When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

Think of invasive pulmonary aspergillosis (IPA) in your patient when she or he has a COPD exacerbation that appears refractory to broad-spectrum antibiotics and high doses of steroids. Heighten your suspicion even more in patients with severe-steroid dependent COPD, presence of a new pulmonary infiltrate or isolation of Aspergillus spp from respiratory cultures. 1

It’s worth remembering that although dyspnea and bronchospasm are found in most COPD patients with IPA, in contrast to haematological patients, fever, chest pain and hemoptysis are usually absent in this patient population.1

Diagnosis of IPA in this patient population is challenging for several reasons including: 1. A definitive or “proven” diagnosis requires histopathologic evidence of Aspergillus invasion of lung tissue which is not possible without subjecting an already fragile patient to invasive procedures (eg, lung aspiration or biopsy); 2. In contrast to IPA in highly susceptible immunocompromised patients with cancer and recipients of hematopoietic stem cell transplants, standardized definition of IPA in patients with COPD is lacking; 1,3 and 3. Frequent colonization of the respiratory tract of COPD patients with Aspergillus spp (16.3 per 1000 COPD admission in 1 study) 4,5, makes it difficult to diagnose IPA based on cultures alone.

Aside from respiratory cultures, another non-invasive test, serum galactomannan (GM, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp and released into the blood during its growth phase 6) may have some utility in suggesting IPA in COPD patients, albeit with a mediocre sensitivity (~30-60%) but respectable specificity (>80 %). In contrast, bronchoalveolar lavage fluid GM may have better sensitivity  (~75%-90%) with similar specificity as that of serum GM in the diagnosis of IPA in these patients 7-8

Bonus pearl: Did you know that the incidence of IPA appears to be increasing in COPD patients requiring ICU admission, with reported mortality rates of 67% to 100%? 7

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References

  1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Res J 2007;30:782-800. https://www.ncbi.nlm.nih.gov/pubmed/17906086
  2. Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patietns with COPD? Eur Resir J 2017;50:1700532 https://www.ncbi.nlm.nih.gov/pubmed/28954783
  3. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of aspergillosis in a cohort of non-neutropenic, non-transplant patients colonized by Aspergillus spp. BMC Infect Dis 2017;17:34. https://link.springer.com/article/10.1186/s12879-016-2143-5
  4. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16:870-77. https://www.sciencedirect.com/science/article/pii/S1198743X14617432
  5. Blot Stijn I, Taccone FS, Van den Abeele A-M, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 202;186:56-64. https://www.atsjournals.org/doi/full/10.1164/rccm.201111-1978OC
  6. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-27. https://academic.oup.com/cid/article/42/10/1417/278148
  7. He H, Ding L, Sun B, et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Critical Care 2012;16:R138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066034/
  8. Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61. https://www.ncbi.nlm.nih.gov/pubmed/28446576
When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

Although there are no consensus guidelines on when to evaluate patients with COPD for antibody deficiency, we should at least consider this possibility in patients with recurrent exacerbations despite maximal inhaled therapy (long-acting beta-2 agonist-LABA, long-acting muscarinic antagonist-LAMA and inhaled corticosteroids).1

Couple of retrospective studies of common variable immunodeficiency (CVID) in patients with COPD have reported a prevalence ranging from 2.4% to 4.5%. 1 In another study involving 42 patients thought to have had 2 or more moderate to severe COPD exacerbations per year—often despite maximal inhaled therapy— 29 were diagnosed  with antibody deficiency syndrome, including 20 with specific antibody deficiency (SAD), 8 with CVID and 1 with selective IgA deficiency.2  Although systemic corticosteroids may lower IgG and IgA levels, the majority of the patients in this study were not taking any corticosteroids at the time of their evaluation.

In another study involving patients undergoing lung transplantation, pre-transplant mild hypogammaglobulinemia was more prevalent among those with COPD (15%) compared to other lung conditions (eg, cystic fibrosis), independent of corticosteroid use.3  A favorable impact of immunoglobulin therapy or chronic suppressive antibiotics on reducing recurrent episodes of COPD exacerbation in patients with antibody deficiency has also been reported, supporting the clinical relevance of hypogammaglobulinemia in these patients. 2,4 

Remember that even normal quantitative serum immunoglobulin levels (IgG, IgA, and IgM) do not necessarily rule out antibody deficiency. Measurement of IgG subclasses, as well as more specific antibodies, such as those against pneumococcal polysaccharides may be required for further evaluation.

