Skin tests in patients with delayed and immediate hypersensitivity to heparins: A case series

Abstract

K E Y W O R D S : alternative, cross-reactions, cutaneous adverse drug reactions, delayed-type hypersensitivity, heparins, immediate-type hypersensitivity, intradermal test, patch test, prick test, skin tests Heparins constitute a group of anticoagulants that are widely used in clinical practice for the prophylaxis and treatment of thromboembolic events. Among the adverse events induced by heparins, delayed-type hypersensitivity (DTH) reactions are commonly reported, mostly as eczematous patches localized on the injection sites. 1 Only a few cases of immediate-type hypersensitivity (ITH) reactions have been described, manifesting as urticaria, angioedema, palmoplantar itch, dyspnoea, and anaphylaxis. 2,3

Skin tests in the diagnosis of adverse drug reactions

“…101 Heparins are known to provoke all types of hypersensitivity reactions. 101 Non-immediate ADR are common, especially eczematous patches localized on the injection sites, after a latency of 2-10 days to 3 weeks; [101][102] however, if heparin treatment is continued, there is a risk of a generalized eruption. 26 Only rarely generalized MPE and exceptionally TEN have been described.…”

“…104 Conversely, only a few cases of immediate ADR have been reported, as urticaria, angioedema, palmoplantar itch, dyspnoea, and anaphylaxis. [101][102] Risk factors for hypersensitivity include obesity, female sex, pregnancy, and prolonged treatment. [102][103][104][105] LMWH were the most frequent culprit heparins, probably because of their widespread use.…”

“…[101][102] Risk factors for hypersensitivity include obesity, female sex, pregnancy, and prolonged treatment. [102][103][104][105] LMWH were the most frequent culprit heparins, probably because of their widespread use. 104 Cross-reactivity among heparins is frequently reported, both for non-immediate ADR and immediate ADR.…”

“…104 Cross-reactivity among heparins is frequently reported, both for non-immediate ADR and immediate ADR. The distribution of cross-reactions is independent of the heparin molecular weight 106,107 , while fondaparinux, which is a fully synthetic pentasaccharide inactivating activated factor X, is considered a safe and effective alternative, 101,102 even though cases of cross-reactivity between fondaparinux and other heparins have been described, with different incidence rate (from 0.4% 101 to 10.4%, 107 up to 25% in small case series 108 ). In case of non-immediate ADR to subcutaneously injected heparin, intravenous administration of the drug should be tolerated, may be because of differential processing on presentation of antigens depending on the route of administration.…”

“…100,101 It is mandatory to perform a correct allergy work-up, not only to identify the incriminated heparin, but also to find a safe alternative, including UFH, LMWHs, and fondaparinux. 102 Neat heparins appear non-irritant and can be used as such for PT and SPT, while can be irritant for IDT. IDT should be started with 1/10 dilution, and further tests 1/100 and 1/1000 dilution should be conducted in the suspect of irritant reaction.…”