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.

Fixed Sunlight Eruption: A Series of 13 Cases in Bogotá, Columbia. / Erupción fija por luz solar, una serie de 13 casos en Bogotá, Colombia.

Few reports describing an association between UV radiation and fixed skin eruptions have been published since 1975. These reactions have received various names, including fixed sunlight eruption, fixed exanthema due to UV radiation, and broad-spectrum abnormal localized photosensitivity syndrome. We present a series of 13 patients (4 men [30.8%] and 9 women [69.2%]) aged between 28 and 56 years who were evaluated for fixed eruptions induced by UV radiation at a dermatology referral hospital in Bogotá, Colombia. The lesions were located on the inner thighs, buttocks, popliteal region, anterior and posterior axilla, and dorsum of the feet. Photoprovocation reproduced lesions in all the affected areas, and histopathology showed changes similar to those seen in fixed drug eruptions. While these UV-provoked reactions may be a type of fixed skin eruption, we cannot rule out that they may also be a distinct condition that simply shares a pathogenic mechanism with fixed eruptions.

COVID-19 Skin Manifestations in Skin of Colour.

Coronavirus disease (COVID-19) skin manifestations have been increasingly reported in medical literature. Recent discussions have identified a lack of images of skin of color (SOC) patients with COVID-19 related skin findings despite people with skin of color being disproportionately affected with the disease. There have been calls to prioritize the identification of COVID-19 skin manifestations in patients with SOC and disseminate these findings. The objective of this article is to review the existing literature on COVID-19 skin manifestations and, where possible, discuss how they may present differently in patients with SOC. Further research is needed to allow primary care physicians and dermatologists to be aware of and easily identify patients with cutaneous findings that may be secondary to COVID-19. Patients presenting with idiopathic dermatologic manifestations should be considered for COVID-19 testing and follow public health guidelines for self-isolation.

Systemic lupus erythematosus and varicella-like rash following COVID-19 in a previously healthy patient.

Emerging reports show that coronavirus disease 2019 (COVID-19) may lead to autoimmune and autoinflammatory diseases. However, COVID-19 triggered systemic lupus erythematosus (SLE) has never been reported to our knowledge. COVID-19 also has associated cutaneous manifestations. Here we present a case of SLE with antiphospholipid antibody syndrome in a previously healthy patient with COVID-19, who subsequently developped a varicella-like exanthem on the trunk. The disease resulted in death of the patient. The pathophysiological mechanisms resulting in overlapping disorders in our patient remain unknown, adding to the growing mystery of this virus and raising questions about the nature of its link with cutaneous, autoimmune, and autoinflammatory manifestations. Sharing the images of this case may benefit physicians dealing with similar patients during this pandemic.

Cutaneous Manifestations of COVID-19: Early Diagnosis and Prognostic Information.

Coronavirus disease 2019 (COVID-19) is a multiple organ disease caused by SARS-CoV-2 virus infection. Among the organs and tissues affected by the disease, the skin has received less attention. Skin is the largest tissue in the body and is responsible for temperature maintenance, protection against external dangers and dehydration, and other roles. Although the skin manifestations of COVID-19 are common, the lack of standardization in the description of its signs makes it difficult to group them together. Considering the literature available so far, the skin manifestations can be divided into 4 patterns: exanthem, urticarial lesions, vascular and acro-papular eruptions. The localization, age, onset, symptoms and severity vary among them. The treatment, when necessary, is usually focused on the inflammatory response control. The pathophysiological mechanisms seem to involve the apoptosis of keratinocytes as well as endothelial cell dysfunction, favouring the establishment of skin inflammation. The better characterization of the skin manifestations is essential to understand the possible effects of COVID-19 on skin as well as for the development of appropriate treatments.

Skin concerns in patients with trisomy 21 (Down syndrome): A Mayo Clinic 22-year retrospective review.

BACKGROUND/OBJECTIVES: Trisomy 21 has known associated clinical phenotypes, including skin and soft tissue concerns. However, the overall prevalence and types of findings are largely unclear. METHODS: A retrospective review of children with trisomy 21 and one or more dermatologic diagnoses, seen from 1/1/1994 to 7/1/2016, was performed to record dermatologic diagnoses. If one or more diagnoses were confirmed, further data were collected, including demographics, medical specialty, referrals to dermatology, treatment, complications, and follow-up. RESULTS: One hundred and seventy-four patients with a diagnosis of trisomy 21 aged 18 years or younger were confirmed to have one or more dermatologic diagnoses. In a total of 479 dermatologic diagnoses, superficial mycoses (12%), skin and soft tissue infections (10%), dermatitis (8%), and folliculitis (8%) were most common. Diagnoses were most commonly made as an outpatient (91%) and by general pediatrics (45%) or dermatology (25%). A significant difference (P < .05) in the frequency of various diagnoses made by different specialties was observed. A significant difference (P < .05) in the treatments recommended by different specialties was also observed. Referrals to dermatology were infrequent (6%). However, a frequent change in diagnosis (61%) or treatment (68%) for patients referred to dermatology was observed. CONCLUSIONS: Children with trisomy 21 are most commonly diagnosed with superficial mycoses, skin and soft tissue infections, dermatitis, and folliculitis. The majority of diagnoses were made by general pediatricians and although dermatology referral was rarely necessary, consultations often resulted in change of diagnosis and/or treatment, supporting consideration of early and frequent dermatology referral.

