Drug eruptions with novel targeted therapies - immune checkpoint and EGFR inhibitors.

Given the increasing use of novel targeted therapies, dermatologists are constantly confronted with novel cutaneous side effects of these agents. A rapid diagnosis and appropriate management of these side effects are crucial to prevent impairment of the patients' quality of life and interruptions of essential cancer treatments. Immune checkpoint and EGFR inhibitors are frequently used targeted therapies for various malignancies and are associated with a distinct spectrum of cutaneous adverse events. Exanthematous drug eruptions represent a particular diagnostic challenge in these patients. Immune checkpoint inhibitors can elicit a plethora of immune-related exanthemas, most commonly maculopapular, lichenoid, and psoriasiform eruptions. Additionally, autoimmune bullous dermatoses and exanthemas associated with connective tissue diseases may arise. In cases of severe, atypical or therapy-resistant presentations an extensive dermatological investigation including a skin biopsy is recommended. Topical and systemic steroids are the mainstay of treatment. Papulopustular eruptions represent the major cutaneous adverse effect of EGFR inhibitor therapy, occurring in up to 90 % of patients within the first two weeks of therapy, depending on the agent. Besides topical antibiotics and steroids, oral tetracyclines are the first choice in systemic treatment and can also be used as prophylaxis.

Comparison of the Safety Profiles of 3 Different Hymenoptera Venom Immunotherapy Protocols: A Retrospective 2-Center Study of 143 Patients.

INTRODUCTION: Venom immunotherapy (VIT) is highly effective and the treatment of choice for patients with a history of systemic anaphylactic reactions to a Hymenoptera sting. It has been assumed that VIT protocols with a rapid dose increase during the induction phase are associated with a higher frequency of systemic reactions (SR); however, study data addressing this issue are conflicting. OBJECTIVE: The aim of this study was to compare the safety of 3 different Hymenoptera VIT protocols (half-day ultra-rush, 3-day rush, 3-week cluster). METHODS: This retrospective 2-center study included 143 Hymenoptera venom-allergic patients, who underwent 147 VIT procedures during the years 2015-2018. Twenty cluster, 75 rush, and 52 ultra-rush VIT protocols were performed with honeybee (54 protocols) and wasp (93 protocols) venom. All documented side effects were classified into large local and SR (Ring and Messmer classification). RESULTS: SR were observed during 11 (7.5%) VIT procedures and did not exceed severity grade II. SR occurred more frequently in cluster compared to accelerated protocols. This result was observed for both honeybee (cluster: 25%, rush: 8.7%, and ultra-rush: 15.8%) and wasp VIT (cluster: 12.5%, rush: 0%, and ultra-rush: 6.1%), though the differences were statistically significant only in the wasp VIT subgroup. Honeybee venom elicited more SR than wasp venom (14.8 and 3.2%, respectively, p = 0.01). The risk for SR did not depend on age, sex, concomitant antihypertensive medication, hypertryptasemia, or severity of the index sting reaction. CONCLUSION: Accelerated VIT protocols, namely, rush and ultra-rush protocols are safe therapeutic options for Hymenoptera venom-allergic patients and displayed fewer SR than cluster VIT protocols in our study.

SARS-CoV-2-Induced Vasculitic Skin Lesions Are Associated with Massive Spike Protein Depositions in Autophagosomes.

In patients infected with severe acute respiratory syndrome coronavirus 2, vasculopathic changes of the skin are associated with a severe prognosis. However, the pathogenesis of this vasculopathy is not conclusively clarified. In this study, 25 prospectively collected skin samples from patients with COVID-19-related skin lesions were examined for vasculopathic changes and, in case of vasculitis, were further analyzed with electron microscopy and immunohistochemistry. Vasculopathy was observed in 76% of all COVID-19-related inflammatory skin lesions. Visual endothelial changes without manifest leukocytoclastic vasculitis were found in 60% of the COVID-19-related skin lesions, whereas leukocytoclastic vasculitis was diagnosed in 16%. In the cases of vasculitis, there were extensive spike protein depositions in microvascular endothelial cells that colocalized with the autophagosome proteins LC3B and LC3C. The autophagy protein complex LC3-associated endocytosis in microvascular endothelial cells seems to be an important pathogenic factor for severe acute respiratory syndrome coronavirus 2-related vasculitis in the skin. On ultrastructural morphology, the vasculitic process was dominated by intracellular vesicle formation and endothelial cell disruption. Direct presence of severe acute respiratory syndrome coronavirus 2 particles in the skin was not observed. Therefore, our results suggest that instead of direct viral infection, dermal vasculitic lesions in COVID-19 are caused by severe acute respiratory syndrome coronavirus 2 spike protein deposition followed by endothelial damage with activation of autophagy.

Identification of Dermatophyte and Non-Dermatophyte Agents in Onychomycosis by PCR and DNA Sequencing-A Retrospective Comparison of Diagnostic Tools.

Rapid and reliable fungal identification is crucial to delineate infectious diseases, and to establish appropriate treatment for onychomycosis. Compared to conventional diagnostic methods, molecular techniques are faster and feature higher accuracy in fungal identification. However, in current clinical practice, molecular mycology is not widely available, and its practical applicability is still under discussion. This study summarizes the results of 16,094 consecutive nail specimens with clinical suspicion of onychomycosis. We performed PCR/sequencing on all primary nail specimens for which conventional mycological diagnostics remained inconclusive. In specimens with a positive direct microscopy but negative or contaminated culture, molecular mycology proved superior and specified a fungal agent in 65% (587/898). In 75% (443/587), the identified pathogen was a dermatophyte. Positive cultures for dermatophytes, yeasts and non-dermatophyte molds (NDMs) were concordant with primary-specimen-DNA PCR/sequencing in 83% (10/12), 34% (22/65) and 45% (76/169), respectively. Among NDMs, agreement was high for Fusarium spp. (32/40; 80%), but low for Penicillium spp. (5/25; 20%) and Alternaria spp. (1/20; 5%). This study underlines the improvement in diagnostic yield by fungal primary-specimen-DNA PCR/sequencing in the event of a negative or contaminated culture, as well as its significance for the diagnosis of dermatophyte and non-dermatophyte onychomycosis. Molecular mycology methods like PCR and DNA sequencing should complement conventional diagnostics in cases of equivocal findings, suspected NDM onychomycosis or treatment-resistant nail pathologies.