Bak R

Delusions of parasitosis (DOP) is a disorder in which patients erroneously insist that they are infested with parasites. These patients have an unshakable belief that their problems are medical. They rarely present to a psychiatrist and are almost always resistant to psychiatric referral. Thus, this disorder proves to be difficult to treat. The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years.1 She may complain of a crawling, biting, burrowing sensation (formication) on or under her skin. She may claim her symptoms originate from insects or other creatures that infest her, her home, or her work. She may actually see the crawling culprits and be able to describe them in detail. This delusion may impinge on her activities of daily living, but she is otherwise a functional well-adjusted person. Oftentimes she will bring in proof of infestation that, under close examination, are pieces of lint or other nonparasitic materials.1 Despite thorough examination and reassurance, the patient relentlessly believes she is infested. She will most likely refuse referral to a psychiatrist, the one clinician with the most experience treating delusional disorders. Thus, it is important for the general practitioner and other nonpsychiatric clinicians to be familiar with DOP and its management.

Medical Management
Medical or psychiatric treatment aimed at eliminating the delusion should be attempted only after rapport with the patient has been established. Koo and Pham2 stated: "The greatest challenge in the treatment of delusional patients is in obtaining their agreement to start treatment with an antipsychotic medication." Numerous case reports have been published in which the clinician was unable to successfully treat DOP because of a lack of patient confidence.3-5 We modified a suggested management strategy first described by Gould and Gragg6 and incorporated strategies from a lecture on promoting a trusting relationship with delusional patients presented by Koo7 at the University of Southern California Dermatology Grand Rounds to create the following management strategy for clinicians:

1. Listen to the patient's story. Give the patient a few minutes to narrate and then proceed with a battery of direct questions. Do not dwell on the patient's psychiatric history, which will encourage trust and allow you to control the dialogue.
2. Thoroughly examine the patient's skin and any evidence of infestation that they bring. This task may seem dishonest when you are convinced the patient is delusional; however, it is possible there is a true infestation. Even if he/she is not infested, developing a bond with the patient will allow you to suggest treatments that the patient may otherwise not accept.2
3. Perform a biopsy if the patient insists, which will show that you genuinely care about his/her problem. Allow the patient to pick the skin area he/she believes is the most involved, but insist that if the biopsy is negative, he/she should entertain the possibility that the ailment may not be due to a living organism.
4. Show concern for how the condition has affected the patient's life. This technique has been shown to have a positive effect on the establishment of a good physician-patient relationship. Furthermore, it can help you individualize a therapeutic strategy for the patient in a way that does not reinforce the delusion. For example, you may say, "We will work diligently to relieve the stress this problem has caused you."
5. Be empathetic, not sympathetic. Let the patient know that you understand how the condition has left him/her feeling isolated.

Be aware that rapport with the patient will not always develop immediately. It may take a few visits before the patient is comfortable enough to accept treatment suggestions. Clinicians are most concerned with discussions with the patient relating to the diagnosis and treatment. Most patients will not accept a psychiatric diagnosis for a condition that they are sure is somatic. The following statements made by clinicians have been used with success:

• "You have a very difficult problem, but I will study the specimens you have brought and will try to help you in any way that I can."6
• "I did not find any parasites today, but I am willing to examine any evidence that you bring me in the future."2
• "I noticed that you have been suffering with this problem and this is really bothering you day and night. Maybe I can offer you a medication that can help relieve some of this distress."2
• "This medication has been known to help others with the same problem."8
• "I would like to refer you to a specialist for this disorder."9 (The patient is not immediately told that the specialist is a psychiatrist, but this fact is not denied if asked.)
• "You may very well have had an infestation initially that was adequately treated, and the only sign now is the residual sensation you feel in your skin. Given the experience you have had, I can understand how you feel that parasites are still there. This is a situation that I have seen before, and the medication that I am going to prescribe is usually very helpful in getting rid of this last remaining discomfort."10

Treating the patient's anxiety should be seriously considered.6 Benzodiazepines such as diazepam and alprazolam are commonly used for short-term treatment of anxiety. These medications are fast acting and can be withdrawn after a few weeks. Consultation with a psychiatrist can be helpful for clinicians who are not familiar or comfortable with these drugs. Treating the symptomatic itching or burning sensation experienced by many patients also should be considered. Crotamiton cream is useful for pruritus and possibly eradicates some organisms. Topical or intramuscular corticosteroids may be useful to alleviate the itching sensation. Additionally, an antihistamine can be useful. Over-the-counter anti-itch medications also can be used.

Treating the Delusion
Until the 1950s, DOP was considered a nontreatable disease. In 1946, Wilson and Miller11 reported that beyond treating the patient for syphilis, if indicated, "there is nothing whatsoever the dermatologist can do for such a patient." While viable treatment options are now available, management remains a challenge for clinicians, especially nonpsychiatrists. A meta-analysis of 1223 case reports of DOP showed marked improvement in full remission rates from the prepsychopharmacologic era (before 1960) to the postpsychopharmacologic era (after 1960)(33.9% to 51.9%, respectively).12 Most cases of DOP need to be treated. There have been few reported cases of spontaneous remission of DOP.13,14 Most experts will agree that referral to a psychiatrist is beneficial. It is debatable if psychiatrists are the only clinicians equipped to handle these patients or if dermatologists may and should prescribe pimozide.15,16 Koblenzer17 stated: "If not treated by the dermatologist, [patients with DOP are] doomed to a prolonged, expensive, and frenetic search from doctor to doctor, to exterminator, to entomologist, and so on, without relief." Regardless of the medication used, the clinician must proceed with caution when suggesting treatment to patients with DOP. Commonly, when a clinician suggests psychiatric referral or medication, the patient responds angrily and does not return.5,18 Patients can become a danger to themselves and others. One man set fire to one of his apartments and flooded another19; other patients have committed suicide.13,20 It is important to note the extreme desperation in which these patients often find themselves. Many patients have tried relentlessly to find a treatment for their supposed infestation and often have found their clinician to be more of a hindrance than a help. One such case resulted in an attempt on the life of a family physician.21

Pimozide
Pimozide is approved by the US Food and Drug Administration for Tourette syndrome. It was first used in 1975 to treat somatic delusions, as reported in 5 patients.22 Since then, this neuroleptic agent has been considered the treatment of choice for DOP. Pimozide is a highly selective dopamine D2 blocker; thus, it is effective in treating psychoses. Pimozide also has some serotonin receptor blocking activity, which is theorized to contribute to its therapeutic effects. Other neurologic effects include blockade of a-adrenergic receptor sites, voltage-gated calcium channels, and opiate receptors. Pimozide has approximately 50% oral bioavailability and its action lasts 24 to 48 hours, allowing for once-daily dosing. It is metabolized in the liver and primarily excreted in the urine.23 The most common side effects of pimozide are extrapyramidal symptoms, including pseudoparkinsonism, akathisia, and dystonia. Pseudoparkinsonism may manifest as muscle and joint stiffness, while akathisia is indicated by restlessness. These effects have been demonstrated in patients treated with a pimozide dosage as low as 2 mg daily.24 Symptoms can be controlled by anticholinergic medications, such as oral benztropine mesylate 1 to 4 mg once or twice daily, as needed, or diphenhydramine hydrochloride 25 mg 4 times daily, as needed. Benztropine mesylate is preferred versus diphenhydramine hydrochloride because it is not sedating. An acute dystonic reaction (ie, muscle spasm) rarely occurs because of the low dose of neuroleptic prescribed; however, the acute reaction also responds to anticholinergic agents.16 To minimize the risk for side effects, initially prescribe pimozide 1 mg daily, titrating up by 1 mg every 5 to 7 days (maximum, 10 mg daily), as needed. Koo and Lee25 recommend using the lowest effective dose of pimozide for the shortest possible duration. Pimozide at high doses has cardiotoxic properties manifested by long QT intervals and arrhythmias. Pretreatment and posttreatment electrocardiograms are recommended for all patients receiving pimozide.26 Discontinue increasing the dose when the QT interval is more than 0.52 seconds in adults or when there is a QT interval increase of 25% or more above the patient's baseline.27 Furthermore, coadministration of other drugs that increase the QT interval should be avoided, including but not limited to chlorpromazine, gatifloxacin, mefloquine, moxifloxacin hydrochloride, other class Ia and III antiarrhythmic agents, quinidine, tacrolimus, thioridazine hydrochloride, and ziprasidone hydrochloride or mesylate.28 Pimozide is the most studied and reported drug used for DOP. Most data on pimozide have come from individual or group case reports, though 2 double-blind placebo-controlled trials have been conducted. Of the 189 patients reported to be treated with pimozide in 22 articles, 79% reported a positive response to pimozide, 17% reported no response, and the rest were lost to follow-up.8,13,24,26,29-46 Side effects reported with pimozide included insomnia, drowsiness, and depression.34,41 Extrapyramidal symptoms such as pseudoparkinsonism and akathisia were not uncommon but generally were easily controlled with anticholinergic agents.13,24,26,34,35,38,40,41,45 Two cases of lethargy were reported with pimozide doses of up to 6 to 24 mg daily.41 An acute dystonic reaction occurred in a patient receiving 8 mg daily.40 The mean dosage of pimozide used for best effect was 5 mg daily, as per the case series for which this information was available.8,13,24,26,29-46 Both single and split dosing were reported as successful methods. The median duration of treatment to best results was 3.5 weeks, with a range of 3 days to 6 months. For patients who were followed long-term (4–12 mo), 100% (n=17) maintained complete or near complete resolution of symptoms (near complete in 1 patient) while receiving maintenance doses of pimozide. Daily doses ranged from 2 to 4 mg. For patients followed long-term who eventually discontinued pimozide, 43% (34/79) had subsequent recurrence of their symptoms. Of those patients re-treated with pimozide, 100% (n=20) had complete resolution of symptoms.8,13,24,26,29-46 Zomer et al46 studied 33 patients with DOP. A total of 61.1% (11/18) of patients reported improvement or full recovery with pimozide compared with the 20% (3/15) not treated. At a mean follow-up of 5 years, none of the patients who had full remission (5/33 with DOP) needed maintenance therapy.46 Hamann and Avnstorp34 conducted a double-blind, placebo-controlled, crossover trial in which participants showed a significant response to pimozide compared with placebo (P

