Cutaneous reactions to antibacterial agents

Antibacterial agents may cause a variety of untoward reactions. Some range from transient, mild erythema to toxic epidermal necrolysis, often resulting in disability and death. Both in vivo and in vitro tests are becoming useful for the diagnosis of the causative agent in drug eruptions. The drug hypersensitivity syndrome may be associated with thyroid abnormalities often occurring months after the drug has been withdrawn. Symmetrical small joint polyarthritis, fever, and malaise may be the presenting findings in a patient with drug-induced lupus erythematosus. Exanthematous drug eruptions without high fever, mucosal involvement, or joint symptoms often resolve without discontinuation of the drug. The differential diagnosis of Stevens-Johnson syndrome and toxic epidermal necrolysis depends on the percentage of epidermal detachment.     

Review of intravenous immunoglobulin in the treatment of stevens-johnson syndrome and toxic epidermal necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and serious cutaneous adverse reactions. There is controversy over the use of intravenous immunoglobulin (IVIG) in the treatment of SJS or TEN. The lack of randomized controlled trials to assess the benefits and risks of IVIG is due to its low prevalence and the high mortality rate associated with these cutaneous adverse reactions, especially in TEN. This article reviews published literature on case series that either supports or refutes the use of IVIG in the treatment of SJS or TEN.     

End-Stage Respiratory Failure Secondary to Bronchiolitis Obliterans Syndrome Induced by Toxic Epidermal Necrosis,Also Known as Lyell Syndrome: A Case Report

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases. They can be associated with systemic manifestations such as bronchiolitis obliterans syndrome (BOS). SJS/TEN-induced BOS is associated with a poor prognosis, and no guidelines exist regarding its management. Several case reports have described the association between SJS/TEN and BOS, with few patients undergoing lung transplantation as a last resort therapy. Unfortunately, in the published reports, none of the transplanted patients were observed for a long period of time after the transplantation; therefore, the long-term mortality as well as the risk of recurrence of BOS could not be inferred from these reports.Case reportWe present the case of a young patient diagnosed with SJS complicated by BOS and end-stage respiratory failure refractory to corticosteroid therapy. She underwent bilateral lung transplantation with an outstanding outcome at 5-year follow-up.ConclusionSJS/TEN-induced BOS might have a favorable evolution and long-term outcomes following lung transplantation. However, prospective studies are needed to confirm this finding.     

Combination therapy: Etanercept and intravenous immunoglobulin for the acute treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis

BackgroundStevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an autoimmune condition with significant morbidity and mortality.MethodsA retrospective review was performed at a single institution. All patients admitted to the LAC + USC burn unit from May 1st 2015–January 1st 2018 with a histologic diagnosis of SJS/TEN were reviewed. Patient characteristics and outcomes were recorded. These outcomes were compared to our previously published cohort.ResultsThirteen total consecutive SJS/TEN patients were treated with etanercept. Compared to non-etanercept treated patients, etanercept-treated patients did not experience a significant difference in mortality (15.4% vs. 10%, P = 0.58), ICU days (6.9 vs. 15.1, P = 0.08), length-of-stay (9.8 vs 16.4, P = 0.11), or infections (38.5% vs. 57.5%, P = 0.58). The standardized mortality ratio in etanercept-treated patients was 0.44 (95% CI, 0.21, 0.65). In general, etanercept-treated patients had higher SCORTENs (3 vs. 2, P = 0.03) and longer delays to presentation (5.2 vs. 2.7 days, P < 0.01).ConclusionsEtanercept can be considered in the treatment of SJS/TEN patients in addition to IVIg, and supportive care in a burn unit.     

