Neutrophilic leukocytosis and erythema nodosum leprosum in leprosy: insights from a retrospective observational study.

Background: Leprosy reactions represent immunologically mediated episodes of acute inflammation that, if not diagnosed and treated promptly, can cause irreversible impairment of nerve function and permanent disabilities. A frequent type of reaction experienced by patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL) is erythema nodosum leprosum (ENL), an inflammatory complication that may become chronic or recur in multiple episodes. Although ENL is commonly described as a neutrophil-mediated immune disease, the role of neutrophils is not fully understood. In this study, we assess neutrophilic leukocytosis in a retrospective cohort of patients affected by BL or LL leprosy. Materials and methods: A retrospective observational study was performed using data from 146 patients with BL and LL leprosy diagnosed and treated at the Souza Araújo Outpatient Clinic, Fiocruz, Rio de Janeiro, Brazil. Clinical, demographic, and hematological data were extracted from medical records. Skin biopsy samples obtained from patients for ENL diagnosis were used for histopathological evaluations. Results: Most patients were male (75%) and had a reactional episode (85%), of which 65% were ENL. Multiple episodes were common, 55% of the 80 patients with ENL presented more than 2 episodes (average of 2.6 episodes). In treatment-naive BL/LL patients, the median blood neutrophil counts of patients who developed ENL at some points of their disease course were higher than those who did not experience any reaction (median= 4,567 cells/mm3 vs 3,731 cells/mm3 respectively, p=0.0286). A correlation between the increase in median neutrophil counts and ENL severity was confirmed (6,066 cells/mm3 for mild ENL vs 10,243 cells/mm3 for moderate/severe ENL, p=0.0009). A longitudinal assessment was also performed in 34 patients, confirming the neutrophilic leukocytosis (BL/LL: 4896 cells/mm3 vs ENL: 8408 cells/mm3, p<0.0001). Moreover, increased NLR was associated with a greater neutrophilic infiltration in ENL lesions. Conclusion: We demonstrate that ENL episodes in patients affected by leprosy are associated with elevated blood leukocyte and neutrophil counts and an increased NLR. These findings highlight the significant involvement of neutrophils in the ENL immunological/inflammatory process.

The causal relationship between inflammatory bowel diseases and erythema nodosum: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) exhibit a heightened likelihood of developing erythema nodosum (EN), but the presence of causal link is unknown. The purpose of the present research was to investigate this connection using a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Summarized statistics for EN were sourced from the FinnGen consortium of European ancestry. The International Inflammatory Bowel Disease Genetic Consortium (IBDGC) was used to extract summary data for IBD. The inverse variance weighted (IVW) technique was the major method used to determine the causative link between them. RESULTS: The study evaluated the reciprocal causal link between IBD and EN. The IVW technique confirmed a positive causal link between IBD and EN (OR = 1.237, 95% CI: 1.109-1.37, p = 1.43 × 10- 8), as well as a strong causality connection between Crohn's disease (CD) and EN (OR = 1.248, 95% CI: 1.156-1.348, p = 1.00 × 10- 4). Nevertheless, a causal connection between ulcerative colitis (UC) and EN could not be established by the data. The reverse MR research findings indicated that analysis indicated that an increase in EN risks decreased the likelihood of UC (OR = 0.927, 95% CI: 0.861-0.997, p = 0.041), but the causal association of EN to IBD and CD could not be established. CONCLUSION: This investigation confirmed that IBD and CD had a causal connection with EN, whereas UC did not. In addition, EN may decrease the likelihood of UC. Further study must be performed to uncover the underlying pathophysiological mechanisms producing that connection.

Erythema nodosum as an unusual skin manifestation of long COVID: A case report.

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.

Erythema nodosum in northern Finland between 1996 and 2019: A register-based study.

