Carlos Gustavo Wambier

Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Introduction The use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity. Methods To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with reduction of the number and the intensity of leprosy reactions. Conclusion These results suggest that BCG-id induces activation of the initial phase of immunocellular activity: innate human immunity (increase in TNF-α, IL-12 and macrophage activation). Therefore, we conclude that the use of BCG-id could be indicated as an adjuvant to multidrug therapy in treatment of leprosy patients.

Gamasoidosis illustrated - from the nest to dermoscopy*

Gamasoidosis (acariasis, avian-mite dermatitis or bird-mite dermatitis) is a challenging diagnosis that is becoming more common because of the frequent use of window air conditioners in tropical countries. These devices may serve as shelters for nests of urban birds such as pigeons. Dermatologists should become familiar with this infestation to establish the correct diagnosis and treatment.

Generalized Serpiginous Eruption during Immunosuppressive Treatment for Leprosy Reactive Neuritis

The authors have declared that no competing interests exist. The authors received no funding for this work.

NFκB activation in cutaneous lesions of leprosy is associated with development of multibacillary infection

Background Nuclear factor kappa B (NFκB) transcription factors play a central role in controlling the expression of genes involved in inflammatory reactions, proliferation, and survival of human cells. However, the in situ evaluation of NFκB activity in leprosy has not been completed previously. The aim of this study was to determine whether NFκB activity correlates with susceptibility or resistance to Mycobacterium leprae infection in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy. Methods The NFκB activation profile was evaluated in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy. NFκB activation was evaluated and quantified by Southwestern histochemistry, and its activation index (range, 0–4) was calculated according to the percentage of nuclear positivity by the histochemistry. Activation index >1 was considered representative of activation of NFκB. Results Fifteen patients (39.5%) demonstrated activated NFκB. Multibacillary leprosy was associated with activated NFκB (54.5%, P=0.028). Borderline leprosy was most strongly associated with NFκB activation (80%), with an odds ratio of 32.7 (P=0.016). These clinical forms are characterized by increased susceptibility to M. leprae and by immunological instability. Activation of NFκB was absent in the granulomas in tuberculoid leprosy, which represents an effective inflammatory reaction pattern against M. leprae. Conclusion These results indicate that NFκB activation could favor susceptibility and immunological instability to M. leprae infection, potentially by the stimulation of phagocytosis and the regulation of apoptotic mechanisms of infected cells, leading to the proliferation of this intracellular bacillus. Further studies are needed to evaluate if inhibition of NFκB activation in multibacillary leprosy could favor resistance and an effective granulomatous immune response.

Syringe lubricant and adverse reactions

c.37G>C mutation was detected in all three secondary tumors associated with nevus sebaceus. Additional novel pathogenic somatic mutations were seen in syringocystadenoma papilliferum (PIK3CA c.1633G>A) and sebaceoma (TP53 c.916C>T); to our knowledge, PIK3CA and TP53 mutations have not been previously identified in syringocystadenoma papilliferum and sebaceomas, respectively. The remaining somatic mutations in sebaceoma and basal cell carcinoma were associated with benign clinical significance likely representing single nucleotide polymorphisms. Taken together, our findings further support the RAS-dependent genetic pathway and second-hit model for secondary tumor development in nevus sebaceus/epidermal nevus. However, additional larger studies with various secondary tumors are necessary to confirm this statement.

QTc prolongation during phenol-croton oil peels

Graphical abstract: Figure. No caption available.

Treatment of reaction to red tattoo ink with intralesional triamcinolone

An Bras Dermatol. 2017;92(5):740-50. How to cite this article: Santos FSD, Mantovam CCA, Duarte RD, Oliveira AML, Bernardes Filho F. Rickettsial diseases in Brazil: report of a case with varicella-like skin lesions. An Bras Dermatol. 2017;92(5):746-8. Mailing address: Fred Bernardes Filho Rua Arnaldo Victaliano, 971, ap. 152 Jardim Palma Travassos 14091-220 Ribeirão Preto, SP – Brazil E-mail:f9filho@gmail.com

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

INTRODUCTION Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. METHODS We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. RESULTS The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. CONCLUSIONS Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.

The common coffee stirrer as a perfect application tool for imiquimod

The proper application of topical medications is a key factor in their effectiveness. The common coffee stirrer with rounded edges: an ideal application tool for imiquimod.

Brazilian blood donation eligibility criteria for dermatologic patients

UNLABELLED A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. DISCUSSION Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.Abstract: A focused and commented review on the impact of dermatologic diseases and interventions in thesolidary act of donating blood is presented to dermatologists to better advise their patients. This is a review ofcurrent Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive#1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of RibeiraoPreto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoim-mune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopicdermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis orparacoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other syste-mic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers,minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occu-pational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterialinfections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Althoughfinasteride was previously considered a drug that imposed permanent inaptitude, according to its short half-life current restriction of 1 month is still too long. Dermatologists should be able to advise their patients aboutproper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to res-pect the designated washout periods.Keywords: Blood banks; Blood transfusion; Teratogenic dangers