PPD Skin Test Research Articles

Follow-up of patients given isoniazid prophylaxis in multiple myeloma patients underwent autologous stem cell transplantation

Aims: With the developments in recent years, multiple myeloma (MM) a plasma cell discrazy has become a disease whose life expectancy is expressed in 10 years. Stem cell transplantation still maintains its place in this disease and post-transplant prophylaxis is important. One of these is antituberculosis prophylaxis. We wanted to introduce this barren subject. Methods: A retrospective screening of patients with MM who were started on isoniazid (INH) prophylaxis and underwent autologous stem cell transplantation was planned. Results: Antituberculosis prophylaxis was given to 25 patients (6.5%) out of 380 MM transplant patients. PPD skin test was positive in 20 of the patients who were given INH prophylaxis. 15 patients had pulmonary findings compatible with latent tuberculosis infection. Ten patients had both. No patients progressed to active tuberculosis. There was no difference between those who used INH/not in terms of obtaining CR or VGPR and other responses (p=0.220). And there was no survival difference between INH users and others. Conclusion: Follow-up of patients receiving INH prophylaxis is also important. Histopathological findings obtained with autopsy of myeloma patients who died with pneumonia after autologous transplantation with INH prophylaxis will answer the question of whether it was tuberculosis.

Multibacillary, cavitary tuberculosis in an immunocompetent child perpetuating to family members - A Case Report

Cavitary tuberculosis in the immunocompetent paediatric age group is not a common occurrence. The cavitary condition of the disease relates to a high bacillary load and such patients are highly infectious. If not treated early, it can cause perpetuation of infection to close contacts in the family who also can eventually turn positive for tuberculosis (TB). Here is a case of an eleven-year-old girl with a history of cough for 2 months present throughout the day, associated with yellowish, non-blood-tinged sputum, fever and chills. The Ziehl Neelson stain revealed acid fast bacilli 3+. Sputum culture by MB/BacT automated system flagged positive on day 12. The MPT64 antigen test confirmed Mycobacterium tuberculosis. The PPD skin test was significantly positive in family members. The child improved with antitubercular treatment and her family members were negative for AFB and chest X-ray findings. Open cases of tuberculosis with cavitary lesions in the paediatric age group need to be recognized early with a high index of clinical suspicion and treated along with contact tracing of close contacts.

Deletion in KARLN intron 5 and predictive relationship with bovine tuberculosis and brucellosis infection phenotype.

Kalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.

Case study on Tuberculous Meningitis (TBM)

Tuberculous Meningitis (TBM) is an inflammation of the meninges (membrane) around the brain or spinal cord and it’s caused by Mycobacterium tuberculosis. The clinical features are headaches, behavioral changes, Fever, stiff neck, vomiting and for older children and adults progress from irritability to confusion, drowsiness and stupor. It’s diagnosed by Examination of the Mycobacterium tuberculosis, blood culture, chest X-ray, CT scan of the head and skin test for tuberculosis (PPD skin test. TB meningitis treatment includes isoniazid, rifampin, pyrazinamide and moxifloxacin or levofloxacin and Corticosteroids.

Kikuchi-Fujimoto Disease: Review of 11 Cases Diagnosed Over 10 Years at a Tertiary Care Hospital in Doha, Qatar.

IntroductionKikuchi-Fujimoto (KF) disease is a rare and self-limiting disorder of unknown aetiology characterized by cervical lymphadenopathy (CLN) and fever. The pathophysiology remains unclear and may be triggered by an infectious agent leading to a self-limiting autoimmune process. There are no confirmatory laboratory tests and lymph node biopsy is required to differentiate KF disease from other serious conditions.Materials and methodsWe report 11 cases of KF disease diagnosed at Hamad General Hospital, Qatar, between 2006 to 2016. The diagnosis is based on clinical presentation, investigations and histopathological examination of lymph nodes.ResultsAll patients had painful neck swelling (average duration of 2.9 weeks) and 10 had fever (average duration of 3.2 weeks). Five patients developed mild leucopenia which resolved completely. HIV and tuberculosis (TB) screening including sputum for AFB, a PPD skin test and chest x-ray was done for all patients and came back negative. Autoimmune screening was done for all patients and excluded any rheumatological disease. Ultrasound and CT of the neck confirmed cervical lymphadenopathy. Except for hepatomegaly in one patient, CT scans of the chest and abdomen were negative for any lymphadenopathy or organomegaly (performed in seven patients). Diagnosis was confirmed on lymph node excision biopsy. Histopathological examination showed findings consistent with the diagnosis of histiocytic necrotizing lymphadenitis (KF disease).ConclusionKF disease should be kept in mind for patients presenting with fever and CLN. Lymphoma, TB and autoimmune diseases like systemic lupus erythematosus should be excluded in such patients.LEARNING POINTSKikuchi-Fujimoto (KF) disease should be kept in mind in patients presenting with fever and cervical lymphadenopathy with or without other constitutional symptoms.There are no confirmatory blood tests and KF disease requires histopathological examination of involved lymph nodes for confirmation.Autoimmune disease like systemic lupus erythematosus, tuberculosis, lymphoma and other malignancies should be ruled out by appropriate investigations.Recurrence of disease, although rare, is a possibility and needs histopathology for confirmation.

