Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study / Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico

Background Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. Objective To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. Methods We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. Results A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. Conclusion Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice (AU)

Antecedentes El carcinoma de células basales (CBC) es el cáncer más prevalente. Una minoría de CBC tiene un comportamiento agresivo (laBCC) y puede requerir inhibidores de la vía del erizo, como sonidegib como tratamiento. Objetivo Describir el uso de sonidegib en un gran número de pacientes y aportar más datos sobre su perfil de eficacia y seguridad en la vida real. Métodos Realizamos un estudio retrospectivo y multicéntrico que incluyó pacientes tratados con sonidegib. Se recogieron datos epidemiológicos, de eficacia y de seguridad. Resultados Se incluyeron un total de 82 pacientes con una edad media de 73,9 años. Diez pacientes tenían síndrome de Gorlin. La mediana de duración del tratamiento fue de 6 meses. La mediana de duración del seguimiento fue de 34,2 meses. Globalmente, el 81,7% de los pacientes mostró mejoría clínica (52,4% respuesta parcial y 29,3% respuesta completa), el 12,2% estabilidad clínica y el 6,1% progresión de la enfermedad. No hubo diferencias estadísticamente significativas en la mejoría clínica entre la posología de sonidegib de 24horas y de 48horas. Después de 6 meses de tratamiento, el 48,8% de los pacientes suspendió sonidegib. El tratamiento previo con vismodegib y el CBC primario recurrente se asociaron con una peor respuesta a sonidegib. A los 6 meses de tratamiento el 68,3% de los pacientes experimentó al menos un efecto adverso. Conclusión Sonidegib muestra un perfil de eficacia y seguridad mejor de lo esperado en la práctica clínica habitual (AU)

[Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico / Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study

Antecedentes El carcinoma de células basales (CBC) es el cáncer más prevalente. Una minoría de CBC tiene un comportamiento agresivo (laBCC) y puede requerir inhibidores de la vía del erizo, como sonidegib como tratamiento. Objetivo Describir el uso de sonidegib en un gran número de pacientes y aportar más datos sobre su perfil de eficacia y seguridad en la vida real. Métodos Realizamos un estudio retrospectivo y multicéntrico que incluyó pacientes tratados con sonidegib. Se recogieron datos epidemiológicos, de eficacia y de seguridad. Resultados Se incluyeron un total de 82 pacientes con una edad media de 73,9 años. Diez pacientes tenían síndrome de Gorlin. La mediana de duración del tratamiento fue de 6 meses. La mediana de duración del seguimiento fue de 34,2 meses. Globalmente, el 81,7% de los pacientes mostró mejoría clínica (52,4% respuesta parcial y 29,3% respuesta completa), el 12,2% estabilidad clínica y el 6,1% progresión de la enfermedad. No hubo diferencias estadísticamente significativas en la mejoría clínica entre la posología de sonidegib de 24horas y de 48horas. Después de 6 meses de tratamiento, el 48,8% de los pacientes suspendió sonidegib. El tratamiento previo con vismodegib y el CBC primario recurrente se asociaron con una peor respuesta a sonidegib. A los 6 meses de tratamiento el 68,3% de los pacientes experimentó al menos un efecto adverso. Conclusión Sonidegib muestra un perfil de eficacia y seguridad mejor de lo esperado en la práctica clínica habitual (AU)

Background Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. Objective To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. Methods We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. Results A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. Conclusion Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice (AU)

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Liquen escleroso extragenital inducido por radioterapia / Extragenital Lichen Sclerosus Induced by Radiotherapy

No disponible

Evolution of Kaposi sarcoma in the past 30 years in a tertiary hospital of the European Mediterranean basin.

BACKGROUND: The incidence of Kaposi sarcoma (KS) has reduced as a result of the introduction of antiretroviral therapy. It is currently considered a rare disease in developed countries, and there has been a paucity of clinical papers on the subject in recent years in Europe. AIM: To analyse the clinical features and evolution of the different clinical forms of KS in the past 30 years. METHODS: Patients with cutaneous lesions of KS diagnosed during the period 1987-2016 at Bellvitge Hospital (an 800-bed university referral centre in Barcelona, Spain) were enrolled. Data recorded included age, sex, ethnicity, involved site, number of lesions, extracutaneous involvement, leg oedema, treatment, blood haemoglobin level, and blood cell (leucocyte, lymphocyte and CD4) counts. RESULTS: Cutaneous lesions of KS were diagnosed in 191 patients (167 men, 24 women, mean ± SD age 51.95 ± 20.16 years). Clinical forms identified were classic KS (n = 53), acquired immunodeficiency syndrome (AIDS)-associated KS (n = 118), immunosuppression-associated KS (n = 18), and African endemic KS (n = 2). The number of patients diagnosed annually reached a maximum in the 1990s because of the AIDS epidemic, and has decreased since 2000. However, both classic KS and immunosuppression-associated KS doubled from the first to the second half of the analysed period. Cutaneous lesions involved the legs in 137 cases, and extracutaneous lesions were detected in 32 patients. In 46 of 118 patients with AIDS, the diagnosis of KS was simultaneous to the detection of human immunodeficiency virus infection. CONCLUSION: After a decrease in incidence since the middle of the 1990s, AIDS-associated KS continues to occur in Europe, and the number of annual cases of classic KS and immunosuppression-associated KS is increasing.

Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea / Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab

Antecedentes y objetivo: Los ensayos pivotales de omalizumab en urticaria crónica espontánea (UCE) tienen un periodo de tratamiento de entre 12 y 24 semanas. Sin embargo, muchos pacientes en práctica clínica requieren periodos de tratamiento más prolongados. Por ello el objetivo es presentar un algoritmo de manejo del fármaco. Materiales y métodos: El documento de consenso que detallamos nace de la puesta en común, aceptación, revisión y confrontación de la literatura reciente del grupo de trabajo de UCE "Xarxa d'Urticària Catalana i Balear" (XUrCB). Resultados: Se inicia el tratamiento a dosis autorizada y se ajusta la dosis en intervalos trimestrales en función del Urticaria Activity Score de los últimos 7 días (UAS7) y/o el Urticarial Control Test (UCT). Conclusiones: El algoritmo propuesto pretende servir de guía respecto a cómo ajustar dosis, cómo y cuándo parar el fármaco y el modo de reintroducirlo en casos de recaída

Background and objective: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. Material and methods: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. Results: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7 days, the Urticaria Control Test, or both. Conclusions: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse

Melanoma subungueal: estudio descriptivo de 34 pacientes / Subungual Melanoma: A Descriptive Study of 34 Patients

INTRODUCCIÓN Y OBJETIVOS: El melanoma subungueal constituye un reto diagnóstico por su presentación clínica frecuentemente atípica. El objetivo del estudio fue revisar las características clínico-patológicas de los pacientes con melanoma subungueal diagnosticados en un hospital universitario de tercer nivel y analizar los factores posiblemente asociados al retraso del diagnóstico. MATERIAL Y MÉTODOS: Fueron analizados los datos de 34 pacientes diagnosticados de melanoma subungueal durante 20 años en nuestro centro. RESULTADOS: Del total de pacientes, 18 eran mujeres y 16 eran varones, con una edad mediana al diagnóstico de 66 años. Únicamente 5 de los pacientes presentaron melanoniquia longitudinal al ser visitados en nuestro Servicio de Dermatología. De los 34 pacientes, 19 presentaron melanoma invasivo al diagnóstico, con una mediana de índice de Breslow de 3,70 mm; 16 presentaron ulceración y 8 invasión ganglionar regional al diagnóstico. Cinco pacientes fueron diagnosticados en fase de melanoma in situ. La mediana del tiempo de evolución de las lesiones desde su aparición hasta la consulta al Centro de Asistencia Primaria fue de 15 meses, y desde la consulta al Centro de Asistencia Primaria hasta el diagnóstico en nuestro hospital fue de 5,5 meses. Las lesiones localizadas en los dedos de los pies presentaron con mayor frecuencia ulceración (p = 0,017) y una mayor probabilidad de invasión ganglionar regional al diagnóstico (p = 0,012). CONCLUSIONES: Los factores que en nuestro estudio se asociaron a un mayor retraso del diagnóstico del melanoma subungueal fueron la ausencia de melanoniquia como presentación clínica inicial y la localización de las lesiones en los dedos de los pies

INTRODUCTION AND OBJECTIVES: Subungual melanoma constitutes a diagnostic challenge because it often has an atypical clinical presentation. The aims of this study were to revise the clinical and pathologic characteristics of patients with subungual melanoma diagnosed at a tertiary care university hospital and analyze the factors potentially associated with a delayed diagnosis. MATERIAL AND METHODS: We analyzed data for 34 patients diagnosed with subungual melanoma at our hospital over a period of 20 years. RESULTS: The study population comprised 18 women and 16 men with a median age at diagnosis of 66 years. Only 5 of the patients had longitudinal melanonychia when examined at the dermatology department. At the time of diagnosis, 19 of the 34 patients had invasive melanoma (median Breslow thickness, 3.70 mm); 16 had ulceration and 8 had regional lymph node involvement. Five patients had subungual melanoma in situ at diagnosis. The median time from appearance of the lesions to consultation at a primary care center was 15 months; the corresponding time from primary care consultation to diagnosis at our hospital was 5.5 months. Lesions located on the toes were more likely to be ulcerated (P = .017) and to be accompanied by regional lymph node involvement at diagnosis (P = .012). CONCLUSIONS: The factors associated with a longer diagnostic delay in patients with subungual melanoma were absence of melanonychia as a presenting feature and involvement of the toes

