Two cases of pancreatic tuberculosis in nonimmunocompromised patients: A diagnostic challenge and a rare cause of portal hypertension

Pancreatic tuberculosis is very rare, especially in immunocompetent patients, and represents a diagnostic challenge. We describe 2 cases of pancreatic tuberculosis mimicking carcinoma on CT scan. In the first case, explorative laparotomy revealed granulomatous inflammation suggestive of tuberculosis. Cultured smears from the pancreatic tail tested positive for Mycobacterium tuberculosis, and the patient responded well to antituberculous medication. In the second case, fine needle aspirate revealed tuberculosis. This case is unique with regard to development of portal hypertension in pancreatic tuberculosis. Antituberculous medication achieved little improvement, then the patient was lost to follow-up. In suspicion of carcinoma the patient underwent laparotomy in another hospital. Malignancy was excluded, and a purulent necrotic pancreas was resected. The patient finally improved without any antituberculous medication and remains well. Both patients were tested HIV-negative. We summarize the etiology, clinical presentation, diagnosis and treatment of a diagnostic dilemma, which should be considered in clinical practice.     

An indeterminate result of QuantiFERON-TB Gold In-Tube for miliary tuberculosis due to a high level of IFN-γ production

The QuantiFERON-TB Gold In-Tube^® test has excellent specificity for Mycobacterium tuberculosis. However, diagnosis of miliary tuberculosis remains challenging, and the interpretation of QuantiFERON^® results in immunocompromised individuals has not been fully established. Here, we present a patient with military tuberculosis who showed an indeterminate QuantiFERON^® result. A 76-year-old male presented with fever and pancytopenia. Radiological tests did not show the classical miliary pattern. Acid-fast staining and polymerase chain reaction of several specimens were negative for M. tuberculosis. The QuantiFERON^® responses were indeterminate on two separate tests, as interferon-γ (IFN-γ) concentration was high in the negative control. The patient did not respond to anti-microbiological therapy, and developed sepsis and disseminated intravascular coagulation, leading to lethal intracranial hemorrhage. An autopsy showed miliary tuberculosis and aplastic anemia. A literature review suggests a tendency towards indeterminate or false-negative QuantiFERON^® results in immunocompromised individuals or patients with miliary tuberculosis due to low production of IFN-γ. Our patient, however, showed substantial amounts of IFN-γ despite lymphocytopenia, which has not been reported in the literature. The present case suggests that indeterminate results of QuantiFERON^® should be interpreted with caution, as IFN-γ production in patients with miliary tuberculosis can vary significantly, even with sustained lymphocytopenia.     

Treatment of pulmonary tuberculosis

Recently the duration of treatment for pulmonary tuberculosis in The Netherlands was shortened from nine to six months. A six months regimen containing isoniazid (H), rifampicin (R) and pyrazinamid (Z) daily for two months, followed by H and R daily for another four months (2HRZ/4HR) has been proven effective for the treatment of pulmonary tuberculosis, provided the cause is a fully susceptible strain of M. tuberculosis. Worldwide there is an increase in drug-resistant tuberculosis. Since at the start of treatment susceptibility tests often are not available, a fourth drug must be added in the intensive phase. Ethambutol is the drug preferred. This means that one always starts with 4 drugs unless the patient is a contact of an index-case with proven susceptibility and one is sure that he will be compliant ór the patient is infected in the past before 1940, he received never tuberculostatic drugs and one is sure that there is no exogenous reinfection. If the patient has been treated previously and anti-tuberculosis drug resistance is likely, treatment regimens should contain at least two drugs with which he has not been treated before, while a fifth drug routinely must be added in the intensive phase. Amikacin is preferred, since there is no cross-resistance to streptomycin. Consensus on the duration of treatment for extra-pulmonary tuberculosis has not yet been reached, but basically the principles for treatment are the same. This is also true for HIV infected tuberculosis patients. In some serious clinical situations (meningitis, miliary, spine tb) duration of treatment still is 9–12 months. Early involvement of the public health nurse of the municipal health department (GGD) is necessary to ensure patient compliance and treatment supervision.     

