Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis caused by Leishmania braziliensis

2021 ◽  
Author(s):  
Tainã Lago ◽  
Lucas Carvalho ◽  
Mauricio Nascimento ◽  
Luiz H Guimarães ◽  
Jamile Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Clinical Presentation ◽  
Clinical Manifestations ◽  
Healing Time ◽  
Response To Therapy ◽  
Leishmania Braziliensis ◽  
Cutaneous Lesions ◽  
Cytokine Levels ◽  
Cure Rates ◽  
The Impact

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates below 60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. Methods A total of 90 age-matched CL patients were included (30 obese, 30 overweight and 30 with normal BMI). CL was diagnosed through documentation of L. braziliensis DNA by PCR or identification of amastigotes in biopsied skin lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (20mg/kg/day) was administered for 20 days. Results Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After one course of Antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (p<0.01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (p<0.05). Conclusions Obesity modifies the clinical presentation of CL and host immune response, and is associated with greater failure to therapy.

scholarly journals Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis

2020 ◽  
Author(s):  
Augusto M Carvalho ◽  
Luiz H Guimarães ◽  
Rúbia Costa ◽  
Maíra G Saldanha ◽  
Iana Prates ◽  
...  
Keyword(s):  
T Cells ◽  
Cutaneous Leishmaniasis ◽  
Cd8 T Cells ◽  
Clinical Presentation ◽  
Granzyme B ◽  
Therapeutic Failure ◽  
Response To Therapy ◽  
Delayed Type Hypersensitivity ◽  
Leishmania Braziliensis ◽  
Th1 Response

Abstract Background Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients. Methods We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST. Results The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8+ T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1β (IL-1β), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response. Conclusions In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology.

scholarly journals A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil

2020 ◽  
Author(s):  
Paulo R L Machado ◽  
Fernanda V O Prates ◽  
Viviane Boaventura ◽  
Tainã Lago ◽  
Luiz H Guimarães ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Combined Treatment ◽  
Healing Time ◽  
Leishmania Braziliensis ◽  
Colony Stimulating Factor ◽  
Double Blind ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Background The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high rate of failure. Miltefosine has proven efficacy for CL caused by L. braziliensis, with a cure rate (CR) of 75%. A combined treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) and miltefosine could increase CR and decrease healing time. Methods A randomized, double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M + GM) vs miltefosine and placebo (M + P) vs Sbv in 133 patients with CL caused by L. braziliensis in Bahia, Brazil. Results The final CR at 180 days after the initiation of treatment was 44.4% in the Sbv group, 76.6% in the M + P group (P = .003 vs Sbv), and 75.6% in the M + GM group (P = .004 vs Sbv). The median healing time for cure was 102 days for the Sbv group and 60 days for both miltefosine groups (P = .0009). During the 6-month follow-up period, 4 relapses were documented: 1 in the Sbv group, 1 in the M + P group, and 2 in the M + GM group. Mild adverse events occurred in 65% of patients from the Sbv group, 76% and 79% from the M + P and M + GM groups respectively. Conclusions Miltefosine is more effective than Sbv for the treatment of CL caused by L. braziliensis in Brazil and accelerates the healing time. Association with GM-CSF does not improve therapeutic outcome. Clinical Trials Registration NCT03023111.