NECROTIZING PNEUMONIA CAUSED BY ACINETOBACTER IIWOFI IN A PREVIOUSLY HEALTHY CHILD

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: With the extensive immunization campaign, the occurrence of Necrotizing Pneumonia has become less through the years. Early recognition and timely intervention of Pneumonia has contributed to the progressive decline in its incidence. Several factors exist causing reemergence of this uncommon complication. CASE PRESENTATION: This is a case of a 2-year-old female with massive pleural effusion of the left lung, presenting as 3-week productive cough, fever and tachypnea. She had respiratory distress, chest lagging on the left, retractions, decreased fremitus and breath sounds, and dullness with crackles on the left mid to base lung. Chest ultrasound and CT scan showed massive pleural effusion with consolidation on the left lung and atelectasis on the right upper lung. Chest tube drain was exudative, culture, KOH and AFB were negative. Cytology testing was consistent with abscess and negative for malignant cells. Blood culture and PPD skin test were negative. Cefotaxime, Clindamycin, Azithromycin, Vancomycin and Piperacillin- Tazobactam were given, but no response and chest CT scan showed necrosis of the parenchyma. Broncheoalveolar lavage was done revealing heavy growth of Acinetobacter iiwofi and Linezolid and Ciprofloxacin were given with noted clinical improvement and was discharged. DISCUSSION: Necrotizing Pneumonia entails necrosis and liquefaction of consolidated lung tissue. Chest xray has poor sensitivity in cavitary lesion, hence CT scan is the standard of imaging. Risk factors in one study revealed children less than 5 years old, absence of existing medical comorbidity, immature polymorphs in peripheral blood smear, CRP >12 mg/dL, and thrombocytopenia, are associated with pneumonia complications. Prolonged antibiotic treatment has been the cornerstone of therapy in necrotizing pneumonia. The patient was initially given Ceftriaxone and Vancomycin with poor response, due to Vancomycin’s poor parenchymal penetration. Linezolid produced better outcome since it inhibits protein synthesis and toxin production. Surgical approach was considered, but with clinical improvement, medical treatment was continued. Follow up with subsequent chest imaging showed gradual improvement, which confirmed the adequacy of the antibiotic given. CONCLUSIONS: Despite rigorous efforts of the government to provide adequate vaccine coverage, increasing occurrence of necrotizing pneumonia are reported. Increasing awareness among healthcare practitioners for early recognition and timely referral to subspecialist should be emphasized. Necrotizing pneumonia is one of the conditions where medical treatment, over surgical approach, offers the greater advantage. With appropriate antibiotic treatment, the prognosis of necrotizing pneumonia is full recovery. Reference #1: 1. Masters B, Isles A, Grimwood K. Necrotizing pneumonia: an emerging problem in children?. NPJ Open Access [Internet]. 2017 July 25 [cited 2018 Oct 1]; 9:11. Available from: https://pneumonia.biomedcentral.com/articles/10.1186/s41479-017-0035-0 DOI 10.1186/s41479-017-0035-0 Reference #2: 2. Erlichman I, Breuer O, Shoseyov D, Cohen-Cymbreknoh M, Koplewitz B, Aver-buch D, et al. Complicated community acquired pneumonia in childhood: Dif-ferent types, clinical course, and outcome. Pediatric Pulmonology [Internet]. 2017 Feb [cited 2018 Oct 1]; 52:2. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.23523 DOI.org/10.1002/ppul.23523 Reference #3: 3. Treatment Guidelines for the Complicated Pneumonia: Parapneumonic Effu-sions, Empyema, Necrotizing Pneumonia, And Pulmonary abscess. Children’s National Medical Center [Internet]. Washington; 2008 Sept 1 [cited 2018 Oct 1]; 13p. Available from: http://www.nccpeds.com/rotations/wrPICU/Algorithms/ Linked%20complicated%20pneumonia%20guidelines%20final.pdf DISCLOSURES: No relevant relationships by shanta carleen magalit, source=Web Response

