Drug Rash With Eosinophilia and Systemic Symptoms Syndrome Induced by Chloral Hydrate in Early Childhood

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, acute and severe life-threatening systemic disease. DRESS syndrome is characterized by fever, lymphadenopathy, rash, hypereosinophilia and involvement of systemic organs. The most commonly implicated drugs are anticonvulsants, sulfonamides and allopurinol. Chloral hydrate is a sedative and hypnotic drug frequently used in pediatric patients. We first report a case of DRESS syndrome induced by chloral hydrate in a 14-month-old female.     

Acute interstitial nephritis during treatment with penicillin and cephalothin

A case of non-oliguric acute interstitial nephritis during treatment with ampicillin, benzylpenicillin and cephalothin is reported. There were symptoms of drug hypersensitivity, including fever, exanthema, eosinophilia and elevated serum IgE. Renal biopsy showed marked interstitial edema and infiltration with numerous eosinophils, some mononuclear cells and giant cells, and scattered tubular damage, but normal glomeruli and vessels. There was no pathological deposition of immunoglobulins or complement in the renal tissue. Renal function recovered after withdrawal of antibiotics and treatment with steroids. The findings suggest a drug-induced, hypersensitivity-mediated pathogenesis of the renal lesions, with participation of both humoral and cell-mediated immunological reactions.     

Leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital: a case report

The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10⁹/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.     

Reactive metabolites and adverse drug reactions: clinical considerations

Idiosycratic reactions can affect many different organ systems, either as-an isolated event (e.g., hepatitis) or as part of a syndrome (e.g., drug hypersensitivity syndrome). Formation of reactive metabolites of drugs in conjunction with a decreased ability for detoxification is believed to be the initiating step in many idiosyncreatic reactions. The drug hypersensitivity syndrome, defined by the presence of fever, rash and internal organ involvement, is estimated to occur in approx 1 in 1000 to 1 in 10,000 exposures with drugs such as anticonvulsants sulfonamide antibiotics, allopurinol and dapsone. Symptoms usually start within 2–8 wk of drug initiations. Serum sicknesslikes reaction, most frequently found after 7–14 d of drug exposure, is distinguished by a fever, cutaneous eruption and arthralgias. Medications such as cefaclor, minocycline and bupropions are most frequently implicated in this reaction. In contrast, drug-induced lupus can occur 1–2 yr after initiation of medication. Drug-induced lupus is characterized by musculoskeletal complaints and fever and weight loss. Drugs most commonly associated with drug-induced lupus include procainamide, hydralazine, chlorpromazine, isoniazid, and minocycline. Management of patients who develop idiosyncratic reactions includes discontinuation of the implicated drug, initiation of corticosteroids (when appropriate), and symptomatic relief as required. Internal organ involvement, which may initially be asymptomatic, should be monitored. Confirmatory or diagnostic tests are not readily available in most areas, except for research purposes.     

Drug rash with eosinophilia and systemic symptoms syndrome following cholestatic hepatitis A: a case report

Hepatitis A virus (HAV) infections occur predominantly in children, and are usually self-limiting. However, 75-95% of the infections in adults are symptomatic (mostly with jaundice), with the illness symptoms usually persisting for a few weeks. Atypical manifestations include relapsing hepatitis, prolonged cholestasis, and complications involving renal injury. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, drug-induced hypersensitivity reaction characterized by skin rash, fever, lymph-node enlargement, and internal organ involvement. We describe a 22-year-old male who presented with acute kidney injury and was diagnosed with prolonged cholestatic hepatitis A. The patient also developed DRESS syndrome due to antibiotic and/or antiviral treatment. To our knowledge, this is the first report of histopathologically confirmed DRESS syndrome due to antibiotic and/or antiviral treatment following HAV infection with cholestatic features and renal injury.     

A Complex Interaction Between Drug Allergy and Viral Infection

A relationship between viral infections and the simultaneous or subsequent development of drug rashes has been observed in a number of clinical situations. We have recently provided evidence to indicate an intimate relationship between reactivation of human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several unique features that cannot be explained by a drug etiology; they include its delayed onset, paradoxical worsening of clinical symptoms after discontinuation of the causative drugs, and a step-wise development of several organ system failures long after clinical resolution. Many aspects of this syndrome suggest close similarities between DIHS and graft-versus-host disease (GVHD). Indeed, a wide variety of complications frequently occurring in GVHD, such as autoimmune diseases, is often observed during the course of this syndrome and even long after clinical resolution. Our recent studies have shown that in DIHS sequential reactivations of several herpesviruses (HHV-6, HHV-7, Epstein-Barr virus, and cytomegalovirus) can be detected coincident with various clinical symptoms in the same order as demonstrated in GVHD. Thus, not only the timing but also the order in which these herpesviruses can be reactivated in the host would be crucial determinant of outcomes of the disease. Our results indicate the importance of recognizing DIHS and other drug rashes associated with viral infections at risk of eventually developing autoimmune diseases.     

