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141-603: DRESS is classified as one form of severe cutaneous adverse reactions (SCARs). In addition to DRESS, SCARs includes four other drug-induced skin reactions: the Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Stevens–Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN) and acute generalized exanthematous pustulosis (AGEP). The SCARs disorders have similar disease mechanisms . New strategies are in use or development to screen individuals at risk for DRESS to aid them in avoiding medications that increase

282-438: A post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges. Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord , may be surrounded with pus  – as may the meningeal vessels. For some causes of meningitis, protection can be provided in the long term through vaccination , or in

423-508: A 99.9% true chance of not developing the DRESS syndrome when treated with carbamazepine. In this particular example, the HLA-A31:01 allele is virtually necessary but clearly not sufficient for developing the DRESS syndrome in response to carbamazepine. The table also shows that: positive predictive values lie between 0.59-55%, i.e. far below 100%; positive as well as negative predictive values vary with

564-537: A CSF leak. Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay in treatment has been associated with a poorer outcome. Thus, treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted. If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered before transfer to hospital. Intravenous fluids should be administered if hypotension (low blood pressure) or shock are present. It

705-427: A cause of meningitis in young children in those countries. In the countries in which the disease burden is highest, however, the vaccine is still too expensive. Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps. Meningococcus vaccines exist against groups A, B, C, W135 and Y. In countries where

846-666: A consequence of the HLA allele and T-cell receptor variants that individuals express in their antigen presentation immune pathways; their ADME , i.e. efficiency in A bsorbing, D istributing to tissues, M etabolizing, and/or E liminating a drug or drug metabolite; and other less well-defined factors. Drugs can cause SCARs by subverting the antigen presentation pathways which recognize and trigger immune responses to non-self epitopes (i.e. antigens ) on foreign proteins. These proteins are taken up by antigen-presenting cells (APC) and degraded into small peptides . The peptides are inserted into

987-551: A couple of weeks before diagnosis. The most common fungal meningitis is cryptococcal meningitis due to Cryptococcus neoformans . In Africa, cryptococcal meningitis is now the most common cause of meningitis in multiple studies, and it accounts for 20–25% of AIDS-related deaths in Africa. Other less common pathogenic fungi which can cause meningitis include: Coccidioides immitis , Histoplasma capsulatum , Blastomyces dermatitidis , and Candida species. A parasitic worm

1128-400: A different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear. Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to

1269-433: A drug or metabolite may stimulate these T cells by inserting into the groove on a HLA protein to serve as a non-self epitope or bind outside of this groove to alter a HLA protein so that it forms a non-self epitope. Importantly, however, non-self epitopes must bind to specific HLA serotypes in order to stimulate T cells. Since the human population expresses some 13,000 different HLA serotypes while an individual expresses only

1410-476: A far more serious acute necrotizing eosinophilic myocarditis which has a mortality rate of more than 50%. Neurological manifestations of the DRESS syndrome include headache, seizure, coma, and motor dysfunction due to meningitis or encephalitis . Rare manifestations of the disorder include inflammation of the pancreas, gastrointestinal tract, and spleen. The following table gives the percentages for organ involvement and blood abnormalities found in individuals with

1551-402: A few HLA proteins. The following table list drugs repeatedly implicated in eliciting SCARs; it also gives the drugs' therapeutic targets, HLA serotypes through which they act, the types of SCARs disorders they trigger, the negative and positive predictive values for the drugs (where known), and the populations afflicted. Positive predictive values give the true percentages of individuals with

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1692-470: A fraction of them and since a DRESSs-inducing drug or metabolite interacts with only one or a few HLA serotypes, a drug's ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or its metabolite. Thus, only rare individuals are predisposed to develop SCARs in response to a particular drug on the basis of their expression of HLA serotypes. Studies have identified several HLA serotypes associated with development of

1833-412: A glass is rolled over it) may also be present. The inflammation may be caused by infection with viruses , bacteria , fungi or parasites . Non-infectious causes include malignancy ( cancer ), subarachnoid hemorrhage , chronic inflammatory disease ( sarcoidosis ) and certain drugs . Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore,

1974-406: A groove on HLA proteins that are part of major histocompatibility complexes (i.e. MHC) and presented to T-cell receptors (TCR) on nearby cytotoxic T cells (i.e. CD8 T cells) or T helper cells (i.e. CD4 T cells). T-cell receptors are heterologous; only a small fraction of them can bind a particular epitope on presented peptides and this binding is restricted to non-self epitopes. Upon binding

2115-402: A group of bacteria that includes Treponema pallidum (the cause of syphilis ) and Borrelia burgdorferi (known for causing Lyme disease ), and may also result from cerebral malaria (malaria infecting the brain). The types of bacteria that cause bacterial meningitis vary according to the infected individual's age group. A head injury potentially allows nasal cavity bacteria to enter

2256-490: A group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose , mouth , and lips. In more severe cases, SCARs also involves serious damage to internal organs. SCARs includes five syndromes: The five disorders have similar pathophysiologies , i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop

2397-506: A higher incidence of relapse compared to topical glucocorticoid treatment and may be associated with a higher rate of opportunistic infection . Accordingly, less severe cases of this disorder may be better treated conservatively with general support and, where needed, topical glucocorticoids. Severer cases, particularly those involving significant internal organ involvement, may require systemic corticosteroids and efforts to support heart, kidney, lung, or other organ dysfunctions. DRESS syndrome

2538-555: A higher likelihood of bacterial meningitis, as does a higher white blood cell count. If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis. Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae , Neisseria meningitidis , Haemophilus influenzae , Escherichia coli and group B streptococci ; its routine use