Phototherapy-induced Purpuric Eruption in a Neonate

Phototherapy is commonly utilized in the treatment of neonatal jaundice. The authors observed a rare cutaneous complication of visible blue light phototherapy in a neonate with hyperbilirubinemia. A three-day-old neonate was evaluated for a purpuric rash after initiation of phototherapy for treatment of hyperbilirubinemia. Cutaneous examination revealed purpuric, nonblanching, well-demarcated lesions on the chest, abdomen, arms, and chin with sparing at shielded sites. The history, physical examination, and laboratory results support the diagnosis of purpuric phototherapy-induced eruption. The authors present a case report of this uncommon cutaneous eruption in a transfused neonate undergoing phototherapy for treatment of hemolytic disease of the newborn.The treatment of choice for unconjugated (indirect) hyperbilirubinemia is visible blue light therapy. Although toxicity from phototherapy is rare, multiple cutaneous eruptions have been reported.1 In infants with cholestasis, a rare complication of phototherapy for neonatal jaundice is the bronze baby syndrome.1,2 Neonates with cholestatic jaundice who are receiving phototherapy may develop purpuric and bullous eruptions.3 Discord and severe blistering during phototherapy may signify congenital porphyria.1 Paller et al4 coined the term “purpuric phototherapy-induced eruption” in 1997 to describe a rare cutaneous complication of phototherapy in neonates with hyperbilirubinemia. All of the neonates received transfusions for hemolytic anemia prior to phototherapy. A blood transfusion was required in five of the six infants for erythroblastosis fetalis. In the sixth neonate, a twin-twin transfusion caused the hemolytic anemia. The photodistributed purpuric “raspberry”-induced eruption was noted at sites of exposure to the lights and spared shielded areas. Lesional skin biopsies revealed extravasated red blood cells, absent necrotic keratinocytes, and a sparse lymphocytic dermal infiltrate. An elevation in plasma porphyrins was noted in two patients. In all six neonates, the photodistributed eruption resolved spontaneously within one week after cessation of phototherapy. The authors speculate the feasibility of circulating porphyrins as the causative agent eliciting the skin rash. During follow-up periods ranging from four to six years, the patients developed no medical or cutaneous problems.4 The authors herein report a case of purpuric phototherapy-induced eruption in a transfused neonate.     

27 years of a single burn centre experience with Stevens–Johnson syndrome and toxic epidermal necrolysis: Analysis of mortality risk for causative agents

Introduction

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life threatening unwanted side effects, mainly from medication. Pathophysiology is still being debated. The disease usually requires treatment in burn units.

Patients and methods

In a retrospective study over 27 years we evaluated 72 patients admitted with SJS, SJS/TEN and TEN to our burns unit. Patients were evaluated for age, gender, total body surface area (TBSA) involved, causing agents, blood transfusion, dialysis, steroid administration, intubation, length of intensive care stay and death rate. Participants were grouped according to TBSA from 0 to 10, 11 to 30, and 31 to 100% and also into causing agent. Statistical analysis was done using a step-wise regression analysis. Because of small sample sizes for each drug group the percentage of related death rates for each drug group was calculated.

Results

The highest incidence of SJS and TEN was in the age group of 61–70 years. Overall mortality was 38%, mainly due to sepsis. For each subgroup SJS/TEN overlap had the highest mortality. The highest mortality for causing agents was found from antibiotic treatment, the lowest from using non-steroidal anti-inflammatory drugs. Most transfusions were done in the antibiotic group also the group underwent the highest number of dialysis events. Step-wise regression analysis identified dialysis, mechanical ventilation and age over 65 years as mortality high risk factors.

Conclusion

When SJS/TEN is caused by antibiotics suspicion of developing a fatal sepsis should be high. Patients’ medical condition when initiating therapy with a potential causing agent also might influence medical outcome.     

Increased risk of strontium ranelate-related SJS/TEN is associated with HLA

Summary

Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN.

Introduction

In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant.

Methods

Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles.

Results

Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n?=?76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n?=?5). The majority of the accrued samples were of Han Chinese descent: controls (n?=?72) and cases (n?=?4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p?=?0.002) and HLA-B*58:01 (p?=?0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles.

Conclusions

This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.

     

Lupus erythematosus with erythema multiforme (Rowell's syndrome). A case report

A patient who presented with erythema multiforme on clinical and histological examination but who subsequently developed fatal, fulminant systemic lupus erythematosus is reported. The prognostic significance of the development of erythema multiforme-type lesions in lupus erythematosus is discussed with reference to cases reported by Rowell et al. and Provost et al. The term 'Rowell's syndrome' is best avoided.     

