Leprosy mimicking autoimmune diseases: a case series.

OBJECTIVES: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Less frequently, there is involvement of the musculoskeletal system, and occurrence of systemic manifestation with non-specific symptoms such as fever, fatigue and myalgia. Therefore, leprosy can often mimic autoimmune diseases such as arthritis, vasculitis, or collagenosis and be mis-diagnosed. METHODS: This study describes a series of cases of leprosy mimicking autoimmune diseases in patients treated in the Rheumatology Department of our centre in the period 2019 to 2023. All patients were investigated regarding leprosy criteria and had clinical evaluation, serum markers, and histopathological analyses recorded. The diagnosis of leprosy was confirmed using skin biopsy followed by testing for acid-fast bacillus (AFB) or smear microscopy. RESULTS: Six patients who were initially investigated for autoimmune diseases were identified as diagnosed as leprosy cases, fulfilling both clinical and histopathologic criteria, two of whom presented with symptoms of polyarthritis with an inflammatory characteristic, two diffuse erythematous-violaceous lesions, three recurrent fever, three arthralgia, and one Raynaud's phenomenon, which are all characteristics present most frequently in rheumatologic diseases. CONCLUSIONS: We must consider the bacillary infection as a differential diagnosis of autoimmune diseases. Histopathological analysis is an important tool and the gold standard for diagnostic confirmation.

Post-Traumatic Hindfoot Arthritis.

The hindfoot is functionally defined as the articulations between the talus, calcaneus, navicular, and cuboid. It is a biomechanically important peritalar unit for shock absorption and propulsion with the subtalar and talonavicular joint essential to its function. The primary cause of hindfoot arthritis is post-traumatic. Other causes include long-term misalignment such as adult-acquired flatfoot, cavus foot, and inflammatory arthritis. Prevention of post-traumatic hindfoot arthritis is the primary objective. Anatomical reduction and fixation of articular hindfoot fractures is the preferred pathway. This article discusses the principles of treatment of hindfoot arthritis. When post-traumatic changes cannot be managed by nonsurgical means, an anatomical well-aligned arthrodesis is indicated. This article addresses the principles of managing this condition, which have been championed by Professor Sigvard T. Hansen. New approaches and techniques are discussed that achieve the goals of a stable, functional plantigrade foot.

Paciente con dermatitis y artritis durante sus embarazos / A patient with dermatitis and arthritis during her two pregnancies

Paciente femenina que presentó durante sus dos embarazos eritema nodoso, úlceras nasales y artritis. Debido a la persistencia del eritema nodoso después del segundo parto, se practicó determinación de ANA y anti-DNA ­ IF, resultando este último positivo, por lo que se plantea el diagnóstico de lupus eritematoso y es referida al Centro Nacional de Enfermedades Reumáticas, (CNER) donde se le practicó biopsia de piel que resultó compatible con lepra: borderline o dimorfa (BB-BL) en estado reaccional tipo II (eritema nodoso leproso: ENL). Se discuten algunos de aspectos de la lepra haciendo especial énfasis en síntomas que presentó la paciente y la exacerbación de los mismos durante los embarazos, posiblemente en relación con algunos cambios inmunológicos adaptativos que son generados para mantener la tolerancia materno fetal(AU)

Female young patient with erythema nodosum, nasal ulcers and arthritis during her two pregnancies. Due to the persistence of the erythema nodosum after the second delivery, ANA and anti-DNA - IF determination were done, the latter being positive, and she was diagnosed with lupus erythematosus and was referred to the National Center for Rheumatic Diseases, where skin biopsy showed to be compatible with leprosy: borderline or dimorphic (BB-BL) in type II reactional state (leprous erythema nodosum: LEN). Some aspects of leprosy are discussed with special emphasis on symptoms that the patient presented and their exacerbation during pregnancies, possibly in relation to some adaptive immunological changes that was generated to maintain maternal fetal tolerance(AU)

Triamcinolone acetonide-loaded PLA/PEG-PDL microparticles for effective intra-articular delivery: synthesis, optimization, in vitro and in vivo evaluation.

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co-polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [3] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL1700, which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications.

Leprosy presenting as remitting seronegative symmetrical synovitis with pitting oedema syndrome - a case report.

