Variedad úlcero-mutilante del Síndrome del Túnel Carpiano / Ulcerating Variety of Carpal Tunnel Syndrome

El síndrome del túnel carpiano es la neuropatía por atrapamiento más común, afectando del 1 al 3% de la población general. No obstante, la elevada frecuencia, las úlceras digitales y lesiones en piel son excepcionalmente asociadas a esta neuropatía. Presentamos un caso de un paciente con úlceras digitales secundarias al síndrome del túnel carpiano.

Carpal tunnel syndrome is the most common entrapment neuropathy, affecting 1 to 3% of the population. Even the fact that is very frequent, digital ulcers and skin lesions are unusually related to this neuropathy. We present the case of a patient with digital ulcers secondary to carpal tunnel syndrome.

Digital ulcers in systemic sclerosis / Úlceras digitales en esclerosis sistémica

ABSTRACT Vascular compromise in systemic sclerosis is a pivotal feature of the disease and plays a fundamental role in its morbidity and mortality. Raynaud's syndrome is present in almost every patient and is often reported as the first clinical manifestation. Digital ulcers may present several etiologies, although an ischemic cause is the most frequent origin and occurs in up to 50% of patients. A profound impact on daily life is often observed due to pain and functional impairment. Their primary pathophysiological mechanism is microvascular compromise, although larger vessels may be affected as well. When recurrent lesions are observed, large vessel compromise should be assessed, which may be due to the disease itself or due to atherosclerosis, whenever risk factors are present. Further, these ulcers present an increased risk of infection and progression to gangrene. The presence of digital lesions may be a marker of severity of the disease, as some reports have suggested an association with pulmonary hypertension and cardiac involvement. Treatment strategies have progressed significantly over the last years. Vasodilatation using calcium channel inhibitors is universally offered. When ischemic signs are observed, treatment should be started readily. Prostacyclin infusions should be considered in severe cases, as they have shown the capacity to foster ulceration healing. Whenever recurring lesions are observed, bosentan may be offered. Management with phosphodiesterase inhibitors may be proposed, although their positioning is unclear. Local treatment is equally important over the course of the disease. Surgical interventions are seldom needed.

RESUMEN El compromiso vascular en la esclerosis sistémica es una característica principal de la enfermedad y desempeña un papel fundamental en su morbimortalidad. El síndrome de Raynaud está presente en casi todos los pacientes, y con frecuencia es reportado como la primera manifestación clínica. Las úlceras digitales pueden tener varias etiologías, aunque una causa isquémica es el origen más frecuente y ocurre hasta en 50% de los pacientes. A menudo se observa un profundo impacto en la vida diaria debido al dolor y al deterioro funcional. Su mecanismo fisiopatológico primario es el compromiso microvascular, aunque los vasos más grandes también pueden verse afectados. Cuando se observan lesiones recurrentes se debe evaluar el compromiso de los vasos grandes, que puede deberse a la enfermedad en sí o a aterosclerosis, siempre que existan factores de riesgo. Además, estas úlceras presentan un mayor riesgo de infección y progresión a gangrena. La presencia de lesiones digitales puede ser un marcador de la gravedad de la enfermedad, ya que algunos informes han sugerido una asociación con hipertensión pulmonar y compromiso cardíaco. Las estrategias de tratamiento han progresado significativamente en los últimos anos. La vasodilatación con inhibidores de los canales de calcio se ofrece universalmente. Cuando se observan signos isquémicos el tratamiento debe iniciarse de inmediato. Las infusiones de prostaciclina se deben considerar en casos graves, ya que han demostrado la capacidad de promover la curación de la ulceración. Siempre que se observen lesiones recurrentes se puede administrar bosentán. Se puede proponer el manejo con inhibidores de la fosfodiesterasa, aunque su posicionamiento no está claro. El tratamiento local es igualmente importante durante el curso de la enfermedad. Las intervenciones quirúrgicas rara vez son necesarias.

