e. those caused by histamine release in the skin): insect bites, allergic skin reactions, cutaneous mastocytosis
• 85% H receptors in skin are H1• 15% H receptors are H2
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NSAIDs for itching?
• Prostaglandins cause itch directly on conjunctiva (but no effect when directly applied to skin)
• Potentiates histamine elicited itchKetorolac eases itch in conjunctiva
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Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 32: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/32.jpg)
Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 33: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/33.jpg)
Substance “P” (“P” for pain and pruritis?)
• Neuropeptide synthesized in C-fibers @ DRG• Transmitted to free nerve endings to modulate
pain and pruritis• Substance P containing C-fibers most abundant
near junction b/epidermis & dermis (esp in lips, fingertips, prepuce and breast)
• Induces pruritis directly & indirectly by releasing histamine from mast cells– Hemodialysis-associated itch– Atopic dermatitis– Psoriasis
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Substance P Depletion
• Capsaicin cream: excites C-fibers release substance P & calcitonin gene-related peptide depletion of both– .025% 5 times a day for notalgia
paraesthetica
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Other Peptides
• Bradykinin: pain, inflammation & itch
• Neurotension, Vasoactive Intestinal Peptide, Somatostatin, Melanocyte-stimulating hormone: histamine release from dermal mast cells
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Acetylcholine
• Intra-dermal injection usually burning• In eczema itching
Independent of histamine
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Serotonin
• Some patients with refractory itch have been relieved by serotonin antagonist odansetron (Zofran)
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Itch & Inflammation
• Cytokines: LMW mediators of inflammatory signals b/cells (e.g. TNF)
• Induce cells to secrete chemokines which cause migration of inflammatory cells from vascular space to inflammatory site
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Chemically induced itching:Systemic Opioids
• Usually face (trigem. nerve), neck, upper thorax• 0-90%• Not necessarily related to dose incidence during pregnancy (interaction b/
estrogen & opiate receptors)• Morphine, sufentanil > fentanyl > butorphenol• Histamine is released, but not the main cause of
itching• Site of injection vs distal to injection
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Opioid induced itching:Systemic vs Local
• Nonimmunologic release of histamine from morphine, codeine, meperidine
Attentuated by opioid receptor antagonists
• Intradermal morphine reduced by H1 antihistamines but not naloxone
• H2 blockers alone not effective but enhance H1 blockers
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Help this patient
• A 12 y/o with Sickle Cell Disease presents to the ED with an acute vaso-occlusive crisis. After his first dose of morphine he experiences generalized intense itching. His pain is still high (7/10).
• So now you have 2 problems - what do you recommend?
![Page 42: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/42.jpg)
Help this patient
• A 12 y/o with Sickle Cell Disease presents to the ED with an acute vaso-occlusive crisis. After his first dose of morphine he experiences intense itching. His pain is still high (7/10).
• So now you have 2 problems - what do you recommend?
Nubain
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Chemically induced itching:Neuroaxial
• Intrathecal, epidural opioids commonly complicated by pruritis
• Direct action on medullary dorsal horn and trigeminal nucleus of medulla – not t/histamine release
• Blocked by naloxone (therefore opioid receptor mediated)
• Also possibly related to antagonism to inhibitory neurotransmitters GABA and Glycine and 5-HT receptors (ondansteron effective)
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Chemically induced itching:Neuroaxial
• Spinal anesthesia with lidocaine: 30-100% pruritis
• Fentanyl:– Intrathecal 67-100%– Epidural 67%
• Morphine– Intrathecal 62-82%– Epidural 65-70%
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Treatments: opioid related pruritis
• Diphenhydramine – for systemic opioids
• For Neuraxial Opioids:– Ondansteron – Naloxone (1-2mcg/kg/hr)– Nalbuphine (10-20 mcg/kg/hr) – Propofol (.5-1mg/kg/hr)– Lidocaine (2mg/kg/hr)– NSAIDs (diclofenac, tenoxicam)– Droperidol
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Chemically induced itching:Antibiotics
• Penicillin: immediate type I hypersensitivity reaction
• Vancomycin: massive nonimmunologic release of histamine “Red Man Syndrome” – (flushing CP, pruritis, muscle spasms, hypotension)– Related to rate of infusion– Potentiated by muscle relaxants and opioids– Attenuated by H1 blockers
• Rifampin
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Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 48: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/48.jpg)
Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron Diphenhydramine• Topical Steroids
![Page 49: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/49.jpg)
Chemically induced itching:Other drugs
• Fentanyl: itching decreased when mixed with bupivicane, increased when mixed with procaine
• Drug induced cholestasis – esp phenothiazenes, estrogens, tolbutamide,
anabolic steroids
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Diseases Associated with Itching
• Renal • Hepatic • H Pylori Infection• Hematologic d/o
• Metabolic/Endocrine• Neurologic• HIV• Skin Diseases
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Eczema & Itching
• Hallmark of atopic dermatitis
• >80% pts recognize stress as a trigger for increased itching
• Alexithyma: Patients with chronic dermatosis who develop abnormal language development as a result of the perception that touch is noxious
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Eczema & Itching: Treatment
cool compresses emollients topical steroids antidepressants anxiolytics antibiotics
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Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 54: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/54.jpg)
Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine Topical Steroids
![Page 55: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/55.jpg)
Systemic Treatment: Histamine blockers
• H1-receptor antagonists: diphenhydramine
• Side effects: anticholinergic effects, paradoxical agitation, excessive sedation
• H2-antagonists may enhance H1-blockers
• No quality studies demonstrating efficacy of oral antihistamines for atopic dermatitis!