2679-435: A later stage to assess for complications of meningitis. In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial meningitis. The cause of hyponatremia, however, is controversial and may include dehydration, the inappropriate secretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration . A lumbar puncture

2820-465: A non-self epitope on a presented peptide, a T-cell receptor becomes active in stimulating its parent cell to mount one of two types of immune responses based on whether the APC presenting the peptide is professional or non-professional in type. Non-professional APC include all nucleated cells; these cells load the processed peptides onto MHC class I (i.e. HLA-A , HLA-B , or HLA-C ) proteins and thereon present

2961-729: A non-self epitope on presented peptides are stimulated to orchestrate various immune reactions that attack soluble proteins, pathogens, and host cells and tissues that express the non-self epitope. SCARs-inducing drugs can act through these pathways to cause CD8 or CD4 T cells to mount immune responses that are inappropriately directed against bodily tissues. Four models propose the underlying mechanisms by which SCARs-inducing drugs may activate T cells to mount immune responses against self: HLA genes are highly polymorphic , i.e. have many different serotypes (i.e. alleles ) while T-cell receptor genes receptors are edited . i.e. altered to encode proteins with different amino acid sequences. Humans, it

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3102-579: A particular place and population. For instance, in the United Kingdom, empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone . In the US, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended. Chloramphenicol , either alone or in combination with ampicillin , however, appears to work equally well. Empirical therapy may be chosen on

3243-433: A particularly severe form of the DRESS syndrome-like reactions to this anti-inflammatory drug . None-genetic ADME factors are also associated with increased risks of developing SCARs. For example, allopurinol is metabolized to oxipurinol , a product with a far slower renal excretion rate than its parent compound. Renal impairment is associated with abnormally high blood levels of oxipurinol and an increased risk of developing

3384-584: A person has meningitis. The jolt accentuation test is not specific or sensitive enough to completely rule out meningitis. If someone is suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein , complete blood count ), as well as blood cultures . If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment, especially if this may be longer than 30 minutes. Often, CT or MRI scans are performed at

3525-441: A person with meningitis has been. Viral meningitis is typically caused by enteroviruses , and is most commonly spread through fecal contamination. The risk of infection can be decreased by changing the behavior that led to transmission. Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as

3666-413: A significant chance of expressing the indicated allele since screening of populations with extremely low incidences of expressing an allele is considered cost-ineffective. Individuals expressing the HLA allele associated with sensitivity to an indicated drug should not be treated with the drug. These recommendations include: Current trials are underway to evaluate the ability of genetic screening to prevent

3807-695: A significant chance of expressing the indicated variant since screening of populations with extremely low incidences of expressing the variant allele is considered cost-ineffective. Individuals expressing the HLA allele associated with sensitivity to an indicated drug should not be treated with the drug. These recommendations include: Current trials are underway to evaluate the cost-effectiveness of genetic screening for HLA-B*13:01 to prevent dapsone-induced SCARs in China and Indonesia. Similar trials are underway in Taiwan to prevent phenytoin-induced SCARs in individuals expressing

3948-454: A spectrum of Type IV, Subtype IVc, delayed hypersensitivity reactions, i.e. reactions initiated by CD8 T cells and natural killer T cells . They are characterized initially by fever and flu-like symptoms followed within days by skin as well as mucous membrane blisters and denudation . Differentiation of the three disorders is based on the extent of disease with SJS involving <10%, SGS/TEN involving 10% to 30%, and TEN involving >30% of

4089-437: A temporary or long-term drainage device, such as a cerebral shunt . The osmotic therapy, glycerol , has an unclear effect on mortality but may decrease hearing problems. Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in

4230-454: A type of meningoencephalitis where not only the meninges are affected but also the brain tissue . Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges ( malignant or neoplastic meningitis ) and certain drugs (mainly non-steroidal anti-inflammatory drugs , antibiotics and intravenous immunoglobulins ). It may also be caused by several inflammatory conditions, such as sarcoidosis (which

4371-463: A vaccine) only elicit a weak response from the immune system , or cross-react with normal human proteins. Still, some countries ( New Zealand , Cuba , Norway and Chile ) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules. Two new vaccines, both approved in 2014, are effective against a wider range of group B meningococci strains. In Africa, until recently,

Drug rash with eosinophilia and systemic symptoms - Misplaced Pages Continue

4512-430: Is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis ). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR). Meningitis can be diagnosed after death has occurred. The findings from

4653-446: Is a SCARs type IV, subtype IVb reaction. This contrasts with SJS, SJS/TEN, and TEN which are type IV, subtype IVc reactions and AGEP which is a type IV subtype IVd reaction. DRESS syndrome therefore differs from the other SCARs disorders in that it involves the tissue-injuring action of CD4 cells and the cell- and tissue-injuring action of eosinophils as well as the release of the following cytokines: Interleukins 5 and 13 which simulate

4794-509: Is a hallmark of the disease), enlarged and sometimes painful lymph nodes , and other symptoms due to inflammation -based internal organ involvement, most commonly liver, less commonly kidney, lung, and heart, and rarely pancreas or other organs. Laboratory findings include increased blood eosinophil and atypical lymphocyte counts, elevated blood markers for systemic inflammation (e.g. erythrocyte sedimentation rate , C-reactive protein ), and evidence of internal organ involvement. Liver involvement

4935-431: Is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis ( enterovirus , herpes simplex virus 2 and mumps in those not vaccinated for this). Serology (identification of antibodies to viruses) may be useful in viral meningitis. If tuberculous meningitis

