Autoantibodies against desmoglein 2 are not pathogenic in pemphigus

Abstract Background Anti-desmoglein 1 and 3 autoantibodies justify acantholysis in pemphigus; however, the pathogenesis of anti-desmoglein 2 is hypothetical. Objective To compare the participation of desmogleins 1, 2 and 3 through the production of serum autoantibodies, and protein and gene expression in the skin/mucosa of patients with pemphigus foliaceus and pemphigus vulgaris. Methods The autoantibodies were titrated by ELISA in 202 samples of pemphigus foliaceus, 131 pemphigus vulgaris, 50 and 57 relatives of patients with pemphigus foliaceus and pemphigus vulgaris, respectively, and 114 controls. Protein and gene expressions were determined by immunohistochemistry and qPCR in the skin/mucosa of 3 patients with pemphigus foliaceus and 3 patients with pemphigus vulgaris. Results Higher titers of anti-desmoglein 2 (optical density) resulted in pemphigus foliaceus and pemphigus vulgaris, when compared to controls (0.166; 0.180; 0.102; respectively; p < 0.0001). There was a correlation between anti-desmoglein 2 and anti-desmoglein 1 titers in pemphigus foliaceus (r = 0.1680; p = 0.0206). There was no cross-reaction of anti-desmoglein 2 with desmoglein 1 and 3. Protein overexpression of desmoglein 2 was observed in intact and lesional skin of patients with pemphigus compared to the skin of controls. Internalization granules of desmoglein 1 and 3, but not of desmoglein 2, were observed in lesions of pemphigus foliaceus and pemphigus vulgaris, respectively. Gene overexpression of desmoglein 2 was observed in the mucosa. Study limitations Small sample size for the statistical analysis of protein and gene expression. Conclusion Autoantibodies against desmoglein 2 are not pathogenic in pemphigus; protein and gene overexpression of desmoglein 2 in the skin and mucosa may be involved in acantholysis repair.

Leprosy case series in the emergency room: A warning sign for a challenging diagnosis

ABSTRACT Leprosy can be considered a dissimulated disease, mainly when presented as atypical cases leading to mistaken diagnosis at the emergency setting. Herein we report six patients referred to the emergence room with hypotheses of acute myocardial infarction and arterial and venous thrombosis, although with chronic neurological symptoms; the seventh patient was referred with a wrong suspicion of infected skin ulcer. Positive findings included hypo-anesthetic skin lesions and thickened nerves; 100% were negative for IgM anti-phenolic glycolipid-I, while 71.4%, 100% and 42.8% were positive for IgA, IgM and IgG Mce1A. RLEP-PCR was positive in all patients. Ultrasound of peripheral nerves showed asymmetric and focal multiple mononeuropathy for all patients. Unfortunately, in many patients leprosy is often misdiagnosed as other medical conditions for long periods thus delaying initiation of specific treatment. This paper is intended to increase physicians' awareness to recognize leprosy cases presented as both classical and unusual forms, including in emergency department.

Evidence of hidden leprosy in a supposedly low endemic area of Brazil.

OBJECTIVES: Show that hidden endemic leprosy exists in a municipality of inner São Paulo state (Brazil) with active surveillance actions based on clinical and immunological evaluations. METHODS: The study sample was composed by people randomly selected by a dermatologist during medical care in the public emergency department and by active surveillance carried out during two days at a mobile clinic. All subjects received a dermato-neurological examination and blood sampling to determine anti-PGL-I antibody titers by enzyme-linked immunosorbent assay (ELISA). RESULTS: From July to December 2015, 24 new cases of leprosy were diagnosed; all were classified as multibacillary (MB) leprosy, one with severe Lucio's phenomenon. Seventeen (75%) were found with grade-1 or 2 disability at the moment of diagnosis. Anti-PGL-I titer was positive in 31/133 (23.3%) individuals, only 6/24 (25%) were positive in newly diagnosed leprosy cases. CONCLUSIONS: During the last ten years before this study, the average new case detection rate (NCDR) in this town was 2.62/100,000 population. After our work, the NCDR was raised to 42.8/100,000. These results indicate a very high number of hidden leprosy cases in this supposedly low endemic area of Brazil.

Evidence of hidden leprosy in a supposedly low endemic area of Brazil

OBJECTIVES Show that hidden endemic leprosy exists in a municipality of inner São Paulo state (Brazil) with active surveillance actions based on clinical and immunological evaluations. METHODS The study sample was composed by people randomly selected by a dermatologist during medical care in the public emergency department and by active surveillance carried out during two days at a mobile clinic. All subjects received a dermato-neurological examination and blood sampling to determine anti-PGL-I antibody titers by enzyme-linked immunosorbent assay (ELISA). RESULTS From July to December 2015, 24 new cases of leprosy were diagnosed; all were classified as multibacillary (MB) leprosy, one with severe Lucio's phenomenon. Seventeen (75%) were found with grade-1 or 2 disability at the moment of diagnosis. Anti-PGL-I titer was positive in 31/133 (23.3%) individuals, only 6/24 (25%) were positive in newly diagnosed leprosy cases. CONCLUSIONS During the last ten years before this study, the average new case detection rate (NCDR) in this town was 2.62/100,000 population. After our work, the NCDR was raised to 42.8/100,000. These results indicate a very high number of hidden leprosy cases in this supposedly low endemic area of Brazil.

Complementary exams in the diagnosis of American tegumentary leishmaniasis.

The diagnosis of American Tegumentary Leishmaniasis is a difficult but essential task when considering the high toxicity profile of the drugs available. Since the discovery of its etiologic agent, numerous diagnostic tests have been developed. None of the tests available today can be considered as the gold standard, since they do not add enough accuracy for the disease detection. Good epidemiological and clinical knowledge of the disease are fundamental precepts of the dermatology practice and precede the rational use of existing diagnostic tests. In this article we aim, through extensive literature review, to recall fundamental concepts of any diagnostic test. Subsequently, based on this information, we will weave important comments about the characteristics of existing diagnostic tests, including immunological tests such as Montenegro's skin test, serology and detection of parasites by direct examination, culture or histopathology. Finally we will discuss the new technologies and options for the diagnosis of Cutaneous Leishmaniasis. The molecular biology technique is considered a promising tool, promoting the rapid identification of the species involved. We also aim to educate dermatologists about a disease with high morbidity and assist in its difficult recognition.

Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice / Os efeitos tóxicos de diferentes doses de ciclofosfamida nos parâmetros reprodutivos de camundongos machos

The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg-1, intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg-1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post- implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg-1. It was observed a reduction in epididymis and liver's weight of the animals treated with the doses 150, 200 e 250 mg.kg-1. Abnormal spermatozoa were found in the doses 200 e 250 mg.kg-1. Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.

A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg-1, via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg-1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que recebeu a dose de 150 mg kg-1. Observou-se redução nos pesos dos epidídimos e fígado dos animais tratados com as doses de 150, 200 e 250 mg kg-1. Espermatozóides anômalos foram encontrados nas doses de 200 e 250mg kg-1. Com base na metodologia empregada e nos resultados obtidos, conclui-se que a ciclofosfamida foi tóxica considerando-se a redução de massa corporal e o peso dos testículos dos animais; promoveu hepatotoxicidade e efeito nefrotóxico; influenciou na espermatogênese dos animais de forma a levá-los a um estado de infertilidade e/ou subfertilidade; diminuiu viabilidade fetal, entretanto não causou malformações significativas na prole.