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Holistic approach to treatment of intractable central neuropathic itch
Holistic approach to treatment of intractable central neuropathic itch Ashley R. Curtis, MD,a Charles Tegeler, MD,b Jonathan Burdette, MD,c and Gil Yosipovitch, MDa Winston-Salem, North Carolina Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch. ( J Am Acad Dermatol 2011;64:955-9.) Key words: central neuropathic itch; generalized pruritus; holistic medicine; neuropathic itch; pruritus treatment.
C
entral neuropathic itch results from lesions in the central nervous system.1-3 It has been associated with cerebral vascular accidents, Wallenberg syndrome, demyelinating disorders, and tumors and abscesses of the central nervous system.1-6 Table I summarizes the list of published causes of central neuropathic itch. This type of pruritus is a therapeutic challenge and literature regarding effective treatment is sparse. We present a case of a patient with a history of traumatic brain injury with intractable pruritus who failed extensive conventional and nonconventional pharmacologic treatment but responded to a holistic approach using a biofield therapy, energy medicine modality, healing touch (HT). A 25-year-old man with a history of a severe traumatic brain injury and subsequent ischemic stroke 3 years earlier presented with a 6-month history of severe intractable pruritus. The onset of the itch coincided with an increase in cognitive function revolving around improved short- and long-term memory. He noted the pruritus changed
From the Departments of Dermatology,a Neurology,b and Radiology,c Wake Forest University Baptist Medical Center. Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Ashley R. Curtis, MD, Department of Dermatology, Wake Forest University Baptist Medical Center, Medical Center Blvd, Winston-Salem, NC 27157. E-mail: acurtis@ wfubmc.edu. Published online February 4, 2011. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.02.023
locations daily, but was mainly located on the face, chest, and arms. The itching was constant, and the patient described it as analogous to ‘‘hundreds of mosquitoes biting me.’’ He rated the itch a 10 on a scale from 1 to 10 and mentioned it repeatedly throughout each day. The patient actively scratched throughout the dermatologic examination and no primary lesions were identified. The initial neurologic injury occurred when the patient was accosted with a baseball bat, with multiple blows to the head. Early surgical decompression of a subdural hematoma was required. This was followed 2 days later by craniectomy to relieve pressure related to brain swelling and mass effect. Neurologic deficits persisting beyond the acute period included loss of peripheral vision bilaterally, posttraumatic amnesia, and impaired cognitive function with mild left hemiparesis, particularly noticeable in the left hand. He also had several seizures about 4 months after the injury, and experienced headaches and disturbed sleep, the latter associated with the pruritus. Both computed tomography and magnetic resonance imaging results demonstrated extensive traumatic ischemic injury, especially to the frontal and occipital regions and clear ischemic injury to the medial thalamus (Figs 1 and 2). A comprehensive laboratory workup including complete blood cell count, complete metabolic panel, and thyroid function revealed normal findings. A chest radiograph also produced normal results. No hydroxyethyl starch was administered after brain trauma. Treatment before presentation consisted of pregabalin in doses up to 300 mg per day, gabapentin up to 3600 mg per day, hydroxyzine at 100 mg per 955
956 Curtis et al
J AM ACAD DERMATOL MAY 2011
day, doxepin up to 75 mg per day, and nonsedating Hypothetical mechanisms proposed for neuropathic antihistamines and topical steroids, none of which itch include local nerve damage with spontaneous provided any relief. In addition, the patient had firing by damaged neurons, central neuronal depritherapy sessions with a psychologist with no effect. vation of afferent input, and central hypersensitivity Prior treatment was discontinued and inhaled butorof nerve fibers.1,8,9 The cause of central itch in our patient is hypothesized to be from central hyperphanol was started at 1 mg/mL increasing to 3 mg per sensitivity of nerve fibers resulting from the day, along with lidocaine/prilocaine 2.5% cream, 5% thalamic infarcts. In addition, lidocaine patch, and 0.1% an improvement in cognitive capsaicin. After 1 month of CAPSULE SUMMARY function may have contribtreatment and no response, uted to the itch sensation. It the butorphanol was disconCentral neuropathic itch results from is well known that itch pertinued and mirtazapine at 15 lesions in the