The use of TKI is associated with unique and dramatic dermatologic side effects.
1. Abnormal scalp, face hair, and/or eyelash growth (Isolated reports)
2. Anaphylactic infusion reaction (cetuximab)
3. Papulopustular eruption 60%-80%
4. Paronychia with/without pyogenic granulomas 6%-12%
5. Telangiectasias
6. Xerosis 4%-35%
Although these new targeted therapies have low systemic toxicity, cutaneous side effects are common and may be serious.
Proper pre-treatment counseling and management will improve the treatment compliance and avoid unnecessary interruption of the TKI use.
TKI induced skin rash appears to be a visible marker of anti-tumor activity and therapeutic efficacy.
Saturday, May 29, 2010
Wednesday, May 26, 2010
Cross-sensitivity of skin rashes with antiepileptic drug use
NEUROLOGY 2008;71:1527-1534
© 2008 American Academy of Neurology
Cross-sensitivity of skin rashes with antiepileptic drug use
L. J. Hirsch, MD, H. Arif, MD, E. A. Nahm, BA, R. Buchsbaum, S. R. Resor, Jr, MD and C. W. Bazil, MD, PhD
Objective:
To determine rates of cross-sensitivity of rash among commonly used antiepileptic drugs (AEDs) in patients with epilepsy.
Methods:
The incidence of AED-related rash was determined in 1875 outpatients (12 years), taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA), or zonisamide (ZNS).
We compared rates of rash for each AED in patients with vs those without a rash to 1) another specific AED; 2) any other AED; 3) any two other AEDs; and 4) any non-epilepsy medication.
Results:
A total of 14.3% (269/1,875) of patients had a rash attributed to at least one AED; 2.8% had a rash to two or more AEDs.
Of patients who had a rash to CBZ and were also prescribed PHT (n = 59), 57.6% had a rash to PHT (abbreviated as CBZ PHT: 57.6%); of patients who had a rash to PHT and were also prescribed CBZ (n = 81), rate of rash was 42% (i.e., PHT CBZ: 42%). Other results: CBZ LTG: 20% (n = 50); LTG CBZ: 26.3% (n = 38); CBZ OXC: 33% (n = 15); OXC CBZ: 71.4% (n = 7); CBZ PB: 26.7% (n = 30); PB CBZ: 66.7% (n = 12); LTG PHT: 38.9% (n = 36); PHT LTG: 18.9% (n = 74); PB PHT: 53.3% (n = 15); PHT PB: 19.5% (n = 41); OXC LTG: 37.5% (n = 8); LTG OXC: 20% (n = 15).
There was evidence of specific cross-sensitivity between CBZ and PHT, and between CBZ and PB.
Conclusion:
Cross-sensitivity rates between certain antiepileptic drugs (AEDs) are high, especially when involving carbamazepine and phenytoin.
Specific cross-sensitivity rates provided here may be useful for AED selection and counseling in individual patients.
Abbreviations: AED = antiepileptic drug; CBZ = carbamazepine; CLB = clobazam; FBM = felbamate; GBP = gabapentin; LEV = levetiracetam; LTG = lamotrigine; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PRM = primidone; TGB = tiagabine; TPM = topiramate; VGB = vigabatrin; VPA = valproic acid; ZNS = zonisamide.
© 2008 American Academy of Neurology
Cross-sensitivity of skin rashes with antiepileptic drug use
L. J. Hirsch, MD, H. Arif, MD, E. A. Nahm, BA, R. Buchsbaum, S. R. Resor, Jr, MD and C. W. Bazil, MD, PhD
Objective:
To determine rates of cross-sensitivity of rash among commonly used antiepileptic drugs (AEDs) in patients with epilepsy.
Methods:
The incidence of AED-related rash was determined in 1875 outpatients (12 years), taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA), or zonisamide (ZNS).
We compared rates of rash for each AED in patients with vs those without a rash to 1) another specific AED; 2) any other AED; 3) any two other AEDs; and 4) any non-epilepsy medication.
Results:
A total of 14.3% (269/1,875) of patients had a rash attributed to at least one AED; 2.8% had a rash to two or more AEDs.