Anti-annexin V autoantibodies and vascular abnormalities in systemic sclerosis: a longitudinal study

Abstract Background: Annexins are a group of conserved proteins which exert several regulatory functions on various cellular activities. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc. Methods: In this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Serum anti-annexin V IgG and IgM antibodies were measured at baseline and after 6, 12 and 24 months of follow-up. Videocapillaroscopy was performed in all patients. Results: Among the 70 SSc patients included anti-annexin V IgG was found in 11 patients (15.7%) (range of 15.88-39.48 U/mL) and anti-annexin V IgM in 10 patients (14.3%) (range of 14.16-22.69 U/mL) at baseline. During follow-up, the number of patients who were positive for anti-annexin V IgG and IgM remained stable over 24 months. Among the patients with positive anti-annexin V IgG at baseline the frequency of patients with necrosis or amputation of extremities, forced vital capacity less than 70% and pulmonary arterial hypertension (PAH) was significantly higher than in patients with negative anti-annexin V IgG antibodies. Patients with anti-annexin V IgG had also a higher Raynaud's Condition Score and a higher Health Assessment Questionnaire Disability Index (HAQ-DI) than patients without these antibodies at baseline. Patients with positive anti-annexin V IgM at baseline presented a higher frequency of PAH, compared to those with negative anti-annexin V IgM at baseline. Conclusions: Anti-annexin V antibodies are stable and do not change their positivity during a 24 month follow-up in SSc patients. Anti-annexin V IgG was associated with more severe interstitial lung involvement and digital microangiopathy, and patients with anti-annexin V IgG or IgM had a higher occurrence of PAH indicating an association of these biomarker with more severe disease.(AU)

Risk of digital ulcers occurrence in systemic sclerosis: a cross-sectional study

Abstract Background/objective: Digital ulcers (DUs) represent a frequent complication of systemic sclerosis (SSc). The aim of this study was to evaluate clinical, serological and capillaroscopy features that are associated with DUs in patients with SSc. Methods: In this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Videocapillaroscopy was performed in all patients. Results: Among the 70 patients included (mean age of 46.8 years, mean disease duration of 9.41 years), 14 (20%) had active DUs. Based on multivariate analysis, the presence of anti-Scl-70 antibodies, the HAQ-DI score, and the capillary loss score were independently associated with DUs with odds ratios of 7.96 (95% CI 1.32-47.99), 55.77 (95% CI 1.76-1764.28), and 16.66 (95% CI 2.07-133.81), respectively. Conclusions: The presence of avascular areas in capillaroscopy, elevation of HAQ-DI score and anti-Scl-70 antibodies were independent factors associated with DUs in patients with SSc.

Treatment of digital ulcers in systemic sclerosis: Case series study of thirteen patients and discussion on outcome / Tratamento de úlceras digitais na esclerose sistêmica: série de casos de 13 doentes e análise crítica dos resultados

Summary Introduction: In systemic sclerosis (SSc), digital ulcers (DU) are debilitating and recurrent. They are markers of prognosis and are associated with disability and mortality. Treatment strategies have been developed to block the proposed mechanisms of this complication. Objective: Clinical description of a population of SSc patients with DU, treatment, complications and outcome. Method: Analysis of 48 SSc patients meeting 2013 ACR-EULAR criteria, followed between 1999-2015; 13 patients had DU. Treatment protocol applied included cycles of 21 days of alprostadil, which can be repeated in the absence of DU healing. After DU healing, bosentan was initiated. Results: DU healing was achieved with intravenous prostanoid in 12 patients; seven patients required repeated treatment for DU healing. Twelve patients were later treated with bosentan; three of them experienced recurrence of DU, while one was anti-B2-GPI positive. Four patients had soft tissue loss and three other suffered digital amputation, these being late diagnosis. Conclusion: Younger patients and early referrals had better outcomes. Endothelin receptor antagonist toxicity should be monitored, particularly in patients previously exposed to hepatotoxic drugs.

