Allopurinol induced erythroderma

Allopurinol, a widely prescribed urate lowering agent is responsible for various adverse drug reactions, including erythroderma. A 45-year-old male patient was admitted with the complaints of fever, redness and scaling all over the body after 3-4 weeks of allopurinol treatment for asymptomatic hyperuricemia. Elevated liver enzymes were detected in his blood analysis. Skin biopsy was consistent with drug induced erythroderma. Allopurinol was stopped and steroids were started. Patient improved over a period of 2 weeks.KEY WORDS: Allopurinol, erythroderma, hyperuricemia     

Generalized pustular psoriasis following withdrawal of efalizumab

Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity for the treatment of chronic plaque psoriasis. Common adverse effects include headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis following discontinuation of the drug has been reported. Relapse events can manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis. We report a second case of withdrawal flare resulting in generalized pustular psoriasis.     

小牛血清去蛋白注射液致广泛斑丘疹1例

1例48岁男性患者,静脉滴注小牛血清去蛋白注射液后出现广泛斑丘疹,予以报道,提醒临床使用该药时注意该种不良反应的发生。     

A rare case of isoniazid-induced erythroderma

Tuberculosis is a common infectious disease in developing countries. Isoniazid is established the first-line antitubercular drug and an essential component of all antitubercular regimens. Erythroderma caused by isoniazid is an uncommon but serious adverse drug reaction. We report here a case of a 63-year-old female patient who presented with generalized redness and scaling with itching after 8 weeks of antitubercular treatment (ATT). ATT was stopped immediately, and antihistaminics were started. The patient improved over a period of 2 weeks. On sequential rechallenge, she developed similar lesions all over the body with isoniazid, hence confirming the diagnosis of isoniazid-induced erythroderma.KEY WORDS: Adverse cutaneous drug reaction, erythroderma, isoniazid     

Drug-induced exanthems

Cutaneous adverse reactions to drugs can comprise a broad spectrum of clinical and histopathological features. Recent evidence from immunohistological and functional studies of drug-reactive T cells suggest that distinct T-cell functions may be responsible for this broad spectrum of different clinical reactions. Maculopapular exanthems represent the most commonly encountered cutaneous drug eruption. Previous studies on maculopapular exanthems indicate that drug-specific CD4+ T cells expressing cytotoxic granule proteins such as perforin and granzyme B are critically involved in killing activated keratinocytes. These cells are particularly found at the dermo-epidermal junction and may contribute to the generation of vacuolar alteration and destruction of basal keratinocytes, which are typical found in drug-induced maculopapular exanthems. In contrast to maculopapular exanthems, the preferential activation of drug-specific cytotoxic CD8+ T cells may lead to more severe reactions like bullous drug eruptions. Furthermore, activation of drug-specific T with distinct cytokine and chemokines profiles may also explain the different clinical features of drug-induced exanthems. IL-5 and eotaxin are upregulated in maculopapular exanthems and explain the eosinophilia often found in these reactions.     

Drug patch testing in systemic cutaneous drug allergy

Patch testing with the suspected compound has been reported to be helpful in determining the cause of a cutaneous adverse drug reaction (CADR) and in studying the pathophysiological mechanisms involved. The main advantages of drug patch tests are that they can be done with no hospital surveillance because they induce only rarely adverse reactions and that any commercialized form of a drug can be used. In contrast, intradermal tests can be performed only with injectable forms or with a pure and sterile form of the drug. It is advised to perform drug patch tests during the 6 months following the CADR as we do not know whether positive results will persist. Due to the possibility that a low concentration might yield false negative results, drug patch tests have to be performed with rather high concentrations of the commercialized form of the drug, mostly diluted at 30% in petrolatum and/or in water. For some drugs and severe CADR, it is necessary to tests with lower concentrations or in other vehicles. Drug patch tests are positive in ca. 32-50% of patients who have developed a CADR. The clinical relevance of drug patch tests depends on the clinical features of the CADR (valuable in testing generalized eczema, systemic contact dermatitis, maculopapular rash, acute generalized exanthematous pustulosis, fixed drug eruption) and on the involved drug. As false positive results can be observed, it is always necessary to consider the relevance of any positive drug patch test. Their specificity and their negative predictive value have not been yet determined.     

Possible cross-sensitivity between sertraline and paroxetine in a panic disorder patient

Cross-sensitivity due to paroxetine and sertraline, the SSRIs, is rarely reported in the literature. We report an adverse drug reaction to paroxetine and sertraline in a patient of panic disorder, who initially developed a maculopapular, erythematous, pruritic rash in the third week with sertraline 50 mg/day. The rash resolved within 2 days of its discontinuation and oral supplementation of diphenhydramine and betamethasone. 10 days following discontinuation of sertraline, the patient was shifted on sustain release paroxetine 12.5 mg/day when another skin reaction with the same appearance and distribution appeared on day 4 of it, suggesting a possibility of cross-sensitivity, a drug class effect. This case report intends to improve the awareness among clinicians to use caution when choosing an alternative SSRIs.     