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Renal Diseases and Itching
• Chronic Renal Failure: 25-86% itching (not in acute renal failure)
• Attrib to accumulation of pruritogens: histamine (mast cells), serotonin Ca, Phos, Mg, Al, vit A also implicated
• 1/3 uremic patients not on dialysis• Maintenance hemodialysis: 70-80%
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Renal Diseases and Itching
• Tx for uremic itching: renal transplant– Effective even when transplant is failing as long as
immunosuppresants are given– Antihistamines not effective
• Also effective: moisturizers, UV-B tx (vit A in skin), oral activated charcoal, cholstyramine, naltrexone, ondansterone, topical capsaicin, azelastin, thalidomide, IV lidocaine, erythropoetin, electric needle stim
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Match D/O with Antipruritic
Lymphoma Chronic Renal
Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
Activated Charcoal• Cimetidine• Toradol Odansetron• Diphenhydramine• Topical Steroids
![Page 59: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/59.jpg)
Hepatic Diseases & Itching
• 20-25% janudiced patients with hepatobiliary disease associated with cholestasis– 100% primary biliary cirrhosis– Viral hepatitis
• Attrib to bile salts in serum and tissues
• Begins palms and soles & spreads inward
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Hepatic Diseases & Itching
• Tx: reverse cholestatis, liver transplant
• Also helpful: oral guar gum (dietary fiber) binds bile acids; cholestyramine; rifampin! (inhibits bile uptake), opioid antagonists, codeine, propofol, ondansetron
• Not helpful: scratching
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Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol Odansetron• Diphenhydramine• Topical Steroids
![Page 62: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/62.jpg)
Hematologic Disease & Itching
• Polycythemia vera (50%) hydroxyurea tx
• iron def anemia,
• lymphomas (Tx: cimetidine)– Hodgkins – 30%– T-cell: almost all
• leukemias, plasma cell dyscrasias, mastocytosis
![Page 63: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/63.jpg)
Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal• Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 64: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/64.jpg)
Match D/O with Antipruritic
Lymphoma Chronic Renal Failure Liver Failure Conjunctivitis Eczema Penicillin Reaction
• Activated Charcoal Cimetidine• Toradol• Odansetron• Diphenhydramine• Topical Steroids
![Page 65: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/65.jpg)
Neurologic Disorders & Itching
• Central: MS, CNS abscess, spinal and cerebral tumors (17%), CVAs– Attrib to effects on descending pathways
which itching
• Neurogenic– Shingles (10-15% in US)– Notalgia paresthetica: sensory entrapment
syndrome causing neuropathy of T2-6 dorsal spinal nerves
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Endocrine D/O & Itching
• Diabetes
• Thyrotoxicosis
• Myxodema
• Postmenopausal syndrome
Most common trigger: mucocutanious candidiasis
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What to Ask of the Itchy Patient
• Local vs generalized?
• Sequence of events: itch vs rash
• Description of sensation
• Timing & severity
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General Approach to Itching
Treat the CauseTreat the Co-morbidities
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Conclusions
• Pruritis is common and often disabling
• Pruritis has many similarities to pain
• Pruritis is related but not identical to pain
• Effective interventions are possible
• Antihistamines are not always the most effective treatment
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Questions?
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![Page 72: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/72.jpg)
Systemic Treatment: Opioids
• Naloxone (.8mg) for biliary cirrhosis
• Nalmefene (5mg BID): – more potent and longer duration (12-48hrs)– May induce w/drawl sx if stopped abruptly
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Take Home Points
Pain and Itching are intimately related– Cause/Triggers– Patho-physiology – Treatment
Different mechanisms for itching call for different treatments
Antihistamines are effective for a select few causes of itching
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![Page 75: Just an Itch? Beyond Benadryl ™ Michael Greenwald, MD Assistant Professor, Pediatrics Emory University Children’s Healthcare of Atlanta.](https://reader030.fdocuments.in/reader030/viewer/2022032600/56649dc05503460f94ab452d/html5/thumbnails/75.jpg)
Treatment
• Cooling skin (eczema and other dermatoses)
• Vibration, TENS for localized and generalized pruritis (effectiveness dissipates w/use)
• UV therapy for chronic renal failure– Inhibits release of histamine and proliferation
of dermal mast cells
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Treatment: Topicals
• Moisturizers, calamine, antihistamines, corticosteroids, EMLA
• Capsaicin cream: excites C-fibers release substance P & calcitonin gene-related peptide depletion of both– .025% 5 times a day for notalgia
paraesthetica
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