Infliximab-induced amicrobial pustulosis of the folds in a patient with Crohn disease.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Evaluating the nature and prevalence of glucocorticoid-induced type 2 diabetes mellitus in patients with autoimmune bullous diseases.

Glucocorticoid use in patients with autoimmune bullous disease is associated with significant morbidity, and in some cases, excess mortality. The hyperglycaemic complications arising from glucocorticoid use have been well-documented and range from mild hyperglycaemia to diabetic ketoacidosis. Patients with pre-existing glucose intolerance or type 2 diabetes mellitus are at increased risk of developing complications. Several other factors have been investigated for their association with steroid-induced hyperglycaemia, including patient age, sex, family history, dose, regimen and duration of therapy. Findings in the current literature, however, are largely conflicting and evidence is limited by methodological weaknesses. Glucocorticoids should be used with caution, and patients using steroids should be closely monitored for adverse effects.

Bullous hemorrhagic dermatosis: A rare cutaneous reaction of heparin.

Bullous hemorrhagic dermatosis is a rare cutaneous reaction of heparin, a commonly used anticoagulant. Exact etiopathogenesis remains elusive but immune related mechanisms as well as dose dependent relationship have been proposed. Clinically, it is characterized by asymptomatic, tense hemorrhagic bullae on extremities or abdomen occurring 5-21 days after initiation of therapy. We report bilateral symmetrically grouped lesions, in a previously unreported distribution of this entity in both the forearms in a 50-year-old male admitted with acute coronary syndrome on oral ecosprin, oral clopidogrel and subcutaneous enoxaparin. The condition is self-resolving and discontinuation of drug is not required.

Pustular lesions in patients with Crohn disease and treatment with tumour necrosis factor-α inhibitors.

We present seven new cases of patients with Crohn disease who developed lesions clinically compatible with amicrobial pustulosis of the flexures during their treatment with anti-tumour necrosis factor therapy.

A 62-year-old man with new-onset bullae.

Cutaneous blisters and/or bullae can occur in autoimmune disorders, infections, genetic diseases, and drug hypersensitivity. We present the case of a 62-year-old man with two autoimmune conditions who was admitted for antibiotic treatment of a lower extremity infection and suddenly developed a bullous rash. His physical examination was significant for tense, bullous lesions that involved his chin, palms, and inner thighs. Narrowing the differential diagnosis for patients with blistering skin lesions is imperative for timely and appropriate management.

Acute generalized exanthematous pustulosis due to Epstein-Barr virus infection in a neonate.

Acute generalized exanthematous pustulosis (AGEP) is an uncommon inflammatory subcorneal pustular dermatosis typically caused by exposure to a medication. Several viral infections have also been implicated in its development. We describe herein a rare case of AGEP associated with acute Epstein-Barr virus (EBV) infection in a neonate.

Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature.

Gefitinib is a selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) used for the treatment of malignant neoplasms. The most frequent skin complication during gefitinib therapy is an acneiform papulopustular eruption, usually distributed in the seborrheic areas but occasionally widespread. We report a patient with erosive pustular dermatosis of the scalp, a neutrophil-mediated skin disease presenting with sterile pustules evolving into erosions and crusts on the scalp, during treatment with the EGFR inhibitor gefitinib for lung cancer. A literature review of the drug-induced cases of this rare entity is provided.

Bullous Drug Reactions.

Bullous drug eruptions are infrequent, but because they pose a challenge both to affected patients and to treating physicians they are considered to be the most severe cutaneous adverse reactions (SCAR). It is important to recognize these conditions and to differentiate them from other clinical entities involving blister formation. There may be early signs and symptoms that indicate a severe bullous drug eruption even before blisters and erosions of the skin and mucous membranes become obvious. Once the diagnosis is suspected, appropriate diagnostic procedures and adequate management must be initiated. The latter includes identification of the potentially inducing drug, although it should be taken into account that not all cases of bullous eruptions are drug-induced. In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately. In addition to best supportive care, immunomodulating therapy may be considered.

Bullous lichen planus and anti-programmed cell death-1 therapy: Case report and literature review.