Teicoplanin: an investigational glycopeptide antibiotic

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, adverse effects, and clinical uses of teicoplanin are reviewed. Teicoplanin, a novel glycopeptide that is similar to vancomycin, was isolated in the mid-1970s. A fermentation product of Actinoplanes teicomyceticus, teicoplanin is a structurally complex compound made up of six fatty-acid components attached to a common aglycone. Teicoplanin's mechanism of action, like that of vancomycin, is inhibition of cell-wall biosynthesis. In vitro activity is comparable to that of vancomycin and includes staphylococci, streptococci, corynebacterium, listeria, and anaerobic cocci. Resistance to teicoplanin has been reported with coagulase-negative staphylococci. Teicoplanin is 50 to 100 times more lipophilic than vancomycin. Teicoplanin is poorly absorbed after oral administration but is 90% bioavailable when administered intramuscularly. The drug distributes widely into body tissue and is eliminated primarily renally. Optimal dosing regimens and therapeutic serum drug concentrations have not been well established. Reported adverse effects have included irreversible ototoxicity, allergic reactions with maculopapular rash and eosinophilia, pain at intramuscular injection site, and elevation of aminotransferases. Initial clinical trials have yielded conflicting results in gram-positive bacteremia, endocarditis, osteomyelitis, and soft-tissue infections. Teicoplanin has shown promise in surgical and dental prophylaxis. Comparative trials with vancomycin and other antimicrobial agents must be completed before teicoplanin's role as a therapeutic agent in the treatment of systemic gram-positive infections is defined.     

Drug eruptions: approaching the diagnosis of drug-induced skin diseases

Adverse drug reactions are a major problem in drug therapy, and cutaneous drug reactions account for a large proportion of all adverse drug reactions. Cutaneous drug reactions are also a challenging diagnostic problem since they can mimic a large variety of skin diseases, including viral exanthema, collagen vascular disease, neoplasia, bacterial infection, psoriasis, and autoimmune blistering disease, among others. Furthermore, determining that a particular medication caused an eruption is often difficult when the patient is taking multiple drugs. In this review, we will describe and illustrate a thoughtful, comprehensive, and clinical approach to the diagnosis and management of adverse cutaneous drug reactions. A morphologic approach to drug eruption includes those that are classified as maculopapular, urticarial, blistering or pustular with or without systemic manifestations. Exanthematous drug eruptions, drug hypersensitivity syndrome, urticaria and angioedema, serum sickness-like reactions, fixed drug eruptions, drug-induced autoimmune blistering diseases, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced acne, acute generalized exanthematous pustulosis, lichenoid drug eruptions and photosensitivity eruptions will be discussed.     

More on periorbital infections following therapy with biological agents

Objective: Valsartan is an angiotensin II receptor blocker (ARB) used for treatment of hypertension. The well-known adverse effects of valsartan are dizziness, headache and cough. Valsartan-related cutaneous side effects have been reported previously in a limited number of case reports.

Materials and methods: A 47-year-old man admitted with diffuse, itchy erythematous maculopapular eruption all over the body. He has been taking 160?mg valsartan daily for 10 days before onset of the eruption. On the third day of valsartan therapy, erythema had appeared over the face and spread throughout the whole body within a week. Histopathologic examination of the lesions showed lymphocyte exocytosis, spongiosis, necrotic keratinocytes in the epidermis, and mixed inflammatory cell infiltrates including perivascular eosinophils in the dermis. The patient was diagnosed as drug reaction due to valsartan with historical, clinical and histopathologic features.

Discussion and conclusion: Most common antihypertensive agents including diuretics, beta blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors have many cutaneous side effects. However, there are a few reports about the cutaneous side effects of ARBs. Physicians should be aware of the cutaneous side effects of this commonly used agent and valsartan should be considered as a triggering factor of an exanthematous drug reactions.     

Erythroderma secondary to gliclazide: a case report

Erythroderma is generalized exfoliative dermatitis, which involves more than 90% of the patient's skin. The most common cause of erythroderma is exacerbation of an underlying skin disease, malignancies or drug reaction. There is a long list of drugs responsible for erythroderma such as antiepileptics, sulfonamides, antibiotics, and angiotensin converting enzyme (ACE) inhibitors. We herein report a case of erythroderma due to gliclazide usage which is also proved by histopathologic examination and patch test. We could not find any case report of gliclazide, an oral antidiabetic, as a cause erythroderma in the literature.     