Severe idiosyncratic drug reactions with epidermal necrolysis: A 5-year study

Introduction:

Idiosyncratic drug reactions (IDRs) are unexpected responses to a drug. The spectrums of severe cutaneous reactions include Stevens–Johnson Syndrome (SJS), SJS/Lyell Syndrome and Toxic Epidermal Necrolysis (TEN). The conditions are associated with high mortality. This study was designed to determine the causal agents, patterns of presentations, review the management and make recommendations to reduce the incidence and mortality of this class of drug reactions.

Materials and Methods:

A retrospective study was made of patients seen with IDR in the Lagos State University Teaching Hospital, LASUTH, between January, 2004 and December, 2008. They were cases admitted with bullous skin eruptions with associated systemic symptoms.

Results:

Sixty-seven patients were seen, with 45 (67.2%) satisfying the inclusion criteria. Fifteen males and 30 females were involved, giving a male to female (M:F) ratio of 1:2. Their ages ranged from 7 to 79 years (mean, 40.02 ± 17.89 years). Peak incidences occurred among the 20–24 and 30–34 year age groups. The causal agents were antibiotics (48.89%), sulphonamides (24.44%), herbal preparations (17.78%) and artemisinin drugs (8.89%).

Conclusions:

The age groups with the peak incidence are the most likely to indulge more in drug abuse in environments with poor drug control. Diagnosis of SJS, SJS/TEN and TEN were missed in many patients at first contact due to the progressive nature of the conditions. Patients needed reviews at regular intervals when IDR was suspected. Health education to prevent drug abuse is important and herbal preparations should be scientifically studied to determine the efficacy and side-effects.KEY WORDS: Idiosyncratic drug reactions, Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, toxic epidermal necrolysis     

Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: A regional burns centre experience

Introduction

Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially fatal desquamative disorders characterised by large areas of partial thickness skin and mucosal loss. The degree of epidermal detachment that occurs has led to SJS/TEN being described as a burn-like condition. These patients benefit from judicious critical care, early debridement and meticulous wound care. This is best undertaken within a multidisciplinary setting led by clinicians experienced in the management of massive skin loss and its sequelae. In this study, we examined the clinical outcomes of SJS/TEN overlap & TEN patients managed by our regional burns service over a 12-year period. We present our treatment model for other burn centres treating SJS/TEN patients.

Treatment of toxic epidermal necrolysis by a multidisciplinary team. A review of literature and treatment results

Background

Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are mucocutaneous hypersensitivity reactions, usually to drugs or their metabolites. TEN is the most severe involving greater than 30% of the total body surface area (TBSA). Management of these patients usually benefits from a large multidisciplinary team for both wound and medical management. Treatment of these patients varies between centers and physicians and there is lack of a standardized treatment protocol in the medical literature.

Lúpus eritematoso sistêmico bolhoso em gestante: relato de caso*

Systemic lupus erythematosus (SLE) can cause numerous skin lesions. Despite being rare, lupus-specifi c bullous lesions demonstrate characteristic clinical and immunopathological features and require differential diagnosis among numerous bullous conditions that may overlap with SLE. The present study presents a case of bullous systemic lupus erythematosus (BSLE) in a pregnant woman.     

Treatment of lupus erythematosus with pulsed dye laser

BACKGROUND AND OBJECTIVES: The treatment of cutaneous lupus erythematosus (CLE) with dye and argon laser has been evaluated in a number of articles in recent years. The improvement of telangiectasias and chronic erythema of the cutaneous lesions was based on the selective photothermolysis ablation of the dilated capillaries and venules. STUDY DESIGN/MATERIALS AND METHODS: We describe the results of the treatment of cutaneous lesions of 14 patients; eight with discoid lupus erythematosus (DLE) and six with systemic lupus erythematosus (SLE). Three patients received a treatment with flashlamp pulsed dye laser (FPDL) (585 nm, 450 microseconds) with fluences in the range from 5 to 7.75 J/cm(2); the other 11 patients were treated with long pulsed dye laser (LPDL) (595 nm, 1.5-10 milliseconds) with fluences in the range from 6 to 13 J/cm(2) depending on the pulse duration. RESULTS: During a median follow-up of 10 months, we observed an average improvement in over 60% of the lesions. A few side effects were observed in all patients: four had transient hyperpigmentation and one patient had light scarring. Three patients had a relapse after more than 1 year; they were then offered conventional treatment. CONCLUSIONS: We confirm that pulsed dye laser is a good alternative treatment for the erythema in active cutaneous lesions of lupus erythematosus (LE).     

Stevens-Johnson syndrome associated with intravenous acetazolamide administration for evaluation of cerebrovascular reactivity. Case report

A 62-year-old man with left middle cerebral artery stenosis manifesting as transient ischemic attack underwent evaluation of regional cerebrovascular reactivity to acetazolamide using single photon emission computed tomography. Three days after intravenous administration of acetazolamide, erythematous eruptions of various sizes appeared on his back and spread over almost his entire body. Subsequently, painful ulcerations developed on his lips, and oral and nasal mucosa, and the conjunctiva became hyperemic, indicating Stevens-Johnson syndrome. The results of the lymphocyte transformation test were positive to only acetazolamide. Stevens-Johnson syndrome, also known as erythema multiforme major, can be life-threatening, and may be induced by intravenous administration of acetazolamide.     

Nursing problems in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in a Dutch burn centre: A 30-year retrospective study

ObjectiveMultiple studies have been published on toxic epidermal necrolysis (TEN) and Stevens-Johnsen syndrome (SJS). Nursing care is an important part of the treatment of TEN patients. Unfortunately, limited information on nursing in TEN/SJS patients has been published in the current literature. Nursing research is needed to improve the complex nursing care required for these rare patients. Therefore, the objective was to assess nursing problems in TEN patients in a burn centre setting over a 30-year period.MethodsThe data for this study were gathered retrospectively from nursing records of all patients with TEN/SJS admitted to Burn Centre Rotterdam between January 1987 and December 2016. Dutch burn centres were recently accepted as expertise centres for TEN patients. Nursing problems were classified using the classification of nursing problems of the Dutch Nursing Society.ResultsA total of 69 patients were admitted with SJS/TEN. Fifty-nine patient files were available. The most frequently reported nursing problems (>20% of the patients) were wounds, threatened or disrupted vital functions, dehydration or fluid imbalance, pain, secretion problems and fever. Furthermore, TEN-specific nursing problems were documented, including oral mucosal lesions and ocular problems. The highest number of concomitant nursing problems occurred during the period between days three and 20 after onset of the disease and varied by nursing problem.ConclusionsThe most frequently reported nursing problems involved physical functions, especially on days three to 20 after onset of the disease. With this knowledge, we can start nursing interventions early in the treatment, address problems at the first sign and inform patients and their families or relatives of these issues early in the disease process. A next step to improve nursing care for TEN patients is to acquire knowledge on the optimal interventions for nursing problems.     

Early diagnosis is key in vancomycin-induced linear IgA bullous dermatosis and Stevens-Johnson syndrome

BACKGROUND: With the emergence of highly resistant beta-lactam gram-positive organisms, vancomycin hydrochloride usage has increased considerably. Consequently, adverse drug reactions, including unfavorable cutaneous events, have also increased. Important adverse skin reactions are linear IgA bullous dermatosis (LABD) and Stevens-Johnson syndrome (SJS). These blistering disorders can have clinical manifestations that are difficult to distinguish; however, it is important to make the distinction because treatment and prognosis are different. OBJECTIVE: The purpose of this study is to review the literature on LABD and SJS and compare important differentiating characteristics to assist physicians in making the correct diagnosis. METHODS: The authors used MEDLINE to search for all published studies on vancomycin adverse events, and combined LABD, SJS, exanthema, and skin rashes each separately with vancomycin adverse events. Furthermore, the authors searched PubMed for all meta-analyses and randomized controlled clinical trials relating to treatment of patients with SJS. RESULTS: Clinically, LABD and SJS both present similarly with bullae. Diagnosis is made by use of perilesional skin biopsy and direct immunofluorescence. Direct immunofluorescence shows linear IgA deposition along the basement membrane zone in LABD, whereas this is absent in SJS. The treatment for both vancomycin-induced SJS and vancomycin-induced LABD is prompt discontinuation of the drug. However, if SJS is diagnosed early, systemic corticosteroids appear to decrease morbidity. CONCLUSIONS: In cases of SJS or LABD that are difficult to distinguish clinically, the authors recommend performing a skin biopsy and direct immunofluorescence early to confirm the diagnosis so that effective treatment can be instituted.     