See a related pearl at https://pearls4peers.com/2015/07/12/my-65-year-old-patient-has-had-several-bouts-of-bacterial-pneumonia-in-the-past-2-years-her-total-serum-immunoglobulins-are-within-normal-range-could-she-still-be-immunodeficient/.

Contributed in part by Sydney Montesi, MD, Mass General Hospital, Boston, MA.

References

  1. Berger M, Geng B, Cameron DW, et al. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Resp Med 2017;132:181-188. https://www.sciencedirect.com/science/article/pii/S0954611117303554
  2. McCullagh BN, Comelias AP, Ballas ZK, et al. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS ONE 2017; 12: e0172437. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0172437
  3. Yip NH, Lederer DJ, Kawut SM, et al. Immunoglobulin G levels before and after lung transplantation 2006;173:917-21.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662910/
  4. Cowan J, Gaudet L, Mulpuru S, et al. A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease. PLoS ONE 2015;10:e0142205. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142205

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Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

It is generally recommended that patients on ≥20 mg of daily prednisone (or its equivalent) for ≥1 month be considered for PCP prophylaxis. 1

Couple of studies in 1990s helped define the dose and duration of corticosteroids (CS) that should prompt PCP prophylaxis. A Mayo Clinic study of patients without AIDS found that a median daily CS dose of 30 mg of prednisone or equivalent—with 25% of patients receiving as little as 16 mg of prednisone daily— was associated with PCP.The median duration of CS therapy before PCP was 12 weeks. A similar study found a mean CS dose of 33 mg of prednisone or equivalent with mean duration of 7 months (range 1-154 months) among patients with PCP without AIDS. 3

A 2018 retrospective study4  of patients with rheumatic diseases receiving prolonged high-dose CS therapy (≥30 mg prednisone for ≥4 weeks) found that PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) resulted in 93% reduction in the incidence of PCP with an overall number needed to treat (NNT) of 52. It was suggested that PCP prophylaxis could be discontinued in patients receiving < 15 mg of prednisone daily.

Bonus Pearl: Did you know that TMP/STX may be given either as double-strength 3x/week or single-strength daily? 5,6

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References

1. Limper AH, Knox KS, Sarosi SA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011;183:96-128. https://www.ncbi.nlm.nih.gov/pubmed/21193785

2. Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996;71:5-13. https://www.sciencedirect.com/science/article/abs/pii/S0025619611649148

3. Arend SM, Kroon FP, van’t Wout JW. Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993: An analysis of 78 cases. Arch Intern Med 1995;155:2436-2441. https://www.ncbi.nlm.nih.gov/pubmed/7503602

4. Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole for Pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoieds. Ann Rheum Dis 2018;77:664-9. https://www.ncbi.nlm.nih.gov/pubmed/29092853

5. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.http://www.pneumon.org/assets/files/789/file483_273.pdf

6. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. https://www.ncbi.nlm.nih.gov/pubmed/25269391

 

When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

There are at least 2 reasons for considering pneumococcal vaccination in hospitalized patients with ulcerative colitis flare.

First, these patients are often on immunosuppressants (eg, glucocorticoids) or biological agents (eg, infliximab) that qualifies them for both 13-valent conjugate (PCV13) and 23-valent polysaccharide (PPSV23) pneumococcal vaccines under the Advisory Committee on Immunization Practices (ACIP) Guidelines’ “Immunocompromised persons” risk group.1-4

Another reason is the possibility of  UC patients having coexisting hyposplenism, a major risk factor for pneumococcal disease. Although this association has been described several times in the literature since 1970s, it is relatively less well known.  In a study of patients with UC, hyposplenism (either by the presence of Howell-Jolly bodies in the peripheral blood smear or prolongation of clearance from blood of injected radioactively labelled heat-damaged red blood cells) was found in over one-third with some developing life-threatening septicemia in the early postcolectomy period.5

Another study found the majority of patients with UC having slow clearance of heat damaged RBCs despite absence of Howell-Jolly bodies in the peripheral smear.6 Fulminant and fatal pneumococcal sepsis has also been reported in patients with UC.7

Although the immunological response to pneumococcal vaccination may be lower among immunosuppressed patients in general, including those with UC, it should still be administered to this population given its potential benefit in reducing the risk of serious pneumococcal disease. 2,3  