central nervous system. ception is highly influenced mg nightly along with croVarious causes include cerebral vascular by memories.7 The pathotamiton 10%, topical menaccidents, demyelinating disorders, logical central itch could be thol, and oatmeal soothing tumors, and abscesses. the result of long-term plastic baths were started. At 1changes along the somatomonth follow-up, the patient This type of itch is hypothesized to be sensory pathways. Because reported no improvement in associated with central hypersensitivity of this long-term plasticity symptoms. Similarly, on exof nerve fibers. damage in central regions, hyamination he had no skin Treatments include neuroleptics, persensitivity develops similar eruptions, and the patient antidepressants, anesthetics, and topical to that of neuropathic pain.10 reported new itching on capsaicin. The resulting sensitization inboth legs. Mirtazapine was Healing touch, a holistically based duces an itch sensation from discontinued and oral mexiltreatment modality, has been used with innocuous stimuli that otheretine was started at 150 mg success as an adjunct to therapy. wise do not produce pruriper day titrating up to 600 mg tus.1 Neuroimaging studies of per day. This was also disitch using positron emission tomography and funccontinued as no improvement was noted with this tional magnetic resonance imaging identified distinct treatment regimen. patterns of activation in the frontal and prefrontal In an attempt to modulate a psychobehavioral cortex, motor and supplementary motor areas, parietal aspect of the pruritus, the patient was referred for HT somatosensory cortex, cingulate cortex, and therapy by a trained HT provider. He was enrolled in cerebellum.7,8,11,12 an ongoing institutional review boardeapproved Treatment reported for central neuropathic itch research study evaluating the effects of HT in neuincludes pharmacologic treatments similar to neurorologic and stress disorders. He received 3 sessions pathic pain including anticonvulsants (gabapentin, of HT in an office setting by an experienced HT pregabalin), mu-opioid receptor antagonists (naltherapist using light touch technique and further HT trexone, naloxone), and antidepressants (tricyclic sessions were subsequently continued on a biweekly antidepressants and selective serotonin reuptake base in the patient’s home by a different therapist. inhibitors). Topical treatments frequently used inThe patient noted a progressive decrease in itching clude the drugs lidocaine and capsaicin and cooling after 1 month and rated the itch 2 of 10. He continues agents such as menthol.1,2,12-14 Table II summarizes to receive HT treatments biweekly. After 4 months of the suggested pharmacologic therapies for central HT therapy, he is currently free of itch. neuropathic itch. To our knowledge the use of Central neuropathic itch can be a lifelong debilmexiletine in the treatment of neuropathic itch has itating condition and a treatment challenge. Reports not previously been reported. Mexiletine is an oral on this type of itch are rare, and have focused on sodium channel blocker successfully used in the demyelinating disorders, vascular injury, tumors, treatment of neuropathic pain.14 There are no conabscesses, and Creutzfeldt-Jakob disease1-6 (Table I). Neuropathic itch shares many characteristics with trolled trials to date for the pharmacologic intervenneuropathic pain including symptomatology (burntion of central neuropathic itch. ing, paresthesia, and anesthesia) and the difficulty in Our patient has diffuse brain damage in areas satisfactory treatment.1,2,7 Its mechanisms are not correlating with the cognitive aspects of itch such as fully understood, but recent research has shed light the prefrontal cortex, thalamus, and bilateral frontal on the pathophysiology. Damage to areas of the lobes. The focus of the treatment of this intractable brain can aggravate or induce chronic itch. itch was on reducing central hypersensitivity of d
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Table I. Causes of central neuropathic itch Demyelinating disorders Multiple sclerosis Vascular injury Cerebral vascular accidents Wallenberg syndrome Tumors Brain tumors Nasal glioma Spinal origin Spinal-cord cavernous hemangioma Ependymoma Brain or spinal abscess Creutzfeldt-Jakob disease (‘‘prion pruritus’’) Phantom itch For detailed review of causes above, refer to references 1, 2, 4, 5, and 6.
Fig 2. T2-weighted axial image from follow-up magnetic resonance imaging examination performed 1 year later shows encephalomalacia in those areas where there was either contusion or infarction with resultant ex vacuo enlargement of ventricular system. Note that there is increased signal in medial thalami and bilateral frontal and occipital lobes.
