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[The trend of the drug eruptions in the last fifteen years].

The drug eruptions are known to often become more severe by the readministration of causative drugs. It is an important theme to prevent the relapse of the drug eruptions. We have been monitoring drug adverse reactions at our hospital since October, 1980. We divided fifteen years from October, 1980 to September, 1995 into three periods; the first period (Oct., 1980-Sep. 1985), the second period (Oct., 1985-Sep., 1990), and the third period (Oct., 1990-Sep., 1995), and discussed the trend of the drug eruptions appeared among these three periods. The number of the drug eruptions increased. But the proportion to the total drug adverse reactions and to the number of patients slightly decreased. The eruptions in women much increased and in the patients of forties or older generations also increased. But in patients of thirties or younger generations decreased. While nonsteroidal anti-inflammatory drugs (NSAIDs) other than pyrines, antibiotics other than penicillins and cephalosporins and drugs affecting the cardiovascular system and the metabolism tend to increase, pyrines, penicillins, iodic and biliary contrast media tend to decrease. The incubation period before the eruption appeared is less than three days in most antibiotics and anti-inflammatory drugs. But it is more than four days in most drugs for chronic diseases. Other symptoms such as nausea, fever and liver dysfunction were shown in 9.2% of the drug eruptions. In 8.9% of the drug eruptions a relapse of allergic reactions included eruptions were also found. In some cases the drug eruptions exacerbate by re-administration of beta-lactam antibiotics. In the case of administration of drugs, it is necessary to pay attention to dermatitis caused by the drugs. And we recognized the importance of the system for the prevention of the relapse of drug eruptions including injections.

Adolescent↗

[Successful salvage therapy with cladribine and rituximab for a patient with a relapsed Asian variant of intravascular large B-cell lymphoma].

The Asian variant of intravascular large B-cell lymphoma (AIVL) is a rare aggressive lymphoma characterized by various clinical symptoms, hemophagocytic syndrome and predominant growth within vessels. We present a 73-year-old man with relapsed AIVL who had been treated with six courses of CHOP regimen. A half year later, he presented with high fever, sweat, dementia and hepatosplenomegaly without lymphadenopathy. A bone marrow biopsy showed prominent hemophagocytosis and immunological staining disclosed an augmented intrasinusal pattern of atypical large lymphocytes characteristic of the CD20+ and CD5+ phenotypes. As salvage therapy, CND-R (rituximab, cladribine, mitoxantrone, dexamethasone) was performed, and the clinical symptoms immediately and dramatically improved. Subsequently, CND-R therapy was repeated every 4 weeks. No serious adverse events were observed with the exception of grade 4 neutropenia and grade 3 thrombocytopenia. After completion of the fifth course, a bone marrow biopsy pathologically confirmed complete remission, leading to termination of this therapy. The patient has remained in remission for more than 15 months. CND-R therapy, which is effective for indolent lymphoma, may be one of the candidates in salvage therapy for relapsed AIVL.

Aged↗

Disseminated histoplasmosis.

OBJECTIVE: To study the clinical features and natural history of disseminated histoplasmosis(DH) in India. METHODS: We retrospectively analyzed the data obtained from the in-patient medical records of adults (age > 13 years) diagnosed to have DH during the period from January 1989 to December 1999. DH was diagnosed when histologically compatible intracellular organisms were present or Histoplasma capsulatum was obtained in culture from the extrapulmonary sites. RESULTS: Nineteen patients (18 male and 1 female) were diagnosed to have DH. Diabetes mellitus and HIV infection were the most common co-morbid conditions. Weight loss, fever and oropharyngeal ulcers were the commonest symptoms. Physical signs included hepatosplenomegaly, oropharyngeal ulcers and lymphadenopathy. The diagnosis was confirmed by histopathology and/or culture from the following sites: bone marrow, adrenal gland, lymph node, oropharyngeal ulcers, rectal mucosa and skin. Two patients were treated with Amphotericin B, 6 with various azoles and 3 had Amphotericin B followed by various azoles. Among the eleven treated, 7 were cured, 2 improved, 1 had a relapse and 1 patient died. CONCLUSION: DH is not uncommon in India and should be considered in the diagnosis of patients with prolonged fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly, lymphadenopathy and adrenal enlargement. Correct diagnosis and treatment leads to a favourable outcome.

Adolescent↗

[Central nervous system relapse with multiple brain masses in an acute promyelocytic leukemia patient treated with all-trans retinoic acid].

A 22-year-old woman with fever and bleeding tendency was given a diagnosis of acute promyelocytic leukemia (APL) on the basis of laboratory findings including a WBC count of 106 x 10(3)/microliter (90% blasts) and a platelet count of 1.6 x 10(4)/microliter. Induction therapy was started with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy. After the patient achieved complete remission, ATRA was discontinued and consolidation chemotherapy was started. However, 4 months after onset, leukemic blasts were detected in cerebrospinal fluid. Temporal central nervous system remission was induced by intrathecal chemotherapy only. However, 2 months later, multiple focal mass lesions had developed in the brain. ATRA (45 mg/m2) was restarted together with multiple intrathecal injections of anticancer drugs, and a third remission was achieved. It is conceivable that the incorporation of ATRA in induction chemotherapy is related to the development of this rather rare complication of APL. The outcome in this case suggested orally administered ATRA may be effective in treating brain metastasis of APL.

Administration, Oral↗

Salmonella typhi infection in adults is not limited to travellers returning from the tropics.

We reviewed the case notes of 23 adult patients infected with Salmonella typhi and admitted to the infectious disease unit, Auckland Hospital between January 1977 and December 1984. Fifteen had typhoid fever and eight were chronic carriers of S typhi. All isolates were sensitive to amoxycillin, chloramphenicol and cotrimoxazole. Ten of those with typhoid fever had recently been in tropical countries, predominantly Pacific Islands. The remaining five all lived in South Auckland and had not travelled out of New Zealand: we suspect that contaminated shellfish collected from the Manukau Harbour in South Auckland were the source. Typhoid fever should be suspected in young travellers returning to New Zealand with fever, diarrhoea, abdominal pain and headache. Similarly this diagnosis should be suspected in Polynesians and Maoris from South Auckland who have not travelled. All but one patient with typhoid fever responded clinically to the initial regimen which was usually oral amoxycillin given for a median 18 days. One other patient relapsed. Cholescystectomy and subsequent oral antibacterials eradicated S typhi from five biliary carriers with abnormal gallbladders. Prolonged high dose oral amoxycillin alone was effective in one of two carrier patients with normal gallbladders. The role of the Department of Health in identifying carriers of S typhi remains important.

Adolescent↗

[PFAPA Syndrome: Current Standard of Knowledge and Relevance for the ENT Specialist].

BACKGROUND: The symptoms fever, aphthous stomatitis, pharyngitis and cervical lymph node enlargement are among the most frequent complaints that particularly make children and adolescents consult an ENT specialist. In cases where these symptoms occur periodically, a PFAPA syndrome may be present. PATIENTS AND METHODS: We report on an atypical process in a 22 year old woman in whom the PFAPA syndrome first occurred during early infancy with recurrences since adolescence. RESULTS: Since the age of eight months the patient suffered from periodically occurring fever and pharyngitis with cervical lymph node enlargement. Therefore, by age four a tonsillectomy was performed and the symptoms disappeared. At age 15 similar symptoms occurred again with fever thrusts over approximately four to five days with temperatures up to 39.8 degrees C associated with pharyngitis, weakness and cervical lymphadenitis. Those symptoms relapsed periodically every four weeks. Treatment regimens with different antibiotics, Dimepranol and Inosin did not show any effect. Hyper-IgD syndrome and cyclic neutropenia were excluded. There were no signs for a humoral or cellular immune defect or a juvenile idiopathic arthritis. CONCLUSIONS: It is often very difficult to make the right diagnosis in a child or a young adolescent presenting with periodically occurring fever. So far the PFAPA syndrome is relatively unknown. Nevertheless, we think that it should be considered in the differential diagnosis by the ENT specialist patients with periodic fever, aphthous stomatitis, pharyngitis and cervical lymphadenopathy.

Adult↗

Fever induced by labetalol.

Fever caused by beta-adrenoceptor blocking agents is rare. We describe fever in two patients who had been treated with labetalol. In both patients, two challenge periods were rapidly followed by a relapse, whereas on each occasion there was normalization of temperature after discontinuation of the drug therapy. This reaction is rare and unpredictable. Because there was a clear sensitization period of three to four weeks, dose independency, and an accelerated reaction to rechallenge, this adverse effect seems to be caused by an immunoallergic reaction.