Gastric Sarcoidosis: A Rare Manifestation of the Disease

Sarcoidosis is a chronic systemic inflammatory disease of unclear etiology characterized by non-caseating granulomas. It can affect nearly every organ system. Alimentary tract sarcoidosis is atypical within which gastric sarcoidosis is the most common form. Involvement of the alimentary tract is usually as a part of systemic disease or rarely as an isolated finding. Symptomatic gastric sarcoidosis is further more distinct. We present a rare case of sarcoidosis initially presenting with gastrointestinal symptoms and without pulmonary symptoms. A 57 years old morbidly obese African American female with PMH of HTN and DM type II presented with epigastric abdominal pain, nausea, vomiting, and a six month history of unintentional 60lb weight loss secondary to early satiety and dysgeusia. She was found to have hypercalcemia of 13.4 mg/dL, AKI and lactic acidosis. A non-contrast CT and subsequent CTA of the abdomen and pelvis showed small bowel wall thickening, abdominal lymphadenopathy, patent celiac axis and mesenteric vessels, and numerous ˜1mm lung base nodules. EGD revealed erythematous mucosa of gastric antrum with erosions and shallow duodenal erosions (Image 1). Gastric biopsy revealed granulomatous inflammation. Duodenal biopsy showed mild villous blunting without granulomas. Stains for fungal elements and AFB was negative. No intestinal metaplasia, dysplasia or malignancy was noted. PTH, PTHrP, and TSH were normal. CT chest revealed centrilobular nodular interstitial opacities with extensive bilateral mediastinal and hilar lymphadenopathy (Image 2). FNA of right hilar lymphadenopathy under EBUS revealed epithelioid histiocytes and lymphocytes suggestive of granulomatous inflammation. No malignant cells were seen. Fungal and AFB stains and AFB culture were negative. PPD skin test was negative. Patient's GI symptoms improved with supportive care. Given the lack of pulmonary symptoms, corticosteroids were not started. Patient has continued to do well during subsequent clinic follow up. Gastric sarcoidosis is among the rarer subsets of the disease. Most cases have been described as posthumous discoveries on autopsy of known sarcoidosis patients as patients are usually asymptomatic. Biopsy proven pulmonary and gastric sarcoidosis presenting with GI symptoms and an anomalous lack of pulmonary symptoms is exceptionally rare and questions a broader understanding for consideration of sarcoidosis diagnosis.2704_A Figure 1. Erythematous mucosa of gastric antrum with erosions on EGD. H. pylori negative.2704_B Figure 2. CT Chest: Centrilobular nodular interstitial opacities throughout both lungs with moderate mediastinal, hilar, and upper abdominal lymphadenopathy

PPD-specific IgG1 antibody subclass upregulate tumour necrosis factor expression in PPD-stimulated monocytes: possible link with disease pathogenesis in tuberculosis.

Cachexia is a prominent feature of advanced tuberculosis, in association with increased expression of the monokine tumour necrosis factor (TNF)-alpha. Monocytes, have high affinity receptors (mannose, complement and Fc gamma1 and gamma111) which mediate antigen uptake and subsequent cytokine activation. Several mycobacterial proteins, including PPD, can stimulate TNF-alpha secretion from monocytes. However, the role of various receptors in stimulating or regulating TNF-alpha secretion is still unclear. We have previously shown selective augmentation of opsonic antibodies (IgG1 and IgG3) in tuberculosis patients with advanced pulmonary disease. We now analyse the role of opsonizing antibodies in modulating TNF-alpha expression in antigen stimulated monocytes. PPD was used as the prototypic mycobacterial antigen to stimulate monocytes from PPD skin test negative donors (n = 7) in the presence of plasma from tuberculosis patients (n = 8), containing known amounts of IgG1 and IgG3 anti-PPD antibodies. TNF-alpha secretion was enhanced in the presence of TB plasma (4/8) but not in the presence of control plasma. Using Spearman Rank analysis (two-tailed Fisher exact test), a significant correlation (rho = 0.762; P = 0. 04) was observed between IgG1 antibodies and enhancement of TNF-alpha secretion. No significant association was observed with IgG2 (rho = 0.310; P = 0.41), IgG3 (rho = 0.089; P = 0.81) or IgG4 (rho = - 0.357; P = 0.347) subclass antibodies. Absorption of IgG1 with protein 'A' removed the enhancement of TNF-alpha secretion activity from the plasma samples. Our results therefore indicate that IgG1 antibodies may enhance the chronic release of TNF-alpha in TB patients with progressive disease and, for the first time, show a direct link between disease pathogenesis and raised antibody levels.

