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.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.

Acute Interstitial Inflammation on Skin Biopsies and Positive Tissue Cultures in Cellulitis Patients Are Associated a Worse Prognosis.

BACKGROUND: Cellulitis is a significant public health burden and lacks a gold standard for diagnosis. Up to 1/3 of patients are incorrectly diagnosed. The skin biopsy has been proposed as the gold standard. OBJECTIVE: In this study, we evaluate the histopathologic characteristics and tissue culture positivity of biopsies in patients diagnosed with cellulitis seen by our inpatient dermatology consultation service. METHODS: This retrospective cohort study examined patients who were hospitalized with a skin and soft tissue infection at our institution between 2011 and 2020 and underwent a skin biopsy. RESULTS: Those with a positive tissue culture were more likely to die within 30 days compared with those with negative tissue cultures (26% vs. 6%, P = 0.048). Patients who died within 30 days were more likely to have acute interstitial inflammation as a feature on histopathology (38%, P = 0.03). LIMITATIONS: Single institutional design, unintentional exclusion of patients with organism-specific diagnosis, and selection for a medically complex patient population because of the nonroutine collection of biopsies. CONCLUSION: Positive tissue cultures and histopathology showing acute interstitial space inflammation on skin and soft tissue infection (SSTI) biopsies are associated with increased mortality and thus may serve as indicators of poor prognosis.

Cutaneous manifestations of chimeric antigen receptor T-cell therapy: An introduction for dermatologists.

Chimeric antigen receptor T-cell therapy is an emerging immunotherapy with promising efficacy for the treatment of previously refractory or relapsed malignancies. As a personalized medicine approach, T cells are genetically engineered to express a receptor designed to bind a specific tumor antigen, leading to selective immune-mediated destruction of tumor cells. Due to the novelty of chimeric antigen receptor T-cell therapy, the safety profile continues to evolve with limited information currently available on cutaneous adverse events. Improved understanding of the spectrum of cutaneous adverse events may facilitate earlier recognition and appropriate management of these toxicities. To explore this knowledge gap, we discuss the available case reports and clinical trial results of cutaneous reactions associated with chimeric antigen receptor T-cell therapy.

An overview of the efficacy of phototherapy in oncodermatology.

BACKGROUND: Cutaneous adverse events (AEs) following cancer immunotherapy, targeted therapy, and chemotherapy have been well-documented in the literature. A number of case reports have identified phototherapy, a form of light therapy that mimics sunlight exposure, as a noninvasive treatment modality for these cutaneous toxicities. By inducing local suppression of the immune system, phototherapy is a skin-directed treatment with minimal effect on tumor response. Phototherapy may therefore be a viable treatment option for cutaneous AEs from cancer therapies. METHODS: We reviewed the literature for patients treated with phototherapy for cutaneous AEs following cancer immunotherapy, targeted therapy, or chemotherapy. We also included three previously unpublished cases from our own institution. RESULTS: We identified 24 patients (80% male, mean age 67 years, range 49-75 years). Patients received the following phototherapy types: NB-UVB (n = 17), PUVA (n = 6), or PDT (n = 1). A topical steroid was used in conjunction with phototherapy in seven patients. At phototherapy onset, cancer treatment was either continued, temporarily discontinued, or discontinued (n = 9, 6, 7, respectively; in two cases, the cancer treatment course was unknown). Improvement of cutaneous AEs was observed in 96% of patients. CONCLUSIONS: Phototherapy resulted in full or partial improvement in all but one patient. A topical steroid was used in nearly a third of patients, suggesting some oncodermatologists co-administer topicals to further boost response. Continuation of cancer therapy in the majority of patients highlights an additional advantage of phototherapy. We believe phototherapy may be an effective adjunctive treatment to topical steroids when treating these cutaneous toxicities.

In vitro diagnostics for the medical dermatologist. Part I: Autoimmune tests.

Despite the expansion of available in vitro laboratory tests at a rate far exceeding that of dermatologic pharmaceuticals, the existing literature is dominated by discussion of the latter. With the advent of numerous new tests, it can be difficult for practicing dermatologists to stay up-to-date on the available options, methodologies, and recommendations for when to order one test over another. Understanding the inherent strengths and weaknesses of these options is necessary to inform appropriate ordering and proper interpretation of the results. The first article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of undifferentiated patients suspected of having dermatologic autoimmune diseases and it provides a general guide to ordering these tests.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

GATA-3 expression in a de-differentiated chondrosarcoma with cutaneous iatrogenic implantation: a diagnostic pitfall with important clinical implications.

De-differentiated chondrosarcoma (DDCS) is an extremely aggressive tumor of the bone characterized by a high-grade, non-chondroid sarcoma adjacent to a low- or intermediate-grade chondrosarcoma. Adequate tumor sampling demonstrating the biphasic features is necessary to make an accurate diagnosis. The diagnosis may be challenging as histopathology may mimic other neoplasms. We present a case of a 76-year-old woman with a history of breast cancer who presented with a pathologic non-displaced fracture. A bone biopsy demonstrated a high-grade neoplasm composed of pleomorphic spindled and epithelioid cells with focal expression of AE1/3 and GATA3, most likely consistent with metastatic breast carcinoma. After a difficult clinical course, the tumor was resected demonstrating a similar morphology to her prior biopsy, as well as an area of a low-grade cartilaginous neoplasm consistent with chondrosarcoma. The biphasic tumor alongside a low-grade chondrosarcoma allowed for a diagnosis of DDCS. Several days after her procedure, the patient developed violaceous nodules overlying and surrounding the surgical site. Skin biopsy demonstrated a malignant epithelioid neoplasm with identical histomorphologic features identical to her prior bone resection. Given the location of the skin lesions directly within the surgical site right after resection, the clinical-pathological picture was that of sarcomatosis cutis by iatrogenic cutaneous implantation.

Viral exanthems: An update on laboratory testing of the adult patient.

Although classic viral exanthems of childhood are well described, they are rarely differentiated in adults. Laboratory techniques for viral identification have advanced without substantial literature to suggest how a dermatologist ought to conduct a cost-effective and diagnostic viral panel. Certain clinical features such as petechiae, vesicles, and dusky macular or morbilliform exanthems point strongly toward a viral exanthem. Differentiation of drug and viral causes of morbilliform eruptions has proven difficult. It is possible that with further diagnostic refinement that unnecessary and fruitless workups of an exanthem and unneeded discontinuation of drugs can be avoided. We review viral exanthems based on clinical features and discuss the available and optimal laboratory techniques to assist the dermatologist in a targeted workup.