Aged↗

[Lineage switch on recurrence from minimally differentiated acute leukemia (M0) to acute megakaryocytic leukemia (M7)].

Phenotypic switch in acute leukemia is a rare phenomenon. We report on a female infant with minimally differentiated acute leukemia (M 0) which underwent a lineage switch on relapse. In March 1997, a 1-year-8-month old girl was admitted to our hospital with a high-grade fever and generalized purpura. Bone marrow showed 84% blasts. The blasts were negative for peroxidase, periodic acid-Schiff and alpha-naphthyl butyrate esterase. Immunophenotypic analyses of the blast cells were positive for CD 13, CD 33 antigens, as well as CD 34. Lymphoid markers all were negative. Though some blasts morphologically demonstrated cytoplasmic blebs, CD 41 was negative and ultrastructural platelet peroxidase was absent. Based on these hematological features, the patient was diagnosed as having AML-M 0. She was treated according to the Children's Cancer and Leukemia Study Group schedule and a complete remission was achieved 1.5 months after starting induction therapy. However, she relapsed in spite of continued chemotherapy in July 1997, when the cytomorphological pattern changed and the patient was diagnosed both morphologically and immunologically as having M 7. Electron microscopy revealed platelet peroxidase (+) and CD 41 (+). Cytogenetic studies on relapse demonstrated inv(3) (q 21 p 25). We attempted aggressive reinduction therapy, but without effect. The patient simultaneously developed severe pneumonia and died in February, 1998. A lineage switch on relapse and resistance to chemotherapy may be associated with the occurrence of genetic aberration.

Acute Disease↗

Typhoid fever: successful therapy with cefoperazone.

We compared cefoperazone with chloramphenicol in a randomized trial involving the treatment of 25 children with severe typhoid fever. The clinical characteristics of the two treatment groups were comparable on entry into the study. Four patients died (three receiving chloramphenicol, one cefoperazone), and an additional two patients received dexamethasone (one per group). Excluding these six patients, the response of the cefoperazone group was comparable or superior to that of the chloramphenicol group in terms of the number of days from initiation of therapy to becoming afebrile (P less than .055) and the number of days until negative blood cultures were obtained (P less than .19). There were no relapses or treatment failures in either group. We conclude that cefoperazone is as effective as chloramphenicol in the treatment of severe typhoid fever.

Adolescent↗

An outbreak of multidrug resistant typhoid fever in Bangalore.

Six hundred and eighty five blood cultures from children clinically diagnosed as enteric fever yielded 176 salmonella strains showing isolation success rate of 25.7%, S. typhi were 164 (93.2%), S. paratyphi A 5 (2.8%), S. choleraesuis 4 (2.3%) and S. typhimurium 3 (1.7%). Antibiogram of 164 isolates of S. typhi showed triple drug resistance (TDR) in 156 strains (95.1%) to chloramphenicol, ampicillin and cotrimoxazole, and sensitivity of 90.2% and 95.1% to norfloxacin and ciprofloxacin respectively. Minimum inhibitory concentrations (MIC) of chloramphenicol were between 360 mcg and 640 mcg per ml. Phage types of 38 strains of TDR S. typhi were predominantly E1 and 0 with prevalences of 47.4% and 36.8% respectively in this region. All children with S. typhi isolates sensitive to quinolones in Vitro responded well to these drugs with almost no relapse and hence, the newer generation of quinolones could be considered as the first choice in the primary treatment of enteric fever.

Anti-Bacterial Agents↗

Polymyalgia rheumatica without significantly increased erythrocyte sedimentation rate. A more benign syndrome.

BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. METHODS: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.

Age Factors↗

Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis.

We have prospectively performed peripheral blood stem cell autotransplants in six patients with hematological malignancies on an entirely outpatient basis. Patients were conditioned with high-dose melphalan and received a median of 4.2 x 10(8)/kg non-cryopreserved, non-purged mononuclear cells, containing a median of 3.9 x 10(6)/kg CD34 + cells. The median time to achieve > 500 granulocytes/microl was 21 days, with a range of 16 to 40, whereas the median time to achieve > 20,000 platelets/microl was 38 days, with a range of 21 to 48. Only three patients were transfused with platelets whereas packed red blood cells were transfused in two. All patients survived 60 days after the autograft and three are alive at 450, 690, and 1,950 days after the autotransplant. One patient was given an allogeneic bone marrow transplant when relapsing after the autotransplant. One patient had to be admitted to the hospital on day +10 because of fever. A median of 6,500.00 USD per patient was calculated as the total cost of each outpatient autotransplant. Since outpatient autologous transplants with non-frozen PBSC are feasible, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.

