Vacuolar Interface Dermatitis Research Articles

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

Clinically amyopathic dermatomyositis: Clinical, laboratory, and histopathological features.

Despite the advancements in the categorization of clinically amyopathic dermatomyositis (CADM), the classification and diagnosis of its subtypes are still challenging. The aim of our study was to describe the clinicopathological features of CADM and assess the differences between amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). This retrospective study included 43 patients with CADM diagnosed at our institution from 2016 to 2020. Patients were subclassed into ADM (n = 30) and HDM (n = 13) groups to assess their clinicopathological differences. All included patients had characteristic cutaneous manifestations of dermatomyositis; 67.4% had myositis-associated auto-antibodies, including ANA (32.6%), RNP (14.0%), anti-Ro52 (9.3%), anti-p155/140 (7.0%), rheumatoid factor (7.0%), anti-NXP-2 (4.7%), anti-MDA5 (2.3%), and anti-Jo-1 (2.3%) antibodies. One patient had associated interstitial lung disease, and another patient had oral squamous cell carcinoma. The histopathological findings included mucin deposition (69.8%), telangiectasia (65.1%), lymphocytic infiltrate (48.8%), vacuolar interface dermatitis (46.5%), and epidermal atrophy (14.0%). Compared to patients with HDM, ADM patients were significantly less likely to have epidermal atrophy, 3.3% versus 38.5% (p = 0.006), and more likely to have mucin deposition, 80.0% versus 46.2% (p = 0.028). We described the clinicopathological features of CADM and highlighted the distinctions between ADM and HDM dermatopathologic findings. This information may prove helpful in diagnosing ambiguous lesions.

Expanding the Histologic Spectrum of Sudden Conjunctivitis, Lymphopenia, and Rash Combined With Hemodynamic Changes.

Sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes (SCoRCH) is a recently described hypersensitivity reaction to trimethoprim-sulfamethoxazole. To date, only 1 case of histologic findings in SCoRCH has been reported, revealing a superficial perivascular dermatitis. In this article, we present a 53-year-old woman with a four-day history of a widespread, confluent, erythematous, and dusky rash after exposure to trimethoprim-sulfamethoxazole. Histologic examination revealed a vacuolar interface dermatitis with several apoptotic keratinocytes at multiple levels of the epidermis, similar to an erythema multiforme-like presentation. As described in SCoRCH, our patient's clinical findings rapidly improved within 48 hours of presentation without treatment. This case adds to the current literature by identifying a newly described histopathological presentation of SCoRCH.

33372 A case of systemic lupus erythematous presenting with macrophage activation syndrome

A 36-year-old male with no significant medical history presented with at least 1 month of intermittent fevers, diffuse arthralgias, malaise, and weakness. During this timeframe, he was treated for possible infectious etiologies without clinical improvement. Ultimately, he was admitted after his wife found him unable to converse normally. Initial workup revealed hyperferritinemia (>40,000), elevated anti-dsDNA serologies, and other diagnostic criteria consistent with acute systemic lupus erythematous (SLE). Dermatology was consulted as well as Rheumatology and Nephrology. On examination, there were scaly, red/violaceous papules and plaques in a photodistribution most prominent over the malar cheeks, forehead, and ears. In addition, there were numerous follicularly-based vesicles over all four extremities and tender erythematous macules involving the palms and soles. Two punch biopsies were obtained (one for H&E and one for immunofluorescence (IF)) which illustrated an intense vacuolar interface dermatitis with dyskeratotic epidermal cells, but a negative IF study. Nephrology performed a renal biopsy which revealed a “full house” staining (IgM, IgG, IgA, C3, and C1q all positive) on IF confirming the diagnosis of lupus. The patient was started on high-dose steroids, hydroxychloroquine, and mycophenolate mofetil with minimal improvement. After discussion with Hematology, a bone marrow biopsy was performed which revealed evidence of hemophagocytosis confirming a diagnosis of macrophage activation syndrome. After prolonged high-dose corticosteroids coupled with other therapies, the patient’s clinical picture improved. We present this patient to highlight a rare complication of SLE as well as underscore the importance of collaborative efforts between different specialties in improving patient outcomes.