Subungual Melanoma: A Descriptive Study of 34 Patients. / Melanoma subungueal: estudio descriptivo de 34 pacientes.

INTRODUCTION AND OBJECTIVES: Subungual melanoma constitutes a diagnostic challenge because it often has an atypical clinical presentation. The aims of this study were to revise the clinical and pathologic characteristics of patients with subungual melanoma diagnosed at a tertiary care university hospital and analyze the factors potentially associated with a delayed diagnosis. MATERIAL AND METHODS: We analyzed data for 34 patients diagnosed with subungual melanoma at our hospital over a period of 20 years. RESULTS: The study population comprised 18 women and 16 men with a median age at diagnosis of 66 years. Only 5 of the patients had longitudinal melanonychia when examined at the dermatology department. At the time of diagnosis, 19 of the 34 patients had invasive melanoma (median Breslow thickness, 3.70mm); 16 had ulceration and 8 had regional lymph node involvement. Five patients had subungual melanoma in situ at diagnosis. The median time from appearance of the lesions to consultation at a primary care center was 15 months; the corresponding time from primary care consultation to diagnosis at our hospital was 5.5 months. Lesions located on the toes were more likely to be ulcerated (P=.017) and to be accompanied by regional lymph node involvement at diagnosis (P=.012). CONCLUSIONS: The factors associated with a longer diagnostic delay in patients with subungual melanoma were absence of melanonychia as a presenting feature and involvement of the toes.

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Cutaneous leishmaniasis associated with anti-tumour necrosis factor-α drugs: an emerging disease.

Leishmaniasis is endemic in several geographic areas of the world. In each of these areas, particular species of Leishmania with differing aggressiveness to humans predominate. In the European Mediterranean basin, cutaneous leishmaniasis usually presents with discrete, self-healing skin lesions. Although it is known that tumour necrosis factor (TNF) inhibitors may increase the risk of developing infections such as tuberculosis, there is scarce literature on Leishmania infections in patients treated with these drugs. In recent months, we have observed three patients resident in the Catalan coast of Spain who were treated with TNF inhibitors for Crohn disease, and who developed unusually large and persistent cutaneous lesions of leishmaniasis. These lesions responded only to treatment with intravenous liposomal amphotericin B. In countries with a high incidence of infection by aggressive species of Leishmania, serological screening may be indicated to detect a possible latent leishmanial infection before prescription of TNF inhibitors.

Sweet syndrome: long-term follow-up of 138 patients.

BACKGROUND: Several studies support a strong association of Sweet syndrome (SS) with malignancy. However, only a few studies analysing the clinical features of malignancy-associated SS have been published in recent years. AIM: To retrospectively study the clinical features of SS that could predict the development of associated malignancies and to analyse the development of malignant neoplasia during long-term follow-up of patients with SS. METHODS: Clinical features of the patients diagnosed with SS syndrome between 1987 and 2013 at Bellvitge Hospital (Barcelona, Spain) were retrospectively analysed. RESULTS: In total, 138 patients were included in the study (66 male, 72 female, mean ± SD age 51.24 ± 14.11 years). SS was associated with haematological malignancy in 31 cases, infection in 23, inflammatory bowel disease in 12, inflammatory systemic disease in 8, and solid tumours in 4. It was drug-induced in 5 cases and idiopathic in 54. In four patients, an underlying haematological disease that was considered related to SS was diagnosed between 4 and 16 months after SS presentation. Variables significantly associated with malignancy in multivariate logistic regression analysis were age (OR = 1.08 for each increasing year, P = 0.01), anaemia (OR = 9.38, P = 0.001), thrombocytopenia (OR = 16.10, P < 0.01) and absence of arthralgia (OR = 11.13, P < 0.01). CONCLUSIONS: Patients with older age, anaemia or thrombocytopenia, and without arthralgia are more likely to have malignancy-associated SS. We recommend that patients with SS without clear aetiology should be followed up for at least 16 months to exclude a possible underlying haematological malignancy.

