Effect of multidrug therapy on the prognosis of Mycobacterium avium complex pulmonary disease.

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.

Follicular mycosis fungoides: Clinicohistopathologic features and outcomes in a series of 12 Chinese cases.

Background Follicular mycosis fungoides is a distinct variant of mycosis fungoides with a broad clinical spectrum. Recently, many studies have indicated that follicular mycosis fungoides should be divided into different subtypes with disparate prognoses. Objective To define the clinicohistopathologic features and outcomes of follicular mycosis fungoides and to identify risk factors that may be related to the prognosis of Chinese patients with follicular mycosis fungoides. Materials and methods We conducted a single-centre retrospective study and reviewed the clinical, histopathologic and immunophenotypic data of 12 patients diagnosed with follicular mycosis fungoides between 2009 and 2020 in the Department of Dermatology of West China Hospital of Sichuan university. Results A total of 12 patients (seven males and five females) with a mean age of 30 ± 14 years (age range 16-55 years) were included. Scalp and face were the most common involved sites (100%). Follicular papules, acneiform lesions, plaques, and nodules, were the main clinical presentations. Histopathological findings were consistent with the classic manifestations of follicular mycosis fungoides, including folliculotropism, perifollicular and intrafollicular lymphocytic infiltrates and mucinous degeneration. Interferon α-1b was the most common treatment. Four patients died of follicular mycosis fungoides in three years. Notably, immunohistochemical analysis revealed a decreased number of CD20+ cells in the deceased patients. Limitations This is a retrospective evaluation with a small number of cases; further prospective studies are warranted to support our inferences. Conclusion Our patients were much younger than in previous studies. The observed difference in this cohort may be explained by race, in addition to the limited number of cases. A decreased number of B cells might be associated with a poor prognosis, and more studies are necessary to discover the role of B cells in follicular mycosis fungoides as well as in mycosis fungoides.

Clinicopathological features and prognosis of pyoderma gangrenosum in Korea: A single centre, retrospective, observational study over 20 years.

BACKGROUND: Pyoderma gangrenosum is a rare autoinflammatory neutrophilic dermatosis that rapidly evolves. However, little is known about the clinicopathological features and prognosis of pyoderma gangrenosum. AIMS: We aimed to document clinicopathologic and prognostic data of the patients with pyoderma gangrenosum. METHODS: In this retrospective observational study, we reviewed case records of patients diagnosed with pyoderma gangrenosum between 1999-2019. RESULTS: Fifty-three patients were identified by reviewing medical records for skin biopsy; of these, 37 were men and 16 were women. Mean age at onset was 43.3 ± 18.5 years. The most frequently affected area was the lower extremities (60.4%), followed by the head and neck (17.0%). The most common subtype was ulcerative (47.2%), followed by bullous (22.6%). 30 cases had underlying diseases and the most common were malignancy (24.5%), followed by inflammatory bowel diseases (18.9%). The proportion of cases with history of trauma were significantly higher in post-operative type (100%) as compared to the bullous type (8.3%). Histologic features of granulation tissue were frequently found in post-operative type (66.7%) and bullous type (58.3%). Granulomas were predominantly found in bullous type (58.3%). Age <60 years appeared to be significantly associated with multiple lesions. Partial-to-complete remission was observed in 40 cases (75.5%). Nine (17.0%) cases experienced recurrence with a median progression-free period of six months (interquartile range of 3.0-9.0 months). Cases with underlying hematologic disorders and the bullous subtype were significantly associated with early recurrence. LIMITATIONS: This study was a single-centre study with a retrospective design. CONCLUSION: Pyoderma gangrenosum appears to have ethnic differences. Underlying haematologic disorders and bullous subtype have a worse prognosis. However, the type of histopathology did not correlate with the clinical outcome of pyoderma gangrenosum.

Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

Background Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results One hundred forty-eight patients were included in the study. The Kaplan-Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5-81.6%), 53.4% (45.7-62.2%), 43.6% (35.9-53%) and 31.3% (23.5-41.7%). The median follow-up among survivors was 48 months (interquartile range: 11-150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients.

Laboratory perspectives for Leprosy: Diagnostic, prognostic and predictive tools.

