Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is classically considered a low-risk, self-limiting eruption lacking systemic manifestations and sparing facial and mucosal areas. We present 7 inpatients meeting diagnostic criteria for SDRIFE with concomitant systemic manifestations ± high-risk facial involvement acutely after antibiotic exposure (mean latency 6.71 days). These cases deviate from classic, self-limited SDRIFE and represent a unique phenotype of SDRIFE, characterized by coexisting extracutaneous manifestations. Onset of systemic stigmata coincided with or preceded cutaneous involvement in 4 and 3 patients, respectively. All patients developed peripheral eosinophilia and 6 patients had ≥ 2 extracutaneous systems involved. Facial involvement, a high-risk feature associated with severe cutaneous adverse reactions but atypical in classic SDRIFE, occurred in 4 cases. Patients had favorable clinical outcomes following drug cessation and treatment with 4-6 week corticosteroid tapers. We suggest that baseline labs be considered in hospitalized patients with antibiotic-induced SDRIFE. These patients may also necessitate systemic therapy given extracutaneous involvement, deviating from standard SDRIFE treatment with drug cessation alone.

Cutaneous drug reactions (CDRs) are common drug-induced allergic reactions that cause severe consequences in HIV/AIDS patients. The CCL17/CCR4 axis is involved in the immune mechanism of allergic diseases, but its role in the CDRs has not been determined. Here, we aimed to determine the role of the CCL17/CCR4 axis and the underlying mechanism involved in CDRs. In this study, the serum cytokine levels in patients with CDR and healthy controls were measured. The CCL17-triggered allergic profile was screened via a PCR array. Apoptosis of keratinocytes cocultured with CCL17-stimulated Th2 cells was analyzed by flow cytometry. An NVP-induced rat CDR model was established, and dynamic inflammatory factor levels and Th2 cells in the peripheral blood of the rats were measured. Rat skin lesions and signaling pathways in Th2 cells were also analyzed. We showed that the serum CCL17 level was significantly upregulated in CDR patients (P = 0.0077), and the Th2 cell subgroup was also significantly elevated in the CDR rats. The CCL17/CCR4 axis induces Th2 cells to release IL-4 and IL-13 via the ERK/STAT3 pathway. The CCR4 antagonist compound 47 can alleviate rash symptoms resulting from NVP-induced drug eruption, Th2 cell subgroup, IL-4, and IL-13 and inhibit keratinocyte apoptosis. Taken together, these findings indicate that the CCL17/CCR4 axis mediates CDR via the ERK/STAT3 pathway in Th2 cells and type 2 cytokine-induced keratinocyte apoptosis.

Acute generalized exanthematous pustulosis (AGEP) is a rare entity characterized by fever associated with the sudden appearance of erythematous lesions, on which multiple sterile, non-follicular pustules develop. We describe a case of a 44-year-old healthy male who developed fever and multiple erythematous and edematous lesions with progressive generalization to the entire body, associated with multiple small non-follicular pustules three days after having started flucloxacillin for the treatment of a furuncle. Considering the characteristics of the exanthema, fever, and association with aminopenicillin initiation, AGEP was considered. A skin biopsy revealed subcorneal and superficial epidermal pustules, with foci of spongiosis, papillary edema, and a superficial, perivascular inflammatory cell infiltrate with neutrophils and eosinophils, consistent with the clinical diagnosis of AGEP. The culprit drug was suspended, and prednisolone was started, considering the rash extension, with progressive and complete improvement. Although it is a rare condition, the hypothesis of AGEP should be considered in acute febrile conditions with disseminated pustules. It resolves spontaneously after discontinuation of the offending drug, and the diagnosis is based on clinical presentation and skin biopsy.

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EGFR tyrosine kinase inhibitors (TKIs) are the front-line treatment in EGFR mutation positive advanced non-small cell lung cancer (aNSCLC) patients. Generally, they are well-tolerated but skin toxicity is common (45-100% of patients) and may adversely affect quality of life. Pathogenesis of cutaneous side effects is usually linked to EGFR expression in normal cells of the epidermis and not immune-related. Subacute cutaneous lupus erythematosus (SCLE) is an autoimmune disease and about 40% of SCLE cases are drug related, but no reports are available involving osimertinib. Our report depicts a drug induced-SCLE (DI-SCLE) caused by erlotinib and worsened by osimertinib. The adverse event is characterized by the absence of systemic symptoms. Diagnosis has been performed by skin biopsy and the conditions improved with systemic steroids administration and EGFR-TKIs discontinuation. The report underlines the importance of a complete dermatologic diagnosis of skin lesions induced by EGFR inhibitors, according to symptom severity and timing of improving with standard clinical management. The diagnosis of immune-related skin toxicity in this context affects the treatment and the outcome of skin toxicity and must be taken into account when planning subsequent treatments, potentially including immune checkpoint inhibitors (ICIs).

