Just an Itch eczema by mikeholy

VIEWS: 8 PAGES: 77

									  Just an Itch?
Beyond Benadryl™
  Michael Greenwald, MD
 Assistant Professor, Pediatrics
        Emory University
 Children’s Healthcare of Atlanta
              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
        #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?
    #2 Match D/O with Antipruritic
   Lymphoma                •   Activated Charcoal
   Chronic Renal Failure   •   Cimetidine
   Liver Failure           •   Toradol
   Conjunctivitis          •   Odansetron
   Eczema                  •   Diphenhydramine
   Penicillin Reaction     •   Topical Steroids
    Part I: Understanding the Itch
•   Definition
•   Epidemiology
•   Pathophysiology
•   Why We Scratch
     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
          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
       Diversity of Causes and
            Presentation

     Many Causes, Many Treatments

          Trivial to Life threatening
       (mosquito bite)   (malignancy)

10-50% of cases with generalized itching have
 systemic disease
           Diseases & Itching
• Infections               • Chronic Renal Failure
• Infestations (scabies)   • Cholestatic liver
• Inflammatory skin          disease
  conditions (eczema,      • Depression/anxiety
  contact derm,
  psoriasis)
     Assessment Challenges
• No assessment tool validated to study
  levels of distress from itching

• Most rely on 0-10 VAS similar to pain
  scores
 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
         Pruritogenic Stimuli
• Pressure
• Low-intensity electrical or punctate stimuli
  (TENS)
• Histamine: acts directly on free nerve
  endings in skin
              Itch Pathways
•   Cutaneous (pruritoceptive)
•   Neurogenic
•   Neuropathic
•   Mixed Psychogenic
         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
              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
               Itch Mediators
•   Histamine         •   Substance P
•   Prostaglandins    •   Proteases
•   Leukotrienes      •   Peptides
•   Serotonin         •   Enzymes
•   Acetylcholine     •   Cytokines
       Why do you scratch?
• Histamine activates both the anterior
  cingulate cortex (sensory, emotions) and
  the supplemental motor area
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
              Pain & Itch
• Painful stimuli (thermal, mechanical,
  chemical) can inhibit itching
• Inhibition of pain (opioids) may enhance
  itching
    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
     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
         NSAIDs for itching?
• Prostaglandins cause itch directly on
  conjunctiva (but no effect when directly
  applied to skin)
• Potentiates histamine elicited itch
Ketorolac eases itch in conjunctiva
      Match D/O with Antipruritic
   Lymphoma                •   Activated Charcoal
   Chronic Renal Failure   •   Cimetidine
   Liver Failure           •   Toradol
   Conjunctivitis          •   Odansetron
   Eczema                  •   Diphenhydramine
   Penicillin Reaction     •   Topical Steroids
      Match D/O with Antipruritic
   Lymphoma                • Activated Charcoal
   Chronic Renal Failure   • Cimetidine
   Liver Failure            Toradol
   Conjunctivitis          • Odansetron
   Eczema                  • Diphenhydramine
   Penicillin Reaction     • Topical Steroids
              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
      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
            Other Peptides
• Bradykinin: pain, inflammation & itch


• Neurotension, Vasoactive Intestinal Peptide,
  Somatostatin, Melanocyte-stimulating hormone:
   histamine release from dermal mast cells
              Acetylcholine
• Intra-dermal injection usually  burning
• In eczema  itching
  Independent of histamine
               Serotonin
• Some patients with refractory itch have
  been relieved by serotonin antagonist
  odansetron (Zofran)
         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
     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
       Opioid induced itching:
     Systemic     vs       Local
• Nonimmunologic          • Intradermal morphine
  release of histamine      reduced by H1
  from morphine,            antihistamines but not
  codeine, meperidine       naloxone
 Attentuated by opioid   • H2 blockers alone not
  receptor antagonists      effective but enhance
                            H1 blockers
           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?
           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
      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)
     Chemically induced itching:
            Neuroaxial
• Spinal anesthesia with lidocaine: 30-100%
  pruritis
• Fentanyl:
  – Intrathecal 67-100%
  – Epidural 67%
• Morphine
  – Intrathecal 62-82%
  – Epidural 65-70%
 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
       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
      Match D/O with Antipruritic
   Lymphoma                •   Activated Charcoal
   Chronic Renal Failure   •   Cimetidine
   Liver Failure           •   Toradol
   Conjunctivitis          •   Odansetron
   Eczema                  •   Diphenhydramine
   Penicillin Reaction     •   Topical Steroids
      Match D/O with Antipruritic
   Lymphoma                • Activated Charcoal
   Chronic Renal Failure   • Cimetidine
   Liver Failure           • Toradol
   Conjunctivitis          • Odansetron
   Eczema                   Diphenhydramine
   Penicillin Reaction     • Topical Steroids
    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
    Diseases Associated with Itching
•   Renal                •   Metabolic/Endocrine
•   Hepatic              •   Neurologic
•   H Pylori Infection   •   HIV
•   Hematologic d/o      •   Skin Diseases
          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
    Eczema & Itching: Treatment
   cool compresses
   emollients
   topical steroids
   antidepressants
   anxiolytics
   antibiotics
      Match D/O with Antipruritic
   Lymphoma                •   Activated Charcoal
   Chronic Renal Failure   •   Cimetidine
   Liver Failure           •   Toradol
   Conjunctivitis          •   Odansetron
   Eczema                  •   Diphenhydramine
   Penicillin Reaction     •   Topical Steroids
      Match D/O with Antipruritic
   Lymphoma                • Activated Charcoal
   Chronic Renal Failure   • Cimetidine
   Liver Failure           • Toradol
   Conjunctivitis          • Odansetron
   Eczema                  • Diphenhydramine
   Penicillin Reaction      Topical Steroids
         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!
    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%
    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
    Match D/O with Antipruritic
 Lymphoma               Activated Charcoal
 Chronic Renal         • Cimetidine
  Failure               • Toradol
 Liver Failure          Odansetron
 Conjunctivitis        • Diphenhydramine
 Eczema                • Topical Steroids
 Penicillin Reaction
   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
   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
      Match D/O with Antipruritic
   Lymphoma                • Activated Charcoal
   Chronic Renal Failure   • Cimetidine
   Liver Failure           • Toradol
   Conjunctivitis           Odansetron
   Eczema                  • Diphenhydramine
   Penicillin Reaction     • Topical Steroids
 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
      Match D/O with Antipruritic
   Lymphoma                •   Activated Charcoal
   Chronic Renal Failure   •   Cimetidine
   Liver Failure           •   Toradol
   Conjunctivitis          •   Odansetron
   Eczema                  •   Diphenhydramine
   Penicillin Reaction     •   Topical Steroids
      Match D/O with Antipruritic
   Lymphoma                • Activated Charcoal
   Chronic Renal Failure    Cimetidine
   Liver Failure           • Toradol
   Conjunctivitis          • Odansetron
   Eczema                  • Diphenhydramine
   Penicillin Reaction     • Topical Steroids
 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
       Endocrine D/O & Itching
•   Diabetes
•   Thyrotoxicosis
•   Myxodema
•   Postmenopausal syndrome

Most common trigger: mucocutanious
 candidiasis
What to Ask of the Itchy Patient
•   Local vs generalized?
•   Sequence of events: itch vs rash
•   Description of sensation
•   Timing & severity
  General Approach to Itching
Treat the Cause
Treat the Co-morbidities
                 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
Questions?
         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
         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
                 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
        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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