Allopurinol hypersensitivity syndrome with acute generalized exanthematous pustulosis manifestations

Allopurinol hypersensitivity syndrome(AHS) is a severe form of cutaneous adverse reaction that is associated with significant morbidity and mortality. We report a case of AHS with the cutaneous manifestation of acute generalised exanthematous pustulosis(AGEP). A 47 year old gentleman, with no previous skin disease, presented with a generalized mildly pruritic erythematous rash on the trunk and all 4 limbs, with patches of superficial non-follicular pustules. Our patient fulfilled both criteria for AGEP and AHS.     

Allopurinol hypersensitivity syndrome with acute generalized exanthematous pustulosis manifestations

Allopurinol hypersensitivity syndrome(AHS) is a severe form of cutaneous adverse reaction that is associated with significant morbidity and mortality. We report a case of AHS with the cutaneous manifestation of acute generalised exanthematous pustulosis(AGEP). A 47 year old gentleman, with no previous skin disease, presented with a generalized mildly pruritic erythematous rash on the trunk and all 4 limbs, with patches of superficial non-follicular pustules. Our patient fulfilled both criteria for AGEP and AHS.     

Anticonvulsant hypersensitivity syndrome: an update

Introduction: Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially life-threatening adverse drug reaction, primarily associated with phenytoin, phenobarbital and carbamazepine. It is characterized by a triad of fever, skin eruption and internal organ involvement (usually liver), which occur two to eight weeks after the initiation of therapy. Anticonvulsant hypersensitivity syndrome has been estimated to occur between 1 and 1000 and 1 in 10,000 exposures; however, its true incidence is unknown because of the variable presentation and inaccurate reporting. Areas covered: This paper presents the incidence, epidemiology and pathogenesis of AHS, along with recommendations for its diagnosis and management. Expert opinion: Avoidance of all aromatic anticonvulsants is recommended in patients who develop AHS with one of these agents, as there is a high degree of crossreactivity among all these agents. There are no universally recognized tests for the prediction of AHS due to aromatic anticonvulsants or lamotrigine. Yet genetic testing in a predictive sense would help guide the choice of an appropriate anticonvulsant medication. Other tests, using cellular surrogates, such as lymphocytes or platelets, have been used primarily for diagnostic testing and do not have the universal practicality afforded to genetic tests.     

Possible atypical cross-sensitivity between phenytoin and carbamazepine in the anticonvulsant hypersensitivity syndrome

Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially life-threatening reaction that occurs in response to common anticonvulsants in predisposed individuals. It is often characterized by fever, rash, lymphadenopathy, hepatitis, and laboratory abnormalities. Consequently, it often is overlooked or even misdiagnosed by practitioners unfamiliar with AHS. Cross-sensitivity manifests frequently between phenytoin, phenobarbital, and carbamazepine as an exacerbation of presenting signs and symptoms. We report a case of AHS in a patient whose clinical features changed significantly when switching from phenytoin to carbamazepine. Physicians and pharmacists must become aware of the extreme variability in AHS manifestation so that the offending anticonvulsant regimen can be discontinued in a timely manner.     

Cross Hypersensitivity Syndrome between Phenytoin and Carbamazepine

Objective: To evaluate the incidence of cross anticonvulsant hypersensitivity syndrome (AHS) between phenytoin (PHT) and carbamazepine (CBZ) in hospitalized patients.Method: Retrospective chart review about the cross AHS was retrieved from pharmacy adverse drug reaction program from 1998 to 2002 in a 450-bed teaching hospital.Main outcome measures: AHS was defined as the appearance of at least two symptoms with the first anticonvulsant drug (ACD). Cross AHS was considered if after withdrawal of a first ACD because of hypersensitivity symptoms, a new episode with similar or new symptoms appeared after exposure to a second ACD. The following symptoms were considered– rash, fever, hepatotoxicity, lymphadenopathies or hematological disturbances.Results: Cross AHS between PHT and CBZ was observed in nine cases (45). After the cross-reaction event, four of them were treated with valproic acid, two with vigabatrin, two with phenobarbital and one with no treatment without developing further AHS.Conclusions: AHS is a severe complication of aromatic ACD that can compromise the future choice of therapy. Because of the high incidence of clinical cross-reaction between these two drugs, non-aromatic ACD alternatives, must be considered.     

