Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study.

INTRODUCTION: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. METHODS: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. RESULTS: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3-14) after stopping treatment. CONCLUSION: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence.

A case report of COVID-19-associated erythema nodosum: a classic presentation with a new trigger.

BACKGROUND: Over the course of the pandemic, cutaneous manifestations of SARS-CoV-2 infections have been increasingly characterized, yet only a few cases of erythema nodosum (EN) are reported in the literature and international registries. CASE PRESENTATION: In this report, we describe a case of tender, erythematous nodules that appeared acutely on the distal legs in a 48-year-old female with renal transplant following SARSs-CoV-2 infection complicated by prolonged fevers and pneumonia. The patient was diagnosed with a classic presentation of EN arising from a new and emerging trigger-COVID-19 infection. The cutaneous lesions resolved with conservative management. CONCLUSIONS: This report highlights the importance of clinician awareness of the potential association of COVID-19 with a classic clinical presentation of EN and underscores that these cases can be managed with the same therapeutic repertoire as EN due to other aetiologies. Of note, use of systemic agents was not employed in this case, as our patient improved with conservative therapy alone.

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE/PRAAS, SAVI, and AGS.

OBJECTIVE: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of "points to consider" to improve diagnosis, treatment, and long-term monitoring of patients with these rare diseases. METHODS: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates, and an allied health care professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires, and consensus methodology, "points to consider" to guide patient management were developed. RESULTS: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment, and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS. CONCLUSION: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment, and management of patients with CANDLE/PRAAS, SAVI, and AGS and aim to standardize and improve care, quality of life, and disease outcomes.

Understanding leprosy reactions and the impact on the lives of people affected: An exploration in two leprosy endemic countries.

BACKGROUND: Leprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions. METHODS/PRINCIPAL FINDINGS: This qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4-6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization. CONCLUSION: Leprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.

Erythema nodosum after COVID-19 vaccine.

The current coronavirus disease 2019 (COVID-19) pandemic is a global challenge with strong medical and socioeconomic implications. Hopes have been placed in the development of various vaccines. As the vaccination campaign is in progress, adverse effects need to be monitored closely. Possible side effects range from minor events to more serious manifestations. In this article, we describe two cases of erythema nodosum (EN) after COVID-19 vaccination in two previously healthy female patients of 59 and 51 years, respectively. Most of the usual etiologies of EN were excluded by laboratory testing. EN was successfully treated with corticosteroids. Remarkably, in the first case, a relapse occurred 48 hours after the second dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. In this case series, we describe two unusual occurrences of EN after vaccination with an mRNA COVID-19 vaccine and a viral vector vaccine, respectively, and we discuss the available related literature.

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.

OBJECTIVE: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. METHODS: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. RESULTS: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. CONCLUSION: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.

Erythema nodosum induced by Covid-19 Pfizer-BioNTech mRNA Vaccine (preprint)

Erythema nodosum (EN), the most form of panniculitis, is mainly caused by numerous infective (especially Beta-hemolytic streptococcal infections) and non-infective (especially sarcoidosis) diseases and drugs. EN associated with vaccines has been rarely reported. We describe herein, an original clinical observation of EN induced by BNT162b2, an mRNA vaccine. A 75-year-old woman presented with diffuse erythematous painful rounded nodular lesions, located symmetrically over her legs. Six days before, she had received the second dose of Covid-19 vaccine (BNT162b2 (Pfizer–BioNTech)), followed by a sudden asthenia, polyarthralgia, throbbing and edema over her lower limbs. She had been given the first dose of the same Covid-19 vaccine 29 days prior to the second without incident. General physical examination was normal. Skin examination showed multiple, erythematous tender, nodules, 10–30 mm in diameter, over the tibial area. Complete blood count, renal and hepatic tests, antistreptolysin O titer, antinuclear antibody, thyroid test and chest radiograph and PCR, were carried out, and found to be normal. Histopathology revealed infiltration of deep dermal vessels and subcutaneous fat with lymphomononuclear cells and neutrophils, consistent with erythema nodosum. Treatment with analgesics led to complete resolution of the lesion after three months. The patient has shown no relapse after follow-up for three months. In conclusion, to our knowledge, this is the first case of EN induced by the second dose of BNT162b2 (Pfizer–BioNTech) Covid-19 vaccine. It is important for clinicians to be aware of this rare, yet potential, adverse effect to this vaccine.

