My patient with acute exacerbation of heart failure also has pneumonia. How often do heart failure and pneumonia coexist?

More often than you might think! The relationship between pneumonia and heart failure (HF) appears bidirectional with pneumonia precipitating heart failure (HF) and HF predisposing to it.

Although It’s often quoted that acute respiratory tract infection accounts for 3-16% of patients hospitalized with decompensated heart failure (HF) (based primarily on small observational studies),1 a 2016 large prospective study involving nearly 100,000 HF admission from 305 US hospitals has reported “pneumonia/respiratory process” as the most common precipitating clinical factor, present in 28.2% of cases (arrhythmia and medication noncompliance came in as 2nd and 3rd).2

Interestingly, the same study reported that pneumonia/respiratory process was most prevalent among patients with preserved (≥50%) ejection fraction (EF) compared to those with borderline ( 40%-49%) or reduced (<40%) EF (33% vs 30% vs 24%, respectively). 2

Pulmonary edema may in turn predispose to bacterial pneumonia through adverse effects of edema fluid on lung bacterial defense mechanisms and establishment of a culture medium for bacterial growth by the presence of fluid in the alveolar space.3

So don’t be surprised if you have to treat for both!

 

References

  1. Thomsen RW, Kasatpibal N, Riis A, et al. The impact of pre-existing heart failure on pneumonia prognosis: Population-based cohort study. J Gen Intern Med 2008;23:1407-13. https://www.ncbi.nlm.nih.gov/pubmed/18574639
  2. Kapoor JR, Kapoor R, Ju C, et al. Precipitating clinical factors, heart failure characterization, and outcomes in patients hospitalized with heart failure with reduced, borderline, and preserved ejection fraction. JACC 2016;4:464-72. https://www.scholars.northwestern.edu/en/publications/precipitating-clinical-factors-heart-failure-characterization-and 
  3. Harris GD, Woods DE, Fine R, et al. The effect of intraalveolar fluid on lung bacterial clearance. Lung 1980; 158;91-100 Harris GD, Woods DE, Fine R, et al. The effect of intraalveolar fluid on lung bacterial clearance. Lung 1980; 158;91-100. https://link.springer.com/article/10.1007/BF02713708
My patient with acute exacerbation of heart failure also has pneumonia. How often do heart failure and pneumonia coexist?

In my patient with a serious infection, when should I worry about a primary immunodeficiency disorder?

You may consider a primary immunodeficiency disorder (PID) when 2 or more of the following “warning signs” are present: 1

  • ≥ 4 ear infections in 1 year
  • ≥ 2 serious sinus infections in 1 year
  • ≥ 2 pneumonias in 1 year
  • Recurrent, deep skin or organ abscesses
  • Persistent thrush in mouth or persistent fungal infection on the skin
  • ≥ 2 deep-seated infections, including septicemia
  • ≥ 2 months on antibiotics with little effect
  • Need for IV antibiotics to clear infections
  • Failure of an infant to gain weight or grow normally
  • Family history of primary immunodeficiency

Other infectious conditions that may be a clue to PID include those in unusual locations (eg, pneumococcal arthritis) or caused by unusual pathogens (eg, Pneumocystis jirovecii).

Among non-infectious conditions, history of granulomas in multiple organs, early-onset eczema refractory to therapy, and autoimmunity (eg, autoimmune cytopenias, autoimmune thyroiditis, celiac disease, vitiligo, type I diabetes mellitus) may also be potential clues.2

But before you embark on searching for PID,  rule out local barrier disorders of the skin or mucosa (eg, foreign body, bronchiectasis, cystic fibrosis) and secondary causes of immunodeficiency (eg, HIV), syndromes of protein loss/deficiency (eg, cirrhosis, nephrotic syndrome, malnutrition), splenectomy, malignancy, and medications (eg, steroids, chemotherapy, tumor necrosis factor inhibitors).2

Final Fun Fact: Did you know that PID affects 1 in 1,200 people in the US? 3

References:

  1. Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci 2011; 1238:7-14 http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2011.06206.x/abstract
  2. Hausmann O, Warnatz K. Immunodeficiency in adults a practical guide for the allergist. Allergo J Int. 2014; 23: 261–268 https://link-springer-com.ezp-prod1.hul.harvard.edu/article/10.1007/s40629-014-0030-4
  3. Boyle JM, Buckley RH. Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol 2007; 27:497  https://link.springer.com/article/10.1007/s10875-007-9103-1

 

Contributed by Yousef Badran, MD, Mass General Hospital, Boston, MA.

