HLH caused by an HSV-2 infection: a case report and review of the literature.

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that can be triggered by infections, malignancies, or auto-immune diseases. Here, we present a patient with rapidly progressive HLH triggered by a herpes simplex virus type 2 (HSV-2) primary infection. The patient was successfully treated with intravenous high-dose acyclovir, immunoglobulins, and dexamethasone. This is the first report of HSV-2-associated HLH in an immunocompetent adult patient.

Are Patients at Risk for Recurrent Disease Activity After Switching From Remicade® to Remsima®? An Observational Study.

Background: Since the late '90s, infliximab (Remicade®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade® (originator infliximab) and its biosimilar Remsima® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade® to Remsima® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade® were switched to Remsima® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima® treatment, one withdrew from the study and one received additional corticosteroid therapy. Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade® to Remsima®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade® to Remsima®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.

Nonsteroidal anti-inflammatory drug hypersensitivity: not always an allergy!

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of hypersensitivity reactions. Several distinct clinical syndromes are described regarding NSAID hypersensitivity. Such a reaction is generally caused by a non-immunological mechanism. In susceptible patients, COX-1 inhibition leads to an imbalance in lipid mediators such as leukotrienes and prostaglandins. It is essential to distinguish multiple nonspecific NSAID hypersensitivity from single NSAID hypersensitivity, since the management of these respective syndromes is essentially different. This review provides an overview on all the aspects of NSAID hypersensitivity reactions, from pathophysiology to clinical symptoms, leading practical recommendations.

Low frequency of acetyl salicylic acid hypersensitivity in mastocytosis: The results of a double-blind, placebo-controlled challenge study.

BACKGROUND: Patients with mastocytosis are at increased risk of anaphylaxis. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often discouraged because of this reason. However, the actual prevalence and severity of NSAID-related hypersensitivity among patients with mastocytosis is unknown. METHODS: A double-blind, placebo-controlled acetylsalicylic acid (ASA) challenge up to a cumulative dose of 520 mg was performed among adult patients with mastocytosis. In addition, a retrospective search of the entire outpatient cohort was performed to obtain "real-life" data on NSAID hypersensitivity. RESULTS: Fifty patients underwent an ASA challenge. Seventy percent had indolent systemic mastocytosis, 18% had mastocytosis in the skin, and 12% had advanced mastocytosis. The ASA challenge was positive in 1 patient who developed urticaria. The additional retrospective chart review revealed that 8 of 191 patients had a history of NSAID-related hypersensitivity reaction(s), of whom 3 reported severe systemic reactions. All 8 patients had already experienced NSAID-related hypersensitivity reactions before mastocytosis was diagnosed. CONCLUSIONS: The frequency of ASA hypersensitivity was 2% in a prospective challenge study and 4.1% in a retrospective chart review of 191 patients with mastocytosis. NSAIDs can be administered safely to most patients with mastocytosis. Extra caution should be taken in patients with a history of hypersensitivity reactions to other drugs, or traditional risk factors for NSAID hypersensitivity.

[A rare cause of insufficiency fractures]. / Een zeldzame oorzaak van insufficiëntiefracturen.

A 41-year-old male with a history of cutaneous sarcoidosis presented with sudden onset pain in his left foot. An X-ray showed cystic lesions in the proximal phalanges of the foot with two insufficiency fractures. The lace-like pattern of these lesions is exemplary for osseous sarcoidosis.

Routine abdominal ultrasonography has limited value in the care for patients with indolent systemic mastocytosis.

OBJECTIVES: Systemic mastocytosis (SM) is a myeloproliferative disease characterized by the accumulation of aberrant mast cells. Since advanced subtypes of SM can lead to organ dysfunction and shortened survival, timely recognition of progressive disease is important for the adequate treatment of SM patients. METHODS: Here, we report the results of our cohort study on the value of routine abdominal ultrasonography for the detection of progression of indolent systemic mastocytosis (ISM). RESULTS: We included 88 patients with ISM, of whom 9 developed new hepatosplenomegaly during follow-up. In this group, the median serum tryptase level increased by 11.60 µg/l, compared with a decrease of -0.20 µg/l in the 79 patients with unchanged ultrasonography results (p = 0.016). A change in liver and/or spleen size never led to a change in clinical classification, nor management. DISCUSSION: Based on the finding that a change in ultrasonography findings did not correlate to disease progression in general, it appears that isolated hepatosplenomegaly does not have prognostic implications in patients with ISM. CONCLUSIONS: Routine abdominal ultrasonography is redundant in the follow-up of patients with ISM. A combination of physical examination with serum tryptase levels can be used to screen for hepatosplenomegaly.