Autoimmune Disease (AD) in Patients with Myelodysplastic Syndrome (MDS): A Retrospective Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4736-4736
Author(s):  
Jeyanthi Ramanarayanan ◽  
Alan N. Baer ◽  
Minoo Battiwalla ◽  
Laurie A. Ford ◽  
Meir Wetzler ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Systemic Vasculitis ◽  
Multiorgan Failure ◽  
Clinical Manifestations ◽  
Response To Therapy ◽  
Entire Cohort ◽  
Double Stranded Dna ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Autoimmune disease (AD) can manifest uncommonly either at the time of diagnosis of MDS or during its course. When present, AD generally responds to immunosuppressive therapies, but cytopenias and immunosuppression associated with MDS compromise delivery of these therapies. Few studies have investigated the impact of co-existing AD on the course and outcome of patients with MDS. Our objective was to evaluate the clinical manifestations, laboratory characteristics, response to therapy and survival of MDS patients with AD. Records of patients evaluated at Roswell Park Cancer Institute with pathologically demonstrated MDS between 1993 and 2003 (n=277) were reviewed and patients with evidence of AD were identified. Patients with laboratory abnormalities without disease manifestations were excluded, as were patients with therapy-related MDS following treatment for AD. 13 patients (4%) were identified with co-existing MDS and AD. The initial presentation was AD in 6 (46%) and MDS in 4 (31%), while 3 patients (23%) had near-simultaneous diagnoses of both conditions. The spectrum of AD in these patients included systemic vasculitis in 3 patients, systemic lupus erythematosus in two and rheumatoid arthritis, temporal arteritis, cryoglobulinemia, aphthous stomatitis, pyoderma gangrenosum, inflammatory bowel disease, erythema nodosum and Evans syndrome in one patient each. Anti-double stranded DNA (levels ≥ 40.0 u/ml; normal range 0.0–3.5u/ml), ANA (≥1:160), cold agglutinins, low C3 and elevated ESR (≥100mm/hr) were the serological abnormalities detected at the time of AD diagnosis. Eleven of 13 patients were female, and median age at diagnosis of MDS was 65 years, while the entire cohort was 44% female (p=0.005) and had a median age of 71 yrs at diagnosis. FAB subtypes were RA (n=7), RAEB (n=3), CMMoL (n=2) and RARS (n=1). Cytogenetics were normal in 5 patients; abnormalities in the other 8 patients included −7, +8, and del(5q). The median survival of patients from diagnosis of MDS was 48 months and the survival from diagnosis of AD was 46 months. Known causes of death in 6 patients included sepsis, intracranial hemorrhage, lung cancer and transplant-associated multiorgan failure. Based on this study, AD occurs in 4% of MDS patients, predominantly affects female patients, and has heterogeneous clinical manifestations.The pathobiologic implication of the occurrence of AD at the same time or after the diagnosis of MDS is that the dysplastic clone might be responsible for the induction of immune dysregulation.

scholarly journals Clinical Presentation and Response to Therapy in Children with Cutaneous Leishmaniasis

2020 ◽  
Vol 102 (4) ◽  
pp. 777-781 ◽  
Author(s):  
Carvel Suprien ◽  
Paulo N. Rocha ◽  
Marina Teixeira ◽  
Lucas P. Carvalho ◽  
Luiz H. Guimarães ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Clinical Presentation ◽  
Response To Therapy

scholarly journals Psycho-social impacts, experiences and perspectives of patients with Cutaneous Leishmaniasis regarding treatment options and case management: An exploratory qualitative study in Tunisia

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242494
Author(s):  
Aicha Boukthir ◽  
Jihene Bettaieb ◽  
Astrid C. Erber ◽  
Hind Bouguerra ◽  
Rym Mallekh ◽  
...  
Keyword(s):  
Case Management ◽  
Cutaneous Leishmaniasis ◽  
Burden Of Disease ◽  
Treatment Options ◽  
Healing Time ◽  
The Body ◽  
Self Healing ◽  
Access To Treatment ◽  
Psychological Burden ◽  
The Impact

Although non-fatal and mostly self-healing in the case of Leishmania (L.) major, cutaneous leishmaniasis (CL) is mainly treated to reduce lesion healing time. Less attention is paid to the improvement of scars, especially in aesthetically relevant areas of the body, which can dramatically affect patients’ wellbeing. We explored patients’ perspectives about treatment options and the social and psychological burden of disease (lesion and scar). Individual in-depth interviews were conducted with ten confirmed CL patients at two L. major endemic sites in Southern Tunisia (Sidi Bouzid and Gafsa). Participants were selected using a sampling approach along a spectrum covering e.g. age, sex, and clinical presentation. Patients’ experiences, opinions and preferences were explored, and their detailed accounts gave an insight on the impact of CL on their everyday lives. The impact of CL was found to be considerable. Most patients were not satisfied with treatment performance and case management. They expected a shorter healing time and better accessibility of the health system. Tolerance of the burden of disease was variable and ranged from acceptance of hidden scars to suicidal thoughts resulting from the fear to become handicapped, and the stress caused by close relatives. Some believed CL to be a form of skin cancer. Unexpectedly, this finding shows the big gap between the perspectives of patients and assumptions of health professionals regarding this disease. This study provided valuable information for better case management emphasizing the importance of improving communication with patients, and accessibility to treatment. It generated context-specific knowledge to policy makers in Tunisia to implement effective case management in a country where access to treatment remains a challenge due to socio-economic and geographic barriers despite a long tradition in CL control.

