COMMENTARY
PHANTOM ITCH, PSEUDOPHANTOM ITCH, AND SENILE PRURITUS JEFFREY D. BERNHARD, M.D.
phantom"; phantom sensations can occur in paraplegics and after accidetits such as brachial plexus avulsion.^ The existence of phantom itch proves that the itch sensation can "arise" within the nervous system even in the absence of skin. It is noteworthy that as early as 1964, Winkelrnann and Muller suggested that itching does not always "reside in the skin," and suggested that in certain situations it "may be analogous to phantom limb sensations."** Central nervous system origination of itch sensations is also supported by the appearance of so-called "neurogenic pruritus" after strokes.^ The occurrence of phantom sensations after nervous system injury begs the question of whether any one of a nutnber of structural, degenerative, or functional changes in the nervous system (such as those associated with aging) may also lead to phantom itchitig. Melzack has proposed a new theory to explain phantom phenomena.^ He suggests that phantom sensations originate iti the brain, and not, for exatnple, from neuromas at the cut end of nerves. He postulates that "the brain contains a neuromatrix, or network of neurons, that, in addition to responding to sensory stimulation, continuously generates a characteristic pattern of impulses indicating that the body is intact and unequivocally one's own." He calls that pattern of continuous impulses a "neurosignature." Furthermore, the neuromatrix continuously analyzes sensory input frotn the periphery, imprints its tieurosignature on it, and generates output that "carries information about sensory input as well as the assurance that the sensation is occurring in one's own body." Melzack proposes that "if such a matrix operated in the absence of sensory inputs from the periphery of the body, it would create the impression of having a limb even when that limb has been removed," and that this is the basis for the occurrence of phantoms. As the determinant of personal boundaries and a major sensory organ, the skin must be a major contributor to the tieurosignature and to the sense that the body is intact and one's own. In this context, itch may be as primordial and important as touch.
"Senile pruritus" has been recognized since at least the time of Robert Willan, who wrote that he knew "matiy persotis, of both sexes, so incessantly tormented with a violent and universal itching, that they were rendered uncomfortable for the remainder of life."' Willan attributed prurigo senilis to the "dry, condensed state of the skin and cuticle," and he also felt that it was "generally connected with a languid state of circulation, and of the digestive power." Regrettably, the cause of senile pruritus remains as mysterious now as it did in 1808. Current theories range from mere dryness of the skin to degenerative changes in peripheral nerve endings.^'^ Writitig in Hebra's monumetital text, Kaposi must have been among the first to raise the neural hypothesis, when he stated, "In what way ... the most peripheral ends of the nerves become affected by the senile atrophy and disposed to take on the abnormal sensation of itching is as yet quite unknown to us."'' Perhaps the most telling cornment is that "senile pruritus" has been defitied as "the common cotnplaint of unexplained itching in the elderly," (emphasis added) and that most definitions proceed from there to explain that it is a diagnosis of exclusion.^''' Kaposi's statement that "The malady is incurable," is as true today as it was over 100 years ago, is yet another testimony to our ignorance. NEURAL THEORY OE SENILE PRURITUS
I would like to develop an elaboration of the neural theory, namely, that senile pruritus may be the consequetice of cetitral nervous systern phenomena similar, if not identical, to those that cause phantom pain. Phantom pain occurs in people who have lost an extremity but who perceive the limb as though it were still there. Two important observations provide a basis for the hypothesis that senile pruritus may arise as a consequence of phantom limb-type phenomena. First, phantom limbs can itch.^ Sometimes, scratching the apparent site of discotnfort can actually relieve the itch! Second, "amputation is not essential for the occurrence of a
One of the critical predictiotis of the tieuromatrix theory is that the brain "can generate sensation on its own," and Melzack's team has provided evidence for this in experimetits, which demonstrate that pain can contitiue even after the nerves through which the pain signals were transmitted are blocked. Indeed, there is experimental evidence that certain cells iti the central nervous system become more active in the absence of
From the Division of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts. Address for correspondence: Jeffrey D. Bernhard, M.D., Division of Dermatology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655. 856
Phiintoin trch, Pscudophantom ttch, and Scnitc Pruritus Bcrnhard
input—so that phantom limbs (atid pari passu, phantom pain, phantom itch, phantom sights, and phantotn sounds) occur "when the brain loses its normal input from a setisory system."^ Because age-related degenerative changes iti cutaneous tierve endings do occur,"' changes in the frequency, intensity, or pattern of signals from the skin to the brain could lead to increased activity of particular neurons in such a way that "itchitig" is generated by the neurotnatrix of the brain. Phantom itch in patients with senile pruritus would be generated in the satne way that other phantom sensations are generated in amputees, in paraplegics, or in people who have sustained severe nerve injuries. The classic picture of ititractable, generalized, "senile" pruritus without any other obvious cause would result. The frequent, if not characteristic, "burning" nature of senile pruritus would make sense, because a burnitig setisatioti is the most cotntnon complaint in phantotn limbs.''