Resumo Introdução: As úlceras digitais (UD) são complicações incapacitantes e recorrentes, associadas a menor qualidade de vida e maior mortalidade na esclerose sistêmica (ES). O tratamento baseia-se em antagonizar os mecanismos fisiopatológicos em causa. Objetivo: Descrever uma amostra de doentes com diagnóstico de ES e UD, o tratamento, as complicações e os resultados clínicos. Método: Série de 48 casos diagnosticados com ES, critérios de classificação ACR-EULAR 2013, seguidos entre 1999 e 2015, dos quais 13 apresentavam UD. O protocolo aplicado incluía ciclos de 21 dias de alprostadil podendo ser repetidos no caso de não existir cicatrização. Nos casos em que houve cicatrização foi iniciado bosentano. Resultados: No tratamento das UD, 12 doentes realizaram prostaciclina endovenosa, com necessidade de tratamentos repetidos em sete doentes. Doze doentes foram posteriormente tratados com bosentano, com recorrência de UD em três doentes, um deles com presença de anti-B2-GPI. Quatro doentes ficaram com cicatrizes e em três houve amputação digital, sendo casos de diagnóstico tardio. Conclusão: Os doentes mais jovens tiveram melhores resultados, possivelmente em razão de melhorias globais nos cuidados de saúde prestados e de referenciação precoce. A toxicidade dos antagonistas dos receptores da endotelina deve ser monitorizada, sobretudo em doentes com exposição prévia a drogas hepatotóxicas.

Frecuencia de úlceras digitales en esclerodermia / Digital ulcers frequency in scleroderma

Nuestro objetivo fue describir la frecuencia de úlceras digitales en una población de pacientes con Esclerosis Sistémica y comparar las características clínicas de los que desarrollaron úlceras de los que no lo hicieron. Se incluyeron en forma retrospectiva pacientes que cumplían criterios ACR para Esclerosis Sistémica. Se recolectaron datos demográficos, clínicos y serológicos de las historias clínicas. Se clasificó a los pacientes en dos grupos: un Grupo A con úlceras digitales y Grupo B aquellos pacientes sin antecedentes de úlceras digitales. Se compararon ambos grupos. Se estudiaron 60 pacientes con diagnóstico de Esclerosis Sistémica, 33% subtipo difuso, edad promedio al diagnóstico de 50,75 ± 14,75 años, el 15% (9 pacientes) eran de sexo masculino. La frecuencia de úlceras digitales fue de 33,33% (n=20). Los pacientes del grupo A eran más jóvenes al momento del diagnóstico (p=0,03) y tenían más tiempo de evolución de la enfermedad (pNS). En este grupo, fue más frecuente la forma difusa (p=0,002) y el fenómeno de Raynaud se inició a edades más precoces (p=0,006). Los pacientes del grupo A presentaron menor capacidad funcional, medida por HAQ score, y mayor frecuencia de patente tardía en la capilaroscopia, aunque no fue estadísticamente significativo. La totalidad de los pacientes de género masculino (n=9) tuvieron úlceras digitales (p <0,0001).Conclusión: El desarrollo de úlceras digitales en nuestro estudio se asoció a inicio más precoz de la enfermedad, a sexo masculino, a la forma difusa y a inicio más temprano de fenómeno de Raynaud.

The aim of this study was to describe digital ulcer frequency ina patient population with Systemic Sclerosis and to compare theclinical features of those who developed ulcers with those who didnot. Retrospectively, patients meeting ACR criteria for SystemicSclerosis were included. Demographic, clinical, and serologicalinformation was obtained from medical records. Patients wereclassified into two groups: Group A comprised patients with digitalulcers, while Group B included patients with no digital ulcers ontheir records. Findings for both groups were compared. We studied60 patients diagnosed with Systemic Sclerosis, 33% with diffusecutaneous subset, the mean age at the time of diagnosis was 50.75± 14.75 years, 15% (9 patients) were males. The frequency of digitalulcers was 33.33% (n=20). Group A patients were younger at thetime of diagnosis (p=0.03) and had longer time of evolution (pNS).The diffuse variant was more frequent in this group (p=0.002) andRaynaud’s phenomenon onset occurred at earlier ages (p=0.006).All male patients (n=9) entered into the study had digital ulcers (p<0.0001).Conclusions: In our study, development of digital ulcers wasassociated with an earlier onset of disease, males, diffuse subsetand an earlier onset of Raynaud’s phenomenon.