Erythema nodosum (EN) is seen at any age with varying and often unidentified etiology. We studied the etiology and characteristics of EN in Northern Finland. Medical records of all patients with a diagnosis code for EN between 1996 and 2019 from Oulu University Hospital were retrieved and analyzed. There were in total 142 EN cases with a female predominance (n = 112, 72.9%). The mean age of the patients was 35.9 years. There were five cases diagnosed with EN in those younger than 2 years of age. Almost one third had EN nodules in multiple anatomical locations. In addition to skin findings, systemic symptoms were common (81.0%), and seen more often in men (p < 0.05). In children and adolescents, the most common etiological factors were gastroenteritis caused by 'Yersinia, Salmonella or Campylobacter', followed by inflammatory bowel diseases and hormonal contraception. Bacterial infections were the most common etiological factor among adults. In 28.2% of the cases there was no identified causative factor. In this study, EN was seen surprisingly often in small children. Etiological factors varied markedly among different age groups and symptoms differed between the sexes in adults. These aspects should be taken into account when diagnosing EN patients.

Successful treatment of erythema nodosum with salazosulfapyridine in a 9-year-old patient with chronic non-bacterial osteomyelitis.

We report a 9-year-old Japanese girl with chronic non-bacterial osteomyelitis (CNO) accompanied by recurrent erythema nodosum (EN) which was successfully treated with salazosulfapyridine (SASP). She was referred to our hospital because of recurrent erythema on her lower extremities and persistent knee and ankle arthralgia, which had been present for approximately 1 year. Although naproxen, a nonsteroidal anti-inflammatory drug, was initiated, her symptoms frequently recurred. Magnetic resonance imaging demonstrated multiple distinct high-intensity signals in the talus bones suggestive of multiple bone oedemas. Additionally, a histological examination of erythematous lesions was consistent with the histopathological findings of EN. She was diagnosed as having CNO complicated by EN, and received 250 mg/day of SASP as a second-line treatment, which showed partial response of both skin and bone lesions. Following increase in the dose of SASP to 500 mg/day resulted in complete remission of her skin and bone lesions. In conclusion, our findings suggest that SASP is effective not only for CNO bone lesions but also for EN. SASP could serve as a second-line therapeutic option at least for some cases of CNO complicated by EN refractory to nonsteroidal anti-inflammatory drugs.

Eritema nodoso: Causas más prevalentes en pacientes que se hospitalizan para estudio, y recomendaciones para el diagnóstico / Erythema nodosum: Analysis of 91 hospitalized patients

Background: Erythema Nodosum (EN) is an acute nodular erythematous cutaneous eruption. It is presumed to be a hypersensitivity reaction and it may be idiopathic, or occur in association with diverse diseases and medications. Aim: To identify the main etiologies of EN among patients admitted to a medicine service of a clinical hospital. Material and Methods: Analysis of medical records of patients discharged with the diagnosis of EN during a ten years period. Patients were considered to have secondary EN when an underlying condition was found, and to have idiopathic EN when no such condition was found. Results: One hundred twenty nine patients were identified, but 91, aged 38 ± 14 years (86% females) had available clinical information. The etiology was idiopathic in 32% and secondary in 68% of patients. The leading etiologies were post-Streptococcal in 32%, followed by sarcoidosis in 11%, primary tuberculosis in 7%, Mycoplasma infection in 3%, Bartonella infection in 3%, Behçet’s syndrome in 2%, inflammatory bowel disease in 2%, drugs in 1% and other etiologies in 8%. Secondary cases of EN had higher levels of C Reactive Protein and leucocytes than idiopathic cases. Conclusions: The distribution of causes in our study population were similar to those reported in the literature (With smaller proportion of idiopathic), as was the man/woman (1/6) ratio, and the preponderance of cases in winter and spring. Infectious diseases were the leading causes of EN in this group of patients, and a reasonable initial approach in the hospital should include a diligent medical history and physical examination, complete blood count, ESR, titles ASO, PPD tuberculin skin test, chest X-ray or CT scan and, where deemed appropriate, specific autoimmune and infectious serology.