Suspected COVID-19-related reticulated purpura of the soles in an infant.

A growing number of skin lesions during the COVID-19 pandemic are being recognized. Acral ischemic lesions identical to chilblains are most typical in children and young adults. We report an infant girl, aged 1 month and 29 days, with a peculiar reticulated purpuric eruption on her soles, with positive immunohistochemistry for SARS-CoV-2 in the endothelia of dermal blood vessels. The patient had an excellent outcome without specific therapy.

Cutaneous manifestations and dermatological sequelae of Covid-19 infection compared to those from other viruses.

In the last few months, there have been numerous reports describing a variety of cutaneous signs associated with COVID-19. Clinicians from Italy were the first to describe the cutaneous manifestations of COVID-19, which were later observed in other parts of the globe. In some cases, cutaneous signs were the only manifestation of COVID-19 rather than the typical syndrome of fever and upper respiratory tract symptoms. However, there is considerable heterogeneity amongst the cutaneous signs described so far, which has been published extensively. Our aim is to summarise the latest studies that have reported the early and late cutaneous signs of COVID-19 and compare them to the most common established viral exanthems.

Atypical Exanthem as Cutaneous Manifestation Related to COVID-19 at a Primary Healthcare Facility.

Coronavirus disease (COVID-19) infection attacks the mucosal structures of the respiratory tract, especially the bronchial mucosa and immune cells. The skin changes and manifestations related to COVID-19 infection remain not clearly understood. Cutaneous manifestations related to COVID-19 had been reported. Our patient manifested atypical cutaneous exanthem on her legs, with no other abnormalities found. We used oral azithromycin 500 mg, dexamethasone 0.5 mg, vitamin C 100 mg, and paracetamol 500 mg, which are available at Badak Baru Primary Health Care. The exanthem has improved after 10 days of treatment.

Comparison of initial and final diagnoses in children with acute febrile illness: A retrospective, descriptive study: Initial and final diagnoses in children with acute fever.

BACKGROUND: This study aimed to elucidate the etiologies and diagnostic errors of early-phase pediatric fever without an obvious cause. METHODS: This single-center, retrospective, descriptive study included 1334 febrile children hospitalized at Beppu Medical Center in Japan between 2014 and 2018. Eligibility criteria were age ≤12 years, axillary temperature ≥38.0°C, and fever duration ≤7 days at admission. Initial diagnoses on the day of admission and final diagnoses at defervescence were divided into initial fever with identified source (FIS) and initial fever without source (FWS) and final FIS and final FWS, respectively. The etiology of initial FWS and diagnostic discordance between initial FIS and final FIS were investigated. RESULTS: Of the 1334 participants, 94 (7.0%) were diagnosed with initial FWS. Among patients with initial FWS, final diagnoses were confirmed in 40 (43%), including Kawasaki disease in 17, urinary tract infection in 5, bacteremia in 4, exanthem subitum in 3, and the others in 11. Among the 1275 patients diagnosed with final FIS, diagnostic discordances between initial and final diagnoses were observed in 131 patients (10%). The multiple logistic regression analysis identified increased serum C-reactive protein value at admission (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.06-1.13), exanthem subitum (OR: 409; 95% CI: 119-1399), and Kawasaki disease (OR: 14.3; 95% CI: 8.7-23.3) as independent risk factors for diagnostic discordance. CONCLUSION: Exanthem subitum and Kawasaki disease may be undiagnosed or misdiagnosed in febrile children with fever duration ≤7 days.

A unique variant of juvenile papular-purpuric gloves and socks syndrome.

Parvovirus B19 is the most common causative agent of papular-purpuric gloves and socks syndrome (PPGSS), an often-underreported condition in the pediatric population. Classically, PPGSS presents with a papular-purpuric and at times petechial eruption of the hands and feet. (Dermatology. 1994;188:85; Int J Dermatol. 1996;35:626) We report a unique variant of juvenile PPGSS with prominent involvement of the flexural and extensor elbows, wrists, and knees.

Varicella-like exanthem associated with COVID-19 in an 8-year-old girl: A diagnostic clue?