Adult↗

Treatment of relapsed B-cell non-Hodgkin's lymphoma with a combination of chimeric anti-CD20 monoclonal antibodies (rituximab) and G-CSF: final report on safety and efficacy.

Antibody-dependent cellular cytotoxicity (ADCC) is one of the possible mechanisms of action of the chimeric CD20 monoclonal antibody IDEC-C2B8 (rituximab). As granulocyte-colony stimulating factor (G-CSF) greatly enhances the cytotoxicity of neutrophils in ADCC, the efficacy of rituximab might be enhanced by the addition of G-CSF. In a phase I/II clinical trial, we investigated the safety and efficacy of the combination of rituximab and G-CSF (5 microg/kg/day, administered for 3 days, starting 2 days before each infusion) in 26 relapsed low-grade lymphoma patients. Adverse events occurred in 25/26 patients and mainly consisted of (grade I/II) fever (29%) and allergic reactions (19%). In phases I and II (375 mg/m(2) rituximab+G-CSF), 19 patients were evaluable for efficacy. The response rate was 42% (8/19; 95% CI 20-67%), with 16% (3/19) complete remissions and 26% (5/19) partial remissions. The median duration of response was 18 months, the median time to progression was 24 months. We conclude that the combination of rituximab and G-CSF is well tolerated. Although the overall response rate seems comparable to that reported for rituximab monotherapy, remission duration in this pilot phase II study is remarkably long. Randomized comparison with rituximab monotherapy should substantiate this promising finding.

Adult↗

Recurring staphylococcal scalded skin syndrome-like bullous mastocytosis: the utility of cytodiagnosis and the rapid regression with steroids.

We report a male infant with onset of an extensive bullous eruption at the age of 45 days. Staphylococcal scalded skin syndrome (SSSS) was suspected. Bullous mastocytosis was diagnosed by cytodiagnosis and confirmed by histologic examination. Three serious relapses were noted in a 2-year follow-up, and SSSS was again suspected because of high fever and leukocytosis with neutrophilia in an infectious context. Cytodiagnosis revealed the presence of mast cells and permitted rapid diagnosis of recurrences of bullous mastocytosis. Systemic corticotherapy dramatically improved the cutaneous lesions and general symptoms. This case report emphasizes the utility of cytodiagnosis in extensive blistering diseases in infancy and the possibility of obtaining rapid healing by using steroids.

Diagnosis, Differential↗

[Churg-Strauss syndrome].

BACKGROUND: The Churg-Strauss syndrome, also known as allergic granulomatosis with angiitis, is a rare necrotizing vasculitis with unknown pathogenesis. The necrotizing granulomatous vasculitis involves small and medium-sized arteries, capillaries and veins, leading to the characteristic changes of intra- and extravascular, eosiniphilic granulomas, accompanied by clinically symptoms: bronchial asthma, hypereosinophilia and fever. Ocular manifestations are rarely reported. CASE REPORT: A 53-year-old woman suffered from bronchial asthma, relapsing lung infiltrates and sinusites since 1994. In August 1997 she suddenly disclosed vasculitic skin manifestations on both legs and a mononeuritis of the left peroneus nerve. At the same time visual acuity of the right eye decreased, before she had shown some attacks of amaurosis fugax. The funduscopy showed a central retinal artery occlusion. LABORATORY FINDINGS: blood eosinophilia of 20%, elevated IgE value to 396 kU/l (normal value < 120 kU/l), and negative parameters for antineutrophil cytoplasmatic antibodies (p- and c-ANCA). CONCLUSION: The clinical and laboratory findings are characteristic signs for the Churg-Strauss syndrome. Without such typical manifestations the histologic examination leads to the diagnosis and helps to differentiate this disease from other necrotizing vasculitides, e.g. panarteriitis nodosa or Wegener's granulomatosis.