Reacciones por lepra en un centro de referencia nacional en Colombia / Leprosy reactions in a Colombian national reference centre

Introducción. Colombia es el país de América con mayor proporción de casos nuevos de lepra con discapacidad grave. Para disminuir tal discapacidad se requiere el control de las reacciones, principal causa del daño neural en esta enfermedad. Objetivo. Describir las características clínicas y epidemiológicas y el tratamiento de los pacientes con reacciones de tipo 1 y 2 que consultaron al Centro Dermatológico Federico Lleras Acosta. Materiales y métodos. Se trata de un estudio descriptivo que incluyó la población de pacientes con diagnóstico clínico de reacciones de tipo 1 y de tipo 2 por lepra, que acudieron al centro entre los años 2003 y 2009. Resultados. Se estudiaron 96 reacciones, 35 del tipo 1 y 61 del tipo 2. El 75 % de los pacientes provenía de los departamentos de Tolima, Cundinamarca, Santander y Boyacá. El 56 % de las reacciones de tipo 1 se presentaron antes de iniciar la poliquimioterapia para la lepra; el dermatólogo tratante consideró que las reacciones que se presentaron después de suspender la poliquimioterapia eran recaídas. El 94 % de las reacciones de tipo 1 se trataron con corticoides orales. El 97 % de los pacientes con reacciones de tipo 2 presentaron eritema nudoso, y todos se trataron con talidomida. Conclusiones.La clínica de la reacción de tipo 1 puede orientar al diagnóstico de la lepra en un paciente sin el antecedente de esta enfermedad (56 %). La reacción de tipo 1 que se inicia después de suspender la poliquimioterapia para la lepra, podría ser una manifestación de recaída de la enfermedad. La reacción de tipo 2 es más frecuente en hombres, con una relación hombre a mujer de 4:1. El 97 % de los pacientes con reacción de tipo 2 presentó eritema nudoso.

Introduction: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. Objective: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. Materials and methods: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. Results: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. Conclusions: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

La lepra y el testículo / Leprosy and the testis

Introducción. La afección testicular es frecuente en la lepra lepromatosa, daño que se incrementa cuando cursa con eritema nudoso leproso. Objetivo. Presentar un paciente con lepra lepromatosa y eritema nudoso leproso con grave compromiso testicular. Materiales y métodos. Se estudió un hombre de 28 años con lepra lepromatosa desde los 22, que durante la poliquimioterapia para la lepra presentó eritema nudoso leproso crónico que afectó ambos testículos y no respondió al manejo convencional. El dolor persistente obligó a practicar orquidectomía izquierda. Resultados. Este testículo presentaba atrofia tubular y fibrosis notorias, conglomerados de macrófagos espumosos, sin bacilos, hiperplasia focal de células de Leydig, endarteritis y arteritis linfocitaria y granulomatosa de vasos pequeños y medianos; estos cambios también estaban presentes en el epidídimo. Un estudio llevado a cabo dos años después de terminar su tratamiento y de la orquidectomía izquierda, demostró azoospermia, testosterona total normal, testosterona libre discretamente disminuida y hormonas lutropina (luteinizante) y folitropina (estimulante del folículo) elevadas. No había disminución de la libido ni de su actividad sexual. Se revisaron los conceptos generales sobre el eritema nudoso leproso y las alteraciones que la lepra produce en el testículo. Conclusión. La lepra lepromatosa puede conducir a hipogonadismo. Los programas de lepra deben contemplar esta complicación para corregir y evitar sus secuelas.

Introduction. Damage of testicles is frequent in lepromatous leprosy and worsened by the presence of erythema nodosum leprosum. Objective. A patient is presented who developed lepromatous leprosy and erythema nodosum leprosum with major testicular compromise. Material and methods. The 28-year-old male patient had lepromatous leprosy since age 22. During a polychemotherapy treatment for the lepromatous leprosy, he presented chronic erythema nodosum leprosum that affected both testicles; he did not respond to the conventional treatment. A left orchidectomy was performed to treat the persistent pain. Results. The extracted testis evidenced the following: tubular atrophy, extensive fibrosis, cumulus of foamy macrophages without rods, focal Leydig cell hyperplasia, linfocitary and granulomatous arteritis and endarteritis of small and medium size vessels. These changes were also observed in the epididymis. Two years after the polychemoterapy and the orchidectomy, the patient exhibited azoospermy, normal total testosterone, slightly diminished free testosterone and elevated levels of luteinizing hormone and follicle-stimulating hormone. No loss of libido or sexual activity was reported. General concepts of erythema nodosum leprosum were reviewed, as well as the pathologic changes produced by leprosy in the testis. Conclusion. Lepromatous leprosy may lead to hypogonadism. This condition is recommended for inclusion in leprosy diagnostic programs in order to detect and treat the consequences of the possible hypogonadism.