perpetuation of several particularly pesky and persistent itches such as anogenital pruritus. Arnold has suggested that paroxysmal pruritus, related to strotig emotions or stress, must originate in the central nervous system;'"^ Melzack's tieurotnatrix theory provides an indication of how the circuits that make this happen tnay be linked. CONCLUSIONS
The brain's continuous pattern of signals, which signify that "the body is intact and unequivocally one's owti," must depend substantially upon input from the skin, because the skin determities the boundaries of self. The related sensatiotis of touch atid itch must be involved not only in telling us what's out there and who we are, but that we exist. Based upon the observation that people often scratch their heads while thinking, Descarte's tnaxim was once revised to "I think, therefore I scratch. I scratch, therefore 1 atn."'' Perhaps it should go, "I atn, therefore 1 itch (especially as I get older)."
IMPLICATIONS
With phatitom sensations classically occurritig after amputation and being most easily conceptualized in that context, the notion of phantom itch in an intact body may be somewhat confusing. For that reason, "quasi-phantom itch" might be appropriate. The lnore that! double irony implicit iti the term "pseudophantom itch" to describe what happens in senile pruritus also has a certaiti appeal, but atiother tertn is tiot really required: pain in a detiervated limb is still called phantotn pain. Resisting the urge to scratch a paronotnastic itch, it is probably best to conclude that at least sotne cases of senile pruritus represent "a form of phantotn itch." If phantotn mechanisms are involved iti the generation of senile pruritus, the inefficacy of tnost topical preparations becotnes predictable, and the occasional effectiveness of centrally active antihistamities and antidepressants begins to make some sense. Because the litnbic system probably plays a role in the neuromatrix, a biologic connection between senile pruritus and depression, with which it often seems to travel, could be explained as well. The suggestion that senile pruritus is a fonn of phantom itch has several itnplications for diagnosis and treatment. First, techniques that could demonstrate the type of neurologic changes postulated in either the peripheral or central nervous systetns might provide positive evidence for the diagnosis of senile pruritus where it has otherwise rested upon the expensive, uncotnfortable, and sometitnes risky process of exclusioti. Second, investigation and tnedications directed at the nervous system should be pursued more vigorously. Third, the mechanistn of "phantom itch" may play a role in a number of other pruritic curiosities that could be related to localized nerve injury, such as notalgia paresthetica'^-^^ and puncta pruritica.'"* Finally, phantom mechanisms and active circuits withiti the neurotnatrix could play a role iti the
REEERENCES
1. 2. 3. 4.
5.
6.
7. 8. 9. 10.
11.
12.
13. 14.
15. 857
Willan R. On cutaneous diseases. Vol. I. Philadelphia: Kimber & Conrad, 1809:64. Cilchrest BA. Skin and aging processes. Boca Raton: CRC Press, 1984:42. Hunter JAA. Seventh age itch. BMJ 1985; 291:842. Hebra F, Kaposi M. On diseases of the skin, including the exanthemata. Vol. 5. Translated and edited by Warcn Tay. London: The New Sydenham Society, 1880:100. Bernhard JD. Clinical aspects of pruritus. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds. Dermatology in general tnedicine. 3rd Ed. New York: McGraw-Hill, 1987:81. Newcomer VD, Young EM. Geriatric dermatology; clinical diagnosis and practical therapy. New York: Igaku-Shoin, 1989:217. Melzack R. Phantom litnbs. Sci Am 1992; 266:120-126. Winkelmann RK, Muller SA. Pruritus. Annu Rev Med 1964; 15:53-64. King CA, Huff FJ, Jorizzo JL. Unilateral neurogenic pruritus: paroxysmal itching associated with central nervous system lesions. Ann Intern Med 1982; 97:222-223. Arnold N, Harriman DG. The incidence of abnormality in control human peripheral nerves studied by single axon dissection. J Neurol Neurosurg Psychiatry 1970; 3,3: 5.5-61. Springall DR, Karanth SS, Kirkhatn N, Darley CR, Polak JM. Symptoms of notalgia paresthetica may be explained by increased dermal innervation. 1 Invest Dermatol 1991; 97:555-561. Bernhard JD. Macular amyloidosis, notalgia paresthetica and pruritus: three sides of the same coin? Dermatologica 1991; 183:53-56. Crissey fT. Puncta pruritica. Int J Dertnatol 1991; 30:722-724. Arnold HL. Paroxysmal pruritus; its clinical characterization and a hypothesis of its pathogenesis. ] Atn Acad Dermatol 1984; 11:322-326. Bernhard JD. Does thinking itch? Lancet 1985; i:589.
PHANTOM ITCH, PSEUDOPHANTOM ITCH, AND SENILE PRURITUS JEFFREY D. BERNHARD, M.D.
phantom"; phantom sensations can occur in paraplegics and after accidetits such as brachial plexus avulsion.^ The existence of phantom itch proves that the itch sensation can "arise" within the nervous system even in the absence of skin. It is noteworthy that as early as 1964, Winkelrnann and Muller suggested that itching does not always "reside in the skin," and suggested that in certain situations it "may be analogous to phantom limb sensations."** Central nervous system origination of itch sensations is also supported by the appearance of so-called "neurogenic pruritus" after strokes.^ The occurrence of phantom sensations after nervous system injury begs the question of whether any one of a nutnber of structural, degenerative, or functional changes in the nervous system (such as those associated with aging) may also lead to phantom itchitig. Melzack has proposed a new theory to explain phantom phenomena.^ He suggests that phantom sensations originate iti the brain, and not, for exatnple, from neuromas at the cut end of nerves. He postulates that "the brain contains a neuromatrix, or network of neurons, that, in addition to responding to sensory stimulation, continuously generates a characteristic pattern of impulses indicating that the body is intact and unequivocally one's own." He calls that pattern of continuous impulses a "neurosignature." Furthermore, the neuromatrix continuously analyzes sensory input frotn the periphery, imprints its tieurosignature on it, and generates output that "carries information about sensory input as well as the assurance that the sensation is occurring in one's own body." Melzack proposes that "if such a matrix operated in the absence of sensory inputs from the periphery of the body, it would create the impression of having a limb even when that limb has been removed," and that this is the basis for the occurrence of phantoms. As the determinant of personal boundaries and a major sensory organ, the skin must be a major contributor to the tieurosignature and to the sense that the body is intact and one's own. In this context, itch may be as primordial and important as touch.
"Senile pruritus" has been recognized since at least the time of Robert Willan, who wrote that he knew "matiy persotis, of both sexes, so incessantly tormented with a violent and universal itching, that they were rendered uncomfortable for the remainder of life."' Willan attributed prurigo senilis to the "dry, condensed state of the skin and cuticle," and he also felt that it was "generally connected with a languid state of circulation, and of the digestive power." Regrettably, the cause of senile pruritus remains as mysterious now as it did in 1808. Current theories range from mere dryness of the skin to degenerative changes in peripheral nerve endings.^'^ Writitig in Hebra's monumetital text, Kaposi must have been among the first to raise the neural hypothesis, when he stated, "In what way ... the most peripheral ends of the nerves become affected by the senile atrophy and disposed to take on the abnormal sensation of itching is as yet quite unknown to us."'' Perhaps the most telling cornment is that "senile pruritus" has been defitied as "the common cotnplaint of unexplained itching in the elderly," (emphasis added) and that most definitions proceed from there to explain that it is a diagnosis of exclusion.^''' Kaposi's statement that "The malady is incurable," is as true today as it was over 100 years ago, is yet another testimony to our ignorance. NEURAL THEORY OE SENILE PRURITUS
I would like to develop an elaboration of the neural theory, namely, that senile pruritus may be the consequetice of cetitral nervous systern phenomena similar, if not identical, to those that cause phantom pain. Phantom pain occurs in people who have lost an extremity but who perceive the limb as though it were still there. Two important observations provide a basis for the hypothesis that senile pruritus may arise as a consequence of phantom limb-type phenomena. First, phantom limbs can itch.^ Sometimes, scratching the apparent site of discotnfort can actually relieve the itch! Second, "amputation is not essential for the occurrence of a
One of the critical predictiotis of the tieuromatrix theory is that the brain "can generate sensation on its own," and Melzack's team has provided evidence for this in experimetits, which demonstrate that pain can contitiue even after the nerves through which the pain signals were transmitted are blocked. Indeed, there is experimental evidence that certain cells iti the central nervous system become more active in the absence of
From the Division of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts. Address for correspondence: Jeffrey D. Bernhard, M.D., Division of Dermatology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655. 856
Phiintoin trch, Pscudophantom ttch, and Scnitc Pruritus Bcrnhard
input—so that phantom limbs (atid pari passu, phantom pain, phantom itch, phantom sights, and phantotn sounds) occur "when the brain loses its normal input from a setisory system."^ Because age-related degenerative changes iti cutaneous tierve endings do occur,"' changes in the frequency, intensity, or pattern of signals from the skin to the brain could lead to increased activity of particular neurons in such a way that "itchitig" is generated by the neurotnatrix of the brain. Phantom itch in patients with senile pruritus would be generated in the satne way that other phantom sensations are generated in amputees, in paraplegics, or in people who have sustained severe nerve injuries. The classic picture of ititractable, generalized, "senile" pruritus without any other obvious cause would result. The frequent, if not characteristic, "burning" nature of senile pruritus would make sense, because a burnitig setisatioti is the most cotntnon complaint in phantotn limbs.''
