Background The mainstay of therapy of autoimmune mucocutaneous blistering diseases has been prolonged high-dose systemic corticosteroids and immunosuppressive agents. Recently, high-dose intravenous ...immunoglobulin (IVIg) has been employed in selected cases, with excellent results in most of them. Objective We sought to evaluate the outcome of the use of IVIg in patients with autoimmune mucocutaneous blistering diseases refractory to conventional therapy or with contraindications for it. Methods We performed a retrospective analysis of clinical response to monthly cycles of IVIg in 19 patients affected with autoimmune mucocutaneous blistering diseases: 10 patients with pemphigus vulgaris (PV), 2 with pemphigus foliaceus (PF), 4 with mucous membrane pemphigoid (MMP), 2 with epidermolysis bullosa acquisita, and one with linear IgA bullous dermatosis. Results Four (21%) of 19 cases presented a complete response (2 PV, 1 MMP and 1 epidermolysis bullosa acquisita). Five (26%) patients did not respond to the treatment (3 PV, 1 PF, 1 MMP). Ten patients (53%) had a partial response. Limitations This was a retrospective noncontrolled study with a heterogeneous group of patients. Conclusion The effectiveness of IVIg was inferior to that previously reported. This difference could be attributed to the preparations employed, the different severity of the disease, or individual responses in each patient dependent on Fc receptor gamma polymorphisms.
To update antiretroviral recommendations in antiretroviral therapy (ART) in HIV-infected children and adolescents.
Theses guidelines have been formulated by a panel of members of the Plan Nacional ...sobre el SIDA (PNS) and the Asociacion Espanola de Pediatria (AEP) by reviewing the current available evidence of efficacy, safety, and pharmacokinetics in pediatric studies. Three levels of evidence have been defined according to the source of data: Level A: randomized and controlled studies; Level B: Cohort and case-control studies; Level C: Descriptive studies and experts' opinion.
When to start ART should be made on an individual basis, discussed with the family, considering the risk of progression according to age, CD4 and viral load, the ART-related complications and adherence. The ART goal is to reach a maximum and durable viral suppression. This is not always possible, even with clinical and immunologic improvement. The difficulties of permanent adherence and side-effects are resulting in a more conservative trend to initiate ART, and to less toxic and simpler strategies. Currently, combinations of at least three drugs are of first choice both in acute and chronic infection. They must include 2 NA 1 1 NN or 2 NA 1 1 PI. ART is recommended in all symptomatic patients and, with few exceptions, in all infants in the first year of life. Older asymptomatic children should start ART according to CD4 count, especially CD4 percentage, that vary with age. Despite potent salvage therapies, it is common not to reach viral undetectability. Therapeutical options when ART fails are scarce due to cross-resistance. The cause of failure must be identified. Occasionally, there exists clinical and/or immunological progression, and a change of therapy with at least two new drugs still active for the patient, is warranted with the aim of increasing the CD4 count to a lower level of risk. Toxicity and adherence must be regularly monitored. Some aspects about post exposure prophylaxis and coinfection with HCV or HBV are discussed.
A higher level of evidence with regard to ART effectiveness and toxicity in pediatrics is currently available, leading to a more conservative and individualized approach. Clinical symptoms and CD4 count are the main determinants to start and change ART.
Laboratory of Molecular Biology, Department of Clinical Pathology, Hospital Universitario La Fe, Valencia, Spain. bolufer_pas@gva.es
BACKGROUND AND OBJECTIVES: The detection of PML-RAR by reverse ...transcription (RT) polymerase chain reaction (PCR) in acute promyelocytic leukemia (APL) patients who are in hematologic remission influences therapeutic decision making in several trials. In the light of this, the Spanish group has recently designed an external quality assessment program (EQAP) of RT-PCR detection of PML-RAR, which includes a study of sensitivity of the participating laboratories. DESIGN AND METHODS: Eighteen laboratories were involved in the program. Ten laboratories followed the method of Biondi et al., 5 employed that of Borrow et al. and the 3 remaining used other protocols. The sensitivity was studied in five rounds of quality control. The first two shipments consisted of dilutions of NB4 RNA into non-APL RNA. The third round consisted of serial dilutions of the NB4 cell line into HL60 cells. The fourth and five rounds consisted of plasmid dilutions containing the bcr1 and bcr3 PML-RAR isoforms. RESULTS: The results showed that the distinct methods allow detection of the PML-RAR hybrid up to a dilution of 10(-4), and exceptionally, up to 10(-5). The laboratories following the method of Biondi et al. usually detected the 10(-3) dilution and less frequently the 10(-4) one, whereas those using other methods usually detected PML-RAR transcript in the 10(-4) dilution, and less commonly in the 10(-5) dilution. However, each of the PCR methods used by EQAP participating laboratories successfully detected at least 50 copies of PML-RAR alpha fusion transcript in plasmid dilution controls. INTERPRETATION AND CONCLUSIONS: The results point to heterogeneous sensitivity amongst participating laboratories. This may reflect differences in methodology, although variations in sample quality may also account for discrepant findings.
