Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report.

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Risk of immune system and skin and subcutaneous tissue related adverse events associated with oxaliplatin combined with immune checkpoint inhibitors: a pharmacovigilance study.

Background: Few studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs). Methods: We evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients. Results: There were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex-mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678. Conclusion: Type II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review.

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Persistent Pruritic Linear Streaks of Adult-Onset Still's Disease: Reconsidering the Yamaguchi Criteria.

Objective Adult-onset Still's disease (AOSD) is a rare orphan disease, the diagnosis of which remains challenging. This study aimed to identify additional clues for establishing early diagnosis beyond the existing criteria. Methods A retrospective longitudinal cohort study was conducted at two community hospitals in Japan between March 2012 and December 2022. The clinical characteristics and medical histories of patients with AOSD were extracted from the clinical records. The primary outcome was to identify the key manifestations of AOSD for an early diagnosis beyond the existing criteria. Results Twenty-one patients (mean age, 58 years) were included in the study. Fever was the first symptom in 13 out of 21 patients (62%). Six out of 21 patients (29%) presented with a pruritic rash only, while two out of 21 (10%) initially presented with a sore throat. All patients visited more than one medical institution. The median time to reach a correct diagnosis was 41 days (IQR 19-138). Nineteen out of 20 patients (95%) exhibited a pruritic rash, identified as persistent pruritic linear streaks, with a median duration of 21 days (IQR 12-64) before the diagnosis of AOSD as a cutaneous manifestation. Conclusions Persistent pruritic linear streaks were a key feature in the context of an early diagnosis of AOSD, offering an option for reconsidering and revising the existing classification criteria.

Acquired reactive perforating collagenosis triggered by trauma with eosinophilia: a case report and literature review.

Acquired reactive perforating collagenosis (ARPC) is a rare dermatological disorder condition defined by the perforation of altered collagen fibers through the epidermis. The presence of underlying conditions such as diabetes or renal disease is helpful in the ARPC diagnosis. Although skin rashes related to ARPC have been reported, the exact causative factors and mechanisms remain unclear. Here, we present a unique case of ARPC triggered by trauma in a 67-year-old male without concurrent systemic alterations. The diagnosis of ARPC with eosinophilia was made following comprehensive diagnostic testing, including clinical presentation, histological results, and blood tests, ruling out other possible diseases. Intriguingly, the histopathological examination revealed collagen penetration into the epidermis at different tissue sections. In addition, we reviewed existing literature on ARPC, which documented the causation. To help confirm the diagnosis, clinicians have to pay attention to traumatic triggers for ARPC and its rare manifestation with eosinophilia.

An Unusual Case of Fever in Paralytic Ileus.

Still's disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed.

A Case of Adult-Onset Still's Disease With Positive Antinuclear Antibodies and Positive Antineutrophil Cytoplasmic Antibodies.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease characterized by nonspecific symptoms such as fever, maculopapular rash, and arthralgias. The exact etiology and pathogenesis remain unclear despite advancements in medical science. Diagnosis is typically established using the Yamaguchi criteria, which include a negative antinuclear antibody (ANA) test as one of the minor criteria. However, some patients with AOSD exhibit positive ANA and even positive antineutrophil cytoplasmic antibodies (ANCA), complicating the diagnostic process. We present the case of a 19-year-old Asian woman of Yakut ethnicity who initially presented with symptoms resembling an upper respiratory tract infection. Laboratory tests revealed the presence of both ANA and ANCA. The diagnosis of AOSD was confirmed based on clinical presentation and the Yamaguchi criteria. Subsequent pulse therapy with prednisolone resulted in significant clinical improvement and a one-year remission. A review of the literature revealed that simultaneous ANCA and ANA positivity in AOSD has not been previously reported. Follow-up over 12 months showed no evidence of other autoimmune or autoinflammatory diseases, suggesting that the positive ANA and ANCA results may be either false positives or atypical laboratory manifestations in AOSD, which should be considered in the diagnosis.

Enteroviruses Associated with Hand Foot and Mouth Disease in Navi Mumbai, Maharashtra, India in 2022.