References

  1. CDC. Intervals between PCV13 and PSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2015;64:944-47. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm
  2. Carrera E, Manzano r, Garrido. Efficacy of the vaccination in inflammatory bowel disease. World J Gastroenterol 2013;19:1349-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602493/
  3. Reich J, Wasan S, Farraye FA. Vaccinating patients with inflammatory bowel disease. Gastroenterol Hepatol 2016;12:540-46. http://www.gastroenterologyandhepatology.net/archives/september-2016/vaccinating-patients-with-inflammatory-bowel-disease/
  4. Chaudrey K, Salvaggio M, Ahmed A, et al. Updates in vaccination: recommendations for adult inflammatory bowel disease patients. World J Gastroenterol 2015;21:3184-96. https://www.ncbi.nlm.nih.gov/pubmed/25805924
  5. Ryan FP, Smart RC, Holdworth CD, et al. Hyposplenism in inflammatory bowel disease. Gut 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411782/
  6. Jewell DP, Berney JJ, Pettit JE. Splenic phagocytic function in patients with inflammatory bowel disease. Pathology 1981;13:717-23. https://www.ncbi.nlm.nih.gov/pubmed/7335378
  7. Van der Hoeven JG, de Koning J, Masclee AM et al. Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infec Dis 1996;22:860-1. https://www.ncbi.nlm.nih.gov/pubmed/8722951

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Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

How can I distinguish cardiac asthma from typical bronchial asthma?

Certain clinical features of cardiac asthma, defined as congestive heart failure (CHF) associated with wheezing, may be useful in distinguishing it from bronchial asthma, particularly in older patients with COPD (1-3).

• Paroxysmal nocturnal dyspnea associated with wheezing
• Presence of rales or crackles, ascites or other signs of CHF
• Poor response to bronchodilators and corticosteroids
• Formal pulmonary function test with bronchoprovocation demonstrating minimal methacholine response.

 
Cardiac asthma is not uncommon. In a prospective study of patients 65 yrs of age or older (mean age 82 yrs) presenting with dyspnea due to CHF, cardiac asthma was diagnosed in 35% of subjects. Even in non-elderly patients, cardiac asthma has been reported in 10-15% of patients with CHF (2).

 
The mechanism(s) underlying cardiac asthma is likely multifactorial. Pulmonary edema and pulmonary vascular congestion have traditionally been considered as key factors either through edema in the interstitial fluid of bronchi squeezing the bronchiolar lumen or by externally compressing the entire airway structure and the bronchiole wall. Reflex bronchoconstriction involving the vagus nerve, bronchial hyperreactivity, systemic inflammation, and airway remodeling may also play a role (1,3). 

 
Treatment of choice for cardiac asthma typically includes diuretics, nitrates and morphine, not bronchodilators or corticosteroids (1,3). 

 
Bonus Pearl: Did you know that the term “cardiac asthma” was first coined by the Scottish physician, James Hope, way back in 1832 to distinguish it from bronchial asthma!

 

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References
1. Litzinger MHJ, Aluen JKN, Cereceres R, et al. Cardiac asthma: not your typical asthma. US Pharm. 2013;38:HS-12-HS-18. https://www.uspharmacist.com/article/cardiac-asthma-not-your-typical-asthma
2. Jorge S, Becquemin MH, Delerme S, et al. Cardiac asthma in elderly patients: incidence, clinical presentation and outcome. BMC Cardiovascular Disorders 2007;7:16. https://www.ncbi.nlm.nih.gov/pubmed/17498318
3. Tanabe T, Rozycki HJ, Kanoh S, et al. Cardiac asthma: new insights into an old disease. Expert Rev Respir Med 2012;6(6), 00-00. https://www.ncbi.nlm.nih.gov/pubmed/23234454

 

How can I distinguish cardiac asthma from typical bronchial asthma?

My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?

The most helpful lab data favoring corticosteroid-induced granulocytosis (CIG) is the absence of a shift to the left in the peripheral WBC (ie, no more than 6% band forms) and toxic granulation.1 Although the total WBC itself is less helpful, experimental studies have reported a mean maximum neutrophil counts 2.4 times the base line after IV injection of hydrocortisone (200 mg) 2, and a mean increase of 4,000 neutrophils/mm3 after prednisone (20-80 mg). 3

Several possible mechanisms for CIG revolving around altered neutrophil characteristics and dynamics have been proposed4, including

  • Reduced egress from blood into tissues
  • Demargination from vascular endothelial surfaces
  • Delayed apoptosis
  • Enhanced release from the bone marrow.

