Febrile ulceronecrotic Mucha-Habermann disease - a case and treatment review.

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.

Zinc fever in a painter and varnisher: a case report.

BACKGROUND: Zinc fever is well described in medical literature, particularly in workers after handling zinc-containing materials at high temperatures e.g., in the welding of hot-dip galvanized steel sheets. It is not known whether zinc fever also occurs at low temperatures. CASE PRESENTATION: We present the case of a 33-year-old Caucasian atopic painter and varnisher with work-related dyspnea, sweating, as well as multiple occurrences of fever. He was sent to Institute for Prevention and Occupational medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA) for the evaluation of isocyanate asthma, but an inhalative challenge with hexamethylene diisocyanate was negative. Since symptoms were closely related to the use of zinc coatings at room temperature without adequate protective measures, the diagnosis of zinc fever was made. After exposure cessation the worker immediately became symptom-free. The work as painter and varnisher may be associated with various exposures to hazardous substances. Besides solvents, epoxy compounds and isocyanates, which can cause obstructive respiratory diseases; additionally, zinc-containing agents should be considered as health hazards. CONCLUSIONS: This case demonstrates that zinc fever may occur also after application of zinc coatings by spray painting at low temperatures.

Association between a past history of nausea and vomiting during pregnancy and fever after the BNT162b2 COVID-19 vaccination.

PURPOSE: Nausea and vomiting during pregnancy (NVP) are common among pregnant women and can be severe enough to require hospitalization. However, the mechanism underlying NVP pathogenesis remains unclear. This study examined factors associated with adverse events after vaccination, including a past history of NVP. METHODS: A questionnaire-based survey was completed by non-pregnant women working at Nagasaki University Hospital who received two doses of the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine. This study primarily examined the association between a past history of NVP and post-vaccination fever, as fever was determined to be the most objective and reliable indicator of the surveyed adverse events. RESULTS: Multivariate logistic regression analysis showed that post-vaccination fever was more strongly associated with a past history of NVP (odds ratio, 1.88; 95% confidence interval, 1.16-3.07) than either age (0.73; 0.56-0.96) or weight (0.85; 0.70-1.15), which were previously considered to be highly associated with the incidence of adverse events following COVID-19 vaccination. CONCLUSION: These results suggest an involvement of a similar pathological condition in developing NVP and post-vaccination fever.

Diagnostic Accuracy of Serum Procalcitonin to Diagnose Sepsis in Advanced Solid Tumor Patients with Fever.

BACKGROUND: Diagnosis of infection in advanced solid tumor patients can be challenging since signs and symptoms might be overlapping due to paraneoplastic condition. Delay diagnosis of existing infection can lead to more severe conditions and increased mortality. Procalcitonin (PCT) has been used to support the diagnosis of bacterial infection and sepsis. Unfortunately, PCT also increases in malignancy even without an infection. We investigated the diagnostic accuracy of PCT in advanced solid tumor patients with fever to diagnose sepsis. METHODS: A cross-sectional study was conducted in solid advanced tumor patients with fever patients who were admitted to Cipto Mangunkusumo Hospitals, Indonesia between June 2016 and April 2018. Sepsis was defined using 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference criteria. The diagnostic accuracy of PCT was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 194 subjects were enrolled in this study. 60.3% were female with a mean age of 49.47±12.87 years old. 143 patients (73.7%) with advanced solid tumors. Among this latter group, 39 patients (27%) were sepsis. The ROC curve showed that the levels of PCT for sepsis in advanced solid tumor patients with fever were in the area under the curve (AUC) 0.853 (95%CI 0.785 - 0.921). The Cut-off of PCT in advanced solid tumor patients with fever to classify as sepsis was 2.87 ng/mL, with a sensitivity of 79.5%, and a specificity of 79.8%. CONCLUSION: PCT has good diagnosis accuracy in advanced solid tumor patients with fever to classify as sepsis, however a higher cut-off compared to non-cancerous patients should be used.

