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Adverse Cutaneous Drug Reactions to Cardiovascular Drugs
Author:
Esen zkaya / Kurtulu Didem Yazganolu
Publisher:
Springer
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2014
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Adverse cutaneous drug reactions (ACDR) are among the most frequent events in patients receiving drug therapy. Cardiovascular (CV) drugs are an important group of drugs with potential risk of developing ACDR especially in elderly as marketing of more new drugs and their prescription continue to increase. However, like with most other drugs the exact incidence of cutaneous side effects from CV drugs is difficult to estimate due to sporadic reporting. Moreover, a reliable designation of a certain drug as the cause of a certain type of reaction can rarely be made. Apart from the well-known angioedema/urticaria from ACE inhibitors, lichen planus / lichenoid reaction from beta adrenergic blockers and photosensitivity from thiazid diuretics, ACDR from CV drugs might be seen in a wide spectrum extending to rare but life-threatening conditions such as erythroderma, Stevens-Johnson syndrome, toxic epidermal necrolysis or drug hypersensitivity syndrome. In this comprehensive review, the reported types of ACDR to CV drugs will be discussed according to drug class and the type of dermatologic reaction with special emphasize on cross-reactions and the role of patch testing in diagnosis.

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Part I
General Aspects of Adverse Cutaneous Drug Reactions

Springer-Verlag London 2014

Esen zkaya and Kurtulu Didem Yazganolu Adverse Cutaneous Drug Reactions to Cardiovascular Drugs 10.1007/978-1-4471-6536-1_1

1. General Aspects of Adverse Cutaneous Drug Reactions

Esen zkaya 1 and Kurtulu Didem Yazganolu 1

(1)

Department of Dermatology and Venereology, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey

Keywords

Drug eruption Cardiovascular drugs Maculopapular Erythema multiforme Acute generalized exanthematous pustulosis Photosensitivity Hyperpigmentation Vasculitis Angioedema Erythroderma StevensJohnson syndrome Toxic epidermal necrolysis Drug rash with eosinophilia and systemic symptoms

Adverse cutaneous drug reactions (ACDR) or drug eruptions represent one of the most common types of adverse reactions to drug therapy. The overall incidence rate is estimated around 23 % in hospitalized patients [].

ACDR cover a wide spectrum of reactions including mild to moderate eruptions such as maculopapular eruption, urticaria, eczematous eruption including drug-induced Baboon syndrome/SDRIFE (symmetrical drug-related intertriginous and flexural exanthema), lichenoid eruption, fixed drug eruption (FDE), erythema multiforme (EM)-like eruption, bullous eruptions like drug-induced pemphigus or pemphigoid, pustular eruption, acneiform eruption, photosensitivity, hyperpigmentation, purpura, vasculitis, and erythema nodosum; or severe eruptions such as angioedema, erythroderma/exfoliative dermatitis, StevensJohnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug hypersensitivity syndrome (DHS)/drug rash with eosinophilia and systemic symptoms (DRESS), lymphomatoid drug eruption/pseudolymphoma syndrome (PLS), and skin necrosis. Drugs may also induce an activation of a preexisting dermatosis such as psoriasis, lichen planus, pityriasis rosea, or even a systemic disease, such as systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), serum sickness-like reaction, or porphyria. Mucosal reactions like oral lichenoid lesions and gingival hyperplasia or adnexal reactions like alopecia, hypertrichosis, or nail disorders may also occur.

Characteristic Features of Adverse Cutaneous Drug Reactions

Maculopapular Drug Eruption

Maculopapular eruption, also known as morbilliform eruption or exanthema, is the most common type of cutaneous drug reactions. It is characterized by small, distinct, bright-red maculopapular lesions with a symmetrical distribution. The eruption often shows a morbilliform pattern resembling measles, but unlike measles and other viral eruptions, which characteristically starts on the face, it usually starts on the trunk, subsequently involving the face and the extremities (Figs. ). The eruption might have a purpuric character on the lower extremities. In rare cases, it may evolve into erythroderma/exfoliative dermatitis.

Fig. 1.1

Maculopapular/morbilliform drug eruption on the trunk and upper extremities showing confluent lesions on the abdominal skin

Fig. 1.2

A close-up of confluent maculopapular lesions on the abdominal skin shown in Fig.

Fig. 1.3

Maculopapular drug eruption on the trunk and upper extremities including the dorsum of the hands

Fig. 1.4

Maculopapular drug eruption on the back skin showing confluence of the lesions

Fig. 1.5

Maculopapular drug eruption on the outer part of the upper arm and the back skin

Fig. 1.6

Maculopapular drug eruption involving the palms

Maculopapular drug eruption might be accompanied by a mild pruritus. Fever and systemic symptoms are usually absent.

Histopathology shows perivascular lymphocytic infiltration with or without eosinophils with minimal epidermal changes [].

Beta-lactam antibiotics such as amoxicillin and ampicillin are the main inducers of this type of drug eruption. Cephalosporins, antiepileptics, sulfonamide antibiotics, and allopurinol may also be frequently associated with maculopapular drug eruption []. The eruption usually starts within a few days to a few weeks of drug therapy. Ampicillin-induced exanthema in patients with infectious mononucleosis might be regarded as a prototype of this eruption. Regarding cardiovascular drugs, maculopapular eruption is seen with angiotensin-converting enzyme inhibitors (ACEIs) (mainly captopril), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), class I antiarrhythmics, diuretics, platelet inhibitors, and aminocaproic acid.

Differential diagnosis should include viral exanthemas and syphilitic roseola. Viral exanthema characteristically starts from the face, and it is usually associated with fever and enlarged lymph nodes. Syphilitic roseola are rich on spirochetes.

Cessation of the causative drug and treatment with topical corticosteroids, systemic antihistamines, and if necessary systemic corticosteroids usually result in recovery of the condition.

Drug-Induced Angioedema/Urticaria

Urticaria is the second most common type of cutaneous drug reactions that is characterized by sudden occurrence of red to pale itchy wheals (Fig. ), eyelids, tongue, or genitalia as deep urticarial papules and plaques. Acute anaphylaxis, and anaphylactoid reactions typically present with angioedema, urticaria, dyspnea, and hypotension.

Fig. 1.7

Pale, itchy wheals with erythematous borders on the neck in urticarial drug eruption

Fig. 1.8

Skin angioedema presenting as deep urticarial papules and plaques on the trunk

Fig. 1.9

Angioedema of the lower lip

Histopathology of drug-induced urticaria is usually consistent with classic urticaria, showing vasodilatation and dermal edema and perivascular lymphocytic infiltration occasionally with a few eosinophils [].

Drug-induced urticaria may be immunologic or non-immunologic. The main inducers of an immunologic urticaria that is frequently associated with type I hypersensitivity reaction are beta-lactam antibiotics. Immunologic urticaria might also be associated with type III hypersensitivity. The main inducers of non-immunologic drug-related urticaria include acetylsalicylic acid, other NSAIDs, radiocontrast media, opiates, and ACEIs. According to a meta-analysis, there is also risk of angioedema with ARBs in patients with prior angioedema associated with ACEIs [].

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