Delusions of parasitosis (DOP) is a disorder in which patients erroneously insist that they are infested with parasites. These patients have an unshakable belief that their problems are medical. They rarely present to a psychiatrist and are almost always resistant to psychiatric referral. Thus, this disorder proves to be difficult to treat. The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years.1 She may complain of a crawling, biting, burrowing sensation (formication) on or under her skin. She may claim her symptoms originate from insects or other creatures that infest her, her home, or her work. She may actually see the crawling culprits and be able to describe them in detail. This delusion may impinge on her activities of daily living, but she is otherwise a functional well-adjusted person. Oftentimes she will bring in proof of infestation that, under close examination, are pieces of lint or other nonparasitic materials.1 Despite thorough examination and reassurance, the patient relentlessly believes she is infested. She will most likely refuse referral to a psychiatrist, the one clinician with the most experience treating delusional disorders. Thus, it is important for the general practitioner and other nonpsychiatric clinicians to be familiar with DOP and its management.

Medical Management
Medical or psychiatric treatment aimed at eliminating the delusion should be attempted only after rapport with the patient has been established. Koo and Pham2 stated: "The greatest challenge in the treatment of delusional patients is in obtaining their agreement to start treatment with an antipsychotic medication." Numerous case reports have been published in which the clinician was unable to successfully treat DOP because of a lack of patient confidence.3-5 We modified a suggested management strategy first described by Gould and Gragg6 and incorporated strategies from a lecture on promoting a trusting relationship with delusional patients presented by Koo7 at the University of Southern California Dermatology Grand Rounds to create the following management strategy for clinicians:

1. Listen to the patient's story. Give the patient a few minutes to narrate and then proceed with a battery of direct questions. Do not dwell on the patient's psychiatric history, which will encourage trust and allow you to control the dialogue.
2. Thoroughly examine the patient's skin and any evidence of infestation that they bring. This task may seem dishonest when you are convinced the patient is delusional; however, it is possible there is a true infestation. Even if he/she is not infested, developing a bond with the patient will allow you to suggest treatments that the patient may otherwise not accept.2
3. Perform a biopsy if the patient insists, which will show that you genuinely care about his/her problem. Allow the patient to pick the skin area he/she believes is the most involved, but insist that if the biopsy is negative, he/she should entertain the possibility that the ailment may not be due to a living organism.
4. Show concern for how the condition has affected the patient's life. This technique has been shown to have a positive effect on the establishment of a good physician-patient relationship. Furthermore, it can help you individualize a therapeutic strategy for the patient in a way that does not reinforce the delusion. For example, you may say, "We will work diligently to relieve the stress this problem has caused you."
5. Be empathetic, not sympathetic. Let the patient know that you understand how the condition has left him/her feeling isolated.

Be aware that rapport with the patient will not always develop immediately. It may take a few visits before the patient is comfortable enough to accept treatment suggestions. Clinicians are most concerned with discussions with the patient relating to the diagnosis and treatment. Most patients will not accept a psychiatric diagnosis for a condition that they are sure is somatic. The following statements made by clinicians have been used with success:

• "You have a very difficult problem, but I will study the specimens you have brought and will try to help you in any way that I can."6
• "I did not find any parasites today, but I am willing to examine any evidence that you bring me in the future."2
• "I noticed that you have been suffering with this problem and this is really bothering you day and night. Maybe I can offer you a medication that can help relieve some of this distress."2
• "This medication has been known to help others with the same problem."8
• "I would like to refer you to a specialist for this disorder."9 (The patient is not immediately told that the specialist is a psychiatrist, but this fact is not denied if asked.)
• "You may very well have had an infestation initially that was adequately treated, and the only sign now is the residual sensation you feel in your skin. Given the experience you have had, I can understand how you feel that parasites are still there. This is a situation that I have seen before, and the medication that I am going to prescribe is usually very helpful in getting rid of this last remaining discomfort."10

Treating the patient's anxiety should be seriously considered.6 Benzodiazepines such as diazepam and alprazolam are commonly used for short-term treatment of anxiety. These medications are fast acting and can be withdrawn after a few weeks. Consultation with a psychiatrist can be helpful for clinicians who are not familiar or comfortable with these drugs. Treating the symptomatic itching or burning sensation experienced by many patients also should be considered. Crotamiton cream is useful for pruritus and possibly eradicates some organisms. Topical or intramuscular corticosteroids may be useful to alleviate the itching sensation. Additionally, an antihistamine can be useful. Over-the-counter anti-itch medications also can be used.

Treating the Delusion
Until the 1950s, DOP was considered a nontreatable disease. In 1946, Wilson and Miller11 reported that beyond treating the patient for syphilis, if indicated, "there is nothing whatsoever the dermatologist can do for such a patient." While viable treatment options are now available, management remains a challenge for clinicians, especially nonpsychiatrists. A meta-analysis of 1223 case reports of DOP showed marked improvement in full remission rates from the prepsychopharmacologic era (before 1960) to the postpsychopharmacologic era (after 1960)(33.9% to 51.9%, respectively).12 Most cases of DOP need to be treated. There have been few reported cases of spontaneous remission of DOP.13,14 Most experts will agree that referral to a psychiatrist is beneficial. It is debatable if psychiatrists are the only clinicians equipped to handle these patients or if dermatologists may and should prescribe pimozide.15,16 Koblenzer17 stated: "If not treated by the dermatologist, [patients with DOP are] doomed to a prolonged, expensive, and frenetic search from doctor to doctor, to exterminator, to entomologist, and so on, without relief." Regardless of the medication used, the clinician must proceed with caution when suggesting treatment to patients with DOP. Commonly, when a clinician suggests psychiatric referral or medication, the patient responds angrily and does not return.5,18 Patients can become a danger to themselves and others. One man set fire to one of his apartments and flooded another19; other patients have committed suicide.13,20 It is important to note the extreme desperation in which these patients often find themselves. Many patients have tried relentlessly to find a treatment for their supposed infestation and often have found their clinician to be more of a hindrance than a help. One such case resulted in an attempt on the life of a family physician.21