Fig 1. T2-weighted axial image from magnetic resonance imaging examination performed 2 days after trauma shows contusions in inferior medial frontal lobes and anterior left temporal lobe. In addition, there are multiple areas of acute ischemic infarctions, including bilateral medial thalami and bilateral occipital lobes.
nerve fibers. To decrease hypersensitization and neuronal transmission, the patient underwent an aggressive regimen of drugs in high doses, none of which were helpful. Furthermore, 10 psychotherapy sessions were not beneficial. Therefore, the patient was offered an approach using complementary, integrative medicine therapy to try to relieve his itch, anxiety, and stress. HT has been reported to
relieve pain, stress, and anxiety.15,16 Furthermore, HT has been used in our center for the treatment of chronic pain particularly in oncology patients.16,17 HT is categorized by the National Institutes of Health National Center for Complementary and Alternative Medicine as a biofield therapy.16,18 The scientific mechanisms for its effects are unknown, but the therapy is based on balancing the patient’s ‘‘energy,’’ as defined metaphysically, through a variety of techniques. HT uses direct touch or placement of the hands just above the body to restore balance, harmony, and a sense of well-being to the patient. Case reports have shown the effect of HT on the autonomic nervous system through heart rate variability. In addition, smaller studies using HT for chronic neuropathic pain have found an improvement in subjective well-being.19 There is a component of stress and anxiety involved in all forms of chronic pruritus similar to chronic pain.20 A biopsychosocial model for itch including neuropathic itch focuses on the effects of external stressors and cognitive and behavioral factors in itch sensation
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Table II. Pharmacologic treatments of central neuropathic itch Oral treatment
Gabapentin 300 mg daily titrated up to 3600 mg daily Pregabalin 75 mg twice daily titrated up to 400 mg daily Mirtazapine 7.5 mg nightly increasing to 15 mg nightly Doxepin 25-100 mg daily Mexiletine 150 mg daily titrating up to 600 mg daily Butorphanol (intranasal) 1-4 mg inhaled daily Naltrexone 12.5-250 mg daily Naloxone 0.002 g/kg/min titrated gradually up to 0.2 g/kg/min over 24 h Carbamazepine 200 mg twice daily increasing up to 1200 mg daily TCAs (amitriptyline 12.5-75 mg daily) SSRIs (paroxetine 20 mg daily) Thalidomide 100-200 mg daily Topical treatment Capsaicin 0.075%-0.1% cream 3 times per day EMLA cream twice daily 5% Lidocaine patch daily Crotamiton 10% lotion twice daily Menthol 1% cream Pramoxine 1%-2.5% lotion 3 times per day
Notes
Weight gain, increased appetite, sedation, peripheral edema Dizziness, weight gain, peripheral edema, sedation Sedation, weight gain Sedation, dry mouth; abrupt cessation may cause confusion; should not administer with other antidepressants Clearance by cardiology before initiation; ECG monitoring Sedation, dizziness, nausea, Hepatotoxicity, nausea, insomnia; contraindicated in patients with liver disease Hepatotoxicity, nausea, insomnia Blood dyscrasias, Stevens-Johnson syndrome/TEN Sedation, anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention) Sedation, nausea, weight gain, impotence Peripheral neuropathy; teratogenicefederally regulated (STEPS program) Possible poor compliance secondary to initial burning sensation
Skin irritation Particularly effective for pruritus of the face
ECG, Electrocardiogram; EMLA, lidocaine/prilocaine 2.5%; TCAs, tricyclic antidepressants; TEN, toxic epidermal necrolysis; SSRIs, selective serotonin reuptake inhibitors; STEPS, system for thalidomide education and prescribing safety. For detailed review of treatments above, refer to references 1, 2, 12, 13, and 14.
reiterating the involvement of stress and anxiety in exacerbating pruritus.21 In this case, extensive pharmacologic and nonpharmacologic treatment for stress and anxiety did not improve symptoms. We propose an unconventional approach to treatment of refractory intractable central neuropathic itch using HT as a therapeutic entity for pruritus. To our knowledge, this is the first case using HT for the treatment of intractable central neuropathic itch. This case highlights an unconventional approach to treatment and should be considered in refractory cases or as an adjunct to conventional treatment for central neuropathic itch. It would be of interest to evaluate this modality in patients of different types of chronic itch. We acknowledge Dr Kathi Kemper, Chair for Holistic and Integrative Medicine, and Dr Rong Tang in the Department of Neurology from Wake Forest University Health Sciences, Winston-Salem, NC, and Dr Anne Louise Oaklander from Massachusetts General Hospital, Boston, MA, for their contributions to this article and assisting in treatment of this complicated patient.