33379 Melanophages save the day: A case of generalized bullous fixed drug eruption

A 29-year-old female was seen via inpatient dermatology consultation for acute erosive stomatitis. Upon admission for sickle cell crisis, the patient had an incidental urinary tract infection and was treated with trimethoprim-sulfamethoxazole for 3 days. On physical examination, she had painful superficial erosions of the upper and lower mucosal lips extending onto the vermillion as well as the distal and ventral tongue. Five large dusky violaceous plaques with overlying superficial erosions were seen on the bilateral proximal medial thighs, arms and on the left lateral abdomen. Punch biopsy of the violaceous plaques revealed a vacuolar interface dermatitis with full thickness necrosis overlying an inflammatory infiltrate with occasional interstitial eosinophils and many melanophages at the level of the superficial vascular plexus. While the pathologic differential diagnosis included EM as well as SJS/TEN, the melanophages, eosinophils and clinical findings favored a diagnosis of generalized bullous fixed drug eruption (GBFDE) secondary to trimethoprim-sulfamethoxazole. GBFDE is a particularly severe variant of FDE which often includes mucosal erosions. Differentiation from SJS/TEN may sometimes be clinically and histologically difficult, and patients may suffer high morbidity and mortality. In our patient, we treated aggressively and cautiously with IV methylprednisolone followed by oral prednisone with no disease progression and eventual complete resolution. The clinical findings suggestive of FDE along with dermal melanophages and eosinophils allowed a cautious but confident diagnosis of GBFDE without need for transferring our patient to a burn unit.

Histopathological and clinical correlation of cutaneous adverse drug reaction

<p><strong>Background:</strong> The aim was to study the histopathological features of cutaneous adverse drug reactions (ADRs) and its correlation to clinical presentation.</p><p><strong>Methods:</strong> We carried our study on 80 patients of drug reactions presented in OPD over a period of 24 months. We noted offending drug, time gap between drug intake and appearance of lesion clinically and performed biopsy to study histopathological patterns and their utility as an aid to diagnosis. WHO-UMC causality assessment method was used in few cases with due diligence. AGEP (acute generalized exanthematous pustulosis) validation score of the EuroSCAR study group was used and SCORTEN for prognosis of SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis). Histopathological correlation and clinical correlation were statistically analysed.</p><p><strong>Results:</strong> The most common histopathological finding was vacuolar interface dermatitis and presence of eosinophils. The most common drug responsible was antimicrobials. Histopathological findings were most consistent in cases of FDE and AGEP and differentiating viral exanthems from maculopapular rash was challenging. Erythroderma showed varying patterns of histopathology</p><p><strong>Conclusions:</strong> Identification of histopathological patterns and clinical correlation is important for distinguishing between cutaneous ADR and the other inflammatory dermatoses. Drug reactions pose clinical challenge thus clinicopathological correlation can help in reaching diagnosis.</p>

Periorbital rash and scaly plaques in a 13-year–old boy

Periorbital rash and scaly plaques in a 13-year–old boy

Do histopathological features correlate with systemic manifestations in dermatomyositis? Analysis of 42 skin biopsy specimens from 22 patients.