In my patient with a serious infection, when should I worry about a primary immunodeficiency disorder?

The urine antigen for Legionella in my patient with severe community-associated pneumonia is negative. How well does it rule out Legionella pneumonia?

Not as well as you might think!

Legionella urine antigens are 60%-80% sensitive (>99% specific) for detecting L. pneumophila serogroup 1 which accounts for about 70%-80% of Legionnaire’s disease (LD) in the US1; there are at least 15 serogroups.2 So as many as 40% or more LD may be missed by urine antigen testing alone. 2 Urine antigen can be excreted as early 3 days after the onset of symptoms and can persist for >300 days which may present a problem in diagnosing a current illness in patients with recurrent pneumonia. 2 One study reported lowest sensitivity (80%) for antigen testing during days 4 to 7 days of symptoms.3Other means of looking for Legionella include culture of respiratory samples for L. pneumophila which can detect all types of Legionella species (sensitivity 20%-80%) but has a lengthy turnaround time. Paired antibody testing may also be performed (sensitivity 70%-80%) in undiagnosed cases of severe pneumonia. 1Take home point: Don’t depend totally on urine antigen testing to rule out LD.

Final fun fact: Did you know that legionellae survive in the aquatic environment by parasitizing free-living protozoa?

References

  1. CDC. Legionellosis: United States, 2000-2009. MMWR 2011;60:1083-86. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6032a3.htm
  2. Fields BS, Benson RF, Besser RE. Legionella and Legionnaire’s disease: 25 years of investigation. Clin Micro Rev 2002;15:506-26. https://www.ncbi.nlm.nih.gov/pubmed/12097254  
  3. Kohler RB, Zimmerman SE, Wilson E, et al. Onset and duration of urinary antigen excretion in Legionnaire’s disease. J Clin Microbiol 20:605-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC271393
The urine antigen for Legionella in my patient with severe community-associated pneumonia is negative. How well does it rule out Legionella pneumonia?

My patient with pulmonary embolism also reports new-onset hiccups. Are the two conditions related?

Hiccups (AKA singultus) are due to the involuntary contraction of the inspiratory muscles, especially the diaphragm. The hiccup reflex involves an afferent limb ( eg, the phrenic and vagus nerves, sympathetic fibers from T6-T12,  brainstem) and an efferent limb, primarily the phrenic nerve1,2.  Thus, the irritation of any part of the arc in the head, neck, chest, or abdomen may potentially lead to hiccups.

Conditions involving the chest cavity that may be associated with hiccups include lung cancer, GERD, herpetic esophagitis, myocardial ischemia, bronchitis, empyema, lung masses, pneumonia, pleuritis, and pacemaker lead injury 1-3.

Reports of patients with PE and persistent hiccups (lasting longer than 48 h) have also appeared in the literature1,3. Of interest, in a report involving 3 patients, 2 had submassive or “large” PE, with one displaying the classic EKG changes of S1Q3T3; the size of PE in another was not reported1.  In another case report, PE was “not small” and involved the anterior and lateral lower lobe segments of pulmonary artery2.  Although the exact mechanism of PE causing hiccups is not clear, irritation of the afferent or efferent limb of the reflex arc in the chest has been postulated.  

References

  1. Hassen GW, Singh MM, Kalantari H, et al. Persistent hiccups as a rare presenting symptom of pulmonary embolism. West J Emerg Med 202;13:479-483.
  2. Durning SJ, Shaw DJ, Oliva AJ et al. Persistent hiccups as the presenting symptom of a pulmonary embolism. Chest Disease Reports 2012;2:e2.
  3. Buyukhatipoglu H, Sezen Y, Yildiz A, et al. Hiccups as a sign of chronic myocardial ischemia. S Med J 2010;103: 1184-85.
My patient with pulmonary embolism also reports new-onset hiccups. Are the two conditions related?

What causes the “tree-in-bud” (TIB) opacities on the chest CT images of my patient with cough?

TIB opacities represent a normally invisible branches of the bronchiole tree (≤1 mm in diameter) that are severely impacted with mucous, pus, or fluid, with resultant dilatation and “budding” of the terminal bronchioles ( ≥2 mm in diameter)1 (photo).