Azathioprine↗

Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Autoimmune paraneoplastic syndromes are commonly encountered in patients with myelodysplastic syndromes (MDS). A review of case reports and small series suggest as many as 10% of MDS patients may experience various autoimmune syndromes. Clinical manifestations of such phenomena may include an acute systemic vasculitic syndrome, skin vasculitis, fever, arthritis, pulmonary infiltrates, peripheral polyneuropathy, inflammatory bowel disease, glomerulonephritis, and even classical connective tissue disorders, such as relapsing polychondritis. On the other hand, asymptomatic immunologic abnormalities have also been reported in these patients. These autoimmune manifestations frequently respond to immunosuppressive agents including steroids and occasional hematologic responses to steroid therapy have also been reported. We report five patients with history of MDS who manifested different spectrums of autoimmune phenomena including: pyoderma gangrenosum (PG), vasculitis, Coombs negative hemolytic anemia, idiopathic thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy (CIDP). We also review the incidence, nature, course and response to therapy of these manifestations and discuss potential pathogenic mechanisms.

Adult↗

Early single dose therapy with ofloxacin for empirical treatment of acute gastroenteritis: a randomised, placebo-controlled double-blind clinical trial.

This study is a double-blind, placebo-controlled, randomised clinical trial to evaluate the clinical and microbiological efficacy and safety of single dose ofloxacin for acute diarrhoea. Eligible patients were 16 years of age or older with a history of acute diarrhoea lasting no more than 48 h; 117 patients were randomised and 97.4% (114/117) were evaluable for efficacy. Of these, 58% were suspected to have ingested contaminated foods. Enteric pathogens were isolated in 61.5% of the patients, Salmonella enteritidis being reported in 87.5%. The patients received either a single 400 mg dose of ofloxacin, or placebo. The average duration of diarrhoea was 2.56 +/- 2.21 days in the ofloxacin group and 3.41 +/- 2.5 in the placebo group (P = 0.117). The average duration of fever was 0.63 +/- 0.95 days in the ofloxacin group and 1.05 +/- 0.96 in the placebo group (P = 0.02). Symptoms remained unchanged for more than 48 h in only 7% of the patients who received ofloxacin, compared with 12% in the placebo group (P = 0.485). Only 32% of patients in the ofloxacin group remained culture positive after 48 h compared with 59% in the placebo group (P = 0.0018). These represent a relative risk reduction (RRR) for stool clearance of 45.5% and absolute risk reduction (ARR) of 27% (95% Cl, 8-44.7), with a number of patients needed to treat (NNT) of 3.7 (95%, 2.7-11.3). After 15 days, 23.3% of patients in the ofloxacin group had a positive culture compared with 28.9% in the placebo (P = 0.63). This represents an RRR of 19%, an ARR of 5.6% and a NNT of 17.8. Adverse events in the ofloxacin group were observed in only one patient who reported headache and in one patient in the placebo group who developed a rash. In summary, empirical treatment with a single dose of ofloxacin in acute diarrhoea did not reduce the intensity or duration of symptoms (except possibly length of fever). It was notable however that stool cultures became negative for S. enteritidis by 48 h, with no relapse after 2 weeks of follow-up.

Acute Disease↗

The role of intensive remission induction and consolidation therapy in patients with acute myeloid leukaemia.

Sixty-one patients with AML, 59 adults and two children, were treated with intensive remission induction and consolidation therapy. The median age was 36 years. Forty-four (72%) patients entered complete remission (CR); 11 patients received a bone marrow transplantation. The median survival of complete remitters was 26.5 months; the probability of remaining in CR at respectively 1 and 2 years was 75% and 62%. The only factor significantly correlated with the outcome of remission induction, survival and duration of CR was age. Patients less than 30 years fared significantly better than those 30 years or older; no difference in outcome was observed between patients aged 30-50 and those over 50 years. In patients less than 30 years the CR rate was 95%; 75% of them were still alive at 2 years and only one (5%) has relapsed. In contrast, in patients 30 years or older the CR rate was 60% and the median survival only 11.5 months, 50% of the complete remitters in this age group have relapsed. Morbidity from intensive consolidation therapy was considerable; more than 50% of consolidation courses were complicated by high fever, needing urgent admission; only four (3%) courses had a fatal event. It is concluded that intensive consolidation therapy may be considered as a major advance in the treatment of younger patients with AML, while its role in older individuals remains questionable. A possible explanation for the completely different outcome in younger and older patients with AML is discussed.

Adolescent↗