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Phenytoin-induced toxic cholestatic hepatitis in a patient with skin lesions: case report.

Phenytoin is a highly effective and widely prescribed anticonvulsant agent, but it can be associated with dose-related side effects and hypersensitivity reactions. We present a case of phenytoin-induced cholestatic hepatotoxicity in a 47-year-old woman who had exfoliative dermatitis, an increase in liver enzymes with a cholestatic pattern, and eosinophilia after 25 days of phenytoin therapy. The diagnostic workup showed no other possible causes, and the results of a percutaneous liver biopsy were consistent with drug-induced toxic hepatitis. Within 3 weeks after discontinuing phenytoin therapy, her liver function tests returned to normal values.

Anticonvulsants↗

Etretinate-induced skeletal muscle damage.

Three patients who received etretinate, two for psoriasis vulgaris and one for exfoliative dermatitis, developed clinical and electromyographic features of muscle damage during treatment. In one patient histological and ultrastructural findings indicated segmental muscle necrosis. Withdrawal of the drug led to clinical recovery and normalization of muscle enzyme levels and electromyogram. To the best of our knowledge, this is the first report to show etretinate-induced reversible skeletal muscle damage.

Adult↗

Epidemiological study of severe cutaneous adverse drug reactions in a city district of China.

BACKGROUND: An epidemiological study of severe cutaneous adverse drug reactions (SCADRs) in China has not been reported. AIMS: To estimate the incidence of SCADRs in a city district of China. METHODS: A retrospective study was performed in Peking University Third Hospital, the only hospital in Haidian district, Beijing with a dermatology ward. The medical records of inpatients with SCADRs from January 1994 to December 2002 were studied. RESULTS: The prevalence rates for overall SCADRs, Stevens-Johnson syndrome (SJS), exfoliative dermatitis (ED), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) among hospitalized patients were 0.32, 0.15, 0.10, 0.04 and 0.07 per thousand, respectively. The risk of SCADRs from systemic drugs among hospitalized patients was 0.03/1000 (0.02/1000 for SJS, and 0.01/1000 for ED and DRESS). The reported incidence of SCADRs in Haidian district was not less than 1.8 per million person-years. The reported incidence of ED, SJS, TEN and DRESS in Haidian district was not less than 0.6, 0.8, 0.05 and 0.4 per million person-years, respectively. The most common underlying disorders were infection, pain-related diseases and epilepsy. Antibiotics were the most common offending drugs followed by anticonvulsants and traditional Chinese medicines (TCM). CONCLUSIONS: These results confirm the relatively low incidence of SCADRs in China. Antibiotics, anticonvulsants and TCM are the most common causative drugs.

Adolescent↗

Allergic rash due to antiepileptic drugs: clinical features and management.

Optimal management of allergic rash from antiepileptic drugs (AEDs) is unclear. We identified 50 patients with 68 reactions (36 to one AED, 10 to two AEDs, and four to three AEDs). The AEDs implicated were carbamazepine, 30; phenobarbital (PB), 20; phenytoin, 16; ethosuximide, one; and AED combination, one. Sixty-three reactions were cutaneous eruptions, three exfoliative dermatitis, and two Stevens-Johnson syndrome. Forty-six reactions were mild (rash only), 18 moderate (systemic symptoms or other organ system involvement), and four life-threatening (all with PB). In most patients with greater than 1 reaction, the second and third reactions were not more severe than the first. Prior antibiotic allergies or nonmedication allergies were no more common than in a control group without reactions. The AED was ceased abruptly in 59 patients (22 of whom did not receive a new AED), tapered in five, and continued unchanged in four. Despite this, there was no status epilepticus (SE) during the reaction or its treatment, and no patient's seizure control deteriorated. In 40 cases, a new AED was added--16 after the reaction had resolved and 24 before total resolution. Rash recurred with the new AED in 50 and 42% respectively (NS). We conclude that, though allergic rashes to AEDs are usually mild, the rare occurrence of severe reactions indicates that the AED should be ceased. This can be done abruptly with minimal risk of SE. A new AED can be added, if necessary, prior to the resolution of the rash without increasing the risk of further reactions.

Adolescent↗

Cutaneous reactions due to diltiazem and cross reactivity with other calcium channel blockers.

