High Precision Quantitative Proteomics Using iTRAQ on an LTQ Orbitrap

Aug 11, 2009 - Georg-August-Universität, Germany, and Institute of Molecular Biotechnology (IMBA), Vienna, Austria. Received May 20, 2009 ... However...
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Letters

Alleviating the Itch-Scratch Cycle in Atopic Dermatitis TO THE EDITOR: Eczema or atopic dermatitis is a chronic, relapsing course of severe pruritus. The sensation experienced by patients with atopic dermatitis is not only tormenting but is also a source of social embarrassment secondary to the appearance of the excoriated skin and the preoccupation with scratching in social situations. Beyond this, damage of the integrity of the skin can create a portal of entry for systemic and devastating infections.1 Excessive scratching or neurotic excoriation is a type of psychogenic excoriation that is characterized by excessive scratching, gouging, or squeezing of normal skin or skin with minor surface irregularities. Excoriation may also occur in response to an itch or other skin sensation or to remove a lesion such as acne.1,2 The typical treatment of atopic dermatitis involves starting with conservative measures (bathing and moisturizing) followed by the use of topical or oral antihistamines. Tricyclic antidepressants have been used for their antihistaminic properties. Topical corticosteroids and antibiotics for a secondary infection are often used.3 Nonpharmacological treatments, such as cognitive behavior therapy, hypnosis, meditation, prayer, biofeedback, and eye movement desensitization and reprocessing, have been used with some success.4,5 Beyond the typical dermatological regimens for atopic dermatitis, there have been some studies looking at psychotropics to treat the itch.6 These include nitrazepam, tricyclic antidepressants, and naltrexone, which have all been shown to decrease the Psychosomatics 46:4, July-August 2005

wheal and flare sensation but were not helpful in decreasing the severity of the itch.7–9 Neuroleptics (chlorpromazine, thioridazine, and thiothixene) have not been shown to suppress histamineinduced pruritis but have been beneficial in nonhistamine-induced or psychogenic pruritis. More recently, case reports on the use of olanzapine for self-induced skin disorders have demonstrated reduced excoriation; this improvement was thought to be a result of a reduction in dissociative symptoms associated with self-mutilation.1,10,11 In contrast to the behavioral effects of neuroleptics, selective serotonin reuptake inhibitors have been shown to result in significant improvement in pruritis.2,12 The use of mirtazapine for refractory pruritis has also been studied in four case reports in which mirtazapine resulted in significant improvement or complete resolution of the pruritis with doses as low as 15 mg/day. Case Report Mr. A was a 62-year-old man with an implanted cardioverter defibrillator who had had 3 months of intermittent fever and 2 weeks of right hip pain. He had a history of recurrent eczema throughout his life and in recent months had been suffering from significant pruritis, frequently resulting in excoriation and bleeding. He felt increased tension and restlessness when cued by his eczema (noticing a lesion or feeling itchy). The subsequent scratching was followed by relief and guilt. His scratching was worse at night and disrupted his sleep. In the hospital, blood cultures were positive for Staphylococcus aureus, and two-dimensional echocardiography revealed vegetations on his

tricuspid leaflets and his implanted cardioverter defibrillator leads. Mr. A required open-heart surgery to remove the leads and to remove the vegetations on the tricuspid valve leaflets. The psychiatric service was consulted because it became apparent that his endocarditis was caused by the portal of entry for Staphylococcus aureus created by excoriation. Specific aspects of Mr. A’s scratching resemble obsessive-compulsive disorder in that it was repetitive, ritualistic, tension-reducing, and ego-dystonic. Other features of his scratching resembled an impulse control disorder in that he acted automatically and experienced an increase in tension before scratching with a brief moment of pleasure immediately following the act.13 Although these facts helped in designing a treatment plan, Mr. A could not fall into these categories because there was a specific medical problem, atopic dermatitis, which was causing the pruitic sensation and consequent scratching. Therefore, we concluded that the most appropriate DSM-IV classification was “psychological factors affecting a medical condition.” We initially implemented both a behavioral (scratching diary) and pharmacological (mirtazapine, 30 mg/day) treatment strategy. After 1 week of treatment, it became apparent that the itch sensation had decreased but was still problematic at night. At this point, olanzapine, 5 mg/day, and imovane, 7.5 mg at bedtime, was started. We could find no literature suggesting the effectiveness of imovane; however, we hypothesized that it would decrease the nocturnal scratching. One week later, Mr. A reported complete cessation of both the itch sensation and the scratching behavior. After discussing the disadvantages of polypharmacy, he prehttp://psy.psychiatryonline.org

