Maculopapular Research Articles

CTNI-45. PHASE 2 STUDY OF SORAFENIB, VALPROIC ACID, AND SILDENAFIL IN THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMA

Abstract PURPOSE Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma. PATIENTS AND METHODS Eligible patients were 18 years of age and older with an Eastern Cooperative Oncology Group performance status of 0-2 and pathologically confirmed high-grade glioma (WHO grade 3 or 4), with documented CT or MRI progression or recurrence and measurable or evaluable disease. The treatment schedule was a combination of sorafenib, valproic acid, and sildenafil, each agent administered orally, twice daily continuously. A cycle consisted of 4 weeks. RESULTS Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRa and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. CONCLUSIONS This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.

Cutaneous manifestations and sequelae of Chikungunya fever: a single centre experience

Background: Chikungunya fever is a common viral illness in the tropical and subtropical areas. Various cutaneous manifestations can develop during the acute phase and post-febrile convalescent phase. Objective: To determine the frequency and types of cutaneous manifestations associated with chikungunya fever in acute and post-febrile phase. Methods: We conducted a prospective, observational study including 20 patients with laboratory-confirmed chikungunya fever. All the patients were followed up for 1 year to detect any cutaneous sequelae. Results: Pruritic maculopapular rash was the most common cutaneous manifestation during the acute febrile phase, noted in 60% of the patients. The rash usually appeared within 1–3 days of fever onset and spread in cephalo-caudal direction. Cutaneous hyperpigmentation was the most common dermatologic sequelae in the post-febrile period, occurring in 3 (15%) patients. In all patients, pigmentation appeared 3–4 weeks after resolution of fever, and started on the nose, gradually spreading to the forehead. The pigmentation improved significantly with topical hydroquinone after 4 weeks. Other additional manifestations of chikungunya fever included joint pain and joint swelling. None of our patients presented with mucosal or systemic involvement. Conclusion: Maculopapular skin rash was the most common manifestation during acute febrile phase of chikungunya fever, while cutaneous hyperpigmentation was the most common dermatologic sequelae after resolution of fever.

The Importance of the Skin Syndrome in the Primary Diagnosis of Connective Tissue Diseases in Children: Case Report

Background. Timely verification of the clinical diagnosis of connective tissue diseases in children based on the onset of the earliest symptoms, including skin manifestations, and timely initiation of treatment can prevent the development of irreversible complications, increase the life expectancy of patients and its quality. The aim of the study. To analyze the nature of skin manifestations as a marker of the onset connective tissue disorders, such as systemic lupus erythematosus (SLE), localized scleroderma (morphea), juvenile dermatomyositis (JDM), juvenile polyarteritis nodosa (PAN), systemic juvenile idiopathic arthritis (SJIA), and the timing of the main clinical diagnosis from the moment of manifestation of connective tissue disorders. To clearly demonstrate the importance of skin syndrome in the timeliness of clinical diagnosis, a clinical case is presented. Methods. Analysis of medical records and prospective observation of 47 patients aged up to 17 years 11 months with an established diagnosis of connective tissue diseases and the presence of skin syndrome at the onset of the disease. Results. Among patients with SLE, only 20.0% of children had skin syndrome only in the form of butterfly rash, and other skin manifestations were noted in 80.0% of patients. The period from the onset of skin syndrome to diagnosis was 8.0 ± 2.1 months. In 57.2% of patients with morphea, skin syndrome was detected exclusively in the form of single or multiple elements, and in 42.8% there was a combination of a pathognomonic morphological element with alopecia and scleroderma. The average time to make a clinical diagnosis of morphea from the onset of the skin syndrome was 11.0 ± 1.9 months. In all patients with JDM, skin manifestations were characterized by polymorphism (papules and Gottron’s sign, heliotrope rash, palmar capillaritis, livedo reticularis, cheilitis). The diagnosis was made 14.0 ± 3.2 months from the onset of skin syndrome. In patients with documented PAN, skin manifestations debuted in the form of erythema, areas of necrosis, palmar capillaritis, livedo reticularis, and cheilitis. The period from the onset of skin syndrome to clinical diagnosis was 6.0 ± 2.4 months. Among patients with SJIA, skin syndrome was represented by a maculopapular rash associated with fever and its regression when body temperature normalized. The period until clinical diagnosis was made from the onset of the skin syndrome was 2.0 ± 1.1 months. Conclusion. In most cases, the skin syndrome in patients at the onset of the disease was characterized by polymorphism and diversity of elements with the involvement of the vascular component. At the same time, the time from the debut of connective tissue disease in the form of the appearance of skin syndrome to the clinical diagnosis varied in the range from 2 to 14 months.

