Extraspinal osteoarticular tuberculosis: A diagnostic and therapeutic challenge.

Tuberculosis (TB) is a major cause of morbidity and mortality, representing a challenge for health-care providers worldwide. Extraspinal osteoarticular tuberculosis (ESOTB) represents a rare location of TB. We aim to describe ESOTB focusing on clinical, diagnostic, and therapeutic characteristics of this entity. We report a retrospective case series of patients diagnosed with ESOTB, treated, and followed up between 2015 and 2022. The diagnosis was based either on bacteriological results (culture and polymerase chain reaction [PCR]) or histological analysis. Five patients with confirmed ESOTB, three women and two men, with a mean age of 46.4 (16-72), were enrolled in study. The affected sites were the elbow (one case), the shoulder (one case), the greater trochanter (one case), the second metatarsal (one case), and the distal interphalangeal joint (one case). The mean delay to diagnosis was 5.8 months (3-10)]. The most common symptoms on presentation were pain (all cases), swelling (all cases), and limited joint range of motion (all cases). One case presented with a draining sinus (20%). Radiological findings were soft tissue swelling (two cases) and periarticular bone destruction (all cases). Four patients presented with pathognomonic histology. PCR was performed in two patients and was positive in both of them. All cases were cured after 9-12 months of oral TB treatment without relapse for the 12-18 months of follow-up. Only one patient underwent surgery for abscess drainage to gain local infection control. ESOTB is a mysterious condition that must not be overlooked and should be suspected in cases of long-standing bone and joint pain and swelling.

Escisión de Glándula Submandibular por Sialoadenitis Crónica Esclerosante Asociada a Sialolito en el Conducto Submandibular / Submandibular Gland Excision Due to Chronic Sclerosing Sialadenitis Associated With Sialolith in Submandibular Duct

La sialoadenitis crónica esclerosante puede extenderse desde una sialoadenitis focal hasta una cirrosis completa de la glándula. Aparece entre los 40 y 70 años de edad y afecta principalmente a la glándula submandibular. Se asocia con sialolitos y agentes infecciosos inespecíficos. La causa más frecuente de sialolitiasis es la formación de cálculos macroscópicamente visibles en una glándula salival o en su conducto excretor, de los cuales el 80 % al 90 % provienen de la glándula submandibular. Esta predilección probablemente se deba a que su conducto excretor es más largo, más ancho y tiene un ángulo casi vertical contra la gravedad, contribuyendo así a la estasis salival. Además, la secreción semimucosa de la misma es más viscosa. El sitio principal de ubicación de los litos en el conducto submandibular es la región hiliar con un 57 %. La sintomatología típica de la sialolitiasis es el cólico con tumefacción de la glándula y los dolores posprandiales. Reportamos el caso de un paciente masculino de 55 años, quien ingresa al servicio de Cirugía Oral y Maxilofacial del Hospital General Balbuena de la Ciudad de México por presentar un aumento de volumen en la región submandibular izquierda de consistencia dura y dolorosa a la palpación de 15 días de evolución, acompañada de aumento de temperatura en la zona compatible con un absceso. Los estudios de imagen reportan un sialolito en la región hiliar del conducto submandibular de 2,0 x 1,7 x 1,0 cm. Debido a su localización y tamaño, el tratamiento ideal en estos casos es la escisión de la glándula junto con el lito previo drenaje del absceso e inicio de terapia antibiótica doble.

Chronic sclerosing sialadenitis can range from focal sialadenitis to complete cirrhosis of the gland. It appears between 40 and 70 years of age and mainly affects the submandibular gland. It is associated with sialoliths and nonspecific infectious agents. The most common cause of sialolithiasis is the formation of macroscopically visible stones in a salivary gland or its excretory duct, of which 80 % to 90 % come from the submandibular gland. This predilection isprobably due to the fact that their excretory duct is longer, wider and has an almost vertical angle against gravity, thus contributing to salivary stasis. In addition, the semimucous secretion of it is more viscous. The main location of the stones in the submandibular duct is the hilar region with 57 %. The typical symptomatology of sialolithiasis is colic with swelling of the gland and postprandial pain. We report the case of a 55-year-old male patient, who was admitted to the Oral and Maxillofacial Surgery Service of the Hospital General Balbuena in Mexico City due to an increase in volumen in the left submandibular region that was hard and painful on palpation of 15 days of evolution, accompanied by increased temperature in the area compatible with an abscess. Imaging studies report a 2.0 x 1.7 x 1.0 cm sialolith in the submandibular duct hilar region. Due to its location and size, the ideal treatment in these cases is excision of the gland together with the stone previous drainage of the abscess and initiation of dual antibiotic therapy.