Pimozide
Pimozide is approved by the US Food and Drug Administration for Tourette syndrome. It was first used in 1975 to treat somatic delusions, as reported in 5 patients.22 Since then, this neuroleptic agent has been considered the treatment of choice for DOP. Pimozide is a highly selective dopamine D2 blocker; thus, it is effective in treating psychoses. Pimozide also has some serotonin receptor blocking activity, which is theorized to contribute to its therapeutic effects. Other neurologic effects include blockade of a-adrenergic receptor sites, voltage-gated calcium channels, and opiate receptors. Pimozide has approximately 50% oral bioavailability and its action lasts 24 to 48 hours, allowing for once-daily dosing. It is metabolized in the liver and primarily excreted in the urine.23 The most common side effects of pimozide are extrapyramidal symptoms, including pseudoparkinsonism, akathisia, and dystonia. Pseudoparkinsonism may manifest as muscle and joint stiffness, while akathisia is indicated by restlessness. These effects have been demonstrated in patients treated with a pimozide dosage as low as 2 mg daily.24 Symptoms can be controlled by anticholinergic medications, such as oral benztropine mesylate 1 to 4 mg once or twice daily, as needed, or diphenhydramine hydrochloride 25 mg 4 times daily, as needed. Benztropine mesylate is preferred versus diphenhydramine hydrochloride because it is not sedating. An acute dystonic reaction (ie, muscle spasm) rarely occurs because of the low dose of neuroleptic prescribed; however, the acute reaction also responds to anticholinergic agents.16 To minimize the risk for side effects, initially prescribe pimozide 1 mg daily, titrating up by 1 mg every 5 to 7 days (maximum, 10 mg daily), as needed. Koo and Lee25 recommend using the lowest effective dose of pimozide for the shortest possible duration. Pimozide at high doses has cardiotoxic properties manifested by long QT intervals and arrhythmias. Pretreatment and posttreatment electrocardiograms are recommended for all patients receiving pimozide.26 Discontinue increasing the dose when the QT interval is more than 0.52 seconds in adults or when there is a QT interval increase of 25% or more above the patient's baseline.27 Furthermore, coadministration of other drugs that increase the QT interval should be avoided, including but not limited to chlorpromazine, gatifloxacin, mefloquine, moxifloxacin hydrochloride, other class Ia and III antiarrhythmic agents, quinidine, tacrolimus, thioridazine hydrochloride, and ziprasidone hydrochloride or mesylate.28 Pimozide is the most studied and reported drug used for DOP. Most data on pimozide have come from individual or group case reports, though 2 double-blind placebo-controlled trials have been conducted. Of the 189 patients reported to be treated with pimozide in 22 articles, 79% reported a positive response to pimozide, 17% reported no response, and the rest were lost to follow-up.8,13,24,26,29-46 Side effects reported with pimozide included insomnia, drowsiness, and depression.34,41 Extrapyramidal symptoms such as pseudoparkinsonism and akathisia were not uncommon but generally were easily controlled with anticholinergic agents.13,24,26,34,35,38,40,41,45 Two cases of lethargy were reported with pimozide doses of up to 6 to 24 mg daily.41 An acute dystonic reaction occurred in a patient receiving 8 mg daily.40 The mean dosage of pimozide used for best effect was 5 mg daily, as per the case series for which this information was available.8,13,24,26,29-46 Both single and split dosing were reported as successful methods. The median duration of treatment to best results was 3.5 weeks, with a range of 3 days to 6 months. For patients who were followed long-term (4–12 mo), 100% (n=17) maintained complete or near complete resolution of symptoms (near complete in 1 patient) while receiving maintenance doses of pimozide. Daily doses ranged from 2 to 4 mg. For patients followed long-term who eventually discontinued pimozide, 43% (34/79) had subsequent recurrence of their symptoms. Of those patients re-treated with pimozide, 100% (n=20) had complete resolution of symptoms.8,13,24,26,29-46 Zomer et al46 studied 33 patients with DOP. A total of 61.1% (11/18) of patients reported improvement or full recovery with pimozide compared with the 20% (3/15) not treated. At a mean follow-up of 5 years, none of the patients who had full remission (5/33 with DOP) needed maintenance therapy.46 Hamann and Avnstorp34 conducted a double-blind, placebo-controlled, crossover trial in which participants showed a significant response to pimozide compared with placebo (P

Delusions of parasitosis (DOP) is a disorder in which patients erroneously insist that they are infested with parasites. These patients have an unshakable belief that their problems are medical. They rarely present to a psychiatrist and are almost always resistant to psychiatric referral. Thus, this disorder proves to be difficult to treat. The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years.1 She may complain of a crawling, biting, burrowing sensation (formication) on or under her skin. She may claim her symptoms originate from insects or other creatures that infest her, her home, or her work. She may actually see the crawling culprits and be able to describe them in detail. This delusion may impinge on her activities of daily living, but she is otherwise a functional well-adjusted person. Oftentimes she will bring in proof of infestation that, under close examination, are pieces of lint or other nonparasitic materials.1 Despite thorough examination and reassurance, the patient relentlessly believes she is infested. She will most likely refuse referral to a psychiatrist, the one clinician with the most experience treating delusional disorders. Thus, it is important for the general practitioner and other nonpsychiatric clinicians to be familiar with DOP and its management.

Medical Management
Medical or psychiatric treatment aimed at eliminating the delusion should be attempted only after rapport with the patient has been established. Koo and Pham2 stated: "The greatest challenge in the treatment of delusional patients is in obtaining their agreement to start treatment with an antipsychotic medication." Numerous case reports have been published in which the clinician was unable to successfully treat DOP because of a lack of patient confidence.3-5 We modified a suggested management strategy first described by Gould and Gragg6 and incorporated strategies from a lecture on promoting a trusting relationship with delusional patients presented by Koo7 at the University of Southern California Dermatology Grand Rounds to create the following management strategy for clinicians:

1. Listen to the patient's story. Give the patient a few minutes to narrate and then proceed with a battery of direct questions. Do not dwell on the patient's psychiatric history, which will encourage trust and allow you to control the dialogue.
2. Thoroughly examine the patient's skin and any evidence of infestation that they bring. This task may seem dishonest when you are convinced the patient is delusional; however, it is possible there is a true infestation. Even if he/she is not infested, developing a bond with the patient will allow you to suggest treatments that the patient may otherwise not accept.2
3. Perform a biopsy if the patient insists, which will show that you genuinely care about his/her problem. Allow the patient to pick the skin area he/she believes is the most involved, but insist that if the biopsy is negative, he/she should entertain the possibility that the ailment may not be due to a living organism.
4. Show concern for how the condition has affected the patient's life. This technique has been shown to have a positive effect on the establishment of a good physician-patient relationship. Furthermore, it can help you individualize a therapeutic strategy for the patient in a way that does not reinforce the delusion. For example, you may say, "We will work diligently to relieve the stress this problem has caused you."
5. Be empathetic, not sympathetic. Let the patient know that you understand how the condition has left him/her feeling isolated.

Be aware that rapport with the patient will not always develop immediately. It may take a few visits before the patient is comfortable enough to accept treatment suggestions. Clinicians are most concerned with discussions with the patient relating to the diagnosis and treatment. Most patients will not accept a psychiatric diagnosis for a condition that they are sure is somatic. The following statements made by clinicians have been used with success:

• "You have a very difficult problem, but I will study the specimens you have brought and will try to help you in any way that I can."6
• "I did not find any parasites today, but I am willing to examine any evidence that you bring me in the future."2
• "I noticed that you have been suffering with this problem and this is really bothering you day and night. Maybe I can offer you a medication that can help relieve some of this distress."2
• "This medication has been known to help others with the same problem."8
• "I would like to refer you to a specialist for this disorder."9 (The patient is not immediately told that the specialist is a psychiatrist, but this fact is not denied if asked.)
• "You may very well have had an infestation initially that was adequately treated, and the only sign now is the residual sensation you feel in your skin. Given the experience you have had, I can understand how you feel that parasites are still there. This is a situation that I have seen before, and the medication that I am going to prescribe is usually very helpful in getting rid of this last remaining discomfort."10

Treating the patient's anxiety should be seriously considered.6 Benzodiazepines such as diazepam and alprazolam are commonly used for short-term treatment of anxiety. These medications are fast acting and can be withdrawn after a few weeks. Consultation with a psychiatrist can be helpful for clinicians who are not familiar or comfortable with these drugs. Treating the symptomatic itching or burning sensation experienced by many patients also should be considered. Crotamiton cream is useful for pruritus and possibly eradicates some organisms. Topical or intramuscular corticosteroids may be useful to alleviate the itching sensation. Additionally, an antihistamine can be useful. Over-the-counter anti-itch medications also can be used.

