Bullous Eruption Research Articles

Dermatomyosite amyopathique avec anticorps anti-MDA-5, associée à une pemphigoïde bulleuse, un syndrome de Sjögren et un lymphome de type MALT

The inflammatory myopathies are a heterogeneous group of muscle diseases and comprise polymyositis, dermatomyositis (DM), myopathies associated with cancers, necrotising myositis and inclusion body myositis. DM occasionally exhibits few or no muscular signs: i.e. hypomyopathic/amyopathic DM. Anti-MDA5 dermatomyositis (DM) is a rare form of dermatomyositis that is frequently amyopathic; the prognosis is linked mainly to pulmonary involvement. A 69-year-old woman treated for mucosa-associated lymphoid tissue (MALT) gastric lymphoma was referred for a bullous eruption. Based on the investigations performed, a diagnosis was made of bullous pemphigoid. At the same time, amyopathic dermatomyositis was discovered together with interstitial lung disease. Systemic steroids were introduced in combination with rituximab. A favourable outcome was achieved. Anti-MDA5 dermatomyositis must be considered systematically in all cases of pulmonary involvement associated with cutaneous signs of dermatomyositis, in which no muscular involvement is generally seen. This condition accounts for up to 7% of DM and carries a severe prognosis due to pulmonary involvement.

Severe generalized bullous drug eruption secondary to alemtuzumab (Lemtrada)—Outcome of re-exposure

Severe generalized bullous drug eruption secondary to alemtuzumab (Lemtrada)—Outcome of re-exposure

Nivolumab-induced bullous lichenoid drug eruption

Nivolumab-induced bullous lichenoid drug eruption

Clinical Case of Toxic Epidermal Necrolysis

Abstract Toxic epidermal necrolysis or Lyell’s syndrome is a severe life-threatening adverse drug reaction with a high mortality rate. The drugs most commonly involved are: antibiotics; anticonvulsants; antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol. Case report: A 68-year-old female, presented with complaints of fever and extensive rashes on the skin of the face, the neck and the trunk, severe itching of the skin, ulcerations and erythema of the conjunctiva and the oral cavity and difficulty in swallowing. She has a period of two or three days of general discomfort and fatigue, rash, fever up to 38°C, sore throat, arthralgia, myalgia, loss of appetite and have been treated with antipyretics, antibiotic – ampicillin, antihistamines, vitamins. Her state worsened during the next 3 days, therefore she was hospitalized in the Toxicology clinic of University Hospital “N. I. Pirogov”. Multiple maculopapular and bullous eruptions, plaques were present all over the body, blisters that cover a substantial portion of the body. The entire skin covering the body surface was denuded and peeled off with minor manipulation – the Nikolsky’s sign. Intraorally, multiple oral ulcers of the buccal mucosa, tongue, palate, labial mucosa, and soft palate were seen. Hemorrhagic erosions were also seen on both the upper and lower lips. Conjunctivitis and ulceration of genitalia were also noted. The lesions got slowly better with serum therapy, fluid and electrolyte replacement, systemic corticosteroids, antihistamines, antibiotic, vitamins, H2 blockers, topical care of mucosal changes. Evolution was satisfactory with epidermization and the patient was discharged from the hospital after 1 month.

Generalized Bullous Drug Eruption to Faropenem - Hitherto Unreported.

Generalized Bullous Drug Eruption to Faropenem - Hitherto Unreported.

Illustration of diagnostic and prognostic difficulties during the early stages of generalized bullous fixed drug eruptions

Bullous drug eruptions are infrequent and potentially serious situations. Bullae are characteristic of two main diagnoses: the spectre of toxic epidermal necrolysis (TEN), the most serious, and the bullous fixed drug eruption (FDE); even if other severe drug reactions can sometimes be bullous. The FDE exceptionally occurs as a bullous and generalized form in western countries [1, 2]. Early recognition is necessary because of a potential emergency situation. The distinction between these two entities [...]

Triggers of exanthematous drug eruptions: Stop intake, treat through or desensitization?

Drug hypersensitivity reactions affect over 7% of the population and are problematic both for patients and doctors. They frequently occur in the form of exanthematous drug eruptions. The clinical manifestation of delayed hypersensitivity reactions is very variable ranging from localized fixed drug eruptions to life-threatening, severe bullous mucocutaneous eruptions or systemic drug hypersensitivity syndromes. In the case of suspicion of an exanthematous drug eruption, the causality should initially be assessed according to the proposed algorithm. If both the chronology and the clinical symptoms are indicative of adelayed drug hypersensitivity reaction, the suspected drug should be avoided. Only in cases of urgent therapeutic indications and if alternative drugs are not available, the options of "treating through" and temporary tolerance induction by "desensitization" should be considered after an individual risk-benefit analysis.

IgA pemphigus showing IgA antibodies to desmoglein 1 and 3.

