The influence of treatment on the development of leishmaniasis recidiva cutis: a 17-year case-control study in Midwestern Brazil.

BACKGROUND: The recurrence of American cutaneous leishmaniasis (ACL) in patients experiencing a long-term cure is often called leishmaniasis recidiva cutis (LRC). LRC is considered an unusual form of ACL. OBJECTIVE: This study aims to estimate the incidence of LRC in ACL patients evaluated at a tertiary dermatologic centre in Midwestern Brazil. We also aim to evaluate the association between various treatment regimens and the development of LRC using multivariate analysis in a case-control study. METHODS: We performed a 17-year epidemiological study using data from patients treated at our dermatologic centre from July 1994 to December 2011. A retrospective analysis was then performed to estimate risk and protective factors related to clinical presentation. We also assessed the influence of treatment regimens in the development of LRC. RESULTS: The incidence of LRC among ACL patients was 1.34%. The analysis included 105 patients; 82 patients (78%) were in the control group, and 23 patients (22%) were in the LRC case group. The data analysis indicated that the standard treatment N-methylglucamine antimoniate (N-MA) reduced the development of LRC in bivariate (odds ratio (OR) = 0.34; 95% CI = 0.13-0.91) and multivariate analyses (OR = 0.16; 95% CI = 0.03-0.86; P = 0.03). However, no differences in LRC incidence were observed when the standard treatment N-MA and alternative drugs, such as pentamidine and amphotericin B, were considered (OR = 0.47; 95% CI = 0.16-1.35) CONCLUSION: We conclude that the standard treatment N-MA, as proposed by the Brazilian Ministry of Health, is effective in the prevention of LRC. Although other drugs have shown promising results in LRC, more scientific evidence is needed to assess their efficacy compared with N-MA.

Dermal dendritic cell number correlates with serum autoantibody titers in Brazilian pemphigus foliaceus patients.

Pemphigus foliaceus (PF) is an autoimmune bullous disease endemic in Brazil. Since serum IL-12 is increased in patients with PF and Langerhans cells (LC) produce IL-12, we titrated serum autoantibodies by indirect immunofluorescence, and quantified epidermal dendritic cells, known as LC, and dermal dendritic cells (DC). Biopsies of blistering lesions were obtained from 22 patients, 13 of whom were submitted to biopsy of both injured and of apparently healthy skin. The control groups consisted of skin from 8 cadavers and from 12 women submitted to breast plastic surgery. LC and DC were identified with anti-CD1a antibody and quantified by morphometric analysis. LC number in the lesion and in apparently healthy skin from PF patients was similar to that of both control groups. DC number in the injured skin (median=0.94 DC/mm basement membrane) was higher than that of the cadaver group (median=0.13 DC/mm basement membrane). In the 13 patients with biopsies of both injured and apparently healthy skin, LC and DC were present in larger numbers in the lesion. There was a direct correlation between DC number in the lesion of the PF group and serum autoantibody titers. This correlation was not observed for LC number. The increased number of DC in the lesion, as well as its direct correlation with serum autoantibody titers suggest the participation of DC in the pathogenesis of PF. The relationship between increased DC number and IL-12 in PF needs to be clarified.

Comparison of the specificity of PCR and the histopathological detection of leishmania for the diagnosis of American cutaneous leishmaniasis.

More precise and rapid diagnostic methods for American cutaneous leishmaniasis (ACL) are necessary because of the growing number of cases observed in Brazil, including the northeastern region of the State of São Paulo. We applied PCR to 54 skin or mucosal biopsies from patients with a clinical and/or laboratory diagnosis of ACL using primers 13A and 13B, with positive results being obtained for 82% of the samples. When the PCR results were compared to those of histopathological leishmania detection, PCR showed superior results with 81.5% sensitivity and 95% CI of 68.0-95.1%. The Montenegro skin test (MST) was positive in 88.7% of patients. Since MST cannot be used as a diagnostic tool in endemic areas, the present results strongly suggest the use of PCR for the etiological confirmation of ACL, with emphasis on the mucosal form.

Serum cytokines in patients with Brazilian pemphigus foliaceus (fogo selvagem).