Formulation and Scale-up of Delamanid Nanoparticles via Emulsification for Oral Tuberculosis Treatment.

Delamanid (DLM) is a hydrophobic small molecule therapeutic used to treat drug-resistant tuberculosis (DR-TB). Due to its hydrophobicity and resulting poor aqueous solubility, formulation strategies such as amorphous solid dispersions (ASDs) have been investigated to enhance its aqueous dissolution kinetics and thereby improve oral bioavailability. However, ASD formulations are susceptible to temperature- and humidity-induced phase separation and recrystallization under harsh storage conditions typically encountered in areas with high tuberculosis incidence. Nanoencapsulation represents an alternative formulation strategy to increase aqueous dissolution kinetics while remaining stable at elevated temperature and humidity. The stabilizer layer coating the nanoparticle drug core limits the formation of large drug domains by diffusion during storage, representing an advantage over ASDs. Initial attempts to form DLM-loaded nanoparticles via precipitation-driven self-assembly were unsuccessful, as the trifluoromethyl and nitro functional groups present on DLM were thought to interfere with surface stabilizer attachment. Therefore, in this work, we investigated the nanoencapsulation of DLM via emulsification, avoiding the formation of a solid drug core and instead keeping DLM dissolved in a dichloromethane dispersed phase during nanoparticle formation. Initial emulsion formulation screening by probe-tip ultrasonication revealed that a 1:1 mass ratio of lecithin and HPMC stabilizers formed 250 nm size-stable emulsion droplets with 40% DLM loading. Scale-up studies were performed to produce nearly identical droplet size distribution at larger scale using high-pressure homogenization, a continuous and industrially scalable technique. The resulting emulsions were spray-dried to form a dried powder, and in vitro dissolution studies showed dramatically enhanced dissolution kinetics compared to both as-received crystalline DLM and micronized crystalline DLM, owing to the increased specific surface area and partially amorphous character of the DLM-loaded nanoparticles. Solid-state NMR and dissolution studies showed good physical stability of the emulsion powders during accelerated stability testing (50 °C/75% RH, open vial).

Can Oral TB develop in susceptible individuals after an oral surgical procedure? 3 case reports.

As opposed to the popular assumption, there have been an increase in the cases of Oral Tuberculosis as of late. Owing to increased drug resistance, there has been a change in the disease pattern leading to an upsurge in the Extra-pulmonary Oral Tuberculosis. According to the WHO, Diagnosis is the first step in the control of TB; but due to the lack of pathognomonic signs associated with Oral Tuberculosis and the rarity of these lesions, diagnosis is often difficult. So, to enable a timely diagnosis, we point out the occurrence of such lesions in the post-operative refractory lesions in susceptible individuals. However, a thorough search of literature did not yield any conclusive results. In this paper we present the clinical, radiographic and histopathological findings of three cases between the ages of 5 and 50 years old who were diagnosed of Oral Tuberculosis. These patients have undergone a recent oral surgical procedure prior to the development of Oral TB lesions. More research is required to increase the awareness of the pattern of this disease and to enable a quicker diagnosis so that the overall morbidity and mortality is reduced.

Investigação da presença do bacilo Mycobacterium tuberculosis em amostras sugestivas de tuberculose oral / Investigation of the presence of Mycobacterium tuberculosis bacillus in samples suggestive of oral tuberculosis

