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.

The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases.

BACKGROUND: Autoinflammatory diseases are rare disorders of the innate immune system characterized by fever and other signs of inflammation. A feared complication of autoinflammatory diseases is the development of AA amyloidosis. AA amyloidosis is caused by extracellular deposition of soluble serum amyloid A (SAA) proteins as insoluble amyloid fibrils leading to organ damage. Prolonged high levels of SAA are a prerequisite to develop AA amyloidosis. Since measurement of SAA is relatively expensive and sometimes unavailable, C-reactive protein (CRP) is often used as a surrogacy marker to test for inflammation. OBJECTIVE: The aim of this research is to evaluate the possible relation between CRP and SAA. METHODS: A retrospective cohort of patients with autoinflammatory diseases (n = 99) where SAA and CRP blood testing was performed in the period between 2015 and 2021 in the University Medical Centre in Groningen was used to investigate the correlation between CRP and SAA. RESULTS: CRP and SAA have a high correlation (rho = 0.755, p < 0.001). A CRP value below 0.45 mg/L results in 100% sensitivity for SAA below 4 mg/L. CRP below 5 mg/L is a good predictor of SAA below 4 mg/L with 85.4% sensitivity and 83.6% specificity. Only prednisone and erythrocyte sedimentation rate (ESR) significantly influence the relation between CRP and log10SAA. CONCLUSION: There was a significant correlation between CRP and SAA in our retrospective cohort. CRP levels below 5 mg/L proved to be highly predictive of SAA levels below 4 mg/L. This may not be true for patients on steroids.

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.

Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study.

UNLABELLED: The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. OBJECTIVE: To establish the prevalence and incidence of SSc and its pulmonary complications. METHODS: Detailed information on patients in the POEMAS registry, "Pulmonary Hypertension Screening, a Multidisciplinary Approach in Scleroderma", consisting of 819 patients, was combined with a nationwide questionnaire. RESULTS: By combining the two sources the prevalence of SSc was found to be 8.9 per 100 000 adults. The incidence was 0.77 patients per 100 000 per year. PAH was diagnosed in 9.9% of SSc patients. The prevalence of interstitial lung disease in SSc varied from 19% to 47% depending on the definition used. CONCLUSION: This study clarifies the epidemiology of SSc in The Netherlands and confirms the frequent occurrence of pulmonary complications, based on 654 cases. This can and will be studied further in the ongoing POEMAS study.

[Amatoxin poisoning due to soup from personally picked deathcap mushrooms (Amanita phalloides)]. / Amatoxine-intoxicatie door soep van zelfgeplukte groene knolamaniet (Amanita phalloides).

Two patients, a 54-year-old man and a 51-year-old woman, presented with abdominal pain, vomiting and diarrhoea; these symptoms developed 9 and 15 hours, respectively, after consumption of soup from mushrooms that they had picked themselves. As a result of these events, a third patient, a 55-year-old woman with diarrhoea who had also eaten the soup, also presented herself. The first patient recognised deathcap or death angel mushrooms (Amanita phalloides) on a photograph. All three patients were treated for amatoxin poisoning with a combination of high-dose penicillin G, silibinin and acetylcysteine intravenously. The poisoning was later confirmed by the results of urinalysis. The patients were discharged in good condition 8 days later.

[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.

[A patient with long-term, unrecognized leishmaniasis]. / Een patiënt met jarenlang niet onderkende mucocutane leishmaniasis.

A man from Surinam presented at the Department of Internal Medicine with a perforated septum and progressive collapse of the nose. This condition had existed for 22 years, though earlier analysis had not revealed the cause. Microscopic analysis showed a granulomatous inflammatory reaction, with cultures revealing of Leishmania. The diagnosis was mucocutaneous leishmaniasis and PCR indicated Leishmania braziliensis complex. The patient was treated for mucocutaneous leishmaniasis by a 28-day course of intravenous sodium-stibogluconate therapy. Initially, treatment was stopped briefly due to neurotoxicity, but was recommenced and successfully completed. After treatment the infection parameters returned to normal and the patient was referred for reconstructive nasal surgery. Due to a low parasitic load mucocutaneous leishmaniasis can be difficult to detect, especially in chronic cases. However, the use of molecular techniques has improved both the sensitivity and specificity of detection. The ability to distinguish between different species and sub-species is of prognostic and therapeutic relevance.

