Cutaneous adverse drug reaction to heparins with hypereosinophilia and high IgE level

Kłos, Krzysztof; Śpiewak, Radosław; Kruszewski, Jerzy; Bant, Andrzej

doi:10.1111/j.1600-0536.2010.01784.x

Cited by 5 publications

(5 citation statements)

References 4 publications

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“…Cutaneous lesions develop as erythematous plaques at injection sites. This reaction can be managed as explained previously for delayed hypersensitivity 3,10 Maculopapular exanthems, flexural exanthems, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms have been reported 1 .…”

Section: Other Less Common Cutaneous Adverse Events Associated With Hmentioning

confidence: 80%

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Cutaneous adverse events associated with heparin

Cid

Celada

et al. 2012

Clinical and Experimental Dermatology

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SummaryHeparin use is associated with various cutaneous reactions, with the most common being immune-mediated skin lesions and bleeding complications. In this review, we compile the dermatological side-effects of heparin reported in the literature, and provide a clear approach to their adequate management. Heparin use and mechanism of actionHeparin (and its analogues) and warfarin are the traditional anticoagulants used for the prevention and treatment of thromboembolic disease. Table 1 shows a simplified classification of anticoagulants.Heparin is an indirect thrombin inhibitor that binds to anti-thrombin, converting this cofactor from a slow to a rapid inactivator of thrombin, factor Xa, and to a lesser extent, factors XIIa, XIa and IXa. Lowmolecular weight heparin (LMWH) drugs have less anti-thrombin activity than does unfractionated heparin (UFH). 1 Unfractionated heparin is used intravenously, and requires monitoring using the activated partial thromboplastin time (APTT). By contrast, LMWH is administered by subcutaneous injection, and the dose can be weightadjusted without monitoring. 1 Epidemiology of cutaneous adverse events associated with heparinOwing to under-reporting, the real incidence of heparininduced skin lesions is unknown.2 However, AEs are reported less often with LMWH than with UFH.3 In a recent prospective study, 2 the incidence and causes of heparin-induced skin lesions were evaluated in a large cohort of patients. An incidence of 7.5% was found, much higher than the 1-2% previously estimated. Delayed-type hypersensitivity reactions were found to be the commonest cutaneous side-effect related to heparin use. Most patients enrolled in the study received LMWH. Classification, aetiology and managementSkin lesions related to heparin use can be classified as: immune-mediated reactions, which covers (i) type I immediate hypersensitivity reactions; (ii) type IV delayed hypersensitivity reactions: (iii) skin necrosis; and non-immune-mediated reactions, covering (iv) bleeding diathesis and (iv) other, less common reactions (Table 2). Immune-mediated reactions Type I immediate hypersensitivity reactionsImmediate hypersensitivity reactions to heparins, 3-5 e.g. pruritus (including palmoplantar pruritus), urticaria ( Fig. 1), angio-oedema, conjunctivitis, rhinitis, bronchial asthma and anaphylaxis, are probably IgE-mediated. These reactions were first reported in the 1940s, after the introduction of heparin for clinical use, and were attributed to contaminant proteins and preservatives. They are now rare because of improved purification procedures.

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Section: Other Less Common Cutaneous Adverse Events Associated With Hmentioning

confidence: 80%

“…Cutaneous lesions develop as erythematous plaques at injection sites. This reaction can be managed as explained previously for delayed hypersensitivity 3,10 …”

Section: Other Less Common Cutaneous Adverse Events Associated With Hmentioning

confidence: 99%

Cutaneous adverse events associated with heparin

Cid

Celada

et al. 2012

Clinical and Experimental Dermatology

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“…While the typical rash associated with sirolimus and temsirolimus is characterized by a non-specific neutrophilic infiltrate, a variant eczematoid eruption with eosinophilic spongiosis has also been reported [79,80]. Likewise, although asymptomatic hypereosinophilia is frequently observed during heparin therapy [81], eosinophilic infiltration of a maculopapular exanthem has also been reported [82].…”

Section: Other Skin and Soft Tissue Reactions Maculopapular Exanthemamentioning

confidence: 99%

Eosinophilic Drug Allergy

Kuruvilla

Khan

2015

Clinic Rev Allerg Immunol

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While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management.

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“…e first related case was reported in 2003 about generalized erythema caused by enoxaparin [15]. In 2010, a study reported appearances of generalized erythema after 40 hours of low-molecular-weight heparin usage [16]. Later, there were some studies which discovered that generalized eczematous reactions could be induced by severe localized reactions at the inject point [4,14,17].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the pathogenesis of generalized urticaria-like reactions, we reviewed the literature and found it is common of eosinophils count increase during long-term subcutaneous heparin treatment [16,18,19]. e continuous antigen presentation activates CD4 + T cells, which leads to the recruitment and activation of eosinophils.…”

Section: Discussionmentioning

confidence: 99%

Localized and Generalized Skin Adverse Drug Reactions to Nadroparin Calcium Injection in 6 Cases of Pregnant Women

Chen

Lan

Sun

et al. 2022

Journal of Healthcare Engineering

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Background. Despite the increasing number of skin adverse drug reactions caused by nadroparin calcium have been reported, mostly, little is known regarding of their details of clinical characteristics, especially for generalized skin adverse drug reactions. We sought to evaluate localized and generalized characteristics of the skin adverse drug reaction to nadroparin calcium injection in pregnant women. Methods. A retrospective study was conducted on 6 pregnant women, who experienced localized and generalized skin adverse drug reactions during long-term nadroparin calcium injection. The patients’ clinical and imaging information were retrieved from medical records. The skin prick test, patch test, and intradermal test were performed after they stopped lactation. Causality assessment of suspected adverse drug reactions was performed on these cases. Results. The average total dose of nadroparin calcium injection in the 6 cases was 64.17 ± 22.66. Localized skin adverse drug reaction, manifested as erythema at the injection point, appeared after 47.5 ± 17.4 days of subcutaneous injection of nadroparin calcium. Generalized urticaria-like lesions, progressing from the injection site on the abdomen, appeared in 5.17 ± 3.60 days after the first appearance of localized reaction, while laboratory test results revealed essential peripheral blood eosinophilia. All rashes in the 6 cases subsided in 2–5 weeks after drug withdrawal. After delivery, 5 of 6 cases received complete skin tests to evaluate drug hypersensitivity. Results presented positive in the intradermal test within 7 days. Both the skin prick test and skin patch test were negative. Localized skin reactions and generalized urticaria-like adverse drug reactions were considered as definitely and probably caused by nadroparin calcium injection, respectively. Conclusion. Subcutaneous injection of nadroparin calcium in pregnant women appears to be at risk of localized and generalized urticaria-like adverse drug reaction. It is important to follow up the pregnant woman during nadroparin calcium injection for evaluating adverse drug reactions. Timely detection of symptoms is pivotal in early diagnosis and treatment of adverse drug reactions.

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Cutaneous adverse drug reaction to heparins with hypereosinophilia and high IgE level

Cited by 5 publications

References 4 publications

Cutaneous adverse events associated with heparin

Cutaneous adverse events associated with heparin

Eosinophilic Drug Allergy

Localized and Generalized Skin Adverse Drug Reactions to Nadroparin Calcium Injection in 6 Cases of Pregnant Women

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