BACKGROUND: The spectrum of cutaneous eruptions in association with calcium channel blockers is extensive, varying from exanthemas to severe adverse events. Reactions due to diltiazem occur more frequently than with other calcium channel blockers. Patch testing has been used as confirmatory testing in patients with extensive cutaneous reactions. Cross-reactivity among these drugs have not been established. MATERIAL: We present 3 patients: 1) A 54-year-old man developed a generalized erythema-multiforme-like reaction followed by erythrodermia and exfoliative dermatitis 6-7 days after starting on diltiazem. The drug was stopped and remission was obtained with emollients and systemic corticosteroids and antihistamines within 12 days. 2) A 80-year-old woman experienced a pruritic exanthematous eruption on her trunk which evolved to generalized erythrodermia and superficial desquamation. This reaction appeared 10 days after taking diltiazem, and gradually improved in 10-12 days after discontinuation of this drug. 3) A 79-year-old man presented with erythema and pruritus initially on the back, and then affecting thorax, extremities and face. He had started treatment with diltiazem three days before. Diltiazem was stopped and steroid and antihistamine therapy was given. His skin condition improved, but 3 days later the patient received verapamil with worsening of previous situation. He recovered within 7 days. METHODS AND RESULTS: Two to six months after the reaction, we carried out epicutaneous tests with calcium channel blockers from different groups. Diltiazem proved positive (at 48 and 96 hours) in the three patients; nifedipine was also positive in patient 2, and verapamil in patient 3. Controlled administration of verapamil was well tolerated in patient 2 after the reaction, and the patient 1 has taken nifedipine without problems. CONCLUSIONS: 1) We report 3 cases of cutaneous reactions due to diltiazem. 2) Epicutaneous tests have been useful for diagnosis. 3) As one of patients had positive patch tests to diltiazem and nifedipine, and other one with diltiazem and verapamil, more studies are needed to demonstrate cross reactions among calcium channel blockers.

Aged↗

Erythroderma and pneumonitis induced by penicillin?

Penicillin and its derivatives are known to cause several dermatologic and pulmonary hypersensitivity reactions. This report describes a patient who presented with combined generalized exfoliative dermatitis and severe pneumonitis caused by penicillin and aggravated by ampicillin, methicillin and mezlocillin. Antibiotic challenges with penicillin caused immediate reappearance of the dermatological manifestation; reactivation of the pneumonitis was probably prevented by immediate discontinuation of the drug.

Adult↗

Generalized vitiligo after erythroderma.

We report a 65-year-old black man whose onset of an erythroderma was followed in 6 weeks by a generalized vitiligo. The etiology of the erythroderma was unclear, although a prostate adenocarcinoma was found on evaluation. This is to our knowledge the first patient reported with a vitiligo following exfoliative dermatitis, and the first report of two uncommon markers of internal malignancy (erythroderma and vitiligo) occurring with prostate adenocarcinoma in the same patient.

Adenocarcinoma↗

Cutaneous reactions in head-injured patients receiving phenytoin for seizure prophylaxis.

Two types of adverse effects are caused by phenytoin, reversible dose-dependent central nervous system effects and non-dose dependent hypersensitivity effects. The most common presenting symptom of the hypersensitivity reaction is the development of a morbilliform rash. During a 45-month period, 151 head-injured patients received phenytoin for seizure prophylaxis using an 11-mg/kg i.v. and a 13-mg/kg i.m. parenteral loading dose followed by an i.m. or p.o. maintenance dose for therapeutic blood concentrations (10 to 20 micrograms/ml). The patients were followed for 18 months. The incidence of skin reaction to phenytoin was 19.4%, or 24 of 124 patients. Cutaneous reactions occurred from Day 5 through Day 91 of phenytoin therapy. Two patients had more serious reactions after the cutaneous reaction. One patient developed exfoliative dermatitis, and 1 had a pseudolymphoma type syndrome. Both recovered. Patients with cutaneous reactions had higher absolute eosinophil counts (P = 0.01). Other laboratory parameters of the white blood count and the total lymphocyte counts did not differ significantly. Patients receiving dexamethasone had a higher incidence of rash, but this did not reach statistical significance. Because recent data have not documented a seizure-prophylactic effect of phenytoin, only a head-injured patient who has experienced a first posttraumatic seizure should receive the drug.

Adolescent↗

Lamotrigine update and its use in mood disorders.