Treating the Delusion
Until the 1950s, DOP was considered a nontreatable disease. In 1946, Wilson and Miller11 reported that beyond treating the patient for syphilis, if indicated, "there is nothing whatsoever the dermatologist can do for such a patient." While viable treatment options are now available, management remains a challenge for clinicians, especially nonpsychiatrists. A meta-analysis of 1223 case reports of DOP showed marked improvement in full remission rates from the prepsychopharmacologic era (before 1960) to the postpsychopharmacologic era (after 1960)(33.9% to 51.9%, respectively).12 Most cases of DOP need to be treated. There have been few reported cases of spontaneous remission of DOP.13,14 Most experts will agree that referral to a psychiatrist is beneficial. It is debatable if psychiatrists are the only clinicians equipped to handle these patients or if dermatologists may and should prescribe pimozide.15,16 Koblenzer17 stated: "If not treated by the dermatologist, [patients with DOP are] doomed to a prolonged, expensive, and frenetic search from doctor to doctor, to exterminator, to entomologist, and so on, without relief." Regardless of the medication used, the clinician must proceed with caution when suggesting treatment to patients with DOP. Commonly, when a clinician suggests psychiatric referral or medication, the patient responds angrily and does not return.5,18 Patients can become a danger to themselves and others. One man set fire to one of his apartments and flooded another19; other patients have committed suicide.13,20 It is important to note the extreme desperation in which these patients often find themselves. Many patients have tried relentlessly to find a treatment for their supposed infestation and often have found their clinician to be more of a hindrance than a help. One such case resulted in an attempt on the life of a family physician.21

Pimozide
Pimozide is approved by the US Food and Drug Administration for Tourette syndrome. It was first used in 1975 to treat somatic delusions, as reported in 5 patients.22 Since then, this neuroleptic agent has been considered the treatment of choice for DOP. Pimozide is a highly selective dopamine D2 blocker; thus, it is effective in treating psychoses. Pimozide also has some serotonin receptor blocking activity, which is theorized to contribute to its therapeutic effects. Other neurologic effects include blockade of a-adrenergic receptor sites, voltage-gated calcium channels, and opiate receptors. Pimozide has approximately 50% oral bioavailability and its action lasts 24 to 48 hours, allowing for once-daily dosing. It is metabolized in the liver and primarily excreted in the urine.23 The most common side effects of pimozide are extrapyramidal symptoms, including pseudoparkinsonism, akathisia, and dystonia. Pseudoparkinsonism may manifest as muscle and joint stiffness, while akathisia is indicated by restlessness. These effects have been demonstrated in patients treated with a pimozide dosage as low as 2 mg daily.24 Symptoms can be controlled by anticholinergic medications, such as oral benztropine mesylate 1 to 4 mg once or twice daily, as needed, or diphenhydramine hydrochloride 25 mg 4 times daily, as needed. Benztropine mesylate is preferred versus diphenhydramine hydrochloride because it is not sedating. An acute dystonic reaction (ie, muscle spasm) rarely occurs because of the low dose of neuroleptic prescribed; however, the acute reaction also responds to anticholinergic agents.16 To minimize the risk for side effects, initially prescribe pimozide 1 mg daily, titrating up by 1 mg every 5 to 7 days (maximum, 10 mg daily), as needed. Koo and Lee25 recommend using the lowest effective dose of pimozide for the shortest possible duration. Pimozide at high doses has cardiotoxic properties manifested by long QT intervals and arrhythmias. Pretreatment and posttreatment electrocardiograms are recommended for all patients receiving pimozide.26 Discontinue increasing the dose when the QT interval is more than 0.52 seconds in adults or when there is a QT interval increase of 25% or more above the patient's baseline.27 Furthermore, coadministration of other drugs that increase the QT interval should be avoided, including but not limited to chlorpromazine, gatifloxacin, mefloquine, moxifloxacin hydrochloride, other class Ia and III antiarrhythmic agents, quinidine, tacrolimus, thioridazine hydrochloride, and ziprasidone hydrochloride or mesylate.28 Pimozide is the most studied and reported drug used for DOP. Most data on pimozide have come from individual or group case reports, though 2 double-blind placebo-controlled trials have been conducted. Of the 189 patients reported to be treated with pimozide in 22 articles, 79% reported a positive response to pimozide, 17% reported no response, and the rest were lost to follow-up.8,13,24,26,29-46 Side effects reported with pimozide included insomnia, drowsiness, and depression.34,41 Extrapyramidal symptoms such as pseudoparkinsonism and akathisia were not uncommon but generally were easily controlled with anticholinergic agents.13,24,26,34,35,38,40,41,45 Two cases of lethargy were reported with pimozide doses of up to 6 to 24 mg daily.41 An acute dystonic reaction occurred in a patient receiving 8 mg daily.40 The mean dosage of pimozide used for best effect was 5 mg daily, as per the case series for which this information was available.8,13,24,26,29-46 Both single and split dosing were reported as successful methods. The median duration of treatment to best results was 3.5 weeks, with a range of 3 days to 6 months. For patients who were followed long-term (4–12 mo), 100% (n=17) maintained complete or near complete resolution of symptoms (near complete in 1 patient) while receiving maintenance doses of pimozide. Daily doses ranged from 2 to 4 mg. For patients followed long-term who eventually discontinued pimozide, 43% (34/79) had subsequent recurrence of their symptoms. Of those patients re-treated with pimozide, 100% (n=20) had complete resolution of symptoms.8,13,24,26,29-46 Zomer et al46 studied 33 patients with DOP. A total of 61.1% (11/18) of patients reported improvement or full recovery with pimozide compared with the 20% (3/15) not treated. At a mean follow-up of 5 years, none of the patients who had full remission (5/33 with DOP) needed maintenance therapy.46 Hamann and Avnstorp34 conducted a double-blind, placebo-controlled, crossover trial in which participants showed a significant response to pimozide compared with placebo (P

Delusions of parasitosis (DOP) is a disorder characterized by patients who erroneously insist that they are infested with parasites. The disorder is encountered by physicians in a wide variety of specialties, including dermatology, family practice, infectious disease, internal medicine, and psychiatry, yet its etiology and impetus for affecting some patients and not others remain unclear. 

Classification
Delusions of parasitosis has been referred to by many names over the years, including parasitophobia1 and acarophobia2; delusions of dermatozoiasis, dermatophobia, entomophobia3; parasitophobic neurodermatitis; Ekbom syndrome4; and most recently, Morgellons disease.5 According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), DOP is considered a form of psychosis.6 Specifically, it is classified as a delusional disorder of a somatic subtype. It is distinguished from paranoia, a disorder in which patients know their fear is irrational.7 Instead, DOP is a fixed false belief of infestation. This belief is nonbizarre; it is conceivable that a person could, in theory, have a parasitic infection. To diagnose DOP, patients must meet the following criteria: (1) a delusion of at least 1 month's duration; (2) no prior diagnosis of schizophrenia8; (3) psychosocial functioning is not impaired other than directly by the delusion; (4) if a mood disorder coexists, the mood disturbance is shorter in duration than the delusion; and (5) the delusion is not caused by substance use or another medical condition.6 Delusions of parasitosis also can be classified as monosymptomatic hypochondriacal psychosis, a term used to emphasize that DOP, among other disorders of this type, is encapsulated. Patients with DOP often are perfectly appropriate in behavior and logic in all other aspects of life.2 However, they have this single, firm, persistent delusion of infestation. Patients with other psychotic disorders, such as schizophrenia, usually have other psychological signs, such as blunted affect and auditory hallucinations, in addition to their delusions.9 Patients can present with parasitic delusions caused by an underlying organic disorder, but they are not true cases of DOP.

