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PubMed1994

Chronic fatigue syndrome: a novel disorder with cutaneous manifestations.

Persistent and disabling fatigue associated with low-grade fever and other constitutional symptoms, without any known disorder that accounts for it, is recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of patients, but their description is inaccurate. Recurrent aphthous stomatitis or persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been reported. Patients may be diagnosed as having CFS only when they fulfill at least 2 major and 8 minor criteria. Major criteria are the presence of debilitating fatigue persisting or recurring for at least 6 months and the absence of any other medical disorder that may explain it. Although different viral or nonviral etiologies have been documented, evidence implicating EBV is gaining support.

Fatigue Syndrome, Chronic↗
PubMed1976

Acute coccidioidal pleural effusion.

Acute coccidioidal pleural effusions were studied in 28 patients. Coccidioidal pleural effusion appeared to be secondary to direct spread of contigous parenchymal infection, rather than to hematogenous dissemination, in more than 90 per cent of these patients. Only 2 of 28 patients had the concomitant development of disseminated infection, and both patients possessed factors known to predispose to dissemination. Because of the excellent prognosis in most patients, therapy in patients with coccidioidal pleural effusion should be expectant. This is true even when substantial increases occur in complement fixation titers; such elevations were frequent in this series. Cultures of pleural biopsy specimens were the most rewarding cultural source in this series, being positive in all 8 patients in whom such biopsy specimens were cultured. Dermal hypersensitivity, including erythema nodosum and erythema multiforme, was commin in patients whose clinical course was uncomplicated.

Adolescent↗
PubMed2000

Toxic epidermal necrolysis in children--an update.

Toxic epidermal necrolysis (TEN) is a relatively rare disease, characterized by generalized erythema, bulla formation, and exfoliation of the epidermis that resembles scalding. It is usually drug-induced and mediated by immune reactions of several types. TEN has to be differentiated from erythema multiforme and Stevens-Johnson syndrome. TEN bears a life-threatening potential and a risk for significant complications such as dehydration; secondary infections; pulmonary, gastrointestinal, and renal involvement; and late scarring with cosmetic and functional implications. Therapeutic interventions include admission in a burn center unit, systemic antibiotics and corticosteroids, topical therapy with antibacterial agents and biological dressings, and supportive measures.

Burn Units↗
PubMed1985

Pathology of an ulcerative dermatitis in Belgian Landrace sows.

Chronic ulcers of the skin were observed in three Belgian Landrace sows. Lesions were located on ears, limbs, and in the mammary region and were resistant to treatment that included corticosteroid therapy. Major histologic changes were located at the dermo-epidermal junction. Ulcers were deep, and the adjacent epidermis had marked hyperkeratosis, acanthosis, and intracellular edema. Dermatitis was prominent, essentially located in the superficial dermis. By electron microscopy, basal lamina appeared disrupted. Dermo-epidermal separation occurred beneath the basal lamina. Collagen was morphologically normal. Desmosomes, hemidesmosomes, and anchorage fibers were present in areas adjacent to lesions. Ulcerative dermatitis of sows is morphologically similar to pemphigus, pemphigoid, systemic lupus erythematosus, epidermolysis bullosa simplex, erythema multiforme, toxic epidermal necrolysis, and drug eruption. However, significant differences exist between ulcerative dermatitis and these conditions.

Animals↗
PubMed1988

Vancomycin-associated exfoliative dermatitis during continuous ambulatory peritoneal dialysis.

Vancomycin is commonly prescribed to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for catheter-related infections and acute episodes of peritonitis. Although adverse dermatological reactions have been reported secondary to the rapid intravenous infusion of vancomycin, the intraperitoneal route of administration has been used routinely during CAPD without these effects. This case report describes a CAPD patient with systemic lupus erythematosus who developed erythema multiforme that progressed to exfoliative dermatitis during intermittent intraperitoneal vancomycin therapy for a catheter-related exit-site/tunnel infection.

Adult↗
PubMed1993

Allopurinol hypersensitivity syndrome: a review.

