Cutaneous Drug Reactions Research Articles

Cutaneous drug reactions in children

Cutaneous drug reactions (CDR) are common in pediatric age group and can be important not only for further therapeutic strategy but also for future of the child. CDR can be classified based on the pathogenesis, morphology, dose relation and predictability. About 3% of patients admitted in hospital have adverse drug reaction. CDR can be due to both immunological and nonimmunological reactions, with nonimmunological reactions being more common. Morphologically CDR in children is divided into five subtypes with exanthematous type being most common. Meticulous history and examination are the basis of diagnosis of CDR. Management is primarily withdrawal of the offending agent and supportive and symptomatic care. Such patients should be advised to carry a drug diary so as to maintain a record of the offending drug/drugs and also to guard against future adverse events.

Toxic epidermal necrolysis due to voriconazole: case report and review

Toxic epidermal necrolysis is an uncommon but potentially life-threatening adverse cutaneous drug reaction characterized by variable degrees of epidermal necrosis and detachment leading to morbidity and risk of mortality. We describe a 67-year-old woman who underwent allogeneic peripheral blood stem cell transplantation as treatment for chronic lymphocytic leukemia. She developed toxic epidermal necrolysis after she was transitioned to voriconazole, which was a component of her post-transplant regimen. The diagnosis of toxic epidermal necrolysis in our patient was made clinically and confirmed histologically. Based on the temporal initiation of voriconazole therapy and the development of her adverse cutaneous reaction, we concluded that voriconazole was the offending agent. There are limited reported cases of voriconazole-induced toxic epidermal necrolysis; we report this case to increase awareness of this potential life-threatening complication.

Acute Respiratory Failure in Patients With Toxic Epidermal Necrolysis

Stevens-Johnson syndrome and toxic epidermal necrolysis are severe adverse cutaneous drug reactions characterized by widespread skin and mucous membrane detachments, including bronchial mucosa, which may be associated with respiratory failure requiring mechanical ventilation. The presentation and outcome of patients requiring mechanical ventilation and the characteristics of bronchial epithelial lesions among ventilated patients are reported. Predictors of mechanical ventilation available on hospital admission were identified using univariate and multivariate logistic regressions. Retrospective cohort study. Medical ICU and dermatology department of a tertiary care hospital, which hosts the French national referral center for toxic epidermal necrolysis. Patients admitted for Stevens-Johnson syndrome/toxic epidermal necrolysis over a 14-year period were included. None. Of the 221 patients included in the study, 56 patients (25.3%) required mechanical ventilation. None of the patients received noninvasive ventilation. Patients requiring mechanical ventilation had a larger baseline detached body surface area, higher Logistic Organ Dysfunction score, and Simplified Acute Physiology Score II, and they presented more often with shock, pulmonary infiltrates, and renal dysfunction (p < 0.0001 for all comparisons). Among patients receiving mechanical ventilation, 57% of the patients died; those having bronchial epithelial lesions (22 of 56) required intubation earlier than others (1 [1-4] vs 4 [1-6] d after hospital admission; p = 0.027). Variables associated with mechanical ventilation in multivariate analysis included serum bicarbonates less than 20 mM (odds ratio, 4.9 [95% CI, 1.1-22.7]; p = 0.041), serum urea greater than 10 mM (odds ratio, 7.0 [95% CI, 2.2-22.8]; p < 0.001), a detached body surface area between 10% and 29% (odds ratio, 3.7 [95% CI, 1.0-13.8]; p = 0.048) or greater than or equal to 30% (odds ratio, 19.7 [95% CI, 4.4-87.4]; p < 0.0001), WBCs more than 12,000/mm3 (odds ratio, 11.6 [95% CI, 2.8-48.1]; p < 0.001), blood hemoglobin less than 8 g/dL (odds ratio, 8.1 [95% CI, 1.2-55.2]; p = 0.032), and more extensive pulmonary infiltrates (odds ratio, 9.7 [95% CI, 3.6-25.9]; p < 0.0001). Mechanical ventilation is required in one of four Stevens-Johnson syndrome/toxic epidermal necrolysis patients and is associated with a poor outcome. Prompt identification of Stevens-Johnson syndrome/toxic epidermal necrolysis patients at higher risk of intubation could help guide their early management, particularly for those having bronchial epithelial lesions.

