Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management.

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

BACKGROUND: Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. METHODS: We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. RESULTS: Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). LIMITATIONS: Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. CONCLUSION: Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

Retiform purpura: A diagnostic approach.

Retiform purpura is a specific morphology within the spectrum of reticulate eruptions of vascular origin. It develops when blood vessels serving the skin are compromised resulting in downstream cutaneous ischemia, purpura, and necrosis. Identifying retiform purpura is important particularly in the acutely ill patient. It may elucidate the underlying diagnosis, provide prognostic information, and suggest a treatment approach. The differential diagnosis of retiform purpura is vast, reflecting the myriad conditions that can lead to cutaneous vessel wall damage or lumen occlusion. In this article, we give an overview of the differential diagnosis of this cutaneous morphology, provide an approach to workup, and highlight updates in treatment of some of the more common conditions that manifest as retiform purpura.

Development and Validation of a Risk Prediction Model for In-Hospital Mortality Among Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis-ABCD-10.

Importance: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of severe mucocutaneous drug reaction associated with significant morbidity and mortality. A previously developed SJS/TEN-specific severity-of-illness model (Score of Toxic Epidermal Necrolysis [SCORTEN]) has been reported to overestimate and underestimate SJS/TEN-related in-hospital mortality in various populations. Objective: To derive a risk prediction model for in-hospital mortality among patients with SJS/TEN and to compare prognostic accuracy with the SCORTEN model in a multi-institutional cohort of patients in the United States. Design, Setting, and Participants: Data from a multicenter cohort of patients 18 years and older treated for SJS/TEN between January 1, 2000, and June 1, 2015, were obtained from inpatient consult databases and electronic medical record systems at 18 medical centers in the United States as part of the Society for Dermatology Hospitalists. A risk model was derived based on data from 370 of these patients. Model discrimination (calculated as area under the receiver operating characteristic curve [AUC]) and calibration (calculated as predicted vs observed mortality, and examined using the Hosmer-Lemeshow goodness-of-fit statistic) were assessed, and the predictive accuracy was compared with that of SCORTEN. All analysis took place between December 2016 and April 2018. Main Outcomes and Measures: In-hospital mortality. Results: Among 370 patients (mean [SD] age 49.0 [19.1] years; 195 [52.7%] women), 54 (15.14%) did not survive to hospital discharge. Five covariates, measured at the time of admission, were independent predictors of in-hospital mortality: age in years (odds ratio [OR], 1.05; 95% CI, 1.02-1.07), body surface area (BSA) in percentage of epidermal detachment (OR, 1.02; 95% CI, 1.01-1.04), serum bicarbonate level below 20 mmol/L (OR, 2.90; 95% CI, 1.43-5.88), active cancer (OR, 4.40; 95% CI, 1.82-10.61), and dialysis prior to admission (OR, 15.94; 95% CI, 3.38-66.30). A severity-of-illness score was calculated by taking the sum of 1 point each for age 50 years or older, epidermal detachment greater than 10% of BSA, and serum bicarbonate level below 20 mmol/L; 2 points for the presence of active cancer; and 3 points for dialysis prior to admission. The score was named ABCD-10 (age, bicarbonate, cancer, dialysis, 10% BSA). The ABCD-10 model showed good discrimination (AUC, 0.816; 95% CI, 0.759-0.872) and calibration (Hosmer-Lemeshow goodness of fit test, P = .30). For SCORTEN, on admission, the AUC was 0.827 (95% CI, 0.774-0.879) and was not significantly different from that of the ABCD-10 model (P = .72). Conclusions and Relevance: In this cohort of patients with SJS/TEN, ABCD-10 accurately predicted in-hospital mortality, with discrimination that was not significantly different from SCORTEN. Additional research is needed to validate ABCD-10 in other populations. Future use of a new mortality prediction model may provide improved prognostic information for contemporary patients, including those enrolled in observational studies and therapeutic trials.

Hospital Dermatology, Introduction.

