- Email: [email protected]
Olanzapine-induced vasculitis
2&K. Duggal et M.
The Americefa Journal of Geriatric I~harmacotherapy
Case Report
Olanzapine-Induced Vasculitis Mahesh K. Duggal, MD, I Amritpal Singh, MD,2Arunabh, MD, ~ James D. Lolis, MD, ~ and Howard J. Guzik, MD ~ I Department of Geriatric Medicine, Wills Memorial Hospital, ~/Vasbington,Georgia; 2Gerber Hospital, Fremont, Michigan; and ~North 5bore University Hospital, Manhasset, New'fork
ABSTRACT Introduction: Blderly patients are particularly vulnerable to adverse drug reactions as a result of polypharmacy and metabolic changes associated with aging. We present a case ofleukocytoclastic vasculitis induced by olanzapine, a medication commonly used in elderly patients. Case summary: An 82 year old woman was admitted to file extended care center for short term rehabilitation after prolonged hospitalization for a pulmonary embolism requiring mechanical ventilation. The pulmonary problem resolved, but her hospitalization and subsequent rehabilitation were complicated by agitated delirium, which was treated wifll olanzapine and modification of contributory l~acmrs. At file time of admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after initiation of olanzapine, erythemamns skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range; however, because warfarin has been associated with subcutaneous bleeding presenting as petechiae and ecchymosis, subcutaneous enoxaparin was substituted for warfarin. The skin lesions continued to worsen over tile next week and developed into palpable lesions. Biopsy of tile rash revealed leukocytoclastic vasculitis. In tile absence of another cause, olanzapine was discontinued and tile rash improved sig nit]candy. When the agitation recurred, risperidone was initiated, but the patient experienced dizziness with this agent. Olanzapine was resumed and the skin lesions recurred. Olanzapine was then changed to quetiapine, and the skin lesions improved over tile next few weeks. Discussion: Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with dementia, delirium, and other psychiatric disorders. Lenkocytoclastic vasculitis is an infrequently reported adverse drug reaction with olanzapine. Its exact pathogenic mechanism is unknown, but both cell mediated and hnmoral immunity appear to play important roles. Because drug-induced vasculitis has an identical clinical presentation and identical serologic/pathologic parameters to idiopathic forms ofvasculitis, a high index of suspicion is necessary for its accurate diagnosis. Conclusions: Because adverse drug reactions are common in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of tile potential for leukocytoclastic vasculitis in association with olanzapine. (Are, J G e r i a t r I'harrnacother. 2005;3:21-24) Copyright © 2005 Excerpta Medica, Inc. Key words: adverse drug reaction, leukocymclastic vasculitis, multiple medications, olanzapine, elderly patients. Accepted tor pubJ~ccTtonjanucTry2J, 2005. Printed in the USA Reproduction in whole or part is not permitted
Copyright @ 2005 Excerpts Medic& Inc
doi:lO I016/j amjopharm.2005.03.003 1543-5946/05/$19.00
Volume 3 ÷ Number
I
M~rch 2005
21
The American Journal of Geriatric Pharmacotherapy
M.K. Duggal et aL
INTRODUCTION
Elderly patients taking muhiple medications are at high risk for adverse drug reactions, which are the most c o m m o n cause o f iatrogenic illness and are responsible for -6% of overall hospital adinissions. Each year, -35% o f older adults experience adverse drug reactions, -81% of which are preventable. 1,2 We present a case o f leukocytoclastic vasculitis induced by olanzapine, a commonly used medication in the elderly. CASE SUMMARY