BackgroundIgA pemphigus is a rare autoimmune vesiculo-pustular skin disease. Only approximately 70 cases have been reported to date. We report a case of IgA pemphigus with IgA antibodies to desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3).Case reportWe report the case of an 60-year-old man with intraepidermal neutrophilic IgA pemphigus with IgA antibodies to Dsg1 and Dsg3. Histologic examination revealed subcorneal neutrophilic pustules with few acantholytic cells. The disease was not effectively controlled by conventional therapeutic regimens (colchicine, dapsone). Systemic treatment with isotretinoin 25 mg/d and prednisone 20 mg/d achieved only a slight effect after six months.ConclusionsOur case confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this type of pemphigus is needed. Physicians should keep IgA pemphigus in mind when approaching patients with bullous eruption.

Mastocytose cutanée diffuse du nourrisson : à propos d’un cas

Mastocytosis is a group of diseases related to abnormal accumulation and proliferation of mast cells in one or more organs. They may be associated with an acquired point mutation and the activation of the receptor tyrosine-kinase c-KIT of CFS (mast cell growth factor). The clinical manifestations are varied and secondary to the release of mast cell mediators and/or infiltration of various organs. There are two main types of mastocytosis: pure cutaneous mastocytosis and systemic mastocytosis when more than two organs are involved in mast cell infiltration (bone marrow, gastrointestinal tract, bone, liver and spleen, lymph nodes). Mastocytosis affects children in two thirds of cases, most frequently as an isolated cutaneous form. The most common clinical form in children is urticaria pigmentosa and solitary mastocytoma; bullous diffuse mastocytosis is rare. We report the case of an 8-month-old infant who presented with a diffuse pruritic bullous eruption. The histology and immunohistochemistry results were suggestive of mastocytosis. A serum tryptase test yielded positive results. Laboratory investigations did not identify systemic involvement. The patient was given antihistamine H1 medication and local care. Advice regarding the disease was offered to the parents. The course of the disease was marked by a decrease in the number of blisters and attenuation of the pruritus at the 6-month follow-up. This observation emphasizes the importance of awareness of this rare entity, which should be considered in all cases of bullous dermatosis in children, thereby allowing for early treatment.

Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy.

Immunotherapy has experienced impressive progress in cancer treatment. Antibodies against PD-1 improved survival in different types of cancer including melanoma. They are generally well tolerated. However, skin toxicities including pruritus, rashes, and vitiligo are reported. Although frequent, they have not been characterized further yet. In this analysis, we aimed to systematically assess and characterize the adverse cutaneous reactions observed in patients with melanoma treated with anti-PD-1 antibodies. Patients with melanoma were treated with anti-PD-1 antibodies within clinical trials and an early-access program. Adverse cutaneous eruptions that emerged in our melanoma patient cohort were systematically investigated and classified using histology and gene expression profiling in comparison with maculopapular drug rash, cutaneous GVHD, and the severe drug eruption toxic epidermal necrolysis (TEN). Between February 2013 and September 2015, 68 patients with stage IV melanoma were treated at the University Hospital Zurich (Zurich, Switzerland); 15 patients (22%) developed cutaneous reactions and 10 (15%) vitiligo. The cutaneous reactions ranged from small erythematous papules with mild pruritus to disseminated erythematous maculopapular rashes (MPR) without signs of epidermal involvement to severe MPRs, including epidermal detachment and mucosal involvement. Although skin involvement varied from mild rash to bullous drug eruptions, gene expression profiling pathogenically classified all investigated cases as TEN-like reactions. As predicted by the PD-1 knockout mouse, anti-PD-1 antibodies frequently cause adverse cutaneous reactions. Gene expression profiling reminds in all cases of a TEN-like pattern, suggesting that PD-1/PD-L1 interaction is required to preserve epidermal integrity during inflammatory skin reactions. Clin Cancer Res; 22(16); 4023-9. ©2016 AACR.

Toxic Epidermal Necrolysis-Like Cutaneous Lupus in Pediatric Patients: A Case Series and Review.

Bullous eruptions in patients with underlying systemic lupus erythematosus (LE) can mimic toxic-epidermal necrolysis (TEN), a rapidly progressive mucocutaneous reaction usually associated with medication use. Differentiating between classic drug-induced TEN and TEN-like cutaneous LE is important but difficult. We report a series of 3 patients with pediatric systemic LE who were admitted with severe worsening of skin disease resembling TEN. However, the initial photo-distribution of the eruption, subacute progression, limited mucosal involvement, mild systemic symptoms, supportive biopsy and laboratory results, and lack of culprit drugs was more suggestive of a TEN-like cutaneous LE. These patients recovered with various systemic immunosuppressive medications including methylprednisolone, intravenous immunoglobulin, and plasmapheresis. Our cases are rare and demonstrate key clinical and histologic features of TEN-like cutaneous LE in young patients and the importance of differentiating this entity from drug-induced TEN.