Necrobiosis lipoídica. Estudio descriptivo de 35 pacientes / Necrobiosis Lipoidica: A Descriptive Study of 35 Cases

Introducción y objetivos: La necrobiosis lipoídica (NL) es una enfermedad granulomatosa idiopática de curso crónico que se considera asociada a la diabetes mellitus (DM). Sin embargo, existen resultados contradictorios respecto a la frecuencia de esta asociación. Nuestro objetivo fue analizar retrospectivamente las características clínicas de nuestros pacientes con NL y su relación con la DM y otras enfermedades. Material y métodos: Todos los pacientes diagnosticados clínica e histológicamente de NL que han sido tratados y controlados en el Servicio de Dermatología del Hospital de Bellvitge de Barcelona fueron incluidos en el estudio. Resultados: Treinta y cinco pacientes fueron diagnosticados de NL entre 1987 y 2013 (6 varones y 29 mujeres, edad media 47,20 años). En el momento del diagnóstico de la NL 31 pacientes presentaban lesiones a nivel pretibial. Trece pacientes (37%) presentaban una única lesión al ser diagnosticados y el número medio de lesiones fue de 3,37. La NL se asoció a DM en 23 pacientes (65,71%) (10 tipo 1, 13 tipo 2). En 20 casos la DM precedió al inicio de las lesiones de NL con un tiempo medio de 135,70 meses. En 3 casos la DM y la NL se diagnosticaron simultáneamente. Ninguno de nuestros pacientes con NL desarrolló DM durante el tiempo de seguimiento. Seis pacientes tenían hipotiroidismo, 4 de los cuales tenían también DM tipo 1. Conclusiones: La NL está frecuentemente asociada a DM, tanto tipo 1 como tipo 2, y aunque esta suele precederla en años, en algún caso la aparición es simultánea (AU)

Introduction and objectives: Necrobiosis lipoidica (NL) is a chronic idiopathic granulomatous disease considered to occur in association with diabetes mellitus. Data on the frequency of this association, however, are inconsistent. Our aim was to retrospectively analyze the clinical characteristics of patients diagnosed with NL at our hospital and to investigate the association with diabetes mellitus and other diseases. Material and methods: We performed a chart review of all patients with a clinical and histologic diagnosis of NL treated and followed in the dermatology department of Hospital de Bellvitge in Barcelona, Spain between 1987 and 2013. Results: Thirty-five patients (6 men and 29 women with a mean age of 47.20 years) were diagnosed with NL in the study period. At the time of diagnosis, 31 patients had pretibial lesions. Thirteen patients (37%) had a single lesion at diagnosis, and the mean number of lesions was 3.37. Twenty-three patients (65.71%) had diabetes mellitus (type 1 in 10 cases and type 2 in 13). In 20 patients, onset of diabetes preceded that of NL by a mean of 135.70 months. The 2 conditions were diagnosed simultaneously in 3 patients. None of the 35 patients developed diabetes mellitus during follow-up. Six patients had hypothyroidism, and 4 of these also had type 1 diabetes. Conclusions: NL is frequently associated with type 1 and 2 diabetes. Although diabetes tends to develop before NL, it can occur simultaneously (AU)

Necrobiosis lipoidica: a descriptive study of 35 cases.

INTRODUCTION AND OBJECTIVES: Necrobiosis lipoidica (NL) is a chronic idiopathic granulomatous disease considered to occur in association with diabetes mellitus. Data on the frequency of this association, however, are inconsistent. Our aim was to retrospectively analyze the clinical characteristics of patients diagnosed with NL at our hospital and to investigate the association with diabetes mellitus and other diseases. MATERIAL AND METHODS: We performed a chart review of all patients with a clinical and histologic diagnosis of NL treated and followed in the dermatology department of Hospital de Bellvitge in Barcelona, Spain between 1987 and 2013. RESULTS: Thirty-five patients (6 men and 29 women with a mean age of 47.20 years) were diagnosed with NL in the study period. At the time of diagnosis, 31 patients had pretibial lesions. Thirteen patients (37%) had a single lesion at diagnosis, and the mean number of lesions was 3.37. Twenty-three patients (65.71%) had diabetes mellitus (type 1 in 10 cases and type 2 in 13). In 20 patients, onset of diabetes preceded that of NL by a mean of 135.70 months. The 2 conditions were diagnosed simultaneously in 3 patients. None of the 35 patients developed diabetes mellitus during follow-up. Six patients had hypothyroidism, and 4 of these also had type 1 diabetes. CONCLUSIONS: NL is frequently associated with type 1 and 2 diabetes. Although diabetes tends to develop before NL, it can occur simultaneously.