Cutaneous tuberculosis. Part I: Pathogenesis, classification, and clinical features.

Tuberculosis is an ancient disease that continues to affect an estimated 10 million people per year and is responsible for 1.4 million deaths per year. Additionally, the HIV epidemic and multidrug resistance present challenges to disease control. Cutaneous tuberculosis is an uncommon, often indolent, manifestation of mycobacterial infection that has a varied presentation. Its diagnosis is challenging, as lesions mimic other, more common conditions and microbiological confirmation is often not possible. Cutaneous tuberculosis can be broadly categorized into multibacillary and paucibacillary forms. Approximately one-third of skin tuberculosis is associated with systemic involvement. By recognizing cutaneous tuberculosis early, dermatologists can play an important role in disease control. The first article in this 2-part continuing medical education series describes the latest epidemiology, microbiology, and pathogenesis of tuberculosis. Furthermore, we review the classification, clinical manifestations, common clinical differentials, and systemic involvement that occur in cutaneous tuberculosis.

Tuberculosis verrucous cutis mimicking chromoblastomycosis: A case report and diagnostic challenges.

Tuberculosis verrucous cutis (TBVc) is a skin infection caused by M. tuberculosis, characterized by the presence of a solitaire verrucous plaque but may present as a varies of different clinical morphologies on the finger and or feet. The diagnosis is often late because of its mimicking other diseases with different etiology. Bacterial culture examination is negative because there are few pathogens in the lesion. Meanwhile, other diagnostic methods provide lower sensitivity and specificity which add further diagnostic challenges. We presented one case report of TBVc mimicking chromoblastomycosis. A 26-year-old man complain a multiple papule-plaque verrucose on the dorsum of the right foot and extending to all of fingers for 2 years ago. The first lesion appears as a small papule verrucous then progressively to form plaque with curst yellow-red and central healing. Examination of bacterial culture with Ziehl-Neelsen stain and GeneXpert did not find M. tuberculosis but could not rule out the diagnosis of TBVc. The diagnosis was established based on the correlation of clinical manifestations and dermoscopy with histopathological examination. To date, there is no gold standard for TBVc testing. Correlation analysis of clinical manifestations, dermoscopy, and histopathology can be considered to establish the diagnosis of TBVc, especially if the culture is negative and the limitations of polymerase chain reaction tools.

[Erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient receiving anti-tumor necrosis factor treatment]. / Eritema indurado de Bazin como una reactivación de una tuberculosis latente en una paciente con tratamiento biológico anti-factor de necrosis tumoral.

Erythema induratum of Bazin is a rare form of cutaneous tuberculosis, considered as part of the spectrum of tuberculids or hipersensitivity reactions to Mycobacterium tuberculosis. Treatment with biologic agents is a known risk factor for tuberculosis reactivation, especially in areas of high incidence like Latin America, which is why screening and treatment protocols must be followed before these therapies are initiated. We present a case of erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient with rheumatoid arthritis treated with golimumab.

Eritema indurado de Bazin como una reactivación de una tuberculosis latente en una paciente con tratamiento biológico anti-factor de necrosis tumoral / Erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient receiving anti-tumor necrosis factor treatment

Resumen El eritema indurado de Bazin es una tuberculosis cutánea rara, considerada una tuberculide o reacción de hipersensibilidad a Mycobacterium tuberculosis. El tratamiento con agentes biológicos es un factor de riesgo conocido para la reactivación de tuberculosis, especialmente en áreas de alta incidencia como Latinoamérica, por lo que existen protocolos de búsqueda y tratamiento antes del inicio de este tipo de terapias. Se presenta un caso clínico de eritema indurado de Bazin como reactivación de una infección tuberculosa latente en una paciente con artritis reumatoide que recibía tratamiento con golimumab.

Abstract Erythema induratum of Bazin is a rare form of cutaneous tuberculosis, considered as part of the spectrum of tuberculids or hipersensitivity reactions to Mycobacterium tuberculosis. Treatment with biologic agents is a known risk factor for tuberculosis reactivation, especially in areas of high incidence like Latin America, which is why screening and treatment protocols must be followed before these therapies are initiated. We present a case of erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient with rheumatoid arthritis treated with golimumab.

