Acutegeneralizedexanthematouspustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate con- sisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotyp- ic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell recep- tor V β -expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced signifi- cantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction.
The patient was aggressively resuscitated with multiple intravenous crystalloid fluid boluses. Vancomycin was stopped and intravenous linezolid was started. Chest radiograph was normal. Brain MRI did not show evi- dence of leptomeningeal enhancement or signs of recur- rent infection. Abdominal ultrasound was unremarkable. The patient was admitted to the infectious disease ward to undergo further work-up. Dermatology was consulted and skin biopsies were obtained. He was started on top- ical steroids for the skin rash, which was suspected to be acutegeneralizedexanthematouspustulosis. However, the patient continued to have fevers, and he remained
AcuteGeneralizedExanthematousPustulosis is characterized by the acute and extensive onset of pustular lesions following the use of drugs, such as antibiotics, which usually has a good prognosis. However, the concomitance of fever and leukocytosis makes it necessary to exclude systemic infectious foci as well as other dermatological differential diagnoses. Therefore, clarification of the clini- cal picture is fundamental for the early diagnosis, since the suspension of the causative drug is necessary to resolve the condition.
reactions often affect the skin, with variable cutaneous symptoms. They usually appear as delayed urticarial and maculopapular eruptions. The clinical manifesta- tion of urticaria is indistinguishable in both immediate and non-immediate reactions, and the only parameter that can differentiate them is the time interval between drug intake and the onset of the reaction. In these cases it is very difficult to differentiate between immediate and non-immediate reactions, as this chronological classifica- tion has limitations as described above. Non-immediate reactions can also appear as more heterogeneous and less frequent clinical entities such as fixed drug eruptions, vasculitis, blistering diseases (such as toxic epidermal necrolysis (TEN), Stevens–Johnson syndrome (SJS) and generalized bullous fixed drug eruptions), drug-induced hypersensitivity syndrome (DHIS)/drug reaction with eosinophilia and systemic symptoms (DRESS), acute gen- eralized exanthematouspustulosis (AGEP) and symmet- ric drug-related intertriginous and flexural exanthemas (SDRIFE). Internal organs can be affected, either alone or with cutaneous symptoms; these include hepatitis, renal failure, pneumonitis, anemia, neutropenia, and thrombo- cytopenia .
Severe pancreatitis is defined by pancreatitis associated with organ failure and/or local complication such as necrosis, abscess or pseudocyst. The natural course of severe acute pancreatitis runs in two phases. The first two weeks are characterized by the systemic inflammatory response syndrome (SIRS) resulting from the release of inflammatory mediators.  In patients with necrotizing pancreatitis, organ failure is common and often occurs in the absence of infection. In addition to organ dysfunction, general derangements include hypovolemia, a hyper dynamic circulatory regulation, fluid loss from the intravascular space and increased capillary permeability.
The cholinergic system is responsible for innervating the sweat glands and acetylcholine (Ach) is the main inducer of sweating. Acetylcholine functions through 2 types of receptors: nicotinic (nAchR) and muscarinic (mAchR). The level of Ach is controlled by Ach nicotinic transferase and this can affect the sweat glands functions. Studies have revealed that the cholinergic system is impli- cated in the inflammatory process, with alterations in the expression of enzymes: acetylcholinesterase and choline acetyltransferase and nicotinic acetylcholine receptors in the skin of PPP patients. 30 It has been demonstrated, due to the fact that there are large amounts of esterase in the lower layers of the acrosiringium in patients with PPP, that the Ach level is lower, as the esterase decompose the neurotransmitter. Nicotine binds to nAch receptors in the absence of Ach. It is believed that the activation of nico- tine Ach receptors by nicotine and not by Ach may play a role in PPP pathogenesis, as it leads to the accumulation of eosinophils and neutrophils, and consequently, to the formation of pustules. In addition, nicotine likewise affects the keratinocytes nearby the sweat glands and causes increased keratosis of the excretory ducts. 27,31 In fact, an association has been described between the cholinergic system and nicotine that appears to be based on the Table 1 Summarizes the Main Clinical Features of Palmoplantar Pustular Psoriasis and Palmoplantar Pustulosis
144. Leverich GS, Altshuler LL, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Kupka RW, Denicoff KD, Nolen WA, Grunze H, Martinez MI, Post RM. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry 2006;163:232‑9. 145. Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW,
The Japanese guideline was published in 2018 by the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases as an update to Umezawa et al ’ s 37 2003 GPP guideline. This guideline by Fujita et al de ﬁ nes GPP as a rare disease in which acute fever, generalized skin rashes, and many sterile pustules develop. Histopathologically, GPP forms subcor- neal pustules characterized by Kogoj ’ s spongiform pus- tules. GPP may or may not be preceded by PV and is characterized by repeated disease recurrence. During the course of the disease, patients have abnormal clinical ﬁ ndings associated with systemic in ﬂ ammation and often present with mucosal symptoms and arthritis as complica- tions. Although rare, GPP may be accompanied by certain eye symptoms and secondary amyloidosis.