Of patients who had a rash to CBZ and were also prescribed PHT (n = 59), 57.6% had a rash to PHT (abbreviated as CBZ PHT: 57.6%); of patients who had a rash to PHT and were also prescribed CBZ (n = 81), rate of rash was 42% (i.e., PHT CBZ: 42%). Other results: CBZ LTG: 20% (n = 50); LTG CBZ: 26.3% (n = 38); CBZ OXC: 33% (n = 15); OXC CBZ: 71.4% (n = 7); CBZ PB: 26.7% (n = 30); PB CBZ: 66.7% (n = 12); LTG PHT: 38.9% (n = 36); PHT LTG: 18.9% (n = 74); PB PHT: 53.3% (n = 15); PHT PB: 19.5% (n = 41); OXC LTG: 37.5% (n = 8); LTG OXC: 20% (n = 15).
There was evidence of specific cross-sensitivity between CBZ and PHT, and between CBZ and PB.
Conclusion:
Cross-sensitivity rates between certain antiepileptic drugs (AEDs) are high, especially when involving carbamazepine and phenytoin.
Specific cross-sensitivity rates provided here may be useful for AED selection and counseling in individual patients.
Abbreviations: AED = antiepileptic drug; CBZ = carbamazepine; CLB = clobazam; FBM = felbamate; GBP = gabapentin; LEV = levetiracetam; LTG = lamotrigine; OXC = oxcarbazepine; PB = phenobarbital; PHT = phenytoin; PRM = primidone; TGB = tiagabine; TPM = topiramate; VGB = vigabatrin; VPA = valproic acid; ZNS = zonisamide.
Tuesday, May 25, 2010
Drug Cross Sensitivty Reaction Part 2
Cross-reactivity of beta-lactam antibiotics
Beta-lactam antibiotics = penicillins, cephalosporins, carbapenems, and monobactams.
The safety of administering beta-lactam antibiotics to penicillin-allergic patients is highly debated and is based mainly on anecdotal information regarding the incidence of cross-reactivity.
CEPHALOSPORINS
Anne et al demonstrated a high incidence of in vitro cross-reactivity (up to 20%) between penicillins and cephalosporins. Cephalosporins involved in these reports included cephalothin and cephaloridine.
Petz et al demonstrated a 4-fold increase in the incidence of cephalosporin reactivity--including cephaloridine, cephalothin, and cephalexin--in patients allergic to penicillins (8.1%) compared with patients not allergic to penicillins (1.9%). When this incidence is compared with the overall incidence of allergic reactions to cephalosporins (4%), there is a 2-fold increase of reactivity in patients allergic to penicillins.
CARBAPENEMS
Already discussued in part 1
MONOBACTAMS
To date, aztreonam has not demonstrated clinical cross-reactivity in penicillin-allergic patients.
Ceftazidime has a side chain identical to that of aztreonam and clinical cross-reactivity has been demonstrated in vitro.
The clinical significance of this has not been studied; however, patients who are allergic to aztreonam should not be administered agents with similar side chains.
References
1. Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987;107:204-215.
2. Neftel KA, Cerny A. Beta-lactam antibiotics other than penicillins and cephalosporins. In Dukes MNG, ed. Meyler's Side Effects of Drugs, 12th ed. Amsterdam: Elsevier, 1992:632-634.
3. Kishiyama JL, Adelman DC. The cross-reactivity and immunology of beta-lactam antibiotics. Drug Saf 1994;10:318-327.
4. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol 1995;74:167-170.
5. Petz LD. Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis 1978;137(Suppl):S74-S79.
6. Preston SL, Briceland LL, Lesar TS. Accuracy of penicillin allergy reporting. Am J Hosp Pharm 1994;51:79-84.
Beta-lactam antibiotics = penicillins, cephalosporins, carbapenems, and monobactams.
The safety of administering beta-lactam antibiotics to penicillin-allergic patients is highly debated and is based mainly on anecdotal information regarding the incidence of cross-reactivity.
CEPHALOSPORINS
Anne et al demonstrated a high incidence of in vitro cross-reactivity (up to 20%) between penicillins and cephalosporins. Cephalosporins involved in these reports included cephalothin and cephaloridine.
Petz et al demonstrated a 4-fold increase in the incidence of cephalosporin reactivity--including cephaloridine, cephalothin, and cephalexin--in patients allergic to penicillins (8.1%) compared with patients not allergic to penicillins (1.9%). When this incidence is compared with the overall incidence of allergic reactions to cephalosporins (4%), there is a 2-fold increase of reactivity in patients allergic to penicillins.
CARBAPENEMS
Already discussued in part 1
MONOBACTAMS
To date, aztreonam has not demonstrated clinical cross-reactivity in penicillin-allergic patients.
Ceftazidime has a side chain identical to that of aztreonam and clinical cross-reactivity has been demonstrated in vitro.
The clinical significance of this has not been studied; however, patients who are allergic to aztreonam should not be administered agents with similar side chains.