BACKGROUND: Leprosy typically manifests with skin and peripheral nerve involvement. Musculoskeletal complaints are the third most common, and can be the sole presenting manifestation. They range from arthralgia/arthritis in reactional states to full mimics of systemic rheumatic diseases. Remitting Seronegative Symmetrical Synovitis with Pitting Oedema syndrome has only been described once in a patient with already diagnosed Leprosy. CASE REPORT: A 68-year-old male, from an endemic region of familial amyloid polyneuropathy, presented with an inaugural Remitting Seronegative Symmetrical Synovitis with Pitting Oedema like syndrome, more that 20 years after travelling to Leprosy endemic areas. Arthritis would resurface whenever oral prednisone was tapered, so methotrexate was started, controlling the complaints. Only one year later, after the appearance of peripheral neuropathy and skin lesions, it was possible to diagnose Leprosy, through the identification of Mycobacterium leprae bacilli in a peripheral nerve biopsy. CONCLUSION: This report is an example of the heterogeneity of manifestations of Leprosy, namely rheumatic, and the challenge of diagnosing it when typical complaints are absent. It is also a reminder that this disease should be considered whenever a patient with a combination of skin/neurologic/rheumatic complaints has travelled to endemic countries in the past.

Rheumatology science and practice in India.

The practice of rheumatology in a country like India presents its own unique challenges, including the need to manage patients in a cost-constrained setting, where the lack of uniform government funding for healthcare merits the need to optimize the use of cheaper medicines, as well as devise innovative strategies to minimize the use of costlier drugs such as biologic disease-modifying agents. Use of immunosuppressive agents is also associated with increased risks of infectious complications, such as the reactivation of tuberculosis. In this narrative review, we provide a flavor of such challenges unique to Rheumatology practice in India, and review the published literature on the management of common rheumatic diseases from India. In addition, we critically review existing guidelines for the management of rheumatic diseases from this part of the world. We also discuss infectious etiologies of rheumatic complaints, such as leprosy, tuberculosis, and Chikungunya arthritis, which are often encountered here, and pose a diagnostic as well as therapeutic challenge for clinicians. There remains a need to identify and test more cost-effective strategies for Indian patients with rheumatic diseases, as well as the requirement for more government participation to enhance scant facilities for the treatment of such diseases as well as foster the development of healthcare services such as specialist nurses, occupational therapists and physiotherapists to enable better management of these conditions.

Leprosy manifesting with type 2 leprae reaction in a patient presenting with chronic fever: A case report.

Leprosy is a chronic granulomatous disease involving the skin and nerves, leading to a debilitating condition. Leprosy has been controlled in most parts of the world; therefore physicians are not very well versed in the recognition, management and assessment of this disease. The protean manifestations of leprosy often lead to delays in diagnosis and increase the morbidity. We present a case of a 33-year-old male with fever, lymphadenopathy, nodular skin lesions, uveitis and arthritis. Lymphnode, bonemarrow and skin biopsy revealed 3+ AFB smear with negative AFB cultures, leading to the diagnosis of leprosy. The course of illness was complicated by flare of Erythema Nodosum Leprosum (ENL).

Using genes to triangulate the pathophysiology of granulomatous autoinflammatory disease: NOD2, PLCG2 and LACC1.

The intersection of granulomatosis and autoinflammatory disease is a rare occurrence that can be generally subdivided into purely granulomatous phenotypes and disease spectra that are inclusive of granulomatous features. NOD2 (nucleotide-binding oligomerization domain-containing protein 2)-related disease, which includes Blau syndrome and early-onset sarcoidosis, is the prototypic example of granulomatous inflammation in the context of monogenic autoinflammation. Granulomatous inflammation has also been observed in two related autoinflammatory diseases caused by mutations in PLCG2 (phospholipase Cγ2). More recently, mutations in LACC1 (laccase domain-containing protein 1) have been identified as the cause of a monogenic form of systemic juvenile idiopathic arthritis, which does not itself manifest granulomatous inflammation, but the same LACC1 mutations have also been shown to cause an early-onset, familial form of a well-known granulomatous condition, Crohn's disease (CD). Rare genetic variants of PLCG2 have also been shown to cause a monogenic form of CD, and moreover common variants of all three of these genes have been implicated in polygenic forms of CD. Additionally, common variants of NOD2 and LACC1 have been implicated in susceptibility to leprosy, a granulomatous infection. Although no specific mechanistic link exists between these three genes, they form an intriguing web of susceptibility to both monogenic and polygenic autoinflammatory and granulomatous phenotypes.