Association between neutrophil-to-lymphocyte ratio and epidural-related maternal fever in Chinese parturients: a prospective cohort study.

OBJECTIVE: Epidural analgesia could increase the risk of maternal fever during labor, and the potential mechanisms involved inflammation. Neutrophil-to-lymphocyte ratio (NLR) was a sensitive inflammatory composite indicator and related to adverse outcomes in parturients. This study aimed to investigate the association between NLR levels and epidural related maternal fever (ERMF). METHODS: This prospective cohort study included 614 parturients who underwent epidural analgesia at the Women's Hospital School of Medicine Zhejiang University from November 2021 to May 2023. NLR level was calculated before epidural analgesia for women. The outcome was ERMF. Univariate and multivariate logistic regression models were utilized to explore the association between NLR level and ERMF. And the association was further investigated in subgroups of age, body mass index (BMI) before pregnancy, and parity of delivery. The results were presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Totally, 614 parturients, of whom 171 (27.85%) had ERMF. High NLR level was associated with higher incidence of ERMF (OR = 2.70, 95% CI: 1.58-4.69). Parturients with ERMF had higher proportion of postpartum hemorrhage, longer labor times, and other adverse outcomes in parturients. The association also observed in subgroups of age <35 years old (OR = 2.74, 95% CI: 1.55-4.29), BMI <24 kg/m2 before pregnancy (OR = 2.32, 95% CI: 1.32-4.13), BMI ≥24 kg/m2 before pregnancy (OR = 38.28, 95%CI: 3.67-854.66), primipara (OR = 2.26, 95% CI:1.27-4.04), and multipara (OR = 30.60, 95% CI: 3.73-734.03). CONCLUSION: High NLR levels were associated with ERMF in women. It indicated that physicians may measure NLR levels as a regular measurement, which may beneficial for pregnancy outcomes.

Effectiveness of ORSL® Variants as an Adjuvant along with Standard-of-care Treatment in the Restoration of Oral Fluid, Electrolytes, and Energy in Patients with Fever and/or General Weakness in Indian Patients in an Outpatient Setting.

BACKGROUND: Dehydration due to reduced intake or increased losses including insensible losses in patients with acute nondiarrheal diseases may lead to fluid, electrolytes, and energy (FEE) deficits. The impact of oral FEE supplementation adjuvant to standard of care (SOC) treatment on recovery in patients with acute nondiarrheal diseases is yet to be evaluated. AIM: To determine the effectiveness of ORSL® variants (ORSL® Apple Drink and ORSL® PLUS Orange Drink), fruit juice-based electrolyte drinks as an adjuvant along with SOC in the restoration of oral FEE in patients with acute nondiarrheal disease with fever and/or general weakness who attended an outpatient department (OPD). MATERIALS AND METHODS: This was a prospective, interventional, open-label, multicenter, real-world, study conducted at eight sites across India. Patients with fever and/or general weakness due to an acute nondiarrheal illness were given either ORSL® Apple Drink or ORSL® PLUS Orange Drink as an adjuvant along with SOC treatment per physician's discretion. The primary endpoint of the study was to assess improvement from baseline in energy or hydration levels after ORSL® variants consumption at 6, 24, and 48 hours measured by a new aided recovery scale (ARS). Secondary endpoints were to assess the improvement in energy and hydration levels at 20, 40, and 60 minutes, as well as energy levels and hydration levels at 20, 40, and 60 minutes, 6, 24, and 48 hours after the consumption of ORSL® Apple Drink or ORSL® PLUS Orange Drink. The patient's consumption of ORSL® variants and treatment experience, physician's experience of recommending ORSL® variants, and product safety were evaluated. RESULTS: In total, 612 patients were enrolled with mean age 38.3 years, of whom 62.9% were male. The mean baseline level of energy and hydration was 1.59 (range 1.0-2.0) on ARS. Statistically significant (p < 0.0001) improvements were observed in energy or hydration 6 hours after first consumption of ORSL formulations. Furthermore, improvement was observed from 40 minutes, and in levels of energy, hydration, and both energy and hydration from 60 minutes. Patients and physicians reported a positive experience with ORSL® variants. CONCLUSION: ORSL® Apple Drink and ORSL® PLUS Orange Drink are clinically proven to provide hydration and/or energy to patients with fever and/or general weakness.

