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Pruritus and Dysesthesia


Definitions

  • Pruritus: an unpleasant sensation of the skin that elicits a desire to scratch.

  • Dysesthesia: an unpleasant, abnormal sensation that can be either spontaneous or evoked; abnormal, unpleasant sensations may include pain, pruritus (“neuropathic itch”), tingling, burning, “pins and needles”.

Pruritus

  • The most common skin-related symptom in dermatology; can have a profound negative impact on a patient’s quality of life.

  • Results from the activation of the sensory nervous system, involving four sequential levels: the peripheral nervous system → the dorsal root ganglia → the spinal cord → and the brain.

  • There are multiple etiologies of pruritus, and it is often a major clinical challenge to diagnose the underlying etiology and to adequately treat.

Etiologies

  • May arise secondary to a number of conditions:

    • –

      Dermatologic disorders ( Table 4.1 , Fig. 4.1 )

      Table 4.1
      Common dermatologic diseases with pruritus as a major symptom.
      BP, bullous pemphigoid; DH, dermatitis herpetiformis; LS, lichen sclerosus; PMLE polymorphous light eruption.
      Infestations/bites and stings

      • Scabies, pediculosis, arthropod bites

      Inflammation

      • Dermatitis: atopic, stasis, allergic > irritant, seborrheic (especially of the scalp)

      • Psoriasis, parapsoriasis

      • Lichen planus

      • Urticaria, dermographism ( Fig. 4.4 ), papular urticaria, urticarial dermatitis

      • Drug eruptions (e.g. morbilliform)

      • Bullous diseases (e.g. BP, DH)

      • Mastocytosis

      • Eosinophilic folliculitis

      • Pruritic papular eruption of HIV

      • LS (especially of the vulva), dermatomyositis, LE (systemic and cutaneous)

      • GVHD

      Infection

      • Bacterial (e.g. folliculitis)

      • Viral (e.g. varicella)

      • Fungal (e.g. inflammatory tinea)

      • Parasitic (e.g. schistosomal cercarial dermatitis)

      Neoplastic

      • Cutaneous T-cell lymphoma (e.g. mycosis fungoides, Sézary syndrome)

      Other

      • Xerosis/eczema craquelé

      • Scar-associated pruritus, post-burn pruritus

      • Fiberglass dermatitis

      • Lichen simplex chronicus, prurigo nodularis

      • Primary cutaneous amyloidosis (macular, lichenoid)

      • Pregnancy dermatoses

      • Neuropathic itch (e.g. notalgia paresthetica)

      • PMLE, actinic prurigo, chronic actinic dermatitis

      • Darier and Hailey–Hailey disease

      • Porphyrias

      • Ichthyoses

      Fig. 4.1, Nonspecific lesions in atopic dermatitis.

    • –

      Allergic or hypersensitivity syndromes

    • –

      Systemic diseases (10–25%) and malignancies ( Figs 4.2 and 4.3 )

      Fig. 4.2, A simplified approach to the patient with pruritus.

      Fig. 4.3, Xerosis and pruritus in a patient with end-stage renal failure on hemodialysis.

      Fig. 4.4, Dermographism.

    • –

      Toxins associated with kidney or liver dysfunction

    • –

      Medications ( Table 4.2 )

      Table 4.2
      Common pharmacologic etiologies of pruritus without a rash.
      Itch may also occur as a direct effect of interleukin 2 therapy. Additional drugs may cause pruritus secondary to cholestatic injury (e.g. sulfonamides, penicillins, erythromycin estolate). CTLA-4, cytotoxic T lymphocyte-associated antigen 4; PD-1, programmed cell death protein 1.
      Most common

      • Opioids: tramadol, codeine, morphine ∗ , ∗∗ , butorphanol ∗ , fentanyl ∗

      • Illicit drugs: methamphetamine, cocaine

      Less common

      • Antihypertensives: calcium channel blockers

      • Antimalarials: chloroquine (most common in individuals of African heritage)

      • Psychotropic drugs: selective serotonin reuptake inhibitors

      • Anti-neoplastic agents : CTLA-4 inhibitors, PD-1 inhibitors, EGFR inhibitors, selective BRAF or MEK inhibitors, tyrosine kinase inhibitors (e.g. sorafenib [especially scalp pruritus])

      • Other: statins, hydroxyethyl starch, omeprazole, paclitaxel, tamoxifen, granulocyte–macrophage colony-stimulating factor, interferon

      ∗ Pruritus is more likely with intrathecal/epidural than systemic administration.

      ∗∗ Also causes nonimmunologic release of histamine from mast cells.

    • –

      Neurologic disorders (see text below)

    • –

      Psychiatric conditions (see Ch. 5 )

  • May also be primary or idiopathic – that is, no readily apparent skin disease, underlying etiology, or associated condition.

  • Most patients with pruritus due to an underlying dermatologic disorder present with characteristic or diagnostic skin lesions (e.g. dermatitis of the flexures in atopic dermatitis; see Table 4.1 ).

  • In primary pruritus and secondary pruritus NOT due to an underlying dermatologic disorder, the lesions are usually nonspecific (e.g. linear excoriations [see Fig. 4.1 ], prurigo simplex, prurigo nodularis [ Figs 4.5 and 4.6 ]).

    Fig. 4.5, Prurigo nodularis.

    Fig. 4.6, Multiple lesions of prurigo nodularis.

Diagnostic Pearls

  • Patients with chronic, idiopathic pruritus need serial examinations because pruritus can antedate clinical manifestations of the underlying disorder (e.g. lymphoma) or with time, more specific lesions may appear (e.g. bullous pemphigoid).

  • Sparing of the mid upper back, an area of patient-hand inaccessibility (‘butterfly sign’) (see Fig. 4.6 ), is suggestive of pruritus NOT associated with a dermatologic disorder; note, however, this sign is not seen in those who use back scratchers or similar devices.

  • Aquagenic pruritus, provoked by cooling of the skin after emergence from a bath, is often idiopathic but may be a sign of polycythemia vera.

  • Of note, some patients may have a combination of specific and nonspecific skin lesions and both may be due to an underlying systemic disorder (e.g. eosinophilic folliculitis associated with HIV infection/AIDS).

Approach to the Patient with Pruritus

  • Identifying the underlying etiology of a patient’s pruritus is important in determining the appropriate management.

  • A simplified approach to the patient with pruritus is presented in Fig. 4.2 and Table 4.3 .

    Table 4.3
    Laboratory and radiographic evaluation of the patient with generalized pruritus of unknown etiology.
    A general physical examination should also be performed by the patient’s primary care physician. Selection of particular tests beyond the basic initial evaluation is based upon the patient’s history, physical examination findings, and pruritus severity. The results of initial testing can also help to direct further evaluation.
    Basic initial evaluation
    CBC with differential and platelet count
    ESR and CRP
    Creatinine, blood urea nitrogen, electrolytes
    Liver transaminases, alkaline phosphatase, bilirubin
    LDH
    Fasting glucose
    TSH ± free thyroxine

    Possible additional evaluation
    Skin biopsy
    Routine histology (if skin lesions are present)
    Direct immunofluorescence studies ∗
    Other laboratory tests
    Serum total and/or allergen-specific IgE
    Serum ferritin, iron, total iron binding capacity
    Hemoglobin A1c
    Parathyroid function (calcium, phosphate and parathyroid hormone levels)
    Stool for ova/parasites and/or occult blood
    Viral hepatitis panel (including hepatitis B and C viruses)
    HIV testing
    Anti-tissue transglutaminase ± epidermal transglutaminase IgA antibodies ∗∗
    Anti-BP180 and anti-BP230 bullous pemphigoid IgG antibodies
    Anti-mitochondrial and anti-smooth muscle antibodies
    Serum tryptase, histamine, and/or chromogranin-A levels
    Urinalysis with sediment evaluation
    24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA; a serotonin metabolite) and porphyrins
    Serum protein electrophoresis, serum immunofixation electrophoresis
    Radiographic studies
    Chest X-ray or CT scan
    Abdominal and pelvic ultrasonography or CT scan
    Lymph node ultrasonography
    Other investigations
    Patch testing
    Prick testing for major atopy and relevant occupational allergens
    Age-appropriate cancer screening (in conjunction with primary care physician)
    If hydroxyethyl starch (HES)-induced pruritus is suspected, electron microscopy of a biopsy sample from normal-appearing skin

    ∗ Biopsy perilesional skin or normal-appearing skin (in vicinity of lesions if present) to assess for bullous pemphigoid and dermatitis herpetiformis, respectively.

    ∗∗ Often performed in conjunction with serum total IgA; in patients with IgA deficiency, anti-tissue transglutaminase IgG antibodies should be assessed.

Management of Pruritus

  • General treatment measures for pruritus are outlined in Table 4.4 .

    Table 4.4
    General measures for the treatment of pruritus and dysesthesia.
    CTCL, cutaneous T-cell lymphoma.
    Skin care

    • Lukewarm baths or showers with minimal use of soap (use mild soaps or non-soap cleansers)

    • Moisturization twice a day, especially while skin still damp (ointment > cream)

    • Avoid woolens, harsh fabrics, fabric softeners

    • Keep nails cut short

    • Address any superimposed dermographism

    Topicals

    • Cooling agents/counterirritants : e.g. menthol, camphor, capsaicin (best for localized itch, especially of neuropathic origin)

    • Anesthetics : e.g. pramoxine, lidocaine, prilocaine, polidocanol, palmitoylethanolamine

    • Anti-inflammatory agents : corticosteroids, calcineurin inhibitors

    Systemic medications

    • Antihistamines : especially if there is a component of dermographism or urticaria; otherwise limited efficacy beyond sedative effects; consider doxepin (beginning with 10–25 mg at bedtime)

    • Neuromodulators : gabapentin, pregabalin (best for neuropathic pruritus, post-herpetic neuralgia, post-burn pruritus)

    • Antidepressants: SSRIs (e.g. fluoxetine, paroxetine, sertraline, venlafaxine), tricyclics (e.g. amitriptyline, doxepin), mirtazapine (sedative effects)

    • Opioid antagonists/agonists: e.g. naltrexone, naloxone, nalfurafine ∗ , butorphanol nasal spray

    • Other: thalidomide, monoclonal antibodies (e.g. nemolizumab, dupilumab; especially for prurigo nodularis); aprepitant (reports of benefit in atopic dermatitis, CTCL, and itch induced by EGFR- and tyrosine kinase-inhibitors)

    Physical modalities

    • Phototherapy : UVB (broadband or narrowband), PUVA, UVA, UVA-1

    • Acupuncture

    Psychological approaches

    • Behavior modification therapy, biofeedback

    • Support groups

    Treatment for renal pruritus

    • Topical measures: capsaicin, pramoxine, γ-linolenic acid, cromolyn sodium

    • Systemic measures (first-line): gabapentin, pregabalin, UVB (broadband or narrowband)

    • Systemic measures (second-line): naltrexone, nalfurafine ∗

    Treatment for hepatic pruritus

    • Systemic measures (first-line): cholestyramine, ursodeoxycholic acid

    • Systemic measures (second-line): rifampin

    • Systemic measures (third-line): naloxone, naltrexone, nalfurafine ∗

    ∗ Kappa-opioid receptor agonist; available in Japan.

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