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?

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?