IFI44L as a Forward Regulator Enhancing Host Antituberculosis Responses.

Interferon-induced protein 44-like (IFI44L) gene is a type I interferon-stimulated gene (ISG) that plays a critical role in antiviral activity and constitutes a promising diagnostic marker. However, its precise role and function in tuberculosis have not been unveiled. This study showed that IFI44L acts as an antimicrobial target and positive modulator in human macrophages. Knockdown of IFI44L led to increased Mycobacterium tuberculosis intracellular survival. Moreover, IFI44L was significantly upregulated, and it restricted the intracellular survival of M. tuberculosis H37Rv strains at 72 h after rifampicin treatment. Individuals with cutaneous tuberculosis (CTB) were found to have significantly higher IFI44L expression after 6 months of rifampicin therapy than after only 1 month. These results demonstrated that IFI44L induced positive regulation and clearance of M. tuberculosis from human macrophages. This antimicrobial activity of IFI44L makes it a possible target for therapeutic applications against M. tuberculosis.

Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population.

BACKGROUND: A definite diagnosis of infectious granulomatous dermatitis (IGD) is difficult for both practicing dermatologists and dermatopathologists due to overlapping clinical and histomorphological features. We aimed to explore the role of multiplex polymerase chain reaction (PCR) for identifying a definite etiological agent for diagnosis and appropriate treatment in IGD in formalin-fixed paraffin-embedded tissue. MATERIALS AND METHODS: Sixty-two cases of IGD were included, excluding leprosy. The histochemical stains including Ziehl-Neelsen, periodic acid-Schiff, and Giemsa were performed in all cases. A multiplex PCR was designed for detection of tuberculosis (TB) (IS6110 and mpt64), fungal infections (ITS1, ITS2; ZM1, and ZM3), and leishmaniasis (kDNA). The results of histomorphology, histochemical stains, and multiplex PCR were compared. RESULTS: Among 62 cases, the sensitivity rate of PCR detection for organisms was 16.7%, 0%, 100%, 72%, 75%, and 66.7% in patients with TB, suggestive of TB, leishmaniasis, fungal infections, and granulomatous dermatitis not otherwise specified and granulomatous dermatitis suggestive of fungus, respectively. The TB PCR using IS6110 primers was negative in all cases; however, PCR using mpt64 primers was positive in 33.33% cases of scrofuloderma. The histochemical stains including Ziehl-Neelsen for acid-fast bacilli, periodic acid-Schiff for fungus, and Giemsa for Leishman-Donovan bodies showed positivity in 11.3%, 43.5%, and 3.2%, respectively. CONCLUSION: A multiplex PCR (Mycobacterium tuberculosis, Leishmania, and panfungal) is highly recommended in all cases of IGD where an etiological agent is difficult to establish by skin biopsy and histochemical stains along with a clinicopathological correlation. This will augment in appropriate treatment and will reduce empirical treatment and morbidity in such patients.

Recurrent Genital Ulcers.

Papulonecrotic tuberculid represents a hypersensitivity reaction to Mycobacterium tuberculosis or its products that disseminate through hematogenous route to the skin from an internal tuberculous focus. It is characterized by recurrent eruptions of asymptomatic, dusky red papules, which undergo ulceration and crusting, and eventually heal after a few weeks with varioliform scarring. Although it most commonly involves extragenital sites, isolated glans penis involvement has been reported very rarely.

Escrofuloderma, una manifestación extrapulmonar de tuberculosis: a propósito de un caso y actualización de esquema de tratamiento en Chile / Scrofuloderma, a manifestation extrapulmonary tuberculosis: about a case and treatment scheme update in Chile

La tuberculosis (TBC) es una enfermedad infecciosa causada por organismos del complejo Mycobacterium tuberculosis. Las presentaciones extrapulmonares constituyen hasta el 25% de los casos de TBC reportados en nuestro país. La TBC cutánea es una manifestación extrapulmonar rara que representa el 1-2% de los casos, siendo el escrofuloderma y el lupus vulgar las formas clínicas más comunes. El escrofuloderma es una manifestación endógena de la infección, como resultado de la extensión contigua a la piel suprayacente desde estructuras adyacentes. La biopsia de piel asociada a técnicas moleculares y cultivo de micobacterias constituyen el gold standard diagnóstico de la TBC cutánea. El tratamiento de la TBC cutánea sigue las mismas recomendaciones que para otras formas de TBC. Presentamos el caso de un paciente con escrofuloderma.