Stevens-Johnson syndrome in a boy with nephrotic syndrome during prednisolone therapy

Stevens-Johnson syndrome (SJS) is a mucocutaneous disease that can be lethal. It can occur in association with altered immunological conditions and the administration of various drugs, including corticosteroids. We report a case of SJS in a 14-year-old male with nephrotic syndrome, who was treated with oral prednisolone for 6 weeks. He presented symptoms of fever, skin lesions consisting of multiple vesiculopapular rashes, pruritic maculae and bullae, and mucosal involvement of the eyes, lips, oral cavity, and anorectal junction. His condition improved without complications following the discontinuation of oral prednisolone and replacement with intravenous methylprednisolone. Following the improvement of the symptoms of SJS, he received alternate-day oral prednisolone without any cutaneous eruption.     

Urticaria Multiforme

Urticaria multiforme is a benign cutaneous hypersensitivity reaction seen in pediatric patients that is characterized by the acute and transient onset of blanchable, annular, polycyclic, erythematous wheals with dusky, ecchymotic centers in association with acral edema. It is most commonly misdiagnosed as erythema multiforme, a serum-sickness-like reaction, or urticarial vasculitis. Since these three diagnoses represent distinct clinical entities with unique prognoses and management strategies, it is important that physicians distinguish urticaria multiforme from its clinical mimics in order to optimize patient care. By performing a thorough history and physical examination, the astute clinician can make the correct diagnosis and develop an appropriate, effective treatment plan while avoiding unnecessary biopsies and laboratory evaluations. The authors report a case of urticaria multiforme in a four-year-old girl in order to emphasize the distinctive morphological manifestations of this rare, albeit unique, disease seen in the pediatric population.Urticaria multiforme, a morphological subtype of acute urticaria, is a benign cutaneous hyper-sensitivity reaction predominantly mediated by histamine that is characterized by the acute and transient onset of blanchable, arcuate, annular, polycyclic, erythematous wheals with dusky, ecchymotic centers.1,2 Also known as acute annular urticaria or acute urticarial hypersensitivity syndrome, urticaria multiforme is commonly misdiagnosed as erythema multiforme, a serum-sickness-like reaction, or urticarial vasculitis.2 Although these different clinical entities may present in a similar manner, it is important for the physician to look for specific clinical features that help distinguish them since each represents a unique diagnosis with different prognoses and management approaches.3 Herein, the authors report a case of urticaria multiforme occurring in a four-year-old girl in order to emphasize the distinctive morphological manifestations of this rare, albeit unique, disease seen in the pediatric population.     

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS): experience with high-dose intravenous immunoglobulins and topical conservative approach. A retrospective analysis

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, drug-induced, severe acute exfoliative skin and mucosal disorders. Several treatments previously proposed have produced contradictory results in small series; in 1998 the use of intravenous immunoglobulins (IVIG) was introduced with excellent clinical findings. Our experience (1999-2005) using IVIG in the therapy of TEN/SJS, together with a local conservative approach, is reported and related to our previous treatments (1993-1998). The SCORTEN and the standardized mortality ratio (SMR) was used to evaluate the efficacy of our therapeutic modalities. Eight patients were treated before IVIG era and 23 patients have been treated with IVIG. There was no significant difference in SCORTEN between the two groups. Concerning the local approach, a conservative wound management in IVIG series replaced an extensive epidermal debridment and coverage with artificial skin substitutes of the pre-IVIG series. Overall mortality in patients treated before IVIG was 75% (6/8), in the IVIG group it decreased to 26% (6/23) with a cessation of further epidermal detachment after an average of 5 days (3-10 days) from the onset of the therapy. The SMR showed a trend to lower actual mortality (not significative) with IVIG treatment than the predicted mortality (SMR=0.728; 95% CI: 0.327-1.620).