Understanding whether specific histopathologic features on skin biopsy are predictive of systemic associations in dermatomyositis (DM) would be useful to guide clinical screening. Through retrospective medical record search, clinical and laboratory findings of patients with DM were documented. Existing skin biopsy slides were re-reviewed blindly. Of all biopsy specimens (n=42), the most frequent histopathological finding was vacuolar interface dermatitis (95%). Other features included perivascular lymphocytic infiltrate (71%), increased dermal mucin (40%), vessel wall thickening (12%), follicular plugging (9.5%), and dermal sclerosis (7%). Neutrophilic infiltrate was observed in three biopsies from a patient with adalimumab-associated DM. Vasculitis was not observed. There was no statistically significant difference in the presence of any histopathological feature and that of various systemic manifestations (i.e., myopathy, interstitial lung disease [ILD] and malignancy). However, we observed that dense lichenoid infiltrate rather than pauci-inflammatory changes correlated with severe itching (p < 0.001). Patients with MDA-5 antibodies were significantly more likely to have vasculopathy than those without (p= 0.029*). No dermatopathologic feature was reliably predictive of myopathy, ILD, or malignancy. This finding implies that, regardless of histopathologic findings, patients should be screened for associated conditions as clinically indicated.

Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis.

The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP.

25656 Vulvar discoid lupus erythematosus: An unusual site for cutaneous lupus erythematosus

A 46-year-old woman presented with a 1-month history of a pruritic rash on trunk and face. On examination, she had well-defined erythematous scaly thin plaques photodistributed on the face, chest, ears, and neck. Biopsy demonstrated an interface dermatitis with increased dermal mucin. Laboratory evaluation was remarkable for a positive ANA 1:1280, but negative Ro/SS-A and La/SS-B antibodies. She was diagnosed with subacute cutaneous lupus erythematosus on the basis of clinical-pathologic findings. Tobacco cessation and strict sun protection were recommended, and she was prescribed hydroxychloroquine 200 mg twice daily and topical triamcinolone ointment. She was lost to follow-up during the COVID pandemic but was seen 6 months later with a persistent painful eruption of the vulva of several months’ duration. The patient had been hospitalized for this eruption and surgical debridement was performed which revealed a nonspecific neutrophilic infiltrate and tissue necrosis. Immunohistochemistry stain was negative for herpesvirus. She was treated with intravenous antibiotics and referred back to us. Upon her return visit, she had stopped smoking but was only taking hydroxychloroquine 200 mg daily. On examination, she had scarred erythematous patches on the labia minora and inguinal folds. Biopsy demonstrated a vacuolar interface dermatitis with superficial epidermal necrosis, dermal edema, and superficial and deep perivascular and periappendageal lymphoplasmacytic inflammation, favoring a diagnosis of discoid lupus erythematosus. We recommended increasing the hydroxychloroquine to 200 mg twice daily and continuing topical triamcinolone ointment.

Erythema Multiforme and its Clinicopathological Features in a Horse in Brazil

Background: Erythema multiforme (EM) is an immune-mediated skin disease which may manifest as cutaneous or mucocutaneous lesions. It is uncommon in horses. EM lesions have a symmetrical bilateral distribution; they are usually urticarial, necrotizing, and, less commonly, ulcerative. In equines, the trigger is usually unknown, and cases are often classified as idiopathic. Diagnosis is based on a thorough history and physical and histopathological examination of lesions. According to the clinical presentation and histopathological characteristics of the cutaneous lesions, this case is the first report to describe diagnosis and treatment of a horse with EM in Brazil. Case: A Quarter Horse filly was followed clinically for 12 months after sudden onset of skin lesions at 18 months of age. The initial lesions were non-alopecic papules with a symmetrical bilateral distribution. Six months after onset, the skin lesions maintained the original distribution pattern; however, they had progressed to papules and plaques with varying annular, arciform, serpiginous, targetoid, or alopecic appearance. At 8 months, the same distribution pattern and appearance remained, but the lesions had become more severe and extensive, with involvement of the labial commissures and perineal region, without any erosions/ulcerations, scaling/crusting, pain, or pruritus. At 12 months, new nodular lesions were found on the medial and lateral surfaces of the hind limbs, neck, bilateral trunk, and root of the tail. The lesions were firm, non-pruritic, and non-tender on palpation. Swabs were obtained from the papular lesions. Skin specimens were also obtained with a 6-mm punch and via incisional biopsy and histological sections were made. Bacterial and fungal cultures were negative. Appropriate stains did not identify fungal structures, were negative for acid-fast bacilli, and did not reveal any metachromatic granules in the sampled cell population. The histopathological findings were characteristic of immune-mediated disease, with a vacuolar interface dermatitis affecting the hair follicles more than the epidermis, necrotic keratinocytes, lymphocyte satellitosis, leukocytoclastic mixed vasculitis of the mid-dermis and deep dermis, and variable granulation tissue, consistent with erythema multiforme and leukocytoclastic vasculitis. Immunosuppressive therapy with corticosteroids and oral supplementation with omega-3 and omega-6 fatty acids and vitamin E were prescribed. After institution of therapy, no new lesions developed, the existing lesions remained stable (though permanent), and hair regrew in the previously alopecic areas. All physiological parameters remained normal throughout the follow-up period. Discussion: Erythema multiforme is rarely reported in horses. According to our literature review, this is the first description of EM in horses in Brazil. EM should be included in the differential diagnosis of horses that present with plaques in a diverse, geographic distribution and a negative initial dermatological screening examination. Further clinical investigation is warranted, with special attention to potential antigenic triggers. A thorough drug and dietary history and close attention to comorbidities are essential, as the suppression of potential culprit factors has important prognostic value and contributes to the elucidation of EM triggers.