5076-463: Is also associated with other maladies caused by high levels of blood eosinophils such as the various hypereosinophilia -related disorders: persistent asthma and allergic rhinitis and, more significantly, eosinophil-based and lymphocyte-based inflammation of the liver (>70% of cases), kidney (20% to 40% of cases), lung (~33% of cases), heart (4% to 27% of cases), and, uncommonly, the meninges , brain, gastrointestinal tract, and spleen. The disorder

5217-579: Is compatible with the notion that specific types of T-cell receptors are involved in the development of specific drug-induced SCARs. Certain variations in ADME (i.e. absorption , distribution , metabolism , and excretion of a drug) are associated with the development of SCARs. These variations influence the levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke SCARs. A prominent example of an ADME-based genetic predisposition to SCARs involves

5358-491: Is detected by measuring blood levels of alanine aminotransferase (ALT), a marker of hepatocyte injury, and alkaline phosphatase (ALP), a marker of bile duct injury, to define three types of injury: hepatocellular (elevated ALP, high ALT/ALP ratio of greater than 5), cholestatic (high ALP, low ALT/ALP ratio of less than 2), and mixed (elevated ALT and ALP, ALT/ALP ratio between 2 and 5, the cutoff values for cholestatic and hepatocellular injury, respectively). Renal involvement

5499-457: Is done by positioning the person, usually lying on the side, applying local anesthetic , and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using a manometer . The pressure is normally between 6 and 18 cm water (cmH 2 O); in bacterial meningitis the pressure

5640-466: Is estimated, express more than 10,000 different HLA class I proteins, 3,000 different HLA class II proteins, and 100 trillion different T-cell receptors. An individual, however, expresses only a fraction of these polymorphic or edited gene products. Since a SCARs-inducing drug interacts with only one or a few types of HLA proteins or T-cell receptors, its ability to induce a SCARs disorder is limited to those individuals who express those HLA proteins that make

5781-414: Is evidence of respiratory failure . If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol ). Seizures are treated with anticonvulsants . Hydrocephalus (obstructed flow of CSF) may require insertion of

Drug rash with eosinophilia and systemic symptoms - Misplaced Pages Continue

5922-507: Is lengthened and worsened in individuals that develop reactivation of latent viruses of the herpes viruses . The estimated mortality rate for the DRESS syndrome is about 10%. Allopurinol and sulfasalazine account for almost 66% of DRESS syndrome cases with minocycline being the third most common cause of the disorder; Strontium ranelate , leflunomide , dapsone , and nonsteroidal anti-inflammatory drugs ( diclofenac , celecoxib , ibuprofen , and phenylbutazone ) are less common causes of

6063-581: Is limited to those individuals whose T cells express a T-cell receptor(s) that can interact with drug or its metabolite. Thus, only rare individuals are predisposed to develop a SCARs disorder in response to a particular drug on the basis of their expression of specific cell receptor types. While the evidence supporting these ideas is limited, one study identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on

6204-403: Is meningitis caused by Mycobacterium tuberculosis , is more common in people from countries in which tuberculosis is endemic, but is also encountered in people with immune problems, such as AIDS . Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system . Anatomical defects allow continuity between

6345-414: Is more prone to occur in older individuals and in those with prior kidney or cardiovascular disease; it may take the form of severe interstitial nephritis , acute tubular necrosis , or vasculitis and may lead to kidney failure and, uncommonly, be lethal. Lung involvement takes the form of interstitial pneumonitis , pleuritis , or the acute respiratory distress syndrome ; minocycline and abacavir are

6486-406: Is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate in CSF indicate

6627-423: Is not clear whether intravenous fluid should be given routinely or whether this should be restricted. Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early and to admit the person to an intensive care unit , if deemed necessary. Mechanical ventilation may be needed if the level of consciousness is very low, or if there

6768-462: Is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful. Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it

6909-552: Is often assumed to be the cause of eosinophilic meningitis when there is a predominance of eosinophils (a type of white blood cell) found in the cerebrospinal fluid. The most common parasites implicated are Angiostrongylus cantonensis , Gnathostoma spinigerum , Schistosoma , as well as the conditions cysticercosis , toxocariasis , baylisascariasis , paragonimiasis , and a number of rarer infections and noninfective conditions. Rarely, free-living parasitic amoebae can cause naegleriasis , also called amebic meningitis ,

7050-753: Is one of several terms that have been used to describe a severe idiosyncratic reaction to a drug that is characterized by a long latency of onset after exposure to the offending medication, a rash, involvement of internal organs, hematologic abnormalities, and systemic illness. Other synonymous names and acronyms include drug-induced hypersensitivity syndrome (DIHS or DHiS), anticonvulsant hypersensitivity syndrome, drug-induced delayed multiorgan hypersensitivity syndrome, drug-induced pseudolymphoma, anticonvulsant hypersensitivity syndrome , allopurinol hypersensitivity syndrome , dapsone syndrome , and dapsone hypersensitivity syndrome . Severe cutaneous adverse reactions Severe cutaneous adverse reactions ( SCARs ) are

7191-436: Is rarely associated with severe complications although superinfection of skin lesions may be life-threatening. Individuals are predisposed to develop SCARs in response to a given drug based on the types of human leukocyte antigen (i.e. HLA) proteins and T-cell receptors that they express; their ability to process an instigating drug or the drug's metabolite(s); and other less well-defined factors. These predispositions are

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7332-409: Is suspected, the sample is processed for Ziehl–Neelsen stain , which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive. A diagnostic and therapeutic difficulty