Epidemiology
While the prevalence of this disorder is unknown, it has been described in the literature as rare.10 However, many researchers have speculated that the prevalence is indeed greater than initially suspected.8,11-13 A retrospective study at the University of Cologne, Germany, reported a prevalence of 67 cases per 1000 psychiatric admissions.14 Various authors have reported incidences in their clinics averaging from 0.6 to 20 cases per year (Table).15-21

The overall prevalence is difficult to assess because the disorder may be referred to by different names; physicians of some specialties will see more cases than others; certain physicians will get more referrals than others based on their history of treating DOP; and while an inpatient population is most easily studied, most patients with DOP are seen on an outpatient basis. Furthermore, physicians depend on the unreliable method of self-reporting to identify this disease. Because infestation is socially unacceptable, patients may be embarrassed to report their symptoms, fearing judgment on their socioeconomic status, hygiene, and mental health. Delusions of parasitosis may be more prevalent in areas where infestation is more commonplace and, consequently, considered a more acceptable diagnosis. Srinivasan et al19 discuss this phenomenon in India. The female to male ratio has ranged from 2 to 1 in 2 UK surveys,10,22 to 2.2 to 1 in a tabulated series,3 to 2.8 to 1 in a single study of 57 cases,23 to 4 to 1 in a retrospective analysis of 20 cases.14 Furthermore, female predominance is reported by Lyell10 to be stronger at an older age. The mean age of onset ranges from 50 to 69 years. A bimodal distribution with some patients presenting in their 20s or 30s also has been described.8 Folie à deux, a delusion shared by another person, was estimated to occur in approximately 8% to 10% of patients (in studies with >100 patients).10,24 The authors reviewed demographic data from 61 articles published on this topic.3,10,15-21,25-76 Delusions of parasitosis was reported in 150 females and 82 males (a 1.8:1 ratio of females to males). The mean age of onset was 57.9 years, with 59.2 years for females and 55.5 years for males. Of cases in which data were available, 11% (16/150) reported evidence of folie à deux and 50% (63/128) presented with proof of infestation. Of 95 cases reported, 34% (32/95) presented to dermatologists and 29% (28/95) presented to psychiatrists (Figure).

Clinical Presentation
The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years. She has probably presented to many physicians in different specialties. She has the unshakable belief that she is infested. She may believe she is infested by a specific insect and even describes the color or shape of the bugs. Despite the lack of clinical evidence, she may claim to actually see the bugs crawling on her77 and feel the sensation of biting or burrowing under the skin (formication). She will commonly bring in proof of infestation, such as visible particles on clear tape or in little plastic bags, which is called the matchbox sign because patients, as described in older literature, brought their evidence in matchboxes. A more recent report appropriately suggested modernizing the term to the Ziploc® sign.77 Upon examination, the particles are nothing more than skin scrapings, lint, or other nonparasitic materials. Frequently, the patient presents with neurotic excoriations or inflammation secondary to scratching or self-prescribed treatments for the infestation, such as abrasive cleaning agents. Despite thorough examination and reassurance by the physician that there is no infestation, the patient clings to his/her beliefs. These patients rarely will accept psychiatric referrals despite the fact that psychiatrists are best trained to deal with delusional disorders.

Etiology
The etiology of DOP remains unknown. It has been speculated that an actual sensation, such as a paresthesia or other pruritus, initiates the disorder,78,79 which would be especially more common among older patients. As the skin becomes more prone to idiopathic pruritus, the nervous system is less adept at interpreting these sensations.80 Subsequently, a real sensation is misperceived and becomes associated with a paranoid idea; from this nidus, a delusion is born.62 Johnson and Anton81 have suggested that pimozide, an antipsychotic, is effective for patients with DOP because of its antipruritic effects mediated through opiate agonism. Pimozide has activity similar to morphine and fentanyl citrate. A controlled trial clinically linked opiate receptor agonism to DOP.82 Fentanyl citrate, an opiate agonist, exaggerated complaints in a patient with DOP but induced euphoria in the control group. Naloxone hydrochloride, an opiate antagonist, alleviated DOP symptoms and caused euphoria in patients with DOP, while the control group reported dysphoria. All changes reverted back to baseline with discontinuation of the drugs.82 Another theory attributes DOP to overactivity of the dopaminergic system in the limbic area of the brain, much like schizophrenia or drug-induced psychosis,83,84 which would explain the sensitivity of the delusions to pimozide, a very specific dopamine blocker. A hypothesis of thalamic involvement also exists.85 It has been suggested that delusions are, in fact, somatic manifestations of underlying anxiety. For patients, the idea of infestation is easier to address and becomes a coping mechanism to avoid facing the real issues that disturb them.15,80 Because of the similarity between symptoms of lysergic acid diethylamide ingestion and monosymptomatic hypochondriacal psychosis, or DOP, it has been postulated that serotonin receptors may play a part in causing symptoms. Furthermore, pimozide is known to have 5-hydroxytryptamine2 receptor–blocking capabilities.86 De Leon et al79 postulated that the suggestible nature of infestation (ie, folie à deux) is caused by the contagious nature of scratching, ease of proving infestation versus another delusion, and the ancestral fear of parasites.

Associated Features
While DOP is associated with many medical and psychiatric conditions, it is important to reiterate that it is a primary disorder and not a consequence of another general medical or psychiatric condition.11,14 Interestingly, in one study, the prevailing psychiatric symptom was misidentification (misidentifying a stimulus) in 65% of patients with DOP compared with 11% of patients with late-onset schizophrenia and 8% of patients with organic mental disorders caused by cerebral arteriosclerosis.14 Many patients report a previous history of skin disorder including previous infestation. They might have complained of some abnormal skin sensation, pruritus, or paresthesia.10,14,62 There is mixed evidence classifying patients with DOP as loners,14,63,64,83 though social isolation is common and often may be secondary to the delusion. There is further evidence suggesting that patients with DOP have a lower than average socioeconomic status.18,83 According to a detailed and intensive psychological study of 5 cases, DOP seemed to be associated with an average intelligence.65

Diagnosis and Differential
Before making the diagnosis of DOP, the delusion must be present for at least one month. It is most important to rule out actual infestation, as an editorial in Lancet quips, "Do look in the matchbox. It may contain real parasites."⁸⁷ One must rule out an actual infestation before assigning the diagnosis of DOP, as parasites such as head lice are ubiquitous. A group of psychiatrists from Austria set out to discover the distribution of all patients presenting with DOP.88 They classified 34 patients into groups based on etiology. Of these patients, 47.1% (16/34) were classified as having a delusional disorder (ie, true DOP as an independent entity). Based on their own study and a review of previous literature, the researchers concluded that secondary DOP can coexist with any other psychiatric disorder: 17.6% (6/34) coexisted with dementia, 5.9% (2/34) with schizophrenia, and 23.5% (8/34) with major affective disorders. Delusions of parasitosis paralleled an organic disorder in 2 patients (5.9%): one patient with methamphetamine and cannabis abuse and one patient with postinfectious chronic fatigue syndrome.88 Parasitic delusions also can be a manifestation of any underlying psychiatric condition, such as schizophrenia, dementia, or psychotic depression.8,10,62,88,89 A single case report notes its association with posttraumatic stress disorder.66 A careful psychiatric evaluation should be administered to find evidence of other disorders. An important difference between DOP and schizophrenia is the lack of prominent first rank symptoms, such as auditory hallucinations, and negative symptoms, such as flattened affect.14 Also, in contrast to schizophrenia, DOP lacks global social impairment, loosening of association, and the delusion is nonbizarre (ie, infestation is a conceivable occurrence).90 Physicians should be careful to distinguish DOP associated with an affective disorder from DOP secondary to an affective disorder. Also confirm that the depression did not predate the delusion; if depression did predate the delusion, confirm that it is not severe. Additionally, ensure that the delusion and tactile sensations do not coincide with the course of the affective illness.90 There are many substances that are associated with parasitic delusions. Cocaine91-93 and methamphetamine94 are notorious for causing tactile sensations associated with parasitic hallucinations. Methylphenidate hydrochloride use is another culprit.95-97 Alcohol use can cause formication during withdrawal.67,98 Indeed, many cases of DOP have been associated with a remote history of long-term alcohol abuse.64,68 Case reports indicate a similar problem with prescription medications such as the monoamine oxidase inhibitor phenelzine sulfate99,100 and corticosteroids.69 One case described an association with pemoline, a central nervous system stimulant used for attention deficit hyperactivity disorder.101 Use of amantadine hydrochloride also has been cited as a cause.102 Parasitic delusions have been reported in patients with general medical conditions, such as vitamin B12 deficiency,10,103 pellagra,10,104 kidney disease,10,75 diabetes mellitus,10,68,70 hypertension,3,68,70 thyroid disease,71 heart failure,3,68 multiple sclerosis,10 hepatitis,10 syphilis,3 cerebrovascular disease,10,69,105 stroke,10,70,76,106 pneumonia,10 tuberculosis,3 lymphoma,105 AIDS,64 pituitary tumor,72,105 and Lyme disease.5 When considering a diagnosis of DOP, one must consider the differential diagnoses and conditions associated with pruritus and paresthesia, as these sensations may be the precipitating idea from which the delusion is derived.62,73 To differentiate these conditions, the following laboratory tests should be conducted: complete blood cell count, chemistry panel, thyroid stimulating hormone, rapid plasma reagin, urinalysis, and urine toxicology screen. Based on the addition of other symptomatology, measuring vitamin B12/folate levels or performing a computed tomographic scan also may be indicated.74

Comment
Delusions of parasitosis remain an interesting and challenging problem for physicians. It is a delusional disorder of a somatic subtype in which patients believe they are infested. By definition, the disease is not secondary to any underlying psychiatric or organic disorder, though the same delusional thoughts may be present in patients with these disorders. This distinction is important because the treatment modalities vary. While most patients with DOP present first to a family or general practitioner, dermatologists or psychiatrists report most cases.107 General practitioners and physicians in other fields to whom these patients commonly present will be integral to early recognition of this psychotic disorder.108 We suspect that this disorder is more common than previously thought and we hope to raise the level of awareness. This article is the first of a 2-part series. The second part on treatment options will appear in a future issue of Cutis®.