Drug reaction with eosinophilia and systemic symptoms: Analysis of cutaneous phenotype as a prognosis factor

Study objectiveThe DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a severe and potentially fatal toxidermia due to various visceral involvements. Identifying factors predisposing to serious complications is essential for clinical and therapeutic management. This study aims to analyze the cutaneous presentation of DRESS and its role as a prognostic factor. Patients and methodsThis is a retrospective, descriptive, and analytical study conducted over nine years at the dermatology department in Fes, including all hospitalized DRESS cases. ResultsThe maculopapular rash was the most frequent phenotype (49.3%), followed by erythroderma, morbilliform exanthem, and polymorphous erythema-like rash. In all, 52.8% of patients had renal involvement and 45.8% had hepatic involvement, while 81.9% exhibited hypereosinophilia. The maculopapular rash and erythroderma were more associated with internal organ involvement, although no significant statistical correlation could be demonstrated. Allopurinol was the most implicated drug in 51.4% of the cases. No correlation was found between the type of medication and the cutaneous presentation. In all, 8.3% of the patients died, primarily those with erythroderma (15.8%). ConclusionOur study demonstrated that maculopapular rash and erythroderma are the most common presentations and are most associated with internal organ complications, with a more unfavorable prognosis for erythrodermic cases.

Simultaneous diagnosis of adult-onset Still's disease and lymphoma: A case report and systematic review of the literature.

Differentiating Adult-Onset Still's Disease (AOSD) from lymphoma is challenging. A 23-year-old female presented with polyarthralgia, fever, rash, lymphadenopathy, and abnormal labs. She met AOSD criteria and was diagnosed with non-Hodgkin lymphoma. Treatment led to improvement. The differentiation between Adult-onset Still's Disease (AOSD) and lymphoma remains challenging in our context. The Faustrel score facilitates the simultaneous diagnosis of these conditions. A 23-year-old woman presented with chronic polyarthralgia in a febrile context. A physical examination revealed peripheral joint syndrome, a maculopapular rash on the trunk, and peripheral lymphadenopathy. Laboratory tests showed neutrophils leukocytosis, hyperferritinemia, and a glycosylated ferritin fraction of 12%. A lymph node biopsy revealed a malignant non-Hodgkin lymphoma, and the patient met the diagnostic criteria for AOSD according to Faustrel. She received corticosteroid therapy and four courses of Rituximab. After 6 months, clinical and biological improvements were noted. It is essential to consider the possibility of an association between atypical clinical presentations of lymphoma and AOSD.

