Combination of gonadotropin-releasing hormone (GnRH) agonists with GnRH antagonists before chemotherapy reduce but does not completely prevent a follicle-stimulating hormone flare-up

Increasing evidence supports GnRH agonists to be an effective treatment to preserve ovarian function during chemotherapy, but the initial flare-up of FSH during the first week after GnRH agonist application still limits its use. The combination of GnRH agonists with GnRH antagonists might solve this problem to some extent as the addition of GnRH antagonists at least significantly reduces the FSH flare-up.

Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis

To evaluate the prognostic value of anterior chamber (AC) laser flare (LF) in uveitis associated with juvenile idiopathic arthritis (JIA).

Drug hypersensitivity: flare-up reactions, cross-reactivity and multiple drug hypersensitivity

In drug hypersensitivity, change of drug treatment and continuation with a new drug may result in reappearance of drug hypersensitivity symptoms. This is not uncommon in patients with chronic infections requiring continued and long-lasting antibiotic treatments. For the clinician, the question arises whether these symptoms are due to cross-reactivity, are due to a new sensitization or are a reflection of a multiple drug hypersensitivity syndrome. Based on the p-i concept (pharmacological interaction with immune receptors), we propose that the efficient stimulation of T cells by a drug is the sum of drug-T-cell receptor affinity and readiness of the T cell to react, and therefore not constant. It heavily depends on the state of underlying immune activation. Consequently, drug hypersensitivity diseases, which go along with massive immune stimulations and often high serum cytokine values, are themselves risk factors for further drug hypersensitivity. The immune stimulation during drug hypersensitivity may, similar to generalized virus infections, lower the threshold of T-cell reactivity to drugs and cause rapid appearance of drug hypersensitivity symptoms to the second drug. We call the second hypersensitivity reaction a "flare-up" reaction; this is clinically important, as in most cases the second drug may be tolerated again, if the cofactors are missing. Moreover, the second treatment is often too short to cause a relevant sensitization.

The Carrington event not observed in most ice core nitrate records

The Carrington Event of 1859 is considered to be among the largest space weather events of the last 150 years. We show that only one out of 14 well-resolved ice core records from Greenland and Antarctica has a nitrate spike dated to 1859. No sharp spikes are observed in the Antarctic cores studied here. In Greenland numerous spikes are observed in the 40 years surrounding 1859, but where other chemistry was measured, all large spikes have the unequivocal signal, including co-located spikes in ammonium, formate, black carbon and vanillic acid, of biomass burning plumes. It seems certain that most spikes in an earlier core, including that claimed for 1859, are also due to biomass burning plumes, and not to solar energetic particle (SEP) events. We conclude that an event as large as the Carrington Event did not leave an observable, widespread imprint in nitrate in polar ice. Nitrate spikes cannot be used to derive the statistics of SEPs.

Flare-up reactions in severe drug hypersensitivity: infection or ongoing T-cell hyperresponsiveness

"Flare-up" reactions are late manifestations of severe T-cell-mediated drug hypersensitivity reactions. Management is anti-inflammatory treatment and avoiding unnecessary medicines. Symptoms like fever, lymph node swelling, and blood count abnormalities may lead to confusion with bacterial infections. For prompt recognition it is important to keep the differential diagnosis in mind.

Eosinophilic vasculitis: an inhabitual and resistant manifestation of a vasculitis

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosuppressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.

Atopic dermatitis - from new pathophysiologic insights to individualized therapy

Recently, important novel insights into the complex pathophysiology of atopic dermatitis (AD) have been gained. However, in most cases the therapy of AD is limited to base line therapy with emollients combined with symptomatic, rather general immunosuppressive treatment approaches of the flare-ups. Latest research findings together with experiences from daily clinical practice, which support the concept that a combination of general disease features together with specific trigger factors in the individual patients drive the disease, might be helpful for a subclassification of patients with AD based on the most relevant pathophysiologic modifications. Subclassification of patients with AD seems indispensable to introduce rationale-based, individualized treatment approaches of AD, which target specific modified pathways. In this review, we provide an overview about a selection of pathophysiologic pathways, which hold promise to represent targets of such therapeutic approaches in the near future.

Molecular epidemiology of a large community-based outbreak of hepatitis B in Bristol, U.K.

A large outbreak of hepatitis B virus (HBV) infection in the U.K. occurred between 2001 and 2005 in Bristol, U.K.

Investigation of a large community-based outbreak of hepatitis B infection in the United Kingdom

We describe the largest outbreak of hepatitis B virus infection reported to date in the UK. Between July 2001 and December 2005, 237 cases were identified in Avon, South West England. The likely route of transmission was injecting drug use in 44% (104/237) and heterosexual intercourse in 30% (71/237) of cases. A case-control study in injectors showed that injecting crack cocaine [adjusted odds ratio (aOR) 23·8, 95% confidence interval (CI) 3·04-186, P<0·001] and sharing injecting paraphernalia in the year before diagnosis (aOR 16·67, 95% CI 1·78-100, P=0·010) were strongly associated with acute hepatitis B. In non-IDUs number of sexual partners and lack of consistent condom use were high compared to a national sample. We describe the control measures implemented in response to the outbreak. This outbreak has highlighted the problems associated with the low uptake from the national hepatitis B vaccination policy which targets high-risk groups, the difficulties of identifying those at risk of acquiring hepatitis B infection through heterosexual sex, and injecting crack cocaine as a risk factor for hepatitis B.

HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans

Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

Therapy of steroid-resistant inflammatory bowel disease

Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant.