Leprosy with type 1 reaction in a patient from Ontario, Canada without recent travel misdiagnosed as vasculitic neuropathy: a case report.

BACKGROUND: Leprosy is rare within non-endemic countries such as Canada, where cases are almost exclusively imported from endemic regions, often presenting after an incubation period of as many as 20 years. Due to its rarity and prolonged incubation period, diagnosis is often delayed, which may result in neurologic impairment prior to the initiation of treatment. In this report we describe a case that is novel in its incubation period, which is the longest reported to-date and may have contributed to diagnostic delay. The case also uniquely demonstrates the challenges of distinguishing leprosy reactions from new rheumatologic manifestations in a patient with established autoimmune disease. CASE PRESENTATION: We describe an 84-year-old male patient with rheumatoid arthritis on methotrexate and hydroxychloroquine, with no travel history outside Canada for 56 years, who presented in 2019 with new-onset paresthesias and rash. His paresthesias persisted despite a short course of prednisone, and his rash recurred after initial improvement. He underwent skin biopsy in May 2021, which eventually led to the diagnosis of leprosy. He was diagnosed with type 1 reaction and was started on rifampin, dapsone, clofazimine and prednisone, with which his rash resolved but his neurologic impairment remained. CONCLUSION: This case report serves to highlight the potential for leprosy to present after markedly prolonged incubation periods. This is especially relevant in non-endemic countries that is home to an aging demographic of individuals who migrated decades ago from endemic countries. The importance of this concept is emphasized by the persistent neurologic impairment suffered by our case due to untreated type 1 reaction. We also demonstrate the necessity of skin biopsy in distinguishing this diagnosis from other autoimmune mimics in a patient with known autoimmune disease.

Phytochemical analysis, anti-inflammatory, antioxidant activity of Calotropis gigantea and its therapeutic applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal remedies can be used to treat a variety of chronic inflammatory illnesses, like rheumatoid arthritis and leprosy. The plant Calotropis gigantea (C. gigantea) belongs to the family Apocynaceae. To treat numerous contagious diseases, C. gigantea is utilized alone or combine with certain medicinal herbs. Traditional Asian and African practitioners employed C. gigantea to treat a variety of inflammatory conditions like boils, rheumatoid arthritis, gout, leprosy and other disorders. AIM OF THE STUDY: The goal of this study is to examine the anti-inflammatory and antioxidant activities of C. gigantea leaf extracts extracted using methanol, petroleum ether, and water. MATERIALS AND METHODS: The leaf extracts of C. gigantea were obtained using the Soxhlet extraction technique. The phytoconstituents present in all three C. gigantea leaf extracts were confirmed by qualitative analysis, and the amounts of the alkaloids, flavonoids, terpenoids and phenols found in the extracts were quantified. C. gigantea crude extracts were subjected to a nitric oxide scavenging experiment to assess their free radical scavenging activities. Protein denaturation and proteinase inhibition assays were used to investigate the effectiveness of extracts to restrict denaturation of protein and to inhibit key enzymes responsible for tissue damage. Further, the membrane stabilization efficacy of plant extracts were examined by the heat-induced hemolysis method. The DPPH and FRAP experiments were performed to determine the antioxidant effectiveness of phytoconstituents extracted using different solvents. The GC-MS study of plant C. gigantea methanolic, aqueous and petroleum ether extracts displayed a broad range of compounds that possess beneficial therapeutic effects. RESULTS: This study reveals that the methanolic extract of C. gigantea provides significantly more anti-inflammatory and antioxidant activity than other extracts. CONCLUSION: Compared to the aqueous and petroleum ether extracts, the methanolic leaf extract of C. gigantea demonstrated greater in vitro anti-inflammatory and antioxidant properties.

Infectious mimics of rheumatoid arthritis.

Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.

Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

Hansen's Disease and Rheumatoid Arthritis Crossover of Clinical Symptoms: A Case Series of 18 Patients in the United States.

Hansen's Disease (HD) is a rare, chronic granulomatous infection of the skin and peripheral nerves caused by the noncultivable organism Mycobacterium leprae. Arthritis is the third most common symptom of HD. Subjects with both confirmed HD on skin biopsy and chronic arthritis were identified at the National Hansen's Disease Program (NHDP). We conducted a series of medical chart reviews and extracted and logged personally deidentified data into a database and carried out descriptive analyses. Eighteen of 261 subjects presented to the NDHP with both HD and chronic arthritis between 2001 and 2015. Among these, 16 were male, 16 were white, and 15 were residents of Louisiana. The median age at diagnosis of HD was 67 years. Ten of these subjects were diagnosed with borderline lepromatous leprosy, seven were diagnosed with lepromatous, and one was diagnosed with borderline tuberculoid leprosy. Patients were symptomatic with arthritis for a median of 5.3 years before HD diagnosis. Sixty-two percent of patients (11) were diagnosed with rheumatoid arthritis (RA) before HD diagnosis, and 10 of which were seronegative RA. Hands, feet, wrists, and elbows were most commonly reported as affected joints. Over half of the patients (61%) had completed HD multidrug therapy at the time of review, and 73% of these subjects had persistent joint pain requiring steroids or methotrexate for symptomatic control. Chronic arthritis in HD patients is present in a series of US-acquired cases of HD. Arthritis did not resolve with successful treatment of HD in most cases.

