Diagnosis of cutaneous tuberculosis (lymph node scrofuloderma) using the Xpert MTB/RIF® method

Cutaneous tuberculosis is a rare infection that is difficult to diagnose, because it shows less sensitivity and specificity in classic complementary exams when compared with the pulmonary form. The Xpert MTB/RIF® method offers an early diagnosis that identifies the DNA of Mycobacterium tuberculosis and the main mutations that give the bacterium resistance to rifampicin. The authors present a case of scrofuloderma whose diagnosis was quickly obtained through the secretion of a cervical lesion, allowing an early diagnosis and the initiation of appropriate treatment.     

Disseminated tuberculosis associated with reactive arthritis of Poncet in an immunocompetent patient

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl–Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.     

Cutaneous tuberculosis: epidemiologic,etiopathogenic and clinical aspects - Part I

Cutaneous tuberculosis (CTB) is the result of a chronic infection by Mycobacterium tuberculosis, M. ovis and occasionally by the Calmette-Guerin bacillus. The clinical manifestations are variable and depend on the interaction of several factors including the site of infection and the host''s immunity. This article revises the current knowledge about this disease''s physiopathology and immunology as well as detailing the possible clinical presentations.     

Update on cutaneous tuberculosis

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction.     

Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.     

Cutaneous Complications of BCG Vaccination in Infants with Immune Disorders: Two Cases and a Review of the Literature

Two infants, one with a T-cell-signaling defect resulting in a primary immunodeficiency syndrome and the other with severe combined immunodeficiency (SCID), are described. Both infants developed cutaneous infections secondary to their bacillus Calmette-Guérin (BCG) vaccinations. Both patients were from countries where BCG is routinely administered in infancy. The infant with the T-cell-signaling defect developed a disseminated infection involving the skin, while the infant with SCID developed a localized cutaneous infection at the site of his BCG immunization. These two cases resemble other reported cases of cutaneous BCG infection following routine vaccination in immunocompromised patients. Mycobacterium bovis infection should be considered in patients with cutaneous eruptions who have received BCG vaccination, especially those who are immunocompromised.     

Panorama actual en el diagnóstico de la tuberculosis cutánea

Pulmonary and cutaneous tuberculosis are caused by Mycobacterium tuberculosis. According to data from the World Health Organization, there are around 8 million new cases per year. The incidence of cutaneous tuberculosis has risen in parallel with that of pulmonary tuberculosis, and coinfection by M tuberculosis and human immunodeficiency virus is considered to be one of the main causes. Current diagnostic methods for pulmonary and extrapulmonary tuberculosis are far from perfect, leading to a delay in starting appropriate therapy. We present a review of these diagnostic methods and of their use in the cutaneous forms. In conclusion, histopathologic findings and isolation of M tuberculosis in cultures of biopsy material or by polymerase chain reaction are the most useful diagnostic tools in cutaneous tuberculosis.     

Lupus vulgaris–a case diagnosed more than 20 years after onset

A 47‐year‐old Turkish woman developed an erythematous scaly plaque on her thigh over 20 years. Cutaneous sarcoidosis had been diagnosed eight years previously on a skin biopsy. We confirmed Mycobacterium tuberculosis infection by polymerase chain reaction and cultivation of the causative organism from lesional skin. After several months of antituberculous treatment with isoniazid, rifampicin, ethambutol and pyrazinamide, the lesion resolved.     

Técnicas basadas en la detección de IFN-γ en el diagnóstico de la infección tuberculosa en pacientes con psoriasis candidatos a terapias biológicas

Although there is no doubt that biologic agents are an effective alternative for the treatment of moderate and severe psoriasis, anti-tumor necrosis factor α therapy has been associated with reactivation of latent tuberculosis infection. Tuberculin skin testing (TST) is used to diagnose tuberculosis infection but it has low specificity in patients who have received the Mycobacterium bovis BCG vaccine and low sensitivity in patients with altered cell-mediated immunity. In vitro assays based on the detection of interferon γ released by T cells stimulated by specific Mycobacterium tuberculosis antigens have emerged as an option for the diagnosis of tuberculosis infection. The results to date show that they are a viable alternative to TST thanks to their higher specificity and sensitivity. Furthermore, these assays are also proving to have high negative predictive value, meaning that we might be able to use them without TST in the short to medium term.     

