Drug patch testing in Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review.

BACKGROUND: The data on patch testing (PT) to identify culprit medications in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are limited to scattered case reports and small case series, without analysis of overall trends to inform clinicians of its utility, methodology, and safety. OBJECTIVE: To conduct a systematic review of the practice of PT in SJS/TEN, quantify the positivity rate of common drug classes, and assess safety during testing. METHODS: PubMed was searched from inception to 2021. Search terms included "patch testing" AND "SJS" OR "TEN" OR "Stevens-Johnson syndrome" OR "toxic epidermal necrolysis" OR "Lyell's syndrome." RESULTS: There were 58 articles that met the inclusion criteria. In total, 82 patients underwent patch testing for SJS/TEN, resulting in 104 positive reactions to 49 unique medications. Antiepileptic drugs were responsible for 48.1% of the positive reactions; antibiotics, 28.8%; and nonsteroidal anti-inflammatory drugs, 6.7%. The positivity rates of antiepileptics, antibiotics, and nonsteroidal anti-inflammatory drugs were 33.1%, 13.1%, and 21.9%, respectively. When accounting for suspected causality, these rates increased to 54.3%, 78.4%, and 54.5%, respectively. Three patients (3.7%), 2 of whom had human immunodeficiency virus infection and active tuberculosis, experienced systemic reactions during PT, which required only conservative treatment. CONCLUSION: Published reports suggest that PT in SJS/TEN is useful and safe. Antiepileptic drugs have been tested most frequently and found to have the highest positivity rate. There is a critical need for large-scale studies with standardized methodology to obtain reproducible data on PT in SJS/TEN.

Lucio phenomenon with concomitant necrotizing fasciitis and acute kidney injury.

Lucio phenomenon is a rare vasculopathy that can occur in patients with Hansen disease, particularly diffuse lepromatous leprosy. It is characterized by retiform purpura and necrotic ulcerations, most commonly affecting the extremities. Diagnosing Lucio phenomenon can be challenging, especially when secondary bacterial infections occur. We report a patient with Lucio phenomenon who presented with acute necrotizing fasciitis of his left upper extremity and a 10-year history of chronic ulcerations. Shortly following admission, he also developed acute kidney injury. The necrotizing fasciitis was treated with prompt surgical debridement and intravenous antibiotics. Biopsy and PCR of a right upper extremity ulcer confirmed the presence of Mycobacterium lepromatosis. Multidrug therapy and prednisone were used to treat the Lucio phenomenon. After initiating treatment, no new lesions developed, kidney function improved, and the patient underwent successful skin graft of his left upper extremity. Although corticosteroid use is controversial, our patient's marked response to multidrug therapy with prednisone highlights the importance of this regimen in severe presentations of Lucio phenomenon. To the best of our knowledge, only two other cases of Lucio phenomenon confirmed to be caused by M. lepromatosis have been reported in living patients (rather than retrospectively identified post-mortem), underscoring the importance of the presented clinical course and treatment regimen.

Use of teledermatology by dermatology hospitalists is effective in the diagnosis and management of inpatient disease.

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Sweet syndrome as an adverse reaction to tyrosine kinase inhibitors: A review.

Tyrosine kinase inhibitors are a class of targeted anticancer drugs that inhibit cancer cell proliferation by inactivating proteins involved in signal transduction cascades. Various cutaneous adverse events have been observed after tyrosine kinase inhibitor administration, including Sweet syndrome. We queried the PubMed database to identify 14 cases of Sweet syndrome thought to be secondary to tyrosine kinase inhibitors. Tyrosine kinase inhibitor-induced Sweet syndrome had a median of 2 months latency following drug administration. All cases but one had morphologic features classic for Sweet syndrome (erythematous and tender papules, plaques, or nodules). All cases also had classic histopathologic findings (dermal neutrophilic infiltrate without vasculitis or necrosis). Using diagnostic criteria for drug-induced Sweet syndrome and the Naranjo Drug Reaction Probability Scale for a drug-induced cutaneous eruption, we found that six cases favored a drug-induced etiology over malignancy, two cases favored a malignancy-associated Sweet syndrome, and the remaining eight met drug-induced Sweet syndrome criteria but had low Naranjo scores. Nine cases resulted in medication discontinuation, while five cases continued anticancer therapy and were treated only with corticosteroids with quick resolution of skin lesions. Dermatologists should be aware of this adverse cutaneous reaction to tyrosine kinase inhibitors and should treat on a case-by-case basis, though limited evidence in this review suggests that oncologic therapy may safely be continued with prompt corticosteroid treatment.