Evidence for a T-lymphocyte dependent mechanism involving proinflammatory cytokines in anticonvulsant hypersensitivity syndrome: a case report

The anticonvulsant drug hypersensitivity syndrome (AHS) is a potentially fatal drug reaction associated with aromatic antiepileptic drugs, the pathogenic mechanisms of which are still unclear. We studied a 2-year-old female affected with AHS after phenobarbital treatment. In vitro experiments showed a T-lymphocyte response to the drug and an increased, dose-related, IL-6 production after drug incubation. These findings suggest that AHS may be caused by a T-lymphocyte dependent mechanism, involving pro-inflammatory cytokines.     

Anticonvulsant hypersensitivity syndrome in children: incidence, prevention and management

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.     

Pathogenesis and clinical approaches to anticonvulsant hypersensitivity syndrome: current state of knowledge

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but severe and potentially fatal, adverse reaction that occurs in patients who are treated with commonly used older anticonvulsant drugs (phenytoin, carbamazepine and phenobarbital) and/or with some newer agents (lamotrigine). Paediatric patients are at an increased risk for the development of AHS for the higher incidence of seizure disorder in the first decade of life. Hypersensitivity reactions range from simple maculopapular skin eruptions to a severe life-threatening disorder. AHS is typically associated with the development of skin rash, fever and internal organ dysfunctions. Recent evidence suggests that AHS is the result of a chemotoxic and immunologically-mediated injury, characterized by skin and mucosal bioactivation of antiepileptic drugs and by major histocompatibility complex-dependent clonal expansion of T cells. Early recognition of AHS and withdrawal of anticonvulsant therapy are essential for a successful outcome. In vivo and vitro tests can be helpful for the diagnosis that actually depends essentially on clinical recognition.     

Anticonvulsant hypersensitivity syndrome: a review

Anticonvulsant hypersensitivity syndrome (AHS), characterised by fever, rash and internal organ involvement, is a rare, but potentially fatal adverse event that occurs most commonly with first-line aromatic anticonvulsants, but can also occur with non-aromatic anticonvulsants such as lamotrigine and valproic acid. AHS can begin anywhere from 1 to 12 weeks after commencement of therapy and has been estimated to occur at a frequency of 1/1000 to 1/ 10,000 exposures. Its true incidence, however, remains unknown due to under-reporting. The disease has protean manifestations mimicking several other conditions, and the diagnosis is thus difficult. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, graft versus host disease, antibody production and viral infections. The one based on toxic metabolites has found the greatest acceptance, perhaps due to the fact that it can be proven by an in vitro test; the lymphocyte toxicity assay. Discontinuation of the offending agent with supportive, symptomatic therapy forms the mainstay of management of AHS. In addition, counselling of both the patient and first degree relatives for susceptibility to AHS is an important aspect of management. In the last decade, several new anticonvulsants have been introduced for epilepsy. In addition, for resource-poor countries, inexpensive and effective first-line drugs such as phenytoin and phenobarbitone will continue to remain important treatment options. Thus, the problem of AHS will continue, and attempts should be made to further understand the molecular basis of and individual susceptibility to AHS. Adverse event monitoring programs must also actively seek AHS reports to estimate its true incidence.     

Anticonvulsant hypersensitivity syndrome: implications for pharmaceutical care

Anticonvulsant hypersensitivity syndrome (AHS) is a delayed adverse drug reaction associated with the use of aromatic anticonvulsant drugs. It has been most commonly reported with the use of phenytoin, carbamazepine, and phenobarbital. Although its occurrence is rare, 1 in every 1000-10,000 exposures, AHS is a serious adverse event often resulting in hospitalization and even death. The clinical manifestations of AHS include a triad of symptoms consisting of dermatologic rashes, fever, and evidence of systemic organ involvement. Diagnosis is most frequently based on the recognition of this triad of symptoms and clinical judgment. The exact mechanism of AHS remains to be determined but is thought to have at least three components: deficiency or abnormality of the epoxide hydroxylase enzyme that detoxifies the metabolites of aromatic amine anticonvulsants, associated reactivation of herpes-type viruses, and ethnic predisposition with certain human leukocyte antigen subtypes. Arene oxides, the toxic intermediaries in the metabolism of anticonvulsant drugs, can accumulate and directly bind to macromolecules, causing cell death, as well as act as prohaptens that bind to T cells, initiating an immune response and systemic reactions. Management of AHS primarily includes discontinuation of the associated anticonvulsant drug. Systemic corticosteroids are usually required for full recovery. An important issue regarding AHS is the cross-sensitivity among aromatic anticonvulsant drugs, which has been reported to be 40-80%. This means that patients with a history of AHS should avoid further use of any aromatic anticonvulsant drug. In addition, a familial association with AHS exists, and family members of the patient with AHS should be educated that they may be at increased risk for developing AHS if they use aromatic anticonvulsant drugs. Anticonvulsant drugs that are generally considered safe are valproic acid and benzodiazepines. Other nonaromatic anticonvulsant drugs should also be acceptable. Pharmacists as health care providers can play an important role in the diagnosis, treatment, and prevention of AHS.     