Eales disease: A case report

The ocular manifestation of Eales Disease results from overlapping stages of vasculitis, occlusion, and neovascularization. This mimics several disease entities ranging from infectious to inflammatory causes. We report a case of a young healthy Filipino male with few months painless monocular sudden blurring of vision. On eye exam, there was vitreous hemorrhage with ultrasound evidence of retinal detachment on the bad eye. The good eye, on the other hand, has perivascular sheathing of peripheral vessels, which, on fluorescein angiography showed dye staining, extravasation, vessel obliteration, capillary dropouts, and collateral formation. Laboratory studies were normal except for positive PPD skin test. Infectious and inflammatory entities were considered less likely and Eales disease as a more probable diagnosis. The patient underwent pars plana vitrectomy on the bad eye where intraoperatively revealed fibrovascular fronds and an attached retina. Pan-retinal photocoagulation was also done on both eyes. Visual acuity after 3 months was 6/6 for both eyes. Management of Eales disease is similar to other vasoocclusive diseases where prevention of further ischemia and neovascularization is the main goal of treatment.

Tuberculous aortitis, an unusual presentation of tuberculosis

51-year-old female who recently emigrated from Mexico with past history of coronary artery disease (CAD) status post coronary artery bypass grafting (CABG) two years prior who presented with chest pain. She reported diffuse anterior chest pain that radiated to the back. She also reported a 4 kg weight loss, night sweats, chills and fevers over the same time period. In the emergency department her EKG was normal, cardiac enzymes were negative and preliminary CTA report was concerning for possible aortitis vs aortic hematoma. Her ESR and CRP were elevated but autoimmune work-up including ANCA and ANA was negative, raising suspicion for an underlying infectious etiology. The patient had a positive PPD skin test with 17 mm induration, a positive quantiferon test and chest X-ray showed numerous lung nodules bilaterally, consistent with a diagnosis of tuberculosis. Transesophageal echocardiogram showed regional thickening of ascending aorta with the major differential being aortitis vs intramural hematoma vs chronic aortic dissection. Her records from her CABG done in Mexico were obtained and described a porcelain aorta, which further supported a diagnosis of TB aortitis. Cardiothoracic surgery was consulted in light of these results, and they believed that the patient’s aortic thickening was caused by diffuse aortitis. Thus she was diagnosed with aortitis secondary to her underlying tuberculosis. Most cases of aortitis are noninfectious in nature. However, although rare, infectious causes should always be considered due to associated high morbidity and mortality as well as potential reversibility. Tuberculosis as a cause of aortitis is very rare even in developing countries. Tuberculous aortitis should always be considered among patients with aortitis or aortic hematomas, especially if they are among high risk population for tuberculosis or have a history of untreated tuberculosis.

Evaluation of ‘Indeterminateʼ Results of QuantiFERON Gold In-tube Assay as Screening Test for Latent Tuberculosis Infection in Liver Transplant Candidates