UNASSIGNED: Skin lesions are either caused by COVID-19 disease or they can be due to other driving forces related to the COVID-19 pandemic.
UNASSIGNED: Considering the fact that the reported data in different articles for the type and prevalence of skin manifestations related to the COVID-19 pandemic are inconsistent, we have described the mechanism and type of skin lesions related to the COVID-19 pandemic.
UNASSIGNED: In this review article, we have searched the Medline database (PubMed) for the combination of the following key terms \"Dermatological Manifestation\", \"cutaneous Manifestation\", \"Skin Manifestation\", \"COVID-19\", \"SARS-CoV-2\".
UNASSIGNED: The prevalence of skin manifestations related to COVID-19 ranged from 0.2% to 20%. The majority of these skin lesions are maculopapular eruptions. The skin presentations related to the COVID-19 pandemic are described below. Traumatic skin conditions such as dermatitis in individuals, especially those with allergies, might initiate secondary to over-washing or rinsing with inappropriate detergents. Also, inappropriate use of personal protective equipment (mask-gloves-shield) can trigger skin lesions on the face and hands or aggravate the lesions of acne, seborrhoeic dermatitis, eczema, etc. Furthermore, cutaneous adverse drug reactions may occur during hospitalization or outpatient treatment of COVID-19 patients. Also, psychocutaneous disorders due to acute stress can trigger or deteriorate several skin manifestations. Moreover, COVID-19 prevalence and course may be changed in patients with autoimmune or chronic inflammatory underlying skin disorders such as psoriasis, lupus erythematosus, pemphigus, scleroderma who are on immunosuppressive or biological medications to control their disorders.
UNASSIGNED: Due to the various dimensions of skin organ involvement and the large population affected, long-term skin conditions following this pandemic can be a lot more problematic than it appears. Serious preventive measures and medical supports are necessary to avoid skin disorders from becoming permanent or even chronic.

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The term \"drug reactions\" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions.

BACKGROUND: In many countries and laboratories, techniques such as direct immunofluorescence (DIF) are not available for the diagnosis of skin diseases. Thus, these laboratories are limited in the full diagnoses of autoimmune skin diseases, vasculitis, and rheumatologic diseases. In our experience with these diseases and the patient\'s skin biopsies, we have noted a positive correlation between periodic acid-Schiff (PAS) staining and immunofluorescence patterns; however, these were just empiric observations. In the current study, we aim to confirm these observations, given the concept that the majority of autoantibodies are glycoproteins and should thus be recognized by PAS staining.
OBJECTIVE: To compare direct immunofluorescent and PAS staining, in multiple autoimmune diseases that are known to exhibit specific direct immunofluorescent patterns.
METHODS: We studied multiple autoimmune skin diseases: Five cases of bullous pemphigoid, five cases of pemphigus vulgaris, ten cases of cutaneous lupus, ten cases of autoimmune vasculitis, ten cases of lichen planus (LP), and five cases of cutaneous drug reactions (including one case of erythema multiforme). In addition, we utilized 45 normal skin control specimens from plastic surgery reductions.
RESULTS: We found a 98% positive correlation between DIF and PAS staining patterns over all the disease samples.
CONCLUSIONS: We recommend that laboratories without access to DIF always perform PAS staining in addition to hematoxylin and eosin (H&E) staining, for a review of the reactivity pattern.

Cutaneous drug reactions are frequent in hospitalized patients and vary from simple manifestations like rash and erythema to severe life threatening conditions like angio-oedema, erythroderma, Stevens-Johnson syndrome and toxic epidermal necrolysis. However drug eruptions with antitubercular drugs are largely unknown except few case reports. We highlight here one similar case which presented with pleomorphic cutaneous manifestations after taking anti tubercular therapy and closely mimicked vasculitis. But when the offending drugs were stopped the lesions disappeared and the patient improved.