REFERENCES 1. Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Dermatol Ther 2008;21:32-41. 2. Yosipovitch G, Goodkin R, Wingard EM, Bernhard J. Neuropathic pruritus. In: Yosipovitch G, Greaves M, Fleischer A, McGlone F, editors. Itch: basic mechanisms and therapy. New York: Marcel Dekker; 2004. pp. 231-9. 3. Sandroni P. Central neuropathic itch: a new treatment option? Neurology 2002;59:778. 4. Dey DD, Orlando L, Oaklander AL. Central neuropathic itch from spinal-cord cavernous hemangioma: a human case, a possible animal model, and hypotheses about pathogenesis. Pain 2005;113:233-7. 5. Oaklander AL. Neuropathic pruritus following Wallenberg syndrome. Neurology 2009;73:1605-6. 6. Wiesner T, Leinweber B, Quasthoff S, Unger B, Komericki P, Hoedl S, et al. Itch, skin lesionseand a stiff neck. Lancet 2007; 370:290. 7. Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamineinduced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol 2009;161: 1072-80. 8. Wallengren J. Neuroanatomy and neurophysiology of itch. Dermatol Ther 2005;18:292-303. 9. Binder A, Koroschetz J, Baron R. Disease mechanisms in neuropathic itch. Nat Clin Pract Neurol 2008;4:329-37.
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10. Zhuo M. Neuronal mechanisms for neuropathic pain. Mol Pain 2007;3:14. 11. Schneider G, Sta¨nder S, Burgmer M, Driesch G, Heuft G, Weckesser M. Significant differences in central imaging of histamine-induced itch between atopic dermatitis and healthy subjects. Eur J Pain 2008;12:834-41. 12. Sta¨nder S, Weisshaar E, Luger TA. Neurophysiological and neurochemical basis of modern pruritus treatment. Exp Dermatol 2008;17:161-9. 13. Sta¨nder S, Bo¨ckenholt B, Schu¨rmeyer-Horst F, Weishaupt C, Heuft G, Luger TA, et al. Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labeled, two-arm proof-of-concept study. Acta Derm Venereol 2009;89:45-51. 14. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132: 237-51. 15. Wilkinson DS, Knox PL, Chatman JE, Johnson TL, Barbour N, Myles Y, et al. The clinical effectiveness of healing touch. J Altern Complement Med 2002;8:33-47.
16. Danhauer SC, Tooze JA, Holder P, Miller C, Jesse MT. Healing touch as a supportive intervention for adult acute leukemia patients: a pilot investigation of effects on distress and symptoms. J Soc Integr Oncol 2008;6:89-97. 17. Kemper KJ, Fletcher NB, Hamilton CA, McLean TW. Impact of healing touch on pediatric oncology outpatients: pilot study. J Soc Integr Oncol 2009;7:12-8. 18. Cook CA, Guerrerio JF, Slater VE. Healing touch and quality of life in women receiving radiation treatment for cancer: a randomized controlled trial. Altern Ther Health Med 2004;10:34-41. 19. Wardell DW, Rintala DH, Duan Z, Tan G. A pilot study of healing touch and progressive relaxation for chronic neuropathic pain in persons with spinal cord injury. J Holist Nurs 2006;24:231-40. 20. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia, and neuropathic pain. Front Biosci 2009;14: 5291-338. 21. Verhoeven EW, de Klerk S, Kraaimaat FW, van de Kerkhof PC, de Jong EM, Evers AW. Biopsychosocial mechanisms of chronic itch in patients with skin diseases: a review. Acta Derm Venereol 2008;88:211-8.