It has been reported that the novel coronavirus disease (COVID-19) may be associated with a papulovesicular skin eruption predominantly involving the trunk. We hereby present a case of COVID-19-associated varicella-like exanthem in an 8-year-old girl with mild systemic symptoms.

Erythema multiforme-like lesions in children and COVID-19.

During examination of cases of chilblains in children and adolescents, we identified four patients who also showed skin lesions similar to erythema multiforme (EM). They had no other known triggers for EM. One of them had a positive PCR for SARS-CoV-2, while the other three were negative. Skin biopsies from two patients showed features not typical of EM, such as deep perivascular and perieccrine infiltrate and absence of necrosis of keratinocytes. Immunohistochemistry for SARS-CoV/SARS-CoV-2 spike protein showed granular positivity in endothelial cells and epithelial cells of eccrine glands in both biopsies. All patients had an excellent outcome, and had minimal or no systemic symptoms. The coincidence of EM, a condition commonly related to viruses, and chilblains in the setting of COVID-19, and the positivity for SARS-CoV/SARS-CoV-2 spike protein by immunohistochemistry strongly suggest a link between EM-like lesions and SARS-CoV-2.

Differential diagnosis of late-type reactions to injected local anaesthetics: Inflammation at the injection site is the only indicator of allergic hypersensitivity.

BACKGROUND: Anaphylaxis-like reactions developing within a few minutes are the most frequent complications of subcutaneous or submucosal injections of local anaesthetics (LAs), and topically applied LAs are potential contact allergens. In addition, injected LAs have been reported to induce delayed reactions, including local inflammation at the injection site, and various general symptoms. OBJECTIVES: To assess the frequency and symptoms of late-type hypersensitivity occurring several hours after LA injections. METHODS: We retrospectively evaluated clinical data and test results from all patients referred to our allergy clinic in a period of 20 years for diagnostic work-up of LA-associated late-type reactions. RESULTS: Of 202 patients reporting symptoms with onset at least 1 hour after LA injection, 40 had cutaneous inflammation confined to the injection site, and 162 reported various systemic symptoms. LA hypersensitivity could be excluded in all patients with systemic complaints by means of skin testing and subsequent subcutaneous provocation. In 8 of the 40 patients (20%) with local inflammatory reactions, late-type allergic LA hypersensitivity was confirmed. CONCLUSIONS: Late-type LA allergy commonly causes inflammatory skin reactions confined to the injection site. Conversely, LAs are highly unlikely to trigger delayed systemic symptoms such as urticarial or exanthematous skin eruptions.

Pediatric generalized lichen nitidus treated with natural sunlight therapy.

Lichen nitidus is a benign inflammatory dermatosis that typically presents in a localized distribution. We present the rare case of a 6-year-old boy with a 1-year history of generalized lichen nitidus with limited access to narrowband ultraviolet B phototherapy. Over the course of a summer, he had complete and lasting resolution of generalized lichen nitidus after daily natural sunlight exposure. This case demonstrates a rare variant of lichen nitidus and a practical treatment alternative to in-office phototherapy.

Hand, foot, and mouth disease photolocalized to sunburn.

Hand, foot, and mouth disease is a common exanthem linked to infection with several non-polio enteroviruses. This case of an 11-year-old boy with an enteroviral infection limited to areas of sunburn is an atypical presentation of hand, foot, and mouth disease. Recognition of this unusual distribution will allow pediatricians and pediatric dermatologists to appropriately manage and counsel patients and parents.

Assessment of histopathological features of maculopapular viral exanthem and drug-induced exanthem.

BACKGROUND: Viral infections and drug reactions are the commonest causes of exanthems in clinical practice. Clinically, their overlapping features may pose a diagnostic challenge. Hematologic, in vitro, and drug provocation tests are either unreliable or impractical. METHODS: This was a descriptive, prospective study to assess and compare histopathological features of maculopapular viral and drug exanthem. Subjects fulfilling case definition of exanthems were included. Serum C-reactive protein (CRP) and absolute eosinophil count (AEC) were also studied. RESULTS: Skin biopsy slides of 48 cases were evaluated and AEC and CRP were performed. Both median AEC and CRP were lower in viral exanthem compared with drug exanthem. On histopathological evaluation, features such as lymphocytic exocytosis, and dermal infiltrate of eosinophils, lymphocytes and histiocytes were seen in a significantly greater number of drug exanthems. Other findings such as focal spongiosis, acanthosis, keratinocyte necrosis, basal cell damage, papillary dermal edema and atypical lymphocytes in the dermis were also observed in higher though not statistically significant number of drug exanthem biopsies. CONCLUSIONS: Certain histopathological features can help to differentiate between the two exanthems and this modality may be used in situations when there is clinical overlap and when drug rechallenge cannot be undertaken.