Although initially described in 1993 as a thin-section chest CT finding in active tuberculosis, TIB opacities are by no means restricted to a specific lung entity, and may be of infectious as well as non-infectious causes.

TIB is most commonly seen with infectious bronchiolitis caused by bacteria (particularly Staphylococcus aureus, Hemophilus influenzae), mycobacteria (including atypical mycobacteria), viruses (eg, respiratory syncytial virus, cytomegalovirus), and fungi (eg, Pneumocystis jirovecii, Aspergillus sp.)1,2.

Non-infectious causes include inhalation of toxic gases, connective tissue disorders (eg, rheumatoid arthritis, Sjögren syndrome), cystic fibrosis, Kartagener syndrome, and non-infectious bronchiolitis (eg, obliterative bronchiolitis). Malignancy-related causes include chronic lymphocytic leukemia and pulmonary tumor embolism in breast, liver, kidney, stomach, prostate and ovarian cancers3.

References

  1. Collins J, Blankenbaker D, Stern EJ. Ct patterns of bronchiolar disease: What is “tree-in’bud”? AJR 1998;171:365-70.
  2. Rossi SE, Franquet T, Volpacchio M, et al. Tree-in-bud pattern a t thin-section CT of the lungs: radiologic-pathologic overview. RadioGraphics 2005;25:789-801.
  3. Terhalle E, Gunther G. “Tree-in-bud”: thinking beyond infectious causes. Respiration 2015;89:162-165.

 

 

Photo: TIB opacities in a 50 year old man with productive cough and shortness of breath caused by infectious bronchiolitis.

treeinbud

 

What causes the “tree-in-bud” (TIB) opacities on the chest CT images of my patient with cough?

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

Howell-Jolly bodies (HJBs, Figure) are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including  sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease (particularly ulcerative colitis), HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-4.

Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3.  Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,5.

HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. 

Final Fun Pearl:  Did you know that  HJBs were named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who was among the first to film mitotic activity in cells?

howelljollymgh

Figure. Howell-Jolly body in an RBC. Photo courtesy of Michael S. Abers, MD

 

References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. https://www.ncbi.nlm.nih.gov/pubmed/21474172
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176. https://www.ncbi.nlm.nih.gov/pubmed/24862308
  3. Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551333
  4. Ryan FP, Smart RC, Holdsworth CD, et al. Hyposplenism in inflammatory bowel disease 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pubmed/624506
  5. Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94.  http://onlinelibrary.wiley.com/doi/10.1111/bjh.13660/full

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

What is the sensitivity of nose swabs in detecting methicillin-resistant Staphylococcus aureus (MRSA) pneumonia?

In MRSA pneumonia, the sensitivity of nasal swab PCR may vary from as low as 24.2% to 88% (1-3). A single center  study involving  patients with possible healthcare-associated pneumonia (HCAP) and a low clinical pulmonary infection score (CPIS) — for whom antibiotics may not be necessary anyway (4)—suggested that discontinuation of empiric vancomycin in patients without an adequate respiratory culture and a negative nose and throat culture may be reasonable (5).  However, a prospective study of ICU patients concluded that “clinicians cannot reliably use the results of initial negative MRSA nasal swab results to withhold empirical MRSA coverage from patients who otherwise are at risk for MRSA infection” (3).

Thus, there is currently insufficient data to support discontinuation of vancomycin based on a negative nasal screen alone, particularly in patients who may be at high risk of MRSA pneumonia.

 

References

  1. Rimawi RH, Ramsey KM, Shah KB, et al. Correlation between methicillin-resistant Staphylococcus aureus nasal sampling, and S. aureus pneumonia in the medical intensive care unit. Infect Control Hosp Epidemiol 2014;35:590-92.
  2. Dangerfield B, Chung A, Webb B, et al. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014;58:859-64.
  3. Sarikonda KV, Micek ST, Doherty JA, et al. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med 2010;38:1991-1995.
  4. Napolitano LM. Use of severity scoring and stratification factors in clinical trials of hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis 2010;51:S67-S80.
  5. Boyce JM, Pop O-F, Abreu-Lanfranco O, et al. A trial of discontinuation of empiric vancomycin therapy in patients with suspected methicillin-resistant Staphylococcus aureus health care-associated pneumonia. Antimicrob Agents Chemother 2013;57:1163-1168.
What is the sensitivity of nose swabs in detecting methicillin-resistant Staphylococcus aureus (MRSA) pneumonia?