C
entral neuropathic itch results from lesions in the central nervous system.1-3 It has been associated with cerebral vascular accidents, Wallenberg syndrome, demyelinating disorders, and tumors and abscesses of the central nervous system.1-6 Table I summarizes the list of published causes of central neuropathic itch. This type of pruritus is a therapeutic challenge and literature regarding effective treatment is sparse. We present a case of a patient with a history of traumatic brain injury with intractable pruritus who failed extensive conventional and nonconventional pharmacologic treatment but responded to a holistic approach using a biofield therapy, energy medicine modality, healing touch (HT). A 25-year-old man with a history of a severe traumatic brain injury and subsequent ischemic stroke 3 years earlier presented with a 6-month history of severe intractable pruritus. The onset of the itch coincided with an increase in cognitive function revolving around improved short- and long-term memory. He noted the pruritus changed
From the Departments of Dermatology,a Neurology,b and Radiology,c Wake Forest University Baptist Medical Center. Funding sources: None. Conflicts of interest: None declared. Reprints not available from the authors. Correspondence to: Ashley R. Curtis, MD, Department of Dermatology, Wake Forest University Baptist Medical Center, Medical Center Blvd, Winston-Salem, NC 27157. E-mail: acurtis@ wfubmc.edu. Published online February 4, 2011. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.02.023
locations daily, but was mainly located on the face, chest, and arms. The itching was constant, and the patient described it as analogous to ‘‘hundreds of mosquitoes biting me.’’ He rated the itch a 10 on a scale from 1 to 10 and mentioned it repeatedly throughout each day. The patient actively scratched throughout the dermatologic examination and no primary lesions were identified. The initial neurologic injury occurred when the patient was accosted with a baseball bat, with multiple blows to the head. Early surgical decompression of a subdural hematoma was required. This was followed 2 days later by craniectomy to relieve pressure related to brain swelling and mass effect. Neurologic deficits persisting beyond the acute period included loss of peripheral vision bilaterally, posttraumatic amnesia, and impaired cognitive function with mild left hemiparesis, particularly noticeable in the left hand. He also had several seizures about 4 months after the injury, and experienced headaches and disturbed sleep, the latter associated with the pruritus. Both computed tomography and magnetic resonance imaging results demonstrated extensive traumatic ischemic injury, especially to the frontal and occipital regions and clear ischemic injury to the medial thalamus (Figs 1 and 2). A comprehensive laboratory workup including complete blood cell count, complete metabolic panel, and thyroid function revealed normal findings. A chest radiograph also produced normal results. No hydroxyethyl starch was administered after brain trauma. Treatment before presentation consisted of pregabalin in doses up to 300 mg per day, gabapentin up to 3600 mg per day, hydroxyzine at 100 mg per 955
956 Curtis et al
J AM ACAD DERMATOL MAY 2011
day, doxepin up to 75 mg per day, and nonsedating Hypothetical mechanisms proposed for neuropathic antihistamines and topical steroids, none of which itch include local nerve damage with spontaneous provided any relief. In addition, the patient had firing by damaged neurons, central neuronal depritherapy sessions with a psychologist with no effect. vation of afferent input, and central hypersensitivity Prior treatment was discontinued and inhaled butorof nerve fibers.1,8,9 The cause of central itch in our patient is hypothesized to be from central hyperphanol was started at 1 mg/mL increasing to 3 mg per sensitivity of nerve fibers resulting from the day, along with lidocaine/prilocaine 2.5% cream, 5% thalamic infarcts. In addition, lidocaine patch, and 0.1% an improvement in cognitive capsaicin. After 1 month of CAPSULE SUMMARY function may have contribtreatment and no response, uted to the itch sensation. It the butorphanol was disconCentral neuropathic itch results from is well known that itch pertinued and mirtazapine at 15 lesions in the central nervous system. ception is highly influenced mg nightly along with croVarious causes include cerebral vascular by memories.7 The pathotamiton 10%, topical menaccidents, demyelinating disorders, logical central itch could be thol, and oatmeal soothing tumors, and abscesses. the result of long-term plastic baths were started. At 1changes along the somatomonth follow-up, the patient This type of itch is hypothesized to be sensory pathways. Because reported no improvement in associated with central hypersensitivity of this long-term plasticity symptoms. Similarly, on exof nerve fibers. damage in central regions, hyamination he had no skin Treatments include neuroleptics, persensitivity develops similar eruptions, and the patient