Delusions of parasitosis (DOP) is a disorder characterized by patients who erroneously insist that they are infested with parasites. The disorder is encountered by physicians in a wide variety of specialties, including dermatology, family practice, infectious disease, internal medicine, and psychiatry, yet its etiology and impetus for affecting some patients and not others remain unclear. 

Classification
Delusions of parasitosis has been referred to by many names over the years, including parasitophobia1 and acarophobia2; delusions of dermatozoiasis, dermatophobia, entomophobia3; parasitophobic neurodermatitis; Ekbom syndrome4; and most recently, Morgellons disease.5 According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), DOP is considered a form of psychosis.6 Specifically, it is classified as a delusional disorder of a somatic subtype. It is distinguished from paranoia, a disorder in which patients know their fear is irrational.7 Instead, DOP is a fixed false belief of infestation. This belief is nonbizarre; it is conceivable that a person could, in theory, have a parasitic infection. To diagnose DOP, patients must meet the following criteria: (1) a delusion of at least 1 month's duration; (2) no prior diagnosis of schizophrenia8; (3) psychosocial functioning is not impaired other than directly by the delusion; (4) if a mood disorder coexists, the mood disturbance is shorter in duration than the delusion; and (5) the delusion is not caused by substance use or another medical condition.6 Delusions of parasitosis also can be classified as monosymptomatic hypochondriacal psychosis, a term used to emphasize that DOP, among other disorders of this type, is encapsulated. Patients with DOP often are perfectly appropriate in behavior and logic in all other aspects of life.2 However, they have this single, firm, persistent delusion of infestation. Patients with other psychotic disorders, such as schizophrenia, usually have other psychological signs, such as blunted affect and auditory hallucinations, in addition to their delusions.9 Patients can present with parasitic delusions caused by an underlying organic disorder, but they are not true cases of DOP.

Epidemiology
While the prevalence of this disorder is unknown, it has been described in the literature as rare.10 However, many researchers have speculated that the prevalence is indeed greater than initially suspected.8,11-13 A retrospective study at the University of Cologne, Germany, reported a prevalence of 67 cases per 1000 psychiatric admissions.14 Various authors have reported incidences in their clinics averaging from 0.6 to 20 cases per year (Table).15-21

The overall prevalence is difficult to assess because the disorder may be referred to by different names; physicians of some specialties will see more cases than others; certain physicians will get more referrals than others based on their history of treating DOP; and while an inpatient population is most easily studied, most patients with DOP are seen on an outpatient basis. Furthermore, physicians depend on the unreliable method of self-reporting to identify this disease. Because infestation is socially unacceptable, patients may be embarrassed to report their symptoms, fearing judgment on their socioeconomic status, hygiene, and mental health. Delusions of parasitosis may be more prevalent in areas where infestation is more commonplace and, consequently, considered a more acceptable diagnosis. Srinivasan et al19 discuss this phenomenon in India. The female to male ratio has ranged from 2 to 1 in 2 UK surveys,10,22 to 2.2 to 1 in a tabulated series,3 to 2.8 to 1 in a single study of 57 cases,23 to 4 to 1 in a retrospective analysis of 20 cases.14 Furthermore, female predominance is reported by Lyell10 to be stronger at an older age. The mean age of onset ranges from 50 to 69 years. A bimodal distribution with some patients presenting in their 20s or 30s also has been described.8 Folie à deux, a delusion shared by another person, was estimated to occur in approximately 8% to 10% of patients (in studies with >100 patients).10,24 The authors reviewed demographic data from 61 articles published on this topic.3,10,15-21,25-76 Delusions of parasitosis was reported in 150 females and 82 males (a 1.8:1 ratio of females to males). The mean age of onset was 57.9 years, with 59.2 years for females and 55.5 years for males. Of cases in which data were available, 11% (16/150) reported evidence of folie à deux and 50% (63/128) presented with proof of infestation. Of 95 cases reported, 34% (32/95) presented to dermatologists and 29% (28/95) presented to psychiatrists (Figure).

Clinical Presentation
The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years. She has probably presented to many physicians in different specialties. She has the unshakable belief that she is infested. She may believe she is infested by a specific insect and even describes the color or shape of the bugs. Despite the lack of clinical evidence, she may claim to actually see the bugs crawling on her77 and feel the sensation of biting or burrowing under the skin (formication). She will commonly bring in proof of infestation, such as visible particles on clear tape or in little plastic bags, which is called the matchbox sign because patients, as described in older literature, brought their evidence in matchboxes. A more recent report appropriately suggested modernizing the term to the Ziploc® sign.77 Upon examination, the particles are nothing more than skin scrapings, lint, or other nonparasitic materials. Frequently, the patient presents with neurotic excoriations or inflammation secondary to scratching or self-prescribed treatments for the infestation, such as abrasive cleaning agents. Despite thorough examination and reassurance by the physician that there is no infestation, the patient clings to his/her beliefs. These patients rarely will accept psychiatric referrals despite the fact that psychiatrists are best trained to deal with delusional disorders.

Etiology
The etiology of DOP remains unknown. It has been speculated that an actual sensation, such as a paresthesia or other pruritus, initiates the disorder,78,79 which would be especially more common among older patients. As the skin becomes more prone to idiopathic pruritus, the nervous system is less adept at interpreting these sensations.80 Subsequently, a real sensation is misperceived and becomes associated with a paranoid idea; from this nidus, a delusion is born.62 Johnson and Anton81 have suggested that pimozide, an antipsychotic, is effective for patients with DOP because of its antipruritic effects mediated through opiate agonism. Pimozide has activity similar to morphine and fentanyl citrate. A controlled trial clinically linked opiate receptor agonism to DOP.82 Fentanyl citrate, an opiate agonist, exaggerated complaints in a patient with DOP but induced euphoria in the control group. Naloxone hydrochloride, an opiate antagonist, alleviated DOP symptoms and caused euphoria in patients with DOP, while the control group reported dysphoria. All changes reverted back to baseline with discontinuation of the drugs.82 Another theory attributes DOP to overactivity of the dopaminergic system in the limbic area of the brain, much like schizophrenia or drug-induced psychosis,83,84 which would explain the sensitivity of the delusions to pimozide, a very specific dopamine blocker. A hypothesis of thalamic involvement also exists.85 It has been suggested that delusions are, in fact, somatic manifestations of underlying anxiety. For patients, the idea of infestation is easier to address and becomes a coping mechanism to avoid facing the real issues that disturb them.15,80 Because of the similarity between symptoms of lysergic acid diethylamide ingestion and monosymptomatic hypochondriacal psychosis, or DOP, it has been postulated that serotonin receptors may play a part in causing symptoms. Furthermore, pimozide is known to have 5-hydroxytryptamine2 receptor–blocking capabilities.86 De Leon et al79 postulated that the suggestible nature of infestation (ie, folie à deux) is caused by the contagious nature of scratching, ease of proving infestation versus another delusion, and the ancestral fear of parasites.

Associated Features
While DOP is associated with many medical and psychiatric conditions, it is important to reiterate that it is a primary disorder and not a consequence of another general medical or psychiatric condition.11,14 Interestingly, in one study, the prevailing psychiatric symptom was misidentification (misidentifying a stimulus) in 65% of patients with DOP compared with 11% of patients with late-onset schizophrenia and 8% of patients with organic mental disorders caused by cerebral arteriosclerosis.14 Many patients report a previous history of skin disorder including previous infestation. They might have complained of some abnormal skin sensation, pruritus, or paresthesia.10,14,62 There is mixed evidence classifying patients with DOP as loners,14,63,64,83 though social isolation is common and often may be secondary to the delusion. There is further evidence suggesting that patients with DOP have a lower than average socioeconomic status.18,83 According to a detailed and intensive psychological study of 5 cases, DOP seemed to be associated with an average intelligence.65

Diagnosis and Differential
Before making the diagnosis of DOP, the delusion must be present for at least one month. It is most important to rule out actual infestation, as an editorial in Lancet quips, "Do look in the matchbox. It may contain real parasites."⁸⁷ One must rule out an actual infestation before assigning the diagnosis of DOP, as parasites such as head lice are ubiquitous. A group of psychiatrists from Austria set out to discover the distribution of all patients presenting with DOP.88 They classified 34 patients into groups based on etiology. Of these patients, 47.1% (16/34) were classified as having a delusional disorder (ie, true DOP as an independent entity). Based on their own study and a review of previous literature, the researchers concluded that secondary DOP can coexist with any other psychiatric disorder: 17.6% (6/34) coexisted with dementia, 5.9% (2/34) with schizophrenia, and 23.5% (8/34) with major affective disorders. Delusions of parasitosis paralleled an organic disorder in 2 patients (5.9%): one patient with methamphetamine and cannabis abuse and one patient with postinfectious chronic fatigue syndrome.88 Parasitic delusions also can be a manifestation of any underlying psychiatric condition, such as schizophrenia, dementia, or psychotic depression.8,10,62,88,89 A single case report notes its association with posttraumatic stress disorder.66 A careful psychiatric evaluation should be administered to find evidence of other disorders. An important difference between DOP and schizophrenia is the lack of prominent first rank symptoms, such as auditory hallucinations, and negative symptoms, such as flattened affect.14 Also, in contrast to schizophrenia, DOP lacks global social impairment, loosening of association, and the delusion is nonbizarre (ie, infestation is a conceivable occurrence).90 Physicians should be careful to distinguish DOP associated with an affective disorder from DOP secondary to an affective disorder. Also confirm that the depression did not predate the delusion; if depression did predate the delusion, confirm that it is not severe. Additionally, ensure that the delusion and tactile sensations do not coincide with the course of the affective illness.90 There are many substances that are associated with parasitic delusions. Cocaine91-93 and methamphetamine94 are notorious for causing tactile sensations associated with parasitic hallucinations. Methylphenidate hydrochloride use is another culprit.95-97 Alcohol use can cause formication during withdrawal.67,98 Indeed, many cases of DOP have been associated with a remote history of long-term alcohol abuse.64,68 Case reports indicate a similar problem with prescription medications such as the monoamine oxidase inhibitor phenelzine sulfate99,100 and corticosteroids.69 One case described an association with pemoline, a central nervous system stimulant used for attention deficit hyperactivity disorder.101 Use of amantadine hydrochloride also has been cited as a cause.102 Parasitic delusions have been reported in patients with general medical conditions, such as vitamin B12 deficiency,10,103 pellagra,10,104 kidney disease,10,75 diabetes mellitus,10,68,70 hypertension,3,68,70 thyroid disease,71 heart failure,3,68 multiple sclerosis,10 hepatitis,10 syphilis,3 cerebrovascular disease,10,69,105 stroke,10,70,76,106 pneumonia,10 tuberculosis,3 lymphoma,105 AIDS,64 pituitary tumor,72,105 and Lyme disease.5 When considering a diagnosis of DOP, one must consider the differential diagnoses and conditions associated with pruritus and paresthesia, as these sensations may be the precipitating idea from which the delusion is derived.62,73 To differentiate these conditions, the following laboratory tests should be conducted: complete blood cell count, chemistry panel, thyroid stimulating hormone, rapid plasma reagin, urinalysis, and urine toxicology screen. Based on the addition of other symptomatology, measuring vitamin B12/folate levels or performing a computed tomographic scan also may be indicated.74

Comment
Delusions of parasitosis remain an interesting and challenging problem for physicians. It is a delusional disorder of a somatic subtype in which patients believe they are infested. By definition, the disease is not secondary to any underlying psychiatric or organic disorder, though the same delusional thoughts may be present in patients with these disorders. This distinction is important because the treatment modalities vary. While most patients with DOP present first to a family or general practitioner, dermatologists or psychiatrists report most cases.107 General practitioners and physicians in other fields to whom these patients commonly present will be integral to early recognition of this psychotic disorder.108 We suspect that this disorder is more common than previously thought and we hope to raise the level of awareness. This article is the first of a 2-part series. The second part on treatment options will appear in a future issue of Cutis®.

Delusions of parasitosis (DOP) is a disorder characterized by patients who erroneously insist that they are infested with parasites. The disorder is encountered by physicians in a wide variety of specialties, including dermatology, family practice, infectious disease, internal medicine, and psychiatry, yet its etiology and impetus for affecting some patients and not others remain unclear. 

Classification
Delusions of parasitosis has been referred to by many names over the years, including parasitophobia1 and acarophobia2; delusions of dermatozoiasis, dermatophobia, entomophobia3; parasitophobic neurodermatitis; Ekbom syndrome4; and most recently, Morgellons disease.5 According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), DOP is considered a form of psychosis.6 Specifically, it is classified as a delusional disorder of a somatic subtype. It is distinguished from paranoia, a disorder in which patients know their fear is irrational.7 Instead, DOP is a fixed false belief of infestation. This belief is nonbizarre; it is conceivable that a person could, in theory, have a parasitic infection. To diagnose DOP, patients must meet the following criteria: (1) a delusion of at least 1 month's duration; (2) no prior diagnosis of schizophrenia8; (3) psychosocial functioning is not impaired other than directly by the delusion; (4) if a mood disorder coexists, the mood disturbance is shorter in duration than the delusion; and (5) the delusion is not caused by substance use or another medical condition.6 Delusions of parasitosis also can be classified as monosymptomatic hypochondriacal psychosis, a term used to emphasize that DOP, among other disorders of this type, is encapsulated. Patients with DOP often are perfectly appropriate in behavior and logic in all other aspects of life.2 However, they have this single, firm, persistent delusion of infestation. Patients with other psychotic disorders, such as schizophrenia, usually have other psychological signs, such as blunted affect and auditory hallucinations, in addition to their delusions.9 Patients can present with parasitic delusions caused by an underlying organic disorder, but they are not true cases of DOP.

Epidemiology
While the prevalence of this disorder is unknown, it has been described in the literature as rare.10 However, many researchers have speculated that the prevalence is indeed greater than initially suspected.8,11-13 A retrospective study at the University of Cologne, Germany, reported a prevalence of 67 cases per 1000 psychiatric admissions.14 Various authors have reported incidences in their clinics averaging from 0.6 to 20 cases per year (Table).15-21

The overall prevalence is difficult to assess because the disorder may be referred to by different names; physicians of some specialties will see more cases than others; certain physicians will get more referrals than others based on their history of treating DOP; and while an inpatient population is most easily studied, most patients with DOP are seen on an outpatient basis. Furthermore, physicians depend on the unreliable method of self-reporting to identify this disease. Because infestation is socially unacceptable, patients may be embarrassed to report their symptoms, fearing judgment on their socioeconomic status, hygiene, and mental health. Delusions of parasitosis may be more prevalent in areas where infestation is more commonplace and, consequently, considered a more acceptable diagnosis. Srinivasan et al19 discuss this phenomenon in India. The female to male ratio has ranged from 2 to 1 in 2 UK surveys,10,22 to 2.2 to 1 in a tabulated series,3 to 2.8 to 1 in a single study of 57 cases,23 to 4 to 1 in a retrospective analysis of 20 cases.14 Furthermore, female predominance is reported by Lyell10 to be stronger at an older age. The mean age of onset ranges from 50 to 69 years. A bimodal distribution with some patients presenting in their 20s or 30s also has been described.8 Folie à deux, a delusion shared by another person, was estimated to occur in approximately 8% to 10% of patients (in studies with >100 patients).10,24 The authors reviewed demographic data from 61 articles published on this topic.3,10,15-21,25-76 Delusions of parasitosis was reported in 150 females and 82 males (a 1.8:1 ratio of females to males). The mean age of onset was 57.9 years, with 59.2 years for females and 55.5 years for males. Of cases in which data were available, 11% (16/150) reported evidence of folie à deux and 50% (63/128) presented with proof of infestation. Of 95 cases reported, 34% (32/95) presented to dermatologists and 29% (28/95) presented to psychiatrists (Figure).

Clinical Presentation
The classic patient with DOP is a middle-aged woman frustrated by unsuccessful attempts to discover the cause of her ailment that has been affecting her for months or years. She has probably presented to many physicians in different specialties. She has the unshakable belief that she is infested. She may believe she is infested by a specific insect and even describes the color or shape of the bugs. Despite the lack of clinical evidence, she may claim to actually see the bugs crawling on her77 and feel the sensation of biting or burrowing under the skin (formication). She will commonly bring in proof of infestation, such as visible particles on clear tape or in little plastic bags, which is called the matchbox sign because patients, as described in older literature, brought their evidence in matchboxes. A more recent report appropriately suggested modernizing the term to the Ziploc® sign.77 Upon examination, the particles are nothing more than skin scrapings, lint, or other nonparasitic materials. Frequently, the patient presents with neurotic excoriations or inflammation secondary to scratching or self-prescribed treatments for the infestation, such as abrasive cleaning agents. Despite thorough examination and reassurance by the physician that there is no infestation, the patient clings to his/her beliefs. These patients rarely will accept psychiatric referrals despite the fact that psychiatrists are best trained to deal with delusional disorders.

Etiology
The etiology of DOP remains unknown. It has been speculated that an actual sensation, such as a paresthesia or other pruritus, initiates the disorder,78,79 which would be especially more common among older patients. As the skin becomes more prone to idiopathic pruritus, the nervous system is less adept at interpreting these sensations.80 Subsequently, a real sensation is misperceived and becomes associated with a paranoid idea; from this nidus, a delusion is born.62 Johnson and Anton81 have suggested that pimozide, an antipsychotic, is effective for patients with DOP because of its antipruritic effects mediated through opiate agonism. Pimozide has activity similar to morphine and fentanyl citrate. A controlled trial clinically linked opiate receptor agonism to DOP.82 Fentanyl citrate, an opiate agonist, exaggerated complaints in a patient with DOP but induced euphoria in the control group. Naloxone hydrochloride, an opiate antagonist, alleviated DOP symptoms and caused euphoria in patients with DOP, while the control group reported dysphoria. All changes reverted back to baseline with discontinuation of the drugs.82 Another theory attributes DOP to overactivity of the dopaminergic system in the limbic area of the brain, much like schizophrenia or drug-induced psychosis,83,84 which would explain the sensitivity of the delusions to pimozide, a very specific dopamine blocker. A hypothesis of thalamic involvement also exists.85 It has been suggested that delusions are, in fact, somatic manifestations of underlying anxiety. For patients, the idea of infestation is easier to address and becomes a coping mechanism to avoid facing the real issues that disturb them.15,80 Because of the similarity between symptoms of lysergic acid diethylamide ingestion and monosymptomatic hypochondriacal psychosis, or DOP, it has been postulated that serotonin receptors may play a part in causing symptoms. Furthermore, pimozide is known to have 5-hydroxytryptamine2 receptor–blocking capabilities.86 De Leon et al79 postulated that the suggestible nature of infestation (ie, folie à deux) is caused by the contagious nature of scratching, ease of proving infestation versus another delusion, and the ancestral fear of parasites.

Associated Features
While DOP is associated with many medical and psychiatric conditions, it is important to reiterate that it is a primary disorder and not a consequence of another general medical or psychiatric condition.11,14 Interestingly, in one study, the prevailing psychiatric symptom was misidentification (misidentifying a stimulus) in 65% of patients with DOP compared with 11% of patients with late-onset schizophrenia and 8% of patients with organic mental disorders caused by cerebral arteriosclerosis.14 Many patients report a previous history of skin disorder including previous infestation. They might have complained of some abnormal skin sensation, pruritus, or paresthesia.10,14,62 There is mixed evidence classifying patients with DOP as loners,14,63,64,83 though social isolation is common and often may be secondary to the delusion. There is further evidence suggesting that patients with DOP have a lower than average socioeconomic status.18,83 According to a detailed and intensive psychological study of 5 cases, DOP seemed to be associated with an average intelligence.65

Diagnosis and Differential
Before making the diagnosis of DOP, the delusion must be present for at least one month. It is most important to rule out actual infestation, as an editorial in Lancet quips, "Do look in the matchbox. It may contain real parasites."⁸⁷ One must rule out an actual infestation before assigning the diagnosis of DOP, as parasites such as head lice are ubiquitous. A group of psychiatrists from Austria set out to discover the distribution of all patients presenting with DOP.88 They classified 34 patients into groups based on etiology. Of these patients, 47.1% (16/34) were classified as having a delusional disorder (ie, true DOP as an independent entity). Based on their own study and a review of previous literature, the researchers concluded that secondary DOP can coexist with any other psychiatric disorder: 17.6% (6/34) coexisted with dementia, 5.9% (2/34) with schizophrenia, and 23.5% (8/34) with major affective disorders. Delusions of parasitosis paralleled an organic disorder in 2 patients (5.9%): one patient with methamphetamine and cannabis abuse and one patient with postinfectious chronic fatigue syndrome.88 Parasitic delusions also can be a manifestation of any underlying psychiatric condition, such as schizophrenia, dementia, or psychotic depression.8,10,62,88,89 A single case report notes its association with posttraumatic stress disorder.66 A careful psychiatric evaluation should be administered to find evidence of other disorders. An important difference between DOP and schizophrenia is the lack of prominent first rank symptoms, such as auditory hallucinations, and negative symptoms, such as flattened affect.14 Also, in contrast to schizophrenia, DOP lacks global social impairment, loosening of association, and the delusion is nonbizarre (ie, infestation is a conceivable occurrence).90 Physicians should be careful to distinguish DOP associated with an affective disorder from DOP secondary to an affective disorder. Also confirm that the depression did not predate the delusion; if depression did predate the delusion, confirm that it is not severe. Additionally, ensure that the delusion and tactile sensations do not coincide with the course of the affective illness.90 There are many substances that are associated with parasitic delusions. Cocaine91-93 and methamphetamine94 are notorious for causing tactile sensations associated with parasitic hallucinations. Methylphenidate hydrochloride use is another culprit.95-97 Alcohol use can cause formication during withdrawal.67,98 Indeed, many cases of DOP have been associated with a remote history of long-term alcohol abuse.64,68 Case reports indicate a similar problem with prescription medications such as the monoamine oxidase inhibitor phenelzine sulfate99,100 and corticosteroids.69 One case described an association with pemoline, a central nervous system stimulant used for attention deficit hyperactivity disorder.101 Use of amantadine hydrochloride also has been cited as a cause.102 Parasitic delusions have been reported in patients with general medical conditions, such as vitamin B12 deficiency,10,103 pellagra,10,104 kidney disease,10,75 diabetes mellitus,10,68,70 hypertension,3,68,70 thyroid disease,71 heart failure,3,68 multiple sclerosis,10 hepatitis,10 syphilis,3 cerebrovascular disease,10,69,105 stroke,10,70,76,106 pneumonia,10 tuberculosis,3 lymphoma,105 AIDS,64 pituitary tumor,72,105 and Lyme disease.5 When considering a diagnosis of DOP, one must consider the differential diagnoses and conditions associated with pruritus and paresthesia, as these sensations may be the precipitating idea from which the delusion is derived.62,73 To differentiate these conditions, the following laboratory tests should be conducted: complete blood cell count, chemistry panel, thyroid stimulating hormone, rapid plasma reagin, urinalysis, and urine toxicology screen. Based on the addition of other symptomatology, measuring vitamin B12/folate levels or performing a computed tomographic scan also may be indicated.74

Comment
Delusions of parasitosis remain an interesting and challenging problem for physicians. It is a delusional disorder of a somatic subtype in which patients believe they are infested. By definition, the disease is not secondary to any underlying psychiatric or organic disorder, though the same delusional thoughts may be present in patients with these disorders. This distinction is important because the treatment modalities vary. While most patients with DOP present first to a family or general practitioner, dermatologists or psychiatrists report most cases.107 General practitioners and physicians in other fields to whom these patients commonly present will be integral to early recognition of this psychotic disorder.108 We suspect that this disorder is more common than previously thought and we hope to raise the level of awareness. This article is the first of a 2-part series. The second part on treatment options will appear in a future issue of Cutis®.