Anticonvulsant hypersensitivity syndrome: a review

Anticonvulsant hypersensitivity syndrome (AHS), characterised by fever, rash and internal organ involvement, is a rare, but potentially fatal adverse event that occurs most commonly with first-line aromatic anticonvulsants, but can also occur with non-aromatic anticonvulsants such as lamotrigine and valproic acid. AHS can begin anywhere from 1 to 12 weeks after commencement of therapy and has been estimated to occur at a frequency of 1/1000 to 1/10,000 exposures. Its true incidence, however, remains unknown due to under-reporting. The disease has protean manifestations mimicking several other conditions, and the diagnosis is thus difficult. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, graft versus host disease, antibody production and viral infections. The one based on toxic metabolites has found the greatest acceptance, perhaps due to the fact that it can be proven by an in vitro test; the lymphocyte toxicity assay. Discontinuation of the offending agent with supportive, symptomatic therapy forms the mainstay of management of AHS. In addition, counselling of both the patient and first degree relatives for susceptibility to AHS is an important aspect of management. In the last decade, several new anticonvulsants have been introduced for epilepsy. In addition, for resource-poor countries, inexpensive and effective first-line drugs such as phenytoin and phenobarbitone will continue to remain important treatment options. Thus, the problem of AHS will continue, and attempts should be made to further understand the molecular basis of and individual susceptibility to AHS. Adverse event monitoring programs must also actively seek AHS reports to estimate its true incidence.     

Exploring the emotional experiences of alcohol hangover syndrome in healthy UK-based adults

Abstract

Alcohol hangover syndrome (AHS) is a highly heterogenous state encompassing a range of physiological and psychological symptoms. The syndrome is experienced regularly among alcohol consumers and remains poorly understood. The present study sought to gain insight into whether certain emotions were tied to AHS and how these emotions were experienced. Twenty participants took part, 14 female and 6 male, aged 21 to 39 years. Inductive thematic analysis of semi structured interview data produced four themes; ‘The Tyranny of the Shoulds’, ‘Bias and the Persistence of Memory’, ‘Staring into the Void’, and ‘Emotive behavioral response’. The four themes demonstrate the complexity of emotional experiences associated with AHS and account for concurrent constructs including cognition, mood, and behavior. Guilt, shame, dread, anger, and regret were all commonly experienced, with rumination, negative interpretation bias, nostalgia, self-flagellation, isolation and camaraderie being essential in how these emotions were described by participants. The study adds greater understanding of the diversity of emotions that can be experienced during AHS, with important implications for the wellbeing of those who suffer most from the state. It is suggested that self-help techniques targeting cognitions could be explored to help alleviate aspects of the negative emotions experienced.     

别嘌醇过敏综合征并肾衰竭死亡

1例68岁女性因高尿酸血症服用别嘌醇0．1g，3次／d治疗。治疗期间曾注射中药针剂3d。用别嘌醇51d后患者出现皮疹。给予氯雷他定和中药治疗后，症状加重。入院前3d，患者皮疹漫延全身并出现呼吸困难。入院后查体示：口唇黏膜溃烂，全身红色斑、丘疹、表面脱屑；实验室检查示BUN由7．10mmol／L升至34．19mmol／L，SCr由131μmol／L升至499μmol／L。诊断为别嘌醇过敏综合征。停用别嘌醇，给予地塞米松10mg，1次／d静脉滴注，患者最终死于肾衰竭和全身感染。     

氨碘肽滴眼液致眼结膜严重充血1例

氨碘肽滴眼液为治疗玻璃体混浊与早期老年性白内障的药物,能改善血液循环,促进新陈代谢,促进玻璃体混浊的吸收和抑制白内障的发展,提高视觉功能。氨碘肽滴眼液临床应用有轻微刺激或灼热现象,一般可自行消失。本病例在应用氨碘肽滴眼液数日后出现迟发性的眼结膜严重出血症状,值得引起临床的重视。     

Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS)

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids.KEY WORDS: Drug reaction with eosinophilia and systemic symptoms syndrome, drug rash, hypersensitivity, nevirapine     

Hepatitis associated with allopurinol

When adverse reactions occur, it is important to identify the etiologic drug. We describe a case of hepatitis associated with allopurinol. A 66-year-old female was admitted for rehabilitation of a cerebral hemorrhage on September 11, 1981. Allopurinol, clofibrate, and baclofen were administered. Severe hepatitis developed on November 13. The clinical laboratory data returned to normal on November 30. Challenge tests were conducted on clofibrate, allopurinol, and baclofen. The challenge test was positive after the administration of allopurinol. Allopurinol hepatitis is most likely a hypersensitivity reaction, as is suggested by the symptoms of eosinophilia and rash. Renal dysfunction may predispose one to develop hepatitis associated with allopurinol.     