Leprosy reactions in postelimination stage: the Bangladesh experience.

BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.

Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy / Manifestações musculoesqueléticas e autoanticorpos em crianças e adolescentes com hanseníase

Objective: To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. Methods: 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis, and myalgia), musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, and tendinitis), and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. Results: At least one musculoskeletal manifestation was observed in 14% of leprosy patients and in none of the controls. Five leprosy patients had asymmetric polyarthritis of small hands joints. Nerve function impairment was observed in 22% of leprosy patients, type 1 leprosy reaction in 18%, and silent neuropathy in 16%. None of the patients and controls presented musculoskeletal pain syndromes, and the frequencies of all antibodies and cyoglobulins were similar in both groups (p > 0.05). Further analysis of leprosy patients demonstrated that the frequencies of nerve function impairment, type 1 leprosy reaction, and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p = 0.0036, p = 0.0001, and p = 0.309, respectively), as well as multibacillary subtypes in leprosy (86% vs. 42%, p = 0.045). The median of physicians' visual analog scale (VAS), patients' VAS, pain VAS, and Childhood Health Assessment Questionnaire (CHAQ) were significantly higher in leprosy patients with musculoskeletal manifestations (p = 0.0001, p = 0.002, p = 0002, and p = 0.001, respectively). Conclusions: This was the first study to identify musculoskeletal manifestations associated with nerve dysfunction in pediatric leprosy patients. Hansen's disease should be included in the differential diagnosis of asymmetric arthritis, especially in endemic regions. .

Objetivo: Avaliar o envolvimento musculoesquelético e os autoanticorpos em pacientes pediátricos com hanseníase. Métodos: Foram avaliados 50 pacientes com hanseníase e 47 crianças e adolescentes saudáveis de acordo com manifestações musculoesqueléticas (artralgia, artrite e mialgia), síndromes dolorosas musculoesqueléticas (fibromialgia juvenil, síndrome de hipermobilidade articular benigna, síndrome miofascial e tendinite) e painel de autoanticorpos e crioglobulinas. Escores de avaliação de saúde e tratamento foram realizados nos pacientes com hanseníase. Resultados: Pelo menos uma manifestação musculoesquelética foi observada em 14% dos pacientes com hanseníase e em nenhum controle. Dentre os pacientes com hanseníase, cinco tinham poliartrite assimétrica das pequenas articulações das mãos. Comprometimento da função do nervo foi observado em 22% dos pacientes com hanseníase, reação tipo I hansênica em 18% e neuropatia silenciosa em 16%. Nenhum dos pacientes e controles apresentou síndromes de dor musculoesquelética e as frequências dos anticorpos e crioglobulinas foram semelhantes nos dois grupos (p > 0,05). Comprometimentos da função nervosa, reação hansênica tipo I e neuropatia silenciosa foram observados em pacientes com vs sem manifestações musculoesqueléticas (p = 0,0036, p = 0,0001 e p = 0,309, respectivamente), bem como subtipos de hanseníase multibacilar (86% vs 42%, p = 0,045). A escala visual analógica (EVA) do médico, dos pacientes, e da dor e o Questionário de Avaliação de Saúde Infantil foram maiores em pacientes com manifestações musculoesqueléticas (p = 0,0001, p = 0,002, p = 0002 e p = 0,001, respectivamente). Conclusão: Este foi o primeiro ...

Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy.