7473-520: Is then called neurosarcoidosis ), connective tissue disorders such as systemic lupus erythematosus , and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçet's disease . Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated. The meninges comprise three membranes that, together with

7614-462: Is thought to be caused by herpes simplex virus type 2 . There are a number of risk factors for fungal meningitis , including the use of immunosuppressants (such as after organ transplantation ), HIV/AIDS , and the loss of immunity associated with aging. It is uncommon in those with a normal immune system but has occurred with medication contamination . Symptom onset is typically more gradual, with headaches and fever being present for at least

7755-474: Is unlikely. Other problems can produce symptoms similar to those above, but from non-meningitic causes. This is called meningism or pseudomeningitis. Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash , which may precede other symptoms. The rash consists of numerous small, irregular purple or red spots ("petechiae") on

7896-452: Is usually caused by viruses, but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or when pathogens infect a space adjacent to the meninges (such as sinusitis ). Endocarditis (an infection of the heart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes ,

8037-482: Is usually elevated. In cryptococcal meningitis , intracranial pressure is markedly elevated. The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis. The CSF sample is examined for presence and types of white blood cells , red blood cells , protein content and glucose level. Gram staining of

8178-621: The Greek μῆνιγξ meninx , 'membrane', and the medical suffix -itis , 'inflammation'. In adults, the most common symptom of meningitis is a severe headache , occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness). The classic triad of diagnostic signs consists of neck stiffness, sudden high fever , and altered mental status ; however, all three features are present in only 44–46% of bacterial meningitis cases. If none of

8319-402: The cerebrospinal fluid , enclose and protect the brain and spinal cord (the central nervous system ). The pia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates

8460-423: The choroid plexus . Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci ; this phenomenon is much less common in adults. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of

8601-714: The dura mater can be identified. The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system . When components of the bacterial cell membrane are identified by the immune cells of the brain ( astrocytes and microglia ), they respond by releasing large amounts of cytokines , hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of

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8742-540: The human leukocyte antigen (i.e. HLA) component of their major histocompatibility complex (i.e. MHC); and presents the MHC-associated peptides to the T-cell receptor on CD8 T or CD4 T cells. Those peptides expressing a drug-related, non-self epitope on their HLA-A , HLA-B , HLA-C , HLA-DM , HLA-DO , HLA-DP , HLA-DQ , or HLA-DR proteins may bind to a T-cell receptor to stimulate the receptor-bearing parent T cell to initiate attacks on self tissues. Alternatively,

8883-546: The pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis. The pneumococcal polysaccharide vaccine , which covers 23 strains, is only administered to certain groups (e.g. those who have had a splenectomy , the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children. Childhood vaccination with Bacillus Calmette-Guérin has been reported to significantly reduce

9024-405: The sensitivity of these tests is limited. They do, however, have very good specificity for meningitis: the signs rarely occur in other diseases. Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in those reporting fever and headache. A person is asked to rapidly rotate the head horizontally; if this does not make the headache worse, meningitis

9165-708: The CYP2C9*3 allele of CYP2C9 or a series of HLA alleles. Meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord , collectively called the meninges . The most common symptoms are fever , intense headache , vomiting and neck stiffness and occasionally photophobia . Other symptoms include confusion or altered consciousness , nausea , and an inability to tolerate light or loud noises . Young children often exhibit only nonspecific symptoms , such as irritability, drowsiness, or poor feeding. A non-blanching rash (a rash that does not fade when

9306-817: The CYP2CP*3 allele of the CYP2C9 gene. CYP2C9, a cytochrome P450 enzyme, metabolizes various substances including phenytoin. The CYP2CP*3 variant of CYP29C has reduced catalytic activity. Individuals studied in Japan or Malaysia, and the Han Chinese in Taiwan that express this variant have an increased chance of developing the DRESS syndrome, SJS, SJS/TEN, or TEN when taking phenytoin while Africans in Mozambique expressing this variant taking phenytoin have an increase risk of developing SJS, SJS/TEN, or TEN. These reactions appear due to increases in

9447-569: The DRESS syndrome based on various studies. There are large variations in the percentages found in different studies and populations. No gold standard exists for diagnosis, and at least two diagnostic criteria have been proposed viz., the RegiSCAR criteria and the Japanese consensus group criteria. These two sets of criteria are detailed in the following table. Drugs that commonly induce DRESS syndrome arranged according to intended clinical action include

9588-437: The DRESS syndrome for dapsone and HLA-B*13:01 in China and Indonesia. Similar trials are underway in Taiwan to prevent phenytoin-induced DRESS syndrome in individuals expressing the CYP2C9*3 allele of CYP2C9 as well as a series of HLA alleles. Immediate discontinuance of the offending drug or drug(s) is the first and critical step in treating any SCARs disorder. In the past, the mainstay treatment of severe cases of DRESS syndrome

9729-516: The DRESS syndrome in response to certain drugs, have developed tests to identify individuals who express some of these serotypes, and thereby have identified individuals who should avoid certain DRESS syndrome-inducing drugs. A drug or its metabolite may also stimulate CD8 T or CD4 T cells to initiate autoimmune responses by directly binding to the T-cell receptors on these T cells. Again, this binding appears to develop only on certain T-cell receptors. Since

9870-399: The DRESS syndrome in response to specific medications. These associations include the following: Like other drug-induced SCARs disorders, the DRESS syndrome is a type IV hypersensitivity reaction in which a drug or its metabolite stimulates cytotoxic T cells (i.e. CD8 T cells) or T helper cells (i.e. CD4 T cells) to initiate autoimmune reactions that attack self tissues. DRESS syndrome