Polymerase chain reaction for non-invasive diagnosis of brain mass lesions caused by Mycobacterium tuberculosis: Report of five cases in human immunodeficiency virus-positive subjects

To investigate whether the polymerase chain reaction (PCR) on the IS6110 sequence of Mycobacterium tuberculosis could permit the early and non-invasive diagnosis of tuberculous brain lesions without meningeal involvement in acquired immunodeficiency virus patients, we examined retrospective cerebrospinal fluid (CSF) samples from five patients diagnosed as having cerebral lesions caused by M. tuberculosis. M. tuberculosis deoxyribonucleic acid was detected in CSF samples obtained from each of the patients studied, but in none of the controls. The PCR results coincided with M. tuberculosis isolation from CSF in two patients. In an additional two subjects, culture for M. tuberculosis on CSF was negative, and the diagnosis of central nervous system tuberculosis was achieved by response to specific therapy. In the last patient the PCR result on CSF was confirmed by isolation of M. tuberculosis from brain biopsy. Interestingly, in this patient the CSF did not yield M. tuberculosis isolation when cultured. The data show the value of PCR as a potentially useful approach for the early and rapid diagnosis of cerebral tuberculosis even without meningitis.     

Peliosis hepatis due to disseminated tuberculosis in a patient with AIDS

Peliosis hepatis is a rare histopathological entity of unknown etiology. We present a case of peliosis hepatis in a 44-year-old man with disseminated tuberculosis and acquired immunodeficiency syndrome. The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. Diagnosis of tuberculosis was confirmed by auramine stain, rRNA amplification and culture of Mycobacterium tuberculosis from synovial fluid of the elbow joint. The patient responded favourably to tuberculostatic treatment with four drugs and the early initiation of highly active antiretroviral therapy. Histopathological evidence of peliosis hepatis, without an obvious cause, makes it necessary to rule out tuberculosis, especially in the context of immunodeficiency diseases and immigrants from endemic areas.     

TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicansand spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host''s immune system and increase the risk of invasive candidiasis in an immunocompetent patient.     

Nosocomial transmission of tuberculosis among mentally-handicapped patients in a long-term care facility

Setting: A long-term care facility at Saint-Brieuc hospital, France.Objective: To investigate a nosocomial outbreak of culture-positive pulmonary tuberculosis in 6 (40%) of 15 mentally handicapped HIV-seronegative patients.Design: The factors contributing to the outbreak were analyzed and the restriction fragment length polymorphism (RFLP) patterns of the six Mycobacterium tuberculosis strains were compared.Results: RFLP analysis of the six strains demonstrated an identical banding pattern, thus confirming the spread of a unique strain. A prolonged period of contagiousness due to a delay in diagnosis of the source patient, as well as crowded living conditions in the facility, probably contributed to the outbreak. Surveillance of residents and staff in contact with the source patient resulted in the detection of five secondary cases. Because effective isolation of mentally handicapped patients in the long-term care facility turned out to be difficult, the six case-patients were transferred to the pneumology department, thus limiting the spread of tuberculosis to other residents and staff.Conclusions: The present outbreak emphasizes the difficulties of implementing control measures for preventing the nosocomial transmission of tuberculosis in long-term care facilities for mentally handicapped patients.     

Recurrence of HIV-related tuberculosis in an endemic area may be due to relapse or reinfection

Setting: Two Research Clinics within Nairobi, Kenya, one in the Infectious Diseases Hospital, the national referral centre for tuberculosis, and one in a community based project in Pumwani district, and the Bacterial Molecular Genetics Unit at the London School of Hygiene and Tropical Medicine.Objective: To determine whether recurrence of tuberculosis after ‘adequate’ treatment was due to reinfection with a different isolate of Mycobacterium tuberculosis or to relapse of the original infection.Design: A retrospective comparison by DNA fingerprinting of sets of isolates of M. tuberculosis from patients with recurrence of tuberculosis and in whom isolates from the original episode had been stored was made. Five patients with recurrence of tuberculosis two to nineteen months after adequate treatment and documented clearance of disease were studied.Results: In one patient, fingerprints of the isolates of M. tuberculosis from the recurrence were quite different to those from the original episode; in the other four, the fingerprints were identical.Conclusion: Reinfection rather than relapse was the cause of recurrence in at least one patient. The high ‘relapse’ rates seen in HIV-related tuberculosis in Africa may in part be due to increased susceptibility to reinfection and not to treatment failure.     