P40 A challenging case of new systemic lupus erythematosus

Abstract Introduction The diagnosis of systemic lupus erythematosus (SLE) and its distinction from systemic infection can be challenging. We present a case of new systemic lupus alongside endocarditis, which illustrates this problem. Case description A previously well, 35-year-old male tarmacer of mixed ethnicity, presented with a three months’ history of general malaise, arthralgia and weight loss of 20kg. Two weeks prior to admission he developed progressive confusion, headaches and imbalance. Clinical assessment revealed a pyrexial patient in delirium without focal neurological signs, a faint maculopapular facial rash, symmetrical synovitis, very few nailfold infarcts, a systolic and diastolic murmur and sterile haemato-proteinuria. No history of IV drug abuse. Investigations showed elevated ESR 61, CRP 217, WBC 11.70 and procalcitonin 7.0. He had AKI stage 2 (eGFR 35 with a urinary protein/creat ratio 162; homogenous ANA (1:1280) with positive dsDNA and crithidia-luciliae binding. C3 and C4 suppressed (0.59 and 0.13, respectively); One blood culture prior to broad spectrum antibiotics was negative. Assuming the possibility of Libman-Sacks endocarditis, the attending acute stroke physician initially also treated with pulsed IV steroids, as well as antibiotics. Due to the delirium, key diagnostic tests were technically difficult, although a transthoracic ECHO showed moderately severe aortic and mitral regurgitation that were not felt to be typical for infective endocarditis by the attending cardiologist. The ITU team offered sedation and controlled ventilation to enable all necessary investigations: trans-oesophageal ECHO showed vegetations of aortic and mitral valve leaflets with perforations of single leaflets, resulting in severe acute aortic and mitral regurgitation; a renal biopsy showed class 3 lupus nephritis and an MRI/A Brain showed widespread cerebral foci of restricted diffusion imaging. Consultation with the regional cardiothoracic centre advised urgent transfer for double metal valve replacement, performed on Day 8 post admission. Surgical inspection confirmed an aortic root abscess, and enrichment culture of the native valve subsequently grew Staph. aureus. In addition to IV antibiotics for infective endocarditis, he was continued on steroid taper and commenced on MMF for lupus nephritis. Discussion It can be difficult to differentiate between infective endocarditis and Libman-Sacks endocarditis, especially when there are no existing risk factors. In cases like these antibiotics and steroids can be started at the same time. In our case, we had a young gentleman with no prior medical history who had multiple compounding factors and barriers to fully investigate. Because of his agitation, he required sedation and that allowed the team to perform life saving investigations (renal biopsy and TOE). He ended up having a double metal valve replacement within 8 days post-admission. Multidisciplinary team involvement and close collaboration was of crucial importance in this case to ensure a safe patient outcome. Key learning points • This case illustrates the need to vigorously chase the possibility of concurrent infection in severe new SLE. Close collaboration between multiple specialities to achieve this is key, especially when a patient lacks agency due to their illness.

P50 Systemic lupus erythematous presenting as Kikuchi-Fujimoto disease complicated with haemophagocytic lymphohistiocytosis: a case report and review of the literature

Abstract Introduction Kikuchi-Fujimoto disease (KFD) or histiocytic necrotising lymphadenitis is a rare, self-limiting inflammatory condition that can be associated with autoimmune connective tissue disorders (CTD) especially systemic lupus erythematosus (SLE). The aetiopathogenesis remains unclear but it is thought to be triggered by an infection in individuals with autoimmune predisposition leading to T-cells mediated apoptosis and inflammatory cascade. This condition most commonly affects children and young adults of Asian descent with a slight female preponderance although it can affect any age and ethnic groups. Cervical lymphadenopathy and fever are the salient manifestations, and it can be fatal if complicated with haemophagocytic lymphohistiocytosis (HLH). Case description A 16 year old girl presented with a 2-month history of persistent fever, progressive bilateral cervical lymphadenopathy, generalised maculopapular rash, angioedema-like facial swelling, oral ulcers and B symptoms. Laboratory investigations revealed pancytopaenia, profound acute phase response and abnormalities consistent with HLH with an HScore of 200 points. A thorough infectious workup was unrevealing apart from serological evidence of past Epstein-Barr virus (EBV) infection. ANA, anti-Sm, anti-RNP and anti-B2GP1 IgG were positive. An ultrasound of her neck showed bilateral multilevel cervical lymphadenopathy and the excision biopsy of her lymph node confirmed features of histiocytic necrotising lymphadenitis and ruled out lymphoma. Notably, there were scattered EBV-positive blasts and the special staining for mycobacteria was negative. A CT scan has also demonstrated bilateral axillary and abdominal lymphadenopathy with no hepatosplenomegaly. There was thrombosis in her right internal jugular vein with no intracranial or cardiac extension of the thrombus. The patient was admitted to ITU for close monitoring due to concerns about possible airway compromise but she did not require any respiratory support. She received intravenous (IV) methylprednisolone pulses for three consecutive days, mycophenolate mofetil, hydroxychloroquine and treatment dose of enoxaparin with good response and did not require IV immunoglobulins (IVIG) and/or interleukin-1 receptor antagonists. However, she subsequently developed an abscess in her neck which was complicated by Staphylococcus aureus bacteraemia and underwent an emergency incision and drainage of the abscess. She recovered well with IV antibiotics and was followed up in the CTD clinic with continuous psychological support from the rheumatology clinical nurse specialists. Discussion KFD most commonly presents with acute to subacute tender cervical lymphadenopathy and fevers which can be associated with other systemic features such as arthralgia, various cutaneous manifestations with great histologic heterogeneity, and neurological manifestations including aseptic meningitis, meningoencephalitis, acute cerebellar syndrome and optic neuritis. Generalised lymphadenopathy has been reported in 22% of cases but hepato- and/or splenomegaly is uncommon (3-5% of cases). Various infectious agents including the EBV have been implicated as the potential trigger of this condition but the evidence remains inconclusive. Our patient’s lymph node biopsy has demonstrated EBV-positive blasts with serological evidence of past EBV infection but a causal relationship between these findings and KFD cannot be established with certainty. It remains a diagnostic challenge to differentiate KFD from the other more sinister pathologies such as lymphoma, various infectious lymphadenitis and autoimmune conditions such as sarcoidosis and Kawasaki disease. Therefore, early excisional biopsy of the affected lymph nodes is essential for establishing the correct diagnosis and may obviate the need for inappropriate treatments. Both KFD and SLE share a complex clinicopathological relationship as SLE may precede, occur concurrently as in this case or develop later following the diagnosis of KFD. Moreover, lupus lymphadenitis can mimic KFD clinically and these two entities can only be distinguished histologically by the demonstration of haematoxylin bodies in lupus lymphadenitis. Our patient developed thrombosis in her right internal jugular vein which was thought to be secondary to the compressive effect from her cervical lymphadenopathy rather than due the antiphospholipid syndrome as her repeat antiphospholipid screen was negative. Key learning points • Clinicians should be aware of this rare clinical entity to make an early diagnosis and avoid unnecessary investigations. Differentiating KFD from the other sinister conditions such as lymphoma remains a diagnostic challenge therefore an early excisional biopsy of the affected lymph nodes would avoid delayed diagnosis and obviate the need for potentially risky treatments. Patients with KFD should be carefully screened and monitored for SLE as it can precede, occur in conjunction with or follow the diagnosis of SLE. Most cases of KFD resolve within 1-6 months although recurrence has been reported in 3-4% and the mortality rate is estimated to be 2.1%. It is crucial to follow up these patients given the increased risk of recurrence which can continue for many years. Despite having a good response to treatments, our patient suffered from significant alopecia and post-inflammatory hyperpigmentation in her skin which has had a great impact on her self-esteem and mental well-being. We would like to highlight in this case the biopsychosocial ramifications of this condition and demonstrate the importance of a multidisciplinary approach in the management of young people with CTD.