10011-478: The DRESS syndrome when taking phenytoin apparently due to increases in the drug's blood and tissue levels. In a second example of a genetically based ADME defect causing SCARs, Japanese individuals bearing slow acetylating variants of the N-acetyltransferase 2 gene, (NAT2), viz., NAT2*6A and NAT2*7B, acetylate sulfasalazine more slowly than individuals homozygous for the wild type gene. Individuals expressing

10152-448: The DRESS syndrome, particularly the more severe forms of this disorder. Dysfunction of the kidney and liver are also suggested to promote SCARs responses to other drugs due to the accumulation of SCARs-inducing drugs or metabolites in blood and tissues. Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to promote SCARs particularly in their more serious forms. During

10293-454: The DRESS syndrome, particularly the more severe forms of this disorder. Dysfunction of the kidney and liver are also suggested to promote this disorder in response to other drugs due to the accumulation of SCARs-inducing drugs or metabolites in blood and tissues. Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to promote SCARs particularly in their more serious forms. During

10434-518: The NAT2*6A and NAT2*7 variants have an increased risk for developing DRESS syndrome-like reactions to this anti-inflammatory drug . None-genetic ADME factors are also associated with increased risks of developing the DRESS syndrome. Allopurinol is metabolized to oxipurinol , a product with a far slower renal excretion rate than its parent compound. Renal impairment is associated with abnormally high blood levels of oxipurinol and an increased risk of developing

10575-610: The SCARs-inducing effects of specific drugs and thereby avoid treatment with them. Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares a similar pathophysiology with SCARs and is caused by some of the same drugs which cause SCARs. Adverse drug reactions are major therapeutic problems estimated to afflict up to 20% of inpatients and 25% of outpatients. About 90% of these adverse reactions take

10716-437: The T cells in the blisters of patients with allopurinol-induced DRESS syndrome. This finding is compatible with the notion that specific types of T-cell receptors are involved in the development of specific drug-induced SCARs. Variations in ADME , i.e. an individual's efficiency in absorbing , distributing , metabolizing , and excreting a drug has been found to occur in cases of the DRESS syndrome. These variations influence

10857-526: The approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the population at risk with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines, though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings. Routine vaccination against Streptococcus pneumoniae with

10998-569: The appropriate HLA/non-self peptide or the T cell that expresses the T-cell receptor that recognize the non-self epitope created by the drug. Thus, only rare individuals are predisposed to develop a SCARs disorder in response to a particular drug on the bases of their expression of specific HLA protein or T-cell receptor types. SCARs disorders are triggered by wide range of drugs with the most commonly reported offenders being Carbamazepine , allopurinol , abacavir , phenytoin , and nevirapine . These drugs evoke SCARs by interacting with one or just

11139-418: The arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater , is a thick durable membrane, which is attached to both the arachnoid membrane and the skull. In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream (hematogenous spread) or through direct contact between the meninges and either the nasal cavity or

11280-468: The basis of the person's age, whether the infection was preceded by a head injury , whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present. In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes . Once the Gram stain results become available, and

11421-472: The brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead to brain herniation . If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar puncture. This applies in 45% of all adult cases. There are no physical tests that can rule out or determine if

11562-494: The brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema . The three forms of cerebral edema all lead to increased intracranial pressure ; together with

11703-484: The broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens. The results of the CSF culture generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics. For an antibiotic to be effective in meningitis it must not only be active against

11844-427: The cause for this possible predilection has not been determined, the altered immune system and the excessive production of cytokines occurring in these disorders could be contributing factors. The tissue injury in SCARs is initiated principally by CD8 or CD4 T cells. Once drug-activated, these lymphocytes elicit immune responses to self tissues that can result in SCARs drug reactions by mechanisms which vary with

11985-737: The cause of meningitis may be the skin signs of hand, foot and mouth disease and genital herpes , both of which are associated with various forms of viral meningitis. Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or worse prognosis. The infection may trigger sepsis , a systemic inflammatory response syndrome of falling blood pressure , fast heart rate , high or abnormally low temperature, and rapid breathing . Very low blood pressure may occur at an early stage, especially but not exclusively in meningococcal meningitis; this may lead to insufficient blood supply to other organs. Disseminated intravascular coagulation ,

12126-470: The commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days. Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified. The likely mechanism is suppression of overactive inflammation. Additional treatment with corticosteroids have

12267-878: The condition is classified as a medical emergency . A lumbar puncture , in which a needle is inserted into the spinal canal to collect a sample of cerebrospinal fluid (CSF), can diagnose or exclude meningitis. Some forms of meningitis are preventable by immunization with the meningococcal , mumps , pneumococcal , and Hib vaccines . Giving antibiotics to people with significant exposure to certain types of meningitis may also be useful for preventing transmission. The first treatment in acute meningitis consists of promptly giving antibiotics and sometimes antiviral drugs . Corticosteroids can be used to prevent complications from excessive inflammation. Meningitis can lead to serious long-term consequences such as deafness , epilepsy , hydrocephalus , or cognitive deficits , especially if not treated quickly. In 2019, meningitis

12408-424: The condition, but does not protect against future infections. Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents. While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is not enough evidence to determine whether this is beneficial or harmful. This applies to those with or without

12549-451: The deaths due to bacterial sepsis, particularly in the acute, early stage of these disorders. The drugs most commonly triggering the SJS, TEN, and SJS/TEN spectrum of disorders are anti-infective sulfonamides , anticonvulsants (e.g. carbamazepine and lamotrigine ), non-steroidal anti-inflammatory drugs, allopurinol , nevirapine , and chlormezanone . Allopurinol appears in some studies to be