An 82-year-old woman was admitted to the extendedcare facility for short-term rehabilitation after a prolonged hospitalization for lower-extremity deep vein thrombosis with pulmonary embolism. She had a history of mild Alzheimer's dementia, hypertension, and osteoarthritis, for which she was receiving donepezil, lisinopril, and acetaminophen, respectively. Her hospitalization had been complicated by agitated delirium. Hypoxia resolved with improvement in the patient's pulmonary problem. Urinary catheterization was discontinued, and fecal impaction and hypokalemia were treated. The patient was encouraged to use her eyeglasses, and more family visits were permitted. All nonessential medications were discontinued: the patient's only remaining medications were warfarin for pulmonary embolism and olanzapine for behavioral disturbance. Her delirium persisted despite all these measures. At the time o f her admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after the initiation of olanzapine, erythematous skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range. However, warfarin therapy is commonly associated with subcutaneous bleeding that presents as petechiae and ecchymosis, and has been associated with rare cases of skin necrosis. In our patient, warfarin was changed to subcutaneous enoxaparin. The skin lesions continued to worsen over the next week and developed into palpable lesions (Figure). The patient had no fever, arthralgias, or diarrhea. Her platelet count, renal function, and complement level were normal. Tests for antinuclear antibodies, antihistone antibodies, rheumatoid factor, cryoglobulins, antineutrophil cytoplasmic antibodies, hepatitis B surface antigen and core antibody, hepatitis C antibody, and H1V were negative. Biopsy of the rash revealed leukocytodastic vasculitis. When no other cause was found, olanzapine was discontinued and the rash improved significantly. When the agitation recurred, risperidone was initiated. However,
22
the patient experienced dizziness with risperidone. Olanzapine was resumed, and the skin lesions recurred. Based on a score of 5 on the Naranjo Adverse Drug Reaction Probability Scale, 3 olaxlzapine was assumed to be the probable cause of the cutaneous reaction. Olaxlzapine was subsequently changed to quetiapine, and the skin lesions improved over the next few weeks. DISCUSSION
Elderly patients are particularly vulnerable to adverse drug reactions as a result o f polypharmacy and metabolic changes associated with aging. Medications from almost every pharmacologic class have been implicated in the development o f drug-induced vasculitis (Table). 4 Leukocytoclastic vasculitis has been associated with many nonsteroidal anti-inflammatory drugs, s,6 betalactmu antibiotics, 7 and gabapentin8; it has recently been associated with tumor necrosis factor-alpha blockers such as etanercept and infliximab. 9 Vasculitis can involve small, medium, or large blood vessels. 1° Depending on the histology and type o f infiltrate, vasculitis can be granulomatous or polymorphonuclear. Drug-induced vasculitis commonly involves capillaries and venules. 3 Cutaneous vasculitis is characterized by a neutrophilic infiltrate in the acute stage, and by a m o n o n u d e a r infiltrate in the subacute and chronic stages, n Erythrocytes often extravasate from the involved blood vessels, leading to palpable pur-
Figure. Skin lesions in an 82-year-old woman receiving olanzapine therapy for delirium.
2¢ZIC Duggal et al.
The Americeta Journal of Geriatric Pharmacotberapy
Table. Drugs implicated in vasculitis. Anticoagulants and thrombolytic agents Heparin Strepto kinase
Cancer chemotherapeutic agents BusuIfan Cyclophosphamide N ethotrexate
Psychoactive drugs Amitri ptjli ne Naprotiline Trazodone
Warfarin Anticonvulsants Carbamazepine Gabapentin Sodium valproate Anti-infective agents Acyclovi r Ampicillin Ciprofloxacin Clindamycin Doxycycline Gentamicin Griseotulvin Ofloxacin Penicillin
Cardiovascular drugs Amiodarone Atenolol Captopril Diltiazem Furosemide Hyd ralazine Hydrochlorothiazide Nethyldopa Procainamide Quinidine Spironolactone Intravenous formulations Iodine-containing radiocontrast media Iron-dextran preparations
Niscellaneous agents AIIopurinol Azathioprine Chlorzoxazone Colchicine D penicillamine Etanercept Filgrastim Gold Infliximab Interteron-alfa blettormin Methylthiouracil Quinine Retinoids
Rifampin Trimethoprim-sultamethoxazole Zidovudine Beta adrenergic-receptor agonists Terbutaline
Nonsteroidal anti-inflammatory agents Diclofenac IbuprotSen Indomethacin Naproxen