[Behçet's disease and the possibilities of modern tumour necrosis factor inhibiting medication]. / De ziekte van Behçet en de mogelijkheden van moderne tumornecrosisfactor-remmende medicatie.

A 25-year-old woman was admitted after having had a fever for one month, headache, nausea, vomiting, dysarthria and right-sided hemiparesis. A 35-year-old man was admitted because of severe loss of vision and a history of focal retinochoroiditis. Both were suffering from Behçet's disease. Behçet's disease can present with systemic symptoms that might be related to aberrant T-cell functions. It is treated with a variety of immunoregulatory drugs. Recently, treatment with tumour necrosis factor (TNF) alpha-inhibiting molecular designed drugs such as infliximab or etanercept has improved the therapeutic prospective of Behçet patients. Both of the patients described above developed refractory disease and responded to treatment with these new drugs.

[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.

Behçet's disease, hospital-based prevalence and manifestations in the Rotterdam area.

INTRODUCTION: Behçet's disease is most prevalent in countries along the former Silk Road. Prevalence varies from 70-420 per 100,000 in Turkey, and 13.5-20 and 1-2 per 100,000 in Asia and Western Europe, respectively. Additionally, disease severity and morbidity might be correlated with ethnicity. We studied demography and morbidity in the Dutch cohort of patients with Behçet's disease and compared those with known figures. PATIENTS AND METHODS: The prevalence of Behçet's patients in the Rotterdam area was determined by comparing the total number of patients within the ethnic population with the number of patients diagnosed with Behçet's disease. Patient files of the Erasmus University Medical Centre (Erasmus MC) were reviewed for morbidity figures and compared with existing data. RESULTS: In total 84 Behçet's patients of Dutch, Turkish or Moroccan descent were identified in the Rotterdam area. Prevalence of Behçet's disease differed per ethnicity: 1, 71 and 39 per 100,000 for Dutch-Caucasians, Turks, and Moroccans, respectively. These figures are comparable with occurrence in West Turkey and Morocco. Within the studied Erasmus MC cohort no significant differences in morbidity appeared between the ethnic groups. However, uveitis and pustules were significantly more common in the Erasmus MC cohort as compared with UK, German, Turkish and Moroccan cohorts. DISCUSSION AND CONCLUSIONS: We present the first epidemiological study of Behçet's disease in the Netherlands. The prevalence of Behçet's disease in the studied Dutch region and in countries of ancestry is similar. Morbidity is equally spread, compared with other countries, but uveitis and pustules seem to be more common in the Netherlands.

[From gene to disease; adrenocortical insufficiency, achalasia and disrupted tear secretion: Allgrove syndrome]. / Van gen naar ziekte; bijnierinsufficiëntie, achalasie en gestoorde traansecretie: de ziekte van Allgrove.

Allgrove syndrome (triple A syndrome) is an autosomal recessive disorder characterised by adrenocortical insufficiency, achalasia and alacrima. Patients also suffer from diverse neurological disorders. Allgrove syndrome is caused by mutations in the AAAS gene located at chromosome 12q13, which encodes for a tryptophan-aspartic acid (WD) repeat protein (aladin). The exact function of this protein is still not known.

[Severe hypokalemia with paralysis in a patient with distal renal tubular acidosis as an initial expression of Sjögren's syndrome]. / Ernstige hypokaliëmie met paralyse bij een patiënte met een distale renale tubulaire acidose als eerste uiting van het syndroom van Sjögren.

In a 33-year-old woman with a recent flaccid paralysis of the arms and legs, laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidosis, thus establishing the diagnosis of distal renal tubular acidosis. The patient made a full recovery after potassium and alkali replacement. Further investigation revealed Sjögren's syndrome as the underlying cause.