Introduction: Screening of latent tuberculosis (LTB) infection is recommended in solid organ transplant recipient because of high risk of severe reactivation of LTB after immunosuppression. Traditionally, screening for LTBI was done by PPD skin test and recently Interferon release assay QuantiFERON test (QFT) has shown similar rates of detecting LTB in liver transplant (LT) candidates. Due to convenience of its use and recent support by AASLD guidelines, LT centers have started using QFT as the initial test for LTB screening. QFT is found to have intrinsic inability to result adequately in immunocompromised patients and this leads to a moderate rate of “indeterminate” (IND) test results in LT candidates. We evaluated our experience with QFT as screening test for LT candidates in this retrospective study. The aim of the study was to explore the clinical parameters which are associated with IND results. Methods: We reviewed the data from consecutive 100 LT candidates who underwent QFT as initial screening test after the change in the policy for LT evaluation at the two particpating liver transplant centers. Results: Our study consisted of adults (56.7yrs), mostly Caucasian (60%) LT candidates with decompensated cirrhosis (96%) mainly from chronic hepatitis C infection (38%). All 100 subjects underwent initial QFT which resulted as positive in 6, negative in 68 and IND in 26 subjects. Most (87%) of the tests were done at a single laboratory with (78%) in outpatient settings. When compared with subjects without IND results, IND result was significantly associated with: lower sodium, albumin, and zinc levels; higher Ferritin and MELD score. No differences in age, gender, medications and etiology of liver cirrhosis were present among subjects with and without IND results after initial QFT. Screening tests were repeated in 15 of 26 subjects with initial IND results. 9 out of 15 had PPD performed and all resulted in negative test. The remaining 6 had QFT repeated, 3 had negative result and 3 stayed as IND results. 9 of the 26 initially IND resulted subjects underwent LT and after a mean of 10 months follow-up none has reactivation of LTB. Conclusion: The clinical parameters which indicate the severity of liver disease and possibly chronic inflammation are associated with QFT IND results, the rates of such results was higher (26%) in our population. Since, IND result cannot establish the absence of LTB we suggest repeating QFT to challenge inter-individual variability related to the timing of the test.

Diagnostic value of enzyme-linked immunospot assay using CFP10/ESAT6 fusion protein as antigen in spinal tuberculosis.

To establish a method of detecting spinal tuberculosis (TB) infection by enzyme-linked immunospot (ELlSPOT) assay and evaluate the value of CFP10/ESAT6 fusion protein for diagnosis of spinal TB. Suspected spinal TB patients were prospectively recruited in two hospitals (First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine; Nanfang Hospital, Southern Medical University) from May 2012 to December 2013. Data on clinical characteristics of the patients and conventional laboratory results were collected. Compare and analyze the positive detection rate in spinal TB diagnosis by different methods including ELISPOT detection and conventional detection methods. 47 patients with spinal TB had available biopsy or surgical specimens for histopathological examination and 41 specimens had pathological features consistent with a diagnosis of TB infection. Among the spinal TB patients and non-TB disease patients,the overall sensitivity, specificity, positive predictive value, and negative predictive value of the ELISPOT assay in spinal TB diagnosis were 82.7%,87.2%,89.6%, and 79.1%,respectively; the 4 indexes of the PPD skin test were 61.5%, 46.2%, 60.4%, and 47.4%, respectively;those of the antibody detection were 55.8%, 61.5%, 65.9%, and 51.1%. The positive rate of ELISPOT was significantly higher than those of PPD skin test and antibody detection test (82.7% vs. 61.5%, Χ² =5.786, P=0.016; 82.7% vs. 55.8%, Χ² =8.847, P=0.003), but not significantly different from the positive rate of pathological examination (82.7% vs. 87.2%, Χ² =0.396, P=0.529). Moderate agreement was found between pathological examination and the ELISPOT assay (87.2%, Κ=0.498, P=0.001). With high sensitivity and specificity, the ELISPOT assay using CFP10/ESAT6 fusion protein as antigen is an effective technique for auxiliary diagnosis of spinal TB.

AB0654 Survey of the Tolerance to the First Anti-TNF Therapy: Reasons for Discontinuation Including Loss of Efficacy and Adverse Effect of Different Anti-TNF Therapies (Data From Moscow Register)

BackgroundAnti-TNF therapy has been proven highly effective in patients with spondyloarthritis, but about 30% of the patients developed secondary inefficacy or adverse effects (AE).ObjectivesEstablishing the reasons and the frequency of...

A Novel Case of Thyroid Dysfunction Associated with Adalimumab Use for Crohnʼs Disease