pura. is The exact pathogenic mechanism of druginduced vasculitis is unknown, but both cell mediated and humoral immunity appear to play important roles, s The clinical manifestations range t~om small-vessel hypersensitivity vasculitis to clinical syndromes that are indistinguishable t~om classic systemic forms of vas culitis, such as Wegener's granulomatosis, polyarteritis nodosa, and Churg Strauss syndrome, is Patients may present with cutaneous involvement alone or with life threatening systemic involvement, s Because the clinical presentation and serologic/ pathologic parameters o f drug induced vasculitis are identical to those of idiopathic forms ofvasculitis, a high index of suspicion is necessary for its accurate diagnosis. Drug induced vasculitis is a poorly defined disorder, as proving the association between vasculitis and exposure to a particular drug is frequently difficult. There are es sentially no findings that reliably indicate a direct con nection between vasculitis and a particular drug exposure. Withdrawal of the offending agent is often snffident m bring prompt resolution of the clinical manifestations without the need for systemic corticosteroids or more powerful forms ofimmunosnppression. 3,14
Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with demen tia, delirium, and other psychiatric disorders, l~ It has occasionally been associated with skin problems 16,17 but never with leukocytoclastic vasculitis. The vasculitic skin lesions in our patient were probably attributable to olanzapine alone or to some unknown interaction. CONCLUSIONS
Because adverse drug reactions are c o m m o n in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of the potential for lenkocyto clastic vasculitis in association with olanzapine. REFERENCES 1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA. 1998;279:1200 1205. 2. Barranco P, Lopez Serrano MC. General and epidemio logical aspects of allergic drug reactions. Clin _FxpAllergy. 1998;28(Suppl 4):61 62.
13
The America~ Jour~M of Geriatric Pharmaco~her~py 3ILK.Duggal et M.
3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol That. i98i;30:239 245. 4. Doyle MK, Cuellar ML. Drug induced vasculitis. Expert Opin Dr~tg Saf 2003;2:401-409. 5. Schapira D, Balbir Gurman A, Nalair AM. Naproxen induced leukocytoclastic vasculitis. Clln Rhe~tmatol. 2000; 19:242-244. 6. Davidson KA, Rhagpfeil F, Lee JB. Ibuprofen induced bullous leukocytoclastic vasculitis. C~ttis. 2001 ;67:303 307. 7. Koutlda P, Mylonakis E, Rounds S, Erickson A. Cuta neous leukocytoclastic vasculitis associated with oxacillin. Diagn Microbiol Infect Dis. 2001 ;39:191-194. 8. Poon DY, Law NM. A case of cutaneous leukocytoclastic vasculitis associated with gabapentin. Singapore Mad J. 2003;44:42-44. 9. Mohan N, Edwards ET, Cupps TR, et al. Leuko cytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents, jr Rhe~tmawl. 2004;31: 1955 1958. 10. Russell JP, Weenig RH. Primary cutaneous small vessel vasculitis. Curt Trent Options Cardiovasc Mad. 2004; 6:139 149. 11. Zax RH, Hodge SJ, Callen JP. Cutaneous leukocyto clastic vasculitis. Serial histopathologic evaluation dam-
12.
13.
14.
15.
i6.
i7.
onstrates the dynamic nature of the infiltrate. Arch Der~natol. 1990;126:69-72. Crowson AN, Brown TJ, Magro CM. Progress in the understanding of the pathology and pathogenesis of cutaneous drug eruptions: Implications for management. A m J Clin Dermatol. 2003;4:407 428. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. A m f Clin Dermatol. 2003;4: 561 572. Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug lay persensitivity: A practice parameter. A n n Allergy Asthma Immunol. 1999;83:665 700. Street JS, Clark WS, Gannon KS, et al, for the HGEU Study Group. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer's disease in nurs ing care facilities: A double blind, randomized, placebo controlled trial. Arch Gen Psychiatry. 2000;57:968-976. Hagg S, Tatting P, Spigset O. Olanzapine mad venous thromboembolism. Int Clln Psychopharmacol. 2003;18: 299-300. Adams BB, /Vlutasim DF. Pustular eruption induced by olanzapine, a novel antipsychotic agent. J A m Acad Dermatol. 1999;41:851-853.