Epidemiological characteristics of the 2019 Measles outbreak in central Tunisia

Abstract Background Measles is still an important public health problem worldwide causing significant morbidity and mortality. Measles represents a vaccine-preventable disease. In Tunisia, vaccination against measles was launched in 1983. In spite of the progress made towards measles elimination, Tunisia experienced an outbreak in 2019. We aimed to describe the measles outbreak in the central region of Tunisia in 2019. Methods We carried out a descriptive study using surveillance data from January to December 2019 in four governorates in Tunisia (Monastir, Mahdia, Kairouan, and Kasserine). All suspected measles cases and declared to regional directorate of primary health care were included. A suspected measles case was defined as any person with fever and generalized maculo-papular rash plus one of the following symptoms: cough or coryza or conjunctivitis. A laboratory confirmed measles case is a suspected case of measles that has been confirmed positive by testing (IgM+). Results A total of 2,688 suspected cases were recorded, of which 369 cases were (14.7%) were confirmed measles through serological testing. The sex ratio was 1.06 for suspected cases and 1.12 for measles cases. Infants under one year old accounted 42.2% of suspected cases. The majority of suspected cases (67.3%) were not vaccinated. Among confirmed measles cases, positivity rates were 81.8% for unvaccinated, 70.0% for those with one dose and 27.2% for those with two doses. The hospitalization rate was 61.5 %; highest rates were observed in infants under one year of age (65.7%) and in the age group over 38 years (69.0%). In total, 27 deaths were reported. The highest lethality rate was observed in the age group under 12 months (2%). Conclusions The 2019 measles outbreak in Tunisia highlighted that this disease remains a serious viral infection. Unvaccinated populations could be a potential source for new outbreaks, imposing substantial public health burdens. Key messages • The country needs to establish a national review committee to monitor measles elimination status. • To address future challenges, immunity gaps in the population should be closed.

