Erythema multiforme in children.

QUESTION: Children who present with rashes with "target" lesions are frequently diagnosed with erythema multiforme (EM). This is a self-limiting condition in most children; how should primary care providers differentiate between this and urticaria or Stevens-Johnson syndrome, and what is the recommended course of treatment? ANSWER: While EM is common in children, urticaria is also very common and tends to be more "waxing and waning" compared with EM's fixed lesions. Stevens-Johnson syndrome and toxic epidermal necrolysis are more severe and distinct conditions; they have much more substantial mucous membrane involvement and contain widespread erythematous or purpuric macules with blisters. Since EM is a self-limiting condition, treatment of EM in children is generally supportive, and rarely do children need hospital admission for rehydration. In more severe cases involving mucous membranes or substantial pain, some patients will benefit from topical steroids or antihistamines. When children present with signs of herpes infection, antiviral treatment (acyclovir) may be of benefit. Systemic steroids should be reserved for the most challenging cases.

Vulvovaginal manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevention and treatment.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

A progressive and severe rash - Answers.

A 73-year-old female patient with epilepsy presented to hospital with a progressive, diffuse macular rash over the trunk and limbs with associated mucosal blistering and discharge. Ocular symptoms initially predominated and she was treated for presumed bacterial conjunctivitis by her General Practitioner the previous day. On the acute medical unit supportive management was initiated for suspected adverse drug reaction (ADR) to a recent lamotrigine dose increase. Skin biopsy confirmed a diagnosis of toxic epidermal necrolysis. We present this case to highlight the importance of medication history taking and raise awareness of indolent presentations of life-threatening ADRs. Caution should be applied following dose changes to anti-epileptics, even if previously stable.

Linear immunoglobulin A dermatosis mimicking toxic epidermal necrolysis: a case report of etanercept treatment.

A 65-year-old pluripathological woman attended our hospital with a cutaneous eruption of sudden appearance after vancomycin treatment. She presented targetoid lesions affecting approximately 25-30% of her body surface, large erosions with mucosal lesions and positive Nikolsky sign. Under the initial clinical suspicion of toxic epidermal necrolysis (TEN), and considering the recent literature of successful use of etanercept in these cases, she was treated with a single dose of this antitumour necrosis factor (anti-TNF) agent. Subsequently, the exanthema progression stopped and resolution of the lesions happened in a few days. Later on, histopathology revealed a subepidermal blister with dense neutrophilic infiltrate and linear deposits of immunoglobulin A (IgA) on the dermoepidermal junction, allowing us to establish the diagnosis of drug-induced linear IgA dermatosis mimicking TEN. Linear IgA dermatosis can have severe clinical manifestations, even mimicking TEN, and can have high mortality, especially in drug-induced cases. We have not found any other report of linear IgA dermatosis treated with etanercept in the English literature. Anti-TNF medications could represent useful therapeutic alternatives in this dermatosis.

Toxic Epidermal Necrolysis: A Dermatologic Emergency and the Role of the Oral and Maxillofacial Surgeon.

Toxic epidermal necrolysis (TEN) is a rare and severe mucocutaneous disorder characterized by mucosal and epidermal necrosis and sloughing. This potentially life-threatening condition, together with the less severe Stevens-Johnson syndrome, is commonly caused by an immunologic reaction to medications and can lead to many long-term complications. The disorder initially presents with fever, malaise, and painful mucosal ulcerations (most commonly oral) but progresses to widespread cutaneous lesions. A 14-year-old male patient was prescribed minocycline for treatment of his acne by his primary care doctor. Three weeks into the antibiotic treatment, he was admitted in distress, with a diagnosis of Stevens-Johnson syndrome that subsequently progressed to TEN. We present a discussion of the importance of early recognition and diagnosis of this condition by oral and maxillofacial surgeons and a description of our patient's treatment and management during his hospital stay.

Severe delayed skin reactions related to drugs in the paediatric age group: A review of the subject by way of three cases (Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS).

Severe delayed drug-induced skin reactions in children are not common but potentially serious. This article describes aspects concerning the etiology, pathogenesis and clinical manifestations of these processes; it presents three paediatric cases, namely STS (Steven Johnson Syndrome), TEN (toxic epidermal necrolysis), probably related to amoxicillin/clavulanate and ibuprofen and DRESS (a drug reaction with eosinophilia and systemic symptoms) secondary to phenytoin; and in relation to them, the diagnosis and the treatment of these processes are discussed and reviewed. The AGEP (acute generalised exanthematous pustulosis) is also reviewed. The aetiological diagnosis of severe non-immediate reactions is difficult, and the value of current allergological testing is not well defined in these cases. Diagnosis is based on clinical history, the empirical risk of drugs to trigger SJS/TEN or DRESS, and the in vivo and in vitro testing of the suspect drug. Skin biopsy confirms that the clinical diagnosis and delayed hypersensitivity tests, especially the patch test and the lymphoblastic transformation test (LTT), may be important to confirm the aetiological diagnosis, in our cases emphasising the latter. These diseases can be life threatening (especially DRESS and TEN) and/or have a high rate of major complications or sequelae (SJS/TEN). The three cases described progressed well without sequelae. All were treated with corticosteroids, which is the most currently accepted treatment although the effect has not been clearly demonstrated.

Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna. A case report of a patient with seronegative rheumatoid arthritis and rheumatoid vasculitis.

Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent.

Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review.

BACKGROUND: Mycoplasma pneumoniae infection is associated with extrapulmonary complications, including mucocutaneous eruptions. These eruptions, which have been termed either "Stevens-Johnson syndrome" or "erythema multiforme" in the literature, may differ from drug-induced Stevens-Johnson syndrome or viral-associated erythema multiforme. OBJECTIVE: We sought to review the literature characterizing morphology and disease course of M pneumoniae-associated mucocutaneous disease. METHODS: A comprehensive literature search identified 95 articles with 202 cases. RESULTS: Patients were often young (mean age: 11.9 years) and male (66%). Cutaneous involvement ranged from absent (34%), to sparse (47%), to moderate (19%). Oral, ocular, and urogenital mucositis was reported in 94%, 82%, and 63% of cases, respectively. Treatments included antibiotics (80%), systemic corticosteroids (35%), supportive care alone (8%), and/or intravenous immunoglobulin (8%). Complications included mucosal damage (10%), cutaneous scarring (5.6%), recurrence (8%), and mortality (3%). LIMITATIONS: Mild cases may not have been published; thus this review may have a bias toward more severe disease. CONCLUSION: M pneumoniae-associated mucocutaneous disease has prominent mucositis and sparse cutaneous involvement, although cutaneous involvement varies. Because of the distinct morphology, mild disease course, and potentially important clinical implications regarding treatment, we propose a revision of the nomenclature system and suggest the term "Mycoplasma-induced rash and mucositis" for these cases.

[Severe drug-induced skin reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis]. / Schwere arzneimittelinduzierte Hautreaktionen. Stevens-Johnson-Syndrom und toxisch epidermale Nekrolyse.

Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are characterized by extensive blistering of the skin and mucosa; they are considered as one disease entity with varying severity. They are rare but potentially life-threatening and accompanied by high mortality. A clear clinical diagnosis is needed to direct specific therapy, but supportive therapy remains most important. In order to identify and withdraw the inducing drug, a very detailed and thorough medication history has to be obtained. Among the highly suspected (strongly associated) agents are allopurinol, antibacterial sulfonamides, non-steroidal anti-inflammatory drugs of the oxicam type, various anti-epileptics and nevaripine. Together they account for more than half of the cases of SJS/TEN. Although a drug is not always the cause, it is considered very like in approximately 75% of cases. Infections have also to be considered as etiologic factors.

Systemic lupus erythematosus presenting as Stevens-Johnson syndrome/toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like lesions in acute cutaneous lupus erythematosus [LE]) are an unusual manifestation of systemic LE. We describe a patient with widespread vesiculobullous lesions diagnosed as SJS/TEN-like acute cutaneous LE as the initial presentation of systemic LE. Stevens-Johnson syndrome/TEN-like LE may be differentiated from other vesiculobullous lesions by factors including a history of recent LE exacerbation, photodistribution of lesions, lack of a precipitating infection or medication exposure, minimal mucosal involvement, a prolonged course, response steroid treatment, and histologic and immunofluorescence findings. It is paramount to identify SJS/TEN-like LE as this condition requires early and aggressive intervention. The optimal treatment approach for SJS/TEN-like LE is unclear, and although some case reports have shown glucocorticoids to be useful, there are also reports of cases in which additional measures, such as intravenous immunoglobulin and plasmapheresis, were required to achieve a response. Our patient's condition was refractory to high-dose corticosteroids and intravenous immunoglobulin but was successfully treated using plasma exchange. As such, this treatment may hold potential for improving the care of other patients with refractory SJS/TEN-like LE.

Stevens-Johnson syndrome complicating adalimumab therapy in rheumatoid arthritis disease.

The efficacy of adalimumab, a fully human anti-tumor necrosis factor-α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with rheumatoid arthritis (RA). In this case report, a 53-year-old woman with RA developed severe mucositis, peripheral rash and desquamation and fever concomitant with the fifth dose of 40 mg adalimumab. Infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Severe skin reactions induced by TNF-α antagonists can be very serious, and prescribers need to be aware of the potential for the mucocutaneous adverse effects from the use of these agents, particularly due to the significant morbidity and mortality that are associated with SJS.