Exercise-induced anaphylactic reaction to shellfish

The syndrome of immediate type I food hypersensitivity, mediated by tissue-bound IgE antibody and mast cell histamine release, is well recorded in the medical literature. This case study represents a previously undescribed late food hypersensitivity, induced only by strenuous exercise. Identification of this new syndrome illustrates classical epidemiologic analysis, improves medical advice for the allergic and athletically inclined, and raises new questions in the areas of allergy and immunology.     

Evaluation of the drug lymphocyte stimulation test (DLST) with shosaikoto]

BACKGROUND: Our aim is to evaluate the significance of DLST by Shosaikoto. METHODS: We clinically evaluated 3 cases of drug-induced pneumonia assumed to be caused by Shosaikoto, and we performed DLST of Shosaikoto for healthy controls, and compared the data with drug-induced pneumonia cases of Shosaikoto. RESULTS: As clinical characteristics of 3 cases, 2 cases were positive for hepatitis C virus antibody, and 1 case was positive for DLST of Shosaikoto. The observed chest high-resolution CT (HRCT) findings showed hypersensitivity pneumonia (HP) pattern in all 3 cases. Prognosis was good in all 3 cases. DLST of Shosaikoto was positive in 27.5% of healthy controls. Stimulation index (S.I.) of DLST in drug-induced pneumonia cases increased depending on drug dilution density, compared to that of healthy controls. CONCLUSION: DLST of Shosaikoto showed high false-positive rate. However, we may be able to distinguish the true-positive cases with the false-positive cases by comparing the S.I. of DLST according to drug dilution density.     

Anticonvulsant hypersensitivity syndrome associated with Epstein-Barr virus reactivation

We describe a 59-year-old female with severe anticonvulsant hypersensitivity syndrome (AHS) associated with Epstein- Barr virus (EBV) infection. The causative drug was speculated to be carbamazepine. Recurrent EBV infection was demonstrated by the presence of anti-EBV early antigen IgM antibodies and anti-EBV nuclear antigen IgG antibodies. To our knowledge, only one case of drug hypersensitivity syndrome (DHS) associated with EBV has been reported in the English- language literature. Our case is the second report of EBV-associated DHS, which suggests that EBV infection may contribute to the pathogenesis of AHS in a few patients.     

Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome

Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.     

AN AUTOPSY CASE OF MULTIPLE INTRAPULMONARY ARTERY ANEURYSMS WITH SYSTEMIC THROMBOENDOPHLEBITIS, THE "HUGHES-STOVIN SYNDROME"

The first case of multiple intrapulmonary artery aneurysms with systemic thrombophlebitis in Japan was reported.
This case belongs to the category of the "Hughes-Stovin syndrome" proposed by Kopp and Green. The clinical and pathological findings of this syndrome was briefly summarized. The main pathological change in the present case was systemic angitis, which appeared to be an underlying cause of the "Hughes-Stovin syndrome"     

Report of a case of Lyell syndrome

Toxic epidermal necrolysis (TEN) is a rare drug-induced disease characterized by extensive epidermal destruction. We reported here a case of Lyell syndrome which happened few hours later after treatment associating lincomycine chlorhydrate with nonsteroidol anti-inflammatory drugs. The 28-year-old female patient developed many visceral complications with biochemical and haematological disorders. This syndrome is a dermatological emergency whose vital prognosis is displayed.     

Drug-induced lupus erythematosus

Drug-induced lupus is a syndrome which share symptoms and laboratory characteristics with idiopathic systemic lupus erythematosus (SLE). The terms drug-induced lupus (DIL) and drug-induced lupus erythematosus (DILE) are preferred, but other ones are also used-drug-related lupus, lupus-like syndrome and lupus erythematosus medicamentosus. The first case of DILE was reported in 1945 and associated with sulfadiazine. In 1953, it was reported that DILE was related to the use of hydralazine. More than 80 drugs have been associated with DILE. The average age of patients with DILE is nearly twice that of patients with idiopathic SLE. Approximately half the patients with drug-induced SLE are women, compared with 90% of patients with idiopathic SLE. Similarly to idiopathic lupus, DILE can be divided into systemic, sub-acute cutaneous and chronic cutaneous lupus. The syndrome is characterised by arthralgia, myalgia, pleurisy, rash and fever in association with antinuclear antibodies in the serum. The clinical and laboratory manifestations of drug-induced SLE are similar to those of idiopathic SLE, but central nervous system and renal involvement are rare in DILE. Recognition of DILE is important because it usually reverts within a few weeks after stopping the drug. This review discusses the general issues in DILE, such as pathogenic mechanisms, clinical forms and diagnostic criteria, and provides more detailed information for some of the most recent implicated drugs: minocycline, statins, anti-TNF-alpha agents.     