12690-671: The disorder based on the medication evoking it, e.g. the anticonvulsant hypersensitivity syndrome , allopurinol hypersensitivity syndrome , and dapsone hypersensitivity syndrome . In 1996, however, the term DRESS syndrome was coined in a report attempting to simplify the terminology and consolidate these various clearly related syndromes into a single underlying disorder. The symptoms of DRESS syndrome usually begin 2 to 6 weeks but uncommonly up to 8–16 weeks after exposure to an offending drug. Symptoms generally include fever, an often itchy rash which may be morbilliform or consist mainly of macules or plaques , facial edema (i.e. swelling, which

12831-416: The disorder. AGEP is a rare Type IV , subtype IVd, hypersensitivity reaction dependent on neutrophils and characterized by the rapid formation of skin pustules on an erythematous background. In one study of 28 patients, the disorder was complicated by involvement of the kidney (36% of cases), lung (27%), and liver (11%). It is the least severe of the SCARs disorders, typically shows a mild course, and

12972-417: The drug's blood and tissue levels. In a second example of a genetically based ADME defect causing SCARs, Japanese individuals bearing slow acetylating variants of the N-acetyltransferase 2 gene, (NAT2), viz., NAT2*6A and NAT2*7B, acetylate sulfasalazine more slowly than individuals homozygous for the wild type gene. Individuals expressing the NAT2*6A and NAT2*7 variants have an increased risk for developing

13113-429: The drug-independent development of this disorder. The pathophysiology for the development of these drug-independent cases of AGEP is unclear. Viral infections have also been observed to be associated with the development of SJS, SJS/TEN, and TEN in the absence of a causative drug. Individuals suffering autoimmune disorders such as systemic lupus erythematosus may have an increased incidence of developing SCARs. While

13254-423: The early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause. Seizures may result from increased pressure and from areas of inflammation in the brain tissue. Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication indicate a poorer long-term outcome. Inflammation of

13395-406: The excessive activation of blood clotting , may obstruct blood flow to organs and paradoxically increase the bleeding risk. Gangrene of limbs can occur in meningococcal disease . Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal glands , leading to Waterhouse-Friderichsen syndrome , which is often fatal. The brain tissue may swell , pressure inside

13536-520: The external environment and the nervous system . The most common cause of recurrent meningitis is a skull fracture , particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids . Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such as complement deficiency , which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to

13677-697: The following: Medications associated with the development of DRESS are often popular, widely used, and/or clinically important for the control of certain diseases. This is evident in the most commonly cited medications that cause the DRESS viz., allopurinol , sulfasalazine , and minocycline , as well as in prominent but less commonly cited causes of the disorder such as strontium ranelate , leflunomide , dapsone , and nonsteroidal anti-inflammatory drugs ( diclofenac , celecoxib , ibuprofen , and phenylbutazone ). Studies have found that certain populations that express particular serotypes (i.e. alleles) of HLA-A, HLA-B, and/or HLA-C have an increased risk of developing

13818-480: The form of benign morbilliform rash hypersensitivity drug reactions such as MPR. However, they also include more serious reactions: Type IV hypersensitivity reactions are off-target drug reactions, i.e. reactions in which a drug causes toxicity by impacting a biological target other than the one(s) for which it is intended. They are T cell -initiated delayed hypersensitivity reactions occurring selectively in individuals who may be predisposed to do so because of

13959-670: The formation of blood clots in the veins ( cerebral venous thrombosis ), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain. Meningitis is typically caused by an infection . Most infections are due to viruses , and others due to bacteria , fungi , and parasites . Mostly the parasites are parasitic worms , but can also rarely include parasitic amoebae . Meningitis may also result from various non-infectious causes. The term aseptic meningitis refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis

14100-408: The genes for these receptors are highly edited , i.e. altered to encode proteins with different amino acid sequences, and since the human population may express more than 100 trillion different (i.e. different amino acid sequences) T-cell receptors while an individual express only a fraction of these, a drug's or its metabolite's ability to induce the DRESS syndrome by interacting with a T-cell receptor

14241-585: The genetically-based types of human leukocyte antigens (i.e. HLA) or T-cell receptors they express; the efficiency with which they absorb, distribute to tissues, metabolize, and eliminate a drug or drug metabolite; or less well-defined idiosyncrasies. Categorizing SCARs as a group focuses on the similarities and differences in their pathophysiologies, clinical presentations, instigating drugs, and recommendations for drug avoidance. Stevens–Johnson syndrome, toxic epidermal necrolysis , and Stevens–Johnson syndrome/Toxic epidermal necrolysis overlap syndrome are

14382-582: The growth, longevity, and activation of eosinophils; Interleukin 4 which promotes the differentiation of naive helper T cells into T h 2 helper cells that then serve to activate eosinophils as well as other types of pro-inflammatory cells; IFNγ which activates macrophages and induces the expression of Class II MHC molecules; and TNFα which promotes inflammation but also has cell-killing actions. Like other SCARs-inducing drugs, DRESS syndrome-inducing drugs or their metabolites stimulate CD8 T or CD4 T cells to initiate autoimmune responses. Studies indicate that

14523-470: The head and neck area, such as otitis media or mastoiditis , can lead to meningitis in a small proportion of people. Recipients of cochlear implants for hearing loss are more at risk for pneumococcal meningitis. In rare cases, Enterococcus spp. can be responsible for meningitis, both community and hospital-acquired, usually as a secondary result of trauma or surgery, or due to intestinal diseases (e.g., strongyloidiasis). Tuberculous meningitis , which