Clinicopathologic characterization of enfortumab vedotin-associated cutaneous toxicity in patients with urothelial carcinoma

Clinicopathologic characterization of enfortumab vedotin-associated cutaneous toxicity in patients with urothelial carcinoma

15397 Paraneoplastic dermatomyositis in a patient with an oligodendroglioma

A previously healthy 26-year-old white man presented with nausea, headache, and rash. Physical examination disclosed coalescing, erythematous to violaceous macules and patches on the eyelids, periorbital regions, cheeks, upper chest, shoulders, upper back, and posterior neck, and mild periorbital edema. Review of systems was positive for myalgias. Histopathologic examination of a shoulder lesion demonstrated vacuolar interface dermatitis and a sparse, superficial perivascular dermal lymphocytic infiltrate. Colloidal iron staining demonstrated dermal mucinosis. Based on these findings, the diagnosis of dermatomyositis was made. Labs demonstrated elevated serum creatine kinase (673 U/L); tests for rheumatoid factor, anti-nuclear antibodies, anti-SSA and anti-SSB antibodies, immunoglobulin subclasses, and a myomarker panel were within normal limits. A head MRI demonstrated a cystic mass in the right insula; stereotactic biopsy was consistent with an oligodendroglioma. He received a 60 mg oral dose of prednisone, and topical triamcinolone 0.1% and hydrocortisone 2.5% ointment. Within 10 days the rash completely resolved. He underwent a craniotomy for tumor resection several weeks after initial presentation. At follow-up four months later, he showed no recurrence of myalgias or rash. Ovarian, lung, and gastrointestinal cancers are most commonly associated with dermatomyositis in the Western world. To our knowledge, only 2 previous cases of dermatomyositis associated with an intracranial neoplasm have been reported: in a 39-year-old man following dendritic cell immunotherapy for an oligoastrocytoma and in a seven-year-old girl with a choroid plexus papilloma. Our case adds oligodendroglioma to the list of potential neoplasms to be considered when assessing a patient with dermatomyositis.

Immunofluorescence and histopathological assessment using ex vivo confocal laser scanning microscopy in lichen planus.

Ex vivo confocal laser scanning microscopy (CLSM) provides rapid, high-resolution imaging, fluorescence detection and digital haematoxylin-eosin (H&E)-like staining. We aimed to assess the performance of ex vivo CLSM in identifying histomorphology and immunoreactivity in lichen planus (LP) and comparing its accuracy with conventional histopathology and direct immunofluorescence (DIF). Thirty-three sections of 17 LP patients stained with acridine orange (AO) and FITC-labelled anti-fibrinogen antibody and 21 control samples stained with AO were examined using ex vivo CLSM. Ex vivo CLSM was in perfect agreement with conventional histopathology in identifying interface dermatitis, vacuolar degeneration and band-like infiltration. ROC analysis showed that the presence of vacuolar degeneration, interface dermatitis and band-like infiltration was useful to distinguish LP sections from controls (p < .0001). The detection rates of fibrinogen deposition using DIF and in conclusion ex vivo CLSM were 93.8% and 62.5%, respectively. ex vivo CLSM enables histopathological and immunofluorescence examination in LP with the advantage of digital H&E-like staining.

