The value of skin tests in in patients with selective responses to NSAID

Klinik und Poliklinik für

Dermatologie und

Allergologie am

Biederstein, Technische

Universität München,

80802 München

Knut Brockow

lammintaustra

Problems in NSAID hypersensitivity skin testing

• For the majority of patients no immunological

mechanism has been demonstrated

• Skin tests remain often negative

• Heterogeneity of elicitors and clinical pictures

• Experience to test drugs has declined

• There is no standard for testing but many

different methods do exist in different centers

Patient, f, 39y, with typical history

• No atopy

• 2 years ago because of headache in Croatia

Plivadon

(paracetamol+propyphenazone+coffeine+codeine)

• “Immediately” generalised pruritus, urticaria,

dypnea and tachycardia

• 1 year ago because of back pain Demex

(propyphenazone): “immediately” dypnea,

vomiting, tachycardia and finger paresthesia

To be known by every allergist

• Skin tests are only positive in allergic reactions

• The negative predictive value depends on the sensitivity of skin tests

• The negative predictive value differs with drug, manifestation and kinetics

• Skin tests should be used as screening tests and do avoid provocation tests

Skin prick test

Intradermal test

Patch test

Skin tests

Specific Not very sensitive Simple to perform

Less specific More sensitive Difficult to perform Risk of false positive reactions

Less sensitive Specific, simple to perform

Skin test methods

ENDA method*

Time interval 6 weeks – 6 months

Skin prick test

Reading 20 min, (D1), D2, D3

Positivity criteria after 15-20 min: wheal > 3 mm + erythema

in late readings: infiltrate + erythema

Intradermal test

Amount 0.02(-0.05) ml

Reading 20 min, (D1), D2, D3

Positivity criteria after 15-20 min: initial wheal > +3 mm

in late readings: infiltrate + erythema

Patch test

Reading D2, D3, (D4)

Positivity criteria EECDRG criteria

*K Brockow et al, Allergy 2002

Time course of allergic reactions

Skin tests in adverse drug reactions

Skin prick test Intradermal test Patch test

Immediate reactions

Non-immediate reactions

20 min reading Late reading (e.g. 48,72h)

Irritative potency of skin tests

• E.g.Histamine-releasing

drugs (e.g. quinolones)

• Irritative potency of

drugs or exipients (e.g.

sodium laurylsulphate,

colchicine, misoprostol)

For each new drug, you always need enough controls or controls tested in the literature!

Results and further allergological workup of patient 1

• Allergy to propyphenazone

• Skin test + provocation to

paracetamol, coffeine,

codeine, ASS negative

• => selective responder to

propyphenazone

• => allergy pass to

pyrazolones

SPT

Propy

phenazone

Own personal experience in Hamburg

Positive skin tests in propyphenazone and metamizole, else rare

What are Pyrazolones?

• Propyphenazone

• Phenazone (Antipyrin)

• Aminophenazone

• Noraminophenazone

• Metamizol (Dipyrone)

25 patients with hypersensitivity to Propyphenazone Aminophenazone Noraminophenazone

12 patients with positive SPT or IDT

83% positive skin test in patients with urticaria and anaphylaxis

Gamboa et al. Allergy 2003: 58: 312–317 Gomez et al. CEA, 39, 1217–1224

Positive skin tests to metamizol in patients evaluated by BAT

Skin tests to pyrazolones may elicit contact urticaria and anaphylaxis

Contact urticaria to pyrazolones in 10 patients with anaphylaxis: -Propyphenazone 6/9 -Metamizol 6/10 -Aminopyrin 6/10 -Phenylbuzation 1/10

Positive skin tests to paracetamol?

Paramo et al. Ann Allergy Asthma Immunol 2000;85:508–511 Galindo et al. Allergolet Immunopathol 1998; 26: 199-200

Conclusions skin tests for anaphylaxis and urticaria

• Pyrazolones should always be tested

• Positive in ca. 20-70% of patients when tested

with pure SPT and 0.1mg/ml IDT

• Other NSAIDs are seldomly positive and testing

may be restricted to expert centers

• Exceptional skin test-positive cases should be

reported with detailed conditions

Patient 3: Clinical reaction after herpes recidivans and Etoricoxib

59yo patient recurrently taking etoricoxib and prednisolone because of pain

Herpes simplex recidivans (lips)

Patient 3: Patch test with etoricoxib on back and in loco (10%/pet.)

Positive in loco with systemic spreading

Back negative

DPT celecoxib negative

Selective fixed drug eruption to etoricoxib

Maculopapular exanthema by Cox-2 inhibitors with positive patch test

Jaeger et al. JACI 2005; 115:1089

Martinez Alonso et al. Contact Dermatitis

Mäkelä et al. Acta Derm Ven 2008; 88:200

Patch test with 10% in petrolatum!

Irritative patch tests with undiluted drugs

Delayed reading SPT and patch test

positive in MPE to metamizol

Delayed readings

(SPT and) IDT

may be positive

SPT 48h

PT 48h

Usefulness of IDT and PT in non-immediate reactions to metamizol

Macias et al. Allergy 2007; 62:1462

Borja et al. Allergy 2003; 58:84

- Positive PT and delayed IDT

- IDT may be more sensitive

Conclusions for non-immediate exanthems

• Patch tests are useful in non-immediate

reactions to NSAIDs

• In FDE in loco testing has to be performed

• 10% concentration in petrolatum is not irritative

• Often selective responders

• Delayed readings of IDT may be more sensitive

Thank you very much for your attention!