Longitudinal IP-10 Serum Levels Are Associated with the Course of Disease Activity and Remission in Patients with Rheumatoid Arthritis.

Although rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease, 10 to 15% of RA patients achieve sustained disease-modifying antirheumatic drug (DMARD)-free remission over time. The biological mechanisms underlying the resolution of persistent inflammation in RA are still unidentified, and there is a lack of prognostic markers. It is well established that increased serum levels of gamma interferon-induced protein 10 (IP-10) are associated with (acute) increased inflammatory responses (e.g., in leprosy). In order to assess the potential of IP-10 as a diagnostic tool for inflammatory episodes of RA, we performed a retrospective study and assessed IP-10 levels in longitudinally banked serum samples obtained from patients upon first diagnosis of RA. The selection consisted of 15 persistent RA patients and 19 patients who achieved DMARD-free sustained remission. IP-10 levels, measured by use of a user-friendly quantitative lateral flow assay (LFA), showed up to 170-fold variation interindividually, and baseline IP-10 levels could not be differentiated between the two patient groups. However, a difference in the change in IP-10 levels between the first and last visits (ΔIP-10) was observed (P = 0.003) between DMARD-free (median ΔIP-10, -662 pg/ml [decrease]) and persistent (median ΔIP-10, 468 pg/ml [increase]) RA patients. Moreover, intraindividual changes in IP-10 levels during the course of disease corresponded to the disease activity score (DAS) (P = 0.05). These data indicate that IP-10 is associated with disease activity and perseverance of RA. The association of IP-10 with DAS indicates that this tool may be a practical diagnostic aid to help in monitoring disease progression in RA patients and may also find applications in other chronic diseases with exacerbated inflammatory episodes.

Novel insight into drug repositioning: Methylthiouracil as a case in point.

Drug repositioning refers to the development of existing drugs for new indications. These drugs may have (I) failed to show efficacy in late stage clinical trials without safety issues; (II) stalled in the development for commercial reasons; (III) passed the point of patent expiry; or (IV) are being explored in new geographic markets. Over the past decade, pressure on the pharmaceutical industry caused by the 'innovation gap' owing to rising development costs and stagnant product output have become major reasons for the growing interest in drug repositioning. Companies that offer a variety of broad platforms for identifying new indications have emerged; some have been successful in building their own pipelines of candidates with reduced risks and timelines associated with further clinical development. The business models and platforms offered by these companies will be validated if they are able to generate positive proof-of-concept clinical data for their repositioned compounds. This review describes the strategy of biomarker-guided repositioning of chemotherapeutic drugs for inflammation therapy, considering the repositioning of methylthiouracil (MTU), an antithyroid drug, as a potential anti-inflammatory reagent.

Arthritis and diagnosis of leprosy: a case report and review of the literature.

Leprosy is clinically characterized by involvement of peripheral nerves and skin. The immunological profile of the individual defines the diversity of clinical manifestations, from skin disorders to systemic manifestations, especially the articulation ones, common in multibacillary forms, which may mimic collagen diseases and often posing diagnostic difficulties in endemic areas. This is a case report of asymmetric polyarthritis of small and large articulations associated with skin lesions which had been treated by a rheumatologist for 2 years with initial clinical diagnosis of rheumatoid arthritis, and later, with the appearance of skin lesions, of systemic lupus erythematosus.

Arthritis and diagnosis of leprosy: a case report and review of the literature

Leprosy is clinically characterized by involvement of peripheral nerves and skin. The immunological profile of the individual defines the diversity of clinical manifestations, from skin disorders to systemic manifestations, especially the articulation ones, common in multibacillary forms, which may mimic collagen diseases and often posing diagnostic difficulties in endemic areas. This is a case report of asymmetric polyarthritis of small and large articulations associated with skin lesions which had been treated by a rheumatologist for 2 years with initial clinical diagnosis of rheumatoid arthritis, and later, with the appearance of skin lesions, of systemic lupus erythematosus.