[Systemic mastocytosis: a heterogeneous disease]. / Systemische mastocytose: een heterogene ziekte.

Systemic mastocytosis (SM) is an acquired myeloproliferative disease, which is caused by an uncontrolled proliferation of aberrant mast cells. SM patients can have very different clinical phenotypes and may therefore initially present to different specialties. Diagnosis is often delayed because many physicians are unfamiliar with this illness. This can lead to substantial morbidity and puts patients at risk of complications such as severe anaphylaxis. Measurement of serum tryptase levels is always a sensible first step in the diagnostic work-up, but a normal serum tryptase does not rule out SM completely, and a bone marrow biopsy is essential for a conclusive diagnosis. Here, we describe two patient cases to illustrate the heterogeneous nature of this disease, and provide an overview of the symptoms, diagnostic work-up and current treatments options for SM.

Two patients with a neuroendocrine tumour of the small intestine and paraneoplastic myasthenia gravis.

UNLABELLED: This paper reports on two patients with a long-standing diagnosis of an ENETS stage IV neuroendocrine tumour (NET) of the small intestine who developed neurological symptoms. The first patient only had bulbar symptoms and tested positive for acetylcholine receptor antibodies. The second patient had more classical symptoms of fatigable diplopia and muscle weakness of the legs, but no detectable antibodies. The diagnosis of paraneoplastical myasthenia gravis (MG) was postulated. Both patients were treated with pyridostigmine for MG and octreotide for the NETs. Interestingly, treatment of the NETs resulted in improvement of myasthenic symptoms. Paraneoplastic MG has been described to occur with certain malignancies, mainly thymoma. Herein, we prove that the association with gastrointestinal NETs, however, rare, is also one to be considered by clinicians dealing with either of these diseases. The pathogenesis has yet to be elucidated. LEARNING POINTS: NETs are rare malignancies with a wide variety of symptoms.Paraneoplastic MG can occur with various types of malignancies.Herein, we provide evidence of paraneoplastic MG in association with a grade IV NET of the small intestine.Treatment of the NETs resulted in remission of myasthenic symptoms in one patient.

The value of the Mortality in Emergency Department Sepsis (MEDS) score, C reactive protein and lactate in predicting 28-day mortality of sepsis in a Dutch emergency department.

BACKGROUND: The tendency of sepsis to progress rapidly and the benefit of an early start of treatment emphasise the importance of fast risk stratification in the emergency department (ED). The aim of the present work was to validate the Mortality in Emergency Department Sepsis (MEDS) score as a predictor of 28-day mortality in ED patients with sepsis in The Netherlands, and to compare its performance to C reactive protein (CRP) and lactate. METHODS: This was a historical cohort study in a secondary and tertiary care university hospital. Patients were included if they were seen by an internist in the ED, fulfilled the clinical criteria for sepsis and were admitted to the hospital. Primary outcome was all-cause in-hospital mortality within 28 days. RESULTS: In the 6-month study period, 331 patients were included, of whom 38 (11.5%) died. Mortality varied significantly per MEDS category: ≤4 points (very low risk: 3.1%), 5-7 points (low risk: 5.3%), 8-12 points (moderate risk 17.3%), 13-15 points (high risk: 40.0%), >15 points (very high risk: 77.8%). Receiver operating characteristic (ROC) analysis showed that the MEDS score predicted 28-day mortality better than CRP (area under the curve (AUC) values of 0.81 (95% CI 0.73 to 0.88) and 0.68 (95% CI 0.58 to 0.78), respectively). Lactate was not measured in enough patients (47) for a valid evaluation, but seemed to predict mortality at least fairly (AUC 0.75, 95% CI 0.60 to 0.90). CONCLUSIONS: The MEDS score is an adequate tool for predicting mortality in patients with sepsis in a Dutch internistic ED population. CRP is less useful in this context. Lactate appears to be at least a fair predictor of mortality, but needs to be investigated more systematically in a larger population.