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Drug eruptions: approaching the diagnosis of drug-induced skin diseases

Journal of Drugs in Dermatology, June, 2003 by Simon Nigen, Sandra R. Knowles, Neil H. Shear 

TABLE 1

Steps in the approach to diagnose a cutaneous adverse
reaction

Working diagnosis
1-Initial clinical impression
2-Differential diagnosis

Data evaluation
3-Analysis of drug exposure
4-Analysis of laboratory results and diagnostic tests
5-Analysis of literature

Final diagnosis
6-Prioritization of diagnosis
including causality assessment

TABLE 2

Prioritization of diagnosis based on:

Analysis of drug exposure
--Timing of drug exposure
--Dechallenge of the drug
--Rechallenge of the drug
--Drug blood level
--Drug interactions

Analysis of literature
--Association of the disease with the drug
--Frequency of the adverse drug reaction with the drug

Analysis of laboratory results and diagnostic tests
--Blood work (CBC, enzymes, biochemistry, etc.)
--Culture (skin, blood, tissue, etc.)
--Medical imaging (X ray, scan, etc.)
--Skin biopsy (histology, immunofluorescence, etc.)
--In vitro testing (LTA, RAST, etc.)
--In vivo testing (skin testing, oral provocation, etc.)

TABLE 3

Drugs commonly associated with
EDE

Allopurinol
Amoxicillin
Amphotericin B
Ampicillin
Barbiturates
Captopril
Carbamazepine
Chlorpromazine
Enalapril
Gold
Lithium
Naproxen
Oral hypoglycemic agents
Penicillin
Phenytoin
Piroxicam
Quinidine
Sulfonamide antibiotics
Thiazides

EDE: Exanthematous drug eruption

TABLE 4

Drugs commonly associated with
DHS
Aromatic anticonvulsants

Carbamazepine
Phenobarbital
Phenytoin
Primidone

Non-aromatic anticonvulsants
Lamotrigine
Sulfonamide antibiotics
Sulfadiazine
Sulfamethoxazole

Others
Allopurinol
Dapsone
Minocycline
Nitrofurantoin
Terbinafine

DHS: Drug hypersensitivity syndrome

TABLE 5

Drugs commonly associated with urticaria

ACE Inhibitors
Aminoglycosides
Anticonvulsants
Azole antifungals
Cephalosporins
Narcotic analgesics
NSAIDs
Oral hypoglycemic agents
Penicillin and its derivatives
Proton pump inhibitors
Radio-contrast dye
Salicylates
Sulfonamide antibiotics
Tetracyclines

ACE: Angiotensin Converting Enzyme
NSAIDs: Non-Steroidal Anti-Inflammatory Drugs

TABLE 6

Drugs commonly associated with
angioedema

ACE inhibitors (lisinopril, enalapril)
Acetaminophen
Acetylsalicylic acid
Amoxicillin
Ampicillin
Azithromycine
Ceftriaxone
Ciprofloxacin
Diclofenac
Hydrochlorothiazide
Ketoprofen
Losartan
Naproxen
Omeprazole
Penicillin
Radio-contrast dye
Sulfamethoxazole-trimethoprim

ACE: Angiotensin converting enzyme

TABLE 7

Drugs commonly associated with
SSLR

Amoxicillin
Ampicillin
Beta-blockers
Bupropion
Cefaclor
Cefprozil
Cephalexin
Doxycycline
Minocycline
Penicillin
Sulfonamide

SSLR: Serum Sickness-Like Reaction

TABLE 8

Drugs commonly associated with
FDE

Acetaminophen
Acetylsalicylic acid
Allopurinol
Chloral hydrate
Dapsone
Dextromethorphan
Diflunisal
Erythromycin
Metamizole
Metronidazole
Nystatin
Penicillin
Phenolphthalein
Piroxicam
Pseudoephedrine
Sulfadiazine
Sulfamethoxazole--trimethoprim
Tetracyclines
Tetrahydrazoline

FDE: fixed drug eruptions

TABLE 9

Drugs commonly associated with drug-induced
pemphigus

Captopril *
Gold sodium thiomalate *
Levodopa
Penicillamine *
Penicillin
Phenobarbital
Piroxicam
Propranolol
Pyritinol *
Rifampin
Thioprine *

* sulfur containing

TABLE 10

Drugs commonly associated with
drug-induced bullous pemphigoid

Ampicillin
Captopril
Chloroquine
Enalapril
Furosemide
Penicillamine
Penicillin
PUVA
Salicylazosulfapyridine
Sulfasalazine

PUVA: Psoralen with Ultra-Violet A

TABLE 11

Drugs commonly associated with
drug-induced linear IgA
dermatosis

Amiodarone
Atorvastatin
Captopril
Ceftriaxone
Diclofenac
Furosemide
Lithium
Metronidazole
Penicillin
Phenytoin
Piroxicam
Rifampin
Sulfamethoxazole--trimethoprim
Vancomycin

IgA: Immunoglobulin A

TABLE 12
Characteristics and distinctions between the EM spectrum and the TEN
spectrum

                           EM minor              EM minor
Target lesions
  -typicals targets     Typical targets      Typical targets
  -atypicals targets                      Raised atypical targets
Distribution                 Acral                Acral
Blisters                      No                   Yes
Epidermal detachment      [empty set]              <10%
Macules                  Erythematous          Erythematous

Shape                       Regular              Regular
Mucous membrane               No               Yes (milder)
Recurrence                    Yes                  Yes
Fever                         No                    No
Severity                                              
Death                         No                    No
Age                         Younger              Younger
Sex                       Male>Female          Male>Female
Association with
  -collagene vascular         No                    No
  disease
  -HIV infection              No                    No
  -cancer                     No                    No
Hispathology
  -necrotic                     Ranging from individual cells
  keratinocytes
  -dermal infiltrate       extensive           intermediate
  -erythrocyte                                        
  extravasation
Cause                         HSV                  HSV

                              SJS                  TEN
Target lesions
  -typicals targets
  -atypicals targetS    Flat atypical     Flat atypical targets
                            targets
Distribution              Widespread            Widespread
Blisters                      Yes                  Yes
Epidermal detachment         <10%                  >30%
Macules                  Erythematous          Erythematous
                           Purpuric              Purpuric
Shape                      Irregular            Irregular
Mucous membrane          Yes (severe)          Yes (severe)
Recurrence                    No                    No
Fever                         Yes                  Yes
Severity                                               
Death                         Yes                  Yes
Age                          Older                Older
Sex                       Male

            
        
    
            																		





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