Histopathological Spectrum and Immunophenotypic Characterization of Symmetrical Drug-Related Intertriginous and Flexural Exanthema.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a clinically very well-defined drug eruption, but the histopathological findings are still considered to be nonspecific. To characterize the histopathological and immunophenotypical features of SDRIFE. We performed a retrospective study that identified 11 biopsies from 9 patients with SDRIFE. The histopathological features were analyzed in conjunction with the immunohistochemical findings. The most common histopathological feature was basal cell vacuolization, which was often associated with necrotic keratinocytes and focal spongiosis. TIA1+ T cells and neutrophils were frequently detected in the epidermis and at the dermoepidermal junction. The dermal inflammatory infiltrate was mixed, consisting of CD3+ T cells, macrophages, granulocytes, low numbers of CD20+ B cells, and plasma cells. A combination of histopathological patterns was observed in 5 cases. The most frequent combined histopathological patterns were interface dermatitis, spongiotic dermatitis, and psoriasiform dermatitis. Other histopathological patterns found in different combinations were pustular dermatitis, perivascular and interstitial neutrophilic dermatitis, and interstitial granulomatous dermatitis. In the other 4 cases, a single histopathological pattern predominated, such as psoriasiform dermatitis, vacuolar interface dermatitis of erythema multiforme-like type, or superficial and deep perivascular and interstitial dermatitis with eosinophils and neutrophils. SDRIFE is characterized histologically by a vacuolar interface dermatitis induced by cytotoxic T lymphocytes and neutrophilic granulocytes. This pattern may be obscured by accompanying spongiotic, psoriasiform, or pustular features combined with a mixed superficial and sometimes deep dermal infiltrate.

Drug Induced Autoimmunity Related Neutrophilic Dermatosis by Calcium Channel Blockers

Autoimmunity Related Neutrophilic Dermatoses (ARND) is a recently described entity characterized by urticarial papules and plaques with histology showing a neutrophilic perivascular and interstitial infiltrates with leukocytoclasis, along with variable vacuolar interface dermatitis. We report a 38 year old Caucasian female with a ten year history of lupus who presented with pruritic urticarial papules and plaques on the face, trunk, upper extremities and thighs. The onset occurred 10 days after she started a calcium channel blocker (CCB), diltiazem. Histopathology revealed scattered dyskeratotic keratinocytes, vacuolar interface dermatitis, and a sparse perivascular and interstitial mixed infiltrate of neutrophils within the dermis. There was focal leukocytoclasis, dermal edema, and rare eosinophils. The patient initially improved with prednisone taper, but flared again upon starting a different CCB, verapamil. Exposure to certain medications such as CCB in the setting of autoimmune connective tissue disorder may be the inciting trigger for a neutrophilic dermatoses. Future studies may provide further information on the pathogenesis of ARND and cutaneous drug eruption in the setting of SLE.

