Drug Eruption Research Articles

Concomitant Eruptive Squamous Atypia and Bullous Drug Eruption Associated with Pembrolizumab

This study involves the case of a rare eruptive squamous atypia (ESA) reaction and concurrent bullous eruption following pembrolizumab treatment for recurrent neck squamous cell carcinoma. This report aims to raise awareness to possible concurrent skin reactions related to PD-1 inhibitor treatment that has otherwise only been reported twice in melanoma patients.

Presumed Levofloxacin-associated Lichenoid Drug Eruption in a Child With Rifampicin-resistant Tuberculosis

Presumed Levofloxacin-associated Lichenoid Drug Eruption in a Child With Rifampicin-resistant Tuberculosis

Erythroderma in the elderly.

Erythroderma is the end-stage condition caused by various inflammatory diseases, presenting with widespread generalized coalesced erythema on the trunk and extremities. Erythroderma is not a disease itself, but rather is a symptom expressing erythrodermic condition, which is frequently associated with inguinal lymphadenopathy, chills, and mild fever. The clinical characteristics include sparing the folds of the trunk and extremities (deck-chair sign), and cobblestone-like disseminated grouping prurigo; however, the deck-chair sign is not specific to papulo-erythroderma (Ofuji disease). Erythroderma is induced by various causes, such as eczema, psoriasis, atopic dermatitis, drug eruption, lymphoma, lichen planus, pityriasis rubra pilaris, autoimmune bullous diseases, graft-versus-host disease, dermatomyositis, internal malignancy, and others. By contrast, it is not uncommon for even thorough investigations to often fail to identify any significant underlying or occult diseases. Such cases are often diagnosed as idiopathic erythroderma. In elderly cases, some regard erythroderma as late-onset atopic dermatitis, even if the patient does not have a history of childhood atopic dermatitis, while others consider it as a distinct condition with immune responses similar to atopic dermatitis. The etiology of erythroderma is suggested to be a Th2-dominant condition with IL-4/IL-13 playing a central role, suggesting that therapies targeting those Th2 molecules may result in sufficient effects. In this review, the characteristics of erythroderma in the elderly and new therapeutic approaches are discussed.

EVALUATION OF CUTANEOUS ADVERSE DRUG REACTIONS IN A TERTIARY CARE HOSPITAL IN SOUTHERN INDIA: A RETROSPECTIVE ANALYSIS

Objective: This study was undertaken to understand the demographic profile, common causative drugs, and the presentations of cutaneous adverse drug reactions (CADR) among the patients of our hospital. Methods: This is a retrospective analytical study. All CADR reported to our adverse drug reaction monitoring center from dermatology outpatient department (OPD), other OPDs, intensive care units, and inpatient wards of our hospital from September 2022 to March 2024 was collected from VIGIFLOW (software used by the pharmacovigilance program of India). The data was then analyzed. Results: A total of 272 CADR were reported over the study period. The median age of presentation was 41 years (Interquartile range=23). Overall 44 (16.18%) serious and 228 (83.82%) non-serious CADR were reported. Erythematous maculopapular rash was the most common clinical presentation (63%). Bullous exfoliative drug eruptions and Stevens Johnson’s syndrome were some of the serious CADR. The most common suspected medications were antibiotics (42.15%) followed by non-steroidal anti-inflammatory drugs (8.92%). In 76% of the cases, the suspected medication was withdrawn. The outcome was reported as “Recovering” in 52% of the cases. On causality assessment, 251 (92%) CADR were classified as “Possible.” Conclusion: A CADR is a common yet preventable health problem. As seen from our study, most of the suspected medications were withdrawn and subsequently the patients were recovering from the CADR. Hence, early diagnosis, identification, and withdrawal of the implicating drugs help in timely recovery and prevention of complications, which in turn help in decreasing the burden on our healthcare system.

Atypical Presentation of Rapidly Progressive Cutaneous Metastases of Clear Cell Renal Carcinoma: A Case Report

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim, suggestive of an inflammatory appearance. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient’s stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. The primary presumptive diagnosis was of cutaneous metastasis, considering the patient’s history of metastatic ccRC. However, given the recent initiation of new pharmacological agents, the rapid progression of the cutaneous lesions, and their clinical presentation, alternative differential diagnoses were considered, including drug-induced reactions such as erythema multiforme or fixed drug eruption. A biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the potential for extremely rapidly evolving cutaneous metastases from ccRC and their capacity to occasionally mimic atypical drug eruptions. Additionally, it reaffirms the poor prognosis of such metastases, as evidenced by the patient’s death within two months.