Esclerose sistêmica e fenômeno de Raynaud: manejo terapêutico / Systemic sclerosis and Raynaud's phenomenon: therapeutic management

O fenômeno de Raynaud (FRy) caracteriza- se por episódios reversíveis de vasoespasmos de extremidades, que ocorrem usualmente após estresse ou exposição ao frio. O FRy pode ser primário ou secundário a uma série de condições, principalmente a doenças do espectro da esclerose sistêmica (ES). Na ES o FRy costuma ser mais grave, e lesões isquêmicas de extremidades são frequentes. Nos últimos anos, avanços no estudo da fisiopatologia do FRy e da doença vascular na ES propiciaram o surgimento de novas opções terapêuticas para esta manifestação. Os bloqueadores de canal de cálcio devem ser utilizados como tratamento de primeira escolha para o FRy. Novas drogas, como os inibidores da fosfodiesterase V e os prostanoides, podem ser utilizadas em pacientes com FRy grave, e a bosentana (antagonista do receptor da endotelina-1) é indicada para a prevenção de úlceras digitais recorrentes.

Raynaud?s phenomenon (RP) is characterized by episodic vasospasm of the extremities, usually in response to stress or cold exposure. It can be primary or secondary to several conditions, especially systemic sclerosis-related diseases. In systemic sclerosis (SSc), RP is usually more severe and digital ischemic lesions are a frequent problem. In recent years, advances in the understanding of the pathophysiology of RP and of SSc vasculopathy led to the development of new therapeutic options for this condition. Calcium-channel blockers are the first choice for the treatment of RP. New drugs, including phosphodiesterase type V inhibitors and prostanoids, can be used for severe RP, and bosentan (endothelin-1 receptor antagonist) for prevention of recurrent digital ulcers.

Esclerose sistêmica e o fenômeno de Raynaud: manejo terapêutico / Systemic sclerosis and Raynaud's phenomenon: therapeutic management

O fenômeno de Raynaud (FRy) caracteriza-se por episódios reversíveis de vasoespasmos de extremidades, que ocorrem usualmente após estresse ou exposição ao frio. O FRy pode ser primário ou secundário a uma série de condições, principalmente a doenças do espectro da esclerose sistêmica (ES). Na ES, o FRy costuma ser mais grave, e lesões isquêmicas de extremidades são frequentes. Nos últimos anos, avanços no estudo da fisiopatologia do FRy e da doença vascular na ES propiciaram o surgimento de novas opções terapêuticas para esta manifestação. Os bloqueadores de canal de cálcio devem ser utilizados como tratamento de primeira escolha para o FRy. Novas drogas, como os inibidores da fosfodiesterase V e os prostanoides, podem ser utilizados em pacientes com FRy grave, e a bosentana (antagonista do receptor da endotelina-1) é indicada para a prevenção de úlceras digitais recorrentes.

Raynaud's phenomenon (RP) is characterized by episodic vasospasm of the extremities, usually in response to stress or cold exposure. It can be primary or secondary to several conditions, especially systemic sclerosis-related diseases. In systemic sclerosis (SSc), RP is usually more severe and digital ischemic lesions are a frequent problem. In recent years, advances in the understanding of the pathophysiology of RP and of SSc vasculopathy led to the development of new therapeutic options for this condition. Calcium-channel blockers are the first choice for the treatment of RP. New drugs including phosphodiesterase type V inhibitors and prostanoids can be used for severe RP, and bosentan (endothelin-1 receptor antagonist) for prevention of recurrent digital ulcers.