Syndrome de Lyell à l’acide fusidique oral d’évolution fatale

Herein, we report the first case of toxic epidermal necrosis due to oral fusidic acid having a fatal outcome. An 82-year-old woman was referred to our dermatology department for generalized bullous skin eruption. Clinical examination showed fever, oral and ocular ulcerations, and epidermal detachment involving more than 70 % of her body surface area together with a positive Nikolsky sign. Lyell's syndrome was diagnosed. Cutaneous histology showed total epidermal necrosis and a normal dermis. Oral fusidic acid had been prescribed 12 days earlier for a chronic sacral pressure sore. No other treatment had been introduced during the previous two months. The outcome was fatal within 24 hours. Fusidic acid is commonly used topically by dermatologists for limited staphylococcal skin infections. Oral treatment is rare and is recommended only for skin, bone or joint infections. This is the first reported case of toxic epidermal necrolysis due to oral fusidic acid. The French national drug safety monitoring register contains only one case in which fusidic acid was a possible culprit. Fusidic acid must be considered a potential source of serious cutaneous adverse reactions, particularly toxic epidermal necrolysis.

Low Molecular Weight Heparin Induced Bullous Hemorrhagic Dermatosis

Heparin-induced bullous hemorrhagic dermatosis is a rare, recently described side-effect of subcutaneous heparin injection. We present a case of a male patient with a bullous hemorrhagic eruption following the administration of subcutaneous LMWH. A diagnosis of Heparin-induced bullous hemorrhagic dermatosis was made by HPE (Histopathological examination) of tissue biopsy from the bullous lesion and the exclusion of other laboratory finding.

Bullous Wells’ syndrome

Wells’ syndrome (WS) is an uncommon inflammatory skin disease which typically presents single or multiple erythematous and edematous urticarial plaques similar to cellulitis. The lesions may evolve into blue-grey morphea-like lesions and may persist for weeks or months. They ultimately heal without scar. Other clinical presentations reported in literature include papular and nodular and, rarely, bullous eruptions. Previously, bullous Wells’ syndrome was rarely reported in the literature. Herein, we describe a case of a female patient with bullous Wells’ syndrome localized to the upper limbs without any associated disorders.

Stevens-Johnson Syndrome-Like Skin Lesions in a Patient with Juvenile Systemic Lupus Erythematosus.

Dear Editor: Skin manifestations in systemic lupus erythematosus (SLE) are very heterogeneous. Recently, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like lupus erythematosus (LE) has been reported. Clinically, this condition presents with photodistributed exanthema and minimal mucositis. The onset of the rash is insidious with a prolonged clinical course1. A 16-year-old Korean woman presented with a 4-week history of gradually progressive development of painful, annular, erythematous, flattened, and blistering eruptions. Crusting presented on the face, V-neck area, upper back, and dorsum of the hands, and involved less than 10% of body surface area. The lips had erosions and crusts (Fig. 1). Eye and genital examinations were unremarkable. Previous medical history included malar rash and diffuse alopecia. No relevant medications had been newly administered. Fig. 1 Photodistributed erythematous flattened vesiculobullous eruptions with crusts on the face, V-neck area and the dorsum of hands and erosion on the lips. Skin biopsy from the back revealed a subepidermal blister with exocytosis and superficial perivascular infiltration of lymphocytes and neutrophils. Marked necrosis of keratinocytes of the suprabasal layer and interface dermatitis were manifested (Fig. 2). Direct immunofluorescence microscopy was remarkable in that linear deposits of immunoglobulin G, C3, and C1q were shown at the basement membrane zone. Fig. 2 Subepidermal blister with exocytosis and superficial perivascular infiltration of lymphocytes and neutrophils, marked necrosis of keratinocytes of the suprabasal layer and interface change (H&E, ×100). Laboratory investigations demonstrated anemia (hemoglobin 10.9 g/dl), leukopenia (3,600/mm3), and a normal platelet count. The antinuclear antibody titer was positive (1:640 homogeneous pattern), anti-double-stranded DNA was positive, anti-Ro/SS-A was positive and anti-La/SS-B was negative. Anti-Sm was positive, anti-nucleosome, anti-histones, and rheumatoid factor were negative. C3 and C4 levels were markedly low at 47.2 g/dl and 13.6 g/dl, respectively. Plasma creatinine was 0.65 mg/dl and the 24-hour urine proteinuria was 1,589 mg/day. Lupus nephritis class IIA was diagnosed from kidney biopsy. Liver function tests were unremarkable. Eventually, SJS-like cutaneous presentation with juvenile SLE was diagnosed based on the above findings. Treatment regimen included oral hydroxychloroquine 200 mg, deflazacort 48 mg per day with gradual tapering. Lesions improved after dressing on the denuded area and applying topical corticosteroid. Skin is the second most commonly affected organ system in SLE2. A bullous eruption in the setting of SLE can be a diagnostic challenge. Classic SJS/TEN, SJS/TEN-like LE, drug-induced cutaneous LE, bullous LE, Rowell's syndrome, and immunobullous diseases need to be considered in the differential diagnosis3. Indirect immunofluorescence is an effective method to diagnose bullous LE, but the present patient did not undergo this test. However, bullous LE appears with various-sized tense blisters, which is clinically different from the patient's presentation. Usually, SJS/TEN-like LE develops as a result of severe inflammatory epidermal basal layer damage. Vacuolar degeneration leads to subepidermal blistering and almost full-thickness epidermal necrosis1,4. SJS/TEN-like LE is often triggered by excessive ultraviolet exposure with an underlying predisposition to SLE. These patients often have anti-Ro antibody. Anti-Ro may be associated with increased risk of photosensitive rash4. The standard treatment of SJS/TEN-like LE remains controversial. Corticosteroids were prescribed in the present case because of continuing lupus activity. Chloroquine was combined for immunomodulation. In previous reports of TEN-like acute cutaneous LE, intravenous immunoglobulin, and plasmapheresis were successful5. To our knowledge, SJS-like skin lesions with juvenile SLE have rarely been reported in the literature. This was the first case reported in Korea.