Réactivation d’une tuberculose sous bithérapie interféron-pégylé et ribavirine pour une hépatite chronique C

Hepatitis C viral infection can be associated with other infectious diseases including viral and bacterial infections such as tuberculosis. Mycobacterium tuberculosis infection may be latent for many years and revealed during an immunodeficiency state. The responsibility of antiviral treatment in the reactivation of tuberculosis is controversial. We report two cases of tuberculous reactivation during bitherapy with pegylated interferon and ribavirin for chronic hepatitis C. A rapid viral response was obtained in both cases. Tuberculous reactivation occurred at 12 and 13 weeks of antiviral treatment, respectively. Tuberculosis involved urinary tract in one patient and lymph nodes in the other. Antituberculous treatment was given and antiviral treatment maintained. The outcome of tuberculosis was favourable and a sustained viral response was obtained for both patients.     

Streptomycin in tuberculosis

Streptomycin is the most effective antibacterial agent known for tuberculosis. In vitro it has a marked bacteriostatic action on the tubercle bacillus, and in vivo it tends to exert a deterrent effect on the disease in both animals and man. Its therapeutic value is limited by the fact that after exposure to streptomycin for weeks or months, strains of Mycobacterium tuberculosis which are resistant to the effects of the drug may be isolated. Hence streptomycin is of most value in conditions in which temporary suppression of the infection will enable the patient to gain the ascendency over his disease; healing then occurs by natural processes.Prolonged arrest of the disease has been achieved by treatment with streptomycin even in cases of hematogenic tuberculosis, including generalized miliary tuberculosis and tuberculous meningitis. For these conditions large doses of streptomycin must be given parenterally for several months, and for meningitis intrathecal injections are imperative also during the early weeks of treatment. Other types of tuberculosis which have responded to treatment with streptomycin include exudative pulmonary disease, ulcerating lesions of the respiratory tract and tuberculous draining sinuses. It has some place in the treatment of bilateral renal tuberculosis or tuberculosis of a solitary kidney. It also is used before and after thoracic surgery for pulmonary tuberculosis. Because of the potential toxicity, use of the drug probably is contraindicated in conditions which will respond satisfactorily to the usual methods of treatment.Our knowledge of streptomycin is still in a state of flux. Now that the drug is undergoing extensive clinical investigation in many institutions its ultimate place in the treatment of tuberculosis will be determined in time. Experience with this antibiotic agent has proved that tuberculosis is a disease amenable to antibacterial therapy and it is hoped that other usable agents will be forthcoming.     

Present-day treatment of tuberculosis and latent tuberculosis infection

The major objectives of tuberculosis (TB) control are to reduce morbidity and mortality via an early and appropriate treatment of the disease, to prevent carriers of the Mycobacterium tuberculosis bacillus from transmitting it to others, and to prevent latent tuberculosis infection (LTB) sufferers from progressing to the disease. To achieve these objectives, it is imperative to start an appropriate, effective antituberculosis treatment as early as possible, as well as identify contacts of the infected TB patient and others at risk of LTB progressing to TB, in order to establish an appropriate treatment for them. Here we review the bases for treating TB and LTB infections, including those produced by strains resistant to anti-TB drugs.     