antidepressants, anesthetics, and topical to that of neuropathic pain.10 reported new itching on capsaicin. The resulting sensitization inboth legs. Mirtazapine was Healing touch, a holistically based duces an itch sensation from discontinued and oral mexiltreatment modality, has been used with innocuous stimuli that otheretine was started at 150 mg success as an adjunct to therapy. wise do not produce pruriper day titrating up to 600 mg tus.1 Neuroimaging studies of per day. This was also disitch using positron emission tomography and funccontinued as no improvement was noted with this tional magnetic resonance imaging identified distinct treatment regimen. patterns of activation in the frontal and prefrontal In an attempt to modulate a psychobehavioral cortex, motor and supplementary motor areas, parietal aspect of the pruritus, the patient was referred for HT somatosensory cortex, cingulate cortex, and therapy by a trained HT provider. He was enrolled in cerebellum.7,8,11,12 an ongoing institutional review boardeapproved Treatment reported for central neuropathic itch research study evaluating the effects of HT in neuincludes pharmacologic treatments similar to neurorologic and stress disorders. He received 3 sessions pathic pain including anticonvulsants (gabapentin, of HT in an office setting by an experienced HT pregabalin), mu-opioid receptor antagonists (naltherapist using light touch technique and further HT trexone, naloxone), and antidepressants (tricyclic sessions were subsequently continued on a biweekly antidepressants and selective serotonin reuptake base in the patient’s home by a different therapist. inhibitors). Topical treatments frequently used inThe patient noted a progressive decrease in itching clude the drugs lidocaine and capsaicin and cooling after 1 month and rated the itch 2 of 10. He continues agents such as menthol.1,2,12-14 Table II summarizes to receive HT treatments biweekly. After 4 months of the suggested pharmacologic therapies for central HT therapy, he is currently free of itch. neuropathic itch. To our knowledge the use of Central neuropathic itch can be a lifelong debilmexiletine in the treatment of neuropathic itch has itating condition and a treatment challenge. Reports not previously been reported. Mexiletine is an oral on this type of itch are rare, and have focused on sodium channel blocker successfully used in the demyelinating disorders, vascular injury, tumors, treatment of neuropathic pain.14 There are no conabscesses, and Creutzfeldt-Jakob disease1-6 (Table I). Neuropathic itch shares many characteristics with trolled trials to date for the pharmacologic intervenneuropathic pain including symptomatology (burntion of central neuropathic itch. ing, paresthesia, and anesthesia) and the difficulty in Our patient has diffuse brain damage in areas satisfactory treatment.1,2,7 Its mechanisms are not correlating with the cognitive aspects of itch such as fully understood, but recent research has shed light the prefrontal cortex, thalamus, and bilateral frontal on the pathophysiology. Damage to areas of the lobes. The focus of the treatment of this intractable brain can aggravate or induce chronic itch. itch was on reducing central hypersensitivity of d
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Table I. Causes of central neuropathic itch Demyelinating disorders Multiple sclerosis Vascular injury Cerebral vascular accidents Wallenberg syndrome Tumors Brain tumors Nasal glioma Spinal origin Spinal-cord cavernous hemangioma Ependymoma Brain or spinal abscess Creutzfeldt-Jakob disease (‘‘prion pruritus’’) Phantom itch For detailed review of causes above, refer to references 1, 2, 4, 5, and 6.
Fig 2. T2-weighted axial image from follow-up magnetic resonance imaging examination performed 1 year later shows encephalomalacia in those areas where there was either contusion or infarction with resultant ex vacuo enlargement of ventricular system. Note that there is increased signal in medial thalami and bilateral frontal and occipital lobes.
Fig 1. T2-weighted axial image from magnetic resonance imaging examination performed 2 days after trauma shows contusions in inferior medial frontal lobes and anterior left temporal lobe. In addition, there are multiple areas of acute ischemic infarctions, including bilateral medial thalami and bilateral occipital lobes.
nerve fibers. To decrease hypersensitization and neuronal transmission, the patient underwent an aggressive regimen of drugs in high doses, none of which were helpful. Furthermore, 10 psychotherapy sessions were not beneficial. Therefore, the patient was offered an approach using complementary, integrative medicine therapy to try to relieve his itch, anxiety, and stress. HT has been reported to