Tuberculosis (TB) is an infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Extrapulmonary presentations may constitutes up to 25% of TB cases. Reported in our country Cutaneous tuberculosis is a rare extrapulmonary manifestation that represents 1-2% of cases, with scrofuloderma and lupus vulgaris being the most common clinical forms. Scrofuloderma is an endogenous manifestation of the infection, because of contiguous extension to the overlying skin from adjacent structures. Skin biopsy associated with molecular techniques and mycobacterial culture constitute the gold standard for diagnosis of cutaneous TB. The treatment of cutaneous TB follows the same recommendations as for other forms of TB. We present the case of a patient with scrofuloderma.

Multi-targeted loop mediated amplification PCR for diagnosis of extrapulmonary tuberculosis.

AIMS: The present study was conceived to evaluate multi-targeted loop mediated amplification (MLAMP) for the rapid diagnosis of extrapulmonary tuberculosis (EPTB). METHODS AND RESULTS: A total of 700 patients were included who were classified into 2 groups: Group 1 (n = 400) included a 100 culture confirmed EPTB patients and 300 culture negative, suspected EPTB patients. Group 2 (n = 300) included negative controls from non-tubercular patients. All samples were subjected to Ziehl-Neelsen microscopy, solid culture on Lowenstein Jensen media, Polymerase chain reaction (PCR) targeting IS6110 gene and LAMP targeting both IS6110 and MPB64 individually and as MLAMP. The overall sensitivity of microscopy, culture, IS6110 PCR, IS6110 LAMP, MPB64 LAMP and the MLAMP assay were 12%, 25%, 72.5%, 80% and 86.6% respectively and the specificity of all the tests was 100%. CONCLUSION: MLAMP is a rapid robust tool for the diagnosis of EPTB and utilizing two targets for M. tuberculosis can improve the overall sensitivity and increase the yield of detection from extrapulmonary samples. The rapidity, ease of performance and low cost make MLAMP an excellent alternative in low-income, resource limited settings.

Lichenoid granulomatous dermatitis as a tuberculid in association with spondylitis due to Mycobacterium tuberculosis.

Lichenoid granulomatous dermatitis (LGD) is a histopathologic pattern with a band-like lymphocytic infiltrate, typical of lichenoid dermatitis, combined with dermal histiocytes and granulomatous inflammation. Prior reports have described cases of LGD caused by non-tuberculous mycobacteria, with evidence of intralesional acid-fast bacilli or mycobacterial DNA. Herein, we report a patient with pulmonary and extrapulmonary Mycobacterium tuberculosis infection who developed LGD. No evidence of M. tuberculosis was detected within the cutaneous lesions, suggesting a potential delayed-type hypersensitivity reaction to tuberculosis.

Cutaneous tuberculosis in Rio de Janeiro, Brazil: description of a series of 75 cases.

BACKGROUND: Brazil is one of the highest tuberculosis (TB) burden countries of the world. Cutaneous tuberculosis (CTB) is a rare form of extrapulmonary manifestation of tuberculosis. This study aimed to describe the clinico-evolutive, laboratory and therapeutic aspects of CTB cases among patients from a cohort with TB in Rio de Janeiro, Brazil. METHODS: Cases of diagnosed CTB with microbiologic confirmation or clinical response to anti-tuberculous treatment associated with positive smear or histopathological findings between the years 2000 and 2016 were selected. RESULTS: Seventy-five patients with CTB were included, most were women (58.7%) with a median age of 42 years. CTB diagnosis was based on culture in only 42.7% of the cases. Scrofuloderma represented 50.7% of the cases, followed by erythema induratum of Bazin (EIB) (18.7%), tuberculous gumma (13.3%), lupus vulgaris (8%), TB verrucosa cutis (4%), orificial TB (2.7%) and associated forms (2.7%). Other TB presentations were pulmonary (22.7%), mammary (6.6%) and osteoarticular (4%). All patients who completed the treatment (97.3%) had their lesions healed. Only two patients (2.6%) needed to change the therapy due to adverse reactions. Fifty percent of EIB patients presented recurrence. CONCLUSIONS: These data highlight the diversity of CTB presentations and the importance of the skin to assist in early identification and treatment of TB. More studies are necessary to improve the knowledge on EIB for a better approach towards these patients, mainly in cases of recurrence.