A Tuberculose (TB) é um considerável problema de saúde pública mundial. Em 2021, de acordo com a Organização Mundial de Saúde (OMS) estimou-se que, no mundo, cerca de 10,6 milhões de pessoas desenvolveram TB e 1,4 milhão morreu devido à doença. Com isso, tornou-se a principal causa de morte por infecção em todo o mundo e uma das dez principais causas de morte em geral. A TB tem o pulmão como o principal sítio de acometimento, sendo denominada de TB Pulmonar (TBP). Porém pode ser diagnosticada em muitos órgãos do corpo de maneira Extrapulmonar (TBEP), sendo o linfonodo o local mais comum. Porém, o envolvimento pleural, neurológico, sinovial, pericárdico, abdominal, geniturinário e oral tem sido descrito, o que mostra a potencial capacidade de disseminação do Mycobacterium tuberculosis (MTB). A detecção do Bacilos Álcool-Ácido Resistentes (BAAR), geralmente ocorre pela observação das características microscópicas da morfologia dos tecidos, presença de granulomas com necrose caseosa, histiócitos epitelióides e células gigantes do tipo Langhans, associada à coloração para BAAR, pela técnica de Ziehl Neelsen (ZN). Ademais, investigação por imuno-histoquímica (IHQ), testes de amplificação de ácido nucleico pela Reação em Cadeia da Polimerase Hemianinhada (nested-PCR) e pelo sistema de detecção automatizado GeneXpert® MTB/RIF são métodos aplicados para o diagnóstico da infecção. Com isso, este estudo teve como objetivo investigar a presença do bacilo Mycobacterium tuberculosis em amostras orais em parafina que continham granulomas com necrose caseosa. Ao todo, como critério de inclusão, foram selecionadas biópsias que apresentaram granulomas com necrose caseosa, sugerindo o diagnóstico de TB. Foram excluídas aquelas que após a revisão das fichas e histológicas, não apresentavam os granulomas exibindo necrose caseosa e aquelas que foram de biópsias intraósseas. O M. tuberculosis foi procurado por meio da coloração de ZN, IHC, nested-PCR e ensaios GeneXpert® MTB/RIF. Foram então selecionadas nove amostras com granulomas com necrose caseosa. Houve predominância de indivíduos do sexo masculino (2,5:1), com idade média de 50 anos (±23,08; 19-89), sendo a língua o local anatômico mais afetado (n=4). O bacilo não foi identificado pela técnica de ZN em nenhuma amostra, e a coloração por IHC mostrou um padrão granular grosseiro, sugerindo M. tuberculosis, em três delas. Nested-PCR e os ensaios GeneXpert® MTB/RIF foram positivos em duas e três das amostras, respectivamente. Conclui-se que testes moleculares e IHC podem ser métodos auxiliares úteis para casos suspeitos de tuberculose.

Tuberculosis (TB) is a significant global public health issue. In 2021, according to the World Health Organization (WHO), it was estimated that approximately 10.6 million people developed TB worldwide, and 1.4 million died from the disease. Consequently, it became the leading cause of death due to infection worldwide and one of the top ten overall causes of death. TB primarily affects the lungs and is referred to as Pulmonary TB (PTB). However, it can be diagnosed in various organs of the body as Extrapulmonary TB (EPTB), with lymph nodes being the most common site of involvement. Moreover, pleural, neurological, synovial, pericardial, abdominal, genitourinary, and oral involvement have been described, demonstrating the potential for Mycobacterium tuberculosis (MTB) dissemination. The detection of Acid-Fast Bacilli (AFB) typically involves the observation of microscopic tissue characteristics, the presence of granulomas with caseous necrosis, epithelioid histiocytes, and Langhans giant cells, along with AFB staining using the Ziehl-Neelsen (ZN) technique. Furthermore, immunohistochemistry (IHC), nucleic acid amplification tests by Nested Polymerase Chain Reaction (nested-PCR), and the automated detection system GeneXpert® MTB/RIF are methods employed for diagnosing the infection. Therefore, the aim of this study was to investigate the presence of Mycobacterium tuberculosis in paraffin-embedded oral samples containing granulomas with caseous necrosis. Inclusion criteria were based on the selection of biopsies displaying granulomas with caseous necrosis, suggesting a diagnosis of TB. Biopsies without these features upon review of records and histological findings, as well as intraosseous biopsies, were excluded. M. tuberculosis was sought using ZN staining, IHC, nested-PCR, and GeneXpert® MTB/RIF assays. Nine samples with granulomas and caseous necrosis were selected. The majority of individuals were male (2.5:1 ratio), with an average age of 50 years (±23.08; range 19-89), and the tongue was the most affected anatomical site (n=4). AFB was not identified by the ZN technique in any of the samples, and IHC staining exhibited a coarse granular pattern, suggestive of M. tuberculosis, in three of them. Nested-PCR and GeneXpert® MTB/RIF assays yielded positive results in two and three of the samples, respectively. In conclusion, molecular tests and IHC can be valuable auxiliary methods for suspected cases of tuberculosis.

Oral tuberculosis: An unusual case report.

Tubercular Lesions of oral cavity are relatively uncommon and are generally missed in the differential diagnosis before the systemic symptoms become evident. The purpose of this article is to know the varied presentation of tuberculosis in the oral cavity and also highlights the prime role of Oral Pathologist in making the diagnosis of this disease.

