Cutaneous Adverse Drug Reactions

Chapter 119


Cutaneous Adverse Drug Reactions



Adverse drug reactions are due to interactions between a pharmacologic agent, such as an antimicrobial, and the immune system. Common cutaneous clinical signs associated with cutaneous adverse drug reactions (CADRs) are listed in Table 119-1 along with the associated pharmacologic agents. These cutaneous signs may develop coincident with other clinical signs involving the gastrointestinal, respiratory, or cardiovascular systems. Signs can vary from lethargy and depression to fever, anemia, systemic hypotension, and shock.



TABLE 119-1


Clinical Presentations of Cutaneous Adverse Drug Eruptions and Associated Pharmacologic Agents




































Clinical Presentation Selected Pharmacologic Agents
Erythema/erythroderma/violaceous lesions Sulfonamides, cephalosporins, penicillins, macrolides, fluoroquinolones, tetracyclines, levothyroxine, acepromazine, levamisole, ivermectin, hydroxyzine, chlorpheniramine, shampoo (e.g., D-limonene), itraconazole, neomycin, propylene glycol
Wheals/hives (urticaria) and angioedema Sulfonamides, cephalosporins, penicillins, tetracycline, allergen-specific immunotherapy, barbiturates, insecticides (e.g., avermectins and amitraz), transfusions
Scaling/exfoliative dermatitis Sulfonamides, cephalosporins, penicillins, macrolides, acepromazine, levamisole, hydroxyzine, chlorpheniramine, shampoo (e.g., tar)
Erosion/ulceration Sulfonamides, cephalosporins, penicillins, retinoids, moxidectin, spironolactone (cats)
Pruritus Sulfonamides, cephalosporins, penicillins, methimazole, propylthiouracil, gentamicin, chloramphenicol, acepromazine, griseofulvin, niacinamide, tetracyclines, doxorubicin, clopidogrel, propranolol, cyclosporine
Vesicles and bullae (blisters), pemphigus-like lesions Sulfonamides, cephalosporins, penicillins, amitraz, diethylcarbamazine, thiabendazole, phenytoin, triamcinolone, neomycin
Papules and macules (maculopapular lesions) Sulfonamides, cephalosporins, penicillins, 5-fluorocytosine, diethylcarbamazine, shampoo, cimetidine, hydroxyzine, procainamide
Petechiae/ecchymosis (purpura) Sulfonamides, cephalosporins, penicillins
Alopecia Sulfonamides (follicular necrosis/atrophy), cephalosporins, penicillins, chemotherapy, corticosteroids, levamisole (follicular necrosis/atrophy)
Otitis (contact dermatitis) Sulfonamides, cephalosporins, penicillins, neomycin, propylene glycol, thiabendazole

Reactions can develop within hours to months of exposure, but CADRs usually occur within 1 to 3 weeks. Many of the cutaneous clinical signs can persist for up to a month, even with medical intervention, and as well as removal and avoidance of a known or suspected offending agent. Diagnosis of CADR is often supported by the results from a skin biopsy.


Principles of management include (1) avoidance or discontinuation of the suspected causative agent(s), (2) supportive symptomatic care as necessary, and (3) client education regarding prevention of future similar reactions.


There are several specific drug eruption syndromes that warrant a more detailed discussion. These were selected for discussion in this chapter. These are erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, itraconazole-associated reactions, methimazole reactions, injection site reactions (vasculitis/ischemic dermatopathy caused by rabies vaccine), reactions associated with flea and tick products, nonsteroidal antiinflammatory subcorneal to follicular neutrophilic dermatitis, cyclosporine-induced psoriasiform-lichenoid dermatosis, and corticosteroid-induced calcinosis cutis.



Erythema Multiforme and Stevens-Johnson Syndrome



Erythema Multiforme


Erythema multiforme (EM) is an uncommon skin disease that is often sudden in onset and can affect skin, mucous membranes, and the mucocutaneous junctions. The condition can wax and wane, and can be self-limiting or require diagnostic workup and therapeutic intervention. It is currently believed that with EM a cell-mediated hypersensitivity reaction is directed against infectious organisms (viral and bacterial), medications (griseofulvin, aurothioglucose, cephalosporins, penicillins, macrolides, gentamicin, tetracyclines, sulfonamides, polythiouracil), foods, antiparasitic agents (ivermectin, levamisole), levothyroxine, or various nutraceutical products (e.g., Glyco-Flex). This disorder also may be associated with neoplasia (paraneoplastic syndrome) or connective tissue disorders. Usually the underlying cause is unknown and the disorder is categorized as idiopathic.


The classic finding is a target lesion that is raised on the borders with erythema centrally. Other lesions include hyperpigmented macules, raised erythematous papules, plaques, scaling, crusting, and oozing. Areas of the skin most affected include the ventral abdomen, inguinal, and axillary regions; oral cavity; pinnae; and footpads. Almost 50% of cases have a mucocutaneous involvement.


Management includes stopping current medications (oral, injectable, and topical) and supplements. The diet may need to be changed as well. More severe cases require corticosteroids and other medications. Treatments have included cyclosporine (5 to 10 mg/kg daily PO), tacrolimus (topical), leflunomide (3 to 4 mg/kg daily PO), pentoxifylline (25 mg/kg twice daily PO), retinoids (e.g., isotretinoin 2 to 3 mg/kg daily PO), chemotherapy medications (azathioprine 2 mg/kg daily PO initially, chlorambucil 0.2 mg/kg daily PO initially), vitamin E (400 to 800 IU daily PO), and the combination of vitamin B (niacinamide 500 mg two or three times daily for ≥15 kg body weight and 250 mg two or three times daily for <15 kg body weight) and doxycycline (5 mg/kg twice daily PO initially). Practicing veterinarians are advised to consult with a dermatologist regarding the best treatment options.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Cutaneous Adverse Drug Reactions
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