Cutaneous manifestations of COVID-19.

The severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has infected patients worldwide. Physicians have increasingly identified cutaneous findings as a significant clinical manifestation of COVID-19. In this review, we describe the clinical presentation, onset, duration, associated symptoms, treatment, and outcome of cutaneous manifestations thus far reported to be related to COVID-19. We have included data from 63 studies and subdivided reported cutaneous manifestations into the categories of viral exanthem, urticarial, vesicular, chilblains/chilblains-like, non-chilblains vasculopathy-related, pityriasis rosea-like, erythema multiforme-like, Kawasaki/Kawasaki-like disease, and others. Physicians should be aware of the known common cutaneous manifestations of COVID-19 and future research is required to better understand the pathophysiology and prognosis of each COVID-19-related skin manifestation.

Bullous Pemphigoid and Malignancy in Two Different Hospital Populations: A Retrospective Cohort Review.

BACKGROUND: Bullous pemphigoid (BP) is a rare autoimmune blistering condition characterized by antibodies to the structural proteins BP1 and BP2 at the dermal-epidermal junction. The link between BP and malignancy remains unclear. Due to the rarity of the disease, there have been few studies with small sample sizes characterizing the association between BP and malignancy. OBJECTIVES: There were two main goals of this retrospective cohort study: (1) to look at the associated risk of malignancy in patients with BP compared to controls and (2) to compare the rates of malignancy in two separate hospitals with differing patient populations. METHOD: We reviewed the medical records of 99 patients diagnosed with BP observed between 2014 and 2019. 66 patients were from Keck Hospital and 33 were from Los Angeles County/University of Southern California (LAC/USC) Hospital. Each patient was age- and sex-matched to a control from the same hospital. RESULTS: Malignancies occurred in 26 BP patients and 29 controls. 7 of the BP patients from LAC/USC Hospital (21.2%) and 19 patients from Keck Hospital (28.8%) had malignancies. CONCLUSIONS: Overall, we did not find an increased risk of malignancy in BP patients compared to controls, nor did we find a statistically differing rate of malignancy in BP patients from various socioeconomic and ethnic backgrounds.

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

Herpes associated erythema multiforme: A retrospective study.

BACKGROUND: Erythema multiforme (EM), an acute dermatologic condition frequently encountered in the Emergency Department, classically presents with a targetoid rash. We reviewed all recent EM cases seen at the LAC-USC County Hospital in order to ascertain the proportion of Herpes associated EM (HAEM) cases and to inform the diagnostic workup of these patients. METHODS: ICD-9 and ICD-10 codes were used to extract a list of EM cases at our institution from 2013 to 2019. Two non-blinded abstractors screened records to confirm an EM diagnosis and entered patient data utilizing a standardized data abstraction form. Cohen's kappa statistic was used to measure inter-rater reliability on various variables. Kappa (κ) values ranged from 0.803 to 1.0. RESULTS: 70 pediatric and 56 adult EM patients were included in the study. A likely etiology was ascribed to 63% of pediatric and adult EM cases. Pediatric EM was most commonly attributed to upper respiratory infection (URI) (n = 23; 33%), Mycoplasma pneumoniae infection (n = 5; 7%), and medications (n = 4; 6%). Adult EM was most commonly attributed to HSV infection (n = 11; 20%), medications (n = 5; 9%), URIs (n = 4; 7%), and other infections (n = 4; 7%). CONCLUSION: HSV-1/2 serologic testing should be considered in most EM patients to potentially prevent repeated ED visits. In EM cases not clearly attributable to herpes or drug exposure, physicians can consider further workup: Mycoplasma serology, nasal PCR, and a respiratory viral panel in pediatric patients. Identification of an etiologic cause may suggest a different treatment approach and prevent mislabeling of medication allergies in patient charts.