Tuberculosis oral. Revisión de la literatura. A propósito de un caso / Oral tuberculosis. Review of the literature. A case report

La tuberculosis (TB) es una enfermedad granulomatosa crónica que afecta de forma primordial a los pulmones. La afectación de la cavidad oral es rara, lo que hace que sea infradiagnosticada e infratratada. Dicha afectación puede ser primaria o secundaria, siendo más común la afectación secundaria. Exponemos el caso de un varón fumador de 39 años que presenta una lesión ulcerada en mucosa yugal izquierda de 3 semanas de evolución. Se tomó biopsia con resultado de mucosa escamosa con ulceración e intensa inflamación crónica granulomatosa no necrotizante. Además, presentaba una lesión cavitada a nivel pulmonar. Escribimos este artículo con el fin de determinar la importancia de realizar un buen diagnóstico diferencial de las lesiones ulcerativas de la cavidad oral y recalcar el manejo multidisciplinar de esta patología. (AU)

Tuberculosis (TB) is a chronic granulomatous disease which affects the lungs in majority of the cases. Tuberculosis of the oral cavity may be overlooked in the differential diagnosis of oral lesions and can be misdiagnosed and managed incorrectly. Oral manifestations of TB are seen both in primary and secondary stages of the disease but are most commonly associated with secondary TB. A 39-year-old smoker man with an ulcerative oral lesion came to the emergency room. A partial incisional biopsy was performed, with the result of squamous mucosa with ulceration and intense chronic non-necrotizing granulomatous inflammation. In addition, he had a cavitated lesion in the lung. We write this article in order to determine the importance of making a good differential diagnosis of ulcerative lesions of the oral cavity and emphasize the multidisciplinary management of this pathology. (AU)

Rare case of tubercular parotid abscess.

Acute parotitis progressing to parotid abscess is rare in children. Staphylococcus aureus is the usual pathogen in parotid abscess. Granulomatous parotid abscess due to tubercular aetiology is extremely rare. Authors report a case of chronic parotid abscess in a child who received multiple courses of antibiotics without any cure. The ultrasonography and CT scan of the parotid gland confirmed the extent of parotid abscess and the changes in the parotid lymph nodes. The surgical drainage and the biopsy of the lymph nodes lead to the diagnosis of granulomatous abscess. The antitubercular therapy finally cured the disease without further recurrence.

ENT manifestations of tuberculosis: an important aspect of ENT practice.

Tuberculosis involving organs other than the lungs is termed as 'extra pulmonary tuberculosis'. Tuberculosis (TB) remains a worldwide public health problem despite the fact that the causative organism was discovered more than 100 years ago. The present study was conducted to assess different manifestations of tuberculosis affecting the ear, nose and throat (ENT) in patients attending the outpatient department in a total of 520 cases of tuberculosis. One hundred and eight cases were of extra pulmonary tuberculosis. Sixty nine cases had the manifestations of TB in the ENT region. These included patients with tuberculous cervical lymphadenopathy (91.35), laryngeal TB (4.3%), tuberculous otitis media (1.4%), nasal TB (1.4%) and oral tuberculosis (1.4%). Extra pulmonary tuberculosis constitutes about 15-20% of all tuberculosis cases as per WHO survey and it is 20.6% in the present study.

Oral Granulomatous Disease.

Granulomatous diseases are chronic inflammatory disorders whose pathogenesis is triggered by an array of infectious and noninfectious agents, and may be localized or a manifestation of systemic, disseminated disease. As in the skin, oral manifestations of granulomatous inflammation are often nonspecific in their clinical appearance. Thus, in the absence of overt foreign material or a recognizable infectious agent, identifying the underlying cause of the inflammation can be challenging. This article highlights various conditions known to induce granulomatous inflammation within the oral soft tissues.

Literature review of oral tuberculosis and report of a case with unique histological presentation.

As a consequence of the emergence of drug resistant tuberculosis (TB) and various immuno-compromised states, there is a re-emergence of many forgotten extrapulmonary manifestations of TB including oral TB, which must be taken into consideration while diagnosing oral lesions. The present article discusses the geographical burden, temporal evolution, demographic variables, clinical presentation and treatment of oral TB. The occurrence is most commonly secondary to pulmonary TB but oral symptoms may precede systemic symptoms. The most common presentation is ulceration (71%) and histopathological specimens demonstrate the characteristic epithelioid and langhans cells. In a unique case, presented here, an ulcerative tuberculous gingival lesion demonstrated dense plasma cell infiltration histologically and closely mimicked plasma cell gingivitis which made the diagnosis challenging.