An experimental animal study reported that only 10% of CIG is related to bone marrow release of neutrophils with the rest related to demargination (61%) and reduced egress from blood or delayed apoptosis (29%).4 This study may explain why high percentage of band forms would not be expected in CIG.

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References

  1. Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis: influence of dosage, method, and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-78. Link
  2. Bishop CR, Athens JW, Boggs DR, et al. Leukokinetic studies: A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis. J Clin Invest 1986;47:249-60. https://www.ncbi.nlm.nih.gov/pubmed/5638121
  3. Dale DC, Fauci AS, Guerry DuPont, et al. Comparison of agents producing a neutrophilic leukocytosis in man. J Clin Invest 1975;56:808-13. PDF
  4. Nakagawa M, Terashma T, D’yachkova YD, et al. Glucocorticoid-induced granulocytosis: Contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98:2307-13. PDF

 

 

My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?

Does my patient about to undergo immunosuppressive therapy need antiviral prophylaxis even if she tests positive for hepatitis B surface antibody?

The presence of hepatitis B surface antibody (HBsab) in patients who also test positive for core antibody does not necessarily confer full protection against hepatitis B virus (HBV) reactivation during immunosuppression (incidence 4.3%). 1 This is because despite having HBsab and no HB surface antigen,  a small portion of patients continue to have detectable HBV DNA in the serum and are therefore at risk of reactivation during severe immunosuppression. 2

In fact, the American Gastroenterological Association recommends against using anti-HBs status to guide antiviral prophylaxis in anti-HBc-positive patients. 1

Overall, antiviral prophylaxis may reduce the risk of HBV reactivation by 87% (C.I. 70%-94%). Antiviral drugs with a high barrier to resistance (eg, entecavir) are preferred over lamivudine.

Immunosuppressants often requiring HBV prophylaxis include: 1-3

  • B cell-depleting agents (eg, rituximab, ofatumumab)
  • Anthracycline derivatives (eg, doxorubicin, epirubicin)
  • Prednisone (4 weeks or more)
  • Tumor necrosis factor inhibitors (eg, etanercept, adalimumab, certolizumab, infliximab)
  • Other cytokine or integrin inhibitors (eg, abatacept, ustekinumab, natalizumab, vedolizumab)

Traditional immunosuppressive agents such as azathioprine, 6-mercaptopurine and methotrexate are often considered “low-risk” and do not generally require prophylaxis. 1

Fun Fact: Did you know that hepatitis B virus is very old and probably originated in birds when dinosaurs roamed the earth? 4

References

  1. Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015;148:215-19. https://www.ncbi.nlm.nih.gov/pubmed/25447850
  2. Gigi E, Georgiou T, Mougiou D, et al. Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatitis B surface antigen treated with rituximab. HIPPOKATRIA 2013;17:91-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738290/
  3. Kim EB, Kim DS, Park SJ, et al. Hepatitis B virus reactivation in a surface antigen-negative and antibody-positive patient after rituximab plus CHOP chemotherapy. Cancer Res Treat 2008;40:36-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699087/
  4. Suh A, Brosius J, Schmitz J, et al. The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B virus. Nature Communications 2013; Article no. 1791. http://www.nature.com/articles/ncomms2798
Does my patient about to undergo immunosuppressive therapy need antiviral prophylaxis even if she tests positive for hepatitis B surface antibody?

What is the utility of bedside skin-fold test in diagnosing Cushing’s syndrome?

Skin atrophy is a common feature of Cushing’s syndrome (CS), a hypercortisol state,  with multiple studies reporting radiographic evidence of reduced skin thickness in this condition1,2.

Measurement of skin thickness on the dorsal aspect of the 2nd or 3rd proximal phalanges on the non-dominant hand by using ECG calipers to pinch together a fold of skin has also been reported to assess skin atrophy in CS, with thickness less than 18 mm correlating strongly with CS3,4; the minimal subcutaneous fat at this location allows for a more accurate measurement of skin thickness.

However, caution should be exercised in interpreting the results of this study. Specifically, some overlap was observed between normal controls and patients with CS.  In addition, the study population was limited to women of reproductive age presenting with oligomenorrhea and hirsutism for at least 2 years, a subset of patients that may account for only 40% of cases with CS5,6.  Further studies are clearly needed to determine the clinical utility of the skin-fold test in patients suspected of CS.