Allopurinol-induced palisaded neutrophilic and granulomatous dermatitis

We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin.     

Pregabalin hypersensitivity in a patient treated for postherpetic neuralgia

Drug hypersensitivity syndrome is characterized by fever, skin rash and internal organ involvement. It is commonly seen with aromatic group of anticonvulsants viz. phenytoin, carbamazepine and phenobarbitone. Here, we report a case of hypersensitivity reaction to pregabalin, used for treating postherpetic neuralgia.KEY WORDS: Drug hypersensitivity, liver enzymes, Naranjo scale, pregabalin     

Antiepileptic drug-induced hypersensitivity syndrome reactions

Host dependent idiosyncratic drug reactions, otherwise known as unpredictable type B reactions, are of a major concern in clinical practice and drug development. Hypersensitivity syndrome reactions are idiosyncratic in nature and may be induced by a variety of agents including antiepileptic drugs (AEDs). The AEDs hypersensitivity syndrome is a rare but potentially life-threatening syndrome that occurs after exposure to phenytoin, carbamazepine or phenobarbital. Phenobarbital, phenytoin and carbamazepine, have shown cross-reactivity; while, no evidence of cross reactivity between other antiepileptic drugs such as valproic acid, gabapentin or lamotrigine has been observed. True hypersensitivity reaction is a systemic disease defined by the triad of fever, skin eruption and multi-organ involvement that occurs 1-8 weeks after exposure to a drug. Because most reactions occur within two months of treatment initiation, it is likely that the true incidence of the syndrome is underestimated. It was hypothesized that reactive metabolite/s (RM) rather than the parent drug, is/are responsible for initiating the sequence of toxic and immunological events that culminate clinically in a drug hypersensitivity syndrome reaction. Cells that possess surface antigens for which T cells have specific receptors then present this antigen. Exanthemas are related to delayed T-cell hypersensitivity so it has been hypothesized that memory T cells might subsequently increase in number in the most severely affected cutaneous sites. To manage hypersensitivity syndrome successfully, the symptoms must recognized early, the use of the offending drug must be terminated immediately, and alternative antiepileptic medication should be prescribed. Currently, the diagnosis of AEDs-induced hypersensitivity syndromes is based on clinical grounds and on in vitro testing. In the field of pharmacogenetics, we bare witness to how effectively the combination of effective screening methods and understanding of the role of genetic polymorphisms play in the metabolic pathways of AEDs facilitating new therapies that allow scientists and physicians to better diagnose and treat patients.     

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear. AIM: To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel syndrome. METHODS: Ninety-two irritable bowel syndrome patients and 17 healthy volunteers underwent a rectal barostat study. The association between specific irritable bowel syndrome symptoms and the presence of hypersensitivity was examined using Area under the Receiver Operating Characteristic curves. RESULTS: Irritable bowel syndrome patients had significantly lower thresholds for discomfort/pain than healthy volunteers: 24 (18-30) and 30 (27-45) mmHg above minimal distending pressure, respectively. Forty-one patients (45%) showed hypersensitivity to rectal distension. Proportions of patients with different predominant bowel habits were similar in hypersensitive and normosensitive subgroups (diarrhoea predominant: 39 and 41%, respectively; alternating type: 27 and 28%, respectively; constipation predominant: 34 and 31%, respectively). Severe abdominal pain was more frequent in hypersensitive, compared with normosensitive patients (88% vs. 67%, P = 0.02), but none of the individual irritable bowel syndrome symptoms could accurately predict the presence of hypersensitivity, as assessed by Area under the Receiver Operating Characteristic curve analysis. CONCLUSIONS: Hypersensitive and normosensitive irritable bowel syndrome patients present with comparable, heterogeneous symptomatology. Therefore, selection based on clinical parameters is unlikely to discriminate individual irritable bowel syndrome patients with visceral hypersensitivity from those with normal visceral sensitivity.