Cutaneous Manifestations of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C)

Background: Characteristics of dermatological manifestations are frequently encountered in pediatric COVID-19, similar to the presentation in multisystem inflammatory syndrome in children (MIS-C), which typically emerges following COVID-19 infection. The rash exhibits considerable diversity and lacks specificity. However, investigations into the dermatological features of COVID-19 in children and MIS-C remain limited. Objective: To investigate cutaneous manifestations in both COVID-19 and MIS-C in children. Materials and Methods: Cross-sectional study between February and August 2022 in hospitalized children with COVID-19 who had cutaneous lesions and all hospitalized children with MIS-C. Results: Forty-six cases of COVID-19 patients with dermatological manifestations were identified among 1,602 COVID-19 patients, constituting 2.9%. Additionally, 35 cases of MIS-C were diagnosed. The majority of COVID-19 patients in the present study exhibited mild symptoms, accounting for 42 cases (91.3%). The median age of COVID-19 patients was 1.8 years, which was significantly lower than that of the MIS-C group, which was 4.3 years, with a statistically significant difference (p=0.024). The most common rash types observed in both groups were urticaria, maculopapular rash, and macular erythema. Other rash types noted in COVID-19 included erythema nodosum, Stevens-Johnson syndrome, erythema multiformelike, vesicles, and livedo reticularis. Among MIS-C patients, 31 cases (88.6%) presented with mucocutaneous manifestations, with 26 cases (74.3%) exhibiting concurrent mucocutaneous involvement. There was no significant difference in the occurrence of cardiac symptoms between the group with mucocutaneous manifestations and/or dermatological symptoms, which was 81.8%, compared to the group without mucocutaneous or dermatological symptoms, which was 100% (p=0.102). Conclusion: The cutaneous manifestations in pediatric COVID-19 and those with MIS-C vary widely and are non-specific. In patients presenting with fever and rash during a COVID-19 outbreak, recognizing these cutaneous symptoms is crucial for prompt diagnosis and treatment especially those who are asymptomatic. Further studies involving COVID-19 patients, both with and without rash, may provide correlation between disease progression and skin manifestation.

Deflazacort-induced Steven-Johnson syndrome: a case report and literature review

Objective: To summarize the clinical features and outcomes of deflazacort-induced Steven Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) to raise awareness among patients with Duchenne muscular dystrophy (DMD), neurologists as well as other deflazacort users. Methods: The clinical data of a boy with DMD who had SJS induced by deflazacort treated at the Department of Rheumatology & Clinical Immunology of Tianjin Children's Hospital in July 2024 was analyzed retrospectively. Taking "deflazacort" "Steven-Johnson syndrome" "toxic epidermal necrolysis" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2024. The clinical characteristics, treatment and outcomes of deflazacort-induced SJS-TEN were summarized. Results: A 12-year-old boy was admitted with a 3-day history of rash. He was diagnosed with DMD at the age of 3 and had been treated with prednisolone since the age of 8. Forty-four days before admission, the patient started deflazacort to replace prednisolone. Three days before admission, progressively worsening erythematous maculopapular rashes, blisters and skin peeling (8% body surface area), oral mucosal erosion, and exudative conjunctivitis occurred, thus deflazacort was discontinued. Complete remission of SJS was achieved after treatment with intravenous immunoglobulin (IVIG, total 1.4 g/kg), 2 doses of etanercept (0.9 mg/kg, once), subcutaneous injection and intravenous methylprednisolone (0.7 mg/(kg·d)). Based on the literature, there were 5 reports in English while none in Chinese, altogether 7 cases were reported. All the patients were male, aged 3-45 years. Duration of deflazacort exposure was 2-8 weeks. Dermatology diagnosis of our case was SJS, and 5 cases were TEN. One patient was diagnosed with exudative erythema multiforme, and subsequent deflazacort oral challenge test was positive. Treatment included methylprednisolone or dexamethasone in 5 cases, IVIG in 6 cases, etanercept in 3 cases and cyclosporine in 1 case. All patients recovered completely. Conclusion: The synthetic corticosteroid deflazacort can cause rare but severe adverse reactions such as SJS-TEN, which needs close monitoring and prompt recognition and management.

Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature

BackgroundStevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature.Case presentationA previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae.ConclusionWe should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Manifestações dermatológicas da Monkeypox

Objective: This study aimed to identify the primary mucocutaneous manifestations secondary toMonkeypox infection and determine the prevalence of coinfection with other sexually transmittedinfections (STIs). Methods: Searches were conducted in the PubMed, LILACS, SciELO, Cochrane Library, andVirtual Health Library databases using the descriptors “monkeypox,” “dermatological,” “dermatology,”“cutaneous,” “skin,” and “mucocutaneous,” combined with the Boolean operators “and” and “or.” All articles published between January 2017 and October 2022 that addressed mucocutaneous manifestations secondary to Monkeypox infection, regardless of language, wereincluded. Technical notes from the Brazilian Ministry of Health and World Health Organization recommendations were also incorporated. The Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of the studies. Data were independently evaluated by three reviewers. Exclusion criteria included the absence of photographic records of the lesions, lack of laboratory confirmation of infection, “letter to the editor” publications, duplicates, and articles primarily focused on systemic manifestations without association with the integumentary system. Results: A total of 22 publications were included in this study. The most frequently affected anatomical sites were the genital and perianal regions, though lesions were also reported on the torso, face, oropharynx, limbs, palms, and soles. There is a possibility that the infection may present nonspecifically as a maculopapular rash. Lesions are typically multiple, with either localized orwidespread distribution. In the latter case, the progression is centrifugal, beginning on the face.The most prevalent characteristic of the elementary lesion is central umbilication, which eventuallydevelops a crusted appearance. Umbilicated papules are often associated with pain, which gradually transitions to varying degrees of pruritus. Coinfection with HIV and other STIs was particularly notable among men who have sex with other men and/or have multiple partners and who use condoms inconsistently.Conclusions: Monkeypox can present with various cutaneous manifestations, none of which arepathognomonic of the disease. The chronological evolution of the elementary lesions (papule, vesicle,pustule, crust) is not always precise, with multiple stages potentially coexisting in the same area of the body. The primary behavioral factor associated with infection is unprotected sexual activity, especially among men who have sex with other men. Coinfections with HIV, syphilis, gonorrhea, chlamydia, and/or herpes were observed in the majority of cases.

Skin manifestations and related clinical characteristics of multisystem inflammatory syndrome in children: A descriptive retrospective cohort study at Texas Children’s Hospital

BackgroundLittle is known about the dermatologic manifestations of MIS-C in children and adolescents ObjectiveWe sought to describe the demographic background, key clinical features, and the clinical consequences of developing rash manifestations in MIS-C patients at Texas Children’s Hospital. MethodsDescriptive retrospective cohort study of 290 hospitalized eligible patients between May 2020 and April 2022. ResultsAmong MIS-C patients, 51% exhibited a rash. We found that younger children (8.62 vs. 9.49 years of age, p=0.006) and white children (p=0.002) had a higher likelihood of developing a rash in association with MIS-C. Additionally, patients without a rash had increased maximum troponin levels (0.11 ng/mL vs. 0.07 ng/mL, p=0.02) and a higher incidence of cardiac involvement (83.1% vs. 72.3%, p=0.03) compared to those with a rash but did not significantly affect the length of hospital stay or clinical course. The most commonly observed rash was an erythematous and maculopapular rash on the trunk and/or extremities. LimitationsRash characteristics were initially described by a variety of physicians on the pediatric primary care services. ConclusionRash manifestations in MIS-C patients is associated with lower Cardiac involvement and decreased troponin levels.

An observational study on the spectrum of Cutaneous Adverse Reactions to Antitubercular drugs and their management

IntroductionTuberculosis (TB) remains a significant global health issue, ranking as the 13th leading cause of death worldwide. Management of tuberculosis requires administration of multiple drugs for varied duration which increases the risk of developing adverse reactions. Among various adverse reactions are cutaneous adverse reactions (CARs) which can be immune mediated or non immune mediated. Aim1. To study the clinical, epidemiological, and morphological characteristics of cutaneous adverse reactions resulting from antitubercular treatment. 2. To study the outcomes of cutaneous adverse reactions to antitubercular therapy using the Modified Hartwig and Seigel severity assessment scale and rechallenge protocol, and assess the effectiveness of management strategies. Methodology: A longitudinal observational study was conducted over a period of 1 year at department of Pulmonology and Dermatology at tertiary care institute to assess CARs in patients on antitubercular treatment. Rechallenge was done in eligible patients. ResultsAmong 3164 TB patients on anti-tubercular treatment (ATT), 56 developed CARs, yielding an incidence rate of 1.77% per year. The study found female preponderance, with the most affected age groups being 21-30 and 41-50 years. Most CARs occurred within the first 30 days of ATT initiation, predominantly manifesting as maculopapular rash. Factors such as multiple medication use, diabetes, elderly age, and positive HIV status were associated with CARs. Ethambutol was identified as the most frequently implicated drug in the occurrence of cutaneous adverse reactions (CARs) upon rechallenge. ConclusionEffective management of CARs involves appropriate treatment, careful monitoring, and rechallenge protocols to identify culprit drugs while minimizing the risk of severe reactions.Upon complete resolution of initial adverse reaction, one must do rechallenge meticulously to pinpoint culprit drug and ensuring effective tuberculosis treatment.