Thiotepa hyperpigmentation preceding epidermal necrosis: malignant intertrigo misdiagnosed as Stevens-Johnson syndrome-toxic epidermal necrolysis overlap.

Thiotepa is a common alkylating agent known to precipitate cutaneous reactions consistent with toxic erythema of chemotherapy, including erythema and hyperpigmentation. Herein, we describe an atypical case of malignant intertrigo involving preferential erythema and desquamation not only of skin folds but also of occluded areas after thiotepa-based conditioning. The diagnosis was complicated by concurrent stomatitis and oral petechiae in the setting of autologous stem cell transplant 11 days prior for diffuse large B-cell lymphoma. Histopathological examination from two cutaneous sites demonstrated epidermal dysmaturation and eccrine gland necrosis consistent with thiotepa-induced desquamation and not Stevens-Johnson syndrome or graft-versus-host-disease. Malignant intertrigo can present with extensive cutaneous involvement, as evidenced by our patient who had 25% body surface area affected. Mucosal involvement is common with most chemotherapeutic regimens and its presence should not deter the astute clinician from consideration of a diagnosis of toxic erythema of chemotherapy. No further interventions were needed and the patient healed spontaneously.

Corrigendum: Thiotepa hyperpigmentation preceding epidermal necrosis: malignant intertrigo misdiagnosed as Stevens-Johnson syndrome-toxic epidermal necrolysis overlap.

The original article was published on February 15, 2020 and corrected on March 15, 2020.The revised version of the article corrects the contact information of the Corresponding Author. The changes appear in the revised online PDF copy of this article.

Neutrophilic dermatoses as adverse effects of checkpoint inhibitors: A review.

Checkpoint inhibitors are a new class of drugs that enhance the immune system's intrinsic ability to destroy tumor cells by blocking signaling through the programmed cell death (PD-1) receptor, its ligand (PD-L1), and the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). The resulting increase in immunologic activity is responsible for a variety of adverse cutaneous reactions, which sometimes include neutrophilic dermatoses. We queried the PubMed database for existing cases of checkpoint inhibitors causing neutrophilic dermatoses. The literature search identified four cases of Sweet syndrome, four cases of pustular eruptions, two cases of pyoderma gangrenosum, and one case of bullous lupus erythematosus secondary to checkpoint inhibitors. All neutrophilic dermatoses were treated with topical or systemic steroids and most (9 of 11) completely resolved. Dermatologists should be aware of these rare, adverse cutaneous reactions to checkpoint inhibitors and how to approach their treatment, especially as their use increases.

Dupilumab in Dermatology: Potential for Uses Beyond Atopic Dermatitis

Dupilumab inhibits the interleukin-4 receptor subunit α and is FDA approved for treatment of moderate-to-severe atopic dermatitis. It is a relatively new drug, and whether it is efficacious for other diseases in dermatology is an area of increasing interest. We searched the literature and ClinicalTrials.gov database for uses of dupilumab beyond atopic dermatitis in dermatology and for ongoing studies on new uses for dupilumab. Off-label reports identified described use of dupilumab for several different dermatologic conditions, including allergic contact dermatitis, hand dermatitis, chronic spontaneous urticaria, prurigo nodularis, and alopecia areata. Overall, there is limited but promising data for dupilumab use beyond atopic dermatitis in dermatology. The relatively safe adverse effect profile of dupilumab may make it an option for certain recalcitrant diseases in dermatology, but further studies will be needed to assess its efficacy and determine its best possible use. J Drugs Dermatol. 2019;18(10):1053-1055.

Verrucous venous malformation.