Abstract. Several speciﬁc types of ordinary and generalized connectedness in a generalized topological space have been deﬁned and investigated for var- ious purposes from time to time in the literature of topological spaces. Our recent research in the ﬁeld of a new type of generalized connectedness in a generalized topological space is reported herein as a starting point for more generalized types.
Empirical treatment can be implemented primary against Gram-negative bacteria and enterococci. The choice of antibiotics is conducted on the basis of in vi- tro assays for antimicrobial susceptibility testing (anti- biogram). Flouroquinolones act very well as initial the- rapy, as well as trimethoprim / sulfamethoxazole. The recommended duration of antibiotic therapy is betwe- en 4 and 6 weeks to prevent complications, as are pros- tate abscess and chronic prostatitis. The auxiliary ther- apy include antipyretics, analgesics, laxant agents, rehydration and rest. Patients with severe complicati- ons, such are: sepsis, immune deficiency and acute uri- nary retention, require hospitalization. Transurethral catheterization or other instrumentation is contraindi- cated during the acute infection. Acute urinary reten- tion should be eliminated by suprapubic drainage until the patient is able to empty the bladder independently.
The implementation of cTNI measurement in routine laboratory testing on admission enabled the acquisition of a large series of patients with cTNI assessment after an acutegeneralized convulsive seizure. Missing patients are unlikely because the data base used is also the basis for hospital payment. Similar to previous investigations, a detailed evaluation of the renal function is not avail- able in our study. As some investigators identified a reduced glomerular filtration rate as potentially respon- sible for increased troponin levels, in this context detailed evaluation of the renal function appears mandatory. In our study increased creatinine levels, allowing certain es- timation of the renal function were not associated with a cTNI increase . Concerning the renal function, there Table 2 Relationship between selected parameters and cTNI elevation in patients with epileptic seizure
ext, fr : P (Ω) −→ P (Ω) are the oldest, and g-Ext g , g-Fr g : P (Ω) −→ P (Ω) are the newest. Thus, the studies of primitive operators of these kinds have evolved from the studies of ordinary exterior and ordinary frontier operators in ordinary topological spaces to the studies of generalized exterior and generalized frontier operators in generalized topological spaces.
Time to antibiotic administration is a key element in sepsis care, and the Surviving Sepsis Campaign (SSC) guidelines (2004, 2008, 2012, and 2016) have repeatedly recommended initiating empirical broad-spectrum ther- apy within 3 h from triage or sepsis recognition [1–4]. However, the updated 2018 SSC guidelines recommend a 1-h window for antibiotic administration following the recognition of sepsis as a reasonable approach ; this update has been significantly debated, and it remains controversial . Although it would be impossible to argue against appropriate and timely antibiotic therapy for sepsis considering its time-sensitive nature, sepsis is different from other emergent conditions such as acute coronary syndrome, stroke, or trauma. Specifically, its recognition by healthcare providers within 1 h of presen- tation may be difficult to achieve in real-life settings be- cause of vague presenting symptoms and the fact that its exact onset is mostly unobservable. Further, the only randomized controlled trial (RCT) that evaluated early antibiotic use in patients with suspected infection failed to reduce mortality, although this was in the pre- hospital setting .