An outbreak of Hand Foot and Mouth Disease (HFMD) which occurred in August-September, 2022 in Navi Mumbai, India was prospectively investigated, to delineate the clinical manifestations and identify the etiological agent. Molecular characterization at ICMR-National Institute of Virology (NIV), Mumbai unit reported 69 (88.5%) cases out of 78 clinically diagnosed HFMD cases positive for enteroviruses. Thirty-nine (56.5%) children were positive for CVA6, 11 (15.9%) for CVA16, and one for CVA4 (1.4%). One case of co-infection (CVA16, CVA6) was reported. Fourteen (17.9%) cases had recurrent disease in the same season. CVA6 was associated with unusual extension of the rash beyond the conventional areas of hands, feet, and mouth, with involvement of body areas including face, axillae and trunk. Whole genome sequencing classified CVA6 as group D3 and CVA16 isolates as group B1c. Co-infection and recurrence of disease with atypical symptoms observed in this study highlight the need for continued vigilance of the evolutionary clinical characteristics of the enteroviruses causing HFMD.

Tebentafusp induces a T cell driven rash in melanocyte-bearing skin as an adverse event consistent with the mechanism of action.

Tebentafusp is a gp100xCD3 bispecific ImmTAC designed to redirect polyclonal T cells against cells presenting the melanocyte lineage specific antigen gp100 on HLA-A*02:01. Skin-related adverse events, predominantly rash, are frequent and occur within a few hours after initial infusions, yet the mechanisms are unknown. Here we analysed clinical data from the randomised phase 3 trial (NCT03070392) of tebentafusp (n=252) versus investigator's choice (n=126). Translational analyses were performed on paired on-treatment skin samples from 19 patients collected in the phase 1 trial (NCT01211262). Our analyses showed that rash is a clinical manifestation of tebentafusp-induced recruitment of T cells to cutaneous melanocytes. Development of rash depended on baseline expression levels of gp100 and other melanin pathway genes in the skin. On treatment, melanocyte number was reduced and expression of melanocytic genes decreased, while gene expression related to immunity and cytokine signalling increased. When adjusted for baseline prognostic features, patients with rash within the first week of tebentafusp treatment had the same overall survival compared to patients without a rash in the phase 3 randomized trial IMCgp100-202 (HR 0.84; 95% CI 0.53-1.32). In summary, skin rash is an off-tumour, on-target effect of tebentafusp against gp100+ melanocytes, in line with the mechanism of action.

Infectious Mononucleosis Revealed by Non-steroidal Anti-inflammatory Drug: A First Clinical Report.

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), is a common viral illness among adolescents and young adults. IM typically presents with symptoms such as fever, lymphadenopathy, and pharyngitis. We present a case of a 32-year-old woman who developed a maculopapular rash following ibuprofen administration, revealing an underlying undiagnosed IM. Laboratory investigations confirmed EBV infection. This represents the first documented case linking non-steroidal anti-inflammatory drugs (NSAIDs) to IM presentation. Awareness of this association is crucial for timely diagnosis and management, especially when evaluating patients with unexplained skin reactions to medications.

"Delabeling" by direct provocation testing in children and adolescents with a suspected history of a delayed reaction to ß-lactam antibiotics: Consensus paper of Gesellschaft für pädiatrische Allergologie und Umweltmedizin (GPAU), Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), and Ärzteverband deutscher Allergologen (ÄDA).

BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. RESULTS: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.

Dermatologic manifestations of zoonotic diseases transmitted by dogs: "Spot" could give you spots.

The bond between humans and dogs is precious and has been treasured since ancient times. Dog ownership is linked to numerous health benefits, such as increased physical activity and social functioning and decreased depression and cardiovascular events. However, dogs can transmit zoonotic diseases to humans, many of which present with cutaneous findings. This review summarizes the dermatologic manifestations, transmission routes, diagnosis, and treatment of zoonotic diseases transmitted by dogs, including vector-borne, bacterial, viral, fungal, and parasitic infections. This review emphasizes the significance of clinicians obtaining a comprehensive exposure history when patients exhibit a rash of unknown origin. Such an approach can provide valuable epidemiological clues related to diagnosing a zoonotic disease transmitted by a pet dog. Furthermore, identifying the dog as an infection source and subsequent veterinary treatment can help prevent recurrent infections in dermatologic patients.

ICH S1 prospective evaluation study and weight of evidence assessments: commentary from industry representatives.