Inpatient dermatology is emerging as a distinct dermatology subspecialty where dermatologists specialize in caring for patients hospitalized with skin disease. While the main focus of inpatient dermatology is the delivery of top-quality and timely dermatologic care to patients in the hospital setting, the practice of hospital-based dermatology has many additional components that are critical to its success.

Dermatology hospital fellowships: present and future.

The question of what makes a successful dermatology hospitalist has risen to the forefront due to the rapidly increasing number of these providers. Inpatient dermatology fellowships have formed as a direct consequence. Though mostly in their infancy, these programs have primary or secondary goals to train providers in the dermatologic care of the hospitalized patient. This article presents a brief synopsis of the history of traditional hospitalist fellowships and extrapolates these findings to existing hospitalist dermatology fellowships. As more of these programs arise, these fellowships are poised to revolutionize dermatologic inpatient care from a systems perspective.

Generalized benign cutaneous reaction to cytarabine.

BACKGROUND: Cytarabine-induced toxicity manifests as various cutaneous morphologies. A generalized papular purpuric eruption has not been well described. OBJECTIVES: We aimed to characterize a distinct cytarabine-related eruption. METHODS: We reviewed all cases of cytarabine-related toxicity with papular purpuric eruptions or violaceous erythema at the University of California, San Francisco between 2006 and 2011. RESULTS: Sixteen cases were identified. The eruption began as erythematous papules that evolved into coalescing purpuric papules and plaques. It had affinity for intertriginous areas, neck, ears, and scalp. Pruritus was common, but no systemic complications were documented. Thirteen patients (81.3%) developed the eruption after completion of chemotherapy. Differential diagnosis often included viral exanthem (62.5%), drug eruption (50%), and vasculitis (37.5%). Histopathology was nonspecific but commonly demonstrated sparse lymphocytic infiltrates, spongiosis, and/or red cell extravasation. Importantly, the eruption was neither predicted by past cytarabine exposure nor predictive of future recurrence. LIMITATIONS: This is a review of cases from a single institution. Observation was limited to acute hospitalization, however, charts were reviewed for subsequent reactions on rechallenge. CONCLUSIONS: The eruption described herein represents a specific skin-limited reaction to cytarabine. Awareness of its characteristic morphology, distribution, and timeline will aid in clinical diagnosis. Reassurance concerning its benign nature will prevent unnecessary intervention or cessation of chemotherapy.

Adult Xanthogranuloma, Reticulohistiocytosis, and Rosai-Dorfman Disease.

Adult xanthogranuloma presents most commonly as an orange-tan firm solitary nodule with no systemic manifestations. Recently, some cases have been reported in conjunction with lymphoproliferative disorders. Adult reticulohistiocytosis classically presents as red to yellow-red dermal nodules. In the multicentric form, lesions have a predilection for hands and elbows, with a classic coral bead periungual presentation, and are often associated with symmetric erosive arthritis, particularly of the hands and wrists. The presentation and course of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, can vary. The classic presentation is extensive, painless bilateral cervical lymphadenopathy, but some cases have been entirely extranodal.

Severe drug-induced dermatoses.

A variety of common dermatoses are known to have drug-induced variants. This article discusses the clinical presentation, time frames, reported culprit medications, pathophysiology and management of drug-induced lupus, cutaneous vasculitis, pemphigus, pemphigoid, linear IgA bullous dermatosis, Sweet's syndrome, erythema nodosum, pyoderma gangrenosum, pseudolymphoma, lichen planus, and psoriasis.

Keratitis, ichthyosis, and deafness syndrome: a review of infectious and neoplastic complications.

Keratitis, ichthyosis, and deafness (KID) syndrome is a rare genodermatosis associated with mutations in the connexin 26 gene. Although characterized by this clinical triad, KID syndrome predisposes to a heterogeneous spectrum of cutaneous manifestations and complications, both infectious and neoplastic in nature. Chronic mucocutaneous candidiasis and/or superinfection of skin lesions commonly occur and warrant aggressive therapeutic intervention. Benign neoplasms, namely trichilemmal tumors, have also been reported and can herald malignant growth and invasive disease. Squamous cell carcinoma of both mucosa and skin, especially acral sites, occurs in approximately 15% of patients. The pathogenesis of KID syndrome can be at least partially explained by the role of connexin 26 in intercellular communication and carcinogenesis, but the precise mechanism of disease remains unclear. Treatment strategies, which have ranged from antifungals and antibiotics to systemic retinoids, pose an ongoing challenge given the spectrum of disease. A review of the literature, with a particular focus on infection and malignancy associated with KID syndrome, and updates on the pathogenesis of disease, is discussed.