The diagnosis of leprosy poses several challenges. The bacillary load, serology, and tissue response are determined by the host immune status, which make individual tests unsuitable across the spectrum. The sensitivity of tests for identifying paucibacillary cases remains limited, on the other hand, many tests lack specificity in differentiating contacts from diseased cases. Nonetheless, a plethora of laboratory tests have been added to the armamentarium of the clinicians dealing with leprosy. In the current review, we critically analyze the tests available for diagnosis, prognostication, and prediction of treatment response in leprosy. We discuss in brief the conventional tests available and detail the newer serologic and molecular tests added over the past few years with an attempt to suggest the pros and cons of each, and the tests best fit for each clinical scenario. Slit skin smears and skin or nerve biopsies are primarily performed to exclude clinical mimics, confirm a diagnosis, and immunologically subtype the case. Antibody titres of phenolic glycolipid-1 and its synthetic variants can be measured in serum and saliva and provide noninvasive means to detect leprosy with good specificity. Conventional, quantitative, real-time, and other variants of PCR can detect M. leprae DNA and have been used to effect in blood, tissue, and urine samples. T helper I and II cytokine signatures can be used to differentiate the subtypes of leprosy. Newer machine learning algorithms use combinations of these tests to predict the development of leprosy in contacts. Tests to detect treatment response, antimicrobial drug resistance, and predict the onset of reactions in leprosy can be used to advantage. We compare the characteristics of these tests and suggest an algorithm for leprosy diagnosis optimally utilizing them in various clinical settings.

Need to restage Korean melanoma patients following publication of the 8th edition of the American Joint Committee on Cancer staging manual.

BACKGROUND: The tumor, nodes and metastasis (TNM) classification and stage grouping have been updated in the 8th edition of the American Joint Committee on Cancer (AJCC) melanoma staging manual. However, restaging all the previous cases are not recommended. AIMS: The aims of the study were to investigate the necessity of restaging Korean melanoma patients staged by the previous edition of the AJCC manual. METHODS: Differences in the staging criteria of the 7th and 8th editions of the AJCC manual were identified. The staging of 276 primary melanomas from January 2011 to December 2018 was classified by both 7th and 8th editions of the manual and their differences were compared. RESULTS: Staging by 7th and 8th edition of the AJCC manual differed in 64 cases (23.2%). The pathological prognostic staging changed in 35 (12.7%), and 29 (10.5%) had changes in only TNM classification but not the pathological staging. None of the patients needed additional sentinel lymph node biopsy or systemic treatment as a result of restaging. Additional counseling was needed for the patients, because melanoma-specific survival was increased in the 8th edition. LIMITATIONS: This is a retrospective study with relatively small number of patients at a single tertiary center in Korea. CONCLUSION: Assessment of the need for additional sentinel lymph node biopsy or systemic treatment is recommended because of the latest changes in the AJCC melanoma staging manual. Although the restaging of previously staged melanomas is not significantly needed in our patients, still the differences in TNM classification and/or pathological prognostic staging suggest the need to separately recognize the patients previously staged by 7th edition and recently staged by 8th edition. Careful counseling about melanoma-specific survival is needed for Asian patients.

[Delay in diagnosis as a prognostic factor for disability in patients with leprosy in Paraguay. Case and control study]. / Retraso en el diagnóstico como factor pronóstico de discapacidad en pacientes con lepra en Paraguay. Estudio de casos y controles.

BACKGROUND: Leprosy, a chronic infectious disease, is one of the major causes of preventable disability. Early treatment prevents neurological damage and disability. AIM: To identify prognostic factors of disability in individuals with multibacillary and paucibacillary leprosy who completed a drug treatment between 2011 and 2017 in Paraguay. METHODS: A case-control study was carried out on 34 patients, of them 9 were cases and 25 controls. Cases were those patients with Grade 1, presented lack of sensation in lower or upper limbs, and those of Grade 2 lagophthalmos, rigidity, visible deformity ulcerations, passive claw, active claw. Controls had no disabilities. RESULTS: Mean age of the patients was 53 ± 15.2 years, 55.9% were male, and 58.9% had primary education or no formal education. Multibacillary leprosy was found in 58.8% of patients; and 64.7% were diagnosed after consulting with two or more physicians. Diagnosis delay of more than one year was significantly (p = 0.047) greater in the cases than in the controls (77.8% vs 12%; OR: 7.44; 95% CI: 1.02-67.86). CONCLUSION: In this study, a diagnosis delay of more than one year is a prognostic factor for disability.