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Letters ferred to attempt long-term treatment because of the positive results he had experienced. Discussion This case illustrates that psychotropic drugs may be an effective treatment for patients with intractable pruritis and excessive scratching. Our case also highlights the need for a multidimensional pharmacological approach that targets the sensation of itching, the behavior of scratching, and possibly the loss of sleep due to nocturnal itching and scratching. It is evident from the reports cited in this article and from this case that there is a need for more empirical research examining the effect of both antidepressants and neuroleptics for pruritis and scratching. Ramona Mahtani, B.Sc. Neal Parekh, B.Sc. Iqwal Mangat, M.D., F.R.C.P.(C.) Shree Bhalerao, B.Sc., M.D., F.R.C.P.C. Toronto, Ont., Canada

References

1. Arnold LM, Starck LO, McElroy SL: Treatment of psychogenic excoriation in the elderly patient. Clin Geriatrics 2002; 10:36–46 2. Arnold LM, Mutasim DF, Dwight MM, Lamerson CL, Morris EM, McElroy SL: An open clinical trial of fluvoxamine treatment of psychogenic excoriation. J Clin Psychopharmacol 1999; 19:15–18 3. Coorreale CE, Walker C, Murphy L, Craig TJ: Atopic dermatitis: a review of diagnosis and treatment. Am Fam Physician 2000; 61:3252 4. Ehlers A, Stangier U, Gieler U: Treatment of atopic dermatitis: a comparison of psychological and dermatological approaches to relapse prevention. J Consult Clin Psychol 1995; 63:624–635 5. Gupta MA, Gupta AK: Use of eye movement desensitization and reprocessing (EMDR) in the treatment of dermatologic disorders. J Cutan Med Surg 2002; 6:415–421 6. Davis MP, Frandsen JL, Walsh D,

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Andresen S, Taylor S: Mirtazapine for pruritus. J Pain Symptom Manage 2003; 25:288–291 7. Ebata T, Izumi H, Aizawa H, Kamide R, Niimura M: Effects of nitrazepam on nocturnal scratching in adults with atopic dermatitis: a double-blind placebocontrolled crossover study. Br J Dermatol 1998; 138:631–634 8. Groene D, Martus P, Heyer G: Doxepin affects acetylcholine induced cutaneous reactions in atopic eczema. Exp Dermatol 2001; 10:110–117 9. Heyer G, Groene D, Martus P: Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema. Exp Dermatol 2002; 11:448–455 10. Gupta MA, Gupta AK: Olanzapine is effective in the management of some self-induced dermatoses: three case reports. Cutis 2000; 66:143–146 11. Garnis-Jones S, Collins S, Rosenthal D: Treatment of self-mutilation with olanzapine. J Cutan Med Surg 2000; 4:161–163 12. Zylicz Z, Krajnik M, Sorge AA, Costantini M: Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. J Pain Symptom Manage 2003; 26:1105–1112 13. Arnold LM, Auchenbach MB, McElroy SL: Psychogenic excoriation. clinical features, proposed diagnostic criteria, epidemiology and approaches to treatment. CNS Drugs 2001; 15:351–359

Delirium Resolving Upon Switching From Risperidone to Quetiapine: Implication of CYP2D6 Genotype TO THE EDITOR: Atypical antipsychotics, such as risperidone, olanzapine, and quetiapine, are expected to show efficacies similar to those of conventional agents for treating psychotic disorders, as well as better tolerability. These medications were reported to have a lower incidence of side effects than conventional antipsychotics. However, even newer atypical antipsychotics can cause side effects, and responses to antipsychotics are very different among patients with various psychotic disorders, including delirium. Recent pharmacogenetic studies

have identified genetic polymorphisms of cytochrome P450 2D6 (CYP2D6), a drug-metabolizing enzyme, as a factor contributing to interindividual differences in metabolism and response to antipsychotics.1 In treating delirium, individual pharmacogenetic profiles are important to consider; yet few reports have addressed this issue. We report a patient whose delirium was treated successfully with quetiapine after switching from risperidone because of prominent extrapyramidal symptoms. We carried out screening for the CYP2D6 genotype of the patient. Case Report Mr. A was diagnosed with senile dementia of the Alzheimer’s type at the age of 73 and manifested acute delirium at the age of 74. He was treated initially at an outpatient clinic, but his psychomotor agitation and excitation became so prominent that he was admitted to a hospital. Mr. A was disoriented and had waxing and waning impairment of consciousness, difficulty in sustaining attention, delayed recall, and emotional lability characterized by angry outbursts and psychomotor agitation. He reported visual hallucinations and showed delusional perceptions. His thought processes were tangential to loose. He was diagnosed with delirium according to DSM-IV. Initial treatment with 1 mg/day of risperidone caused adverse reactions, including severe truncal dystonia, dysarthria, dysphagia, tremor, and rigidity 2 days after initiation of treatment. These extrapyramidal symptoms lessened 1 week after discontinuation of risperidone, but his delirium persisted. Switching to 25 mg/day of quetiapine was effective in allowing good sleep on the first day of administration. His bePsychosomatics 46:4, July-August 2005