Vancomycin-associated DRESS demonstrates delay in AST abnormalities.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse drug eruption characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and organ dysfunction. Identifying causative agents and monitoring disease course in DRESS syndrome is crucial to prevent end-organ damage. The temporal relationship between causative medications including vancomycin and laboratory abnormalities in DRESS has not been studied, limiting the utility of laboratory data in monitoring disease course. Our study aims to investigate associations between medication class and peak serum laboratory values using simple linear regression (absolute eosinophils, creatinine, alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). We found a significant difference between timing of peak AST values among vancomycin-triggered DRESS compared to other trigger groups. These findings draw attention to the increased role of AST as a diagnostic and monitoring tool in DRESS.

Semaglutide-Induced Fixed Drug Eruption

Semaglutide-Induced Fixed Drug Eruption

Evaluation of the common skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments

Purpose The diversity of skin diseases in patients with malignancies leads to diagnostic difficulties and complicate cancer treatment. Furthermore, the increasing use of chemotherapy drugs and novel treatment regimens raises the risk of the development of various cutaneous side effects and the need for dermatologists during cancer management. We investigated the skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments. Methods Medical records of cancer patients evaluated in the Dermatology clinic between July 2018 and April 2023 were retrospectively reviewed. Results This study included 872 cancer patients, 374 females and 498 males. Acute myeloid leukaemia was the most common malignancy, followed by multiple myeloma and invasive ductal breast carcinoma. Graft versus host disease was observed in 89 (10.2%) patients after stem cell transplantation and radiodermatitis developed in 16 (1.8%) patients. Maculopapular drug eruption and hand foot syndrome were the most common cutaneous side effects of chemotherapy drugs. Capecitabine was the most common etiologic agent in hand foot syndrome. Cellulitis was the most frequent bacterial infection in cancer patients, whereas herpes zoster was the most frequent viral infection. Among the chemotherapy drugs that caused acneiform drug eruption, cetuximab and cytarabine were notable. Facial erythema was associated with cytarabine use in 27.3% of patients. Conclusion Identifying the common skin diseases in cancer patients and cutaneous side effects due to chemotherapy drugs may help to take preventive measures, develop specific and effective treatments, determine the most appropriate cancer treatment options, and increase patients’ compliance with cancer treatment.

First reported case of thymoma-associated multiorgan autoimmunity induced by COVID-19.

Thymoma-associated multiorgan autoimmunity (TAMA) presents with skin symptoms similar to those of graft-versus-host disease (GVHD), liver dysfunction, and enteritis, in the absence of a history of hematopoietic stem cell or bone marrow transplantation. TAMA is a type of paraneoplastic syndrome associated with thymoma. Its etiology is unclear but is thought to be a result of breakdown of immune tolerance. Histopathologically, TAMA is characterized by epidermal acanthosis with parakeratosis, individual cell keratinization, liquefaction degeneration, and intraepidermal infiltration of CD8-positive lymphocytes. A 64-year-old female patient with a history of myasthenia gravis and thymoma treated with prednisolone (10 mg/day) and cyclosporine (150 mg/day) experienced erythema on her trunk after coronavirus disease 2019 (COVID-19) onset. A psoriatic drug eruption was suspected and the possible causative drug was discontinued, but the skin rash failed to improve. A skin biopsy demonstrated GVHD-like histopathological findings. Diarrhea, abdominal pain, and duodenal perforation occurred concurrently, leading to the diagnosis of TAMA. Thereafter, the patient continued prednisolone and cyclosporine in the same doses as the TAMA treatment and added topical steroids. During the disease course, candida fungemia and cytomegalovirus infection developed, resulting in the patient's death. The TAMA was considered to have been caused by the release of inflammatory cytokines, autoreactive T cell activation, and regulatory T cell dysfunction induced by COVID-19.

Successful desensitization in a patient with metastatic colorectal cancer presenting with regorafenib-mediated fix drug eruption.