Eritema nodoso / Erythema Nodosum

Os autores fazem uma revisão bibliográfica sobre eritema nodoso, incluindo suas diversas causas, manifestações clínicas, investigação e diagnósticos diferenciais. É enfatizada que eritema nodoso pode ser a manifestação cutânea de uma doença sistêmica, logo, essa situação deve ser afastada

Lepra urbana: un llamado de atención / Urban leprosy: call for attention

Se presenta una paciente de sexo femenino de 16 años de edad, oriunda de Capital Federal y residente en esta ciudad desde su nacimiento, que consulta por la presencia de nódulos eritemato-violáceos localizados principalmente en cara anterior de piernas y muslos, sin otro compromiso cutáneo, de mucosas o faneras. El diagnóstico final fue de lepra lepromatosa en reacción: eritenma nudoso leproso (ENL). La paciente tenía 2 tíos, un primo y una abuela, todos residentes en Capital Federal, afectados de lepra. Con este motivo, se discute un nuevo fenómeno epidemiológico que es la Lepra Urbana y la importancia de su consideración en el diagnóstico y tratamiento precoz de la enfermedad, sin esperar la presencia de estigmas crónicos

Reactional states in multibacillary Hansen disease patients during multidrug therapy

Reacoes sao ocorrencias comuns no curso da hanseniase e sao responsaveis pelo agravamento das lesoes neurais. Uma coorte de 162 pacientes recem-diagnosticados, baciloscopicamente positivos, em acompanhamento no Ambulatorio de Hanseniase da Fundacao Oswaldo Cruz (FIOCRUZ) foi selecionada para estudo. Observou-se que 46 por cento dos pacientes multibacilares submetidos a 24 doses fixas de poliquimioterapia (PQT) apresentaram reacoes durante o tratamento; todos multibacilares eram suscetiveis e cuidados e atencao constantes eram necessarios. Quatorze por cento foram classificados como BB, 52 por cento como BL e 33 por cento foram classificados como LL. Nenhuma das variaveis em estudo, tais como: sexo, idade, forma clinica, tempo de doenca, extensao das lesoes dermatologicas, indice baciloscopico (IB), ou grau de incapacidade associaram-se a reacao entre os pacientes estudados...

Eritema nodoso / Erythema nodosum

Eritema nodoso é uma síndrome de hipersensibilidade do grupo das paniculites, caracterizada por nódulos eritematosos dolorosos que aparecem mais freqüentemente na superfície extensora das pernas. A doença pode ser associada a vários agentes infecciosos, não-infecciosos e a drogas. Neste artigo revisamos os principais aspectos relacionados ao eritema nodoso, destacando os agentes etiológicos, achados clínicos e laboratoriais, diagnósticos diferenciais e tratamento.

Erythema nodosum is a hypersensitivity syndrome of panniculitis group, characterized by painfull erythematous nodules thar appear most commonly on the extensor surfaces of the legs. The disease may be associated with many infeccious of not infeccious agents and drugs. In the article, we rewiew the mainly aspects related to the erythema nodosum, such as clinical and laboratory findings, differential diagnosis and treatment.

Eritema nodoso: estudio prospectivo de su etiología en treinta y ocho pacientes / Erythema nodosum: prospective study of its etiology in 38 patients

Objetivo del trabajo: Hallar la etiología del EN en los pacientes de nuestra institución y determinar si existen caracteres clínicos o exámenes complementarios sugestivos de esas etiologías. Material y métodos: Entre abril de 1988 y abril de 1995 se estudiaron en forma prospectiva 38 pacientes con EN. Todos fueron examinados mediante una matriz de datos clínicos única y a todos se les solicitó los mismos estudios de laboratorio. En 34 pacientes se obtuvo una biopsia de piel. Se definieron previamente los criterios diagnósticos que permitieran establecer luego la etiología del EN (estreptocócico, medicamentoso, tuberculoso, etc). Resultados: La etiología pudo ser determinada en el 69 por ciento de los pacientes. En 18 casos EN estreptocócico, en 4 casos coincidió con medicamentos, en 3 casos fue atribuido al embarazo, en otros 3 a TBC (2 casos de adenitis TBC y uno asociado a tuberculide papulonecrótica) y en un caso se diagnosticó una enfermedad de Hodgkin. En una paciente, el EN se asoció a síndrome de Sweet y en otra a necrobiosis lipoídica