References

  1. Sheppard RH, Meema HE. Skin thickness in endocrine disease. A roentgenographic study. Ann Intern Med 1967;66:531-9.
  2. Ferguson JK, Donald RA, Weston TS, et al. Skin thickness in patients with acromegaly and Cushing’s syndrome and response to treatment. Clin Endocrinol (Oxf) 1983;18:347-53.
  3. Corenblum B, Kwan T, Gee S, et al. Bedside assessment of skin-fold thickness: A useful measurement for distinguishing Cushing’s disease from other causes of hirsutism and oligomenorrhea. Arch Intern Med. 1994;154:777-781.
  4. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017;376:1451-9.
  5. Lindholm J, Juul S, Jorgensen JOL, et al: Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 2001;86:117–123.
  6. Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, et al. Menstrual abnormalities in women with Cushing’s disease are correlated with hypercortisolemia rather than raised circulating androgen levels. J Clin Endocrinol Metab. 1998;83:3083-8.

Contributed by Sagar Raju, Medical Student, Harvard Medical School

What is the utility of bedside skin-fold test in diagnosing Cushing’s syndrome?

When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?

The most significant risk factor for PCP prophylaxis is defect in cell-mediated immunity including high-dose glucocorticoid (HDGC, ≥20 mg of prednisone daily) treatment1.  A systematic review concluded that at a PCP rate of 6.2% in control groups, PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) is highly effective (85% risk reduction) in non-HIV patients with acute leukemia or solid organ/autologous bone marrow  transplantation (number needed to treat 19)2.

Other Indications for PCP prophylaxis include1:

  1. HDGC treatment for ≥1month plus another cause of immunocompromise.
  2. Combination of immunosuppressive drugs, such as tumor-necrosing factor- α inhibitors plus HDGC or other immunosuppression.
  3. Polymyositis/dermatomyositis with interstitial pulmonary fibrosis on glucocorticoids.
  4. Certain primary immunodeficiencies (eg idiopathic CD4-lymphopenia, hyper-IgM syndrome).
  5. Granulomatosis with polyangiitis (Wegener’s) on methotrexate and HDGC
  6. Rheumatologic diseases on HDGC and a second immunosuppressive drug
  7. T-cell depleting agents (eg, fludarabine)
  8. Severe malnutrition

TMP/STX may be given either as double-strength 3x/week or single-strength daily1,2.

 

References

  1. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.
  2. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. 
When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?

My patient with autoimmune hepatitis has been on less than 20 mg of prednisone daily for the past month and now complains of dyspnea. What is the dose of prednisone that should make me worry about Pneumocystis jirovecii pneumonia (PCP) in her?

The risk of infection in patients on glucocorticoids (GCs) is likely determined not only by the dose and duration of treatment but also by the nature of the underlying disease requiring GC therapy (eg, asthma, autoimmune disease, malignancy),   use of additional immunosuppressants, as well as individual host sensitivity to the effects of GCs1,2.  For these reasons, it is often difficult to determine how much GCs will be too much for a specific patient when discussing opportunistic infections such as PCP in patients without HIV infection.

In patients with an autoimmune disease such as ours, as little as 12 mg/day of prednisone on presentation or as few as 5 days of GC therapy has been associated with PCP3.  Because the critical amount of immunosuppression necessary for PCP to cause disease is unclear4, and autoimmunity is often associated with T-cell dysregulation5, it is prudent to consider PCP in the differential of diagnosis of dyspnea (along with fever or pulmonary infiltrates if present) in this patient despite not receiving “high” doses of prednisone daily.  It is also important to remember that many cases of PCP occur during GC taper4.

 

References

  1. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet 2003;362:1828-38.
  2. Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroids. Rheum Dis Clin N Am 2016; 42; 157-176.
  3. Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996;71:5-13.
  4. Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. Arch Intern Med 1995;1125-28.
  5. Arkwright PD, Abinun M, Cant AJ. Autoimmunity in human immunodeficiency diseases. Blood 2002;99:2694-2707.
My patient with autoimmune hepatitis has been on less than 20 mg of prednisone daily for the past month and now complains of dyspnea. What is the dose of prednisone that should make me worry about Pneumocystis jirovecii pneumonia (PCP) in her?