Identifying the Probable Etiology of Acute Undifferentiated Fever through Inflammatory Markers.

BACKGROUND: Acute undifferentiated fever (AUF) is defined as any febrile illness with a duration of ≤14 days without evidence of localized infection. Most outpatient services and a significant inpatient load in India are contributed by AUF. COVID-19 has recently added to the existing list of common etiologies of AUF. While the rapid diagnostic test (RDT) kits, which are widely used for the detection of common etiologies of AUF, are unreliable, the rise of various inflammatory markers may help identify the probable etiology. This not only results in better diagnosis but also prepares the physician for close monitoring and pooling of resources. AIM: To identify the probable etiology of AUF through inflammatory markers. OBJECTIVE: To understand the clinical and biochemical parameters as possible predictors of adverse outcomes in AUF. MATERIALS AND METHODS: This was a prospective observational study carried out in the Department of Medicine in a tertiary care hospital. The total duration of the study was 1 year. A total of 400 AUF patients [both outpatient department (OPD) and inpatient department (IPD)] fulfilling the eligibility criteria were taken up for the study after consent. Various inflammatory markers, namely erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin levels along with basic blood and biochemical tests were measured in all qualifying patients at their first visit. The level of rise of all the measured inflammatory markers was analyzed for clues toward identifying the etiology. Also, the possible predictors of adverse outcomes, as defined in the study, were analyzed. Outcome variables are described as mean ± standard deviation. All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, New York, United States of America) and SPSS (Statistical Product and Service Solutions; SPSS Inc., United States of America) version 21. RESULTS: The common etiologies in our study contributing to AUF were dengue (31.5%), COVID-19 (18.5%), enteric fever (12.7%), scrub typhus (9.0%), and malaria (6.0%). In 76 cases (19%), the fever was undiagnosed. Enteric fever had highly elevated CRP (>30 mg/L) and moderately elevated D-dimer, ferritin, and procalcitonin. Both nonsevere dengue and COVID-19 had highly elevated D-dimer (>750 ng/mL), but in nonsevere dengue, CRP, ferritin, and procalcitonin were only mildly elevated, whereas in COVID-19, CRP and ferritin were moderately elevated with mildly elevated procalcitonin. Scrub typhus had highly elevated CRP and ferritin [more than four times the upper limit of normal (ULN)], but D-dimer and procalcitonin were only mildly elevated. The mean serum procalcitonin level in enteric fever is significantly higher than the other etiologies of AUF. Our study was correctly able to identify 90.8% of nonsevere dengue, 87.8% of typhoid, 83.6% of COVID-19, and 91.4% of scrub typhus patients based on the inflammatory markers level. Obesity, diabetes (both types 1 and 2), hypertension, coronary artery disease (CAD), malignancy, chronic kidney disease (CKD), and chronic lung disease were significantly associated with adverse outcomes. A significant delay in visiting the hospital after the onset of fever was found in all etiologies of AUF, which had adverse outcomes. CONCLUSION: Our study is one of the few studies comparing the rise in the level of various inflammatory markers among the common etiologies of AUF. The novelty of the study is that it aids in identifying the probable etiology of AUF with good confidence through the levels of inflammatory markers. Also, our study highlights the high-risk factors associated with adverse outcomes in AUF.

Safely Doing Less for Febrile Infants: Reviewing Management in the Setting of the 2021 American Academy of Pediatrics Clinical Practice Guideline.