Case Report: Post SARS-CoV2 Infection Erythema Nodosum (preprint)

Background: Although, preliminary reports of Post SARS-CoV2 Infection Erythema Nodosum suggest it may be due to dysregulated immune response caused by coronavirus.Case presentation: The patient was a 9-year-old boy who referred to the pediatric Rheumatology clinic of Shiraz University of Medical Sciences due to bilateral painful erythematous nodules on his bilateral calves. He reported a history of fever from 4 days before his referral which was followed by erythema, warmth, stiffness, and swelling of his calves. The patient’s father had afflicted COVID-19 two months prior to the incidence. In his course of admission, COVID-19 serology tests were performed for him which was positive for SARS-CoV-2 IgG and negative for SARS-CoV-2 IgM.Conclusion: Another etiologic factor for EN might be coronaviruses such as SARS-CoV-2 which is important to be taken into consideration during the COVID-19 pandemic.

Erythema nodosum-like eruption in coronavirus disease 2019: A case report and literature review of Asian countries.

In the worldwide coronavirus disease 2019 (COVID-19) outbreak, skin manifestations were seen in COVID-19 patients. We report a case in which a COVID-19 patient developed cutaneous lesions that were diagnosed as erythema nodosum-like lesions, which were associated with COVID-19. Nasopharyngeal swab polymerase chain reaction (PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathologically, extensive inflammation was seen from the epidermis to the fat tissue. An organized thrombus and disrupted inner elastic lamina were seen in an intradermal vessel. These findings suggest septal panniculitis with cutaneous polyarteritis nodosa. The results of PCR using the specimen of skin lesion was negative. The patient took non-steroidal anti-inflammatory drugs and the skin lesion improved in 3 weeks. To characterize the skin eruption, we reviewed previous reports on COVID-19 (confirmed by the detection of SARS-CoV-2 infection) from Asian countries. The type of eruption and timing of its appearance in this case seemed rare. Differences in skin manifestations between Western and Asian countries were noted.

Severe type 2 leprosy reaction with COVID-19 with a favourable outcome despite continued use of corticosteroids and methotrexate and a hypothesis on the possible immunological consequences.

Type 2 leprosy reaction (T2LR), or Erythema Nodosum Leprosum (ENL), often poses a therapeutic challenge to clinicians and commonly requires long courses of steroids for control. While immunosuppressants are known to achieve control and lower steroid dependence in T2LR, the prospect of managing a severe T2LR in conjunction with COVID-19, with the concern of worsening COVID-19 with long-term immunosuppression has not previously been encountered. We report a case of severe T2LR treated with oral steroids and methotrexate, with COVID-19 infection acquired during hospital stay, and a favourable outcome achieved despite the continued use of immunosuppressants. We discuss the possible reasons for this both in terms of the drug pharmacodynamics and the immunological profile of T2LR.

COVID-19 in persons affected by Hansen's disease in Brazil (preprint)

BackgroundHansens disease (HD) is endemic in Brazil, a country with the third highest number of COVID-19 cases in the world and the second highest number of COVID-19 deaths. COVID-19 in persons affected by HD has not been described at population level in this country. MethodsWe collated numbers of COVID-19 cases and deaths among patients who were receiving routine treatment for HD at six centres across Brazil (Belem, Bauru, Brasilia, Vitoria, Petrolina, Palmas) between 1st March and 10th December 2020. ResultsOf 1,333 HD patients receiving treatment, 70 (5.2%) reported having had COVID-19. Almost all patients (97% (1,296/1,333)) including all but one of the COVID-19 cases were receiving MDT comprising rifampicin (600mg once per month), dapsone (100mg daily), and clofazimine (50 mg daily plus 300 mg once per month). Four patients died, including a patient in their 30s on MDT who had a severe type 2 HD reaction (erythema nodosum leprosum) and who was taking clofazimine 100mg daily. ConclusionsWe cannot determine from these preliminary data whether persons affected by Hansens disease have a higher or lower risk of COVID-19 and related mortality compared with the general population. We will continue to monitor the effects of COVID-19 in persons affected by and treated for HD and extend this to monitor SARS-CoV-2 vaccine effectiveness in this group of patients.