EUH Resident Report: An Overview of KHSV inflammatory cytokine syndrome (KICS)

The Bottom Line:

The clinical manifestations of KICS are protean, and none are specific to the syndrome. Rather, they likely reflect common endpoints of proinflammatory cytokine deregulation in the setting of KSHV lytic replication and pathologic expression of KSHV encoded genes such as vIL-6. These symptoms may also be observed in other inflammatory states, and at times can be confused clinically with sepsis. KICS is therefore a diagnosis of exclusion, requiring pathologic exclusion of MCD; careful evaluation to exclude alternate explanations for the clinical manifestations, such as serious intercurrent infection; demonstration of systemic inflammation; and demonstration of KSHV viral activity.

Summary:

Its clinical manifestations resemble those of KSHV–multicentric Castleman disease (KSHV-MCD) but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe KS or primary effusion lymphoma.

Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein.

Additional research is needed to better define the clinical spectrum of KICS and its relationship to KSHV–MCD. Research is also needed to better understand the pathogenesis and epidemiology of both KICS and KSHV–MCD, as well as the optimal therapy for both of these disorders.

Reference:

Polizzotto MN, Uldrick TS, Duosho H, Yarchoan R. Clinical manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric castleman disease (KSHV-MCD) and the KSHV inflammatory cytokine syndrome. Frontiers in Microbiology. 2012; 3:73.

Posted in Background question, Diagnosis, EUH

EUH Resident Report: What is the sensitivity/specificity of the urine test for streptococcus pneumoniae?

The Bottom Line: Studies show considerate variance in their results.

Horita N, et al (2013): The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias.

Boulware DR, et al (2007): The performance of the urine antigen ICT was independent of HIV-status (sensitivity 81%, specificity 98%, positive (PPV) and negative predictive values (NPV) 98%, and 82%, respectively). The sensitivity of sputum Gram’s stain was 58% (34/59) with sputum unable to be provided by 16%. The CRP response was identical in HIV-infected (mean+/-SD) 133+/-88 vs. seronegative 135+/-104 mg/L (p=0.9). In the systematic review, the ICT performance revealed 74% sensitivity (95% CI 72-77%) and 94% specificity (95% CI 93-95%). Urine antigen testing increases etiologic diagnosis by 23% (range: 10-59%) when testing adults with community acquired pneumonia of unknown etiology.

References:

Boulaware DR, et al. Rapid diagnosis of pneumococcal pneumonia among HIV-infected adults with urine antigen detection. The Journal of Infection. 2007 Oct; 55(4):300-309.

Horita N, et al. Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis. Respirology. 2013 Nov; 18(8):1177-1183. doi:10.1111/resp.12163.

Posted in Background question, Diagnosis, EUH

Grady Report: What are the current guidelines for the pharmacological management of prostatitis?

The Bottom Line: For healthcare providers, the focus of therapy is symptomatic relief. The first therapeutic measure is often a 4- to 6-week course of a fluoroquinolone, which provides relief in 50% of men and is more efficacious if prescribed soon after symptoms begin. Second-line pharmacotherapy involves anti-inflammatory agents for pain symptoms and alpha-adrenergic receptor antagonists (alpha-blockers) for urinary symptoms. Potentially more effective is pelvic floor training/biofeedback, but randomized controlled trials are needed to confirm this. Third-line agents include 5alpha-reductase inhibitors, glycosaminoglycans, quercetin, cernilton (CN-009) and saw palmetto.  Pain and urinary symptoms can be ameliorated with anti-inflammatories and alpha-blockers.

Summary: CP/CPPS has many clinical presentations and treatment options, with fluoroquinolones as the only FDA-approved first-line agents. Combination therapy of an α-blocker for ≥12 weeks with a fluoroquinolone may be considered a multimodal first-line therapy. Differentiating CP/CPPS from the other NIH prostatitis subtypes helps healthcare professionals design treatment plans that optimize response.

Reference: Murphy AB, et al. “Chronic prostatitis: management strategies.Drugs 2009; 69(1):71-84.

Posted in Background question, Grady, Therapy

VA Report: What are the causes of QRS prolongation in an otherwise structurally normal heart?

Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non–life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm.

Eric N Prystowsky Benzy J Padanilam Sandeep Joshi Richard I Fogel Ventricular arrhythmias in the absence of structural heart disease.
Journal of the American College of Cardiology , 2012, Vol.59(20), p.1733-1744

Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias.

Table 1 Classification of Ventricular Arrhythmias in the Absence of Structural Heart Disease. : Page 1734

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EUHM Report: What is the incidence of muscle twitch in hypercalcemia

The novel family of genetically encoded calcium indicators, named ‘Twitch’ sensors, fulfill the majority of criteria and represent a major improvement over most existing indicators. The name of the indicators originates from the fact that their calcium sensor is derived from troponin C, a calcium-binding protein found in skeletal and cardiac muscle (but not neurons) that regulates muscle twitching.

Wilms, C., & Häusser, M. (n.d.). Twitching towards the ideal calcium sensor. Nature Methods., 11(2), 139-140.

Calcium is an exquisitely versatile signaling molecule, determining both cell differentiation and death as well as triggering neurotransmission and regulating synaptic plasticity. Consequently, determining the spatial and temporal dynamics of intracellular calcium concentration, [Ca2+], is crucial not only in cell biology but also for understanding immune physiology and brain function. Unsurprisingly, measuring [Ca2+] dynamics is one of the main uses of fluorescence microscopy and has spurred the development of new indicators for many decades

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VA Report: What are the most common clinical characteristics of Human Monocytic Erlichiosis?

Human monocytic ehrlichiosis commonly presents as a self-limited sickness with symptoms that most often include fever, headache, myalgias, nausea, arthralgias, and malaise. In rare cases, it manifests as a life-threatening illness with features of toxic shock-like syndrome and end-organ damage; this mostly occurs in the immunocompromised, geriatric, or pediatric populations. The most important determinant in the diagnosis of human monocytic ehrlichiosis is clinical suspicion. In addition to symptoms, pancytopenia is an important hematologic abnormality that is frequently associated with human monocytic ehrlichiosis. Thrombocytopenia is detected in 70-90% of patients over the course of the illness, leukopenia is observed within the first week in 60-70%, and anemia is noted within the first 2 weeks of presentation in 50% of patients. Elevated hepatic transaminases are present in almost 90% of patients

Hilal, T., & Snapp, W. (n.d.). The perils of country life: Human monocytic ehrlichiosis. The American Journal of Medicine, 128(8), 831-833.

The current recommended regimen for the treatment of human monocytic ehrlichiosis is doxycycline, 100 mg, twice daily for 5-14 days. Patients with a delay in treatment have a significantly increased rate of transfer to the intensive care unit, increased risk for mechanical ventilation, longer hospital stay, and longer duration of illness. Encephalopathy, acute renal failure, pulmonary infiltrates, and death have been reported in patients with severe human monocytic ehrlichiosis.

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VA Resident Report: What is the etiology and therapy options for Postobstructive community-acquired pneumonia?

The Bottom Line: This study encourages more limited antibiotic use in patients with PO-CAP. Our experience has been that when patients fail to respond to a first course of antibiotics, physicians repeat sputum cultures, which now are contaminated with newly acquired gram-negative colonizing organisms, and then give additional antibiotics to cover these newly recognized bacteria

Abers, M., Sandvall, B., Sampath, R., Zuno, C., Uy, N., Yu, V., . . . Musher, D. (n.d.). Postobstructive Pneumonia: An Underdescribed Syndrome. Clinical Infectious Diseases, 62(8), 957-961.

Postobstructive pneumonia, a pulmonary infiltrate distal to a bronchial obstruction that, in adults, is generally due to malignancy, has been reported in about 2% of patients hospitalized for community-acquired pneumonia (CAP). Opinion varies as to whether infection is responsible for POCAP. Some believe that infection is generally not involved, whereas others regard bacterial infection as the usual cause. Because conventional practice is to treat all POCAP with antibiotics, we performed a prospective study to characterize the clinical and laboratory findings in patients with this disease, with particular attention to the role of bacterial infection.

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