Potential of recombinant LiHyQ, a novel Leishmania infantum protein, for the diagnosis of canine visceral leishmaniasis and as a diagnostic and prognostic marker for human leishmaniasis and human immunodeficiency virus co-infection: A preliminary study.

Laboratory diagnosis of leishmaniasis shows variable efficacy in detecting infected mammalian hosts and there is a need to identify suitable antigens to improve the accuracy of diagnostic tests. In the present study, a L. infantum hypothetical protein called LiHyQ was evaluated for the diagnosis of tegumentary (TL) and visceral (VL) leishmaniasis using canine and human samples. A collection of dog sera (n=155) were tested and contained samples from asymptomatic (n=20) and symptomatic (n=25) VL animals, from healthy dogs living in endemic (n=25) or non-endemic (n=25) areas of disease, from Leish-Tec® vaccinated dogs (n=20) or from dogs infected with Ehrlichia canis (n=15), Babesia canis (n=10) and Trypanosoma cruzi (n=15). Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with L. infantum Soluble Leishmania Antigen (SLA) preparation were 60.0%, 99.0%, 96.0% and 86.0%, respectively. A collection of human sera (n=305) were tested and contained samples from TL (n=50) and VL (n=40) patients, from VL/HIV co-infected patients (n=35), from patients infected with HIV alone (n=30), Chagas Disease (n=30), malaria (n=10), tuberculosis (n=10), paracoccidioidomycosis (n=15), leprosy (n=30) or aspergillosis (n=15); and from healthy subjects (n=40). Se, Sp, PPV and NPV values of 100% were observed for rLiHyQ with these samples, whereas the Se, Sp, PPV and NPV values with SLA were 58.0%, 76.0%, 50.0% and 82.0%, respectively. The antibody reactivity against the protein was compared with commercial kits, and the kappa index varied from 0.95 to 1.00 for rLiHyQ, and of 0.55 to 0.82 for the kits. In addition, the serological follow-up of treated patients showed a significant reduction in rLiHyQ-specific IgG antibody levels. All canine and human samples were tested at the same time using the same reagents, in order to reduce experimental variation and interference in data interpretation. In conclusion, our preliminary data suggest a diagnostic and prognostic role for rLiHyQ against leishmaniasis.

Retraso en el diagnóstico como factor pronóstico de discapacidad en pacientes con lepra en Paraguay: estudio de casos y controles / Delay in diagnosis as a prognostic factor for disability in patients with leprosy in Paraguay: case and control study

INTRODUCCIÓN: La lepra, una infección crónica, es una de las mayores causas de discapacidad prevenible. El inicio temprano del tratamiento previene el desarrollo de discapacidad. OBJETIVO: Identificar los factores pronóstico de discapacidad en individuos con lepra multibacilar y paucibacilar que culminaron el tratamiento farmacológico entre el 2011 y 2017 en Paraguay. PACIENTES Y MÉTODOS: Se realizó un estudio de casos y controles, con 34 pacientes, 9 casos, 25 controles. Los casos fueron pacientes con discapacidad Grado 1 que presentaban falta de sensibilidad en miembros inferiores o superiores, y los de Grado 2, lagoftalmos, rigidez, ulceraciones, garra pasiva, garra activa. Los controles no presentaron discapacidad. RESULTADOS: La edad media de los pacientes fue 53 ± 15,2 años, el 55,9% fue de sexo masculino y 58,9% tenía educación primaria o no tenía educación formal. El 58,8% de los pacientes presentó lepra multibacilar; y el 64,7% fue diagnosticado tras consultar con dos o más médicos. Retraso en el diagnóstico mayor a un año fue significativamente (p = 0,047) mayor en los casos que en los controles (77,8 vs 12%; OR: 7,44; IC95%: 1,02-67,86). CONCLUSIÓN: El retraso en el diagnóstico mayor a un año es un factor pronóstico de discapacidad.