Use of an expanded immunohistochemical panel to distinguish cutaneous Hodgkin lymphoma from histopathologic imitators.

In lymph nodes, classical Hodgkin lymphoma can typically be distinguished from non-Hodgkin lymphoma (NHL) by the presence of Hodgkin and Reed-Sternberg cells that co-express CD30 and CD15. However, anaplastic large cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL) can show identical features, and some cases of classical Hodgkin lymphoma lack CD15 expression, rendering them difficult to differentiate from CD30-positive NHL. The differential diagnosis of cutaneous Hodgkin lymphoma similarly includes ALCL and DLBCL, and, additionally, tumors of mycosis fungoides. Recent studies have shown that classical Hodgkin lymphoma is of B-cell origin in virtually all cases, and shows at least focal weak expression of the B-cell marker PAX5 and often focal weak expression and no expression of the B-cell markers Oct-2 and BOB.1, respectively. All three of these markers are almost invariably absent in T-cell lymphomas and are strongly expressed in B-cell lymphomas. We report a 40-year-old man with classical Hodgkin lymphoma who developed cutaneous nodules. A biopsy from one revealed Hodgkin/Reed-Sternberg cells with a similar immunophenotype to the diagnostic lymph node biopsy, namely CD30+/CD15+, diffusely but weakly PAX5+, focally weakly Oct-2+ and lacking BOB.1 expression, thereby confirming a diagnosis of cutaneous Hodgkin lymphoma. To our knowledge, this is the first report of the expression pattern of the combination of PAX5, Oct-2 and BOB.1 in the context of cutaneous involvement by Hodgkin lymphoma.

20q- clonality in a case of oral sweet syndrome and myelodysplasia.

We report the case of a patient with myelodysplasia who had Sweet syndrome of the oral cavity. An atypical myeloid immunophenotype was present in the gingival biopsy specimen and in a concurrent bone marrow specimen. Fluorescence in situ hybridization performed on the gingival biopsy specimen demonstrated the same del(20q) cytogenetic abnormality present in the bone marrow, confirming the presence of a clonally related myeloid proliferation in both tissues. This is the first reported case of Sweet syndrome and myelodysplasia in which the chromosomal abnormality was identified in the neutrophilic infiltrate, confirming the neutrophilic infiltrate to be clonally related to the underlying myeloid neoplasm.

Angioinvasive Fusarium and concomitant Enterococcus infection arising in association with leukemia cutis.

Leukemia cutis represents the cutaneous infiltration of neoplastic leukocytes or their precursors that results in clinically identifiable skin lesions. For patients with myelodysplastic syndrome, developing such a lesion may indicate impending leukemic transition. These patients are also often immunocompromised, putting them at risk for infection by opportunistic fungal pathogens such as Fusarium. We describe an 85-year-old man with myelodysplastic syndrome who presented with a reddish-purple nodule with a surrounding erythematous plaque on his shin. Histopathologic examination revealed a dense diffuse infiltrate of large atypical cells in the reticular dermis, with ulceration and necrosis. Immunohistochemical studies showed positive staining with CD15, CD68 and myeloperoxidase of constituent large cells. Concurrently, there were branching and septate hyphae with occasional macroconidia-like structures throughout the infiltrate. Cultures from this lesion grew Fusarium and Enterococcus, supporting the diagnosis: leukemia cutis with superinfection involving both Fusarium and Enterococcus. To our knowledge, this is a novel report of two separate infections occurring in a lesion of leukemia cutis. This case shows that in patients with a hematologic malignancy and skin lesions, a high index of suspicion for infection is necessary when reviewing both the clinical and histopathological data to avoid overlooking an important occult infectious agent.