Case Report: A 58-year-old male with history of Crohn's iliocolitis diagnosed in 1997, status post right hemicolectomy secondary to obstruction in 2007, was being evaluated for abdominal pain, nausea, and vomiting of 2 days duration. His medications included mesalamine 2.4 gm per day, losartan, and omeprazole. Vital signs were unremarkable and physical examination revealed slightly distended abdomen with hypoactive bowel sounds. Flat and upright x-ray of abdomen was unremarkable without evidence of obstruction. Computerized tomography scan of abdomen showed early or partial small bowel obstruction most likely secondary to adhesions. Patient was given trial of prednisone with improvement in his symptoms. After all the appropriate workup including negative PPD skin test and hepatitis panel, patient was started on adalimumab. Patient did well with initial injections but developed injection site erythema along with facial swelling and tightness in the throat with second dose. He was treated with methylprednisolone and adalimumab was discontinued. TSH came back elevated at 28.60 mcIU/mL (ref range: 0.465-4.68 mcIU/mL). As the patient did not have any history of thyroid disease, repeat TSH was ordered for confirmation of initial result and it showed worsening of TSH at 45.3 mcIU/mL in just 3 days. Free T4 was low at 0.59 ng/dL (ref range 0.78-2.19ng/dL). Thyroid peroxidase antibody was elevated at 150 IU/mL (ref range: 0- 34 IU/mL) and anti-thyroglubulin antibody was negative. Patient was started on levothyroxine 50 mcg per day. Repeat lab works in 2 months showed normal free T4 along with improvement in TSH to 19.6 mcIU/mL. Patient is currently being treated with azathioprine for his Crohn's disease. Discussion: We report a rare case of thyroid dysfunction associated with adalimumab use. Adalimumab is a recombinant anti-tumor necrosis factor alpha (TNF-alpha) IgG1 monoclonal antibody which blocks inflammatory activity of TNF-alpha. Major indications for use of adalimumab are moderate to severe Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, and other autoimmune diseases. The most common adverse reactions are infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. A study by eHealthMe has reported 15 patients out of 130,505 developing autoimmune thyroiditis while taking adalimumab which accounts for incidence rate of 0.01%. Majority of patients were female (84.21%). A case of subacute thyroiditis after being treated with Adalimumab for refractory palmo-plantar pustular psoriasis has also been described in the literature.

Evaluation of an enzyme-linked immunospot assay for the immunodiagnosis of atypical spinal tuberculosis (atypical clinical presentation/atypical radiographic presentation) in China

BackgroundAtypical spinal tuberculosis (TB) usually presents in a slowly indolent manner with nonspecific clinical presentations making the diagnosis a great challenge for physicians. New technologies for the detection of atypical spinal TB are urgently needed. The aim of this study was to assess the diagnostic value of an enzyme-linked immunospot (ELISPOT) assay in clinically suspected cases of atypical spinal TB in China. MethodsFrom March 2011 to September 2012, a total of 65 patients with suspected atypical spinal TB were enrolled. In addition to conventional tests for TB, we used ELISPOT assays to measure the IFN-γ response to ESAT-6 and CFP-10 in T-cells in samples of peripheral blood mononuclear cells. Patients with suspected atypical spinal TB were classified by diagnostic category. Data on clinical characteristics of the patients and conventional laboratory results were collected. ResultsOut of 65 patients, 4 were excluded from the study. 18 (29.5%) subjects had culture-confirmed TB, 11 (18.0%) subjects had probable TB, and the remaining 32 (52.5%) subjects did not have TB. Generally, the features of atypical spinal TB include the following aspects: (1) worm-eaten destruction of vertebral endplate; (2) destruction of centricity of the vertebral body or concentric collapse of vertebral body; (3) tuberculous abscess with no identifiable osseous lesion; (4) contiguous or skipped vertebral body destruction. 26 patients with atypical spinal TB had available biopsy or surgical specimens for histopathologic examination and 23 (88.5%) specimens had pathologic features consistent with TB infection. The sensitivities of the PPD skin test and ELISPOT assay for atypical spinal TB were 58.6% and 82.8%, and their specificities were 59.4% and 81.3%, respectively. Malnutrition and age were associated with ELISPOT positivity in atypical spinal TB patients. ConclusionsThe ELISPOT assay is a useful adjunct to current tests for diagnosis of atypical spinal TB.

