Allergic reactions to cyclophosphamide: Delayed clinical expression associated with positive immediate skin tests to drug metabolites in five patients

Popescu, N; Sheehan, Michael G.; Kouides, Peter A.; Loughner, John; Condemi, John J.; Looney, R. John; Leddy, John P.

doi:10.1016/s0091-6749(96)70279-8

Cited by 37 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another explanation, of course, is that the culprit source of the cutaneous ADR was not the native drug itself but one of its metabolites. 14 Such a mechanism was noted recently by Popescu et al 41 who demonstrated using prick tests and IDR that five patients with allergic reactions to cyclophosphamide had immediate positive skin tests when performed with two cyclophosphamide metabolites but not with the native drug. Appropriate delayed readings have to be performed.…”

Section: Discussionmentioning

confidence: 87%

The use of skin testing in the investigation of cutaneous adverse drug reactions

Barbaud¹,

Reichert-Pénétrat²,

Tréchot³

et al. 1998

Br J Dermatol

236

204

View full text Add to dashboard Cite

Skin testing with the suspected compound has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (ADRs), but the value and specificity of these tests need to be determined. In this study, 72 patients with presumed drug eruptions (27 maculopapular, 18 urticarial, seven erythrodermic, nine eczematous, four photosensitivity, three fixed drug eruptions, three with pruritus and one with acute generalized exanthematous pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and 30 had intradermal tests (performed on hospitalized patients using a sterile solution of the suspected drug, diluted sequentially) with immediate and delayed readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%, 24% and 67% in patch, prick and intradermal skin tests, respectively. The results of skin tests varied with the drug tested and with the clinical type of cutaneous ADR, as a significantly higher number of positive patch tests was observed in maculopapular rashes than in urticarial reactions (P = 0.001). This study supports the value of careful sequential drug skin testing in establishing the cause of cutaneous ADR. Guidelines are proposed for performing these tests, and these include the use of appropriate negative control patients to avoid false-positive results.

show abstract

Section: Discussionmentioning

confidence: 87%

The use of skin testing in the investigation of cutaneous adverse drug reactions

Barbaud¹,

Reichert-Pénétrat²,

Tréchot³

et al. 1998

Br J Dermatol

236

204

View full text Add to dashboard Cite

show abstract

“…Clinical delay in late-onset anaphylactic reactions is thought to reflect the time to metabolize the drug and then generate metabolite-dependent allergens. 8 Popescu et al 4 demonstrated the positive immediate skin test results of CY metabolites, such as 4-hydroxycyclophosphamide and phosphoramide mustard, but not CY itself, in all of the five patients with lateonset type I hypersensitivity, including four patients with 8-16 h of delay and a patient with 10 days of delay, indicating that immunoglobulin E-mediated allergic reaction to these two metabolites is a major mechanism underlying late-onset anaphylactic reactions. Given that 4-hydroxycyclophosphamide and phosphoramide mustard reach peak levels within 0.5-3 h and 3-6 h after IVCY, respectively, 9 there may be other mechanisms due to underlying autoimmune diseases, such as altered metabolism of CY in the liver, to induce these reactions several days after IVCY.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Importantly, there also have been reports of late-onset type I hypersensitivity to CY in patients with malignant neoplasms, which occurs several hours to several days after the infusion and is associated with acute allergic reaction to CY metabolites, such as phosphoramide mustard and 4-hydroxycyclophosphamide. 4 Although immediate anaphylactic reactions related to i.v. CY pulse (IVCY) have been reported in systemic lupus erythematosus (SLE) patients, 5,6 there is no report of late-onset type I hypersensitivity in patients with collagen vascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Late‐onset anaphylactic reactions following i.v. cyclophosphamide pulse in a patient with systemic sclerosis and systemic lupus erythematosus overlap syndrome

Taniguchi

Asano

Tamaki

et al. 2014

The Journal of Dermatology

View full text Add to dashboard Cite

Late-onset anaphylactic reaction is a rare adverse effect of i.v. cyclophosphamide pulse (IVCY), which is caused by cyclophosphamide metabolites. We herein report a case of scleroderma and lupus overlap syndrome who developed anaphylactic reactions 3 h to 4 days after IVCY. Long time lapses between IVCY and appearance of symptoms are compatible with type I hypersensitivity to cyclophosphamide metabolites, appearing as late-onset anaphylactic reaction. Albeit unusual, this is an important anaphylactic reaction to be aware of following IVCY.

show abstract

“…Some beta-lactam-allergic individuals exhibit specific IgE antibodies to structures of the beta-lactam ring and may show cross-reactivity to other beta-lactam antibiotics, but others are highly selective in their recognition pattern and have IgE antibodies specific to side chains and thus react only to a single or few beta-lactam antibiotics [17][18][19]. Examples of other IgE-mediated drug hypersensitivities include reactions to immunoglobulins, insulins, chemotherapeutic agents and streptomycin [6,20].…”

Section: Ige-mediated Drug Allergymentioning

confidence: 99%

Adverse Drug Reactions: Mechanisms and Assessment

Ring

Brockow

2002

Eur Surg Res

View full text Add to dashboard Cite

Adverse drug reactions (ADR) are an important clinical problem. They account for about 5% of all hospital admissions and cause death in approximately 0.01% of surgical patients. The mechanisms leading to ADR beyond IgE-mediated allergy are still poorly understood. The importance of chemically reactive drug metabolites and the involvement of T-lymphocytes in many drug hypersensitivity reactions have been highlighted in recent years. ADR are diagnosed on clinical grounds and the temporal relation between drug intake and the appearance of the symptoms. Allergy tests are required in the further assessment of the reaction. By means of skin tests, in vitro tests and provocation tests information about the culprit drug, the mechanism involved and possible alternatives can be obtained.

show abstract

Allergic reactions to cyclophosphamide: Delayed clinical expression associated with positive immediate skin tests to drug metabolites in five patients

Cited by 37 publications

References 24 publications

The use of skin testing in the investigation of cutaneous adverse drug reactions

The use of skin testing in the investigation of cutaneous adverse drug reactions

Late‐onset anaphylactic reactions following i.v. cyclophosphamide pulse in a patient with systemic sclerosis and systemic lupus erythematosus overlap syndrome

Adverse Drug Reactions: Mechanisms and Assessment

Contact Info

Product

Resources

About