No increased prevalence of adrenocortical insufficiency in human immunodeficiency virus-associated tuberculosis

Setting: Acute medical wards, Kenyatta National Hospital, Nairobi, Kenya.Objective: To determine the prevalence of adrenocortical insufficiency in human immunodeficiency virus (HIV)-1 infected and non-infected patients with tuberculosis.Design: One hundred and seventy-four patients with proven tuberculosis (90 HIV-1 positive and 84 HIV-1 negative) were assessed for adrenocortical insufficiency with a 30 min synacthen stimulation test.Results: Fifty-one percent of those with pulmonary tuberculosis and 56% of those with extra-pulmonary tuberculosis had a subnormal cortisol response. However there was no statistically significant difference between the HIV-1 infected and non-infected patients in either group.Conclusion: While an impaired cortisol response is common in tuberculosis, it is no more prevalent in HIV-1 infected patients than non-infected patients with tuberculosis.     

A case of tuberculosis verrucosa cutis in Brazil undiagnosed for 15 years

Tuberculosis verrucosa cutis is a rare medical condition that is caused by the inoculation of Mycobacterium tuberculosis into the skin of a previously sensitized individual. This clinical form of tuberculosis corresponds to 1–2% of all cases of tuberculosis and due to the paucibacillary characteristic of the lesions, patients can be misdiagnosed, accounting for the chronification of the skin infection. Herein, we report the case of a 26-year-old male farmer, presenting plaques with verrucosa and hyperkeratosis features in the left thigh and buttocks during 15 years. M. tuberculosis was identified by PCR and the patient was treated with standard anti-tuberculosis drugs, with subsequent improvement of the skin lesions.     

Pulmonary Mycobacterium abscessus in an AIDS Patient

Mycobacterium abscessus is an unusual pathogen in HIV/AIDS patients. We report a case of M abscessus with review of the literature, which revealed 1 confirmed case in an HIV/AIDS patient. Preliminary diagnosis was presumed to be pulmonary tuberculosis secondary to positive acid-fast bacilli in sputum stain. After initial treatment failure, sputum stains were repeated, and the species was identified; therefore the antibiotic regimen was tailored for M abscessus. Early recognition and treatment of nontuberculous mycobacteria is vital in the reduction of complications and mortality in HIV/AIDS patients. M abscessus is a highly virulent and should be considered as a potential offending pathogen on differential diagnosis in an immunocompromised host.     

Short-course therapy of pulmonary tuberculosis: Doctor's compliance

Objective: The present study, conducted from 1986 to 1991, investigated the accuracy of treatment monitoring performed by practitioners in the out-patient treatment of pulmonary tuberculosis.Design: All patients with smear or culture positive pulmonary tuberculosis, receiving 6-month short-course chemotherapy with Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z), were included. Treatment had been initiated either in our unit, or shortly before, with discharge after an average time of 8 weeks. Practitioners were sent a flow sheet advising how to perform standardized ambulatory controls.Results: Forty-three patients were included in the study, four of whom did not visit their practitioner after discharge. It must be assumed that they did not complete treatment. The average follow-up time of the remaining 39 patients was 159 weeks.In 13 cases the treatment was prolonged without obvious reason. For four patients who had not converted to a negative sputum culture at discharge, negativity was never been proven thereafter. Objective means of assessing patient compliance by H-urine strip testing were undertaken only in three cases. X-ray controls were performed adequately in 44.4% of the cases. By contrast monthly checks of liver enzymes had been done only in 23.1% of the patients.Conclusion: We conclude that even a highly standardized protocol of short-course tuberculosis treatment requires a certain level of experience and compliance on the part of the practitioner. We accordingly recommend that every case of pulmonary tuberculosis should be reviewed at least twice by a chest physician.     