Regorafenib is an oral protein kinase inhinitor approved fot the treatment of metastatic colorecral cancer. We present a first successful case of desensitization in regorafenib-related fix-drug eruption in the literature. A 44-year-old female patient was diagnosed with metastatic colorectal adenocarcinoma. The patient received regorafenib treatment for malignancy recurrence. The patient was admitted to adult allergy clinic with developing recurrent fix drug eruption in the second cycle, on the 10th day of regorafenib treatment. The patient was given the third cycle of regorafenib treatment with a 6-day desensitization protocol, the first day of which consisted of 6 steps and and the third cycle was successfully completed. Regorafenib-mediated delayed hypersensitivity reactions occur less frequently and and regorafenib hypersensitivity reactions are difficult to manage and experience is limited. This is the first successful desensitization protocol developed by us for regorafenib-related fix drug eruption and more cases are needed to be reported to confirm the desensitization protocol. There is only one successful regorafenib desensitization protocol for severe delayed hypersensivity reaction in the literature, but there is no protocol developed for mild type delayed hypersensivity reaction. The management of fix-drug eruption primarily involves discontinuation and avoidance of the offending drug but our patient had a mild delayed-type reaction and there was no alternative to regarofenib treatment. We developed the rapid 6-step desensitization protocol (Day 1). According to this protocol, the patient was able to continue regorafenib treatment successfully.

Paracetamol-related fixed drug eruption in paediatric patients

Paracetamol-related fixed drug eruption in paediatric patients

Diagnostic And Post-Therapeutic Histopathology Of Hansen’s Disease in a Man With Rheumatoid Arthritis

Abstract Introduction/Objective Hansen’s Disease (leprosy), caused by Mycobacterium leprae, is a chronic infectious disease primarily affecting the skin and peripheral nerves. In the United States, leprosy remains rare, with less than 200 cases per year reported to the CDC. Diagnosis is often delayed, due to low clinical suspicion and lack of experience among healthcare providers, leading to potentially severe complications and increased transmission risk. Methods/Case Report A 71-year-old man presented to dermatology with a progressive, non-tender erythematous rash involving the arms and chest. He denied any travel history, or exposure to armadillos, and had no family history of a similar rash. His medical history was significant for rheumatoid arthritis, for which he was receiving methotrexate. The clinical differential included drug eruption, tinea infection, or sarcoidosis. Skin biopsy revealed extensive infiltration of the dermis by noncaseating granulomas surrounding cutaneous nerves, and AFB stain highlighted numerous bacilli consistent with Mycobacterium leprae, leading to the diagnosis of Hansen’s disease. The WHO classification was multibacillary leprosy, and the Ridley-Jopling classification was borderline tuberculoid (BT) to perhaps mid borderline (BB), based on clinical and histologic features. He was started on triple therapy, and biopsies performed during treatment, as well as at three years follow up showed marked improvement, with some remaining disease detected in unresolved rash. Results (if a Case Study enter NA) NA Conclusion This case presents a diagnostic challenge given the absence of typical risk factors for Mycobacterium leprae transmission. The patient’s immunocompromised status due to methotrexate therapy may have predisposed him to the disease. Documented cases of Hansen’s disease have more than doubled in the southeastern states since 2013, with concern for endemic regions emerging in Florida. Early recognition, classification, and prompt treatment are essential to prevent disease progression and reduce transmission. Increased education and awareness among healthcare providers are crucial to improving diagnostic accuracy and patient outcomes in cases of leprosy.

Fixed drug eruption and generalized bullous fixed drug eruption: Insights from an analysis of the FDA Adverse Event Reporting System

Fixed drug eruption and generalized bullous fixed drug eruption: Insights from an analysis of the FDA Adverse Event Reporting System

Metabolomic differences between exanthematous drug eruption and infectious mononucleosis.

Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed. A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography-mass spectrometry metabolomics. A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA-cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D-glutamine and D-glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle. The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases.

Fixed drug eruption due to ibuprofen.

Fixed drug eruption due to ibuprofen.

P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways

BackgroundCell death constitutes a pivotal biological phenomenon essential for the preservation of homeostasis within living organisms. In the context of maintaining a functional skin barrier, keratinocytes exert positively and negatively control cell death signals. However, in patients with severe drug eruptions, anomalous overexpression of the formyl peptide receptor 1 (FPR1) in keratinocytes elicits a distinctive mode of cell death known as necroptosis, thereby suffering a loss of the skin barrier. The precise molecular mechanisms connecting FPR1 activation to this cell death remain unclear. ObjectiveWe have investigated the intracellular signal transduction cascade governing FPR1-mediated cell death in cultured keratinocytes. MethodsWe used HaCaT cells as a model keratinocyte. The expression of FPR1 was detected with qPCR. The presence of cell death events was monitored through live-cell fluorescent staining and LDH release assays. Furthermore, the phosphorylation of ERK was assessed via Western blot analysis. Intracellular signal pathways were investigated using specific inhibitors. ResultsLigand stimulation of an endogenous ion channel, purinergic receptor P2X7 (P2X7R), increased the FPR1 expression level. This upregulated FPR1 demonstrated functional competence in the phosphorylation of downstream MAP kinase and the initiation of cell death. Notably, this cell death was ameliorated upon the administration of inhibitors targeting Gβγ, ERK, and caspases. ConclusionThe induction and stimulation of FPR1 initiated apoptosis in keratinocytes via the Gβγ-pERK signaling pathway. Our findings postulate that the downstream components of FPR1 represent an alternative therapeutic target for preventing unintended keratinocyte cell death.

