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.

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.

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.

Miliary tuberculosis involving the central nervous system.

A woman with chronic systemic lupus erythematosus (SLE) was treated with prednisone, and developed an acute febrile neuroinfection. The magnetic resonance images (MRI) showed miliary micronodular lesions distributed diffusely within the central nervous system and lungs. Lumbar puncture showed pleocytosis with predominance of polymorphonuclear leukocytes, hypoglycorrhachia, elevated proteins and smears positive for acid-fast bacilli. The diagnosis was confirmed by culture of Mycobacterium tuberculosis in the cerebrospinal fluid and bronchial biopsy tissue. She was treated with ethambutol, rifampin, isoniazid and pyrazinamide. MRI taken one month later showed significant improvement, but leg weakness persisted. Epidemiologic research showed her uncle with cavitary tuberculosis as the source of infection. He was also treated with combined antituberculous chemotherapy.

Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country.

SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To define the clinical characteristics and outcome of miliary tuberculosis (TB) patients from a low human immunodeficiency virus (HIV) prevalence country. DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001. Clinical characteristics of those dying from miliary TB were compared with those of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or elderly, with a female preponderance. An underlying medical condition was present in 47%. Presenting symptoms were of several weeks' duration, and mostly constitutional (fever and weight loss). Common laboratory findings included anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was observed in 77% of radiographs. Sputum smear and culture were positive in respectively 36% and 52% of those tested. Biopsy was performed in selected patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died were significantly older than survivors and had a more fulminant course. Presence of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the need for ventilation were associated with increased mortality. CONCLUSION: Miliary TB carries a high mortality. It should be considered in patients who present with prolonged systemic symptoms. A positive TB culture or biopsy is needed to establish a diagnosis.

Miliary tuberculosis presenting as acute respiratory distress syndrome, septic shock, DIC, and multiorgan failure.

A 48-year-old Hispanic man developed acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), fulminant hepatic failure, renal dysfunction, pancytopenia and septic shock, and died on his fourth day of hospitalization. The postmortem examination revealed caseating and non-caseating granulomas in all sampled organs. Antemortem sputum and postmortem pulmonary tissue cultures were positive for Mycobacterium tuberculosis. Miliary tuberculosis (TB) was diagnosed. Factors associated with mortality include delayed diagnosis/therapy and presence of ARDS, DIC, septic shock, and multiorgan failure.

Cutaneous tuberculosis: diagnosis and treatment.

As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multi-drug resistant pulmonary tuberculosis. Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine cause tuberculosis involving the skin. True cutaneous tuberculosis lesions can be acquired either exogenously or endogenously, show a wide spectrum of morphology and M. tuberculosis can be diagnosed by acid-fast bacilli (AFB) stains, culture or polymerase chain reaction (PCR). These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid. The tuberculids, like cutaneous tuberculosis, show a wide spectrum of morphology but M. tuberculosis is not identified by AFB stains, culture or PCR. These lesions include lichen scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis, most cases of erythema induratum of Bazin and some cases of papulonecrotic tuberculid. Diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with diagnostic testing; in addition to traditional AFB smears and cultures, there has been increased utilization of PCR because of its rapidity, sensitivity and specificity. Since most cases of cutaneous tuberculosis are a manifestation of systemic involvement, and the bacillary load in cutaneous tuberculosis is usually less than in pulmonary tuberculosis, treatment regimens are similar to that of tuberculosis in general. In the immunocompromised, such as an HIV infected patient with disseminated miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are paramount. Unfortunately, despite even the most aggressive efforts, the prognosis in these individuals is poor when multi-drug resistant mycobacterium are present. An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasingly common skin disorder.

Tuberculose miliar: relato de caso / Miliary tuberculosis: report of a case

This is a case report of generalized miliary tuberculous infection in a 80-year old white male without the acquired immunodeficiency syndrome, whose death was caused by progressive hematogenous seeding similar to those cases of preantibiotic era. The importance of autopsy studies to uncover silent or protean infections specially in cases of cryptic or chronic hematogenous miliary tuberculosis, is emphasized.

Relata-se caso da forma miliar generalizada da infecção tuberculosa, em homem de 80 anos não portador da síndrome da imunodeficiência adquirida (SIDA) cujo óbito decorreu de progressiva disseminação hematogênica, semelhante a casos da era pré-antibiótica. Enfatiza-se a associação com estados de subnutrição e imunodepressão, a dificuldade na abordagem clínica e a importância da necropsia para estabelecer o diagnóstico da disseminação miliar hematogênica crônica ou críptica.

Tuberculosis hematógena tardía / Late tuberculosis

La tuberculosis hematógena tardía es una forma de tuberculosis miliar que se presenta mucho tiempo después de la infección primaria, a partir de un foco extrapulmonar, por lo general silente. Es forma de tuberculosis se produce debido a una disminución de la inmunidad celular y humoral, generada por una causa intercurrente. Entre estas se pueden citar las terapias inmunosupresoras, neoplasias, diabetes, insuficiencia renal crónica y enfermedades virales. Tiene una alta mortalidad, que se estima en un 85 por ciento de los afectados. Se presenta un paciente de sexo masculino, de 56 años de edad que ingresa al Servicio de Clínica Médica para ser estudiado con diagnóstico de síndrome febril prolongado. Se concluye señalando que, para disminuir la alta mortalidad de esta entidad, debe realizarse su diagnóstico y tratamiento en forma precoz, y para ello hay que tenerla presente en el diagnóstico diferencial del síndrome febril prolongado

Quatro casos de presumível coroidite tuberculosa em pacientes infectados pelo HIV / Four cases of probable tuberculous choroiditis in patients HIV infected

Desde o início dos anos 80 tem-se observado um aumento da associaçäo da infecçäo pelo Mycobacterium tuberculosis e o paciente infectado pelo HIV ou com AIDS. Quatro pacientes portadores de AIDS, tuberculose e manifestaçöes oculares säo descritos pelos autores. Dois pacientes eram portadores de tuberculose miliar, um com tuberculose pulmonar com padräo radiológico atípico e um paciente com tuberculose ganglionar. Até a presente data, este é o primeiro relato de presumível coroidite tuberculosa em pacientes com AIDS, apesar da alta prevalência da tuberculose no Brasil

[Late disseminated tuberculosis. Anatomo-clinical correlations in 40 cases]. / Tuberculose disséminée tardive. Corrélation anatomo-clinique de 40 cas.

Late disseminated tuberculosis has a diversity of clinical presentations and is difficult to diagnose. This disease has a growing importance in industrialised countries and we decided to study forty cases correlating autopsy findings with the clinical date. This diffuse form of miliary tuberculosis occurs long after the primary infection. It is a disease of the elderly (72.5% greater than 65, 32.5% greater than 80). It represented 42.5% of serious tuberculous cases observed at autopsy over the same period. At the top of the list of clinical presentations is fever (57.5%) followed by loss of weight (42.5%) and respiratory symptoms (32.5%). The diagnosis of tuberculosis was only considered in 37.5% of cases (15/40), however the pulmonary radiograph suggested the diagnosis in the majority of cases. In 62.5% of cases (25/40) tuberculous disease was not recognised in the clinic, the presenting symptomatology was attributed in nearly half the cases to neoplastic disease. Autopsy showed that the primary disease was caseous tuberculosis in 25% of cases and in 25% there was a cancer. Our observations underline the diagnostic challenge of late disseminated tuberculosis in clinical practice and also discern the particular clinical characteristics and anatomo-pathological features.