For more than 4 decades, pediatricians have sought the best practices for effectively managing well-appearing young febrile infants. In 2021, the American Academy of Pediatrics released a clinical practice guideline for the management of well-appearing febrile infants aged 8 to 60 days. The guideline incorporates advancements in testing, such as biomarkers and diagnostic testing in the setting of changing epidemiology, to help risk stratify infants in the newly formed group age 22 to 28 days as well as the group age 29 to 60 days. The new guideline uses inflammatory markers (procalcitonin, C-reactive protein, absolute neutrophil count, and a temperature >38.4°C) to identify infants at low risk for invasive bacterial infection who can potentially avoid the invasive procedures of lumbar puncture, hospitalization, and broad-spectrum antimicrobials. Because of continued ambiguity, incorporating shared decision-making with families in the care of these infants will be important, as will ongoing clinical research to better inform future practice. [Pediatr Ann. 2024;53(6):e202-e207.].

A rare case of infected urachal cyst leading to intestinal obstruction in a 3-month-old boy with febrile urinary tract infection: Case report.

RATIONALE: Urachal anomalies are rare and can present with various clinical manifestations. Urachal remnants, in particular, can be difficult to diagnose because of atypical symptoms at presentation. This study reports a case of intestinal obstruction in an infant secondary to an infected urachal cyst. PATIENTS CONCERNS: A 3-month-old boy with a known febrile urinary tract infection developed acute abdominal distension. DIAGNOSES: Abdominal ultrasound (US) and computed tomography (CT) revealed a nonspecific, ill-defined soft tissue density at the mid-abdomen, associated with intestinal obstruction. INTERVENTIONS: Emergency exploratory laparotomy was performed. The site of the obstruction was found to be at the mid-small bowel; the proximal small bowel was markedly distended, and the small bowel and sigmoid colon were adherent to urachal remnant. The urachal remnant was excised, and the peritoneal adhesions were lysed. OUTCOMES: The day after surgery, the patient was discharged without any complications. LESSONS: Intestinal obstruction is an exceedingly rare presentation of urachal remnants. This case highlights that urachal anomalies should be considered in the differential diagnosis in patients with intestinal obstruction and a concurrent febrile urinary tract infection.

Delayed presentation is associated with serious bacterial infections among febrile infants: A prospective cohort study.

Introduction: Febrile young infants are at risk of serious bacterial infections (SBIs), which are potentially life-threatening. This study aims to investigate the association between delayed presentation and the risk of SBIs among febrile infants. Method: We performed a prospective cohort study on febrile infants ≤90 days old presenting to a Singapore paediatric emergency department (ED) between November 2017 and July 2022. We defined delayed presentation as presentation to the ED >24 hours from fever onset. We compared the proportion of SBIs in infants who had delayed presentation compared to those without, and their clinical outcomes. We also performed a multivariable logistic regression to study if delayed presentation was independently associated with the presence of SBIs. Results: Among 1911 febrile infants analysed, 198 infants (10%) had delayed presentation. Febrile infants with delayed presentation were more likely to have SBIs (28.8% versus [vs] 16.3%, P<0.001). A higher proportion of infants with delayed presentation required intravenous antibiotics (64.1% vs 51.9%, P=0.001). After adjusting for age, sex and severity index score, delayed presentation was independently associated with the presence of SBI (adjusted odds ratio [AOR] 1.78, 95% confidence interval 1.26-2.52, P<0.001). Conclusion: Febrile infants with delayed presentation are at higher risk of SBI. Frontline clinicians should take this into account when assessing febrile infants.

[Clinical characteristics and treatment in adults and children with histiocytic necroti-zing lymphadenitis].