relieve pain, stress, and anxiety.15,16 Furthermore, HT has been used in our center for the treatment of chronic pain particularly in oncology patients.16,17 HT is categorized by the National Institutes of Health National Center for Complementary and Alternative Medicine as a biofield therapy.16,18 The scientific mechanisms for its effects are unknown, but the therapy is based on balancing the patient’s ‘‘energy,’’ as defined metaphysically, through a variety of techniques. HT uses direct touch or placement of the hands just above the body to restore balance, harmony, and a sense of well-being to the patient. Case reports have shown the effect of HT on the autonomic nervous system through heart rate variability. In addition, smaller studies using HT for chronic neuropathic pain have found an improvement in subjective well-being.19 There is a component of stress and anxiety involved in all forms of chronic pruritus similar to chronic pain.20 A biopsychosocial model for itch including neuropathic itch focuses on the effects of external stressors and cognitive and behavioral factors in itch sensation
958 Curtis et al
J AM ACAD DERMATOL MAY 2011
Table II. Pharmacologic treatments of central neuropathic itch Oral treatment
Gabapentin 300 mg daily titrated up to 3600 mg daily Pregabalin 75 mg twice daily titrated up to 400 mg daily Mirtazapine 7.5 mg nightly increasing to 15 mg nightly Doxepin 25-100 mg daily Mexiletine 150 mg daily titrating up to 600 mg daily Butorphanol (intranasal) 1-4 mg inhaled daily Naltrexone 12.5-250 mg daily Naloxone 0.002 g/kg/min titrated gradually up to 0.2 g/kg/min over 24 h Carbamazepine 200 mg twice daily increasing up to 1200 mg daily TCAs (amitriptyline 12.5-75 mg daily) SSRIs (paroxetine 20 mg daily) Thalidomide 100-200 mg daily Topical treatment Capsaicin 0.075%-0.1% cream 3 times per day EMLA cream twice daily 5% Lidocaine patch daily Crotamiton 10% lotion twice daily Menthol 1% cream Pramoxine 1%-2.5% lotion 3 times per day
Notes
Weight gain, increased appetite, sedation, peripheral edema Dizziness, weight gain, peripheral edema, sedation Sedation, weight gain Sedation, dry mouth; abrupt cessation may cause confusion; should not administer with other antidepressants Clearance by cardiology before initiation; ECG monitoring Sedation, dizziness, nausea, Hepatotoxicity, nausea, insomnia; contraindicated in patients with liver disease Hepatotoxicity, nausea, insomnia Blood dyscrasias, Stevens-Johnson syndrome/TEN Sedation, anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention) Sedation, nausea, weight gain, impotence Peripheral neuropathy; teratogenicefederally regulated (STEPS program) Possible poor compliance secondary to initial burning sensation
Skin irritation Particularly effective for pruritus of the face
ECG, Electrocardiogram; EMLA, lidocaine/prilocaine 2.5%; TCAs, tricyclic antidepressants; TEN, toxic epidermal necrolysis; SSRIs, selective serotonin reuptake inhibitors; STEPS, system for thalidomide education and prescribing safety. For detailed review of treatments above, refer to references 1, 2, 12, 13, and 14.
reiterating the involvement of stress and anxiety in exacerbating pruritus.21 In this case, extensive pharmacologic and nonpharmacologic treatment for stress and anxiety did not improve symptoms. We propose an unconventional approach to treatment of refractory intractable central neuropathic itch using HT as a therapeutic entity for pruritus. To our knowledge, this is the first case using HT for the treatment of intractable central neuropathic itch. This case highlights an unconventional approach to treatment and should be considered in refractory cases or as an adjunct to conventional treatment for central neuropathic itch. It would be of interest to evaluate this modality in patients of different types of chronic itch. We acknowledge Dr Kathi Kemper, Chair for Holistic and Integrative Medicine, and Dr Rong Tang in the Department of Neurology from Wake Forest University Health Sciences, Winston-Salem, NC, and Dr Anne Louise Oaklander from Massachusetts General Hospital, Boston, MA, for their contributions to this article and assisting in treatment of this complicated patient.
REFERENCES 1. Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Dermatol Ther 2008;21:32-41. 2. Yosipovitch G, Goodkin R, Wingard EM, Bernhard J. Neuropathic pruritus. In: Yosipovitch G, Greaves M, Fleischer A, McGlone F, editors. Itch: basic mechanisms and therapy. New York: Marcel Dekker; 2004. pp. 231-9. 3. Sandroni P. Central neuropathic itch: a new treatment option? Neurology 2002;59:778. 4. Dey DD, Orlando L, Oaklander AL. Central neuropathic itch from spinal-cord cavernous hemangioma: a human case, a possible animal model, and hypotheses about pathogenesis. Pain 2005;113:233-7. 5. Oaklander AL. Neuropathic pruritus following Wallenberg syndrome. Neurology 2009;73:1605-6. 6. Wiesner T, Leinweber B, Quasthoff S, Unger B, Komericki P, Hoedl S, et al. Itch, skin lesionseand a stiff neck. Lancet 2007; 370:290. 7. Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamineinduced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol 2009;161: 1072-80. 8. Wallengren J. Neuroanatomy and neurophysiology of itch. Dermatol Ther 2005;18:292-303. 9. Binder A, Koroschetz J, Baron R. Disease mechanisms in neuropathic itch. Nat Clin Pract Neurol 2008;4:329-37.
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