Address correspondence to: Mahesh K. Duggal, MD, Department of Geriatric Medicine, Wills Memorial Hospital, 123 Gordon Street, Washington, GA 30673. E mail: mkduggal@nu z.net
24
The Americefa Journal of Geriatric I~harmacotherapy
Case Report
Olanzapine-Induced Vasculitis Mahesh K. Duggal, MD, I Amritpal Singh, MD,2Arunabh, MD, ~ James D. Lolis, MD, ~ and Howard J. Guzik, MD ~ I Department of Geriatric Medicine, Wills Memorial Hospital, ~/Vasbington,Georgia; 2Gerber Hospital, Fremont, Michigan; and ~North 5bore University Hospital, Manhasset, New'fork
ABSTRACT Introduction: Blderly patients are particularly vulnerable to adverse drug reactions as a result of polypharmacy and metabolic changes associated with aging. We present a case ofleukocytoclastic vasculitis induced by olanzapine, a medication commonly used in elderly patients. Case summary: An 82 year old woman was admitted to file extended care center for short term rehabilitation after prolonged hospitalization for a pulmonary embolism requiring mechanical ventilation. The pulmonary problem resolved, but her hospitalization and subsequent rehabilitation were complicated by agitated delirium, which was treated wifll olanzapine and modification of contributory l~acmrs. At file time of admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after initiation of olanzapine, erythemamns skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range; however, because warfarin has been associated with subcutaneous bleeding presenting as petechiae and ecchymosis, subcutaneous enoxaparin was substituted for warfarin. The skin lesions continued to worsen over tile next week and developed into palpable lesions. Biopsy of tile rash revealed leukocytoclastic vasculitis. In tile absence of another cause, olanzapine was discontinued and tile rash improved sig nit]candy. When the agitation recurred, risperidone was initiated, but the patient experienced dizziness with this agent. Olanzapine was resumed and the skin lesions recurred. Olanzapine was then changed to quetiapine, and the skin lesions improved over tile next few weeks. Discussion: Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with dementia, delirium, and other psychiatric disorders. Lenkocytoclastic vasculitis is an infrequently reported adverse drug reaction with olanzapine. Its exact pathogenic mechanism is unknown, but both cell mediated and hnmoral immunity appear to play important roles. Because drug-induced vasculitis has an identical clinical presentation and identical serologic/pathologic parameters to idiopathic forms ofvasculitis, a high index of suspicion is necessary for its accurate diagnosis. Conclusions: Because adverse drug reactions are common in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of tile potential for leukocytoclastic vasculitis in association with olanzapine. (Are, J G e r i a t r I'harrnacother. 2005;3:21-24) Copyright © 2005 Excerpta Medica, Inc. Key words: adverse drug reaction, leukocymclastic vasculitis, multiple medications, olanzapine, elderly patients. Accepted tor pubJ~ccTtonjanucTry2J, 2005. Printed in the USA Reproduction in whole or part is not permitted
Copyright @ 2005 Excerpts Medic& Inc
doi:lO I016/j amjopharm.2005.03.003 1543-5946/05/$19.00
Volume 3 ÷ Number
I
M~rch 2005
21
The American Journal of Geriatric Pharmacotherapy
M.K. Duggal et aL
INTRODUCTION
Elderly patients taking muhiple medications are at high risk for adverse drug reactions, which are the most c o m m o n cause o f iatrogenic illness and are responsible for -6% of overall hospital adinissions. Each year, -35% o f older adults experience adverse drug reactions, -81% of which are preventable. 1,2 We present a case o f leukocytoclastic vasculitis induced by olanzapine, a commonly used medication in the elderly. CASE SUMMARY