Bullous, Multifocal Fixed Drug Eruption to Pseudoephedrine: A Case Report

Adverse reactions to medications are extremely common and display a characteristic clinical morphology including fixed drug eruption (FDE), urticaria, Stevens-Johnson syndrome, hypersensitivity syndrome, morbilliform exanthem, pigmentary changes and so on. Fixed drug eruption is commonly seen with antimicrobials and analgesics. Here we report a case of a 45 year-old male who presented to us with multiple bullous eruptions over the trunk, upper limbs and thighs after repeated doses of pseudoephedrine.

Fluconazole induced multifocal bullous eruptions: a case report

Fluconazole induced multifocal bullous eruptions: a case report

Bullous Fixed Drug Eruption Probably Induced by Paracetamol.

We report a case of a 42-year-old male who presented with second episode of bullous eruptions after ingestion of paracetamol. There were no systemic complaints. The temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous fixed drug due to paracetamol. Applying Naranjo's algorithm, a causality score of 8 was obtained and was categorized as probable reaction to paracetamol. Clinicians should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Drug alert cards could play an important role in preventing recurrences.

Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection.

Background and ObjectiveSpontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection.MethodsA signal detection strategy, focused on a limited set of adverse events deemed important in pharmacovigilance, was performed retrospectively in two data sources—(1) the Exploring and Understanding Adverse Drug Reactions (EU-ADR) database network and (2) the EudraVigilance database—using data between 2000 and 2010. Five events were considered for analysis: (1) acute myocardial infarction (AMI); (2) bullous eruption; (3) hip fracture; (4) acute pancreatitis; and (5) upper gastrointestinal bleeding (UGIB). Potential signals identified in each system were verified using the current published literature. The complementarity of the two systems to detect signals was expressed as the percentage of the unilaterally identified signals out of the total number of confirmed signals. As a proxy for the associated costs, the number of signals that needed to be reviewed to detect one true signal (number needed to detect [NND]) was calculated. The relationship between the background frequency of the events and the capability of each system to detect signals was also investigated.ResultsThe contribution of each system to signal detection appeared to be correlated with the background incidence of the events, being directly proportional to the incidence in EU-ADR and inversely proportional in EudraVigilance. EudraVigilance was particularly valuable in identifying bullous eruption and acute pancreatitis (71 and 42 % of signals were correctly identified from the total pool of known associations, respectively), while EU-ADR was most useful in identifying hip fractures (60 %). Both systems contributed reasonably well to identification of signals related to UGIB (45 % in EudraVigilance, 40 % in EU-ADR) but only fairly for signals related to AMI (25 % in EU-ADR, 20 % in EudraVigilance). The costs associated with detection of signals were variable across events; however, it was often more costly to detect safety signals in EU-ADR than in EudraVigilance (median NNDs: 7 versus 5).ConclusionAn EHR-based system may have additional value for signal detection, alongside already established systems, especially in the presence of adverse events with a high background incidence. While the SRS appeared to be more cost effective overall, for some events the costs associated with signal detection in the EHR might be justifiable.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-015-0341-5) contains supplementary material, which is available to authorized users.

Generalized bullous fixed Drug eruption: a case series

Generalized bullous fixed drug eruption (GBFDE) is a rare and severe form of fixed drug eruption (FDE) that may be misdiagnosed with other forms of bullous drug eruptions (BDE). Herein, we report three cases of GBFDE.