Industry representatives on the ICH S1B(R1) Expert Working Group (EWG) worked closely with colleagues from the Drug Regulatory Authorities to develop an addendum to the ICH S1B guideline on carcinogenicity studies that allows for a weight-of-evidence (WoE) carcinogenicity assessment in some cases, rather than conducting a 2-year rat carcinogenicity study. A subgroup of the EWG composed of regulators have published in this issue a detailed analysis of the Prospective Evaluation Study (PES) conducted under the auspices of the ICH S1B(R1) EWG. Based on the experience gained through the Prospective Evaluation Study (PES) process, industry members of the EWG have prepared the following commentary to aid sponsors in assessing the standard WoE factors, considering how novel investigative approaches may be used to support a WoE assessment, and preparing appropriate documentation of the WoE assessment for presentation to regulatory authorities. The commentary also reviews some of the implementation challenges sponsors must consider in developing a carcinogenicity assessment strategy. Finally, case examples drawn from previously marketed products are provided as a supplement to this commentary to provide additional examples of how WoE criteria may be applied. The information and opinions expressed in this commentary are aimed at increasing the quality of WoE assessments to ensure the successful implementation of this approach.

Methicillin-Sensitive Staphylococcus aureus-Associated Leukocytoclastic Vasculitis: A Case Report and Literature Review.

The association of Staphylococcus aureus with vasculitis remains relatively rare and poorly understood. In this report, we present a case of Methicillin-sensitive Staphylococcus aureus (MSSA)-associated leukocytoclastic vasculitis (LCV) following a surgical site infection, adding to the limited body of knowledge on this intriguing clinical entity. A 52-year-old male with a medical history significant for type 2 diabetes mellitus, hypertension, hyperlipidemia, and coronary artery disease presented with progressively worsening generalized petechial rash and migratory joint pains with associated joint swelling. The patient's symptoms began following surgical repair for a rectus abdominis incisional hernia with mesh placement that was complicated by an abdominal wall abscess at the surgical site, prompting drain placement. Cultures from the abscess aspirate revealed Methicillin-sensitive Staphylococcus aureus infection. A punch biopsy of the petechial lesions revealed findings consistent with leukocytoclastic vasculitis. The rash and joint pains resolved approximately one week after initiation of treatment with antibiotics and steroids. This case sheds light on the rare but clinically significant association between Methicillin-sensitive Staphylococcus aureus infection and leukocytoclastic vasculitis, particularly following surgical site infections. The prompt recognition and treatment of underlying MSSA infection, along with the targeted management of LCV, resulted in the resolution of symptoms in our patient. This case emphasizes the importance of a comprehensive diagnostic approach and highlights the efficacy of antibiotic therapy in mitigating MSSA-associated vasculitic manifestations.

A Case of Perianal Annular Rash: Atypical Presentation of Recurrent Secondary Syphilis.

Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.

Approach to fever in children.

BACKGROUND: Fever in children is one of the most common reasons for outpatient visits as well as in-patient evaluation, often causing anxiety among parents and caregivers. Fever can be a standalone feature or be associated with other localising symptoms and signs like rash, lymphadenopathy, or any other organ system involvement with or without a focus of infection. The etiologies of fever vary depending on the clinical setting and epidemiology. India being a tropical country, sees a distinct spectrum of tropical infections. Physicians need to stay updated on the prevalent diseases in their region and the unique factors that may influence the clinical presentations and course of fever in the cohort of children they manage. The challenge lies in balancing the benefit of early treatment for severe diseases versus the harms of unnecessary investigations and treatment for self-resolving illnesses. OBJECTIVES: This review aims to provide a comprehensive overview of fever in children, covering its etiology, clinical features, and management strategies. This review offers an algorithmic approach to fever tailored to the Indian setting to guide physicians in identifying the disease based on clinical symptoms and signs, ordering essential laboratory investigations, and initiating appropriate management promptly. CONTENT: The review categorises fever into various segments like fever with localising signs like rash, lymphadenopathy, fever due to infection localised to a particular organ system, and fever without a focus including fever of unknown origin. It delves into the diverse etiological factors contributing to fever in each of these categories, encompassing infectious and non-infectious origins. It gives pointers to identify the etiology from history, examination, and confirm them with judicious use of diagnostic investigations with emphasis on identifying the red flag signs that require immediate attention, especially in vulnerable groups like neonates and young infants.