OBJECTIVE: To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. METHODS: 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis, and myalgia), musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, and tendinitis), and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. RESULTS: At least one musculoskeletal manifestation was observed in 14% of leprosy patients and in none of the controls. Five leprosy patients had asymmetric polyarthritis of small hands joints. Nerve function impairment was observed in 22% of leprosy patients, type 1 leprosy reaction in 18%, and silent neuropathy in 16%. None of the patients and controls presented musculoskeletal pain syndromes, and the frequencies of all antibodies and cyoglobulins were similar in both groups (p > 0.05). Further analysis of leprosy patients demonstrated that the frequencies of nerve function impairment, type 1 leprosy reaction, and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p = 0.0036, p = 0.0001, and p = 0.309, respectively), as well as multibacillary subtypes in leprosy (86% vs. 42%, p = 0.045). The median of physicians' visual analog scale (VAS), patients' VAS, pain VAS, and Childhood Health Assessment Questionnaire (CHAQ) were significantly higher in leprosy patients with musculoskeletal manifestations (p = 0.0001, p = 0.002, p = 0002, and p = 0.001, respectively). CONCLUSIONS: This was the first study to identify musculoskeletal manifestations associated with nerve dysfunction in pediatric leprosy patients. Hansen's disease should be included in the differential diagnosis of asymmetric arthritis, especially in endemic regions.

Manifestações músculoesqueléticas e auto-anticorpos em crianças e adolescentes com hanseníase / Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy

Introdução: A hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae. É considerada um dos maiores problemas de saúde pública nos países em desenvolvimento. Os principais sinais clínicos são manchas de pele com perda de sensibilidade e envolvimento de nervos periféricos. Manifestações musculoesqueléticas são descritas em adultos, mas este envolvimento é raramente descrito na população pediátrica. Objetivo: Avaliar envolvimento musculoesquelético e auto-anticorpos em pacientes pediátricos com hanseníase. Métodos: Foram avaliados 50 pacientes com hanseníase e 47 crianças e adolescentes saudáveis de acordo com manifestações musculoesqueléticas (artralgia, artrite e mialgia), síndromes dolorosas musculoesqueléticas (fibromialgia juvenil, síndrome de hipermobilidade articular benigna, síndrome miofascial e tendinite) e painel de auto-anticorpos e crioglobulinas. Escores de avaliação de saúde e tratamento foram realizados nos pacientes com hanseníase. Resultados: A frequência de manifestações musculoesqueléticas foi maior em pacientes com hanseníase comparada aos controles (14% vs. 0%, p=0,0012). Cinco pacientes com hanseníase tinham poliartrite assimétrica das pequenas articulações das mãos (10% vs. 0%, p=0,057). Comprometimentos da função do nervo, reação tipo I hansênica, e neuropatia silenciosa foram observados nos pacientes com hanseníase (p=0,0006; p=0,003; p=0,0059; respectivamente). Nenhum dos pacientes e controles apresentou síndromes de dor musculoesquelética e as frequências dos anticorpos e crioglobulinas foram semelhantes nos dois grupos (p > 0,05). Comprometimentos da função nervosa, reação hansênica tipo I e neuropatia silenciosa foram observados em pacientes com versus sem manifestações musculoesqueléticas (p=0,0036; p=0,0001; p=0,309; respectivamente), bem como subtipos de hanseníase multibacilar (86% vs. 42%, p=0,045). A escala visual analógica do médico (VAS), dos pacientes (VAS), de dor (VAS) e CHAQ foram maiores em...

Introduction: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is considered one of major public health issue in developing countries. The important clinical signs of leprosy are hypopigmented or reddish localized skin lesions with loss of sensation and peripheral nerves involvement. Musculoskeletal manifestations were described in leprosy adult patients and these involvements were rarely described in pediatric leprosy population. Objective: To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. Methods: 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis and myalgia), musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome and tendinitis) and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. Results: The frequency of at least one musculoskeletal manifestation was significantly higher in leprosy patients compared to controls (14% vs. 0%, p=0.0012) and five leprosy patients had asymmetric polyarthritis of small hands joints (10% vs. 0%, p=0.057), Nerve function impairment, type I leprosy reaction and silent neuropathy were significantly observed in leprosy patients (p=0.0006; p=0.003; p=0.0059; respectively). None of the patients and controls presented musculoskeletal pain syndromes and the frequencies of all antibodies and cyoglobulins were similar in both groups (p>0.05). Further analysis of leprosy patients showed that the frequencies of nerve function impairment, type I leprosy reaction and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p=0.0036; p=0.0001; p=0.309; respectively), as well as multibacillary subtypes in leprosy (86% vs. 42%, p=0.045). The median of physician visual analogue scale (VAS)...