Pemphigus foliaceus (PF) is characterized by acantholysis determined by IgG4 binding to desmoglein I, a 160-kDa desmosomal glycoprotein. To investigate the immunopathological aspects of Brazilian PF, we determined levels of serum cytokines in patients with PF. Twenty-five patients with PF and a control group consisting of 10 healthy individuals were studied. Serum IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-gamma were measured in the two groups by ELISA. The median concentration of IL-2 was lower in PF patients compared to the control group (0.45 and 9.50 pg/ml, respectively), as also was the concentration of IL-4 (0.26 and 10.16 pg/ml, respectively). The same was observed for IL-5 (7.94 and 15.74 pg/ml, respectively) and for IFN-gamma (5.90 and 8.58 pg/ml, respectively). For IL-10 and IL-12, higher concentrations were observed in PF compared to the control group (IL-10: 24.76 and 20.92; IL-12: 2.92 and 1.17 pg/ml, respectively). Considering the Th1/Th2 paradigm, it seems that a Th2 profile, mainly represented by IL-10, predominates in PF.

Endemic Pemphigus foliaceus ("Fogo selvagem"): a series from the Northeastern region of the State of São Paulo, Brazil, 1973-1998.

UNLABELLED: Endemic Pemphigus Foliaceus (EPF) is a bullous autoimmune skin disease whose incidence used to be high in the State of São Paulo (SP), Brazil, during the forties, but has declined thereafter. OBJECTIVES: to report a series of EPF patients from the northeastern region of SP. METHODS: a retrospective study concerning demographic and epidemiological data of patients seen from 1973 to 1998 was conducted at the University Hospital, Faculty of Medicine of Ribeirão Preto, SP. RESULTS: bullous disease was diagnosed in 340 patients, 245 with EPF (72.1%), 9.4 cases per year, 60.4% females, and 70.2% white, 7 to 82 year-old (29.4% in their teens); 46.9% lived in the rural zone. Concerning profession, housewives predominated among women (67.6%) and agricultural workers among men (40.2%). The time of disease was less than 1 year in 62.0% of cases, followed by 1 and 5 years (27%), and more than 5 years for the remaining patients (11%). 36.7% of patients were referred by the Direção Regional de Saúde (DIR) XVIII of Ribeirão Preto, with the largest number of cases being from Ribeirão Preto and Batatais: 33.3% and 23.3%, respectively; 22% from DIR XIII (Franca); 13.5% from DIR VII (Araraquara); 2.9% from DIR IX (Barretos); 4.1% from other DIRs of SP, and 20.8% from other States (16.7% from Minas Gerais). Thirteen (5.3%) patients reported occurrence of the disease in some relative, and 4 (1.6%) in neighbors. CONCLUSIONS: the present data characterize the northeastern region of the state of São Paulo as a remaining endemic focus of EPF.

Nephrotoxicity attributed to meglumine antimoniate (Glucantime) in the treatment of generalized cutaneous leishmaniasis.

BACKGROUND: Pentavalent antimonials have became of basic importance for the treatment of leishmaniasis. Their most severe side effects have been reported to be increased hepatic enzyme levels and electrocardiographic abnormalities. Nephrotoxicity has been rarely related. OBSERVATIONS: We report a case of generalized cutaneous leishmaniasis involving a 50-year old male patient who was submitted to treatment with meglumine antimoniate (Glucantime). He developed acute renal failure (ARF) due to acute tubular necrosis (ATN), followed by death after receiving a total of 53 ampoules of Glucantime. CONCLUSIONS: The treatment with Glucantime was responsible by ARF diagnosed in this patient. The previous urine osmolarity and serum creatinine levels were normal and the autopsy showed ATN. It should be pointed out if ARF may also be explained by massive deposits of immunocomplexes by leishmania antibodies and antigens due to the antigenic break by the antimonial compound, since our patient presented countless lesions covering the entire tegument, similar to the Hexheimer phenomenon, but at the autopsy no glomerular alterations were seen.

Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.

In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.

Anti-nucleosome and anti-chromatin antibodies are present in active systemic lupus erythematosus but not in the cutaneous form of the disease.