Sporotrichoid presentation of lupus vulgaris mimicking mycetoma.

Most common form of cutaneous tuberculosis (TB) is lupus vulgaris (LV). Atypical presentation of LV is rare and may lead to delay in diagnosis and hence increase in morbidity. Here, we report a case of sporotrichoid form of LV in a 38 year old male who presented as cutaneous lesions mimicking mycetoma. High index of clinical suspicion and relevant investigations play a vital role in confirmation of diagnosis wherever atypical form of cutaneous TB is suspected.

Cutaneous Tuberculosis and Nontuberculous Mycobacterial Infections at a National Specialized Hospital in China.

To identify the microorganism distribution clinical characteristics and management of cutaneous Mycobacterium tuberculosis and nontuberculous mycobacterial infectious diseases in the past 10 years we collected and analyzed the patient records of all cutaneous M. tuberculosis and nontuberculous mycobacterial infection cases diagnosed by culture and/or PCR from 2008 to 2017 in the Hospital of Dermatology Chinese Academy of Medical Sciences. Among 203 cases including 89 M. tuberculosis infections and 114 nontuberculous mycobacterial infections M. tuberculosis was the most common species in all patients and M. marinum predominated among the nontuberculous mycobacterial followed by M. abscessus. Cases of cutaneous mycobacterial infection especially nontuberculous mycobacterial infection increased in the past 10 years and infection with rapidly growing mycobacteria significantly increased in the last 5 years in this national hospital in Southeast China. Injuries were common causative factors. Approximately 91.3% of patients responded well to longstanding antibiotic therapy.

Tuberculosis, onychomycosis and immune deficiency in complicated Crohn's disease.

The immune system is composed of innate humoral defence and adaptive immunity. One of the key mechanisms of the innate humoral defence is through complement activation. Mutations of certain enzyme may affect the complement activation and result in decreased defence against microorganisms. Mannan-binding lectin serine protease 2 (MASP-2) mutation was associated with recurrent infections and autoimmune diseases. Tuberculosis (TB) has been linked with mannose-binding lectin and MASP-2 gene polymorphism. We report a case of a paediatric patient with MASP-2 deficiency with classical and atypical features associated with Crohn's, onychomycosis and severe cutaneous infections including TB. We also report the presence of a new mutation variant in MASP-2 reported in whole exome sequencing of our patient.

Cutaneous tuberculosis: A great imitator.

Tuberculosis (TB) is still prevalent in many developing countries and can pose a new potential threat to global health due to international migration. As an uncommon form of extrapulmonary TB, cutaneous TB is complicated in its clinical manifestation, pathogenesis, and classification. Cutaneous TB can be divided into two major categories, true cutaneous TB and tuberculid, depending on the source of infection, the route of transmission, the amount of bacteria, and the immune state of the host. Clinical manifestations may include patches and plaques (lupus vulgaris, TB verrucosa cutis), macules and papules (acute miliary TB, papulonecrotid tuberculid, lichen scrofulosorum), nodules, and abscesses (erythema induratum of Bazin, tuberculous gumma), erosions, and ulcers (tuberculous chancre, orificial TB, scrofuloderma), mimicking diverse skin diseases. Uncommon localizations such as external genitalia, unusual presentations such as nodular granulomatous phlebitis, and coexistence with other morbidities such as Behçet disease and acne inversa or hidradenitis suppurativa deserve special attention. Treatment of both true and tuberculid cutaneous TB follows the same drug regimens of the World Health Organization's recommendation for treatment of new cases of pulmonary TB. Erythema induratum of Bazin may need longer treatment duration and adjuvants such as dapsone, potassium iodide, doxycycline, and corticosteroids to tackle inflammation. Misdiagnosis and undertreatment in daily practice are likely, and contemplation of this classic great imitator in dermatology is warranted.

Lesiones cutáneas de muy larga evolución / Very long evolution skin injuries

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