Verrucous venous malformation, also known as verrucous hemangioma, is a superficial vascular malformation with a variable degree of hyperkeratosis that is composed of capillaries and veins in the dermis and sometimes subcutaneous tissue. We describe a 53-year-old man who presented with a large hyperkeratotic plaque of the left dorsal and plantar foot. Biopsy revealed verrucous acanthosis of the epidermis and a proliferation of thin-walled vessels in the dermis. We provide a brief review of the clinical and histopathologic presentation, differential diagnosis, and management of this rare entity.

Twenty-year-old woman presenting with typical Kawasaki disease.

We describe adult-onset Kawasaki disease (KD) and review clinical manifestations and treatment guidelines. Our patient is a 20-year-old female who initially presented to an outside hospital for fever, cervical lymphadenopathy, malaise, exudative tonsillitis, and skin eruption. She received antibiotics for suspected exudative pharyngitis, but experienced continued fevers and presented to the UCLA emergency room one week later. She had diffuse petechial macules coalescing into reticulated patches, fingertip peeling, conjunctival injection, oral erosions, and tongue swelling. Despite her age, given her constellation of symptoms, a diagnosis of typical KD was favored. She was started on high dose aspirin and IVIG, with improvement of rash and conjunctivitis. She was discharged on 325mg of aspirin daily with close follow-up. This case highlights the challenge of diagnosing KD in adults. Although this patient had classic symptoms, she was likely misdiagnosed because KD is rare in adults and without validated criteria. Our patient met the pediatric criteria, suggesting these should be considered when clinical suspicion for adult-onset KD is high. Adult-onset KD is most commonly misdiagnosed as toxic shock syndrome or drug-induced hypersensitivity syndrome and these are important to rule-out. Treatment with high-dose aspirin and IVIG is well established and should be initiated promptly.

The use of etanercept for treatment of toxic epidermal necrolysis when toxic shock syndrome is in the differential.

Toxic shock syndrome (TSS) can sometimes mimic Steven Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN). Tumor necrosis factor (TNF) alpha is thought to play a role in the pathogenesis of both TSS and SJS/TEN. Etanercept, a TNF-alpha inhibitor has been recently shown to treat and decrease mortality of SJS/TEN. We report a 51-year-old female with history of SJS presenting with painful skin and bullae 2 days following cystoscopy with botulinum toxin injection into the bladder. Due to initial concern for SJS/TEN, the patient was treated with 50 mg of subcutaneous etanercept. Punch biopsies were not consistent with SJS, and the patient fulfilled five out of five criteria for a confirmed case of TSS. The patient ultimately had a favorable outcome despite etanercept treatment. Ultimately, TNF-alpha antagonists are an emerging therapy to treat SJS/TEN, and are unlikely to worsen TSS prognosis. Given that etanercept can be used to successfully treat SJS/TEN and TNF-alpha levels are elevated in TSS, if a dermatologist chooses to treat TEN with etanercept, consideration of TSS on the differential should not necessarily exclude etanercept as a reasonable treatment option.

Successful Treatment of Severe Alopecia Areata With Oral or Topical Tofacitinib.

Alopecia areata is an autoimmune disease involving the hair follicle with a chronic, relapsing course. Tofacitinib is Janus kinase inhibitor approved for treatment of rheumatoid arthritis that has been shown to be effective in treatment of alopecia areata. We present a case series of 11 patients with severe alopecia areata on longstanding, regular to high dose oral tofacitinib with marked hair regrowth. Additionally, we present a case of moderate to severe alopecia areata successfully treated with topical tofacitinib cream. J Drugs Dermatol. 2018;17(7):800-803.

Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm.

A 10-year-old girl with a history of blastic plasmacytoid dendritic cell neoplasm, a rare malignancy in children, presented with recurrent skin eruptions beginning while on maintenance chemotherapy, including mildly pruritic skin-colored plaques, tender indurated nodules, and violaceous bound-down plaques. This case highlights an unusual presentation of relapsed blastic plasmacytoid dendritic cell neoplasm on chemotherapy, with skin lesions providing important clues to the progression of systemic disease.