The objective of this study is to investigate the presence of anti-nucleosome (anti-NCS) and anti-chromatin (anti-CRT) antibodies in patients with cutaneous lupus erythematosus (CLE) compared with active and inactive systemic lupus erythematosus (SLE). A total of 154 subjects were evaluated: 54 patients presenting CLE, 66 patients with active SLE and 34 with inactive SLE. Lupus activity was assessed using the disease activity index (SLEDAI). Anti-NCS and anti-CRT antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Only one of 54 patients with CLE tested positive for both anti-NCS and anti-CRT antibodies. The prevalence of anti-CRT antibodies was significantly higher in active SLE (84.8%) when compared with inactive SLE (26.4%) and CLE (1.8%) (P < 0.001). Anti-NCS antibodies were also more prevalent in active SLE patients (74.2%) than inactive SLE (11.7%) and CLE patients (1.8%) (P < 0.001). The presence of anti-CRT and anti-NCS antibodies was correlated to disease activity in patients with SLE (r = 0.4937, r = 0.5621, respectively). Furthermore, the detection of both antibodies was correlated with disease activity in patients with SLE who tested negative for anti-dsDNA antibodies (r = 0.4754 for anti-NCS and r = 0.4281 for anti-CRT). The presence of these two auto-antibodies was strongly associated with renal damage in patients with SLE (OR = 13.1, for anti-CRT antibodies and OR = 25.83, for anti-NCS antibodies). The anti-NCS and anti-CRT antibodies were not found in CLE. In patients with SLE, there is a correlation of these antibodies with disease activity and active nephritis. When compared with anti-dsDNA antibodies, anti-NCS and anti-CRT antibodies were more sensitive in detecting disease activity and kidney damage in lupus patients.

Leishmania (Viannia) braziliensis is the main species causing cutaneous leishmaniasis in the Federal District of Brazil

The first autochthonous case of American cutaneous leishmaniasis was reported in the Federal District in 1980, and the species involved in this type of leishmaniasis was unknown. This study aimed to identify the species that causes the disease in the Federal District and to investigate its clinical and epidemiological aspects. Between 2000 and 2007, 71 autochthonous cases of leishmaniasis were reported in the Federal District. Leishmania species were identified by means of direct immunofluorescence reactions using monoclonal antibodies and restriction fragment length polymorphism. The species of 40 (56.33%) out of 71 samples were identified. Thirty-six (90%) were identified as Leishmania (Viannia) braziliensis and four (10%) were identified as Leishmania (Leishmania) amazonensis. In this area, the disease had clinical and epidemiological characteristics similar to those found in other Brazilian regions.

Oral leishmaniasis: a clinicopathological study of 11 cases.

Leishmaniasis is a parasitic disease with diverse clinical manifestations, and considered a public health problem in endemic countries such as Brazil. Mucosal lesions usually involve the upper respiratory tract, with a predilection for nose and larynx. Oral involvement is unusual and in most cases it becomes evident after several years of resolution of the original cutaneous lesions. Oral lesions classically appear as mucosal ulcerations, mainly in the hard or soft palate. This report describes the clinicopathological data of 11 cases of mucocutaneous leishmaniasis with oral manifestations. Two cases of Leishmania (Viannia) braziliensis and one case of Leishmania (Leishmania) amazonensis were confirmed by polymerase chain reaction-restriction fragment length polymorphism or DNA sequencing in mucosal samples.

Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem).

BACKGROUND: Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated. OBJECTIVES: As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities. METHODS: Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates. RESULTS: Compared with controls, plasma HK levels were decreased (P = 0.031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0.001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls. CONCLUSIONS: Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification.

Dermatoses among Brazilian HIV-positive patients: correlation with the evolutionary phases of AIDS.

BACKGROUND: The presence of dermatoses is very common in Acquired Human Immunodeficiency Syndrome (AIDS). The present study was undertaken to correlate the various dermatoses with the evolutionary phases of AIDS. METHODS: We examined 223 HIV-infected patients older than 13 seen at the University of São Paulo, Faculty of Medicine of Ribeirão Preto, from 1989 to 1993. Patients were divided according to the CDC classification and assigned to groups I, II and III (initial stages of AIDS) and to group IV (fully symptomatic stage of AIDS). RESULTS: The mean frequency of dermatoses detected in patients with AIDS was higher compared to the early phases of HIV infection. The most frequently detected dermatoses were, in decreasing order of occurrence, dermatoses of fungal etiology, and desquamating disorders, such as psoriasis, seborrheic dermatitis, xerosis, and viral dermatoses. CONCLUSIONS: A careful examination of skin and mucosae may be highly useful for the diagnosis of HIV infection. The number of dermatoses tended to increase during the more advanced stages of infection.