T-SPOT.TB in the diagnosis of tuberculous peritonitis

To evaluate the value of T-SPOT.TB in the diagnosis of tuberculous peritonitis (TBP). A total of 50 patients with clinically suspected TBP admitted from August 2011 to July 2012 from the Third Xiangya Hospital were enrolled in this prospective cohort study. Peripheral blood T-SPOT.TB, purified protein derivatives of tuberculin (PPD) skin test, serum tuberculosis antibody (TB-Ab) and ascitic adenosine deaminase (ADA) were measured in the 50 patients and we compared the diagnostic value of the 4 methods. According to the standard of diagnosis of TBP and grouping, 24 patients were diagnosed with TBP, 17 non-TBP and 9 undiagnosed in the end. The sensitivity of T-SPOT.TB for the diagnosis of TBP was 91.7% (22/24), with statistical significance when compared with PPD skin test 37.5% (9/24), serum TB-Ab 16.7% (4/24), and ascitic ADA 36.4% (8/22) (P<0.01). The specificity of T-SPOT.TB for the identification of non-TBP was 76.5% (13/17), without statistical significance when compared with PPD skin test 70.0% (7/10), serum TB-Ab 78.6% (11/14), and ascitic ADA 100% (14/14) (P>0.05). The positive prediction value of T-SPOT.TB for the diagnosis of TBP was 84.6% (22/26), without statistical significance when compared with PPD skin test 75.0% (9/12), serum TB-Ab 57.1% (4/7), and ascitic ADA 100%(8/8) (P>0.05). The negative prediction value of T-SPOT.TB for the identification of non-TBP was 86.7% (13/15), with statistical significance when compared with PPD skin test 31.8% (7/22), serum TB-Ab 35.5% (11/31), and ascitic ADA 50.0% (14/28) (P<0.05). Peripheral blood T-SPOT.TB for the diagnosis of TBP is highly sensitive, which is better than PPD skin test, serum TB-Ab, and ascitic ADA. T-SPOT.TB has an important reference for diagnosing suspected TBP quickly and accurately.

Evaluation of Tuberculin Skin Test Response and Interfering Factors in Patients with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disease in pediatric age group. Mycobacterium tuberculosis infection (TB) is an important cause of mortality and morbidity in patients with inflammatory rheumatologic disease. The objective of this study is to determine to what extent active disease and use of drugs in JIA affects response to PPD skin test and thus to investigate the significance of PPD skin test in the diagnosis of latent TB. 77 children diagnosed with JIA according to ILAR diagnostic criteria and routinely followed by our rheumatology clinic were included in the patient group. Patients were grouped according to subtypes of disease, activity status and drugs they used. Control group was formed from 58 healthy children. PPD skin test was applied to each subject and the number of BCG scars of all cases was recorded. We found no significant difference in PPD induration diameters between JIA and control group (p > 0.05). The number of BCG scar is similar in both groups. In the control group, age and number of BCG scars and PPD skin test diameter are positively correlated. But there is no such significant relationship in patients with JIA (p > 0.05). PPD induration diameter of patients with active disease is significantly shorter than patients in remission (p > 0.05). PPD induration diameter of patients treated with steroid and disease modifying anti-rheumatic drug (DMARD) and underwent remission were not significantly different from the control group. When compared with patients using other drugs, patients on remission using steroid and DMARD have shorter PPD induration diameter. Activity of disease and drugs used (steroid, DMARD) affects PPD response. In the diagnosis of latent TB, normal range of PPD diameter in healthy child changes in JIA patient with active disease. That the PPD diameter is shorter than normal range could indicate underlying TB infection. This fact should be considered in the follow-up of the patients with JIA.

Intraocular Tuberculosis

ABSTRACT Intraocular tuberculosis remains a major diagnostic challenge and it is extremely important to establish the diagnosis as the specific treatment helps in reducing the recurrences, thus reducing ocular morbidity. The present review aims to describe the global epidemiology and pathogenesis of intraocular tuberculosis with clinical spectrum and different presentations. The challenges in establishing the diagnosis with role of conventional tests like PPD skin test as well as current diagnostic tests including interferon gamma release assay and molecular diagnostic tests are discussed. The treatment requires anti-tuberculosis therapy with the use of concomitant corticosteroids and carries good prognosis provided the treatment is started in the early stage. How to cite this article Parchand S, Gupta V, Gupta A, Sharma A. Intraocular Tuberculosis. J Postgrad Med Edu Res 2013;47(4):193-201.

