acyclovir and Drug-Hypersensitivity

We report a case of zona ophthalmica complicated with a complete ophthalmoplegia. In the literature only 19 cases have been reported the last 30 years, with a variety of possible pathophysiological mechanisms. Our patient's mydriasis reacted to diluted pilocarpine 0.125% which is a sign of Adie's pupil and is not supposed to occur in mydriasis caused by a third nerve palsy. We review the literature on the possible pathogenesis of this hypersensitivity.

Topics: Acyclovir; Aged; Alzheimer Disease; Benzimidazoles; Drug Hypersensitivity; Drug Therapy, Combination; Female; Herpes Zoster Ophthalmicus; Humans; Hyperthyroidism; Injections, Intravenous; Ophthalmoplegia; Ovarian Neoplasms; Pilocarpine

The incidence of acyclovir-induced hypersensitivity is rare. To our knowledge, there are four published case reports of oral acyclovir desensitization in adults. Evidence-based guidelines prompt the use of acyclovir for herpes simplex virus (HSV) prophylaxis and treatment. Literature on the cross-reactivity of structurally similar antiviral agents is conflicting, presenting a clinical challenge when choosing an alternative agent. This is a case of successful acyclovir desensitization in an allogeneic stem cell transplant patient.. A 69-year-old female patient, diagnosed with myelodysplastic/myeloproliferative neoplasm, presented to the hospital for donor mismatch allogeneic bone marrow transplant. The patient reported acyclovir-induced angioedema while receiving treatment for non-complicated herpes zoster (shingles) infection.

Topics: Acyclovir; Aged; Angioedema; Antiviral Agents; Bone Marrow Transplantation; Desensitization, Immunologic; Drug Hypersensitivity; Female; Herpes Simplex; Humans

Topics: Acyclovir; Anaphylaxis; Basal Ganglia; Brain; Child; Dexamethasone; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Hypersensitivity; Immunoglobulin E; Seizures; Skin Tests

Herpes simplex virus and varicella zoster virus reactivation can occur in up to 32% and 40% of patients, respectively in the first year post-transplant without prophylaxis. Antiviral therapy consisting of acyclovir or valacyclovir is recommended for at least 1 year post stem cell transplant per evidence-based guidelines.. In the event of a contraindication or hypersensitivity reaction to either drug, an alternative is essential based on the proven efficacy in reducing clinically significant herpes simplex virus and varicella zoster virus reactivations. We report two cases of successful initiation of famciclovir in stem cell transplant recipients experiencing hypersensitivity to valacyclovir or acyclovir.. In both cases, there were no hypersensitivity reactions or breakthrough viral infections after famciclovir initiation but this observation is limited by a small patient population.. Due to the limited data available, famciclovir appears to be a reasonable option in immunocompromised patients with a mild valacyclovir or acyclovir hypersensitivity reaction.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Drug Hypersensitivity; Famciclovir; Female; Humans; Immunocompromised Host; Middle Aged; Stem Cell Transplantation; Valacyclovir; Valine

Immune mediated adverse drug reactions (IM-ADRs) remain a significant source of patient morbidity that have more recently been shown to be associated with specific class I and/or II human leukocyte antigen (HLA) alleles. Abacavir-induced hypersensitivity syndrome is a CD8+ T cell dependent IM-ADR that is exclusively mediated by HLA-B*57:01. We and others have previously shown that abacavir can occupy the floor of the peptide binding groove of HLA-B*57:01 molecules, increasing the affinity of certain self peptides resulting in an altered peptide-binding repertoire. Here, we have identified another drug, acyclovir, which appears to act in a similar fashion. As with abacavir, acyclovir showed a dose dependent increase in affinity for peptides with valine and isoleucine at their C-terminus. In agreement with the binding studies, HLA-B*57:01 peptide-elution studies performed in the presence of acyclovir revealed an increased number of endogenously bound peptides with a C-terminal isoleucine. Accordingly, we have hypothesized that acyclovir acts by the same mechanism as abacavir, although our data also suggest the overall effect is much smaller: the largest changes of peptide affinity for acyclovir were 2-5 fold, whereas for abacavir this effect was as much as 1000-fold. Unlike abacavir, acyclovir is not known to cause IM-ADRs. We conclude that the modest effect of acyclovir on HLA binding affinity in contrast to the large effect of abacavir is insufficient to trigger a hypersensitivity syndrome. We further support this by functional in vitro studies where acyclovir, unlike abacavir, was unable to produce an increase in IFN-γ upon expansion of HLA-B*57:01+ PBMCs from healthy donors. Using abacavir and acyclovir as examples we therefore propose an in vitro pre-clinical screening strategy, whereby thresholds can be applied to MHC-peptide binding assays to determine the likelihood that a drug could cause a clinically relevant IM-ADR.