A case report of a tongue ulcer presented as the first sign of occult tuberculosis.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease with considerable fatality, typically affecting the pulmonary system and, rarely, other body organs including the oral cavity. Due to the rarity of oral TB, it is frequently overlooked in differential diagnosis of oral lesions. Despite a declining trend in TB incidence in recent years, it is still a major public health problem with high contagiousness, thereby requiring the early diagnosis and prompt treatment. CASE PRESENTATION: A 57-year-old male patient presented with chief complaint of painful ulcer on tip of his tongue. He reported that the ulcer developed without any remarkable event such as mechanical trauma, vesicle formation or systemic illness. His past medical history revealed the TB over 40 years ago, which had reportedly healed after pharmacological treatments. As the ulceration persisted after topical steroid application and careful education about avoiding possible mechanical stimuli, biopsy was performed and histological finding showed typical findings of oral tuberculosis including intense granulomatous inflammatory features with small red rods of mycobacterial organisms as well as epithelioid cells and Langhans giant cells. After suitable antituberculosis treatments, oral tuberculosis ulcer was almost completely healed. We present a case of oral TB affecting tip of the tongue in a patient with a history of pulmonary TB and emphasize the understanding of intraoral manifestations for early diagnosis and prompt treatment of TB. CONCLUSIONS: The present case represented the importance of understanding oral tuberculosis manifestations for dental clinicians who might be frequently the first health care professionals to encounter various oral lesions.

Head and neck tuberculosis: Literature review and meta-analysis.

BACKGROUND: Head and neck tuberculosis (HNTB), including cervical lymphadenopathy, is the most common extrapulmonary manifestation of TB. The proposed study investigated the epidemiologic and clinical characteristics of HNTB. MATERIALS AND METHODS: A literature search was conducted via PubMed, Embase, Cochrane Library and Wanfang for keywords (tuberculosis, head and neck, laryngeal, pharyngeal, tongue, oropharyngeal, nasopharyngeal, and oral cavity). Scientific articles published from January 1990 through July 2017 were selected and reviewed to assess the epidemiology, presentation, diagnosis and treatment of HNTB disease. RESULTS: Results from the included 57 studies revealed that the majority of HNTB cases were age<40 years and female. The most common HNTB sites were cervical lymph nodes (87.9%), followed by larynx (8.7%). Involvement of other HN-regions was rare (3.4%). Multidrug resistant TB was not common among the majority of studies. Given the paucibacillary nature of HNTB, sputum tests did not have a good performance on HNTB diagnosis. Most of HNTB cases were diagnosed by fine-needle aspiration, cytology and excision biopsies in combination with clinical presentations. CONCLUSION: HNTB disease is an important manifestation in the diagnostic process in an otolaryngologist practice. The developments of rapid, ultrasensitive, simple and cost-effective high-throughput methods for early diagnosis of HNTB are urgently needed.

Oral tuberculosis mimicking a traumatic denture ulcer.

Tuberculosis (TB) of the oral cavity may be overlooked in the differential diagnosis of oral lesions and can be misdiagnosed and managed incorrectly. A 66-year-old man with complete dentures presented with a nonhealing mucosal ulcer in the upper lip. Despite the treatments performed by a local medical clinic, the ulcerative lesion on the denture-bearing area had not improved over 5 months. A partial excisional biopsy was performed to investigate further. Histopathologic examination revealed granulomatous inflammation caused by TB, and a chest radiograph showed consolidation and cavitation of the upper lobes. The patient was diagnosed with pulmonary TB. This clinical report describes the management of oral TB mimicking a traumatic denture ulcer in a patient with long-term complete denture use.

Disseminated tuberculosis caused by Mycobacterium bovis presenting as a tongue base mass.

An 80-year-old woman presented with dysphagia, odynophagia and progressive weight loss. Initial investigations suggested a large base of tongue squamous cell carcinoma. At panendoscopy, biopsies were taken which revealed granulomatous inflammation with multinucleated giant cells and areas of caseous necrosis. Acid-fast bacilli were identified on Ziehl-Neelsen stain and the appearances were consistent with Mycobacterium bovis Closer inspection of the patient's medical history revealed that she had previously undergone right hemicolectomy for an ascending colon stricture. The histology had shown granulomatous inflammation consistent with intestinal tuberculosis but no systemic treatment had been instigated at the time. This case highlights the importance of taking a detailed clinical history as well as the need to be cognisant of tuberculosis masquerading as cancer in the head and neck.

Extrapulmonary tuberculosis: atypical presentation in otorhinolaryngology.

Tuberculosis (TB) continues to be a major health burden globally more so in low/middle-income countries like India. There is an increase in the prevalence of extrapulmonary TB (EPTB) because of HIV epidemics and increased usage of immunomodulating drugs. EPTB constitutes 15%-20% of all patients with TB and >50% of HIV-TB coinfected patients. We present three such atypical presentations of EPTB in head and neck region. EPTB can mimic any disease, hence knowledge of the unusual presentations helps in making early diagnosis and thereby reduces the morbidity and mortality involved with the disease.