Successful Desensitization With ELX/TEZ/IVA

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was given US Food and Drug Administration approval based on its therapeutic benefits to treat patients with cystic fibrosis (CF) who had at least 1 allele of the CF transmembrane conductance regulator (CFTR) with phenylalanine deleted at position 508 (F508del). The increase in genotyping studies has increased the frequency of use of CFTR modulators; however, severe allergic reactions to CFTR modulators have also been described. It is critical to avoid the offending medication and select alternative treatments while dealing with drug allergies. Drug desensitization may be taken into consideration in situations where there is no other option. This article describes home desensitization treatment for a patient with CF who developed a maculopapular rash following CFTR modulator medication. There are currently no alternative drugs for CFTR modulators, which are crucial for patients with CF, and limited experience is available with allergic reactions to these drugs. It is important to establish desensitization protocols in order to control drug reactions to CFTR modulators, which are vital for individuals with CF.

A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors.

Combining a checkpoint inhibitor with an inhibitor of extracellular signal-regulated kinase (ERK) may result in synergistic antitumor activity. We evaluated MK-8353, an ERK1 and ERK2 inhibitor, plus pembrolizumab in a phase 1b study in patients with advanced solid tumors.This open-label, nonrandomized, dose-escalation study (NCT02972034) enrolled adults with advanced solid tumors previously treated with 1‒5 prior lines of therapy. MK-8353 was administered orally in combination with pembrolizumab 200mg every 3weeks as follows: twice daily (arm A; MK-8353 50‒350mg), once daily (arm B; MK-8353 50‒600mg), or once daily every other week (arm C; MK-8353 50‒300mg). The primary objective was evaluation of safety via occurrence of dose-limiting toxicities (DLTs). A secondary objective was objective response by RECIST v1.1 per investigator assessment.Among 110 evaluable patients (arm A, n = 22; arm B, n = 50; arm C, n = 38), median age was 58.0 (range, 35‒79) years and 50% had received 1 or 2 prior lines of therapy. DLTs occurred in 19 patients (n = 6 [27%], n = 8 [16%], and n = 5 [13%], respectively); the most frequent was grade 3 maculopapular rash (n = 15). Grade 3/4 treatment-related AEs occurred in 35% of patients; the most common were maculopapular rash (13%) and increased lipase (5%); none were grade 5. Eight patients (7%) attained an objective response (arm B, n = 7 [complete response, n = 1; partial response, n = 6]; arm C, n = 1 [complete response]).In conclusion,MK-8353 once daily plus pembrolizumab could be administered with a manageable toxicity profile but had modest antitumor activity in patients with advanced solid tumors.

Congenital Sepsis with Candida albicans-A Rare Event in the Neonatal Period: Report of Two Cases and Literature Review.

Candida spp. is rarely found in neonatal early-onset sepsis (EOS) etiology. However, candidemia is associated with increased mortality and morbidity, as in late-onset sepsis. Congenital candidiasis may present as a mucocutaneous infection or, more rarely, as a systemic infection in term and preterm infants. This paper presents case reports of two cases of congenital systemic candidiasis (CSC) caused by Candida albicans and a review of the data in the literature. An electronic search of PubMed, Scopus, and Google Scholar was performed to identify publications on congenital candidiasis. Both neonates were male, born vaginally, with risk factors for congenital candidiasis. One of the infants was born at term and presented with an almost generalized maculopapular rash at birth and congenital candidemia; parenteral fluconazole was used successfully. The other infant was born prematurely at 28 weeks of gestation; blood culture, gastric aspirate, and maternal vaginal cultures sampled at birth were positive for C. albicans. Liver and kidney involvement became apparent on the third day of life, while lung involvement was clinically evident on the fourth day. Prolonged parenteral fluconazole was administered due to multiple organ involvement and persistent candidemia. Our experience with the presented cases, similar to data in the literature, suggests that CSC may occur at any gestational age, with various clinical pictures, sometimes mimicking bacterial sepsis, and even in the absence of the rash. Careful anamnesis and a high index of suspicion are important for the prompt recognition and treatment of CSC, optimizing the short- and long-term outcomes. Further research should focus on CSC to improve its diagnosis.

Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children

Introduction: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. Methods: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1–6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. Results: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. Conclusion: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

Clinical Presentations of Parvovirus B19: A Case Series.

Parvovirus B19 (PVB19) is a small, nonenveloped, single-stranded DNA virus commonly causing asymptomatic infections or mild, flu-like symptoms. In children, PVB19 can lead to various clinical conditions, including erythema infectiosum, arthropathy, transient aplastic crisis and papular-purpuric eruptions, among others. We present 3 pediatric cases treated at Luigi Sacco University Hospital in Milan, Italy, in March 2024, each demonstrating distinct manifestations of PVB19 infection. Case 1 involved a 7-year-old girl with a maculopapular rash and panniculitis-like symptoms. Case 2 described an 8-year-old boy with a maculopapular rash, vasculitis component and mild thrombocytopenia. Case 3 focused on a 7-year-old girl with petechial and purpuric eruptions and a mild decrease in platelets. Serological tests confirmed PVB19 infection in all cases. The discussed cases highlight the heterogeneous clinical spectrum of PVB19 infection and emphasize its potential to cause thrombocytopenia even in healthy children. The recent surge in PVB19 cases in Europe, aligned with known epidemiological cycles, underscores the importance of vigilance in diagnosis, particularly during peak seasons. Additionally, concerning the role of serological testing in the diagnostic process, the potential for cross-reactivity among viral antigens is pointed out. PVB19 is a common infection with a broad range of clinical presentations. Awareness of its potential complications, including thrombocytopenia, even in nonimmunocompromised children, is crucial. Moreover, understanding the epidemiological patterns of PVB19 can aid in anticipating and managing outbreaks, thus minimizing its impact on pediatric health.

Frequency of Scabies in Pediatric Allergy Clinic and Evaluation of Demographic Characteristics of Affected Patients

Objective: There has been an increase in the number of cases as pediatricians mistakenly refer scabies to an allergy clinic, misdiagnosing it as allergic illnesses, particularly atopic dermatitis (AD), because of the presence of symptoms such as itching and eczematous lesions. The objective of our study was to examine the prevalence of scabies in children who were referred to the pediatric allergy clinic after being misdiagnosed with AD. We also aimed to determine the clinical and demographic distinctions between individuals with AD and scabies. Methods: The files of 610 patients those referred to Sakarya Training and Research Hospital Pediatric Allergy Clinics between February-December 2022 with complaints of 'itching and rash' were documented retrospectively. Cases of acute urticaria, chronic urticaria, mastocytosis, insect bite, maculopapular rash with viral infection, drug-induced reactions were excluded. Patients whose final diagnosis was AD and who were diagnosed with 'definite scabies' were included in the study. Results: A total of 404 patients were included in the study. The rate of definite diagnosis of scabies was 18.5% (n:75/404). The median age at presentation was 19 months (IQR 8-51) in patients diagnosed with AD and 53 months (IQR 17-117) in patients diagnosed with scabies (p<0.005). The median time from symptom onset to diagnosis was seven months (IQR 2.5-24) in the AD group and two months (IQR 1-4) in the scabies group (p<0.005). Only 20% (n:15/75) of patients with scabies had family history, 16% of patients (n:12/75) had received one or more treatments before. Pruritis was present in only 72% (54/75) of children. Hospitalization rate was 0.05% (n:4/75). Conclusion: We recommend that scabies should be considered as a potential diagnosis for patients who visit to any clinic with symptoms of itching and a skin rash. Timely identification and medical intervention for scabies in children is crucial in order to minimize the spread of the disease throughout the community and prevent potential complications.