scholarly journals The Impact of Oral-Gut Inflammation in Cerebral Palsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Cristina Fernandes Maria Ferreira ◽  
Ryan J. Eveloff ◽  
Marcelo Freire ◽  
Maria Teresa Botti Rodrigues Santos
Keyword(s):  
Cerebral Palsy ◽  
Statistical Significance ◽  
Severe Form ◽  
Response To Therapy ◽  
Gamma Aminobutyric Acid ◽  
Gut Inflammation ◽  
Medication Intake ◽  
Cytokine Levels ◽  
Highly Correlated ◽  
The Impact

Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL). We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy.Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis.Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1β levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292).Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.

Influence of Intestinal Helminth Burden on Clinical Manifestations, Therapeutic Response, and Leishmania braziliensis Load in Patients with New World Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Brady Page ◽  
Alex Lago ◽  
Juliana Almeida Silva ◽  
Albert Schriefer ◽  
Jamile Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Therapeutic Response ◽  
Helminth Infection ◽  
Clinical Manifestations ◽  
Response To Treatment ◽  
Stool Examination ◽  
Clinical Aspects ◽  
Intestinal Helminth ◽  
Leishmania Braziliensis ◽  
Cure Rate

Leishmania braziliensis is the most important cause of cutaneous leishmaniasis (CL) in the Americas. A Th1-type immune response is required to control Leishmania infection, but an exaggerated inflammatory response leads to the development of ulcers seen in CL. Infection with intestinal helminths has the potential to inhibit the Th1 response in a manner that depends both on the species of helminth present as well as the burden of helminthiasis. We conducted a prospective cohort study of CL patients from an endemic area between January and December 2017 with either negative or high intestinal helminth burden to characterize relationships between helminth burden, L. braziliensis quantification within CL lesions, clinical aspects of CL, and therapeutic response. Of 234 participants with leishmaniasis who underwent stool examination at the time of diagnosis, 45% had detectable helminth infection. The overall cure rate after 90 days was 66%, with a median time to resolution of disease of 40 days (interquartile range: 30–65 days). There was no significant association between the type of helminth infection or the magnitude of intestinal helminth burden at the time of diagnosis and L. braziliensis genomic DNA (gDNA) detected in biopsies from CL lesions. Likewise, there was no association between helminth burden and response to treatment after 90 days. Considering quantification of parasite DNA in CL lesions, participants who were cured at 90 days had a median of 0.017 ng/mg gDNA, and participants who failed therapy had a median of 0.091 ng/mg gDNA (P = 0.03). The results indicate that cutaneous Leishmania load may influence therapeutic response in CL.

scholarly journals BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy

2016 ◽  
Vol 34 (25) ◽  
pp. 3023-3030 ◽  
Author(s):  
Sébastien Héritier ◽  
Jean-François Emile ◽  
Mohamed-Aziz Barkaoui ◽  
Caroline Thomas ◽  
Sylvie Fraitag ◽  
...  
Keyword(s):  
High Risk ◽  
Langerhans Cell Histiocytosis ◽  
Clinical Manifestations ◽  
Langerhans Cell ◽  
Response To Therapy ◽  
Organ Involvement ◽  
Wild Type ◽  
Response To Chemotherapy ◽  
The Impact

Purpose Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAFV600E mutation occurs frequently, but clinical significance remains to be determined. Patients and Methods BRAFV600E mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. Results Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAFV600E mutation. Patients with BRAFV600E manifested more severe disease than did those with wild-type BRAF. Patients with BRAFV600E comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAFV600E mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAFV600E more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). Conclusion In children with LCH, BRAFV600E mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy.

scholarly journals Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Alexsandro S Lago ◽  
Filipe R Lima ◽  
Augusto M Carvalho ◽  
Camilla Sampaio ◽  
Neuza Lago ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Interferon Γ ◽  
Cure Rate ◽  
Cutaneous Lesions ◽  
Inflammatory Cytokine Production ◽  
Polymerase Chain ◽  
And Gender ◽  
Histopathologic Findings