OBJECTIVE: To review the pathophysiology, pathology, and clinical findings of allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse effect of allopurinol therapy. DATA SOURCES: A MEDLINE search (key terms hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson syndrome) was used to identify cases reported in the literature through the end of 1990. STUDY SELECTION: All cases evaluated met Singer and Wallace's diagnostic criteria for AHS. DATA EXTRACTION: We extracted data from 101 cases of AHS reported in the literature. The following information, when available, was analyzed: (1) patient data (age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration of treatment, indications, concomitant medications, and (3) adverse-event data. DATA SYNTHESIS: Patients were mostly middle-aged men with hypertension and/or renal failure receiving excessive doses of allopurinol primarily for asymptomatic hyperuricemia. Cutaneous rash and fever were the most common clinical findings. CONCLUSIONS: Although the pathophysiologic pathway leading to the development of AHS is unknown, it probably involves an immunologic mechanism following allopurinol accumulation in patients with poor renal function. Our findings suggest that the accepted diagnostic criteria for AHS may be too broad, and we recommend the application of more restrictive criteria. There is no effective treatment for AHS. The use of allopurinol only for accepted indications and in dosages adjusted for a patient's renal function may be the only means of minimizing the incidence of AHS.

Adult↗
PubMed2004

ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive drug metabolite; S, substrate for CYP isoform; SJS, Stevens-Johnson syndrome; SLE, systemic lupus erythematosus; and TEN, toxic epidermal necrolysis.

Journal Article↗
PubMed2004

Adverse reactions during imatinib and lansoprazole treatment in gastrointestinal stromal tumors.

OBJECTIVE: To report the case of a patient affected by gastrointestinal stromal tumors (GIST) who developed cutaneous adverse drug reactions during treatment with imatinib and lansoprazole. CASE SUMMARY: After 2 months of treatment with imatinib 400 mg/day, a 60-year-old white female affected by GIST developed bilateral palpebral edema with hyperemic conjunctivae and labial edema when lansoprazole 15 mg/day was introduced to treat dyspeptic symptomatology. Treatment was discontinued, and on reintroduction of both drugs, the patient developed Stevens-Johnson syndrome. Two months later, generalized cutaneous reactions appeared immediately following reintroduction of low-dose imatinib with corticosteroid plus lansoprazole treatment. After discontinuation of all drugs, with the exception of the corticosteroid, the progression of cutaneous lesions stopped. DISCUSSION: The use of imatinib is commonly associated with a high dose-dependent rate of rash and edema. Several cases of Stevens-Johnson syndrome have also been described, although not in patients affected by GIST. Severe skin reactions have been reported for lansoprazole including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Applying Naranjo's algorithm, the adverse events were considered possible due to imatinib and probable due to lansoprazole. CONCLUSIONS: On the basis of the data reported, we conclude that the adverse reactions described may be attributed to either drug alone. However, combined use of drugs may increase the risk of onset of these adverse reactions due to a potential drug interaction involving CYP3A4.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Ofloxacin: a probable cause of toxic epidermal necrolysis.

OBJECTIVE: To report a fatal case of toxic epidermal necrolysis in a man who was treated with oral ofloxacin for epididymitis. CASE SUMMARY: A 75-year-old white man received 23.6 grams of ofloxacin over a 51-day period for epididymitis. He experienced a severe skin reaction diagnosed as toxic epidermal necrolysis. The man died from complications related to toxic epidermal necrolysis. DISCUSSION: Toxic epidermal necrolysis is an infrequent, yet often fatal, severe, systemic, cutaneous disease most often the result of an adverse drug reaction. Fluoroquinolones have rarely been implicated in cases of toxic epidermal necrolysis. A MEDLINE search from 1966 to December 2000 revealed no reports of toxic epidermal necrolysis, erythema multiforme, or Stevens-Johnson syndrome due to ofloxacin therapy. However, a large case-control study included three cases of either Stevens-Johnson syndrome or toxic epidermal necrolysis associated with ofloxacin use, but no details of the cases were given. This report rules out other causes of toxic epidermal necrolysis and implicates ofloxacin in what appears to be an atypical presentation of drug-induced toxic epidermal necrolysis. CONCLUSIONS: There is very little published information regarding ofloxacin-induced toxic epidermal necrolysis. There are a few case reports of other fluoroquinolones that have been associated with toxic epidermal necrolysis. It is hoped that this case report creates awareness that ofloxacin-induced toxic epidermal necrolysis is possible.

Aged↗
PubMed2005

Paraneoplastic pemphigus in a dog with splenic sarcoma.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering skin disease of humans that consists of characteristic skin lesions associated with concurrent neoplasia. In this study we provide histologic and serologic evidence to support a diagnosis of PNP in a dog with splenic sarcoma. Skin lesions consisted of widespread erosions involving haired skin, mucocutaneous junctions, and oral mucosa. Microscopic examination of skin and mucosae revealed lesions consistent with both pemphigus vulgaris and erythema multiforme. Immunoprecipitation confirmed that circulating IgG autoantibodies from this patient recognized five distinct antigens, presumed to represent epidermal plakins. Clinical, histopathologic, and immunologic findings in this patient were similar to those observed in human patients with PNP. The splenic neoplasia in this dog was diagnosed as a phenotypically variable spindle cell sarcoma. To date, only one other dog has been reported with PNP. This is the second reported case of canine PNP and the first patient in whom skin lesions were identified in association with splenic neoplasia.

Animals↗
PubMed1975

Hand, foot, and mouth disease: a viral disease of importance to dentists.

Hand, foot, and mouth disease is a disease of viral origin that produces characteristic lesions in the mouth and on the hands and feet. Knowledge of the disease is important to dentists since the oral vesicular and ulcerative lesions are usually the first clinical signs of the disease, and the epidemiclike patterns of the disease make it likely that the dentist will contract the disease himself or possibly become a carrier of the virus. The lesions of hand, foot, and mouth disease usually regress in two to three weeks, and complications are rare. Treatment is basically palliative to reduce the pain and irritation. Differential diagnosis of the disease must include consideration of herpes simplex, herpangina, recurrent aphthae, erythema multiforme, and animal foot and mouth disease. A case involving a dentist and his family is reported.

Adult↗
PubMed1979

Study of a bland dentifrice for persons with radiation-induced mucositis and vesiculo-erosive disease.

Althought the patient group was limited to persons with radiation-induced mucositis, lichen planus, and erythema multiforme, the study indicates the potential usefulness of a bland dentifrice to other patients with sensitive mouths. Although it is presumed that regular brushing habits will aid in oral hygiene and health, the specific effect of a bland dentifrice on control of plaque, caries, and periodontal disease cannot be assessed in this preliminary study. Also, no comparison was made with cleaning techniques in which dentifrice is not used. Therefore, this study indicated only that dentifrice with reduced flavor, like the one used in this study, may encourage better oral hygiene through continued brushing when irritation from regular dentifrices discouages it.

Adult↗
PubMed1987

Red, blistering, and erosive lesions of the oral mucosa.

Clinical diagnosis among the vesiculobullous diseases is difficult. Benign mucous membrane pemphigoid is a chronic condition, whereas bullous pemphigoid and erythema multiforme are self-limiting. Oral lesions can be the initial appearing feature of the disease. Therefore, routine histological examination with immunofluorescent studies and a good medical history will aid in differentiating among them. The case report described here shows a benign mucous membrane (cicatricial) pemphigoid in a 52-year-old female whose initial symptoms involved the oral mucosa with subsequent skin lesions. There is no other apparent mucosal involvement at this time. The symptoms are palliated with use of topical fluocinonide, but continued follow-up care is indicated.

Diagnosis, Differential↗
PubMed2002

Adverse effects of antiretroviral therapy: focus on orofacial effects.