BACKGROUND: Leprosy, a chronic infectious disease, is one of the major causes of preventable disability. Early treatment prevents neurological damage and disability. AIM: To identify prognostic factors of disability in individuals with multibacillary and paucibacillary leprosy who completed a drug treatment between 2011 and 2017 in Paraguay. METHODS: A case-control study was carried out on 34 patients, of them 9 were cases and 25 controls. Cases were those patients with Grade 1, presented lack of sensation in lower or upper limbs, and those of Grade 2 lagophthalmos, rigidity, visible deformity ulcerations, passive claw, active claw. Controls had no disabilities. RESULTS: Mean age of the patients was 53 ± 15.2 years, 55.9% were male, and 58.9% had primary education or no formal education. Multibacillary leprosy was found in 58.8% of patients; and 64.7% were diagnosed after consulting with two or more physicians. Diagnosis delay of more than one year was significantly (p = 0.047) greater in the cases than in the controls (77.8% vs 12%; OR: 7.44; 95% CI: 1.02-67.86). CONCLUSION: In this study, a diagnosis delay of more than one year is a prognostic factor for disability.

Oral submucous fibrosis: An overview of a challenging entity.

The oral cavity is considered to be a mirror of the body's health, as it reflects the manifestations of various systemic disorders. Most of the oral mucosa is derived embryologically from an invagination of ectoderm and thus, like other similar orifices, it may become involved in the disorders that are primarily associated with the skin. Oral submucous fibrosis is one of the commonest precancerous conditions of the oral mucosa involving any part of the oral cavity resulting in tissue scarring, dysphagia and trismus. It is a collagen-related disorder characterized by excessive fibrosis in the oral submucosa, hyalinization and degenerative changes in the muscles. This disease has become a challenging entity for dermatologists due to resemblance of its features to various mucocutaneous conditions. An improper diagnosis can lead to wrong treatment and additional complications. Dermatologists need to be aware of the characteristic features of this disease which can distinguish it from other similar conditions. This review aims to focus on the detailed aspects of oral submucous fibrosis including its historical background, etiological factors, pathogenesis, clinical features, differential diagnosis, investigations, management and future perspectives.

Different progression pattern between acral and nonacral melanoma: A retrospective, comparative, clinicoprognostic study of 492 cases of primary cutaneous melanoma according to tumor site.

BACKGROUND: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma. AIMS: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes. METHODS: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database. RESULTS: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma. LIMITATIONS: This study is a retrospective, single-center design. CONCLUSION: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.

Prognostic comparison of the FRIEND and Wasserman/Hansen peak VO2 equations applied to a submaximal walking test in outpatients with cardiovascular disease.

AIMS: The aim of this study was to determine the ability to predict all-cause mortality using established per cent-predicted (%PRED) equations for peak oxygen consumption (VO2peak) estimated by a submaximal walk test in outpatients with cardiovascular disease. METHODS: Male patients (N = 1491) aged 62 ± 10 years at baseline underwent a moderate and perceptually regulated (11-13 on the 6-20 Borg scale) 1-km treadmill-walking test to estimate VO2peak. %PRED was derived from the Fitness Registry and the Importance of Exercise: A National Data Base (FRIEND) and the Wasserman/Hansen equations. RESULTS: There were 215 deaths during a median 9.4-year follow-up. The FRIEND prediction equation provided better prognostic information with receiver operating curve analysis showing significantly different areas under the curve (0.72 and 0.69 for the FRIEND and the Wasserman/Hansen equations respectively, p = 0.001). Overall mortality rate was higher across decreasing tertiles of %PRED using FRIEND, with 26%, 11% and 5% for the least fit, intermediate and high fit tertiles, respectively (p for trend < 0.0001). Compared with the least fit tertile, the adjusted hazard ratios for the second and third tertiles were 0.54 (95% confidence interval 0.34-0.87, p = 0.01) and 0.45 (95% confidence interval 0.25-0.81, p = 0.008), respectively. Each 1% increase in %PRED conferred a 3% improvement in survival (p = 0.0004). CONCLUSION: Low %PRED VO2peak in cardiac outpatients determined by the FRIEND equation was associated with a high mortality rate independent of traditional cardiovascular risk factors and clinical history. The FRIEND equation may provide a suitable normal standard when applied to clinically stable outpatients with cardiovascular disease.

