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This article briefly reviews potential mucocutaneous adverse reactions to medicaments, with special attention to the commonest used drugs in Denmark. More than 70 different adverse events are associated with the intake of various drugs, which means that, irrespective of the presentation and morphology of the exanthema, a drug-induced eruption should always be considered a possibility.
Exanthema is characterized by extensive generalized eruptions of the skin and mucosa that show a typical temporal spread. Potential noxae include medications, foodstuffs, infections (viral, bacterial, mycotic, parasitic), and malignancies, but unexplained causes may also present. A knowledge of the cutaneous changes may contribute decisively to ensuring that specific diagnostic and therapeutic measures are initiated without delay.
In the treatment of exanthems, the first step is the elimination of the causal agent. Of great importance also is the symptomatic treatment of the cutaneous changes and such associated symptoms as itching and pain. The choice of the appropriate external medication and its vehicle will depend on the clinical findings, skin type, and the location of the skin lesions. The most important therapeutic principles are discussed taking drug-induced exanthema, acute urticaria and (herpes) zoster as examples.
The author deals with the epidemiology of the sixth disease--exanthema subitum which is caused by the herpes virus hominis type 6. There are nine forms of the disease. The haemogram is characterized by granulocytopenia, eosinopenia with relative lymphocytosis, thrombocytopenia.
Eye drops contain several ophthalmic medications which can produce allergic reactions. We report the case of a patient with contact dermatitis from neomycin and a probable fixed exanthema after parenteral administration of tobramycin who tolerated topical tobramycin and other aminoglycosides.
Equine coital exanthema can be produced experimentally in stallions by inoculation with an equine herpesvirus (strain 65/61) and be transmitted during coitus with an infected mare. Serological responses to this infection include the production of complement-fixing and serum-neutralizing antibodies which reach maximum levels 14 to 21 days after infection. Complement-fixing antibodies decline rapidly and are usually not detectable by 60 days after infection, whereas serum-neutralizing antibody activity is maintained for at least 1 year. This disparity provides a useful method for the diagnosis of recent infections and estimation of the temporal incidence of infection in groups of mares. It seems likely that clinically normal carrier mares spread the virus on studs where the disease has previously not occurred.
The well-known condition of erythema infectiosum is caused by parvovirus B19, a single-stranded DNA virus discovered in 1975. The characteristic erythema obviously does not always appear: antibodies are present in 50%-60% of all adults. The virus is transmitted by airborne droplets, and the incubation period is 13-17 days. Clinically, there are unspecific prodromes, and aside from exanthema these can take the form of lymphadenopathy, influenza-like symptoms, and arthralgia. Parvovirus B19 has a marked affinity for erythropoietic cells. The infection may be of clinical importance in patients with haematological disease and can cause fetal death during pregnancy. The diagnosis is confirmed by detection of specific antibodies of the IgM or IgG class.
Report on a 50-year-old patient with cryofibrinogenemia, suffering from a recurrent exanthema induced by cold exposure.
The Authors performed ona group a patients suffering from drug exanthema a thorough clinico-anamnestic and allergo-immunological investigation (skin reactions, patch-tests, Prausnitz-Küstner passive transport, in vitro lymphocyte blastization, total serum IgE radioimmunoassay). The results obtained do not support an immunoallergical pathogenesis of this syndrome. The possible alternative hypotheses and the future perspectives of study are discussed.
Two similar calici agents, San Miguel sea lion virus (SMSV) and vesicular exanthema of swine virus (VESV) are susceptible to the virucidal activity of disinfectants of differing formulation. Ten of 12 compounds were effective against six log10 plaque forming units (PFU) of SMSV in a 2-min exposure at 4, 25 and 37 degrees C. However, only seven of these 10 SMSV-positive compounds inactivated VESV under the same conditions of temperature and time. Two compounds were not effective against SMSV in a 20-min exposure at 4 and 25 degrees C, but were effective at 37 degrees C. Two of the three compounds not effective against VESV in a 20-min exposure at 4 and 25 degrees C were also effective at 37 degrees C. The test iodophor compound inactivated SMSV completely but had only minimal inactivating activity against VESV at the three temperatures tested.
A 68-year-old man who was treated for febrile angina with gentamicin, doxycycline, phenoxymethylpenicillin K, and minocycline developed a generalized pustular exanthema favoring the predilected areas (hands, feet). Apart from a subepidermal pustule, the most noteworthy histological finding was a pronounced leukocytoclastic vasculitis. After disappearance of the skin lesions an intradermal test using cilligen (penicilloyl-polylysin) was conducted. The test gave a strongly positive early reaction, and 48 h after this an acute pustular outbreak developed analogous to the original manifestation. Doxycycline tested late, produced no exacerbation even though it was positive in the intradermal test. This pustular allergical drug rash can be classified as a vasculitis leucocytoclastica allergica which, as we know, appears in various clinical forms. It does not form a new disease entity. Terms used so far, such as "pustular necrotizing angiitis", "generalized pustular drug rash", "acute generalized pustular bacterid", "pustulosis acuta generalisata", only partially correspond to the actual pathoetiology.