Fixed drug eruption due to fluconazole: A case report

Fluconazole is commonly used in treatment of candidiasis and dermatophyte infections. Fluconazole-induced fixed drug eruption (FDE) is one of the rare adverse cutaneous drug reactions reported in literature. We report a case of a 23-year-old man who developed FDE after intake of fluconazole, which resolved after the drug was discontinued. Thus, for safe use of medicines, continued reporting of such rare adverse effects of drugs is required.

A case of toxic epidermal necrolysis in a young infant successfully treated with intravenous immunoglobulin

Toxic epidermal necrolysis (TEN) is a severe adverse cutaneous drug reaction characterized by widespread keratinocyte death. Clinically, TEN is characterized by rapidly progressing erythematous, purpuric rash to widespread blistering and denudation of skin and severe mucositis, with fatal complications like sepsis and multiorgan failure. TEN is considered to be rare in infants and usually has a fatal outcome due to sepsis. As yet, only few reports have been documented in the literature. We hereby report a case of TEN in a young infant successfully treated with intravenous immunoglobulin (IVIG).

Stevens-Johnson syndrome and toxic epidermal necrolysis: retrospective study of 185 cases in Abidjan (Côte d’Ivoire)

Cutaneous bullous adverse drug eruptions are a dreaded complication of drug use. The purpose of this study was to document the epidemiological features, outcomes, and causes of these reactions, in particular, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell disease), in a teaching hospital in Abidjan (Côte d'Ivoire). A retrospective study reviewed the records of severe cutaneous drug reactions in patients managed in the dermatology department of the University Hospital of Treichville (Abidjan) over a period of ten years (from September 2000 through August 2010). These diseases were diagnosed in 185 patients during the study period. Their mean age was 31.8 years (range: 2-70 years) and the M/F sex ratio was 0.6 The most frequent reactions, as expected, were Stevens-Johnson syndrome (73%) and toxic epidermal necrolysis (27%). The drugs most commonly involved were the antibacterial sulfonamides (22.1%), followed by the antiviral nevirapine (11.1%), and the antimalarial agent, sulfadoxine/pyrimethamine. The fatality rate was 22.5%, including 46% of the patients with toxic epidermal necrolysis and 14.6% of those with Stevens-Johnson syndrome. Respiratory distress (39.5%) and dehydration (23.4%) were the primary direct causes of death. Antibacterial sulfonamides are the leading drugs implicated in the occurrence of bullous drug eruptions in Abidjan.

Stevens-Johnson syndrome and toxic epidermal necrolysis

Stevens-Johnson syndrome and toxic epidermal necrolysis are potentially life-threatening adverse cutaneous drug reactions. Clinically, it manifests as a rash, often morbilliform, or atypical target lesions that evolve to epidermal detachment. There is mucosal involvement in almost all patients. The loss of skin's barrier function has important implications in the maintaining of homeostasis in these patients, often determining its internment in Burn Units or Intensive Care Units. The drugs most often involved are allopurinol, antibiotics, including ß-lactams and sulfonamides, anti-inflammatory drugs (NSAIDs) and aromatic anticonvulsants. The clinical manifestations appear on average 7 to 21 days after the onset of the involved drug. The diagnosis is clinical and supported by histopathology, whose main finding is keratinocytes' necrosis and cleavage of the dermo-epidermal junction. The differential diagnosis is carried out with erythema multiforme, acute generalized exanthematous pustulosis, staphylococcal scalded skin syndrome, paraneoplastic pemphigus and graft versus host disease. A timely recognition of these situations is of utmost importance in order to intervene as early as possible. The suspension of the drug believed to be involved is paramount.