Febrile ulceronecrotic Mucha-Habermann disease (pityriasis lichenoides et varioliformis acuta fulminans) presenting as Stevens-Johnson syndrome.

We present two pediatric patients with pityriasis lichenoides et varioliformis acuta fulminans whose admitting diagnosis was Stevens Johnson Syndrome. The patients were successfully treated with methotrexate and prednisone. These cases highlight the importance of early recognition and treatment of this disease to prevent further morbidity and a potentially fatal prognosis.

Mycoplasma pneumoniae and mucositis--part of the Stevens-Johnson syndrome spectrum.

BACKGROUND: Mycoplasma pneumoniae may induce mucosal inflammation, referred to as M. pneumoniae-associated mucositis (MPAM). There is no generally accepted definition of MPAM, since there may be mucosal lesions only, or mucosal and minimal skin lesions. PATIENTS AND METHODS: We conducted a literature review of MPAM, paying particular attention to pathogenesis, clinical manifestations, treatment decisions, and prognosis. RESULTS: We identified 32 cases of MPAM (median age 13.5 years), whereof 23 patients were otherwise healthy children and young adolescents (72%). M. pneumoniae infection was associated with fever and respiratory symptoms in all calls; it was confirmed by serology (n = 30) and/or PCR (n = 9). Oral lesions were present in all cases, followed by ocular (97%) and uro-genital lesions (78%). Despite the syndrome's name postulating the absence of cutaneous involvement, minimal skin lesions occurred in 31%. Treatment regimens included systemic antibiotics (100%) and systemic anti-inflammatory treatment with corticosteroids (31%) or immunoglobulins (9%). Macrolides were given in 81%, with failure, relapse, and/or worsening in one-third of patients. No patient suffered long-term sequelae. CONCLUSION: MPAM is a distinct extra-pulmonary manifestation falling into the continuum of Stevens-Johnson syndrome. This entity may be due to inflammatory mechanisms suggesting that systemic anti-inflammatory treatment is even more important than antimicrobials.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions that are medication-induced in most instances. While the clinical manifestations of SJS and TEN are well-defined, the optimal treatment for these disorders is not. Case reports have shown benefit with the use of a variety of agents including tumor necrosis factor-alpha inhibitors and cyclophosphamide, whereas thalidomide was associated with an increased mortality. Plasmapheresis and cyclosporine have also demonstrated efficacy anecdotally, albeit with an even smaller number of cases in the literature. Most of the reporting has focused on the use of systemic corticosteroids and intravenous immunoglobulin (IVIG) for these severe reactions. The majority of studies analyzing the use of IVIG in the treatment of SJS/TEN show a benefit, though more recent series cast doubt upon this conclusion. The results of these studies are summarized in this present review study.

Toxic epidermal necrolysis with prominent facial pustules: a case with reactivation of human herpesvirus 7.

A 37-year-old Japanese man presented with confluent erythemas and progressive erosive lesions on the almost entire body including the oral mucosa and genitalia. This was accompanied with prominent facial pustules. Although a lymphocyte stimulation test was positive only for acetaminophen, he took other agents including carbamazepine for his depression. He was diagnosed as having toxic epidermal necrolysis with prominent facial pustules and treated by methylprednisolone pulse therapy, which resulted in a good response. During the course, human herpesvirus 7 (HHV-7) DNA was detected in his peripheral blood. The HHV-7 reactivation might be related to facial pustulosis, which is occasionally observed in drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms.

Erythematous and bullous rash strongly indicating toxic epidermal necrolysis associated with the use of intravenous ritodrine hydrochloride.

Toxic epidermal necrolysis (TEN) is a very rare drug reaction associated with a high mortality rate. This condition warrants prompt recognition, diagnosis and treatment. Only one case report of TEN that was possibly induced by ritodrine hydrochloride, a tocolytic agent, was found in English literature. Here, we report the case of a 26-year-old pregnant woman who was suspected with TEN following the intravenous administration of ritodrine hydrochloride in the 35(th) week of gestation. An emergency cesarean section was performed because the labor pains caused systemic intolerable haphalgesia. After the surgery, intensive dermatological treatment commenced, which helped her recover from the serious condition. The result of the drug-induced lymphocyte stimulation test for ritodrine hydrochloride was positive. When a skin eruption appears during the administration of ritodrine, we must consider the benefits as well as the risks of continuous use of tocolytic agents because there is a risk of Stevens-Johnson syndrome or TEN.