An 82-year-old woman was admitted to the extendedcare facility for short-term rehabilitation after a prolonged hospitalization for lower-extremity deep vein thrombosis with pulmonary embolism. She had a history of mild Alzheimer's dementia, hypertension, and osteoarthritis, for which she was receiving donepezil, lisinopril, and acetaminophen, respectively. Her hospitalization had been complicated by agitated delirium. Hypoxia resolved with improvement in the patient's pulmonary problem. Urinary catheterization was discontinued, and fecal impaction and hypokalemia were treated. The patient was encouraged to use her eyeglasses, and more family visits were permitted. All nonessential medications were discontinued: the patient's only remaining medications were warfarin for pulmonary embolism and olanzapine for behavioral disturbance. Her delirium persisted despite all these measures. At the time o f her admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after the initiation of olanzapine, erythematous skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range. However, warfarin therapy is commonly associated with subcutaneous bleeding that presents as petechiae and ecchymosis, and has been associated with rare cases of skin necrosis. In our patient, warfarin was changed to subcutaneous enoxaparin. The skin lesions continued to worsen over the next week and developed into palpable lesions (Figure). The patient had no fever, arthralgias, or diarrhea. Her platelet count, renal function, and complement level were normal. Tests for antinuclear antibodies, antihistone antibodies, rheumatoid factor, cryoglobulins, antineutrophil cytoplasmic antibodies, hepatitis B surface antigen and core antibody, hepatitis C antibody, and H1V were negative. Biopsy of the rash revealed leukocytodastic vasculitis. When no other cause was found, olanzapine was discontinued and the rash improved significantly. When the agitation recurred, risperidone was initiated. However,
22
the patient experienced dizziness with risperidone. Olanzapine was resumed, and the skin lesions recurred. Based on a score of 5 on the Naranjo Adverse Drug Reaction Probability Scale, 3 olaxlzapine was assumed to be the probable cause of the cutaneous reaction. Olaxlzapine was subsequently changed to quetiapine, and the skin lesions improved over the next few weeks. DISCUSSION
Elderly patients are particularly vulnerable to adverse drug reactions as a result o f polypharmacy and metabolic changes associated with aging. Medications from almost every pharmacologic class have been implicated in the development o f drug-induced vasculitis (Table). 4 Leukocytoclastic vasculitis has been associated with many nonsteroidal anti-inflammatory drugs, s,6 betalactmu antibiotics, 7 and gabapentin8; it has recently been associated with tumor necrosis factor-alpha blockers such as etanercept and infliximab. 9 Vasculitis can involve small, medium, or large blood vessels. 1° Depending on the histology and type o f infiltrate, vasculitis can be granulomatous or polymorphonuclear. Drug-induced vasculitis commonly involves capillaries and venules. 3 Cutaneous vasculitis is characterized by a neutrophilic infiltrate in the acute stage, and by a m o n o n u d e a r infiltrate in the subacute and chronic stages, n Erythrocytes often extravasate from the involved blood vessels, leading to palpable pur-
Figure. Skin lesions in an 82-year-old woman receiving olanzapine therapy for delirium.
2¢ZIC Duggal et al.
The Americeta Journal of Geriatric Pharmacotberapy
Table. Drugs implicated in vasculitis. Anticoagulants and thrombolytic agents Heparin Strepto kinase
Cancer chemotherapeutic agents BusuIfan Cyclophosphamide N ethotrexate
Psychoactive drugs Amitri ptjli ne Naprotiline Trazodone
Warfarin Anticonvulsants Carbamazepine Gabapentin Sodium valproate Anti-infective agents Acyclovi r Ampicillin Ciprofloxacin Clindamycin Doxycycline Gentamicin Griseotulvin Ofloxacin Penicillin
Cardiovascular drugs Amiodarone Atenolol Captopril Diltiazem Furosemide Hyd ralazine Hydrochlorothiazide Nethyldopa Procainamide Quinidine Spironolactone Intravenous formulations Iodine-containing radiocontrast media Iron-dextran preparations
Niscellaneous agents AIIopurinol Azathioprine Chlorzoxazone Colchicine D penicillamine Etanercept Filgrastim Gold Infliximab Interteron-alfa blettormin Methylthiouracil Quinine Retinoids
Rifampin Trimethoprim-sultamethoxazole Zidovudine Beta adrenergic-receptor agonists Terbutaline
Nonsteroidal anti-inflammatory agents Diclofenac IbuprotSen Indomethacin Naproxen
pura. is The exact pathogenic mechanism of druginduced vasculitis is unknown, but both cell mediated and humoral immunity appear to play important roles, s The clinical manifestations range t~om small-vessel hypersensitivity vasculitis to clinical syndromes that are indistinguishable t~om classic systemic forms of vas culitis, such as Wegener's granulomatosis, polyarteritis nodosa, and Churg Strauss syndrome, is Patients may present with cutaneous involvement alone or with life threatening systemic involvement, s Because the clinical presentation and serologic/ pathologic parameters o f drug induced vasculitis are identical to those of idiopathic forms ofvasculitis, a high index of suspicion is necessary for its accurate diagnosis. Drug induced vasculitis is a poorly defined disorder, as proving the association between vasculitis and exposure to a particular drug is frequently difficult. There are es sentially no findings that reliably indicate a direct con nection between vasculitis and a particular drug exposure. Withdrawal of the offending agent is often snffident m bring prompt resolution of the clinical manifestations without the need for systemic corticosteroids or more powerful forms ofimmunosnppression. 3,14
Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with demen tia, delirium, and other psychiatric disorders, l~ It has occasionally been associated with skin problems 16,17 but never with leukocytoclastic vasculitis. The vasculitic skin lesions in our patient were probably attributable to olanzapine alone or to some unknown interaction. CONCLUSIONS
Because adverse drug reactions are c o m m o n in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of the potential for lenkocyto clastic vasculitis in association with olanzapine. REFERENCES 1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA. 1998;279:1200 1205. 2. Barranco P, Lopez Serrano MC. General and epidemio logical aspects of allergic drug reactions. Clin _FxpAllergy. 1998;28(Suppl 4):61 62.
13
The America~ Jour~M of Geriatric Pharmaco~her~py 3ILK.Duggal et M.
3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol That. i98i;30:239 245. 4. Doyle MK, Cuellar ML. Drug induced vasculitis. Expert Opin Dr~tg Saf 2003;2:401-409. 5. Schapira D, Balbir Gurman A, Nalair AM. Naproxen induced leukocytoclastic vasculitis. Clln Rhe~tmatol. 2000; 19:242-244. 6. Davidson KA, Rhagpfeil F, Lee JB. Ibuprofen induced bullous leukocytoclastic vasculitis. C~ttis. 2001 ;67:303 307. 7. Koutlda P, Mylonakis E, Rounds S, Erickson A. Cuta neous leukocytoclastic vasculitis associated with oxacillin. Diagn Microbiol Infect Dis. 2001 ;39:191-194. 8. Poon DY, Law NM. A case of cutaneous leukocytoclastic vasculitis associated with gabapentin. Singapore Mad J. 2003;44:42-44. 9. Mohan N, Edwards ET, Cupps TR, et al. Leuko cytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents, jr Rhe~tmawl. 2004;31: 1955 1958. 10. Russell JP, Weenig RH. Primary cutaneous small vessel vasculitis. Curt Trent Options Cardiovasc Mad. 2004; 6:139 149. 11. Zax RH, Hodge SJ, Callen JP. Cutaneous leukocyto clastic vasculitis. Serial histopathologic evaluation dam-
12.
13.
14.
15.
i6.
i7.
onstrates the dynamic nature of the infiltrate. Arch Der~natol. 1990;126:69-72. Crowson AN, Brown TJ, Magro CM. Progress in the understanding of the pathology and pathogenesis of cutaneous drug eruptions: Implications for management. A m J Clin Dermatol. 2003;4:407 428. Bachot N, Roujeau JC. Differential diagnosis of severe cutaneous drug eruptions. A m f Clin Dermatol. 2003;4: 561 572. Joint Task Force on Practice Parameters of the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug lay persensitivity: A practice parameter. A n n Allergy Asthma Immunol. 1999;83:665 700. Street JS, Clark WS, Gannon KS, et al, for the HGEU Study Group. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer's disease in nurs ing care facilities: A double blind, randomized, placebo controlled trial. Arch Gen Psychiatry. 2000;57:968-976. Hagg S, Tatting P, Spigset O. Olanzapine mad venous thromboembolism. Int Clln Psychopharmacol. 2003;18: 299-300. Adams BB, /Vlutasim DF. Pustular eruption induced by olanzapine, a novel antipsychotic agent. J A m Acad Dermatol. 1999;41:851-853.
Address correspondence to: Mahesh K. Duggal, MD, Department of Geriatric Medicine, Wills Memorial Hospital, 123 Gordon Street, Washington, GA 30673. E mail: mkduggal@nu z.net
24