OBJECTIVE: To provide a qualitative, systematic update and review of the pharmacology, pharmacokinetics, efficacy in mood disorders, adverse effects, and costs of lamotrigine. DATA SOURCES: Citations obtained from MEDLINE searches (1985-September 2001) using lamotrigine as a text word, articles identified in reference lists of pertinent articles, abstracts presented at conferences, and research data from GlaxoSmithKline. DATA EXTRACTION: English-language articles were considered for possible inclusion. Each title and abstract was examined to determine whether the publication contained up-to-date information relevant to the objective. Twenty clinical trials that provided data on response rates in mood disorders were tabulated. DATA SYNTHESIS: Lamotrigine's primary action is to modulate voltage-gated sodium channels. Evidence suggests that it decreases glutamate transmission, directly reduces calcium influx, mildly blocks transmitter reuptake, and alters intracellular mechanisms of resting transmitter release. The average half-life of lamotrigine is approximately 24 hours, but decreases to approximately 7.4 hours when used concurrently with phenytoin, and increases to approximately 59 hours with valproic acid. Seven of the 20 clinical trials were randomized, double-blind, and controlled. Existing data are inadequate to evaluate lamotrigine use in major depression. The pooled response rates for patients with depressed, manic, mixed, and rapid cycling bipolar disorder were similar, ranging from 52% to 63%. Adverse effects are infrequent when the drug is used alone, but become more frequent when lamotrigine is combined with other anticonvulsants. While most rashes are mild, approximately 1 in 500 patients develops exfoliative dermatitis. A slow upward dose titration is recommended to reduce the incidence of serious rash, but this may delay the attainment of adequate dosage for 6 weeks. Lamotrigine has positive effects on cognitive function, but occasionally produces insomnia. Lamotrigine costs 2-4 times more than lithium, carbamazepine, and generic valproic acid. CONCLUSIONS: When efficacy, adverse effects, and cost are considered, lamotrigine should probably be reserved as a second-line agent for bipolar depression.

Acetates↗

Human herpesvirus 6 reactivation in trichloroethylene-exposed workers suffering from generalized skin disorders accompanied by hepatic dysfunction.

Idiosyncratic generalized skin disorders resembling serious drug hypersensitivities have reportedly occurred after occupational exposure to trichloroethylene. However, factors associated with the disorders remain unknown except for trichloroethylene exposure. This study aimed at clarifying whether infectious diseases contributed to the development of rash or hepatitis in patients with trichloroethylene-related generalized skin disorders. Fifty-nine patients consecutively hospitalized between March 2002 and December 2003 and 59 healthy exposed workers selected on an age-matched basis in the patients' factories were enrolled in the study. Information on possible risk factors for rash and hepatitis was collected with structured checklists. Antibody titers were measured for hepatitis A, B and C viruses, Mycoplasma pneumoniae, herpes simplex viruses 1 and 2, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, measles and rubella virus. Thirty-six cases (59%) showed exfoliative dermatitis, 17 (28%) erythema multiforme, 4 (7%) Stevens-Johnson syndrome, and 4 (7%) toxic epidermal necrolysis. Before the onset of rash, 16 (27%) cases had received medication prescribed for the preceding fever, a main first symptom of the disorders. Marked increases in anti-human herpesvirus 6 IgG titer (> or =256), which indicated viral reactivation, were noted in 14 (25%) patients, while no abnormal increase was detected in the controls (p<0.001). Anti-measles IgM titer was positive in 2 (7%) cases but not in the controls (p=0.49). The involvement of other known risk factors of rash or hepatitis was ruled out. These results suggest that part of trichloroethylene-related generalized cutaneous disorders occurring in China and drug-induced hypersensitivity syndrome overlap in terms of human herpesvirus 6 reactivation.

Adolescent↗

Parapsoriasis and related conditions.

Classification of parapsoriases is revised into a simple practical table. Pityriasis lichenoides (guttate parapsoriasis) is not a type of parapsoriasis. The clinical features of small patch and large plaque parapsoriasis are described in detail. Six clinical varieties of large plaque parapsoriasis and three clinical varieties of exfoliative dermatitis including Sézary syndrome have been clearly recognized as distinctive categories. Histopathology is useful for the diagnosis of parapsoriasis and mycosis fungoides. Sézary cell count is not significant for the diagnosis of Sézary syndrome.

Dermatitis, Exfoliative↗

Erythroderma, hypogammaglobulinemia, and T-cell lymphocytosis. Occurrence following therapy with phenytoin.

Erythroderma and exfoliative dermatitis developed in a 17-year-old boy following therapy with phenytoin sodium. Immunologic studies performed early in the course of the dermatitis disclosed panhypogammaglobulinemia and a marked increase in T lymphocytes that responded poorly in vitro to T-cell mitogens. After therapy with prednisone, the dermatitis improved somewhat, and the patient's lymphocytes proliferated in vitro when exposed to phenytoin. We speculate that our patient's acute hypersensitivity reaction may have been mediated by an excessive number of phenytoin-sensitized suppressor-cytotoxic T lymphocytes and may represent a disorder of immunoregulatory T cells.

Adolescent↗

Severe side-effects of captopril in advanced chronic kidney insufficiency.