Topics: Acyclovir; Antiviral Agents; Cells, Cultured; Drug Hypersensitivity; HLA-B Antigens; Humans; Protein Binding

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Aged; Antibodies, Viral; Anticonvulsants; Antiviral Agents; Drug Hypersensitivity; Eosinophilia; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Retrospective Studies; Virus Activation

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Cyclosporine; Dexamethasone; Drug Hypersensitivity; Exanthema Subitum; Herpesvirus 3, Human; Herpesvirus 6, Human; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Prednisone; Pyrazines; Syndrome; Virus Activation

Topics: Acyclovir; Administration, Topical; Allergens; Dermatitis, Allergic Contact; Drug Hypersensitivity; Female; Follow-Up Studies; Herpes Simplex; Humans; Patch Tests; Risk Assessment; Young Adult

Topics: Acyclovir; Antiviral Agents; Basophils; Drug Hypersensitivity; Female; Flow Cytometry; Herpes Genitalis; Humans; Hypersensitivity, Immediate; Lymphocyte Activation; Middle Aged; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Skin Tests; Valacyclovir; Valine

Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a severe multiorgan reaction with reactivation of herpesviruses. Various features are often seen during the course of the disease. Many aspects of this syndrome suggest close similarities between DIHS/DRESS and graft-versus-host disease. We describe a patient with phenobarbital-induced hypersensitivity syndrome who revealed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with limbic encephalitis during the course of the disease. In view of previous reports that SIADH and limbic encephalitis are caused by reactivation of latent herpesviruses after transplantation, both conditions may be secondarily caused by reactivation of latent herpesviruses, which is typically observed in DIHS/DRESS. These neurological symptoms should be added to a growing list of important complications of DIHS/DRESS because of the high mortality rate associated with them.

Topics: Acyclovir; Aged; Anticonvulsants; Antiviral Agents; Coma; Drug Hypersensitivity; Encephalitis; Epilepsy; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Phenobarbital; Syndrome; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Injections, Intravenous; Middle Aged; Valacyclovir; Valine

Topics: Acyclovir; Adult; Antiviral Agents; Drug Hypersensitivity; Eczema; Exanthema; Eye Diseases; Eyelids; Face; Humans; Kaposi Varicelliform Eruption; Male; Penicillins; Staphylococcal Infections

An immunocompetent woman presented with a hypersensitivity skin reaction following suppressive therapy with aciclovir for recurrent culture proved genital herpes simplex virus infection. She developed a similar reaction when treatment was changed to famciclovir. Without antiviral suppression her recurrences were frequent and distressing. Graded challenge was performed and she became tolerant to aciclovir. She successfully continued suppressive therapy for 1 year with no further hypersensitivity reactions or recurrences.

Topics: Acyclovir; Antiviral Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Middle Aged; Recurrence

Topics: 2-Aminopurine; Acyclovir; Adult; Antiviral Agents; Dermatitis, Allergic Contact; Drug Hypersensitivity; Famciclovir; Female; Herpes Labialis; Humans; Keratitis, Herpetic

A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy. Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity. Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity. Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens. Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity. This report is an example of acyclovir hypersensitivity and successful oral desensitization.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Aged; Desensitization, Immunologic; Drug Hypersensitivity; Female; Herpes Simplex; Humans; Skin Diseases, Infectious