Multi-Indication Carbamazepine and the Risk of Severe Cutaneous Adverse Drug Reactions in Korean Elderly Patients: A Korean Health Insurance Data-Based Study

ObjectiveTo evaluate the risk of severe cutaneous adverse drug reactions (SCAR) after exposure to multi-indication antiepileptic drugs for in Korean elderly patients.MethodsWe used a nationwide database from the Korean Health Insurance Review and Assessment Service claims constructed for the monitoring of drug utilization among the entire Korean elderly population from January 2005 to June 2006. We identified cases of SCARs among inpatients aged ≥65 years and those newly diagnosed with erythema multiforme according to the International Classification of Diseases, 10th revision code (L51). Each case was matched to four controls for gender, age, and the first hospitalization date as the index date. The use of carbamazepine, gabapentin, lamotrigine, topiramate, phenobarbital, phenytoin, and valproate during a 60-day period before the index date was compared. A conditional logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of SCARs for antiepileptic drug.ResultsWe identified 286 cases of SCAR and 1,144 matched controls. Among the 25 patients who were prescribed antiepileptic drugs within 60 days of the index date. There were 11 cases (3.8%) of severe ocular manifestations, and most elderly patients were first-time or short-term users of antiepileptic drugs. Among the 10 cases of carbamazepine use, only 2 cases were prescribed carbamazepine for seizure. All antiepileptic drugs were associated with an increased SCAR risk (adjusted OR = 3.42, 95% CI: 1.75–6.63). The SCAR risk was highest in patients treated with carbamazepine (adjusted OR = 10.39, 95% CI: 2.64–40.86, for multi-indication; adjusted OR = 6.84, 95% CI: 1.55–30.10, for neuropathic pain).ConclusionCarbamazepine use was associated with a nearly 10-fold increase in severe cutaneous drug reactions in Korean elderly patients. This association was consistently high with SCAR patients who received carbamazepine for neuropathic pain.

Clinical Presentations of Severe Cutaneous Drug Reactions in HIV-Infected Africans

Sub-Saharan Africa is the epicenter of the HIV pandemic and HIV-infected people are more susceptible to inflammatory dermatoses, infections, and drug eruptions. Many of the drugs used for HIV-associated opportunistic infections are associated with a higher incidence of drug-related toxicities and drug interactions. This article discusses the epidemiology, pharmacogenetics, and clinical features of idiosyncratic drug reactions in HIV-infected Africans. Special considerations in this population, including immune reconstitution inflammatory syndrome, multiple drug hypersensitivity syndrome, drug reactions in pregnancy, drug rechallenge in lichenoid drug eruptions, and anxiety/depression after cutaneous adverse drug reactions, are also briefly discussed.

Toxocarosis and putative DRESS syndrome in an oncological patient: a case report

Toxocarosis is a parasitic infection caused by Toxocara canis or Toxocara cati. Their definite hosts are the domestic dog and cat, where their adult forms live within the lumen of the small intestine. In humans, infective larvae hatch after ingestion of eggs, but the juvenile stages fail to develop into mature adult worms. Instead, they migrate through the body with the potential to affect virtually every body site. DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a serious cutaneous drug reaction, which also involves other organ systems. We report on a 45-year-old man who was admitted with fever up to 40 °C, skin rash and pruritus not responding to amoxicillin/clavulanic acid. Laboratory results showed a slightly elevated white blood cell count, with 62 % eosinophils. History revealed contact to roaming cats. Travel history was unremarkable. Extensive diagnostic workup was performed, and the patient was finally diagnosed with DRESS syndrome, responded to systemic corticosteroid therapy and was discharged. Serology for Toxocara came back positive a few days later. Stool was again sent for microscopy and was found positive for Giardia lamblia, which was treated with a 5-day course of metronidazole. The patient had again developed rash and eosinophilia (62 %). Total immunoglobulin (Ig)E was 1,689 U/l (normal limit: < 100 689 U/l). Follow-up serology showed a marked increase of Toxocara TES ELISA IgG (70 U, normal limit: < 20 U), confirming toxocarosis. Antiparasitic treatment with albendazole 400 mg bid for 5 days was initiated; eosinophilia resolved; and the patient had no further complaints. Although generalized exanthema due to Toxocara has not yet been described in literature, toxocarosis is known to cause a wide spectrum of cutaneous manifestations. Whether our patient had both, a drug reaction with eosinophilia and systemic symptoms and a parasitic infection, or whether a hypersensitivity reaction to Toxocara antigen was mimicking a DRESS syndrome remains unclear.

Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore

ObjectivesTo determine the association between severe cutaneous drug reactions (SCDR), HLA-B*1502 allelism, carbamazepine dose and treatment duration in a Singapore paediatric population.MethodCase–control study of SCDR with carbamazepine and HLA-B*1502. We...

Clinical Features and Prognostic Factors in Severe Cutaneous Drug Reactions

Background: Severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). SJS and TEN (SJS/TEN) and DRESS are thought to be different diseases; however, they share some clinical and laboratory features. Although SCORTEN serves as an excellent prognostic marker for SJS/TEN, there is still a need for development of other prognostic markers for SCARs. Methods: The study population consisted of 88 SCAR patients. Clinical characteristics and clinical manifestations were compared between SJS/TEN and DRESS. Risk factor analyses for prolonged hospitalization were performed. Results: Of the 88 patients, 41 were SJS/TEN and 47 were DRESS. Mortality rates of TEN and DRESS were 9.8 and 2.1%, respectively. Allopurinol and carbamazepine were the most common causes of both SJS/TEN and DRESS (34.7 and 62.9%, respectively). Some of the systemic presentations, such as fever and laboratory abnormalities were common in both phenotypes. Thrombocytopenia tended to be related to prolonged hospitalization (longer than 3 weeks) in SJS/TEN (odds ratio, OR = 5.1, 95% confidence interval, CI 0.8-31.8, p = 0.076). In DRESS patients, leukocytosis at presentation (OR 4.8, 95% CI 1.1-20.3, p = 0.03) was related to prolonged hospitalization. Conclusions: Clinical features of SCARs in a tertiary hospital in Korea were similar to those reported previously. SJS/TEN and DRESS shared some clinical and laboratory features. Thrombocytopenia for SJS/TEN and leukocytosis at presentation for DRESS may be useful prognostic markers for prolonged hospitalization.

PSS13 - Costs Comparison of Cutaneous Drug Reactions Treatment Divided by Diagnosis Groups

PSS13 - Costs Comparison of Cutaneous Drug Reactions Treatment Divided by Diagnosis Groups

Acute kidney injury in patients with severe rash on vemurafenib treatment for metastatic melanomas

Vemurafenib, a selective BRAF (v-raf murine sarcoma viral oncogene homologue B1) kinase inhibitor, is a new targeted biotherapy that improves survival in patients with metastatic melanomas harbouring the BRAF V600E mutation. However, this drug has significant dermatological adverse effects. We report a new severe cutaneous reaction to this drug associated with acute kidney injury (AKI). Four patients presented a generalized grade 3 (Common Terminology Criteria for Adverse Events) erythematous eruption with hyperkeratosis pilaris, 5-14days after the introduction of vemurafenib. These symptoms were associated with AKI in all cases and transitory hypereosinophilia in two cases. Vemurafenib treatment was stopped in three patients and the dose was reduced in the fourth, leading to a gradual improvement of skin symptoms and renal function. Positron-emission tomography scans showed a complete response in three cases and a major response in one case. Vemurafenib was reintroduced at a lower dose, without a relapse of the rash, but renal function again deteriorated. Thus, we report a cluster of four cases of AKI associated with similar, severe, grade 3 cutaneous drug reactions related to vemurafenib.

Anti-epileptic drugs and severe cutaneous drug reactions in certain ethnic populations &amp; HLA association

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse reactions, which could be induced by a variety of drugs. It was proposed that human leukocyte antigen (HLA)-restricted presentation of antigens (drugs or their metabolites) to T lymphocytes initiates the immune reactions of SJS-TEN. The genetic susceptibility and the exact immunological pathogenesis were not clear until the recent studies. It was first identified that HLA-B*1502 is strongly associated with carbamazepine (CBZ)-induced SJS-TEN and HLA-B*5801 with allopurinol-SJS- TEN in Han Chinese. The same associations had been validated across different human populations. For the downstream danger signals, Fas-Fas ligand (FasL) and perforin -granzyme B had been advocated as cytotoxic mediators for keratinocyte death in SJS-TEN. However, expression levels of these cytotoxic proteins from the skin lesions were too low to explain the distinct and extensive epidermal necrosis. In recent study it was identified that the granulysin, a cytotoxic protein released from cytotoxic T cells or natural killer (NK) cells, is a key mediator for disseminated keratinocyte death in SJS-TEN. The article aims to provide an outlay of both of the genomic and immunologic perspectives of SJS-TEN. These studies give us a better understanding of the immune mechanisms, biomarkers for disease prevention and early diagnosis, as well as providing the therapeutic targets for the treatments of SJS-TEN.