Using equal or lower than manufacturer's recommended doses of Captopril in 10 hypertensive patients with creatinine clearance less than 30 ml/min severe side-effects were observed in four cases. The adverse reactions continued after stopping the drug. One case developed symptomatic thrombocytopenia; one other, a lethal infected exfoliative dermatitis and an irreversible deterioration of her renal function. The other two cases demonstrated severe aggravation of their CRF, one requiring dialysis. The protective effect of dialysis against these side-effects is obvious in this series and dialysis may also accelerate the resolution of the complications. Suggestions for the management of this kind of patient with Captopril are made.

Acute Kidney Injury↗

[Clinical aspects and etiology of erythroderma: an analysis of 64 cases].

The difficulty of exfoliative dermatitis lies in the finding of underlying causes. In the present study the profile of 64 patients with erythroderma diagnosed between 1.1.1990 and 31.12.1999 were analysed. Clinical, histological and laboratory findings and their relationship to the aetiology were investigated. A masculine:feminine ratio of 2.6:1 was found. Among these patients the most common causative factors were pre-existing dermatoses (58%) and drugs (16%). In about eleven percent of the patients exfoliative dermatitis was associated with malignancy. Six out of seven malignancies were found in males, five of them suffering from pre-existing dermatosis. In 16 percent of the patients no aetiology of erythroderma could be found. No laboratory or clinical findings were indicative for an underlying malignant condition. Since we demonstrated underlying neoplastic disorders in seven (11%) of the cases, five of them also suffering from pre-existing dermatosis, we consider it absolutely necessary to screen for such diseases in the presence of the diagnosis exfoliative dermatitis.

Adult↗

Erythroderma with fulminant hepatitis: a possible association.

Exfoliative dermatitis or erythroderma may be a sign of systemic disease, usually a T-cell lymphoma, although other malignancies may also be associated. We observed two patients in whom severe hepatitis and an exfoliative dermatitis occurred simultaneously. We believe that this association has not been reported previously.

Adult↗

Patch testing in cutaneous reactions caused by carbamazepine.

The usefulness of patch testing in the diagnosis of carbamazepine-induced allergic skin eruptions was studied in 18 patients with previous histories of skin eruptions caused by carbamazepine. The etiological role of carbamazepine was ascertained by peroral or topical provocation in 15 (out of 18) patients. The clinical reactions caused by the drug were classified as maculopapular exanthema with general symptoms (7 patients), other type of exanthema (3), exfoliative dermatitis (erythroderma) (3), fixed drug eruption (3), erythema multiforme (1) and urticaria (1). Patch testing showed positive reactions to carbamazepine in 7 patients; in addition, 2 patients had doubtful reactions. Positive patch test reactions were seen only in patients with exfoliative dermatitis (all 3 patients) and maculopapular exanthema (4 out of 7). None of the patients with fixed drug eruption, erythema multiforme or urticaria, or the control subjects, had positive patch test reactions to carbamazepine. The present study suggests that patch testing is useful in the diagnosis of carbamazepine allergy in patients with maculopapular eruptions or erythrodermas.

Adolescent↗

Overcoming recurrent cutaneous reactions from imatinib using once-weekly dosing.

OBJECTIVE: To describe the use of once-weekly imatinib in a patient who developed recurrent cutaneous reactions associated with imatinib. CASE SUMMARY: A 65-year-old Asian woman received investigational treatment with imatinib 300 mg/d as maintenance therapy for acute lymphoblastic leukemia. Exfoliative dermatitis developed after 3 weeks of administration. Attempts to resume imatinib at lower dosages, with or without a low-dose corticosteroid, resulted in recurrent reactions. Once-weekly administration of imatinib, however, produced a tolerable, less severe reaction. After the woman had experienced exfoliative dermatitis for 4 months, the reaction subsided and disappeared. DISCUSSION: Once-weekly administration of imatinib allowed imatinib therapy to continue, and this dosing schedule appeared safe. Patients with severe cutaneous reactions who need to continue imatinib may benefit from this strategy, along with lowering of the dosage and premedication with a corticosteroid. CONCLUSIONS: In a patient with recurrent cutaneous reactions due to imatinib, a once-weekly dosing schedule was safe, well tolerated, and associated with eventual disappearance of the reaction.

Administration, Cutaneous↗

[Paraneoplastic erythroderma: apropos of a case].

A 63-year-old male patient had severe exfoliative dermatitis (erythroderma) which led to the discovery of squamous cell carcinoma of the larynx. The possibility of paraneoplastic erythroderma is discussed. Although such an aetiology is rare, 5 cases with a similar paraneoplastic syndrome have been previously reported, which cannot be considered as a merely fortuitous association of exfoliative dermatitis and visceral cancer.

Carcinoma, Squamous Cell↗