perpetuation of several particularly pesky and persistent itches such as anogenital pruritus. Arnold has suggested that paroxysmal pruritus, related to strotig emotions or stress, must originate in the central nervous system;'"^ Melzack's tieurotnatrix theory provides an indication of how the circuits that make this happen tnay be linked. CONCLUSIONS
The brain's continuous pattern of signals, which signify that "the body is intact and unequivocally one's owti," must depend substantially upon input from the skin, because the skin determities the boundaries of self. The related sensatiotis of touch atid itch must be involved not only in telling us what's out there and who we are, but that we exist. Based upon the observation that people often scratch their heads while thinking, Descarte's tnaxim was once revised to "I think, therefore I scratch. I scratch, therefore 1 atn."'' Perhaps it should go, "I atn, therefore 1 itch (especially as I get older)."
IMPLICATIONS
With phatitom sensations classically occurritig after amputation and being most easily conceptualized in that context, the notion of phantom itch in an intact body may be somewhat confusing. For that reason, "quasi-phantom itch" might be appropriate. The lnore that! double irony implicit iti the term "pseudophantom itch" to describe what happens in senile pruritus also has a certaiti appeal, but atiother tertn is tiot really required: pain in a detiervated limb is still called phantotn pain. Resisting the urge to scratch a paronotnastic itch, it is probably best to conclude that at least sotne cases of senile pruritus represent "a form of phantotn itch." If phantotn mechanisms are involved iti the generation of senile pruritus, the inefficacy of tnost topical preparations becotnes predictable, and the occasional effectiveness of centrally active antihistamities and antidepressants begins to make some sense. Because the litnbic system probably plays a role in the neuromatrix, a biologic connection between senile pruritus and depression, with which it often seems to travel, could be explained as well. The suggestion that senile pruritus is a fonn of phantom itch has several itnplications for diagnosis and treatment. First, techniques that could demonstrate the type of neurologic changes postulated in either the peripheral or central nervous systetns might provide positive evidence for the diagnosis of senile pruritus where it has otherwise rested upon the expensive, uncotnfortable, and sometitnes risky process of exclusioti. Second, investigation and tnedications directed at the nervous system should be pursued more vigorously. Third, the mechanistn of "phantom itch" may play a role in a number of other pruritic curiosities that could be related to localized nerve injury, such as notalgia paresthetica'^-^^ and puncta pruritica.'"* Finally, phantom mechanisms and active circuits withiti the neurotnatrix could play a role iti the
REEERENCES
1. 2. 3. 4.
5.
6.
7. 8. 9. 10.
11.
12.
13. 14.
15. 857
Willan R. On cutaneous diseases. Vol. I. Philadelphia: Kimber & Conrad, 1809:64. Cilchrest BA. Skin and aging processes. Boca Raton: CRC Press, 1984:42. Hunter JAA. Seventh age itch. BMJ 1985; 291:842. Hebra F, Kaposi M. On diseases of the skin, including the exanthemata. Vol. 5. Translated and edited by Warcn Tay. London: The New Sydenham Society, 1880:100. Bernhard JD. Clinical aspects of pruritus. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds. Dermatology in general tnedicine. 3rd Ed. New York: McGraw-Hill, 1987:81. Newcomer VD, Young EM. Geriatric dermatology; clinical diagnosis and practical therapy. New York: Igaku-Shoin, 1989:217. Melzack R. Phantom litnbs. Sci Am 1992; 266:120-126. Winkelmann RK, Muller SA. Pruritus. Annu Rev Med 1964; 15:53-64. King CA, Huff FJ, Jorizzo JL. Unilateral neurogenic pruritus: paroxysmal itching associated with central nervous system lesions. Ann Intern Med 1982; 97:222-223. Arnold N, Harriman DG. The incidence of abnormality in control human peripheral nerves studied by single axon dissection. J Neurol Neurosurg Psychiatry 1970; 3,3: 5.5-61. Springall DR, Karanth SS, Kirkhatn N, Darley CR, Polak JM. Symptoms of notalgia paresthetica may be explained by increased dermal innervation. 1 Invest Dermatol 1991; 97:555-561. Bernhard JD. Macular amyloidosis, notalgia paresthetica and pruritus: three sides of the same coin? Dermatologica 1991; 183:53-56. Crissey fT. Puncta pruritica. Int J Dertnatol 1991; 30:722-724. Arnold HL. Paroxysmal pruritus; its clinical characterization and a hypothesis of its pathogenesis. ] Atn Acad Dermatol 1984; 11:322-326. Bernhard JD. Does thinking itch? Lancet 1985; i:589.