References
1. Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987;107:204-215.
2. Neftel KA, Cerny A. Beta-lactam antibiotics other than penicillins and cephalosporins. In Dukes MNG, ed. Meyler's Side Effects of Drugs, 12th ed. Amsterdam: Elsevier, 1992:632-634.
3. Kishiyama JL, Adelman DC. The cross-reactivity and immunology of beta-lactam antibiotics. Drug Saf 1994;10:318-327.
4. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol 1995;74:167-170.
5. Petz LD. Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis 1978;137(Suppl):S74-S79.
6. Preston SL, Briceland LL, Lesar TS. Accuracy of penicillin allergy reporting. Am J Hosp Pharm 1994;51:79-84.
Drug Cross Sensitivity
Cross-reactivity with drugs is an important clinical problem in drug hypersensitivity. Once a patient is labeled 'drug-allergic' all drugs of the same class are withheld and future therapeutic interventions are limited.
Antiepileptics
Development of drug hypersensitivity is one of the major complication of their usage. Antiepileptics are blamed for 20% of all drug rashes and are commonly incriminated drugs in severe cutaneous adverse reactions like Stevens-Johnson syndrome(SJS) or toxic epidermal necrolysis (TEN). The overall prevalence of rash is 2-3% due to antiepileptic drugs in epilepsy patients.
Cross-reactivity between phenytoin, phenobarbital and carbamazepine is thought to exceed 50%.
In patients suspected of having Anticonvulsant Hypersensitivity Syndrome (AHS), anticonvulsant therapy should be discontinued immediately; seizure control may be attempted with a benzodiazepine.
Another alternative for patients with partial or secondarily generalized seizures is gabapentin, which is thought to be safe for administration during the acute phase of AHS.
Valproic acid reportedly has been successful as well but should not be administered during the acute phase of AHS as it is metabolized hepatically.
Refenrence
Cross-Sensitivity between Phenytoin and Carbamazepine. Pharmacotherapy. 2001;21(4) © 2001 Pharmacotherapy Publications. http://www.medscape.com/viewarticle/409706_4.
Penicillin
The risk of cross-reactivity to carbapenems among patients with documented or self-reported penicillin allergy is more than five times higher in patients with a history of penicillin allergy than in those without such a history.
Physicians to be cautious when administering a carbapenem to patients with a history of penicillin allergy, particularly if the allergy has been documented by a health care professional. Cephalosporins should be used cautiously as well.
Penicillins, carbapenems, and cephalosporins are alike in that they have a characteristic bicyclic core structure, which is believed to play a large role in β-lactam hypersensitivity.
Physician should consider a different type of antibiotic, such as a fluoroquinolone, for patients with a history of penicillin sensitivity.
References
1. Apter AJ, Kinman JL, Bilker WB, et al. Represcription of penicillin after allergic-like events. J Allergy Clin Immunol. 2004;113:764-770.
2. Prescott WA, DePestel DD, Ellis JJ, Regal RE. Incidence of carbapenem-associated allergic-type reactions among patients with versus patients without a reported penicillin allergy. Clin Infect Dis. 2004;38:1102-1107.
Antiepileptics
Development of drug hypersensitivity is one of the major complication of their usage. Antiepileptics are blamed for 20% of all drug rashes and are commonly incriminated drugs in severe cutaneous adverse reactions like Stevens-Johnson syndrome(SJS) or toxic epidermal necrolysis (TEN). The overall prevalence of rash is 2-3% due to antiepileptic drugs in epilepsy patients.
Cross-reactivity between phenytoin, phenobarbital and carbamazepine is thought to exceed 50%.
In patients suspected of having Anticonvulsant Hypersensitivity Syndrome (AHS), anticonvulsant therapy should be discontinued immediately; seizure control may be attempted with a benzodiazepine.
Another alternative for patients with partial or secondarily generalized seizures is gabapentin, which is thought to be safe for administration during the acute phase of AHS.
Valproic acid reportedly has been successful as well but should not be administered during the acute phase of AHS as it is metabolized hepatically.
Refenrence
Cross-Sensitivity between Phenytoin and Carbamazepine. Pharmacotherapy. 2001;21(4) © 2001 Pharmacotherapy Publications. http://www.medscape.com/viewarticle/409706_4.
Penicillin
The risk of cross-reactivity to carbapenems among patients with documented or self-reported penicillin allergy is more than five times higher in patients with a history of penicillin allergy than in those without such a history.
Physicians to be cautious when administering a carbapenem to patients with a history of penicillin allergy, particularly if the allergy has been documented by a health care professional. Cephalosporins should be used cautiously as well.
