Serum Interleukin-18 Provides a Clue to the Diagnosis of Adult-Onset Still's Disease: Findings from 6 Japanese Patients with Adult-Onset Still's Disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder accompanied by skin eruption. However, typical skin eruptions, such as evanescent, salmon-pink erythema, are not specific to AOSD and dermatologists often face difficulty in diagnosing AOSD. In this study, we examined serum IL-18 levels as well as IL-6, ferritin and C-reactive protein in 6 Japanese patients with AOSD. METHODS: Serum levels of IL-6 and IL-18 were evaluated in the acute phase and at the time of remission. Serum levels of IL-6 were analyzed using a commercial chemiluminescent enzyme immunoassay (CLEIA; SRL, Tokyo, Japan). Serum IL-18 levels were measured using a commercial ELISA kit (Medical & Biological Laboratories Co., LTD. Nagoya, Japan). RESULT: In active AOSD, serum ferritin levels and CRP levels were above normal range in 6 patients. In remission, serum ferritin levels of 3 patients were slightly above the normal range, while CRP serum levels of 6 patients were all normalized. Serum IL-18 levels were markedly elevated in 5 cases during the acute phase. In remission, serum IL-18 levels remained at higher values than the normal range in 5 cases. Serum IL-6 levels were also highly elevated in 5 patients in active AOSD and became normalized in remission except in case 2. CONCLUSION: High levels of serum IL-18 will be a clue to the diagnosis of AOSD. CRP is also useful biomarker for monitoring disease activity compared with IL-6 and IL-18.

Increase in cetuximab-induced skin rash and hypomagnesemia in patients receiving concomitant treatment with proton pump inhibitors (PPIs): a possible drug interaction?

INTRODUCTION: In a previous study, we found that co-administration of proton pump inhibitors (PPIs) with cetuximab was associated with increased skin toxicity. Both these drugs can induce hypomagnesemia. The aim of this study was to retrospectively explore the possible influence of PPI drugs on cetuximab skin toxicity and the potential synergistic effect of hypomagnesemia. PATIENTS AND METHODS: The files of all eligible patients treated with cetuximab during 2015-2016 with metastatic colorectal carcinoma (mCRC) or head and neck (H&N) carcinoma were reviewed. The concomitant use of PPIs was defined if a drug belonging to that class was included in the patient's chronic medications list. RESULTS: One hundred eighteen patients (61 with H&N carcinoma, 57 with mCRC) were included in the study, and 58 of the 118 patients received PPIs concomitantly with cetuximab. Skin toxicity of any grade was reported in 33/58 (56.9%) patients on PPIs compared with 22/60 (36.7%) patients (p = 0.08) with grade 3-4 in 19/58 (32.8%) and 2/60 (3.3%), respectively (p = 0.001). Hypomagnesemia (Mg serum level < 1.2 mg/dL) was reported in 14/58 (25.9%) PPI-treated patients, compared with 5/60 (10.4%) patients not on PPIs (p = 0.08). Grade 3-4 skin toxicity or hypomagnesemia (Mg < 0.9 mg/dL) was reported in 23/58 (39.7%) patients on concomitant treatment with PPIs, compared with 3/60 (5%) patients not on PPIs (p = 0.001). CONCLUSIONS: Both the rate and the severity of cetuximab-induced skin toxicity and hypomagnesemia were increased by chronic concomitant administration of PPIs. A prospective study is needed to confirm the possible interaction between cetuximab and PPIs.

Correlation of plasma erlotinib trough concentration with skin rash in Chinese NSCLC patients harboring exon 19 deletion mutation.

PURPOSE: Erlotinib is an essential drug for non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations. The relationship between the pharmacokinetics and skin rash and diarrhea of erlotinib in Chinese patients with EGFR mutated NSCLC is unknown. In this study, we evaluated the variability in erlotinib trough concentration and its relationship with the severity of skin rash and diarrhea in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R. PATIENTS AND METHODS: EGFR mutation-positive Chinese patients (n = 52) treated with erlotinib were included in our study; the steady-state trough concentrations were assessed; and the occurrence and severity of skin rash and diarrhea after the onset of treatment with erlotinib were recorded. The patients were divided into two groups by mutation type (exon 19 deletions or exon 21 L858R point mutations). Occurrence and severity of skin rash and diarrhea was analyzed in both groups. RESULTS: The overall mean (± SD) steady-state trough concentration for erlotinib was 1380 ± 663 ng/mL, and there was no significant difference of erlotinib concentrations between the two mutation groups. Occurrence and severity of skin rash was significantly associated with trough concentration in patients with exon 19 deletions but not exon 21 L858R point mutations. Significant association of erlotinib concentrations with diarrhea was found neither in the exon 19 deletions group nor in the exon 21 L858R point mutation group. CONCLUSIONS: The occurrence and severity of skin rash correlated with increase in erlotinib trough concentrations only in Chinese patients with exon 19 deletion; the erlotinib trough concentrations were not associated with diarrhea.

Pruritus in hemodialysis patients: association with phosphorus intake and serum calcium level. / Prurido no paciente em hemodiálise: associação com ingestão de fósforo e nível sérico de cálcio.

OBJECTIVE: To analyze the association between the occurrence of pruritus and adherence to the prescribed diet, biochemical indicators of renal function and the quality of hemodialysis in chronic renal patients. METHOD: A cross-sectional study performed at a dialysis clinic in the Northeast of Brazil, with 200 patients undergoing hemodialysis in the first half of 2015.To analyze the data, inferential statistics were used, using Chi-Square and Fisher's Exact tests; and Mann Whitney U test. RESULTS: The pruritus was present in 51% of the sample, being associated statistically with phosphorus consumption (P = 0.024) and elevation of serum calcium (P = 0.009). CONCLUSION: Pruritus in chronic renal patients undergoing hemodialysis is influenced by adequate nonadherence to the prescribed diet, in addition to the elevation of biochemical indicators of renal function.