BACKGROUND: Cutaneous adverse effects of immunotherapies are being seen with increasing frequency in general practice. While anti-PD1 lichenoid reactions are well known, only a few cases of bullous lichen planus have so far been reported in the medical literature. Herein we described a case of secondary bullous lichen planus associated with nivolumab and we present a systematic review of all anti-P1-induced cases reported in the literature. PATIENTS AND METHODS: Three months after beginning treatment with nivolumab for metastatic clear-cell renal carcinoma, a 68-year-old man presented pruritic purplish papules on his limbs that subsequently became bullous. Clinical-histological correlation led us to a diagnosis of secondary bullous lichen planus induced by nivolumab. Systemic steroids and withdrawal of immunotherapy resulted in clinical improvement. REVIEW OF THE LITERATURE: Our systematic review revealed 20 cases of lichen planus induced by anti-PD1 (nivolumab and pembrolizumab) published between 2016 and 2018, 6 of which were of the bullous form. Treatment and maintenance or discontinuation of anti-PD1 were dependent on severity. DISCUSSION: Bullous lichen planus has been reported only rarely in the context of nivolumab therapy. The timeline for development of cutaneous adverse reactions under anti-PD1 immunotherapy may last weeks or months and regular monitoring is required. Withdrawal of immunotherapy should only be considered where the outcome under systemic corticosteroids is unfavourable.

[Hemorrhagic bullous dermatosis (HBD): A rare side-effect of heparins]. / Dermatose bulleuse hémorragique (DBH) : un effet indésirable rare des héparines.

BACKGROUND: Bullous haemorrhagic dermatosis (BHD) induced by heparin is a rare and benign side effect of which we report two cases. PATIENTS AND METHODS: Case 1: an 81-year-old man presented haemorrhagic bullae on the limbs and trunk 7 days after starting enoxaparin. The laboratory haemostasis assessment was normal. A diagnosis was made of BHD induced by enoxaparin and the patient's treatment was switched to apixaban, resulting in a favourable outcome with resolution of the lesions within 15 days. Case 2: a 71-year-old woman hospitalised for pulmonary embolism was given tinzaparin. At two months of treatment, haemorrhagic bullae were observed on her forearms at distance from the injection sites. A diagnosis of BHD induced by tinzaparin was made. Treatment with tinzaparin was continued and the lesions resolved within 15 days. DISCUSSION: Heparin-induced BHD is a rare entity initially described in 2006. Ninety-five cases of heparin-induced BHD have been reported. It is characterized by multiple haemorrhagic bullae at a distance from the injection sites. Time to onset of lesions after heparin initiation ranges from 24h to 4 months. Laboratory assessment should be routinely performed to rule out any haemostasis disorders. Lesions subside within 15 days whether heparin is continued or withdrawn. CONCLUSION: Heparin-induced BHD is a rare but benign side effect of heparins. In the absence of recommendations, therapeutic management should be adapted to the individual situation.

[DRESS syndrome with pustules and cardiac impairment]. / DRESS avec pustulose et atteinte cardiaque.

INTRODUCTION: An original case of DRESS syndrome is reported herein with a particular cutaneous presentation and etiology. OBSERVATION: A 52-year-old man developed a febrile pustular rash after being treated with methotrexate and celecoxib for inflammatory rheumatism and with amoxicillin-clavulanic acid over the previous 2 days. Eighty percent of his body surface was covered with pustular infiltrated plaques. On the following days, the patient developed persistent fever, with polyadenopathy, hepatic cytolysis, eosinophilia, interstitial lung disease and cardiac involvement. Cutaneous biopsy was consistent with a drug eruption. Epstein Barr Virus PCR was positive. A diagnosis of DRESS syndrome was made with a RegiSCAR score above 5. Systemic corticosteroids were given, resulting in cessation of the fever and complete recovery with regard to dermatosis, laboratory abnormalities and cardiac function. DISCUSSION: The present case is original, with a febrile pustular eruption mimicking acute generalized exanthematous pustulosis and cardiac anomalies with electrical changes and impairment of ventricular function. Epstein Barr Virus may have played a role in the presentation. No previous cases of DRESS syndrome caused by methotrexate have been described. Amoxicillin was probably not involved in the present case of DRESS syndrome as it was taken for only two days, but its role as a co-factor in association with the EBV viral reactivation should not be ruled out. CONCLUSION: We report an original case of DRESS syndrome in terms of pustular cutaneous presentation and cardiac impairment. EBV reactivation associated with amoxicillin may be suspected.

Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy.

BACKGROUND: Bullous disorders associated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established. OBJECTIVE: To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-PD-1/PD-L1 therapy. METHODS: We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. RESULTS: We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were treated with an-PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression. LIMITATIONS: This was a retrospective study from a single tertiary care center. CONCLUSIONS: Bullous disorders developed in approximately 1% of patients treated with anti-PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.