Clinical evaluation of MPT-64 and MPT-59, two proteins secreted from Mycobacterium tuberculosis,for skin test reagents

Setting: Department of Pulmonary Medicine P, Bispebjerg Hospital, Copenhagen, Denmark.Objective: To study the ability of two proteins secreted from Mycobacterium tuberculosis, MPT-64 and MPT-59 to induce delayed type hypersensitivity (DTH) reactions following intradermal administration.Design: In a small scale clinical investigation, skin reactions to these antigens were compared to reactions to tuberculin PPD RT23 in 1) patients with active tuberculosis, 2) BCG vaccinated healthy subjects with close contact with tuberculous patients, and 3) BCG vaccinated healthy subjects without contact with tuberculous patients. Tests for in vitro reactivity to these antigens were carried out in similar groups.Results: All subjects gave positive reaction to tuberculin PPD RT23, whereas approximately half of the subjects in each of the three groups reacted to MPT-59. Two subjects (one patient with tuberculosis and one healthy bacille Calmette-Guérin vaccinated subject without patient contact) reacted to MPT-64. The studies of cell proliferation and induction of interferon-γ (IFN-γ) following stimulation with tuberculin PPD and MPT-64 supported this profile of reactivity.Conclusion: None of the experimental skin test antigens had properties superior to tuberculin PPD RT23 in humans. The failure of MPT-64 to induce delayed type hypersensitivity reactions in the majority of tuberculosis patients is discussed, in view of the potent reactivity to MPT-64 in tuberculous guinea pigs.     

Humoral response to Mycobacterium tuberculosis-specific antigens in African tuberculosis patients with high prevalence of Human immunodeficiency virus infection

Setting: The applicability of serodiagnosis of tuberculosis using Mycobacterium tuberculosis-complex-specific antigens in a Tanzanian population with high prevalence of HIV.Objective: This study was performed to evaluate the usefulness, sensitivity and specificity of serology using M. tuberculosis-specific antigens in the diagnosis of tuberculosis in patients with and without HIV co-infection.Design: Patients with proven pulmonary and extrapulmonary tuberculosis at a major referral centre in Tanzania were enrolled in the study. The control group consisted of patients without a history of previous tuberculosis admitted to the trauma ward and of healthy volunteers. Sera were analysed by an enzyme linked immunoassay (ELISA) using two M. tuberculosis specific proteins as antigen: the 38 kDa protein [3t]and a 17 kDa protein. In addition was recorded presence or absence of BCG scar and tuberculin sensitivity and the sera were tested for HIV and analysed for β-2-microglobulin content.Result: Sensitivity and specificity were markedly reduced in tuberculosis patients with HIV co-infection compared to patients without this disease (73% and 70% versus 52% and 50% respectively).Conclusion: Serology for diagnosis of tuberculosis is not feasible in an HIV endemic region.     

A rare case of primary sinonasal tuberculosis presented with phlyctenular keratoconjunctivitis in a pediatric patient: A case report and literature review

Rationale:Tuberculosis is a common cause of phlyctenular keratoconjunctivitis, especially for patients who live in a high endemic area of tuberculosis. We report a rare case of pediatric phlyctenular keratoconjunctivitis associated with primary sinonasal tuberculosis.Patient concerns:A 7-year-old boy presented with a 5-month history of redness of the left eye accompanied by mild visual impairment. Physical examination revealed elevated pinkish-white nodules with a circumcorneal hypervascularized lesion on the left conjunctiva.Diagnosis:Computed tomography revealed an enhancing soft tissue mass in the left maxillary sinus with bone destruction. Histopathology of maxillary tissue showed chronic inflammation without granuloma. Special stain, culture and polymerase chain reaction for mycobacterium were initially negative. Left maxillary sinus tuberculosis was diagnosed by positive Mycobacterium tuberculosis polymerase chain reaction from formalin-fixed paraffin-embedded maxillary tissue.Interventions:Two month of oral isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 10 months of oral isoniazid and rifampicin without topical eye drops agent were prescribed.Outcomes:Two months after initiation of treatment, the phlyctenular lesion had significantly improved. A follow-up computed tomography showed a significant reduction in the size of the maxillary sinus lesion and the extent of adjacent bone destruction.Lessons:Primary sinonasal tuberculosis is an uncommon cause of phlyctenular keratoconjunctivitis in children. When microbiological and histopathological evidences are absent, polymerase chain reaction analysis has a crucial role in the diagnosis of tuberculosis, especially in patient with uncommon presentation.