Pigmentary changes in a patient treated with imatinib

Imatinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase with additional inhibitory effects on platelet derived growth factor (PDGF) receptors alpha and beta, and KIT. It has revolutionized the treatment of adult and pediatric patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and is also FDA-approved for KIT-positive advanced gastrointestinal tumor (GIST) and dermatofibrosarcoma protuberans. A wide spectrum of dermatologic toxicities has been associated with this agent, among which a maculopapular rash is the most common event. In addition, a variety of pigmentary abnormalities of the skin and mucosal surfaces have been reported. Hypopigmentation is a well-recognized adverse effect. In contrast, paradoxical hyperpigmentation has only rarely been documented. In this case report we describe imatinib-induced cutaneous hyperpigmentation and graying of hair occurring in the same patient with dermatofibrosarcoma protuberans treated with imatinib.     

Nonbloody, red stools from coadministration of cefdinir and iron-supplemented infant formulas

Cefdinir is an extended-spectrum, third-generation cephalosporin that may be used for treatment of acute otitis media in patients allergic to penicillin. When administered with iron-containing products, including infant formulas, cefdinir or one of its metabolites may bind to ferric ions, forming a nonabsorbable complex that imparts a reddish color to the stool. We describe a 9-month-old infant with failure to thrive and acute otitis media who developed an erythematous maculopapular rash during treatment with amoxicillin-clavulanate. His antibiotic therapy was changed to cefdinir. Five days into a 10-day course of therapy, the infant's mother brought him to the pediatric clinic and reported the appearance of red stools. He had no associated gastrointestinal symptoms (vomiting, abdominal pain, or diarrhea). His hematocrit and hemoglobin level were normal, and Clostridium difficile antigen studies and tests for species of Shigella, Salmonella, and Camphylobacter as well as ova and parasites were all negative. Cefdinir was discontinued, and his stools returned to normal within 48 hours. Three weeks later, he again received cefdinir for recurrent otitis media. Red stools reappeared 48 hours later, were determined to be guaiac negative, and resolved within hours of drug discontinuation. During both occurrences of red stools, the infant had been breastfed and was receiving supplemental feedings with an iron-containing infant formula. In the product labeling of cefdinir, this adverse event is described as a consequence of the drug-drug interaction; however, it is not listed in the adverse drug reaction section of the labeling. As such, one may miss the association between cefdinir and reddish stools when investigating this event as a potential adverse reaction to cefdinir. When using the Naranjo adverse drug reaction probability scale to assess causality in our patient's case, this adverse drug reaction was determined as highly probable. As this infant had been breastfed, the use of a supplemental iron-containing infant formula was not identified as a potential contributing factor until the second occurrence of red stools. Health care professionals should review the entire product labeling, including the drug-drug interaction section, when investigating a potential adverse drug reaction. With the recent approval of generic formulations of cefdinir, clinicians should be aware of this drug-drug interaction with iron-containing products to prevent unnecessary alarm by parents and caregivers, as well as costly medical evaluations for gastrointestinal bleeding.     

某院2016-2018年184例儿童药品不良反应分析

目的:了解某儿童医院药品不良反应(ADR)发生的规律和特点,为促进临床合理用药、保障儿童用药安全提供参考.方法:采用回顾性分析方法,收集2016-2018年该院上报的184例ADR报告进行统计分析.结果:184例ADR中,男103例(55.98％),女81例(44.02％);1～6岁年龄组ADR发生率最高(60.33％...     

Hypersensitivity reactions to complementary and alternative medicine products

Complementary and alternative medicine (CAM) is becoming increasingly popular, and is often used for treating hypersensitivity diseases. Virtually all alternative remedies can cause hypersensitivity reactions, but the most frequently involved ones are tea tree oil, members of the Compositae family, propolis, oils used in aromatherapy, substances responsible for photosensitization, and metal-containing compounds. The main target organ is skin, with manifestations ranging from contact dermatitis (the most common) to urticaria-angioedema, maculopapular eruptions, photosensitivity reactions, and the Stevens-Johnson syndrome. Other types of reactions are possible, including respiratory and anaphylactic ones. Different pathogenic mechanisms have been suggested for CAM product reactions, including immunologic ones. Basophils and mast cells participate in IgE-mediated reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most delayed reactions, particularly contact dermatitis and maculopapular eruptions. Skin tests and serum specific IgE assays are carried out to diagnose immediate hypersensitivity reactions, while patch tests and lymphocyte transformation tests are usually performed to evaluate delayed hypersensitivity reactions. Thus clinicians should know about the potential of CAM products for causing adverse reactions. Our study is aimed at highlighting the risk of hypersensitive reactions to CAM remedies on the basis of the numerous cases reported in the literature. Because little is known about adverse reactions to CAM products, further systematic studies and an appropriate regulation by heath authorities are necessary.     