Cutaneous Drug Reactions in Children: An Update

Cutaneous drug reactions account for a large proportion of adverse drug reactions. Cutaneous drug reactions can be very challenging to diagnose. They can mimic many other skin diseases; this is especially evident during childhood, when viral exanthems are commonplace. Also, if a patient is taking numerous medications, establishing causality to a specific drug can be multifaceted and difficult. The purpose of this review is to highlight an approach to the diagnosis of a suspected cutaneous drug reaction in a child. We have classified different types of drug eruptions by morphology: exanthematous, urticarial, pustular, and bullous. Within each of these groups we have divided them into simple, benign, or non-febrile and complex or febrile reactions. We also include a miscellaneous group to ensure a methodical review.

Cutaneous drug reactions in intensive care

Rashes are common on the wards and in intensive care, and can be the cause of the admission, an extension of an underlying pathology or a side effect of a drug. This review discusses the frequency and causes of these drug rashes, whether they are benign or life threatening, and looks at how to identify and manage them.

Immune response in a cutaneous allergic drug reaction secondary to imidapril, benazapril and metformin

Introduction: Cutaneous drug reactions may be classified with regard to pathogenesis and clinical morphology. They may be mediated by both immunologic and non-immunologic mechanisms. Case report: A 56 year old female presented with widespread patches and macules, concentrated on her face, trunk and extremities. The lesions were pruritic, and temporally associated with intake of benzapril hydrochloride, imidapril and metformin. Methods: Biopsies for hematoxylin and eosin (H&E) examination, as well as for immunohistochemistry (IHC) and direct immunofluorescence (DIF) analysis were performed for diagnostic purposes, and also to evaluate the lesional immune response. Results: Hematoxylin and eosin staining demonstrated a histologically unremarkable epidermis. Within the dermis, a moderately florid, superficial and deep, perivascular infiltrate of lymphocytes, plasmacytoid lymphocytes, histiocytes and rare eosinophils was identified, consistent with an allergic drug reaction. DIF demonstrated deposits of IgE, Complement/C3 and fibrinogen around dermal blood vessels. IHC demonstrated positive staining with HAM-56 and myeloid/histoid antigen in the cell infiltrate around the upper dermal blood vessels. HLA-ABC was overexpressed around those vessels, as well as around dermal sweat glands. COX-2 demonstrated positive staining in both the epidermis and upper dermis. Conclusion: Drug reactions are significant causes of skin rashes. In the current case, we were able to identify multiple antigen presenting cells in the area of the main inflammatory process. The immunologic case findings suggest that allergic drug eruptions may represent complex processes. An allergic drug reaction should be suspected whenever dermal, perivascular deposits of fibrinogen, Complement/C3 and other markers such as IgE are identified via DIF.

Mimics of Cutaneous Lymphoma

The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.

Evaluation of Dermatological Consultations of Patients treated in Intensive Care Unit

Background: Skin disorders which require treatment are a common development in patients treated in intensive care units (ICUs). There are very few prospective studies about skin complications in adult ICUs. Objective: The aim of this study is to evaluate skin disorders in ICU-treated adult patients who were consulted for dermatological problems. Methods: Eighty-two of 591 patients admitted to ICUs who were consulted for dermatological problems were included in the study. The correlation between skin complications and associated comorbidities, age, gender and ICU length of stay were analyzed. Results: Ninety dermatological complications were observed. Cutaneous drug reactions were significantly more frequent in female patients than males (p = 0.020). Candidal intertrigo was more frequent in diabetic patients than in nondiabetic patients (p = 0.042). Conclusion: Patients in ICUs may develop various skin disorders that need to be evaluated by dermatological consultations. Clinical features of the patients, especially gender and comorbidities, may predispose skin complications.