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by 1 or multiple well-limited ulcerated lesions. Diabetes mellitus (DM) impairs neutrophil and monocyte function, and there is a report of vegetative lesions in a patient with both diseases in Morocco. Here we evaluate the influence of DM on clinical manifestations, immune response, and in the treatment of CL. Methods The participants were 36 DM patients with CL and 36 patients with CL without DM, matched by age and gender. The diagnosis of CL was performed by documentation of DNA of L. braziliensis by polymerase chain reaction in the lesion biopsy and histopathologic findings. All patients were treated with Glucantime (Sanofi-Aventis) 20 mg/kg of weight per day for 20 days. Results There was no difference in the majority of the clinical variables between the groups, and the cure rate in patients with CL and DM (67%) was similar to that observed in CL patients (56%; P ˃ .05). The most important finding was the documentation that 36% of the patients with DM and CL had atypical cutaneous lesions characterized by large superficial ulcers without defined borders. High levels of interferon-γ, tumor necrosis facor, and interleukin-1β were detected in the supernatants of mononuclear cells stimulated with Leishmania antigen in patients with DM and atypical CL. Moreover, while cure was observed in only 33% of the patients with DM and atypical CL lesions, it was observed in 85% of patients with typical lesions (P &lt; .05). Conclusions DM modifies the clinical presentation of CL, enhances pro-inflammatory cytokine production, and impairs response to antimony therapy.

Comparison of Clinical Presentation and Outcomes of Peritonitis in the Elderly and Younger Peritoneal Dialysis Patients

2019 ◽  
Vol 39 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Htay Htay ◽  
Jun Jie Benjamin Seng ◽  
Mei Hui Amanda Yong ◽  
Suh Chien Pang ◽  
Sin Yan Wu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Elderly Patients ◽  
Clinical Presentation ◽  
Removal Rate ◽  
Demographic Data ◽  
Clinical Manifestations ◽  
The Elderly ◽  
Catheter Removal ◽  
Younger Patients ◽  
Cure Rates

Background The incidence of elderly patients receiving peritoneal dialysis (PD) has increased. This study aimed to examine the clinical presentation and outcomes of peritonitis in elderly PD patients compared with younger PD patients. Methods This single-center, retrospective, observational cohort study included all adult PD patients who developed peritonitis between January 2011 and December 2014. Elderly was defined as ≥ 65 years old at PD initiation. The primary outcome was medical cure, defined as a peritonitis episode cured by antibiotics without being complicated by catheter removal, transfer to hemodialysis (HD), relapsing peritonitis, or death. The secondary outcomes were clinical manifestations (fever, cloudy dialysate) and complications (catheter removal, transfer to HD, relapse, hospitalization, and mortality). Peritonitis outcomes were compared using multivariable logistic regression. Results Overall, 377 peritonitis episodes occurred in 247 patients. Of these, 126 episodes occurred in 79 elderly patients and 251 episodes occurred in 168 younger patients. Baseline demographic data were comparable between the 2 groups, except that elderly patients were significantly more likely to have diabetes mellitus (66% vs 46%), diabetic nephropathy (55% vs 39%), and a lower serum albumin than younger patients. Medical cure was comparable between the 2 groups (71% vs 72%, respectively, p = 0.67, adjusted odds ratio [AOR] 0.89, 95% confidence interval [CI]: 0.52 – 1.53). Compared with younger patients, elderly patients experiencing peritonitis had lower odds of fever (OR 0.53, 95% CI: 0.30 – 0.94), cloudy dialysate (OR 0.45, 95% CI: 0.23 – 0.88), and catheter removal (AOR 0.50, 95% CI: 0.26 – 0.98), but similar odds of transfer to HD (AOR 0.70, 95% CI: 0.32 – 1.51), relapse (AOR 1.57, 95% CI: 0.46 – 5.40), hospitalization (AOR 1.55, 95% CI: 0.52 – 4.56), and all-cause mortality (AOR 1.88, 95% CI: 0.83 – 4.26). Conclusions Compared with younger patients, elderly PD patients with peritonitis achieved similar medical cure rates, a lower catheter removal rate, and comparable rates of HD transfer, relapse, hospitalization, and death. Elderly PD patients experiencing peritonitis were less likely to present with fever or cloudy dialysate.

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