Serum-neutralizing antibodies to both vesicular exanthema of swine virus (VESV) and San Miguel sea lion virus (SMSV) were found in a number of animal species having an association with the southern California coastal zones. California sea lions (Zalophus californianus) had antibodies to 9 VESV types (A48, C52, D53, E54, F54, G55, I55, J56, and K56). Fur seals (Callorhinus ursinus) and elephant seal pups (Mirounga angustirostris) were tested for antibodies to 6 VESV types and all were negative. California gray whales (Eschrichtius robustus) were tested for antibodies to 9 VESV types, and sperm whale (Physeter catodon), finback whale (Balaenoptera physalus), and sei whale (Balaenoptera borealis) were tested for 6 VESV types. Among the last 4 species, antibodies were present for each VESV type except C52, and all species were positive for antibodies to 2 or more VESV types. Feral swine from both Santa Cruz Island and Santa Catalina Island were tested and antibodies were present for 8 of 9 VESV types and all SMSV types except SMSV-4. One donkey from San Miguel Island was positive for VESV I55 and 2 were positive for SMSV-2.
We report on a 30-year-old female patient with therapy-refractory polymorphous exanthema and widespread erosions in the oral and genital mucosa. The alterations demonstrated in the skin and genital mucosa were associated with a malignant thymoma with metastases being interpretatet as a paraneoplastic syndrome. There was a remarkably large spectrum of circulating antibodies, which had no corresponding clinical correlation. Our examination results indicate a dysregulation between cellular and humoral immunity, obviously caused by the malignant thymoma, with an extraordinary, uncontrolled production of antibodies against structures belonging to the body and alien structures.
Human Herpesvirus 6 (HHV-6) is the sixth human pathogenic Herpesvirus. It was isolated for the first time in 1986. The virus is isolated from blood and saliva and it is probable that it is latent in salivary glands and possibly also in blood. The most probable route of infection is droplet infection via saliva and thereafter possibly by blood. Sero-epidemiological investigations demonstrate that newly born infants are practically all passively immunised via maternal antibodies. At about the age of six months, HHV-6 antibody can be demonstrated in a minority of children. From the age of two years and until 50 years, HHV-6 antibody is present in 90-100% of the population. This is in agreement with the extensive HHV-6 infection in the age group from six months to two years. It is demonstrated that HHV-6 is the cause of exanthema subitum. It is uncertain whether HHV-6 is of pathogenetic significance for other diseases.
We examined long-term neurological outcome of 12 patients, whose first febrile seizures had occurred during exanthema subitum (ES) and who had been treated with continuous daily administration of anticonvulsant drugs. Six of 12 children had a family history of febrile or afebrile convulsions and in a sister of one patient, athetoid palsy followed the status of afebrile convulsion (AC) during ES. Twelve cases were clinically classified into four groups; (A) 2 patients in whom ACs were repeated as soon as the fever of ES had dropped, (B) 6 patients in whom frequent recurrences of febrile convulsion followed ES, showing epileptic EEG abnormalities, (C) 1 patient who had suffered from later epilepsy, (D) 3 patients who showed complex type of febrile convulsion only during ES without any EEG abnormalities. Except one patient in group (A), who showed residual hemiparesis on the left, 11 cases demonstrated normal psychomotor development, and in 5 of all 12 cases, the treatment with anti-convulsant drugs could be discontinued. Unless severe neurological sequelae are complicated, long-term prognosis is not so poor in children whose first febrile convulsion occurred during ES.
A serendipitous discovery during early AIDS investigations was human herpes virus type 6 (HHV-6). Two years later (1988) it was shown that HHV-6 and later on also HHV-7 are the causes of exanthema subitum, a childhood disease with previously unknown causation. HHV-6 and HHV-7 are the main cause of febrile seizures. It is assumed that 90% of children are infected before they are three years old. The viruses are also found in adults; HHV-6 may cause mononucleosis and hepatitis. HHV-6 and HHV-7 infect CD4+ cells and may influence the course of HIV infection. In AIDS patients HHV-6 and cytomegalovirus are often isolated together from the lungs, possibly because they activate each other. Another possibility is that the circumstances in the lungs are favourable to both. HHV-6 and HHV-7 infection may be serologically diagnosed. There is little experience with antiviral treatment.
The 17-year-old was admitted for investigation of a fever persisting for three weeks in spite of antibiotic treatment. Based on the clinical picture presenting with fugitive exanthema during febrile episodes, myalgia, polyserositis, leucocytosis with toxic granulations and-- after an antibiotic window--negative cultures of all investigated fluids (blood, pleural and peritoneal fluid), adult-type Still's disease was diagnosed. Treatment with steroids and indomethacine was only temporarily successful. Therapeutic stabilization first occurred under administration of phenylbutazone. The course was complicated by three surgical abdominal interventions because of an unclear acute abdomen, a strangulation ileus and a small-bowel perforation.
A 30-year-old female entered the emergency room for medical advice because of progressive deterioration of general health with headache, arthralgias, myalgias and fever after a vacation of three weeks in Malaysia and Hong Kong. Because of persistent fever, lymphadenopathy, slight leuco- and thrombocytopenia and only insignificantly elevated humoral signs of an inflammatory process, the patient was treated symptomatically after exclusion of malaria. A viral disease was suspected. Two days later, an exanthema erupted suddenly on the trunk. Pinhead-sized livid, flat macules, increasing in size within hours and spreading to the extremities, were observed. Further investigations revealed a significantly elevated titer of IgG directed against rickettsia conorii, leading to the diagnosis of Mediterranean spotted fever. Under antibiotic treatment with tetracycline, the aforementioned findings regressed within few days, and the patient recovered completely.