Hydronephrosis associated with ureteral wall thickness: Question

A 12-year old male patient presented for elevated blood urea nitrogen and creatinine levels that were noticed during evaluation for anorexia, vomiting and weight loss for the preceding 2 weeks. Past medical history was characterized by right hydronephrosis determined 6 months ago upon evaluation for flank pain. At that time, although imaging tests had suggested suspicious right lower ureteral stone, cystoscopy had revealed fibrotic changes without stone in the lower right ureter. A temporary ureteral stent had been placed and removed during follow up. Physical examination was normal apart from pallor. Laboratory tests revealed normal urinalysis, low hemoglobin (8.5 g/dL), low MCV (74.5 fL), elevated acute phase response (erythrocyte sedimentation rate 54 mm/h, C-reactive protein 17.5 mg/L), impaired renal functions (BUN 23 mg/ dL, creatinine 2.34 mg/dL, creatinine clearance 30 mL/min/ 1.73 m, fractional Na excretion 3.6 %). Urinary system ultrasonography (USG) showed bilateral hydroureteronephrosis and increased renal echogenity. Magnetic resonance (MR) urography disclosed increased wall thickness in all segments of right ureter. Diagnostic ureteroscopy and retrograde pyelography revealed segmental areas of stenosis in both ureters (Fig. 1) and both ureters were catheterized. Renal functions were normalized shortly afterwards. Diagnostic tests for the diseases associated with ureteral wall thickening including urine culture, PPD skin test, chest X-ray, immunological tests for vasculitides and MEFV gene mutation screening were normal.

Upper tract urothelial cell carcinoma presenting as fever of unknown origin and acid-sterile pyuria

Urothelial carcinomas are the fourth most common tumors. They can be divided in carcinomas of the lower urinary tract, if located in the bladder or urethra, or upper urinary tract carcinomas if located in the pyelocaliceal cavities and ureter. Bladder tumors represent the most common malignancy of the urinary tract, and account for the 90–95 % of urothelial carcinomas. On the other hand, upper tract urothelial carcinomas are uncommon, and account only for 5–10 % of urothelial tumors [1, 2]. We report a case of a 63-year-old woman referred to our department in February 2011 for a fever of unknown origin (FUO). She had suffered 30 months prior from mammary ductal carcinoma (staged pT1bN0), treated with quadrantectomy and tamoxifen, switched to exemestane after 2 years (of therapy); moreover, she was affected from HCV-related chronic hepatitis (viraemia: 1.22 9 10 IU/ mL, genotype 1b; naive) discovered in 1997. She complained of fevers up to 39 C mostly ‘‘nocturnal’’ sometimes accompanied by diarrhea, malaise, loss of appetite, weight loss and profuse sweating begun 4 months before. The patient was previously admitted in a different department of internal medicine for the same clinical status. During the hospitalization an abdomen computed tomography (CT scan) was performed that revealed only a reduced enhancement of contrast media in the upper pole of the left kidney. The patient was therefore discharged with a diagnosis of ‘‘fever in remission and renal ischemia’’. 1 month later, the temperature was still elevated, and the patient was admitted to our department. The physical examination revealed an emaciated facies, a body temperature of 37.8 C, a blood pressure of 160/80 mm Hg, and a murmur 2/6 Levine of the mitral valve; the remainder of the physical examination was normal. A complete blood count (CBC) showed a neutrophil leucocytosis (WBC: 11,200/mm, Ne 79.3 %) and a microcytic hypochromic anemia (related to a b-thalassemia trait). Other laboratory tests: GOT, GPT and c-GT were mildly elevated (1.25 ULN), C-reactive protein (CRP) was 1.77 mg/dL (normal value \0.5 mg/dL); electrolytes, erythrocyte sedimentation rate (ESR), blood culture, chest X-ray and urine culture were negative. At echocardiography, performed to exclude a subacute infective endocarditis, the patient presented only a mild mitral regurgitation with left atrial enlargement; there was no sign of valvular vegetations. At urine analysis the patient presented acid-sterile pyuria. Since the most common cause of sterile pyuria is renal tuberculosis, we proceeded with PPD skin test and Koch bacillus research in the urine; both were negative. As the patient was still febrile, an abdomen-CT scan with contrast media infusion was repeated, and revealed again an impairment of perfusion of the left kidney upper pole (reported as renal ischemia), but this time revealed also many lymphoadenopathies near the left renal vein and in the para-aortic region; the biggest one was 1.3 cm in the lumbar para-aortic region. Therefore, we decided to proceed with a total body F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) to better evaluate the abdominal lymphoadenopathies, and to indentify a possible focus responsible of the fever. The only site with high FDG uptake was the lymph node in the lumbar region (max-standardized uptake value 8.7). About 20 days after admission the patient still presented M. Di Capua (&) P. Ierano E. Marrone A. M. Cerbone G. Di Minno Department of Clinical and Experimental Medicine, Regional Reference Centre for Coagulation Disorders, Federico II University of Naples, Via S. Pansini, 5, 80131 Naples, Italy e-mail: mirdica@hotmail.com