Corticosteroid-induced exacerbation of cryptic miliary tuberculosis to acute respiratory distress syndrome: A case report.

RATIONALE: Steroid is known to cause generalized immunosuppression, thereby increasing the risk of new infection or recurrence of tuberculosis. However, corticosteroid as a culprit for exacerbation of miliary tuberculosis-from a cryptic to an overt form-has rarely been described in the literature. Moreover, miliary tuberculosis is hardly diagnosed in a living patient as a primary cause of ARDS even in TB-endemic regions. To the best of our knowledge, this is the first case of a steroid-induced progression of cryptic miliary tuberculosis to ARDS, provided with clear depiction of its radiologic evolution. PATIENT CONCERNS: A 36-year-old male was treated with corticosteroid under suspicion of adult onset still's disease for six-week history of fever. Within 2 weeks since the initiation of corticosteroid therapy, the patient experienced acute exacerbation of cryptic miliary tuberculosis, which evolved to an overt form, appearing as miliary nodules on both chest radiograph and HRCT. Then, his condition suddenly deteriorated to severe acute respiratory distress syndrome in less than a day. DIAGNOSIS: The final diagnosis was miliary tuberculosis complicated by severe acute respiratory distress syndrome. INTERVENTIONS: The patient was placed on classic quadruple anti-TB treatment (isoniazide, ethambutol, rifampin, and pyrazinamide). OUTCOMES: His fever subsided in about 6 weeks and 3 consecutive sputum AFB smears collected on different days were confirmed negative. Diffuse infiltrates on his chest x-ray were completely resolved. LESSONS: The case described here draws a clinical and radiological picture of how an occult form of miliary TB evolved to an overt form with use of steroid, and then suddenly progressed to acute respiratory distress syndrome in an immunocompetent young male. This raises awareness on the potential risk of using corticosteroid in patients with cryptic miliary TB. There is formidable challenge in the diagnosis of miliary TB, especially in the early stages. Atypical or even normal outcomes of clinical, microbiochemical, and radiologic evaluation should not be overlooked and dedicated diagnostic work-up should be performed. For equivocal cases, active surveillance with serial radiographs can be helpful.

Miliary Sarcoidosis: does it exist? A case series and systematic review of literature.

BACKGROUND AND OBJECTIVES: Sarcoidosis typically presents with peribronchovascular and perilymphatic nodules on high-resolution computed tomography (HRCT); a miliary pattern is reported but not well described. DESIGN SETTING: We describe four patients with miliary sarcoidosis and results of a systematic review of all previously reported cases from 1985 onwards. RESULTS: We identified only 27 cases of "miliary" sarcoidosis in the HRCT era. These patients were older (85.2% older than 40 years), had more co-morbidities (72.7%) and were symptomatic compared to "typical" sarcoidosis. Respiratory symptoms were present in 61.9% at diagnosis. Hypercalcemia was seen in 28.5%. On review of HRCT images, only 34.6% (9/26) had a "true miliary" pattern without fissural nodules. In our series, prominent perivascular granulomas were seen on histopathology in all. 44.4% (12/27) had tuberculosis preceding or concurrent to miliary sarcoidosis. Of the eight true associations, tuberculosis preceded sarcoidosis by 52 (median, IQR 36) weeks in six and occurred concurrently in another two. The diagnosis of tuberculosis was clinical in all with concurrent diagnosis of tuberculosis and sarcoidosis. Treatment with steroids had 100% response and 14.2% relapse. CONCLUSIONS: A true miliary pattern in the HRCT era is very rare in sarcoidosis and subtle perilymphatic pattern is nearly always seen; this should be labeled "pseudo-miliary". Prominent perivascular granulomas are associated with true miliary pattern. Miliary sarcoidosis patients are older and symptomatic, needing treatment at diagnosis. "Miliary" sarcoidosis may follow treatment for tuberculosis; concurrent cases possibly indicate the difficulty in differentiating both or a "tuberculo-sarcoid" presentation. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 53-65).

Incidental detection of disseminated peritoneal tuberculosis-varied presentation.

BACKGROUND: Incidental peritoneal tuberculosis represents an uncommon variety of peritoneal tuberculosis and surgeons must be aware of this entity particularly in tuberculosis endemic zones. METHODS: We prospectively analysed cases of incidental peritoneal tuberculosis detected during surgery over a period of last six months. RESULTS: We herein describe three such cases of incidental peritoneal TB detected during surgical exploration for other reasons. CONCLUSION: Diagnosis of disseminated peritoneal tuberculosis often remains a challenging task owing to its non specific clinical presentation and difficulty arises on seeing such a picture intraoperative and raises a question whether to proceed with the decided surgery or not. Frozen section can help in guiding further management but it is not definitive.

Fatal Unusual Miliary Tuberculosis in which a Patient Developed Acute Respiratory Distress Syndrome Induced by Infliximab: An Autopsy Case Report.

Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB. It is important, particularly for patients receiving anti-TNFα agents, to constantly consider the possibility of TB and to prepare for appropriate management.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country.

The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB).We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16-89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion.The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases.Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.

Autologous cytokine-induced killer (CIK) immunotherapy in a case of disseminated tuberculosis.

A 23-year-old woman had dry cough, fever and chest tightness for 1 months. Through thoracic CT scan and serological examination, the patient was clinically diagnosed as disseminated tuberculosis. she was given anti-tuberculosis therapy combined with autologous cytokine-induced killer (CIK) immunotherapy. Through the close follow-ups we found that after immunotherapy Her condition would have a swift improvement and she do not appear liver damage after a large doses of antibiotic therapy. In conclusion, adjuvant autologous CIK immunotherapy is an effective approach for disseminated tuberculosis.

Miliary tuberculosis accompanying paravertebral tuberculosis abscess in an adolescent.

Although miliary tuberculosis (TB) is well known, the incidence of miliary TB accompanying paravertebral abscess is extremely rare in adolescent children. We report a case of paravertebral TB abscess and miliary TB in a 17-year-old male initially presenting with fever, general weakness, back pain, sweating, cough, dyspnea and weight loss. The patient was diagnosed as paravertebral TB abscess and miliary TB. The anti-tuberculous drugs were started and the follow-up imaging showed that the lesions had disappeared without surgery. Although seldom observed, TB should be kept in mind in the differential diagnosis of paravertebral abscess.

FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis.

RATIONALE: The inadequacy of effector T-cell response in containment of tubercle bacilli is believed to result in the development of disseminated forms of tuberculosis (TB), such as miliary tuberculosis (MTB). Regulatory T cells (Treg) plausibly play a critical role in the immunopathogenesis of disseminated TB by suppression of effector immune response against Mycobacterium tuberculosis at the pathologic site(s). To understand the role of Treg cells in disseminated tuberculosis, we studied the frequency and function of Treg cells derived from the local disease site specimens (LDSS) of patients with TB pleural effusion and MTB as clinical models of contained and disseminated forms of disease, respectively. OBJECTIVES: To (1) enumerate the frequency of Treg cells in bronchoalveolar lavage (BAL) fluid of patients with MTB and compare with that of peripheral blood, (2) study the role of Treg cells in suppression of local T-cell response, and (3) study the selective recruitment of Treg cells at the local disease site(s). METHODS: Flow cytometry, reverse transcriptase polymerase chain reaction, and 3-(4,5-dimethylthythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-based cell proliferation assay. MEASUREMENTS AND MAIN RESULTS: Frequency of Treg cells (CD4(+)CD25(+)FoxP3(+)) was significantly higher in LDSS in MTB along with higher levels of FoxP3 mRNA. Importantly, FoxP3(+) Treg cells obtained from the BAL of patients with MTB predominantly produced IL-10 and could suppress the autologous T-cell proliferation in response to M. tuberculosis antigen. CONCLUSIONS: Our results highlight the importance of Treg cells in suppression of effector immune response and their influence on bacillary dissemination, disease manifestation, and severity.

Fever of unknown origin (FUO) caused by miliary tuberculosis: diagnostic significance of morning temperature spikes.

Miliary or disseminated Mycobacterium tuberculosis continues to be a difficult diagnostic challenge. The clinical signs and symptoms of miliary tuberculosis (TB) depend on the extent and severity of both pulmonary and extrapulmonary organ involvement. When miliary TB presents as a fever of unknown origin (FUO), the diagnosis of miliary TB can be particularly perplexing. Because only 10% to 20% of patients have a history of antecedent TB, the diagnosis of miliary TB often goes unsuspected until suggested by miliary calcifications on the chest x-ray. High-resolution computed tomography of the chest has enhanced the diagnosis of miliary TB. In patients with miliary TB, acid-fast smear positivity for acid-fast bacilli is low in sputum, urine, and cerebrospinal fluid. Traditionally, miliary TB has been diagnosed by demonstrating granulomas in liver or bone marrow specimens. Transbronchial biopsy may be used when liver and bone marrow biopsies are negative. We present a case of FUO due to miliary TB with miliary calcifications on the chest x-ray but with negative liver and bone marrow biopsies. The clinical diagnosis of miliary TB was further enhanced by finding daily morning temperature spikes characteristic of miliary TB. Morning temperature spikes are associated with only 2 other entities, that is, typhoid fever and periarteritis nodosa, which are unlikely to be confused clinically with miliary TB. Although fever curves/patterns are diagnostically unhelpful in many febrile conditions, characteristic fever curves/patterns are most useful in the most diagnostically difficult cases with obceure fevers, particularly FUOs. Clinicians should take care to analyze the fever curves/patterns in such patients, which may provide an important clue to the diagnosis and prompt specific diagnostic testing.

[Cosyntropin test in severe active tuberculosis]. / Prueba de cosintropina en tuberculosis activa grave.

BACKGROUND: Frequency of adrenal insufficiency in patients with tuberculosis varies from 0 to 58%; however, all published series excluded severely ill patients. Our objective was to investigate adrenal insufficiency with the low-dose cosyntropin test in patients with severe active tuberculosis. METHOD: From two large university affiliated hospitals, 18 patients with tuberculosis and criteria of sepsis or severe sepsis according to SCCM/ACCP criteria, defined by the present authors as severe active tuberculosis, participated in the study. A low-dose ACTH test with 10 mg of ACTH was performed. After ACTH test, all patients received a stress dose of hydrocortisone (240 mg/day) during their entire hospitalization along with four antituberculous drugs. Abnormal response was considered when elevation of serum cortisol was <7 microg/dl with respect to basal level, 60 min after ACTH administration. RESULTS: Adrenal insufficiency was found in seven patients (39%); no clinical or laboratory data were associated with the presence of abnormal adrenal response. Except in one patient with HIV infection, all the signs and symptoms improved after antituberculous and hydrocortisone treatment. The increment in serum cortisol value post-ACTH test was lower in patients with hypoalbuminemia. CONCLUSIONS: Adrenal insufficiency is frequent in severe active tuberculosis. The efficacy and security of supplemental steroid treatment in severe active tuberculosis should be established by a randomized clinical trial.

Prueba de cosintropina en tuberculosis activa grave / Cosyntropin test in severe active tuberculosis

BACKGROUND: Frequency of adrenal insufficiency in patients with tuberculosis varies from 0 to 58%; however, all published series excluded severely ill patients. Our objective was to investigate adrenal insufficiency with the low-dose cosyntropin test in patients with severe active tuberculosis. METHOD: From two large university affiliated hospitals, 18 patients with tuberculosis and criteria of sepsis or severe sepsis according to SCCM/ACCP criteria, defined by the present authors as severe active tuberculosis, participated in the study. A low-dose ACTH test with 10 mg of ACTH was performed. After ACTH test, all patients received a stress dose of hydrocortisone (240 mg/day) during their entire hospitalization along with four antituberculous drugs. Abnormal response was considered when elevation of serum cortisol was <7 microg/dl with respect to basal level, 60 min after ACTH administration. RESULTS: Adrenal insufficiency was found in seven patients (39%); no clinical or laboratory data were associated with the presence of abnormal adrenal response. Except in one patient with HIV infection, all the signs and symptoms improved after antituberculous and hydrocortisone treatment. The increment in serum cortisol value post-ACTH test was lower in patients with hypoalbuminemia. CONCLUSIONS: Adrenal insufficiency is frequent in severe active tuberculosis. The efficacy and security of supplemental steroid treatment in severe active tuberculosis should be established by a randomized clinical trial.

Diagnostic delay in a multi-organ tuberculosis immunocompetent patient: a case report.

A 67-year-old immunocompetent male presented with intermittent fever for 3 months associated with urinary incontinence, altered bowel habits and history of loss of appetite and weight. He was treated as having enteric fever at various clinics in the city by different physicians. On evaluation the patient was found to have disseminated tuberculosis with involvement of the lungs, eyes, testes, brain, bone, kidneys, liver, spleen and possibly the gastrointestinal tract. This paper reports a case of disseminated tuberculosis to many organs with significant diagnostic delay more than twelve decades after the discovery of the tuberculosis bacillus by Robert Koch.