Lichenoid Drug Eruption Secondary to Apalutamide Treatment

Lichenoid Drug Eruption Secondary to Apalutamide Treatment

A case of chronic spontaneous urticaria with wheals lasting for more than a week.

Urticaria is characterized by the development of wheals which usually disappear within a day, and are not present beyond a few days. A 58-year-old man began to develop edematous, partially ring-shaped erythematous lesions accompanied by severe body itching without any particular cause, approximately 2 months before his first visit to our hospital. Each rash emerged as being about 5 mm in diameter, gradually enlarging over several days, and disappeared in up to 10 days. Despite oral treatment with several antihistamines and 10 mg of prednisolone, there was no improvement. Most eruptions disappeared without a trace, but the erythema that appeared on the palms left desquamation. The patient had a history of shellfish allergy, but otherwise no atopic diseases. Drug eruption was ruled out due to a lack of regular taking other medications. Histopathological findings of the skin lesions showed moderate lymphocytic and few eosinophilic infiltrates with edema, but no evidence of vasculitis. Despite the concomitant use of two second-generation antihistamines and montelukast, the rash did not improve. The symptoms began to improve following oral intake of 1.5 mg of betamethasone, which was tapered off with the addition of 150 mg of cyclosporin. The use of all medications was stopped at 4 months from the first visit without recurrence. Wheals of chronic spontaneous urticaria may last for longer than a week without apparent histopathological findings of vasculitis.

Dermatological manifestations, and drug-induced reactions in COVID-19 patients: an observational study from İstanbul, Turkiye

Aims: The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID-19) include fever, cough, sneezing, sore throat, rhinitis, dyspnoea, chest pain, malaise, fatigue, anorexia, and headache. Moreover, cutaneous manifestations have been observed in 0.2% to 20.4% of cases. This investigation further explores the dermatological manifestations associated with COVID-19 and reactions induced by its pharmacological treatments. Conducted at a university hospital, the study examined 841 patients and identified skin manifestations in 1.5% of cases. It differentiates between symptoms directly attributed to the viral infection and those arising from treatment, highlighting the need for clinical vigilance and adaptability in managing these manifestations. COVID-19 has been linked to a wide range of clinical symptoms, extending beyond the well-known respiratory effects to include various dermatological manifestations. These manifestations, which range from mild rashes to severe conditions like vasculitis, may complicate diagnosis and management, particularly when similar symptoms are induced by therapeutic drugs used in COVID-19 treatment. Methods: This cross-sectional study included 841 patients treated in the COVID-19 outpatient and inpatient units of the university hospital between March and May 2020. The assessment involved clinical examinations and telemedicine consultations, focusing on differentiating between viral and drug-induced dermatological reactions. Results: Dermatological manifestations were observed in 1.5% of the 841 patients. Direct virus-related skin changes were noted in 1% (n=8) of patients, including maculopapular eruptions (50%, n=4) on the face and trunk, trunk-localized urticaria (25%, n=2), and purpuric lesions (12.5%, n=1) on the lower extremities. Drug-induced dermatological reactions were identified in 0.5% (n=5) of patients, featuring conditions such as bullous drug reactions, psoriasiform drug eruptions, hypertrichosis, and urticaria. Conclusion: These findings highlight the complex interplay between COVID-19 and its treatment, where both the virus and pharmacological agents can trigger significant dermatological reactions. The need for healthcare providers to consider both viral and drug-induced factors in the diagnosis and management of skin manifestations in COVID-19 patients is underscored. Further studies are essential to refine treatment protocols and reduce adverse dermatological outcomes.

Generalized Fixed Drug Eruption Secondary to Etoricoxib

Generalized Fixed Drug Eruption Secondary to Etoricoxib