Biological agents: investigation into leprosy and other infectious diseases before indication.

Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil.

Biological agents: investigation into leprosy and other infectious diseases before indication / Agentes biologicos: pesquisa de hanseniase e outras doencas infecciosas antes da indicacao

Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil.

Os agentes biológicos são amplamente utilizados em diversas doenças imuno-mediadas, com marcante eficácia no tratamento da Artrite Reumatóide (AR), Psoríase, Artrite Psoriática, Espondilite Anquilosante e Doença de Crohn. No entanto, deve-se atentar quanto aos efeitos adversos de tais terapêuticas, como o risco de reativar doenças infecciosas granulomatosas latentes, como a tuberculose, hanseníase, sífilis, leishmaniose, entre outras. O objetivo deste artigo é descrever um caso de hanseníase em paciente portador de AR em uso de terapia anti-TNF alfa, mostrando, assim, a necessidade de investigação sistematizada de lesões cutâneas sugestivas de hanseníase em pacientes com indicação de terapia anti-TNF alfa, especialmente, em regiões endêmicas como o Brasil.

Leprosy and rheumatoid arthritis: consequence or association?

Leprosy or Hansen's disease is a chronic granulomatous infectious disease caused by Mycobacterium leprae with a high prevalence in some developing countries however, it is rarely seen in non-endemic regions. Arthritis has been described in all types of Hansen's disease. Chronic arthritis is known to exist even in paucibacillary forms, resolved or treated disease and in patients without reaction, suggesting a perpetuated inflammatory process. In these cases leprosy can mimic some autoimmune diseases such as rheumatoid arthritis. When a patient with a history of leprosy presents with a symmetric, distal, polyarthritis the diagnosis may not be linear. Possibly it is a rheumatoid-like leprous arthritis with M leprae acting as the trigger element for the chronic process or it is an overlap condition, with a concomitant rheumatoid arthritis? A case report of a patient with a chronic inflammatory arthritis with 10 years of evolution is presented. The differential diagnosis between leprous and rheumatoid arthritis is discussed.

Quantiferon-TB Gold in tube assay for the screening of tuberculosis before and during treatment with tumor necrosis factor alpha antagonists.

INTRODUCTION: The usefulness of interferon-gamma (IFN-γ) release assays for tuberculosis screening before tumor necrosis factor-alpha (TNF-α) antagonists and for monitoring during treatment is a contraversial issue. The aims of this study were to determine whether TNF-α antagonists affect the results of the Quantiferon-TB Gold in-tube assay (QTF); to assess how QTF performs in comparison with the tuberculin skin test (TST) in rheumatoid arthritis (RA) patients who are about to start treatment with TNF-α antagonists, RA patients who are not candidates for treatment with TNF-α antagonists, rheumatology patients with confirmed current or past tuberculosis infection, and healthy controls, and to determine the specificity of the QTF test to differentiate leprosy patients, another group of patients infected with mycobacteria. METHODS: The 38 RA patients who were prescribed TNF-α antagonists, 40 RA patients who were not considered for TNF-α antagonist use, 30 rheumatology patients with a history or new diagnosis of tuberculosis, 23 leprosy patients, and 41 healthy controls were studied. QTF and TST were done on the same day, and both were repeated after a mean of 3.6 ± 0.2 months in patients who used TNF-α antagonists. RESULTS: Treatment with TNF-α antagonists did not cause a significant change in the QTF or TST positivity rate (34% versus 42%; P = 0.64; and 24% versus 37%; P = 0.22). Patients with leprosy had a trend for a higher mean IFN-γ level (7.3 ± 8.0) and QTF positivity (61%) than did the other groups; however, the difference was not significant (P = 0.09 and P = 0.43). CONCLUSIONS: Treatment with TNF-α antagonists does not seem to affect the QTF test to an appreciable degree. The higher IFN-γ levels in leprosy patients deserves further attention.

Development of leprosy in a patient with rheumatoid arthritis during treatment with etanercept: a case report.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder. There is a clear association between some disease-modifying drugs used to treat RA and infection. The introduction of the anti-tumor necrosis factor (TNF) therapies has improved the outcome of severe RA. The TNF-antagonism may increase susceptibility to granulomatous pathogens such as Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum. METHODS: We report the case of a 37-year-old woman with RA receiving an anti-TNF agent, who developed a rash on her back and both legs, which was finally diagnosed as tuberculoid leprosy. RESULTS: This is the first case of leprosy due to anti-TNF therapy reported in Europe. CONCLUSIONS: Clinicians should be aware of this and other types of atypical and serious infections that patients may suffer from when treated with anti-TNF agents.