Eritema nodoso / Erythema nodosum

El eritema nodoso es una afección relativamente frecuente de carácter reactivo frente a diversos factores etiológicos. Su cuadro clínico es generalmente característico aunque ocasionalmente atípico. Se manifiesta por nódulos inflamatorios, eritematosos y dolorosos de las extremidades inferiores, acompañados de fiebre y artralgias. La afección plantea básicamente los siguientes problemas: diferenciación de otros cuadros capaces de producir nódulos de las extremidades, precisión de su posible etiología, lo que en un elevado porcentaje de casos no es posible y prescripción de un tratamiento sintomático que acorte la evolución y evite las recurrencias

Acné fulminans, eritema nodoso y complejos inmunes circulantes postratamiento con isotretinoína / Acne fulminans, erythema nodosum and C.I.C. after isotretinoin treatment

La isotretinoína es una droga efectiva para el tratamiento del acné. Su uso puede acompañarse de diversas reacciones adversas, tales como queilitis, xerodermia, epistaxis, prurito, trastornos oculares y cefalea. Presentamos un paciente de 17 años que desarrolló acné fulminans, eritema nodoso y complejos inmunes circulantes, diez días después de haber comenzado el tratamiento con isotretinoína. Se discuten los aspectos etiopatogénicos del acné fulminans

Eritema nudoso asociado a fibrosis quística del páncreas / Erithema nodosum associated with pancreatic cystic fibrosis

Presentamos el caso de una paciente de 11 años de edad, con fibrosis quística del páncreas y eritema nudoso, cuya causa desencadenante fue la colonización por staphylococcus aureus del árbol bronquial. La vasculitis leucocitoclásica y la dermatitis semejante a acrodermatitis enteropática son las manifestaciones dermatológicas descritas asociadas a la fibrosis quística. Realizamos la revisión bibliográfica de las causas desencadenantes de eritema nudoso relatadas en la literatura en los últimos años

Eritema nodoso na criança: relato de quatro casos / Erythema nodosum in children: report of four cases

Foram estudadas quatro crianças com diagnóstico clínico e histopatológico de eritema nodoso. Como fatores citológicos: tuberculose pulmonar (um caso), infecçåo estreptocócica (um caso), Dipirona (um caso); em um caso nåo se detectou a etiologia. Destacam-se a ausência de publicaçöes em nosso meioe o interesse do eritema nodoso no diagnóstico de doenças gerais associadas

Alguns aspectos clínicos da reaçäo tipo II em pacientes hansenianos submetidos à poliquimioterapia / Some clinical aspects of type II reaction in hansenian patients submitted to polychemotherapy

Os autores estudaram os aspectos clínicos do Erythema Nodosum Leprosum (ENL) em 51 pacientes lepromatosos com relaçäo à idade, sexo, IB e regime quimioterápico. Três grupos diferentes foram identificados de acordo com a intensidade dos sintomas clínicos observados durante o ENL. Oito pacientes classificados no grupo III apresentam eritema multiforme como lesöes associadas às lesöes típicas do ENL indicando que este tipo de alteraçöes näo säo raras na reaçäo tipo II. Em sessenta por cento dos pacientes observou-se mais de um episódio reacional sugerindo que um tratamento mais eficaz ou prolongado seria necessário para evitar o ENL. A talidomida foi excluída apenas dos casos em que näo era indicada a sua utilizaçäo. Nestes pacientes o corticóide foi adotado. Näo houve correlaçäo entre a observaçäo de incapacidade e os grupos clínicos. Um longo período de acompanhamento ajudaria a esclarecer alguns pontos obscuros da evoluçäo dos pacientes com diferentes graus de ENL