Penicillins, carbapenems, and cephalosporins are alike in that they have a characteristic bicyclic core structure, which is believed to play a large role in β-lactam hypersensitivity.
Physician should consider a different type of antibiotic, such as a fluoroquinolone, for patients with a history of penicillin sensitivity.
References
1. Apter AJ, Kinman JL, Bilker WB, et al. Represcription of penicillin after allergic-like events. J Allergy Clin Immunol. 2004;113:764-770.
2. Prescott WA, DePestel DD, Ellis JJ, Regal RE. Incidence of carbapenem-associated allergic-type reactions among patients with versus patients without a reported penicillin allergy. Clin Infect Dis. 2004;38:1102-1107.
Monday, May 17, 2010
Are topical anti-fungals all the same?
1. Whitfield's ointment (benzoic acid) - useful for web intertrigo
2. Polyenes (ineffective for dermatophyte infection)
Nystatin (Nilstat®; Mycostatin®)
3. Imidazoles
Clotrimazole (Canesten®; Clocreme®; Clomazol®, Fungizid®)
Econazole (Ecreme®; Pevaryl®)
Ketoconazole (Daktagold®; Ketopine®, Nizoral®; Sebizole®)
Miconazole (Daktarin®; Micreme®; Resolve®; Tinasolve®)
Tioconazole
4. Allylamine (higher cure rates & more rapid responses)
Terbinafine (Lamisil®)
2. Polyenes (ineffective for dermatophyte infection)
Nystatin (Nilstat®; Mycostatin®)
3. Imidazoles
Clotrimazole (Canesten®; Clocreme®; Clomazol®, Fungizid®)
Econazole (Ecreme®; Pevaryl®)
Ketoconazole (Daktagold®; Ketopine®, Nizoral®; Sebizole®)
Miconazole (Daktarin®; Micreme®; Resolve®; Tinasolve®)
Tioconazole
4. Allylamine (higher cure rates & more rapid responses)
Terbinafine (Lamisil®)
Topical Anti-fungal
Topical antifungal creams can be used
1. As monotherapy to treat Dermatophyte, Yeast infections & mould skin infections.
2. As an adjunct to oral therapy for tinea capitis and tinea barbae.
The creams are applied to the affected area 2x / day for 2-4 weeks, including a margin of several centimetres of normal skin.
Continue for 1-2 weeks after the last visible rash has cleared. Repeated treatment is often necessary
1. As monotherapy to treat Dermatophyte, Yeast infections & mould skin infections.
2. As an adjunct to oral therapy for tinea capitis and tinea barbae.
The creams are applied to the affected area 2x / day for 2-4 weeks, including a margin of several centimetres of normal skin.
Continue for 1-2 weeks after the last visible rash has cleared. Repeated treatment is often necessary
Principle of Prescribing Topical Dermatological Therapy
1. Correct diagnosis is the key to correct treatment
2. Be familiar with the treatment & their preparation
3. Know the do’s & don’ts of each topical medications
4. Give clear instructions to patient &alert them the possible events / side effect
5. Cure Sometimes; Relief Often; Comfort Always; Harm Never
2. Be familiar with the treatment & their preparation
3. Know the do’s & don’ts of each topical medications
4. Give clear instructions to patient &alert them the possible events / side effect
5. Cure Sometimes; Relief Often; Comfort Always; Harm Never
Wednesday, May 5, 2010
HIV & SKIN
HIV infection leads to progressive failure of cell-mediated immunity due to HIV- mediated loss of CD4 helper T cells. Virtually all HIV infected persons will develop some skin disorder during the course of their illness.
Dermatological manifestations can be the first sign of asymptomatic HIV disease. They can be important markers for the diagnosis of HIV infection. Certain skin diseases typically appear at certain stages of HIV infection, sometimes allowing the physician to predict the stage of HIV infection.
The skin changes in HIV / AIDS can be classified into 4 categories:
I. Infections
II. Inflammatory diseases
III. Neoplasms
IV. Cutaneous Adverse Drug Reactions (CADR)
Dermatological manifestations can be the first sign of asymptomatic HIV disease. They can be important markers for the diagnosis of HIV infection. Certain skin diseases typically appear at certain stages of HIV infection, sometimes allowing the physician to predict the stage of HIV infection.
The skin changes in HIV / AIDS can be classified into 4 categories:
I. Infections
II. Inflammatory diseases
III. Neoplasms
IV. Cutaneous Adverse Drug Reactions (CADR)
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