PIP: The frequency of dermatologic disorders--a common symptom in HIV-infected men and women--was investigated in 223 HIV-positive patients at various stages of disease recruited from the University of Sao Paulo, Faculty of Medicine, in Ribeirao Preto, Brazil, in 1989-93. Of these 223 patients, 152 had full-blown AIDS and the remaining 71 were asymptomatic. A total of 488 dermatoses were diagnosed. The mean number of diagnoses was 2.45 in AIDS patients and 1.61 in the asymptomatic groups. Seborrheic dermatitis, more extensive and of more abrupt onset than that observed in the general population, was the most frequent disorder, affecting 24% of patients in the initial stages of HIV and 30.3% of those with AIDS. The prevalence of viral dermatoses--primarily herpes simplex--was equivalent in both AIDS and asymptomatic patients (14.5% and 14.8%, respectively). Disorders of bacterial etiology--primarily impetigo, ecthyma, and sexually transmitted diseases--were more common in asymptomatic (16.5%) than AIDS patients (3.8%), while fungal dermatoses--predominantly oral moniliasis and tineas--were more frequent in AIDS patients (32.4%) than asymptomatic patients (22.6%). These findings suggest that careful examination of skin and mucosa may be useful for the diagnosis of HIV infection.

Cytokines in the pruritic papular eruption of HIV.

BACKGROUND: The immunopathogenic mechanism of the pruritic papular eruption (PPE) of patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is poorly understood, and the objective of the present study was to determine the concentration of the serum cytokines interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12, and gamma-interferon (gamma-IFN) in an attempt to recognize the pattern of CD4+/CD8+ lymphocytes occurring in this dermatosis. MATERIALS AND METHODS: The study was conducted on 11 HIV-positive PPE patients, matched for sex and age with eight HIV-infected patients with no dermatosis and 10 healthy HIV-negative individuals. Cytokines were quantified by enzyme-linked immunoabsorbent assay (ELISA) using monoclonal antibodies (R & D Systems) and the data were analyzed by the Mann-Whitney, Kruskall-Wallis, and Spearman correlation tests. RESULTS: An increased concentration of IL-2 was observed in both the HIV-positive (77.65 pg/mL, P < 0.001) and PPE (20.42 pg/mL, P < 0.05) groups when compared with the HIV-negative group (9.50 pg/mL). The IL-2 concentration was significantly higher (P < 0.05) in the HIV-positive group than in the PPE group. Similarly, the gamma-IFN concentration was higher in the HIV-positive (14.97 pg/mL) and PPE (12.67 pg/mL) groups when compared with the HIV-negative group (8.58 pg/mL). The IL-12 concentration was similar in the PPE and HIV-positive groups (1.82 and 1.68 pg/mL, respectively), but higher than in the HIV-negative group (1.17 pg/mL). The same occurred with IL-5 (17.78, 17.79, and 15.74 pg/mL, respectively). There was no significant difference in IL-4 concentration among the PPE, HIV-positive, and HIV-negative groups (10.95, 7.88, and 10.16 pg/mL, respectively), and the same was observed for IL-10 (22.41, 21.13, and 20.92, respectively). There was a negative correlation between serum gamma-IFN concentration and peripheral CD4+ lymphocyte number (r = - 0.6256) in the PPE group (P < 0.05). CONCLUSIONS: The lower levels of IL-2 and gamma-IFN and the negative correlation between gamma-IFN and peripheral CD4+ lymphocytes may indicate an early phase of immunosuppression in PPE.

Lucio's phenomenon: clinical and therapeutic aspects.

We report four cases of necrotizing reactions of the Lucio's phenomenon type, an entity rarely observed in Brazil despite the high prevalence of leprosy. Clinical, histopathological and therapeutic aspects are described and compared to those reported in the literature for cases classified as diffuse, non-nodular lepromatous leprosy with Lucio's phenomenon.

Kininogens and kallikrein in pruritic papular eruption.

Pruritic papular eruption (PPE) is a common inflammatory cutaneous lesion observed only in HIV/AIDS patients. Since kinin is an important mediator in inflammation, we evaluated the levels of total kininogen (TKg), low and high molecular weight kininogen (LKg and HKg, respectively) and the activity of kallikrein in plasma of 11 patients (median age = 31.4) with AIDS and PPE (PPE+), eight patients (median age = 31.5) with AIDS without PPE (PPE-) and in 12 control individuals (median age = 32.9) with anti-HIV negative serum. Kininogens were measured by ELISA and expressed in median (m) of BK Equivalent/ml plasma and the kallikrein by its activity upon selective chromogenic substrate, and expressed as U kallikrein/ml of plasma. TKg or LKg concentrations in PPE+ patients (m = 4.11 and 4.5) and in PPE- patients (m = 6.23 and 4.54) were significantly higher when compared to control (m = 2.10 and 1.17). Compared to controls PPE- patients presented similar values of HKg (m = 0.78 and 0.61), whereas PPE+ patients presented undetectable values. Plasma kallikrein activity was significantly decreased in PPE+ and PPE- (m = 0.6 and 0.89, respectively) when compared with control individuals (m = 2.23).