医院2008—2019年皮肤药物不良反应回顾性分析

目的 探讨南京医科大学附属儿童医院皮肤药物不良反应（cutaneous adverse drug reactions，CADRs）发生的特点及规律，为儿童安全用药提供参考。方法 通过国家药品不良反应监测系统导出2008年1月—2019年12月医院上报的1 290例CADRs病例报告，收集这些患儿发生CADRs的临床表现、类别、涉及的药物及患儿治疗病程等信息并建立数据库。结果 1 290例CADRs病例报告中，男性患儿802例，占比62.17%，其CADRs病例报告明显高于女性患儿，同时本研究发现幼儿期（1~6岁）儿童CADRs发生率最高；共涉及药品137种，主要类型为抗菌药物和中药及其提取物，涉及的药品剂型以注射剂为主，给药途径以静脉滴注为主，最为常见的皮肤黏膜损害为斑丘疹（694例，54.56%）。CADRs中罕见的严重皮肤黏膜损害有18例，涉及的主要药物类型为抗癫痫药物及抗感染药物，皮肤黏膜损害以重症多形红斑以及抗癫痫药物高敏综合征为主，绝大部分严重皮肤药品不良反应经对症治疗后好转，但有1例患儿死亡。结论 根据CADRs发生的规律和特点，临床医师要及时观察CADRs的发生以减少药源性不良反应的发生，同时重点监护特殊人群用药，保障患者安全用药。     

Pathophysiological characterization of drug hypersensitivity to tribenoside

Background

Tribenoside is a semisynthetic sugar derivative that is mainly indicated for treatment of chronic venous insufficiency. Up to 10% of patients treated by tribenoside can suffer from skin side effects. The adverse effects usually present as angioedema, urticaria, or maculopapular exanthema. The pathophysiology of the reaction has not as yet been elucidated.

Methods

In this study, we examined 22 patients with drug eruptions caused by tribenoside. Patch tests were performed to investigate in vivo cellular reactions. Laboratory investigations were carried out by lymphocyte transformation tests and basophil activation tests.

Results

We found a positive patch test reaction to tribenoside in one patient. The lymphocyte transformation test elicited a borderline positive reaction in one patient, and the basophil activation test gave a clearly positive reaction in another patient.

Conclusion

The diagnosis of drug hypersensitivity reactions is a challenge. Both delayed and immediate immunologic response may play a role in the etiology of tribenoside-induced exanthemas. Our investigation and results indicate that benzoic acid could be the antigenic determinant in drug hypersensitivity to tribenoside.     

Cutaneous allergic drug reactions: update on pathophysiology,diagnostic procedures and differential diagnosic

Important changes in the understanding and management of drug hypersensitivity reactions during the last years result from the increasing importance of biologics in medical practice, which differ in their spectrum of adverse drug reactions (ADRs) from the classical covalent drugs. With regard to covalent drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause of anaphylactic and photosensitivity reactions. Especially in allergic reactions to NSAIDs, pseudoallergic reactions should be considered in the differential diagnosis. In opposite to the main cutaneous allergic drug reactions such as urticaria or maculopapular skin rash, in which antibiotics are the main culprits, in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN (Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are the main causes. Similar mutations in the IL36R gene, which were found in both patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular psoriasis, make the differential diagnosis more difficult and raise the question whether there is a difference between these diseases or whether AGEP is not just a drug induced pustular psoriasis. Finally, some special aspects of side effects of biologics and targeted therapies respectively are discussed.     

The adverse-effect profile of lacosamide

ABSTRACT

Introduction: Lacosamide has been used in epilepsy patients in the United States, Europe and Asia since it was approved by the FDA in 2008. Many patients have benefited from this drug as a new generation of sodium channel blocker. With the worldwide use of this drug, its adverse effects have gradually emerged, especially some rare adverse events.

Areas covered: The present review aims to summarize the adverse effects of lacosamide reported in the literature in recent years to promote the safe clinical application of the drug.

Expert opinion: In more than 10 years of experience in drug usage, adverse reactions of lacosamide have also been gradually discovered. The review showed that lacosamide is safe and effective in antiepileptic treatment, and its common side effects are dizziness, headache, drowsiness, diplopia, and cardiovascular abnormalities. Skin rashes, hematotoxicity and heart damage, psychological symptoms and suicide risk have also been reported and emphasized.