14664-475: The indicated HLA gene allele (identified as a serotype ) that develop the cited drug-induced SCARs; negative predictive values give the percentage of individuals without the indicated serotype that fail to develop the cited drug-induced SCARs. For example, Chinese, Korean, Japanese, and European individuals that express the HLA-A31:01 allele have a 1% true chance of developing the DRESS syndrome while HLA-A31:01 negative individuals in these specific populations have

14805-475: The levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke the DRESS syndrome. For example, the CYP2C9 gene codes for CYP2C9, a cytochrome P450 enzyme which metabolizes various substances including phenytoin. The CYP2CP*3 variant of CYP29C has reduced catalytic activity; individuals expressing this variant show an increased incidence of developing

14946-437: The lowered blood pressure often encountered in sepsis , this means that it is harder for blood to enter the brain; consequently brain cells are deprived of oxygen and undergo apoptosis ( programmed cell death ). Administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as

15087-400: The lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer. Fluid given intravenously are an essential part of treatment of bacterial meningitis. There is no difference in terms of mortality or acute severe neurological complications in children given a maintenance regimen over restricted-fluid regimen, but evidence is in favor of

15228-429: The main culprit drugs causing severe lung involvement. However, lung involvement in this disorder typically resolves. Cardiac involvement usually presents with evidence of left ventricular dysfunction and ECG changes; it occurs more often in individuals taking minocycline, ampicillin, or sulfonamides, and is either a cardiac hypersensitivity reaction classified as an eosinophilic myocarditis which generally resolves or

15369-591: The maintenance regimen in terms of emergence of chronic severe neurological complications. Additional treatment with corticosteroids (usually dexamethasone ) has shown some benefits, such as a reduction of hearing loss , and better short term neurological outcomes in adolescents and adults from high-income countries with low rates of HIV. Some research has found reduced rates of death while other research has not. They also appear to be beneficial in those with tuberculosis meningitis, at least in those who are HIV negative. Professional guidelines therefore recommend

15510-404: The mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the antigen presentation pathways of the innate immune system. The drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope . An antigen-presenting cell (APC) takes up these alter proteins; digests them into small peptides; places the peptides in a groove on

15651-427: The meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts , extraventricular drains or Ommaya reservoirs , carry an increased risk of meningitis. In these cases, people are more likely to be infected with Staphylococci , Pseudomonas , and other Gram-negative bacteria . These pathogens are also associated with meningitis in people with an impaired immune system . An infection in

15792-415: The meninges may lead to abnormalities of the cranial nerves , a group of nerves arising from the brain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing. Visual symptoms and hearing loss may persist after an episode of meningitis. Inflammation of the brain ( encephalitis ) or its blood vessels ( cerebral vasculitis ), as well as

15933-439: The meninges. Viruses that cause meningitis include enteroviruses , herpes simplex virus (generally type 2, which produces most genital sores; less commonly type 1), varicella zoster virus (known for causing chickenpox and shingles ), mumps virus , HIV , LCMV , Arboviruses (acquired from a mosquito or other insect), and the influenza virus . Mollaret's meningitis is a chronic recurrent form of herpes meningitis; it

16074-556: The most common instigator of these disorders. Any new biological or herbal remedy , it is suggested, should be considered a possible cause of these disorders under the proper clinical circumstances. The DRESS syndrome is a Type IV, Subtype IVb, hypersensitivity drug reaction, i.e. a reaction dependent on CD4(+) cells and the cell- and tissue-injuring action of eosinophils. Skin lesions inflict 73% to 100% of afflicted individuals; they are generally infiltrative macules and plaques . About 75% of cases exhibit facial edema . The syndrome

16215-454: The number of diverse T-cell receptors expressed is estimated to be as high as 10 trillion. This has made it difficult to identify specific T-cell receptor types that are uniquely associated with the development of SCARs. One study, however, identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on the T cells in the blisters of patients with allopurinol-induced SCARs. This finding

16356-459: The order just given. Reactivation of these viruses is associated with a flare-up in symptoms, a prolonged course, and increased disease severity which includes significant organ involvement and the development of certain autoimmune diseases viz., systemic lupus erythematosus , autoimmune thyroiditis , and type 1 diabetes mellitus . While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in

16497-469: The order just given. Reactivation of these viruses is associated with sequential flare-ups in symptoms, a prolonged course, and increased disease severity which includes significant organ involvement and the development of certain autoimmune diseases viz., systemic lupus erythematosus , autoimmune thyroiditis , and type 1 diabetes mellitus . While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in

16638-495: The organism in 70–85% of cases) but results can take up to 48 hours to become available. The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant), although at the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others. The concentration of glucose in CSF

16779-399: The pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Currently, screening individuals for the expression of certain HLA alleles before initiating treatment of patients with DRESS-inducing drugs is recommended. These recommendations typically apply only to specific populations that have

16920-478: The pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Rare case reports have associated the SJS/TEN spectrum of SCARs with reactivation of human herpesvirus 6; reactivation of cytomegalovirus has also been proposed to be associated with AGEP although a large study failed to observe the latter association. In all cases,

17061-467: The pathogenic bacterium but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on people with meningitis in clinical trials . Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits . Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of

17202-464: The peptides to CD8 T cells. Those CD8 T cells whose T-cell receptors bind a non-self epitope on the peptides are stimulated to attack cells or pathogens expressing this epitope. Professional APC are dendritic cells , macrophages , and B cells . They load processed peptides onto MHC class II (i.e. HLA-DM , HLA-DO , HLA-DP , HLA-DQ , or HLA-DR ) proteins and thereon present the peptides to CD4 T cells. Those CD4 T cells whose T-cell receptors bind

17343-401: The population tested; a drug may cause more than one type of SCARs disorder or interact with more than one HLA serotype to cause SCARs; and the level of susceptibility to a drug varies between populations. These findings indicate that other factors, generally regarded as due to unspecified population-related genetic differences, contribute decisively to developing SCARs. Due to gene editing.