Treatment outcomes of drug susceptible Tuberculosis in private health facilities in Lagos, South-West Nigeria.

BACKGROUND: The Lagos State Tuberculosis, Buruli Ulcer, and Leprosy Control Program (LSTBLCP) started engaging private hospitals under the Public-Private Mix (PPM) Program in 2008. The study aimed to evaluate the trend and predictors of successful Tuberculosis (TB) treatment outcomes of patients managed across these private health facilities between 2010-2016 in Lagos, Nigeria. METHODS: Retrospective review of TB treatment register and treatment cards of patients commenced on TB treatment between January 2010 and December 2016 in 36 private health facilities engaged by the LSTBLCP. Between December 2016 and February 2017, data were collected and entered into Microsoft Excel by trained data entry clerks. The analysis was done using SPSS software. Independent predictors of successful treatment outcomes were determined using multivariate analysis at the statistical significance of p<0.05 and 95% confidence interval. RESULTS: A total of 1660 records of TB patients were reviewed. 1535 (92.47%) commenced treatment, while 1337 (87.10%) of all records had documented treatment outcomes. Of the 1337 patients with outcomes, 1044 (78.09%) had a successful treatment outcome, and 293 (21.91%) had an unsuccessful outcome. Majority were male, 980 (59.04%), Human Immunodeficiency Virus (HIV) negative status, 1295 (80.24%), diagnosed with smear, 1141 (73.14%), treated in private not-for-profit (PNFP) hospital, 1097 (66.08%), treated for TB between 2014-2016 (18.96%-19.52%). In multivariate analysis, age>20years (aOR = 0.26, p = 0.001), receiving TB treatment in 2013 (aOR = 0.39, p = 0.001), having genexpert for TB diagnosis (aOR = 0.26, p = 0.031) and being HIV positive (aOR = 0.37, p = 0.001) significantly reduced likelihood of successful treatment outcome. The site of TB, being on ART or CPT, were confounding determinants of successful treatment outcomes as they became non-significant at the multivariate analysis level. CONCLUSION: Treatment outcome among Lagos private hospitals was low compared with NTBLCP and World Health Organization (WHO) target. We urge the government and TB stakeholders to strengthen the PPM interventions to improve adherence, particularly among People Living with HIV (PLHIV) and older TB patients. Hence, promotion of early care-seeking, improving diagnostic and case holding efficiencies of health facilities, and TB/HIV collaborative interventions can reduce the risk of an unsuccessful outcome.

Erythroderma: a prospective study of 309 patients followed for 12 years in a tertiary center.

Erythroderma is characterized by erythema and scaling affecting more than 80% of the body surface area. It is potentially life-threatening, and diagnosis of the underlying disease is a challenge. Despite laboratory improvements, many cases remain idiopathic. We aimed to analyze clinical and laboratory findings of 309 erythrodermic patients to find clues to the etiologic diagnosis. We performed a prospective study at the University of São Paulo Medical School, from 2007 to 2018, with patients with acquired erythroderma. Clinical, laboratory, histology, and molecular biology data were collected. The median age at diagnosis was 57 years, with a male-to-female ratio of 2.2. Eczema was the most frequent etiology (20.7%), followed by psoriasis (16.8%), Sézary syndrome (12.3%), drug eruption (12.3%), atopic dermatitis (8.7%), and mycosis fungoides (5.5%). Other diagnoses (6.8%) included pemphigus foliaceous, paraneoplastic erythroderma, adult T-cell leukemia/lymphoma, dermatomyositis, pityriasis rubra pilaris, lichen planus, bullous pemphigoid, and leprosy. In 52 patients (16.8%), it was not possible to elucidate erythroderma etiology. Atopic dermatitis developed erythroderma at an earlier age (median 25 years; P = 0.0001). Acute onset was associated with drug reactions and atopic dermatitis (median time from erythroderma to diagnosis of 1 and 1.5 months, respectively; P = 0.0001). Higher immunoglobulin E levels were observed in atopic dermatitis (median 24,600 U/L; P = 0.0001). Histopathology was helpful and was consistent with the final diagnosis in 72.4%. Monoclonal T-cell proliferation in the skin was observed in mycosis fungoides (33.3%) and Sézary syndrome (90.9%). At the last assessment, 211 patients (69.3%) were alive with disease, 65 (21.7%) were alive without disease, and 27 (9.1%) died with active disease. Erythroderma is a challenging syndrome with a difficult diagnostic approach. Younger age and higher immunoglobulin E levels are associated with atopic dermatitis; acute onset is observed in drug eruptions and atopic dermatitis. Histopathology and molecular biology tests are essential tools in the investigation of erythroderma.

Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study.

Early diagnosis of leprosy is challenging, particularly its inflammatory reactions, the major cause of irreversible neuropathy in leprosy. Current diagnostics cannot identify which patients are at risk of developing reactions. This study assessed blood RNA expression levels as potential biomarkers for leprosy. Prospective cohorts of newly diagnosed leprosy patients, including reactions, and healthy controls were recruited in Bangladesh, Brazil, Ethiopia and Nepal. RNA expression in 1,090 whole blood samples was determined for 103 target genes for innate and adaptive immune profiling by dual color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) followed by cluster analysis. We identified transcriptomic biomarkers associated with leprosy disease, different leprosy phenotypes as well as high exposure to Mycobacterium leprae which respectively allow improved diagnosis and classification of leprosy patients and detection of infection. Importantly, a transcriptomic signature of risk for reversal reactions consisting of five genes (CCL2, CD8A, IL2, IL15 and MARCO) was identified based on cross-sectional comparison of RNA expression. In addition, intra-individual longitudinal analyses of leprosy patients before, during and after treatment of reversal reactions, indicated that several IFN-induced genes increased significantly at onset of reaction whereas IL15 decreased. This multi-site study, situated in four leprosy endemic areas, demonstrates the potential of host transcriptomic biomarkers as correlates of risk for leprosy. Importantly, a prospective five-gene signature for reversal reactions could predict reversal reactions at least 2 weeks before onset. Thus, transcriptomic biomarkers provide promise for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.

Ankle Fracture Stability-Based Classification: A Study of Reproducibility and Clinical Prognostic Ability.

OBJECTIVE: To compare the reproducibility and prognostic capacity of 2 commonly used ankle fracture classifications to the stability-based classification. METHODS: One hundred ninety-three consecutive rotational-type ankle fractures treated during a year at our institution in patients older than 18 years were retrospectively analyzed. Pilon and pathologic fractures were excluded. The fractures were treated by attending physicians who were unaware of the stability-based classification system. Three observers classified injury radiographs using the Lauge-Hansen, Weber/AO, and stability-based classifications systems. Reproducibility (interobserver variation) of each classification system was calculated using kappa statistics. Prognostic values were evaluated by calculating the area under the curve for the receiver-operating characteristic curves (using surgery as the positive outcome). RESULTS: The stability-based and Weber/AO classifications showed better reproducibility [kappa 0.938 (95% confidence interval 0.921-0.952), kappa 0.97 (0.961-0.976)], respectively, than the Lauge-Hansen [kappa 0.74 (0.664-0.795); P < 0.05]. The stability-based classification was more accurate (P < 0.001) in predicting surgical treatment [area under the curve 0.883 (95% confidence interval 0.852-0.914)] compared with the other 2 classifications [0.626 (0.576-0.675) and 0.698 (0.641-0.755)], respectively. CONCLUSIONS: The stability-based classification was both highly reproducible (kappa 0.938) and had superior prognostic capacity to identify patients who needed surgical intervention compared with both the Lauge-Hansen and AO/Weber classification systems. Importantly, there were no patients who were classified as stable who failed nonoperative treatment. This extends earlier studies by directly demonstrating its prognostic advantage to other classification systems.

Evaluation of the cutaneous sensation of the face in patients with different clinical forms of leprosy.

BACKGROUND: Leprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed. OBJECTIVES: The aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals. METHODOLOGY: 19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve. RESULTS: The predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases. CONCLUSION: The face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy.