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Patients with erythema multiforme (EM) often have chronic or recurring oral lesions that cause intense pain and interfere with a variety of functions including eating and speech. Previous studies suggest that levamisole restores to normal the function of phagocytes and T lymphocytes, and activates the inflammatory response. In our previous double-blind study 8 of 13 patients with EM had a decrease in severity and frequency of attacks. The purpose of this open prospective study was to evaluate short-term and long-term clinical efficacy of levamisole in patients with mucocutaneous EM. Thirty-nine patients with mucocutaneous EM seen in the Oral Medicine Clinic, School of Dentistry, University of California-San Francisco, comprised our study group. Levamisole was used alone in 17 patients or in combination with prednisone in 22 patients and was given as a single dose of 150 mg/day for 3 consecutive days. Thirty-one patients showed a complete response from levamisole (alone in 13 and in combination with prednisone in 18). Four showed a partial response of signs and symptoms, and four others had no benefits from levamisole whether alone or in combination. The most common side effects from levamisole were skin rash, tiredness, weakness, myalgia, taste change, and insomnia.
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PMID:Clinical response to levamisole in thirty-nine patients with erythema multiforme. An open prospective study. 140 89

Within the clinical spectrum of erythema multiforme, two subgroups have been recently identified: recurrent erythema multiforme and the rare persistent erythema multiforme. Two additional cases of persistent erythema multiforme are described. Lesions were widespread and resistant to traditional therapies. One of the patients had an underlying malignancy; the other exhibited a symptom complex characterized by fatigue, fever, sore throat and lymphadenopathy, and an abnormal Epstein-Barr virus serologic profile suggestive of endogenous reactivation of Epstein-Barr virus infection.
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PMID:Persistent erythema multiforme: report of two new cases and review of literature. 761 87

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.
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PMID:Chronic fatigue syndrome: a novel disorder with cutaneous manifestations. 830 53

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.
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PMID:Smallpox vaccination and adverse reactions. Guidance for clinicians. 1261 10

A 37-year-old Caucasian woman presented with subacute, symmetrical inflammatory arthralgia, which was affecting her work. Apart from fatigue, she had no other constitutional symptoms. She had undergone cosmetic bilateral silicone breast implant surgery in 2008. Blood tests revealed erythrocyte sedimentation rate 53 mm/h, weakly positive antinuclear antibodies and IgG cardiolipin antibody, while breast ultrasound revealed a ruptured left silicone implant. The working diagnosis was systemic inflammatory disease of uncertain origin. She decided to have replacement, rather than removal, of her silicone breast implants privately, but her symptoms persisted postoperatively with a new erythema multiforme-like rash despite treatment with methotrexate and moderate dose prednisolone. Following further consultation with a National Health Service breast surgeon, her silicone implants were removed. Within 10 weeks of surgery, all immunomodulatory treatment was discontinued with complete symptom and inflammatory response resolution. This case illustrates that implant silicone can induce clinically significant systemic inflammatory disease and implant removal is essential for disease resolution.
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PMID:Systemic inflammatory disease resolution following cosmetic silicone breast implant removal. 2561 80

Recurrent erythema multiforme (REM) is a chronic disease characterized by frequent episodes of target cutaneous lesions in an acral distribution. Conventional treatment includes systemic corticosteroids and antiviral therapy. The aim of this study was to evaluate dapsone as a potential steroid sparing-agent for the treatment of REM after a failed trial of at least one antiviral therapy (acyclovir, famciclovir, or valacyclovir). A retrospective chart review was conducted on thirteen patients with a diagnosis of REM who underwent treatment with dapsone after failing at least one antiviral therapy. Out of 13 patients, 6 showed complete response (CR) and 5 showed partial response (PR). The underlying cause was identified in 5 patients with all showing at least PR. Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug-induced lupus erythematosus. A continuous course of dapsone, titrated up from 25 mg/day to a dose at which clinical improvement is seen with acceptable patient tolerance, is a viable steroid sparing-agent for REM treatment after a failed trial of antiviral therapy.
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PMID:Treatment of antiviral-resistant recurrent erythema multiforme with dapsone. 2786 Jan 66

Erythema multiforme (EM) is an acute and usually self-limited immune-mediated mucocutaneous disorder that is a hypersensitivity reaction to drugs, infections, and vaccines. Clinically, it is characterized by maculopapular, target-like lesions symmetrically distributed on the extremities (minor form) or additionally affecting one or more mucous membranes and causing epidermal detachment involving < 10% of the total body surface area (major form). We report a novel association between pneumococcal vaccination and the development of EM in a 2.5-year-old boy. The introduction of 13-valent-polysaccharide-pneumococcal-conjugate vaccine (PCV13) into vaccination programs has resulted in a reduced incidence of pneumococcal disorders. Systemic side effects of PCV13 include chills, fever, headache, vomiting, fatigue, arthralgia, myalgias, decreased appetite, and diarrhea, whereas its cutaneous adverse reactions are local injection site reactions, Sweet's syndrome, and deep morphea. EM is triggered by a variety of vaccines; however, as far as we know, it has not previously been reported in association with pneumococcal vaccine. Although a fortuitous occurrence of EM in our patient cannot be absolutely excluded, it appears very likely that PCV13 caused the patient's eruption, considering the history and the laboratory data, which point toward a lack of any other causative factors.
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PMID:Erythema multiforme following pneumococcal vaccination. 2835 33

Autoimmune progesterone dermatitis (APD) is rare autoimmune response to endogenous progesterone or to earlier exposure to exogenous progesterone (1). Skin lesions typically occur due to increases in progesterone during the luteal phase of the menstrual cycle (2). A-31-year-old mother of two children presented to our Department with a 5-year history of pruritic and painful erythematosus macules, papules, and patches on her neck, pectoral region, and face, which appeared 2-3 days before the onset of menses and gradually resolved 7-10 days later (Figure 1). The lesions first appeared 10 months after her second pregnancy and a few months after she had started using oral contraceptive pills (OCP) containing gestodene combined with ethinyloestradiol. A few months before presenting to us, the lesions had started spreading on her forearms, elbows, and pretibial areas. Since one year prior to our visit she had complained of occasional urticaria with angioedema one week prior to menses, which resolved after menses. The lesions were accompanied by malaise, headache, and fatigue. The patient was asymptomatic between the outbreaks. She reported that she had been using various local corticosteroids, peroral antihistamines, and prednisone for the treatment of her skin lesions, but this treatment had not improved her symptoms. She suffered from mild seasonal rhinoconjunctivitis. We performed multiple laboratory tests that were unremarkable. Histopathological examination of a biopsy taken from a lesion on the neck showed epidermal hyperplasia and nonspecific mild dermal inflammation. Since progesterone was not available in aqueous solution in our country, we did not perform an intradermal test, but we performed a lymphocyte transformation test (LTT) to medroxyprogesterone and estradiol. The patient's lymphocytes showed markedly enhanced proliferation to medroxyprogesterone in vitro, while being negative to estradiol. We had performed control LTT in 10 healthy controls and 10 patients with atopy, and such hyperactivity was not observed in any of them. We performed an oral provocation test with OCP containing gestodene combined with ethinyloestradiol. Two days after commencing treatment, the patient developed widespread dermatitis (Figure 2) with nausea, malaise, and angioedema. The patient was informed about treatment options and possible side-effects. She started with OCP with the lowest amount of progesterone, containing ethinyloestradiol and dropirenone for treatment of APD, but terminated treatment after the second cycle due to a worsening of the skin lesions and urticaria accompanied with angioedema. At the time of writing, our patient continues to have premenstrual flares. The typical symptoms of APD are skin lesions such as eczema, erythema multiforme, prurigo, stomatitis, papulopustular lesions, folliculitis, urticaria, angioedema, and rarely anaphylaxis (2) that develop 3-10 days before and subside 1-2 days after menses, with recurrent cyclic aggravation (1,3,4). Frequently, patients have a history of exogenous progesterone intake (1,5,6), as in our patient, which could have resulted in antibody formation. The diagnosis of APD is established by an appropriate clinical history (premenstrual flare of skin lesions), a progesterone intradermal test, an intramuscular (7), oral (8), or intravaginal (1, 6) progesterone challenge test, and circulating antibodies to progesterone. Progesterone testing has not been standardized. Most of the sex hormones are not suitable for testing since they contain an oily component that can produce an irritant test reaction. Gestodene, which was used for the oral provocation test in our patient, is a potent progesterone (9). The LTT shows reactions to circulating lymphocytes and reflects immune reactions within the body. The goal of treatment is suppression of ovulation. Currently, the first-line choice of therapy is a combination oral contraceptive (3). We believe that OCP have a limited effect because all of them contain a progesterone component. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releasing hormone analogs (3,4,6), conjugated estrogens (7), tamoxifen, oophorectomy (8), and progestogen desensitization (10) with varying success.
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PMID:Autoimmune Progesterone Dermatitis Diagnosed by Lymphocyte Transformation Test and Progesterone Provocation Test. 3039 Jul 35

Modafinil is a nonamphetamine nootropic drug with an increasingly therapeutic interest due to its different sites of action and behavioral effects in comparison to cocaine or amphetamine. A review of modafinil (and of its prodrug adrafinil and its R-enantiomer armodafinil) chemical, pharmacokinetic, pharmacodynamic, toxicological, clinical and forensic aspects was performed, aiming to better understand possible health problems associated to its unconscious and unruled use. Modafinil is a racemate metabolized mainly in the liver into its inactive acid and sulfone metabolites, which undergo primarily renal excretion. Although not fully clarified, major effects seem to be associated to inhibition of dopamine reuptake and modulation of several other neurochemical pathways, namely noradrenergic, serotoninergic, orexinergic, histaminergic, glutamatergic and GABAergic. Due its wake-promoting effects, modafinil is used for the treatment of daily sleepiness associated to narcolepsy, obstructive sleep apnea and shift work sleep disorder. Its psychotropic and cognitive effects are also attractive in several other pathologies and conditions that affect sleep structure, induce fatigue and lethargy, and impair cognitive abilities. Additionally, in health subjects, including students, modafinil is being used off-label to overcome sleepiness, increase concentration and improve cognitive potential. The most common adverse effects associated to modafinil intake are headache, insomnia, anxiety, diarrhea, dry mouth and raise in blood pressure and heart rate. Infrequently, severe dermatologic effects in children, including maculopapular and morbilliform rash, erythema multiforme and Stevens-Johnson Syndrome have been reported. Intoxication and dependence associated to modafinil are uncommon. Further research on effects and health implications of modafinil and its analogs is steel needed to create evidence-based policies.
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PMID:Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects. 3195 4