17484-458: The presence of positive Kernig's sign or Brudziński sign . Kernig's sign is assessed with the person lying supine , with the hip and knee flexed to 90 degrees. In a person with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's sign and Brudzinski's sign are both commonly used to screen for meningitis,

17625-501: The progression of the DRESS syndrome certain viruses that previously infected an individual and then became latent are reactivated and proliferate. Viruses known to do so include certain members of the Herpesviridae family of Herpes viruses viz., Epstein–Barr virus , human herpesvirus 6 , human herpesvirus 7 , and cytomegalovirus . Individuals with DRESS syndrome may exhibit sequential reactivation of these four viruses, typically in

17766-454: The progression of the DRESS syndrome certain viruses which previously infected an individual and then became latent are reactivated and proliferate. Viruses known to do so include certain members of the Herpesviridae family of Herpes viruses viz., Epstein–Barr virus , human herpesvirus 6 , human herpesvirus 7 , and cytomegalovirus . Individuals suffering the DRESS syndrome may exhibit sequential reactivation of these four virus, typically in

17907-420: The rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine. Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, preventative treatment in close contacts with antibiotics (e.g. rifampicin , ciprofloxacin or ceftriaxone ) can reduce their risk of contracting

18048-416: The relationships of viral reactivation to the development and severity of any SCARs disorder is uncertain and requires further study. Although more than 90% of AGEP are associated with the intake of a presumptively offending drug, reports have associated infection with Parvovirus B19 , mycoplasma , cytomegalovirus , coxsackie B4 virus, Chlamydophila pneumoniae , E. coli , and Echinococcus with

18189-415: The risk of DRESS. Alternative medications are used in all individuals testing positive for these predispositions. Prior to 1996, there were numerous reports on individuals presenting with a medication-induced disorder now recognized as the DRESS syndrome. For example, anticonvulsants in the 1930s, phenytoin in 1950, and other medications in the ensuing years were reported to do so. The reports often named

18330-420: The sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such as listeriosis . Microbiological culture of the sample is more sensitive (it identifies

18471-405: The short term with antibiotics . Some behavioral measures may also be effective. Bacterial and viral meningitis are contagious, but neither is as contagious as the common cold or flu . Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but bacterial meningitis cannot be spread by only breathing the air where

18612-417: The skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live on mucosal surfaces such as the nasal cavity . This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucosal surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood–brain barrier is vulnerable – such as

18753-404: The skull may increase and the swollen brain may herniate through the skull base. This may be noticed by a decreasing level of consciousness , loss of the pupillary light reflex , and abnormal posturing . The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain ( hydrocephalus ). Seizures may occur for various reasons; in children, seizures are common in

18894-675: The three signs are present, acute meningitis is extremely unlikely. Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable and look unwell. The fontanelle (the soft spot on the top of a baby's head) can bulge in infants aged up to 6 months. Other features that distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color . Neck stiffness occurs in 70% of bacterial meningitis in adults. Other signs include

19035-420: The total bodily skin area. This spectrum of disorders is complicated by inflammation in and damage to internal organs such as the liver and, less commonly, kidney and heart. More importantly, they are also complicated by sepsis due to the loss of skin and mucous membrane epithelial barriers. In one study, SJS, TEN, and SJS/TEN mortality rates were 4.8%, 19.4%, and 14.8%, respectively, with an important portion of

19176-451: The trunk, lower extremities , mucous membranes, conjunctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching ; the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria. Other clues on

19317-484: The type of disorder that develops. Salient elements mediating tissue injury for each type of disorder include: Future studies may find that drugs which neutralize one or more of these effectors to be useful for treating SCARs disorders. Screening individuals for the expression of certain variant alleles of HLA genes before initiating treatment with particular SCARs-inducing drugs is recommended. These recommendations typically apply only to specific populations that have

19458-406: The use of corticosteroids , are aimed at dampening the immune system's response to this phenomenon. Diagnosing meningitis as promptly as possible can improve outcomes. There are no specific signs or symptoms that can indicate meningitis, and a lumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis. Lumbar puncture is contraindicated if there is a mass in

19599-490: The vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. A quadrivalent vaccine now exists, which combines four vaccines with the exception of B; immunization with this ACW135Y vaccine is now a visa requirement for taking part in Hajj . Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make

19740-439: Was diagnosed in about 7.7 million people worldwide, of whom 236,000 died, down from 433,000 deaths in 1990. With appropriate treatment, the risk of death in bacterial meningitis is less than 15%. Outbreaks of bacterial meningitis occur between December and June each year in an area of sub-Saharan Africa known as the meningitis belt . Smaller outbreaks may also occur in other areas of the world. The word meningitis comes from

19881-404: Was the use, often at high-dosage, of systemic glucocorticoids , relying on the anti-inflammatory actions of these drugs to suppress the eosinophil- and T cell-induced tissue damage caused by the disorder. However, there have been no randomized control trials reporting on the systemic use of these drugs. Rather, there are suggestions that treatment with systemic glucocorticoids is associated with

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