The optimum anti-HIV drug has yet to be found. This paper will summarise some of the oral adverse effects associated with antiretroviral agents against HIV. The development of antiretroviral drugs for the treatment of HIV infection has been aimed at the inactivation of two HIV enzymes: reverse transcriptase and proteases. Erythema multiforme, ulcers and xerostomia are the main oral side effects associated with reverse transcriptase inhibitors. Parotid lipomatosis, taste disturbance, xerostomia and perioral paraesthesia are oral adverse effects, which are mainly related to protease inhibitor therapy. The search for new antiretrovirals with different active mechanisms and patterns of resistance constitutes a key question in HIV treatment. The use of new drugs and drug combinations will lead to the appearance of oral lesions, which will be difficult to identify and treat and which cannot be ignored by the practitioner.

Anti-HIV Agents↗
PubMed2006

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↗
PubMed2005

Incidence of mucocutaneous reactions in children treated with niflumic acid, other nonsteroidal antiinflammatory drugs, or nonopioid analgesics.

BACKGROUND AND OBJECTIVE: Results from a relatively small case-control study recently showed that niflumic acid increases the risk of serious mucocutaneous reactions in children. As a consequence, the Italian Ministry of Health sent a "Dear Doctor" letter in June 2001 to warn pediatricians about the alleged adverse effects. The objective of this study was to estimate and compare the incidence of mild and severe mucocutaneous reactions among children using niflumic acid, other nonsteroidal antiinflammatory drugs (NSAIDs), or nonopioid analgesics. DESIGN: Retrospective cohort study. SETTING: Italy is one of the few countries in which a specific primary care system is devoted to children up to 14 years of age: every child is registered at birth and receives free medical care from 1 of the approximately 6000 family pediatricians working for the National Health Service. This study was conducted with the Pedianet network of Italian family pediatricians who use computerized electronic patient records for routine care; 185 pediatricians participated in the study. The patient records comprise information on demographics, diagnoses, symptoms, prescriptions, referrals, laboratory examinations, and hospitalizations. PARTICIPANTS: Children aged 0 to 14 years and registered with 1 of the collaborating pediatricians between January 1, 1998, and May 31, 2001. MAIN OUTCOME MEASURES: The incidence rate of severe (hospitalized or referred) and mild mucocutaneous reactions (exanthema, disseminated or localized pruritus, urticaria, angioedema, fixed eruption, dermatitis, erythema multiforme, vesicles, bullae, pustules, toxic epidermal necrolysis, purpura, and vasculitis) was estimated during use of niflumic acid, other NSAIDs, or nonopioid analgesics. For each episode of drug use, the following covariates were assessed: age, gender, region, year, indication for study drug, use of antibiotics, antimycotic agents, glucocorticoids, and other NSAIDs. Multivariate Poisson regression analysis was used to estimate the adjusted relative risk of mucocutaneous disorders during use of niflumic acid compared with use of other NSAIDs or use of acetaminophen alone. RESULTS: The population included 193727 children, 45351 of whom received at least 1 of the study drugs. The most frequently prescribed drugs were niflumic acid, acetaminophen, and propionic acid derivatives (ketoprofen and flurbiprofen). Users of niflumic acid (n = 32150) were younger and slightly more often had otitis media or upper respiratory tract infections as an indication compared with the other NSAIDs. During use of the various study drugs we identified 1451 mild mucocutaneous events and 42 severe reactions. The incidence rates of severe and mild mucocutaneous reactions after the administration of any study drug were 10.3 per 100000 exposure person-days and 3.7 per 1000 exposure person-days, respectively. Both incidence rates decreased strongly with increasing age. In comparison with other NSAIDs, the adjusted relative risks of niflumic acid were 0.5 (95% confidence interval: 0.23-1.27) for severe and 0.9 (95% confidence interval: 0.79-1.11) for mild mucocutaneous reactions. The use of acetaminophen as a reference category instead of other NSAIDs, restriction of the children to those who received NSAIDs for respiratory tract infections, or restriction to those who did not use antibiotics never revealed an increased risk of serious or mild mucocutaneous reactions during use of niflumic acid. CONCLUSIONS: In comparison with other NSAIDs or acetaminophen, niflumic acid is not associated with an increased risk of severe or mild mucocutaneous reactions in children. This was true for the different age groups and various types of mucocutaneous reactions, was independent of the concomitant use of antibiotics, and was not sensitive to changes in our assumptions regarding exposure and outcomes.

Adolescent↗