Drug Rash with eosinophilia and systemic symptoms versus Stevens-Johnson Syndrome--a case that indicates a stumbling block in the current classification

A 43-year-old man developed a skin eruption characterized by 'macules with blisters' typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6 degrees C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.     

Scarlatiniform rash and urticaria due to codeine

Scarlatiniform rash and urticaria were observed twice in the same patient following codeine intake. This rare drug-induced eruption may lead to mis-diagnosis in patients taking mild analgesics containing codeine. The side effects of codeine, hypersensitivity mechanisms, and the use of analgesic combination products are discussed.     

Liver lesions induced by dihydralazine and propranolol

The antihypertensive drugs dihydralazine and propranolol can produce identical liver injuries which must be distinguished clinically and morphologically from acute viral hepatitis. In 19 cases selected from our biopsy file during the last two years, clinical and morphological findings suggested that the liver injury diagnosed by light microscopy had been caused by an adverse reaction to dihydralazine and/or propranolol. In order to establish a causal relation the lymphocyte proliferation test (LPT) was performed with dihydralazine in 11 cases. Positive results were observed in 9 cases, demonstrating an etiologic role for dihydralazine in liver injury in these cases. The dihydralazine and/or propranolol induced liver injury consisted mainly of drug-induced hepatitis with confluent (bridging) necrosis. Different findings were observed in three cases: In two of these drug-induced hepatitis with confluent necrosis was observed together with eosinophilic cholangio-cholangiolitis. In one other case the histologic changes corresponded to drug hepatitis resembling viral hepatitis. Each of the three cases showed conspicuous centrolobular cholestasis, a feature which is unusual in drug-induced hepatitis with confluent necrosis irrespective of serum bilirubin levels. In one third of our cases we found morphological features of hypersensitivity reactions in the liver biopsies. Considered together with the results of LPT these features emphasize the role of cell mediated immune reaction in the mechanism of liver injury caused by dihydralazine and/or propranolol.     

Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains

Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient''s hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins.     

Drug hypersensitivity to previously tolerated phenytoin by carbamazepine-induced DRESS syndrome

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome associated with anticonvulsant drugs is a rare but potentially life-threatening disease that occurs in response to arene oxide producing anticonvulsant such as phenytoin and carbamazepine. There have been many reports of cross reactivity among the anticonvulsants upon first exposure to the offending drugs. However, there has been few data describing the development of DRESS syndrome after switching medication from previously well-tolerated phenytoin to carbamazepine, and the induction of hypersensitivity to phenytoin by DRESS to carbamazepine. We experienced a case of a 40-yr-old man who had uncontrolled seizure that led to the change of medication from the long-term used phenytoin to carbamazepine. He developed DRESS syndrome after changing the drugs. We stopped carbamazepine and restored phenytoin for seizure control, but his clinical manifestations progressively worsened and he recovered only when both drugs were discontinued. Patch tests with several anticonvulsants showed positive reactions to both carbamazepine and phenytoin. Our case suggests that hypersensitivity to a previously tolerated anticonvulsant can be induced by DRESS to another anticonvulsant, and that the patch test may be a useful method for detecting cross-reactive drugs in anticonvulsant-associated DRESS syndrome.     

Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl

We report on an 11-year-old Japanese girl with combined immunodeficiency and chromosomal instability. She had postnatal growth deficiency and microcephaly, preaxial polydactyly of the left hand, and susceptibility to infections. Immunological studies showed marked lymphocytopenia (around 500/ll), reduced lymphocyte response to various mitogens, and reduced or absent serum IgA, IgG, and IgM. Cell biological studies of her primary skin fibroblasts demonstrated spontaneous chromosome aberrations and radiation hypersensitivity. The combination of immunodeficiency, chromosomal instability, and radiation hypersensitivity as seen in the girl is present in both ataxia-telangiectasia and Nijmegen breakage syndrome. Ataxia-telangiectasia was excluded because of differences in clinical features and laboratory data. Likewise, Nijmegen breakage syndrome is unlikely to be the case because the characteristic face, hyperpigmented spots, and mental retardation present in the syndrome were missing in the girl. Sequence analysis of a Nijmegen breakage syndrome responsible gene, NBS1, revealed no mutations. A normal NBS1 product was also demonstrated by immunoblot analysis using an anti-NBS1 antibody. We propose that the disorder in the girl represents a new combination of combined immunodeficiency and chromosomal instability.