Ethosuximide-induced Stevens-Johnson syndrome: Beneficial effect of early intervention with high-dose corticosteroid therapy.

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens-Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

CONTEXT: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. OBJECTIVE: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). MATERIALS AND METHODS: One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. RESULTS: There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. CONCLUSIONS: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

Prurido no paciente em hemodiálise: associação com ingestão de fósforo e nível sérico de cálcio / Prurido en el paciente en hemodiálisis: asociación con ingestión de fósforo y nivel sérico de cálcio / Pruritus in hemodialysis patients: association with phosphorus intake and serum calcium level

Resumo OBJETIVO Analisar a associação entre a ocorrência do prurido e a adesão à dieta prescrita, indicadores bioquímicos da função renal e a qualidade da hemodiálise, em pacientes renais crônicos. MÉTODO Estudo transversal, realizado em uma clínica de diálise no Nordeste do Brasil, com 200 pacientes submetidos à hemodiálise, no primeiro semestre de 2015. Para análise dos dados fez-se uso da estatística inferencial, através dos testes de Qui-Quadrado e Exato de Fisher; e teste de U de Mann Whitney. RESULTADOS O prurido esteve presente em 51% da amostra, associando-se estatisticamente com o consumo de fósforo (P=0,024) e a elevação do cálcio sérico (P=0,009). CONCLUSÃO O prurido em pacientes renais crônicos submetidos à hemodiálise sofre influência da não adesão adequada à dieta prescrita, além da elevação de indicadores bioquímicos da função renal.

Resumen OBJETIVO Analizar la asociación entre la ocurrencia del prurito y la adhesión a la dieta prescrita, indicadores bioquímicos de la función renal y la calidad de la hemodiálisis, en pacientes renales crónicos. MÉTODO Estudio transversal, realizado en una clínica de diálisis en el Nordeste de Brasil, con 200 pacientes sometidos a la hemodiálisis, en el primer semestre de 2015. Para el análisis de los datos se utilizó la estadística inferencial, a través de las pruebas de Qui-Cuadrado y Exacto de Fisher; y prueba de U de Mann Whitney. RESULTADOS El prurito estuvo presente en el 51% de la muestra, asociándose estadísticamente con el consumo de fósforo (P = 0,024) y la elevación del calcio sérico (P = 0,009). CONCLUSIÓN El prurito en pacientes renales crónicos sometidos a la hemodiálisis sufre influencia de la no adhesión adecuada a la dieta prescrita, además de la elevación de indicadores bioquímicos de la función renal.

Abstract OBJECTIVE To analyze the association between the occurrence of pruritus and adherence to the prescribed diet, biochemical indicators of renal function and the quality of hemodialysis in chronic renal patients. METHOD A cross-sectional study performed at a dialysis clinic in the Northeast of Brazil, with 200 patients undergoing hemodialysis in the first half of 2015.To analyze the data, inferential statistics were used, using Chi-Square and Fisher's Exact tests; and Mann Whitney U test. RESULTS The pruritus was present in 51% of the sample, being associated statistically with phosphorus consumption (P = 0.024) and elevation of serum calcium (P = 0.009). CONCLUSION Pruritus in chronic renal patients undergoing hemodialysis is influenced by adequate nonadherence to the prescribed diet, in addition to the elevation of biochemical indicators of renal function.

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N-acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms.

Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash.

Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. With a predictive value for the rash these biomarkers may also have a prognostic value for survival and disease outcome.The concentrations of amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by specific enzyme-linked immunosorbent assays in plasma samples from 211 patients.We observed a significant inverse correlation between the plasma concentration of HGF and overall survival in patients with an inhibitor-induced rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240 days) but not in patients without rash. The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers.

Avoiding "Rash" Conclusions: Challenge of IgA Vasculitis in Adults.

IgA vasculitis is primarily a pediatric disease that is rarely encountered in adults. With adults, gastrointestinal manifestations are quite common, yet are nonspecific and may overlap with other diseases, particularly Crohn's disease, which can make the diagnosis a challenging task. Treatment is controversial given the disease course is usually self-limited with few serious complications. We present a case of IgA vasculitis in an adult patient with limited extraintestinal findings illustrating the complexity of arriving at the correct diagnosis.

Pseudozyma and other non-Candida opportunistic yeast bloodstream infections in a large stem cell transplant center.

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.

A rash diagnosis: Gemcitabine-associated pseudocellulitis.

Gemcitabine is an antitumor agent with broad clinical application. The most common cutaneous toxicities are mild rash and pruritus; however, a severe 'pseudocellulitis' rash, which resembles infectious cellulitis in clinical presentation, has increasingly been recognized as a rare complication of this agent. Though the specific pathophysiology related to this condition is not clear, it has been observed to occur primarily in regions of significant lymphadenopathy or prior radiation exposure typically after 24-48 h following administration of gemcitabine. It is a self-limiting reaction, with most cases resolving within two to seven days of onset without any specific treatment for the rash. Treatment with gemcitabine may be safely continued in patients with this complication, though recurrence of the rash is common following repeated doses. We report a case of biopsy confirmed gemcitabine associated pseudocellulitis in a patient treated for metastatic pancreatic adenocarcinoma. Knowledge of this complication is important to avoid unwarranted hospitalizations and antibiotic use in patients treated with gemcitabine.