Heparin-induced haemorrhagic bullous dermatosis.

BACKGROUND: Heparin-induced haemorrhagic bullous dermatosis (HBD) is a rare but probably underdiagnosed reaction to heparin, with 26 cases reported in the English literature. Currently, there is no consensus regarding the treatment. AIM: To assess our new cases of HBD and review the previously reported cases, in order to draw conclusions about this adverse skin reaction to heparin. METHODS: A PubMed search was performed for articles containing the terms '(heparin-induced AND (blister OR bulla OR bullae)) OR (hemorrhagic bullous dermatosis AND heparin) OR heparin bullous dermatosis'. Descriptive statistical data analysis was performed using Microsoft Excel. RESULTS: We assessed five new cases of HBD. In addition, our literature search revealed 26 previously reported patients. Combining these, we found that the mean ± SD age of patients with HBD was 71.4 ± 14 years. HBD affects men more commonly than women (men 22/31; P = 0.02). Patients develop tense bullae most frequently on the extremities, approximately 8 days (mean ± SD 7.5 ± 6.4 days) after starting treatment with a heparin product, usually enoxaparin. CONCLUSIONS: The typical clinical course is spontaneous resolution within days to weeks irrespective of continuation of heparin therapy. Because of its self-limiting nature, interruption of heparin therapy may not be required.

Bullous Fixed Drug Eruption Caused by Doxycycline.

A 50-year-old woman presented to our dermatology clinic with pruritic lesions on her hands that had appeared 24 hours earlier. The clinical manifestations had started 24 hours after taking 100 mg of doxycycline for acute bronchitis. She had no history of allergic disease or allergic reactions to drugs. The dermatologic examination revealed multiple erythematous, purplish annular patches with overlying bullae with hemorrhagic content on both palms (Figure 1). The patient had no fever, and the rest of the physical examination did not reveal any abnormalities. Results of laboratory tests were within normal limits. A skin biopsy was performed, showing hydrophic degenerations of the basal membrane, a superficial perivascular infiltrate consisting of lymphocytes and eosinophils, and red blood cells in the dermis (Figure 2). A pharmacovigilance investigation was conducted, and doxycycline was confirmed as the agent responsible for the bullous fixed drug eruption (FDE) in our patient.

Pheniramine maleate: an apparently safe drug causing bullous fixed drug eruption.

Fixed drug eruption is a delayed type hypersensitivity reaction to a drug seen most frequently with antibiotics such as tetracyclines, sulfonamides, and NSAIDs such as naproxen and ibuprofen. Although H1-antihistamines rarely elicit cutaneous adverse effects, there have been a few reports in the literature implicating them in causing fixed drug eruption, particularly the piperazine derivatives (hydroxyzine, cetirizine, levocetirizine), and loratadine. However, cutaneous drug reactions with the alkylamine derivatives like pheniramine maleate are extremely uncommon and fixed drug eruptions have not been reported with any of the alkylamine antihistamines to date. We herein report a case of multifocal bullous fixed drug eruption following ingestion of pheniramine maleate.

Pseudo-Bullous Dermatosis Induced by Topical Anesthetic Agent-Clues to This Localized Toxic Reaction.

Eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA AstraZeneca, DE) is a widely used topical anesthetic cream for preprocedural cutaneous analgesia. In addition to potential clinical cutaneous and systemic adverse effects, EMLA may also induce microscopic changes detectable by light and electron microscopy leading to difficulty in accurate diagnosis. We report the case of a biopsy demonstrating EMLA-induced histopathologic changes. The biopsy was taken from the back of a 5-month-old infant and submitted to rule out psoriasis. Hematoxylin and eosin (H&E) staining of the biopsy demonstrated spongiosis and a noninflammatory subepidermal bulla, raising the histopathologic possibility of epidermolysis bullosa. Further investigation confirmed that EMLA was applied under occlusion before biopsy. A second biopsy without topical anesthetic did not demonstrate a bulla and supported the clinical diagnosis of psoriasiform dermatitis. Our case highlights the importance of awareness of EMLA-induced histopathologic changes to avoid potential misdiagnosis. The histopathologic findings of this case in conjunction with other previously reported cases of EMLA-induced bullae were analyzed. Vacuolization of the basal and suprabasilar layer, pallor and swelling of upper layer epidermal keratinocytes, a pauci-inflammatory cleavage beneath or within the basal layer, basophilic granular karyorrhectic debris in the subepidermal cleft, and congestion of papillary dermal vessels characterized the biopsy findings of this localized adverse reaction.