Utility of anti-bacillus Calmette-Guérin antibodies as a screen for organisms in sporotrichoid infections

BACKGROUND: Sporotrichoid infections often present a diagnostic challenge for the dermatopathologist. Therefore an affordable, reliable method of easier recognition of organisms is desired. Recently, immunohistochemical staining with antibodies against Mycobacterium bovis (bacillus Calmette-Guérin, BCG) was found to be useful in identifying various fungi and mycobacteria with minimal background staining. OBJECTIVE: The purpose of this study was to demonstrate the usefulness of anti-BCG antibodies as a screen for organisms in sporotrichoid infections. METHODS: Thirteen specimens of suspected sporotrichosis were selected for staining with anti-BCG antibody. Sporotrichoid infection was confirmed by histochemical staining, biopsy, and follow-up results. RESULTS: Twelve of the 13 specimens stained positively using anti-BCG antibody. Of the 5 cultures done, 2 were positive for M. marinum, and 1 grew Sporothrix schenckii. CONCLUSION: Immunohistochemical staining with anti-BCG antibody offers another screening method to identify organisms in sporotrichoid infections because of its ease, cost-effectiveness, and simplicity.     

Erythema induratum Bazin nach Lungentuberkulose

Summary: Mycobacterium tuberculosis can be directly demonstrated in lesions of cutaneous tuberculosis, but mostly could not be demonstrated in Tuberculids. These include erythema induratum of Bazin, papulonecrotic tuberculid as well as lichen scorphulosorum. Tuberculids result from the hematogenous spread of Mycobacteria tuberculosis in a person with a high degree of immunity. We report on a 63‐year‐old woman with erythema induratum of Bazin and pulmonary tuberculosis in medical history, with hightened tuberculin sensitivity and negative bacterial cultures. Polymerase chain reaction (PCR) could not detect Mycobacterium tuberculosis‐specific DNA. After eight weeks only, the patient responded well to a course of antituberculosis therapy (isoniazid, ethambutol, rifampicin and pyracinamide) with marked resolution of the lesions. The tuberculous origin of erythema induratum of Bazin is still controversal, since mycobacteria cannot be cultured from skin lesions. Since the availability of PCR‐diagnostic, in some cases, but not in our patient, PCR was positive für Mycobacterium tuberculosis‐specific DNA. The good response to antituberculosis therapy is a further argument for the association of erythema induratum of Bazin and Mycobacterium tuberculosis     

Adjuvant treatment in stage I and II malignant melanoma: a randomized trial between chemoimmunotherapy and immunotherapy.

A randomized trial comparing chemoimmunotherapy (bacillus Calmette-Guérin + chemotherapy) and immunotherapy (bacillus Calmette-Guérin alone) was carried out in high-risk stage I and II malignant melanoma patients. Eight-two evaluable patients were included. The follow-up median duration was 11 years. Recurrent melanoma developed in 28 patients (34%). The overall survival rate was 76% at 5 years and 65% at 10 years. There were no statistical differences in survival probability or disease-free survival (DFS) probability between the two treatment groups. Survival and DFS were also analyzed in relation to various prognostic factors. Statistically significant differences were only seen in a subset of 33 patients with lower limb malignant melanoma, the prognosis being better for the chemoimmunotherapy group in this location. Because of the small number of patients in each group, a week positive effect of either of these two treatments cannot be ruled out. Chemoimmunotherapy only seems to improve the prognosis of stage I or II malignant melanoma of the legs.     

Disseminated Bacille Calmette‐Guérin infection in a patient with severe combined immunodeficiency caused by JAK3 gene mutation

Bacille Calmette‐Guérin (BCG), a live attenuated vaccine prepared using Mycobacterium bovis, can prevent tuberculosis in children and is routinely administered to infants in China and many other countries. A serious complication following vaccination is disseminated BCG infection. The risk is greatly increased in patients with severe combined immunodeficiency disease (SCID), a syndrome characterized by deficiency of both humoral and cellular immunity. We report a case of disseminated BCG infection in an infant with SCID caused by two novel janus kinase 3 (JAK3) gene mutations.     

A Case of Tuberculosis Cutis Orificialis with Perianal Involvement

Tuberculosis cutis orificialis (TCO) is a rare manifestation of cutaneous tuberculosis that is caused by auto-inoculation of mycobacteria in patients with advanced internal tuberculosis. TCO occurs in oral, perianal, or genital mucosa and adjacent skin. The tongue is the most frequently affected site, but the perianal area can also be affected. A 39-year-old male presented with a 4-month history of painful ulcers on the perianal area. The histopathologic findings revealed granulomatous infiltrates composed of epithelioid cells and Langhans-type giant cells in the dermis, and a few acid-fast bacilli noted on Ziehl-Neelsen staining. The polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis and the chest X-ray showed findings consistent with active pulmonary tuberculosis in both upper lung zones. The skin lesion showed complete resolution 2 months after the start of treatment with antituberculosis agents. We report a case of TCO with perianal involvement in a patient with underlying active pulmonary tuberculosis.     

Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study

Various forms of immunotherapy utilizing bacille Calmette-Guérin vaccine or vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against tuberculosis and smallpox, has, however, never been studied in epidemiologic investigations on risk factors for melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between melanoma risk and previous bacille Calmette-Guérin vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against tuberculosis and smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic theory of melanoma development provides a sound basis for understanding the biologic plausibility of the findings that have to be confirmed in future studies.     

Disseminated tuberculosis presenting as medium-vessel vasculitis in an immunocompromised host

Cutaneous tuberculosis is an uncommon entity with several clinical forms recognized. Histopathologically, most cases are characterized by granulomatous inflammation and caseating necrosis, although less common findings, including vasculitis, have also been described. We report a 55-year-old male with a history of recently diagnosed dermatomyositis receiving immunosuppression with mycophenolate mofetil and prednisone, who developed multifocal soft tissue abscesses and an indurated erythematous plaque on the back. Skin biopsy of the back revealed a necrotizing medium-vessel vasculitis. Mycobacterium tuberculosis was detected in the skin via acid-fast bacilli stain and confirmed by tissue culture and polymerase chain reaction. Cutaneous findings improved rapidly with antituberculosis therapy. This case illustrates an uncommon clinical and histopathologic presentation of disseminated tuberculosis.     

A clinicoepidemiological study of 50 cases of cutaneous tuberculosis in a tertiary care teaching hospital in pokhara, Nepal

Background:

Cutaneous tuberculosis (TB) is essentially an invasion of the skin by Mycobacterium tuberculosis, the same bacteria that causes pulmonary tuberculosis.

Aim:

This study was conducted to study the common types of cutaneous TB and to find the management pattern in a tertiary teaching hospital in Pokhara, Nepal.

Materials and Methods:

All the cases of cutaneous TB were biopsied and furthermore investigated by performing Mantoux test, sputum examination, fine needle aspiration cytology, chest X-ray and ELISA.

Results:

In this study, we found that tuberculosis verrucous cutis (48%) had a higher incidence than other types of cutaneous TB. More males were affected than were females (1.2:1). Commonly affected sites were the limb and the buttock (48%). The most commonly affected age group was 16–25 years (40%). All cases (except two) were more than 15 mm in size in the Mantoux test. The histopathological picture was typical in all except three cases. All patients were treated with antitubercular treatment as per the national guidelines.

Conclusion:

The most common type of cutaneous TB was tuberculosis verrucous cutis and the most commonly affected sites were the limb and the buttock. As cutaneous TB sometimes reflects the presence of pulmonary tuberculosis, its incidence should not be ignored.     

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.     

Tuberculosis Verrucosa Cutis Presenting as Diffuse Plantar Keratoderma: An Unusual Sight

Tuberculosis verrucosa cutis (TVC) is a common cutaneous form of paucibacillary tuberculosis in an individual with moderate to high degree of immunity to Mycobacterium tuberculosis infection. Clinical appearance of TVC is mostly very typical with well-defined warty plaques presenting mostly on hands, knees, ankle, and buttocks; however several atypical morphology of the lesions have also been described. We hereby report a case of TVC, masquerading as asymptomatic diffuse keratoderma of left foot for nine months, in an otherwise healthy individual, obstructing easy diagnosis of cutaneous tuberculosis. Diagnosis was confirmed by histopathology.     

Disseminated cutaneous bacille Calmette-Guérin infection identified by polymerase chain reaction in a patient with X-linked severe combined immunodeficiency

An 8-month-old boy developed a disseminated cutaneous mycobacterial infection at 6 months of age that responded poorly to treatment. Further immunologic study and sequence analysis showed the presence of a missense mutation in the IL2RG gene, and X-linked severe combined immunodeficiency was diagnosed. To identify the strain of the microorganism causing the cutaneous infection, polymerase chain reaction with four pairs of primers was performed on skin biopsy specimens positive for acid-fast bacilli. Sequence analysis showed 99.36% homology with a bacilli Calmette-Guérin positive control. Disseminated bacilli Calmette-Guérin disease must be considered in any infant with cutaneous mycobacterial lesions, especially those with atypical histologic findings or who are immunocompromised. Testing by polymerase chain reaction using the proper primers may help in making a precise diagnosis.