OBJECTIVE: To analyze the clinical data of histiocytic necrotizing lymphadenitis(HNL), comparing the similarities and differences between children and adults, to deepen the understanding of the disease by clinical physicians, and to improve diagnostic rate and reduce misdiagnosis and mistreatment. METHODS: The clinical data of hospitalized patients with histiocytic necrotizing lymphadenitis diagnosed by biopsy from January 2010 to August 2023 in Peking University First Hospital were collec-ted, and the clinical features, laboratory examinations, pathological features, treatments with antibiotics and glucocorticoids, and prognosis of histiocytic necrotic lymphadenitis were analyzed. Grouped based on age, the differences of clinical characteristics, laboratory tests, treatment, and prognosis between the children group (< 16 years old) and the adult group (≥16 years old) were compared. RESULTS: Among the 81 enrolled patients, there were 42 males and 39 females. The median age was 21(14, 29) years, the median duration of disease was 20.0(13.0, 30.0) days, and the median length of hospital stay was 13.0 (10.0, 15.0) days. The first symptoms were fever, lymphadenopathy, and both. All the patients had enlarged lymph nodes with different parts and sizes, 96.3% (78 of 81) of the patients had cervical lymphadenopathy, 50.6% (41 of 81) had bilateral cervical lymphadenopathy, 55.6% (45 of 81) had supraclavicular, axillary or inguinal lymphadenopathy, and the median lymph node diameter was 20.0(20.0, 30.0) mm. Only one patient had no fever, the other 80 patients had fever, the median peak body temperature was 39.0(38.0, 39.8) ℃. Accompanying symptoms: rash (8.6%, 7/81), fatigue (34.6%, 28/81), night sweating (8.6%, 7/81), chills (25.3%, 25/81), muscle soreness (13.6%, 11/81), and joint pain (6.2%, 5/81). There were 17 cases (21.0%, 17/81) of hepatosplenomegaly, of which 12 cases (70.6%, 12/17) were splenomegaly. 68.8%(55/80) of patients had a decrease in white blood cell (WBC) count, with 47.5%(38/80)increased in lymphocyte(LY)proportion, 53.4%(39/73) increased in high-sensitivity C-reactive protein(CRP), 79.2%(57/72) increased in erythrocyte sedimentation rate(ESR), 22.2%(18/81) increased in alanine transaminase(ALT), 27.2%(22/81) elevated in aspartate transaminase(AST), and 81.6%(62/76) elevated in lactate dehydrogenase(LDH). All the 81 patients underwent lymph node biopsy, and 77.8%(63/81) of the patients showed that most of the structures in the lymph nodes were destroyed or disappeared, and 16.0%(13/81) of the lymph nodes were still in existence, hyperplasia and normal lymph node were 1.2%(1/81) respectively, and 3.7%(3/81) had normal lymph node structures. Immunohistochemical staining was performed in 67 cases. The percentages of CD3+ and CD68(KP1)+ were respectively 97.0%(65/67), and MPO+ were 94.0%(63/67). In the study, 51 patients (63.0%, 51/81) were treated with glucocorticoid therapy after diagnosis. The median time for temperature to return to normal was 1.0(1.0, 4.0) days after glucocorticoid therapy. when the glucocorticoid treatment worked best, the body temperature could drop to normal on the same day. There were significant differences in length of stay, predisposing factors, chills, the rate of increase in high-sensitivity CRP, antibiotic and glucocorticoid treatment between the adults and children groups (P < 0.05). CONCLUSION: In clinical practice, if there are cases with unexplained fever, superficial lymph node enlargement, and reduced white blood cells as clinical characteristics, and general antibiotics treatment is ineffective, histiocytic necrotic lymphadenitis should be considered. Lymph node biopsy should be performed as early as possible to clarify the diagnosis, reduce misdiagnosis and mistreatment, and symptomatic treatment should be the main treatment. Glucocorticoids therapy has a definite therapeutic effect.

Neglected etiologies of prolonged febrile illnesses in tropical and subtropical regions: A systematic review.

BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments. METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias. RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles. CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.