2279 DRESS Causing a Subacute Fulminant Hepatitis Secondary to Sulfasalazine

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening hypersensitivity reaction most often due to anti-epileptics. It is characterized by a maculopapular rash, eosinophilia, lymphadenopathy, and visceral organ involvement. Here we present a case of DRESS caused by sulfasalazine which resulted in subacute fulminant hepatitis. CASE DESCRIPTION/METHODS: A 24-year-old male with ulcerative colitis was started on sulfasalazine. After being on sulfasalazine for one month, he ran out of the medication. Ten days later, he developed a diffuse pruritic morbilliform rash. He initially presented with the following lab values: total bilirubin 0.7 mg/dL, AST 175 U/L, ALT 354 U/L, alkaline phosphatase 208 U/L, and INR of 1.1. Skin biopsy revealed focal vacuolar interface dermatitis and superficial perivascular lymphocytic infiltrate with neutrophils and eosinophils, consistent with drug eruption. He was started on prednisone 50mg daily and was discharged home. Ten days later, he returned to the hospital with jaundice and the following lab values suggestive of subacute fulminant hepatitis: total bilirubin 6.5 mg/dL (conjugated bilirubin 3.4 mg/dL), AST 3475 U/L, ALT 4171 U/L, alkaline phosphatase 308 U/L, and INR 2.6. Due to the degree of his hepatocellular injury, he was started on prednisone 2mg/kg. The rash, liver chemistries and INR improved over the next week. DISCUSSION: Sulfasalazine is a rare, but known cause of DRESS and idiosyncratic liver injury. This case is notable because he developed a subacute fulminant hepatitis 10 days after initial presentation and 20 days after discontinuation of sulfasalazine. This highlights the fact that liver injury can evolve into acute liver failure despite withdrawal of the culprit drug several days prior; this latency period is characteristic of sulfasalazine induced acute liver injury and thus supports our diagnosis. AST and bilirubin levels are the most important prognostic indicators for liver transplantation and/or death. DRESS due to sulfasalazine with significantly elevated transaminase levels ( &gt;2000 U/L) has been reported, however, to our knowledge, this is the third reported case with this degree of hepatocellular injury that did not result in liver transplantation. Given the fact that acute liver failure is often the cause of mortality in patients with DRESS, this case illustrates that serial lab monitoring is essential in such patients as liver injury can persist long after the offending agent has been discontinued.

Histopathologic features distinguishing secondary syphilis from its mimickers

Syphilis is often misdiagnosed clinically, and biopsies might be required. To determine histopathologic features that distinguish secondary syphilis from pityriasis lichenoides (PL), pityriasis rosea (PR), and early mycosis fungoides (MF). Histopathologic features of 100 cases of syphilis, 110 cases of PL, 72 cases of PR, and 101 cases of MF were compared. Elongated rete ridges and interstitial inflammation favor syphilis over PL (likelihood ratios 3.44 and 2.72, respectively), but no feature reliably distinguishes between them. Secondary syphilis and PR can be distinguished by neutrophils in the stratum corneum, plasma cells, interface dermatitis with lymphocytes and vacuoles, and lymphocytes with ample cytoplasm. Plasma cells and lymphocytes with ample cytoplasm are rare in early MF and can be used as distinguishing features. Histopathologic features characteristic of syphilis can be seen in PL, PR, and early MF. Distinguishing syphilis from PL can be difficult histologically, and a high index of suspicion is required. Although elongation of rete and interstitial inflammation favor syphilis, plasma cells (historically considered a significant feature of syphilis) are often encountered in PL. Vacuolar interface dermatitis with a lymphocyte in every vacuole is considered characteristic of PL, but this feature appears to be more common in syphilis.

Continuing Medical Education: Paraneoplastic pemphigus: a clinical, laboratorial, and therapeutic overview

AbstractParaneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and a-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.

Cutaneous toxicity associated with enfortumab vedotin treatment of metastatic urothelial carcinoma

Enfortumab vedotin is an antibody-drug conjugate targeting nectin-4 and is being studied in the treatment of various epithelial carcinomas including urothelial carcinoma; early data suggests efficacy and tolerability. Rash has been described as an adverse event associated with treatment with enfortumab vedotin, but has not been characterized to date. We report a patient with metastatic urothelial carcinoma treated with enfortumab vedotin who developed erythematous, scaly papules and plaques on his torso and extremities with corresponding histologic features of vacuolar interface dermatitis and maturation disarray of keratinocytes. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates.